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A TLR4-triggered complex inflammation in pancreatic islets causes beta-cell failure in diabetes
No full textType 2 Diabetes (T2D) is strongly associated with obesity and characterized by chronic insulin resistance, progressive failure of pancreatic beta-cells, and ultimately hyperglycaemia. The association of T2D with chronic sterile inflammation has been extensively demonstrated, and the elevation of inflammatory mediators can predict type 2 diabetes progression. Pro-inflammatory cytokines and chemokines can cause insulin resistance in peripheral insulin-sensing tissues like fat, liver and muscle, and also lead to progressive beta-cell failure. This eventually shifts metabolism from relative insulin insufficiency - due to the greater insulin demand in obesity - to definite insulin deficiency, while on the beta-cell level - from compensation to decompensation. Toll-like receptor (TLR)-4 signaling is one of the major pro-inflammatory pathways activated by exogenous pathogen-related or endogenous danger-related molecules. Its ligands, including the classical ligand LPS as well as saturated fatty acids and CXCL10, among others, are increased systemically in patients with T2D as well as in at-risk individuals. TLR4-deficiency or its pharmacological inhibition have been shown to ameliorate obesity- or lipid-induced tissue inflammation and insulin resistance in humans and in mouse models. Increasing evidence also connects TLR4 to islet inflammation and beta-cell dysfunction in the context of the pathogenesis of T2D, but many underlying mechanisms remain unknown. In the first part of this thesis, I aimed to uncover the role of TLR4 activation by lipopolysaccharide (LPS), the classical TLR4 ligand, in islet inflammation and beta-cell function in human islets. My special focus was to identify the inflammatory mechanism in the intercellular level â the possible interplay among different cells in human islets. I found that LPS-triggered TLR4 activation in cultured human islets induced beta-cell dysfunction, apoptosis and a pro-inflammatory profile with markedly increased IL-1beta, IL-6, TNFalpha and IL-8 production. Macrophage-depletion demonstrates that islet resident macrophages are responsible for the production of IL-1beta, while all the other cyto-/chemokines are predominantly produced from islet endocrine cells. IL-6 is partially responsible for the LPS-induced beta-cell dysfunction, while IL-8 produced from alpha-cells is responsible for monocyte migration to islets during TLR4-activation-induced islet inflammation. This complex inflammatory response in islets is further potentiated in obese individuals, with more IL-1beta, IL-6 and IL-8 expression and a tendency to more islet macrophage accumulation, suggesting a possibly self-augmented inflammatory cycle involving alpha-cells, beta-cells and islet macrophages, which may explain the higher susceptibility of obese individuals to the development of beta-cell damage und eventually T2D. Ageing is known to be associated to elevated T2D risk, though the underlying mechanism remains largely undiscovered. In the second part of this thesis, I aimed to find out if ageing could aggravate obesity-induced T2D, and further focus on the effects on beta-cell function and the role of inflammation in such processes. In a mouse model of high fat diet induced obesity, I found an adverse potentiation of impaired glucose homeostasis, beta-cell dysfunction and chronic tissue inflammation by the combination of obesity and aging. In contrast, TLR4-deficiency exhibited a protection against those deleterious effects through inhibiting pro-inflammatory cytokine expression and switching tissue macrophage activation to a more anti-inflammatory phenotype. In both parts of this thesis, I provide further evidence that TLR4 and inflammation play a causative role in the development of T2D, and thereby support the concept of TLR4- or inflammation-targeted therapeutic strategies
PISA, Public Participation and Policy Making in Education : the Impact of Online Social Movements and the Shift in Public Involvement in the Basic and Secondary Education Decision Making Processes in Indonesia
Get PDFAbstract What was social mediaa s role in the establishment of online activism in the education sector? Can this online movement affect policy making in the education sector? The utilization of social media as an alternative to raising a social movement aimed to change a political system is not a new phenomenon in social sciences. The Arab Spring, Tunisian revolution, Egypt revolution, and the Tsunami Blanco in Guatemala are some examples of how powerful online activism can be in forcing a change in the sociopolitical life of a country. The current study focuses on exposing the phenomena of online movements resulting in the shift of public positions in policy making. While previous research usually talks about online activism in political revolutions, natural preservation, or human rights, I elucidate further the correlation among social media, online movements, and the improvement of public participation in the decision-making process in the education sector. For that reason, I analyze the emergence of the phenomena in Indonesian basic and secondary education as a case study. Moreover, the existing research rarely discusses the struggle of developing countries in improving education quality as well as their competitiveness level internationally, especially those which perform poorly in the Rankings & Ratings, namely the PISA survey. In this dissertation, I build a theoretical framework developed to answer two research questions: How did the online movement, stimulated via social media, affect and shift both the paradigm of the policy makers and the public in the basic and secondary education policy making processes in Indonesia? What was the impact of social media in driving the online movement as well as changing the policy making process in Indonesia? Theoretically, the output of the study contributes to understanding the emergence of online activism affecting policy making processes in the field of education. To explain the phenomena, I use a theoretical framework emphasizing three components of social movement proposed by Meyer (2004): organizational consciousness, resources, and political opportunities. I also apply four main theoretical approaches, which are public participation, collective identity, resources mobilization theory, and political opportunity structure. Additionally, I use relative deprivation, rational actor theory, and advocacy 2.0. as supporting theories to explain the possible driving reasons behind the occurrence of the three elements of social movement. Methodologically, this study was performed with the qualitative technique of process tracing of the basic and secondary education policy making process from 2002 to 2013. In the data collection and analysis, I conducted semi-structured and in-depth models of expert interviews involving 22 interviewees consisting of government officials, legislative members, teacher association members, NGOs, Academics, Activists, and Media experts. I also applied document analysis to policy documents, international documents, and news material related to the topic of study. From the study, it is concluded that the online movement can change the education policy making process because of three reasons: the pre-existing activists as entrepreneurs successfully evoked the public awareness to educational issues, social media created internal and external collaboration between stakeholders, and a more opened of current political opportunity in Indonesia. Furthermore, the research also reveals three roles of social media in the online movement in the Indonesian education sector, mainly in the increase of public involvement, resources mobilization, and the change of political communication. Additionally, the study revealed several other important factors. First of all, the shared feeling of deprivation in the society caused by the previous authoritarian regime had been an important entry point used by the entrepreneurs of the online movement to raise an online-based collective action. Second, the existence of pre-existing activists as top leaders in the government increased the openness of the political institutions and created a more collaborative policy making process. Finally, the political communication change resulting from the social media era created a condition where the public perception directly influences the policy making process in Indonesia
Bedeutung des subjektiven sozialen Status für die gesundheitliche Lage von Männern und Frauen in Deutschland
No full textIn health research and epidemiology, socioeconomic status (SES) is traditionally determined using objective indicators such as education, occupation, and income. Since the early 2000s, studies have additionally examined the health implications of subjective social status (SSS). Whereas objective SES indicators are used to classify people as belonging to a specific socioeconomic group, SSS describes how people self-evaluate their position in the social hierarchy and with which status group they feel affiliated. Most studies using this approach are from the USA. In Germany, research on the association between SSS and health is very scarce. This dissertation is the first study using German national data to examine the health implications of SSS among men and women living in Germany. The statistical analyses are based on cross-sectional data derived from the German General Social Survey (ALLBUS) and from the Robert Koch Institute's German Health Update (GEDA) study. Associations between SSS and several health indicators were explored using correlation and regression analysis, while adjustments were made for objective SES indicators and potential confounders. The construct validity of a German version of the MacArthur scale, which has been established internationally as a standard instrument to measure SSS, was examined using correlation and factor analysis. Low SSS was associated with physical and mental health problems in men and women. Many of the associations persisted after adjusting for objective SES indicators and potential confounders, partly with differences between men and women. Mediation analyses revealed a significant indirect relationship between objective SES and depressive symptoms through SSS. With regard to the construct validity of the German MacArthur Scale, the scale showed stronger correlations with measures of similar constructs than with measures of dissimilar constructs. Factor analysis did not show considerable loadings of the scale on external factors of mental well-being and depressiveness. This dissertation presents the first national results for Germany on the association between SSS and health. The results indicate that low SSS may have adverse health implications in men and women beyond the impact of objective SES, which is consistent with previous studies from other countries. Moreover, perceptions of social disadvantage may partly explain the link between objective SES and health. Hence, the concept of SSS offers innovative potential for describing and explaining health inequalities. Stronger theoretical grounding and longitudinal data are needed to further establish the concept of SSS in health research and epidemiology
Molecular Dynamics Simulations of the Protein Adsorption Process on Oxides
Get PDFThe adsorption of chymotrypsin and lysozyme on amorphous silica and titania is studied by molecular dynamics (MD) simulations in comparison to experiments. The simulations allow an atomistic view of the adsorption process including long-range interactions, multi-protein effects, contact analysis and surface-induced conformational changes. The surface contact stability is investigated by Steered MD simulations and Atomic Force Spectroscopy experiments. Surface-induced conformational changes are studied by classical and further developed free energy MD methods based on Metadynamics, Replica Exchange Solute Tempering and Umbrella sampling and are compared to circular dichroism experiments. The protein orientation is highly influenced by its dipole moment whereas protein binding motifs are formed mainly by positively charged amino acids. The comparison to the experiment shows that protein-protein interactions and the hydration shell of oxide and protein need to be considered as well
Reacting to uncertainty in partial Democracies : the role of negative framing in power struggles in Ukrainian energy politics, 1990s-2000s.
Get PDFThe thesis is about the processes and effects of strategic public elite communication in partial democracies, and Ukraine is used as a case study. The study is situated within the field of comparative politics that investigates the internal dynamics of partial democracies defined here as highly competitive and institutionally weak hybrid regimes. The central argument of this thesis is that the contextual uncertainty inherent in partial democracies produces incentives for political actors to rely on negative framing as a strategy in power struggles, which, in effect, reproduces contextual uncertainty. To understand how negativity functions in partial democracies, the thesis explores the psychological mechanisms of negative framing, its characteristics as a strategy, its conditions of success and effects on the political regime. It advances an innovative analytical framework that connects literatures across different subdisciplines of the social sciences. The theoretical model is derived from a qualitative study of the delegitimization of two state patronage schemes in Ukrainian gas politics. The first case study is confined to a detailed analysis of events and discourses in 1997-1998, i.e., the period when the gas patronage scheme built by the Prime Minister Pavlo Lazarenko became contested and actors involved in its operation were delegitimized. The second case study is devoted to the power struggle around the gas intermediary within the Orange coalition during the presidency of Viktor Yushchenko in 2005-2009. In both cases, I analyze how key political actors involved in these struggles construct their frames, legitimize certain actions and address accusations of misconduct and corruption. The research results show that negative framing aimed at discrediting a political opponent is standard behavior in Ukraine. Overall, such discursive practices have a very negative effect on the political regime and political culture of Ukraine. The result is a cynical population that mistrusts politics and politicians, which in turn reinforces political uncertainty and contributes to the dwindling legitimacy of the government
Signal Processing for Compressed Sensing Multiuser Detection
Get PDFThe era of human based communication was longly believed to be the main driver for the development of communication systems. Already nowadays we observe that other types of communication impact the discussions of how future communication system will look like. One emerging technology in this direction is machine to machine (M2M) communication. M2M addresses the communication between autonomous entities without human interaction in mind. A very challenging aspect is the fact that M2M strongly differ from what communication system were designed for. Compared to human based communication, M2M is often characterized by small and sporadic uplink transmissions with limited data-rate constraints. While current communication systems can cope with several 100 transmissions, M2M envisions a massive number of devices that simultaneously communicate to a central base-station. Therefore, future communication systems need to be equipped with novel technologies facilitating the aggregation of massive M2M. The key design challenge lies in the efficient design of medium access technologies that allows for efficient communication with small data packets. Further, novel physical layer aspects have to be considered in order to reliable detect the massive uplink communication. Within this thesis physical layer concepts are introduced for a novel medium access technology tailored to the demands of sporadic M2M. This concept combines advances from the field of sporadic signal processing and communications. The main idea is to exploit the sporadic structure of the M2M traffic to design physical layer algorithms utilizing this side information. This concept considers that the base-station has to jointly detect the activity and the data of the M2M nodes. The whole framework of joint activity and data detection in sporadic M2M is known as Compressed Sensing Multiuser Detection (CS-MUD). This thesis introduces new physical layer concepts for CS-MUD. One important aspect is the question of how the activity detection impacts the data detection. It is shown that activity errors have a fundamentally different impact on the underlying communication system than data errors have. To address this impact, this thesis introduces new algorithms that aim at controlling or even avoiding the activity errors in a system. It is shown that a separate activity and data detection is a possible approach to control activity errors in M2M. This becomes possible by considering the activity detection task in a Bayesian framework based on soft activity information. This concept allows maintaining a constant and predictable activity error rate in a system. Beyond separate activity and data detection, the joint activity and data detection problem is addressed. Here a novel detector based on message passing is introduced. The main driver for this concept is the extrinsic information exchange between different entities being part of a graphical representation of the whole estimation problem. It can be shown that this detector is superior to state-of-the-art concepts for CS-MUD. Besides analyzing the concepts introduced simulatively, this thesis also shows an implementation of CS-MUD on a hardware demonstrator platform using the algorithms developed within this thesis. This implementation validates that the advantages of CS-MUD via over-the-air transmissions and measurements under practical constraints
Modelling the Multispecies Fishery of Chwaka Bay, Zanzibar - Basis for Exploration of Use and Conservation Scenarios
Get PDFSmall-scale fisheries are essential livelihood and protein providers for coastal communities in developing countries. On the semi-autonomous island state Zanzibar (Tanzania) and, in particular, in Chwaka Bay, located on the east coast of the island, the dependency on small-scale fisheries is very high. Perceived decreases in individual catches and the use of destructive gears and small mesh sizes has led to concerns for an unsustainable use of the baya s fisheries resources. Particularly, the increasing use of the destructive dragnets has led to resource concerns and to strong conflicts between fishermen. However, the lack of knowledge on the state and dynamic of the fishery strongly impedes the potential for the development of proper management plans. The aim of the present dissertation is, therefore, to assess the status of Chwaka Baya s ecosystem and its fishery, as well as to evaluate potential use scenarios for a sustainable fisheries management. Furthermore, using Chwaka Bay as a reference site, the dissertation aims at approaching the answer to the question of the sustainability of Zanzibara s nearshore fisheries. The approach used in this dissertation is twofold: 1) length-based stock assessments were conducted for six of the main target species; and 2) a trophic flow model of the bay was constructed using Ecopath with Ecosim/Ecospace. The data used in both approaches were collected through an extensive field survey conducted over an annual cycle in 2014. A review of the literature about the state of Zanzibara s fisheries reveals that no fisheries assessments have been conducted after 2000. Analyses of the annual reported landings between 1990 and 2014 suggest that, except for clupeioids, none of the target groups of the fishery can be classified as overfished. Most studies aimed at evaluating the status of Zanzibara s resources have been focusing on ecological surveys and fishermena s perception. None of the ecological surveys appropriately link fishing effort and/or fishing pattern with resource state nor provide tangible thresholds for management. The stock assessment of the key target species of Chwaka Bay suggests that the exploitation rate of three out of the six target species exceeds recommended levels (E0.1). Despite high juvenile retention rates and length at first capture being below optimum length at first capture, fishing mortalities are highest for adults. Due to the nursery characteristics and the topography of the bay, juveniles might occur in higher abundances and larger fish may concentrate further outside the bay area. Consequently, an increase in mesh size only seems economically viable, if the radius of the fishery was increased to capture larger specimens outside the shallow bay area. The trophic model indicates that the Chwaka Bay ecosystem is comparatively mature. The bay is strongly bottom-up driven, with biomass concentrations around the first and second trophic level and a low overall fish biomass. The strongest impact on the ecosystem is exerted by dragnets and traps. Both gears potentially destabilize the ecosystem by reducing the biomass of top-down controlling species. Together with handlines, dragnets and traps are the least selective fishing methods. In addition, traps exert the highest fishing pressure on 4 out of the 6 selected key species. While the dragnet fishery is the least profitable, it also provides the highest number of jobs for the community, as it is a labor-intensive fishing method. Simulations of different use scenarios suggest that the elimination of dragnets would lead to the highest increase in overall fish biomass and profits. Nevertheless, this scenario would leave 58 % of fishermen without job and is, therefore, not feasible under the current lack of alternative livelihoods and the high dependency on fisheries resources. The complete reallocation of dragnets is likewise not feasible, since current effort is already high, and a further increase will lead to strong biomass reductions of target species and losses in individual profits of fishermen. Without compromising individual profits (-20 %) and biomass structure of the ecosystem (-30 %), only a part of the dragnet fishermen can be reallocated, leaving 37 % of fisher without jobs. In conclusion, the fishery of Chwaka Bay is fully exploited with some groups experiencing overfishing and does not provide scope for further expansion. Emperor fish together with similar vulnerable target resources such as Serranidae might be unsustainably harvested throughout the island. The lack of recognition for the capacity of dragnet boats to absorb surplus labour and their marginalization is likely hindering the development of feasible management plans aimed at regulating their use. In order to stop the use of dragnets on Zanzibar, management should focus on an effort control of this gear, while investing in the diversification of livelihoods
When Work Comes First: Young Adults in Vocational Education and Training in Norway
Get PDFSince reforms implemented in 1994, vocational education and training (VET) in Norway has been integrated and standardized as part of upper-secondary education. When young people enter upper-secondary education at the age of 15 or 16, they can choose either a vocational programme or a general academic programme. The standard model in vocational programmes is 2 years of school-based education, followed by 2 years of apprenticeship training. However, in practice, only a minority follow the standard route and acquire a trade certificate within 4 years. The average age upon completion of a vocational programme in Norway is 28 years, which is among the highest in the OECD. The purpose of this study was to explore personal trajectories within the Norwegian context to gain a better understanding of why people choose to obtain a trade certificate as young adults, instead of following the standardized route, drawn up by policy makers. Qualitative interviews were conducted with 34 people who obtained a trade certificate when they were aged between 25 and 35 years. The study showed that the opportunity to acquire formal VET qualifications through workplace learning provides an important second chance for many young adults in Norway. Based on the findings, we argue that policy makers need to see educational achievement in a long-term perspective and to design institutional structures that support learning opportunities at work, as well as in formal educational settings
Hazard Assessment of Liquid Organic Hydrogen Carriers (LOHCs) in Terrestrial Environment
No full textLiquid Organic Hydrogen Carriers (LOHCs) are part of a novel energy system that can efficiently and relatively safely store and transport hydrogen, which is a clean, high energy density fuel. LOHCs have high hydrogen holding capacities and are superior to most current energy sources, such as fossil fuels, because they have the potential to reduce CO2 emission and have advantages in operational and handling safety; they are also adaptable to renewable energy. Therefore, massive integration and circulation of hundreds of thousands of tons of LOHCs in the market are anticipated in the near future. However, LOHC chemicals will likely be released into the environment during the process of producing and circulating the large forecasted volumes of these compounds. In addition to the interest in developing LOHC systems to improve the technological performance, increasing attention has been focused on the behavior, fate and toxicity of LOHCs in the environment. When LOHCs enter the environment, the behavior and subsequent toxic effects of LOHCs on organisms are critical metrics used to evaluate and predict the environmental hazards of LOHCs. However, limited data are available to perform such comprehensive predictions. To help fill this gap, this thesis was conducted to characterize the potential adsorption and mobility behavior of different LOHC candidates in soils. Specifically, the organic carbon-water partition coefficient (Koc), soil-water partition coefficient (Kd) and leaching capacity of LOHCs were investigated via instrumental analyses and software predictions. These outcomes were correlated to the physicochemical properties of the compounds to determine their potential adsorption mechanisms. In general, the Koc values were correlated to hydrophobicity in the following order: indoles quinaldines carbazole derivatives benzyltoluenes dibenzyltoluene. When ionizable LOHC structures were investigated, the Kd and leaching capacity (with quinaldines as examples) revealed adsorption governed by ionic interactions. In such a case, ionization corrected octanol-water partition coefficient (log D) was found a propriate indicator for the prediction of adsorption. Ecotoxicity tests for acute and chronic toxicity were conducted in soil (quinaldines) and aquatic (quinaldines and carbazole derivatives) test scenarios. Data were compiled and integrated with the adsorption and mobility of LOHCs in soils to interpret the extent of the exposure, bioavailability and mode of toxic action. The toxicity of LOHCs appeared to be dominated by hydrophobicity. With the deduction of toxicity classification and predicted no-effect concentrations (PNECs) as well as the evaluations for the behavior and fate, a proactive assessment of the potential environmental hazards of these chemicals was ultimately conducted in the context of realistic environmental conditions and potential application quantities. A comparative analysis showed that LOHCs presented fewer potential environmental hazards than traditional energy systems (e.g., gasoline, diesel, and oil) and analogous compound structures, such as typical N-PAHs (nitrogen-substituted polycyclic aromatic hydrocarbon, which share a similar structure with certain LOHCs). Although LOHCs seem not appear to present the same hazards as these equivalent energy sources, further studies regarding several key considerations are recommended for a better understanding of the potential environmental hazards of LOHCs. The careful application of LOHCs under appropriate monitors is suggested because of the likelihood that these compounds will be used in large application volumes in the future
Ground based remote sensing of atmospheric greenhouse gases using mobile FTIR spectrometers
No full textThis work was performed at the Institute for Environmental Physics (IUP) at the University of Bremen and is divided into five parts, all referring to ground based solar absorption measurements of CO and the greenhouse gases CO 2 and CH 4 . After an introduction in chapter 2, two modifcations are discussed in chapter 3 to further improve the precision of the already well organized TCCON network. TCCON performs and provides high precision total column measurements of greenhouse gases for validating satellites, in particular OCO-2. A possible inconsistency within the phase correction during processing the spectra from the recorded interferograms was found. This could lead to irregular intensities in the spectra, separated for forward and reverse scans. For the a?ected sites, this lead to a split up of the retrieved results between forward and reverse scans of up to 1.5%, which is not acceptable for a network performing high precision data products. The issue could be fixed by modifying a parameter within the processing. Secondly an error in the time recording of the FTIR spectrometer, used within TCCON and NDACC, could be found. The timing issue lead to an error in the retrieved results within the precision of the measurements of a 0.2%, but still would increase the precision if avoided. For our automated TCCON sites, we now take the measurement time from the log files instead of the time recorded from the instrument. Chapter 4 is about including smaller mobile instruments to improve the latitudinal and longitudinal coverage and to measure with higher spatial resolution in areas of interest. To achieve this, it is desirable to increase the number of measurement sites in a cost-effective way. This work demonstrate the possibility to use smaller mobile FTIR instruments as supplement to the high standard FTIR measurement networks NDACC and TCCON. Two similar mobile high resolution spectrometer and two low resolution pendulum spectrometer have been successfully tested. In chapter 5, the prospects of a rapid data delivery are discussed, which could be performed within this work and which is already used to improve the quality of forecast models. The rapid data delivery has been set up for our TCCON sites in Orleans and Bialystok first, now also Bremen and Ny-A lesund could be included. Within chapter 6, the CO data product of the two networks NDACC and TCCON are compared in accuracy, precision and sensitivity. A different response behavior on higher CO concentrations has been found and is discussed. Finally in chapter 7, results from the mobile instruments Bruker IFS120-5M in Paramaribo, Suriname and the Bruker IFS125M in Kourovka, Russia are discussed as potential supplement to TCCON data, in regions where TCCON is not present. A CH 4 event has been identified with the retrieved data from Kourovka, and could be verified with satellite measurements from the GOSAT satellite. The cause of the enhancement could be a natural blowout, which sometimes take place in Siberia but usually not in this area, or a huge leakage of a gas pipeline