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The estimation of water balance components as well as water-related indicators on the land surface by means of global hydrological models have evolved in recent decades. Results of such models are frequently used in global- and continental-scale assessments of the current and future state of the terrestrial water cycle and provide a valuable data basis, e.g., for the Intergovernmental Panel on Climate Change. The Water – Global Assessment and Prognosis (WaterGAP) model is one of the state-of-the-art models in that field and has been in development and application for around 20 years. The evaluation, modification and application of WaterGAP is the subject of this thesis. In particular, the sensitivity of climate input data on radiation calculation and simulated water fluxes and storages is evaluated in the first part. Effects of model modification such as updated spatial input datasets, improved process representation or an alternative calibration scheme are the focus of the second part. Finally, three applications of WaterGAP give insight into the capabilities of that model, namely an estimate of global and continental water balance components, an assessment of groundwater depletion and the impact of climate change on river flow regimes. Model experiments, which are described in six journal papers as well as the appendices, were used as the basis for answering the total of 13 research questions. One of the major foci was to quantify the sensitivity of simulated water fluxes and storages to alternative climate input data. It was found that the handling of precipitation undercatch leads to the greatest difference in water balance components, especially in those areas where WaterGAP is not calibrated due to a lack of river discharge observations. The modifications of WaterGAP in the last few decades has led in general to an improved simulation of monthly river discharge, but process representation in semi-arid and arid regions still requires improvements. With the most current model version, WaterGAP 2.2b, and for the time period 1971–2000, river discharge to the oceans and inland sinks is estimated to be 40 000 km3 yr-1, whereas actual evapotranspiration is simulated as 70 500 km3 yr-1. Future research needs for WaterGAP in particular but also for the global hydrological model community in general are defined, promoting a community-driven effort for a robust assessment of the continental water cycle.
In this paper we propose a way forward towards increased financial resilience in times of growing disagreement concerning open borders, free trade and global regulatory standards. In light of these concerns, financial resilience remains a highly valued policy objective. We wish to contribute by suggesting an agenda of concrete, do-able steps supporting an enhanced level of resilience, combined with a deeper understanding of its relevance in the public domain.
First, remove inconsistencies across regulatory rules and territorial regimes, and ensure their credibility concerning implementation. Second, discourage the use of financial regulatory standards as means of international competition. Third, give more weight to pedagogically explaining the established regulatory standards in public, to strengthen their societal backing.
Die Berichterstattung über den Nahostkonflikt gehört seit Jahrzehnten zum Standardrepertoire der Nachrichten. Hierzulande hat fast jeder eine Meinung zum israelisch-arabischen Konflikt, doch wenige verstehen, um was es den Konfliktparteien eigentlich geht, was in bisherigen Verhandlungen erreicht worden ist und wo genau die Hürden für eine Konfliktregelung liegen. Dieses Buch liefert eine kompakte und zugleich anschauliche und detaillierte Analyse des Konflikts zwischen Israel und seinen arabischen Nachbarn. Dabei stehen die lokalen und regionalen Akteure im Mittelpunkt. Um die Konfliktdynamiken zu erklären, geht das Buch vor allem auf die konkurrierenden Interessen und Narrative der Konfliktparteien sowie ihre Wechselwirkungen ein.
Background: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active ‘probe’ molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors. Here we describe the use of a high-content cellular immunofluorescence assay as a method for demonstrating target engagement in cells.
Results: A panel of assays for the Jumonji C subfamily of KDMs was developed to encompass all major branches of the JmjC phylogenetic tree. These assays compare compound activity against wild-type KDM proteins to a catalytically inactive version of the KDM, in which residues involved in the active-site iron coordination are mutated to inactivate the enzyme activity. These mutants are critical for assessing the specific effect of KDM inhibitors and for revealing indirect effects on histone methylation status. The reported assays make use of ectopically expressed demethylases, and we demonstrate their use to profile several recently identified classes of KDM inhibitors and their structurally matched inactive controls. The generated data correlate well with assay results assessing endogenous KDM inhibition and confirm the selectivity observed in biochemical assays with isolated enzymes. We find that both cellular permeability and competition with 2-oxoglutarate affect the translation of biochemical activity to cellular inhibition.
Conclusions: High-content-based immunofluorescence assays have been established for eight KDM members of the 2-oxoglutarate-dependent oxygenases covering all major branches of the JmjC-KDM phylogenetic tree. The usage of both full-length, wild-type and catalytically inactive mutant ectopically expressed protein, as well as structure-matched inactive control compounds, allowed for detection of nonspecific effects causing changes in histone methylation as a result of compound toxicity. The developed assays offer a histone lysine demethylase family-wide tool for assessing KDM inhibitors for cell activity and on-target efficacy. In addition, the presented data may inform further studies to assess the cell-based activity of histone lysine methylation inhibitors.
The amyloid precursor protein (APP) was discovered in the 1980s as the precursor protein of the amyloid A4 peptide. The amyloid A4 peptide, also known as A-beta (Aβ), is the main constituent of senile plaques implicated in Alzheimer’s disease (AD). In association with the amyloid deposits, increasing impairments in learning and memory as well as the degeneration of neurons especially in the hippocampus formation are hallmarks of the pathogenesis of AD. Within the last decades much effort has been expended into understanding the pathogenesis of AD. However, little is known about the physiological role of APP within the central nervous system (CNS). Allocating APP to the proteome of the highly dynamic presynaptic active zone (PAZ) identified APP as a novel player within this neuronal communication and signaling network. The analysis of the hippocampal PAZ proteome derived from APP-mutant mice demonstrates that APP is tightly embedded in the underlying protein network. Strikingly, APP deletion accounts for major dysregulation within the PAZ proteome network. Ca2+-homeostasis, neurotransmitter release and mitochondrial function are affected and resemble the outcome during the pathogenesis of AD. The observed changes in protein abundance that occur in the absence of APP as well as in AD suggest that APP is a structural and functional regulator within the hippocampal PAZ proteome. Within this review article, we intend to introduce APP as an important player within the hippocampal PAZ proteome and to outline the impact of APP deletion on individual PAZ proteome subcommunities.
We compare the cost effectiveness of two pronatalist policies:
(a) child allowances; and
(b) daycare subsidies.
We pay special attention to estimating how intended fertility (fertility before children are born) responds to these policies. We use two evaluation tools:
(i) a dynamic model on fertility, labor supply, outsourced childcare time, parental time, asset accumulation and consumption; and
(ii) randomized vignette-survey policy experiments.
We implement both tools in the United States and Germany, finding consistent evidence that daycare subsidies are more cost effective. Nevertheless, the required public expenditure to increase fertility to the replacement level might be viewed as prohibitively high.
We extend the classical ”martingale-plus-noise” model for high-frequency prices by an error correction mechanism originating from prevailing mispricing. The speed of price reversal is a natural measure for informational efficiency. The strength of the price reversal relative to the signal-to-noise ratio determines the signs of the return serial correlation and the bias in standard realized variance estimates. We derive the model’s properties and locally estimate it based on mid-quote returns of the NASDAQ 100 constituents. There is evidence of mildly persistent local regimes of positive and negative serial correlation, arising from lagged feedback effects and sluggish price adjustments. The model performance is decidedly superior to existing stylized microstructure models. Finally, we document intraday periodicities in the speed of price reversion and noise-to-signal ratios.
Fit to play : posture and seating position analysis with professional musicians - a study protocol
(2017)
Background: Musical performance-associated musculoskeletal disorders (MSD) are a common health problem among professional musicians. Considering the manifold consequences arising for the musicians, they can be seen as a threat for their professional activity. String players are the most affected group of musicians in this matter. Faults in upper body posture while playing the instrument, causing un-ergonomic static strain on the back and unergonomic limp-movements, are a main reason for musculoskeletal disorders and pain syndromes.
Methods: A total of 66 professional musicians, divided into three groups, are measured.
The division is performed by average duration of performance, intensity of daily exercise and professional experience. Video raster stereography, a three-dimensional analysis of the body posture, is used to analyse the instrument-specific posture. Furthermore the pressure distribution during seating is analysed. Measurements are performed because the musician is sitting on varying music chairs differing in structure and/or construction of the seating surface. The measurements take place in habitual seating position as well as during playing the instrument.
Results: To analyse the influence of different chairs, ANOVA for repeated measurements or Friedman-test is used, depending on normality assumptions. Comparison of posture between amateur musicians, students, and professional orchestral musicians is carried out the non-parametric Jonckheere-Terpstra-test.
Conclusions: Our method attempts to give the musicians indications for the right music chair choice by analyzing the chair concepts, so that thereby preemptively MSD can be reduced or prevented.
The critical debates of liberal peace are grounded in a "paradox of liberalism" (Sabaratnam 2013): Western liberalism is criticized as oppressive, colonial and bellicose, but also implicitly relied on as the source of emancipation. This has not rejected in a rejection of liberal interventionism, but rather in demands for more cultural sensitivity, more local participation or an efficient control to save the idea of liberal peace...
Die Wahlen über den Verbleib Großbritanniens in der EU haben die europäische Ordnung erschüttert. Der Vortrag/Die Präsentation soll nicht nur die Hintergründe beleuchten, sondern auch zeigen, welche Chancen die neue Situation eröffnet, Chancen, die es vorher so nicht gegeben hat...
"European" interventions
(2017)
While conflicts can be managed and resolved to the extent of peace keeping, evolving to state of peace and peace society is a far larger and challenging experience. The armed forces by definition and global practice are nurtured and trained to violence. However, it takes a lot more time and enough maturity and strength for a non-violent struggle...
Far-right parties gained considerable support in many European countries in recent years. Austria comes within a whisker of becoming the first country in the history of the European Union to elect a far-right president, Horbert Hofer, the candidate from the Freedom Party. Similarly, in France, Marie Le Pen is expected to be Front National’s (FN) candidate in the 2017 presidential election and probably to make it to the second round of voting...
Security, arms control, disarmament and confidence building measures in the Baltic sea region
(2017)
Taking into consideration the stalemete of all disarmament negotiations as well as the worsening situation in the Baltic Sea region, I would like to present another paper as well, discussing the security trends in the Baltic Sea region and the potential of confidence building measures in this region as well as to discuss in this context the prospects of arms control and disarmament in general as well as specifically in Europeparticularly in the Baltic Sea region...
Conflict and insecurity have largely been the major driving factors behind the current wave of population influx in Europe. It is desirable that to understand the current migrant crisis in Europe, it is essential to understand the nature of the on-going conflict and existing insecurities in the home states from where the migrants are coming...
When Donald Trump arrived to power, many experts were concerned regarding his ideas on U.S. nuclear weapons. Particular attention was paid to his tweet about strengthening the U.S. nuclear arsenal after 25 years of the consistent WMD-disarmament under "The Cooperative Threat Reduction Program" (aka "Nunn-Lugar Program" an array of START treaties). In that preiod, U.S. and Russia removed more than 8,000 warheads and elements of the nuclear triad – submarines, ICBMs and long-range bombers. Now, experts worry that Trump’s aspirations will bury the U.S.-Russian nuclear cooperation aimed at global security...
Rethinking concepts of peace
(2017)
Motivated by a structural blind spot of Peace Studies regarding the (manifoldness of) definitions of its central concept "peace", I argue that this blind spot is especially manifested in the Eurocentric view on peace. My claim: Non-"Western" concepts of peace should be considered more in Peace Studies...
The overall aim of my work is to contribute to a future theory of epistemic violence – thereby enabling us to gain a better understanding of the various forms of direct, physical violence which are usually analysed within peace studies, IR, political theory and related fields. My perspective starts from transdisciplinary peace studies, is concerned with the sociology of knowledge, and informed by post- and de-colonial theory as well as by feminist critique and political theory...
For feminists, reflexivity has always meant more than a methodological tool...
AFK-EUPRA – 13 : feminist interventionism, postcolonial critique and non-western feminist approaches
(2017)