219 research outputs found

    Group membership and its adverse psychological effects in \u3cem\u3eThe Ox-Bow Incident\u3c/em\u3e

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    This paper examines and analyzes the causes and motivations of groups in the book The Ox-Bow Incident

    Radical Right Populist Parties in Britain and the Netherlands: Explaining Electoral Success

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    Radical right-wing populist parties have recently emerged throughout Europe, but the electoral success among these parties is incredibly inconsistent. In the Netherlands, Geert Wilders’ Dutch Party for Freedom (PVV) has become established in the country’s political system, while the British National Party (BNP) and the United Kingdom Independence Party (UKIP) struggle to gain even a single seat in British parliament. Models outlining a formula for the rise and success of populist parties can help explain why some parties achieve an electoral breakthrough and others do not. Researcher of radical right populism Pippa Norris’ model of electoral success is divided into a political demand side that focuses on the public grievances driving these parties, and a political supply side that focuses on internal party activity as well as external factors shaping opportunity structure. This essay compares Britain’s two radical right populist parties, the BNP and the UKIP, with the PVV in the Netherlands, and applies Norris’ framework to explain the greater electoral success of the PVV. It concludes that while Britain and Netherlands are similar in terms of political demand, populist parties have seen more success in the Netherlands because supply-side factors are more favorable

    Simulation of the Eemian Greenland ice sheet

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    This thesis focuses on the simulation of the Greenland ice sheet (GrIS) during the Eemian interglacial period (~125,000 years ago). The warm Eemian summers on Greenland are used as a past analogue for future warmer conditions. The aim of this work is a contribution to the improvement of future sea level rise predictions and to better understand how model uncertainties propagate through the chain of models necessary to simulate ice sheet evolution in past climates. Firstly, the influence of surface mass balance (SMB) models and climate model resolution on the simulation of the Eemian SMB is investigated. The corresponding study shows that both, the selection of the SMB model as well as the climate model resolution are essential for simulating the Eemian SMB, and either of these two factors can have a dominating effect on the results. However, which factor dominates the results depends on the climate state (cold or warm) and particularly the prevailing insolation regime. It is shown that an inclusion of insolation in the selected SMB model is essential for the simulated warm early Eemian conditions. Secondly, the influence of SMB forcing on millennial time scale ice sheet modeling is tested. The simulations with two different SMB forcings reveal a large difference in the evolution of the ice sheet, while ice flow sensitivity tests with changed basal friction and changed ice flow approximation show small differences. Thirdly, regional climate simulations with a full surface energy balance model are analyzed focusing on Greenland surface melt. This analysis shows that all Greenland ice core locations, also GRIP near the summit of Greenland, are affected by surface melt during the Eemian interglacial period. Elevated levels of Eemian surface melt indicate that ice cores might be affected more strongly than previously considered. Therefore, caution needs to be applied when interpreting Greenland ice core records from warm periods such as the Eemian interglacial period. This thesis shows that forcing from a single climate model can lead to a wide range of SMBs and ice sheets. To quantify this large uncertainty, a systematic approach of model intercomparison, similar to what is used to constrain future climate projections, is advised. Climate and SMB model biases and uncertainties need to be explored and outliers rejected, to be able to provide a most likely range for the Eemian GrIS topography and its contribution to sea level

    Judicial Practice Makes Perfect: Explaining Asylum Recognition in the European Union

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    Vast disparities in asylum recognition rates have persisted in the European Union despite legislative efforts to standardize the asylum determination process. National judiciaries play an important role in this process and scholars mostly agree that differences in judicial practice pose a challenge to the harmonization of recognition rates. However, no study has specifically analyzed the relationship between these two variables. The aim of this research is to determine whether differences in judicial practice account for the variation in asylum recognition rates in the EU. To observe these differences, precedent relating to three areas of the refugee determination process is identified in selected EU states. Application of this precedent is then analyzed in order to identify restrictive judicial practices. Analyses reveal that differences in judicial practice impact the outcomes of asylum cases, and therefore recognition rates

    A review of hydrophilic silicon wafer bonding

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    Hydrophilically activated direct wafer bonding is a technique for gluelessly attaching oxide-coated wafers together. This ability is a vital step in the construction of many microelectronic and microelectromechanical (MEMS) devices. In particular this technique is widely used in the production of 3d interconnected devices due to the lack of interlayer

    Evolution of substrate specificity and protein-protein interactions in three enzyme superfamilies

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    Superfamilies are a classification system to combine proteins that are related through a common evolutionary origin, share similar sequences, structures, and core reaction mechanisms, but exert different functions. Today, for most superfamilies tens of thousands of sequences and hundreds of structures are known and most of the different functions of their members have been elucidated. Superfamilies thus provide a formal and biologically sensible framework to study evolutionary relationships between proteins. In the present work, the frameworks of three enzyme superfamilies were utilized to get insights into several important aspects of enzyme evolution. The first part of this work addresses the question how enzymatic mono- and bi-functionality have evolved in the superfamily of ribose-binding (βα)8-barrel sugar isomerases. This superfamily contains the homologous enzymes HisA and TrpF, which catalyze similar reactions in histidine and tryptophan biosynthesis, as well as the bi-functional enzyme PriA, which catalyzes both the HisA and TrpF isomerization reactions. HisA and TrpF are ubiquitous in Archaea and Bacteria, whereas PriA is only found in certain Actinobacteria. These species have lost the dedicated TrpF enzyme and PriA is consequently part of both tryptophan and histidine biosynthesis. Much has been speculated on the evolutionary relationship of these enzymes and whether the bi-functionality of PriA is a remnant from ancient evolutionary times or a more recent development in Actinobacteria. Using ancestral sequence reconstruction it was demonstrated in this work that evolutionary ancestors of modern HisA enzymes display bi-functionality, reminiscent of PriA. A detailed enzymatic characterization of three reconstructed HisA ancestors showed that they catalyze not only the HisA but also the TrpF reaction with comparable catalytic efficiencies in vitro. Metabolic complementation experiments with hisA and trpF deficient Escherichia coli strains furthermore demonstrated that the bi-functional HisA ancestors could support both histidine and tryptophan biosynthesis in vivo. By a combination of sequence- and network-based in silicomethods, several modern HisA enzymes were subsequently identified that possess sequence motifs typical for bi-functional PriA enzymes. The enzymatic characterization of three such modern HisA representatives revealed that they are also bi-functional, albeit to a lesser extent, although the respective organisms possess dedicated TrpF enzymes. Thus, the ancestral bi-functionality has pertained for billions of years in HisA enzymes, without any obvious selective pressure. Consequently, a new model for the evolution of HisA, TrpF, and PriA was proposed: The bi-functionality of ancient HisA variants may have played an important role in maintaining early metabolism by supporting both histidine and tryptophan biosynthesis. After the emergence of dedicated TrpF enzymes the bi-functionality of the ancestors became expendable and diminished to the level observed in modern HisA enzymes. However, the inherent bi-functionality of HisA contributed to the robustness of microbial metabolism and made possible to compensate the loss of a dedicated trpF gene in some Actinobacteria. In these organisms, the available bi-functionality of HisA was exploited, selected for, and enhanced, which eventually led to the modern PriA enzymes. The second part of this work deals with the evolution of substrate specificity and secondary metabolic enzymes in a superfamily of chorismate-utilizing enzymes, named MST-superfamily. Chorismate is a central metabolic node molecule and the starting point for the biosynthesis of various important metabolites, including aromatic amino acids, folate, or iron-chelating siderophores. The MST-enzymes catalyze the committed steps of these biosynthetic pathways and are highly similar in sequence, structure, and reaction mechanism. However, the MST-enzymes that are part of primary metabolic pathways employ exclusively ammonia as a nucleophile to aminate chorismate, whereas those that are part of secondary metabolic pathways exclusively employ water as a nucleophile to hydroxylate chorismate. Based on the notion that secondary metabolic enzymes are descendants of primary metabolic ones, it was investigated in this part of this work by which mechanism the transition from primary metabolic to secondary metabolic MSTenzymes went along with a change in nucleophile-specificity from ammonia to water. Initially, network-based, phylogenetic, and structure-based in silicomethods were applied to identify two key amino acids in the nucleophile access channel of the active site that distinguish primary-metabolic/ammonia-utilizing and secondary-metabolic/water-utilizing MST-enzymes. The importance of these key positions was subsequently examined by rationally designing sixteen variants of the MST-enzyme anthranilate synthase, which normally employs ammonia as a nucleophile. The enzymatic characterization of these variants by HPLC-MS showed that the right combination of amino acids at the two key positions indeed resulted in a broadening of nucleophile specificity to also include water. These anthranilate synthase variants hydroxylated chorismate and formed isochorismate with efficiencies comparable to native secondary-metabolic/water-utilizing isochorismate synthases. Moreover, these variants were still able to employ ammonia as a nucleophile and formed their native product anthranilate; hence they were bi-functional. These experiments demonstrated that nucleophile specificity in the MST-superfamily can readily switch from ammonia to water. Moreover, the observed bi-functionality of the anthranilate synthase variants argues that the evolution of secondary metabolic MST-enzymes may have proceeded through bi-functional intermediates. Such metabolic generalists may have allowed for the formation of novel metabolites (isochorismate) while maintaining the formation of important primary metabolic metabolites (anthranilate). This scenario consequently does not a priorirequire gene duplication events and thus precludes negative metabolic effects linked to retaining redundant gene copies. The third part of this work pursues the question how protein-protein interaction specificity is assured in superfamilies of structurally related protein complexes and how the determinants of interaction specificity have evolved. Specific interactions between proteins are vital for almost all cellular functions. This specificity is usually achieved by shape and electrostatic complementarity of protein interfaces. However, the number of different protein folds and interface geometries found in Nature is limited, due to the constraints imposed by efficiently packing hydrogen-bonded secondary structure elements. It is thus a challenging question how interaction specificity is achieved despite structural limitations and how the formation of non-physiological complexes is avoided when several possible interaction partners with similar interface geometries are available. In order to address this problem, initially a comprehensive computational survey of the interface geometries of over 300 bacterial, heteromeric protein complexes and all their homologs of respective superfamilies was performed. This survey revealed that in about 10% of the superfamilies interface geometries vary significantly between related complexes that share homologous subunits. In these cases interfaces were extended by socalled interface add-ons, which typically comprise 10-20 amino acids, form well-defined secondary structure elements, and significantly contribute to complex stability. These characteristics suggested that interface add-ons differentiate between structurally related protein complexes and contribute to interaction specificity through negative design. In order to back this assumption, the case of the interface add-on found in a superfamily of glutamine amidotransferase complexes involved in tryptophan and folate biosynthesis was subsequently analyzed in detail. These complexes comprise synthase and glutaminase subunits that interact to transfer ammonia from glutamine to an acceptor substrate. A subset of synthase subunits exclusively involved in tryptophan biosynthesis contains the interface add-on, whereas it is absent in all other homologous synthase subunits, including those exclusively involved in folate biosynthesis. The comprehensive experimental characterization of 54 combinations of different synthase and glutaminase subunits by chromatographic methods, light scattering, mass spectrometry, and enzyme kinetics demonstrated that the presence or absence of the interface add-on determines interaction specificity. An in silicogenetic profiling of over 15000 archaeal and bacterial genomes together with in vivogrowth assays showed that the interface add-on found in complexes of tryptophan biosynthesis is biologically relevant for preventing cross-interactions with the homologous complexes of folate biosynthesis, which would lead to harmful metabolic cross-talk that negatively affects cellular fitness. It was finally shown by protein design that the evolution of the interface add-on in these complexes most likely proceeded via intermediary complexes with relaxed interaction specificity. In conclusion, this part of this work demonstrates that interface add-ons are evolutionary tools to facilitate interaction specificity in superfamilies of homologous proteins or in cases where a protein has to discriminate between several potential interaction partners that share similar interface geometries. In summary, the presented work leads to an improved understanding of the mechanisms behind the evolution of enzymatic mono- and bi-functionality, emphasizes the importance of generalist, bi- or multi-functional enzymes for the evolution of secondary metabolic pathways, and finally describes a so far overlooked structural tool for the evolutionary specification of protein-protein interactions

    COVID-19 policy interventions and fertility dynamics in the context of pre-pandemic welfare support

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    This paper focuses on nonpharmaceutical interventions (NPIs) to explain fertility dy-namics during the pandemic, while considering countries’ institutional context. Weargue that containment policies disrupted people’s lives and increased their uncer-tainty more in countries with weak welfare support systems, while health-relatedand economic support NPIs mitigated such disruptions much more there, as theywere less expected by citizens. We estimate monthly “excess” crude birth rates (CBRs)and find that countries with low public support—Southern Europe, East Asia, andEastern Europe—experienced larger decreases and less of a rebound in CBRs thancountries with histories of high public spending—Western, Central, and NorthernEurope. However, in low support countries, NPIs are much more strongly associ-ated with excess CBRs—containment NPIs more negatively and health and economicsupport NPIs more positively—with the exception of the one-month lag of contain-ment NPIs, for which the opposite holds. When putting these coefficients into broaderperspective, our findings suggest that the actual implementation of all NPIs takentogether mitigated fertility declines. This is especially the case for low public supportcountries, whereas one might have seen a birth decline even in high support countriesif the NPIs were not implemented
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