Das Handbuch Internationale Organisationen führt sowohl in relevante Theorien als auch in Ziele, Aufgaben und Strukturen konkreter Organisationen wie die Vereinten Nationen, die Europäische Union ...oder die Weltbank ein. Es vermittelt theoretische Grundlagen und spürt im lexikalischen Teil der Bedeutung ausgewählter internationaler Organisationen in der globalen Politik und ihrem Beitrag zur globalen Sicherheit und Entwicklung nach.
Phosphorylation of the inhibitory protein IkappaBalpha by the activated IkappaB kinase (IKK) is a crucial step in the activation of the transcription factor NF-kappaB. In neurons of the mammalian ...central nervous system, constitutive activation of NF-kappaB has been previously documented. The cellular compartments involved in this activation have not yet been fully identified. Here we document a striking enrichment of several molecules involved in NF-kappaB activation in the axon initial segment (AIS) of neurons: Phosphorylated-IkappaBalpha (pIkappaBalpha), activated IKK, and p65 phosphorylated at serine 536 were found to be enriched in the AIS in vivo as well as in vitro. Both, pIkappaBalpha and activated IKK, were associated with cytoskeletal components of the AIS. Activated IKK was associated with the membrane cytoskeleton, whereas pIkappaBalpha was sequestered to microtubules of the AIS. Colchicine-induced depolymerization of microtubules resulted in the loss of pIkappaBalpha in the AIS, demonstrating that the integrity of the axonal cytoskeleton is essential for the clustering of this NF-kappaB pathway component. These data provide the first evidence for a compartmentalized clustering of NF-kappaB pathway components in the AIS and implicate this neuronal compartment in the activation of NF-kappaB.
Mutations in the amyloid precursor protein (APP) gene are known as causative factors in the pathogenesis of early-onset familial Alzheimer's disease (FAD). In this study, the influence of the Swedish ...double-mutation form of APP (APPsw; KM670/671NL) on apoptosis regulation in PC12 cells was investigated. APPsw-transfected PC12 cells were compared with wild-type APP (APPwt)-expressing and vector-transfected PC12 cells with regard to their susceptibility to cell death induced by the reduction of trophic support or by additional treatment with staurosporine. Expression of APPsw markedly enhanced the level of apoptotic PC12 cells induced by serum reduction. A similar hypersensitivity of APPsw-expressing PC12 cells could be detected after differentiation with nerve growth factor under serum-reduced conditions. Likewise, the expression of APPsw rendered PC12 cells more vulnerable to staurosporine but only under serum-reduced conditions. This APPsw-effect disappeared in high serum-containing medium. Thus, expression of APPsw seems to enhance cellular sensitivity not in general but after the reduction of trophic factors probably by causing oxidative stress. This, in turn, may sensitize cells to secondary apoptotic stimuli. Moreover, the mutation-specific increase in vulnerability to cell death was only seen at the stage of apoptotic nuclei, but not using methods measuring cell death by determining metabolic activity or membrane integrity. Therefore, the expression of APPsw seems to affect specifically apoptotic cell death rather than overall cell death in vitro. Our study further emphasizes the pathogenic role of mutant APP and may provide new insights in the mechanisms underlying the massive neurodegeneration in brain from patients bearing the APPsw mutation.
How does the way we think and feel about the world around us affect the existence and administration of the death penalty? What role does capital punishment play in defining our political and ...cultural identity?After centuries during which capital punishment was a normal and self-evident part of criminal punishment, it has now taken on a life of its own in various arenas far beyond the limits of the penal sphere. In this volume, the authors argue that in order to understand the death penalty, we need to know more about the "cultural lives"—past and present—of the state's ultimate sanction. They undertake this "cultural voyage" comparatively—examining the dynamics of the death penalty in Mexico, the United States, Poland, Kyrgyzstan, India, Israel, Palestine, Japan, China, Singapore, and South Korea—arguing that we need to look beyond the United States to see how capital punishment "lives" or "dies" in the rest of the world, how images of state killing are produced and consumed elsewhere, and how they are reflected, back and forth, in the emerging international judicial and political discourse on the penalty of death and its abolition. Contributors: Sangmin Bae Christian Boulanger Julia Eckert Agata Fijalkowski Evi GirlingVirgil K.Y. Ho David T. Johnson Botagoz Kassymbekova Shai LaviJürgen Martschukat Alfred Oehlers Judith RandleJudith Mendelsohn RoodAustin Sarat Patrick TimmonsNicole Tarulevicz Louise Tyler
Situation-Based Policy Enforcement Buntrock, Thomas; Esperer, Hans-Christian; Eckert, Claudia
Trust, Privacy and Security in Digital Business
Book Chapter
Peer reviewed
Current operating systems enforce access control policies based on completely static rules, a method originating from a time where computers were expensive and had to serve several users ...simultaneously. Today, as computers are cheap, a trend to mobile workstations can be realized, where a single device is used to perform a dedicated task under unpredictable, changing conditions. However, the static access rules still remain, while their use in mobile environments is limited, because in changing environments, access rights must constantly be adjusted to guarantee data integrity in all situations. With dynamically adjusting rules, in turn, it is not sufficient anymore to check access to data only once; instead, access rights must be revalidated every time data is actually accessed, even if part of that data is cached by an application. In this paper, we present a method to dynamically and retrospectively enforce access control policies based on the context a device is operating in, while tracing data beyond disk accesses.
Proteoglycans and collagen molecules are interacting with each other thereby forming various connective tissues. The sulfation pattern of proteoglycans differs depending on the kind of tissue and/or ...the degree of maturation. Tissues from Cnidaria are suitable examples for exploration of the effects in relation to the presence and the absence of sulfate groups, when studying characteristic fragments of the long proteoglycan carbohydrate chains in silico. It has been described that a non-sulfated chondroitin appears as a scaffold in early morphogenesis of all nematocyst types in Hydra. On the other hand, sulfated glucosaminoglycans play an important role in various developmental processes of Cnidaria. In order to understand this biological phenomenon on a sub-molecular level we have analysed the structures of sulfated and non-sulfated proteoglycan carbohydrate chains as well as the structure of diverse collagen molecules with computational methods including quantum chemical calculations. The strong interactions between the sulfate groups of the carbohydrates moieties in proteoglycans and positively charged regions of collagen are essential in stabilizing various Cnidaria tissues but could hinder the nematocyst formation and its proper function. The results of our quantum chemical calculations show that the sulfation pattern has a significant effect on the conformation of chondroitin structures under study.
In the family of cytokines and cytokine receptors, alternative splicing of pre-mRNA is a frequently observed process that generates different protein isoforms from a single genetic locus. The ...splicing-derived cytokine receptor protein isoforms are mostly soluble receptors or show alterations in their cytoplasmic domain. It is possible that receptor abnormalities or a pathological ratio of different isoforms may contribute to leukaemia by circumventing normal growth factor control or altering the balance of proliferation and differentiation. IL-7 plays a critical role in early stages of both B and T cell maturation. Moreover, it stimulates the expansion of mature T cells including anti-tumour reactive cells as well as a number of T and B cell malignancies underlining its potential importance for deregulated lymphoid proliferation and leukaemogenesis. Here, we present detailed data on the expression of the interleukin 7 receptor α chain (IL-7Rα) in leukaemic cells from 210 children with acute lymphoblastic leukaemia (ALL) and describe two novel alternatively spliced transcripts of human IL-7Rα coding for truncated receptor proteins which are still capable of binding IL-7. IL-7Rα mRNA expression was more frequent in more mature pre-B ALL 91% (30/33) than in common 81% (81/100) or pro-B ALL 64% (18/28), or even in T ALL 64% (29/45). These results are in concordance with flow cytometric analyses on the proportion of IL-7Rα bearing cells among total blast cell population. Our results lead us to assume that splicing derived IL-7Rα isoforms play a potential role in modulating IL-7 signal transduction and might be important for the pathogenesis of leukaemia.
We report velocity measurements in a vertical turbulent convection flow cell that is filled with the eutectic liquid metal alloy gallium-indium-tin by the use of local Lorentz force velocimetry ...(LLFV) and ultrasound Doppler velocimetry (UDV). We demonstrate the applicability of LLFV for a thermal convection flow and reproduce a linear dependence of the measured force in the range of micronewtons on the local flow velocity magnitude. Furthermore, the presented experiment is used to explore scaling laws of the global turbulent transport of heat and momentum in this low-Prandtl-number convection flow. Our results are found to be consistent with theoretical predictions and recent direct numerical simulations.
Increasing evidence suggests an important role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease. Thus,
we investigated the effects of acute and chronic exposure to increasing ...concentrations of amyloid β (Aβ) on mitochondrial
function and nitric oxide (NO) production in vitro and in vivo . Our data demonstrate that PC12 cells and human embryonic kidney cells bearing the Swedish double mutation in the amyloid
precursor protein gene (APPsw), exhibiting substantial Aβ levels, have increased NO levels and reduced ATP levels. The inhibition
of intracellular Aβ production by a functional γ-secretase inhibitor normalizes NO and ATP levels, indicating a direct involvement
of Aβ in these processes. Extracellular treatment of PC12 cells with comparable Aβ concentrations only leads to weak changes,
demonstrating the important role of intracellular Aβ. In 3-month-old APP transgenic (tg) mice, which exhibit no plaques but
already detectable Aβ levels in the brain, reduced ATP levels can also be observed showing the in vivo relevance of our findings. Moreover, we could demonstrate that APP is present in the mitochondria of APPsw PC12 cells. This
presence might be directly involved in the impairment of cytochrome c oxidase activity and depletion of ATP levels in APPsw PC12 cells. In addition, APPsw human embryonic kidney cells, which
produce 20-fold increased Aβ levels compared with APPsw PC12 cells, and APP tg mice already show a significantly decreased
mitochondrial membrane potential under basal conditions. We suggest a hypothetical sequence of pathogenic steps linking mutant
APP expression and amyloid production with enhanced NO production and mitochondrial dysfunction finally leading to cell death.
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