Universitätspublikationen
Refine
Year of publication
- 2015 (1739) (remove)
Document Type
- Article (603)
- Doctoral Thesis (187)
- Working Paper (169)
- Contribution to a Periodical (164)
- Book (159)
- Report (157)
- Part of Periodical (124)
- Review (70)
- Preprint (55)
- Conference Proceeding (22)
- magisterthesis (7)
- Part of a Book (6)
- Master's Thesis (5)
- Periodical (5)
- Bachelor Thesis (4)
- Habilitation (1)
- Magister's Thesis (1)
Language
- English (863)
- German (835)
- Spanish (14)
- Italian (11)
- Portuguese (11)
- French (3)
- Multiple languages (1)
- Russian (1)
Is part of the Bibliography
- no (1739)
Keywords
- Islamischer Staat (34)
- IS (25)
- Terrorismus (23)
- Deutschland (16)
- Dschihadismus (13)
- Syrien (12)
- Terror (11)
- Irak (10)
- Islamismus (10)
- Salafismus (10)
Institute
- Präsidium (336)
- Medizin (252)
- Gesellschaftswissenschaften (230)
- Physik (184)
- Wirtschaftswissenschaften (149)
- Exzellenzcluster Die Herausbildung normativer Ordnungen (116)
- Center for Financial Studies (CFS) (115)
- Biowissenschaften (99)
- Informatik (96)
- Frankfurt Institute for Advanced Studies (FIAS) (95)
In der ersten Netzschau im Neuen Jahr geht es um das (vermeintliche) Aussterben des Folterverbots in den USA, Drohnen in Europa, Demokratisierungstrends in den kommenden zehn Jahren, die Finanzierung des UN-Menschenrechtspfeilers und die Konkurrenz zwischen al Qaida und dem Islamischen Staat – auch im Lichte der Anschläge von Paris.
Die AG Internationale Beziehungen der Deutschen Nachwuchsgesellschaft für Politik- und Sozialwissenschaft (DNGPS) hält die Fachtagung 2016 zum Thema “Gesucht: Europäische Außenpolitik” vom 16. bis 18. März 2016 in Trier ab. Alle weiteren Infos findet Ihr im Call for Paper, der sich an Studierende und Promovierende richtet!
Vom 14. bis 15. Januar 2016 findet in Kassel eine Konferenz zum Thema "Beyond the Master's Tools: Post- and Decolonial Approaches to Research Methodology and Methods in the Social Sciences" statt. Veranstaltet wird die Konferenz von den Fachbereichen Postkoloniale Studien und Soziologie der Diversität der Universität Kassel.
Die HBO-Serie The Wire erzählt eine Geschichte von Kriminalität, Polizeiarbeit und Politik in Baltimore. Eine ihrer Stärken liegt darin, wie sie die Ambivalenz des sozialen und politischen Lebens nachzeichnet. Eine zentrale Rolle spielt dabei allgegenwärtige Korruption. Ihre Ambivalenz bricht sich nicht zuletzt in der Darstellung der Figur des State Senator Clay Davis.
Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body's regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting "blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation". In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs.
Promove-se uma recuperação do debate endógeno estabelecido entre alguns pensadores da Escola de Frankfurt, sobretudo no que se refere às diferentes perspectivas de análise sobre as relações entre ação e estrutura social, bem como as distintas percepções acerca das racionalidades (prática ou comunicativa) que organizam a conexão entre os indivíduos e a sociedade. Verifica-se o modo como os autores ligados à teoria crítica compreenderam as relações entre esferas subjetivas e estruturais em termos de possibilidades de emancipação social e de exercício de práticas deliberativas. Nessa perspectiva, considera-se uma cisão teórica estabelecida no interior da própria escola, cuja expressão se dá a partir das diferenças epistemológicas existentes entre o núcleo central do pensamento frankfurtiano e um conjunto de autores periféricos. Os trabalhos produzidos por esse núcleo “marginal”, bem como seu posterior refinamento na obra de Habermas, apresentam alternativas teóricas de caráter relacional que contrapõem a visão estrutural e cética presente nos trabalhos de Horkheimer, Adorno e Marcuse. É justamente na recuperação dessas fronteiras endógenas que se pretende ponderar as possíveis contribuições do pensamento frankfurtiano para uma perspectiva crítica da sociedade contemporânea.
Although much is known about the critical importance of active verbal rehearsal for successful recall, knowledge about the mechanisms of rehearsal and their respective development in children is very limited. To be able to rehearse several items together, these items have to be available, or, if presented and rehearsed previously, retrieved from memory. Therefore, joint rehearsal of several items may itself be considered recall. Accordingly, by analyzing free recall, one cannot only gain insight into how recall and rehearsal unfold, but also into how principles that govern children’s recall govern children’s rehearsal. Over a period of three and a half years (beginning at grade 3) 54 children were longitudinally assessed seven times on several overt rehearsal free recall trials. A first set of analyses on recall revealed significant age-related increases in the primacy effect and an age-invariant recency effect. In the middle portion of the list, wave-shaped recall characteristics emerged and increased with age, indicating grouping of the list into subsequences. In a second set of analyses, overt rehearsal behavior was decomposed into distinct rehearsal sets. Analyses of these sets revealed that the distribution of rehearsals within each set resembled the serial position curves with one- or two-item primacy and recency effects and wave-shaped rehearsal patterns in between. In addition, rehearsal behavior throughout the list was characterized by a decreasing tendency to begin rehearsal sets with the first list item. This result parallels the phenomenon of beginning recall with the first item on short lists and with the last item on longer lists.
Background: Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown.
Methods: We conducted a cross-sectional survey study among pre-clinical medical students in a German University hospital to assess the social cognitive predictors of influenza vaccination, as well as reasons for refusal and acceptance of the vaccine.
Results: Findings show that pre-clinical medical students have comparable knowledge gaps and negative attitudes towards influenza vaccination that have previously been reported among HCP. Lower injunctive norms and higher feelings of autonomy contribute to no intention to get vaccinated against influenza, while a positive instrumental attitude and higher feelings of autonomy contribute to a high intention to get vaccinated. The variables in the regression model explained 20% of the variance in intention to get vaccinated. Conclusions: The identified factors should be addressed early in medical education, and hospitals might benefit from a more inclusive vaccination program and accessibility of free vaccines for their medical students.
Synesthesia is a phenomenon in which additional perceptual experiences are elicited by sensory stimuli or cognitive concepts. Synesthetes possess a unique type of phenomenal experiences not directly triggered by sensory stimulation. Therefore, for better understanding of consciousness it is relevant to identify the mental and physiological processes that subserve synesthetic experience. In the present work we suggest several reasons why synesthesia has merit for research on consciousness. We first review the research on the dynamic and rapidly growing field of the studies of synesthesia. We particularly draw attention to the role of semantics in synesthesia, which is important for establishing synesthetic associations in the brain. We then propose that the interplay between semantics and sensory input in synesthesia can be helpful for the study of the neural correlates of consciousness, especially when making use of ambiguous stimuli for inducing synesthesia. Finally, synesthesia-related alterations of brain networks and functional connectivity can be of merit for the study of consciousness.
African trypanosomes cause a parasitic disease known as sleeping sickness. Mitochondrial transcript maturation in these organisms requires a RNA editing reaction that is characterized by the insertion and deletion of U-nucleotides into otherwise non-functional mRNAs. Editing represents an ideal target for a parasite-specific therapeutic intervention since the reaction cycle is absent in the infected host. In addition, editing relies on a macromolecular protein complex, the editosome, that only exists in the parasite. Therefore, all attempts to search for editing interfering compounds have been focused on molecules that bind to proteins of the editing machinery. However, in analogy to other RNA-driven biochemical pathways it should be possible to stall the reaction by targeting its substrate RNAs. Here we demonstrate inhibition of editing by specific aminoglycosides. The molecules bind into the major groove of the gRNA/pre-mRNA editing substrates thereby causing a stabilization of the RNA molecules through charge compensation and an increase in stacking. The data shed light on mechanistic details of the editing process and identify critical parameters for the development of new trypanocidal compounds.
This thesis covers the analysis of radix sort, radix select and the path length of digital trees under a stochastic input assumption known as the Markov model.
The main results are asymptotic expansions of mean and variance as well as a central limit theorem for the complexity of radix sort and the path length of tries, PATRICIA tries and digital search trees.
Concerning radix select, a variety of different models for ranks are discussed including a law of large numbers for the worst case behavior, a limit theorem for the grand averages model and the first order asymptotic of the average complexity in the quantile model.
Some of the results are achieved by moment transfer techniques, the limit laws are based on a novel use of the contraction method suited for systems of stochastic recurrences.
Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia) on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent) and red foxes (in the south). Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall), our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.
In der Großregion Saarland-Lothringen-Luxemburg-Rheinland-Pfalz-Wallonie-Deutsch-sprachige Gemeinschaft Belgiens ist ein rasanter demografischer Wandel zu erwarten, die Altersstruktur der Bevölkerung wird sich erheblich verändern. Die Zahl der über 80-jährigen, hochaltrigen Einwohnerinnen und Einwohner in der Großregion wird bis zum Jahr 2030 voraussichtlich um 29,4% steigen. Im Jahr 2013 lebten 626.065 Menschen im Alter von über 80 Jahren in der Großregion, im Jahr 2030 werden es 812.657 sein. Besonders stark dürfte der Anstieg der hochaltrigen Bevölkerung in der DG Belgien (+44,4%) und in Luxemburg (+36,2%) ausfallen. Da mit einer älter werdenden Bevölkerung auch die Zahl der Personen steigt, die auf professionelle Pflege angewiesen sind, steht die Großregion vor folgender Herausforderung: Mit einer ausreichenden Zahl an Pflegekräften muss die pflegerische Versorgung für den erhöhten Bedarf sichergestellt werden. Dafür ist eine Bedarfsanalyse für die kommenden Jahre notwendig.
This study examines the urban heat island (UHI) of Brussels, for both current (2000–2009) and projected future (2060–2069) climate conditions, by employing very high resolution (250 m) modelling experiments, using the urban boundary layer climate model UrbClim. Meteorological parameters that are related to the intensity of the UHI are identified and it is investigated how these parameters and the magnitude of the UHI evolve for two plausible trajectories for future climate conditions. UHI intensity is found to be strongly correlated to the inversion strength in the lowest 100 m of the atmosphere. The results for the future scenarios indicate that the magnitude of the UHI is expected to decrease slightly due to global warming. This can be attributed to the increased incoming longwave radiation, caused by higher air temperature and humidity values. The presence of the UHI also has a significant impact on the frequency of extreme temperature events in the city area, both in present and future climates, and exacerbates the impact of climate change on the urban population as the amount of heat wave days in the city increases twice as fast as in the rural surroundings.
Background: Emerging evidence indicates that mesenchymal stromal cells (MSCs) isolated from different tissue sources may be used in vivo as tissue restorative agents. To date, there is no evidence, however, on migration and proliferation ("wound healing") potential of different subsets of MSCs. The main goal of this study was therefore to compare the in vitro "wound healing" capacity of MSCs generated from positively selected CD271+ bone marrow mononuclear cells (CD271-MSCs) and MSCs generated by plastic adherence (PA-MSCs).
Methods: The in vitro model of wound healing (CytoSelect™ 24-Well Wound Healing Assay) was used in order to compare the migration and proliferation potential of CD271-MSCs and PA-MSCs of passage 2 and 4 cultured in presence or absence of growth factors or cytokines.
Results: CD271-MSCs of both passages when compared to PA-MSCs demonstrated a significantly higher potential to close the wound 12 and 24 h after initiation of the wound healing assay (P < 0.003 and P < 0.002, respectively). Noteworthy, the migration capacity of PA-MSCs of second passage was significantly improved after stimulation with FGF-2 (P < 0.02), PDGF-BB (P < 0.006), MCP-1 (P < 0.002) and IL-6 (P < 0.03), whereas only TGF-β enhanced significantly migration process of PA-MSCs of P4 12 h after the treatment (P < 0.02). Interestingly, treatment of CD271-MSCs of both passages with growth factors or cytokines did not affect their migratory potential.
Conclusions: Our in vitro data provide the first evidence that CD271-MSCs are significantly more potent in "wound healing" than their counterparts PA-MSCs.
Type 1 Diabetes (T1D) is an autoimmune disorder in which the own immune system attacks the insulin producing _-cells in the pancreas. Therapy of T1D with anti-CD3 antibodies (aCD3) leads to a blockade of the autoimmune process in animal models and patients resulting in reduced insulin need. Unfortunately, this effect is only temporal and the insulin need increases after a few years. In the first approach, I aimed at a blockade of the cellular re-entry into the islets of Langerhans after aCD3 treatment by neutralising the key chemokine CXCL10, which is important for the T cell migration. In the second approach I tried to block the transmigration of leukocytes trough the endothelial layer into inflamed tissue with an anti-JAM-C antibody (aJAM-C) after aCD3 treatment.
I used the well-established RIP-LCMV-GP mouse model of T1D. As target autoantigen in the _-cells, such mice express the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter (RIP). These mice develop T1D within 10 to 14 days only after LCMV-infection. In the combination therapy (CT) I treated diabetic RIP-LCMV-GP mice with 3 5g aCD3 per mouse (3 injections in 3 days) followed by administration of a neutralising anti-CXCL10 (CT) or aJAM-C (CT-J) monoclonal antibody (8 injections of 100 5g per mouse over 2.5 weeks).
CT reverted T1D in RIP-LCMV-GP mice significantly (CT: 67 % reversion; control: 16 % reversion) and with superior efficacy to monotherapies with aCD3 (38 % reversion) and aCXCL10 (36 % reversion).
The CD8 T cells in the spleen have fully regenerated at day 31 after infection. However, the frequency of islet antigen (GP)-specific CD8 T-cells was significantly reduced by 73 % in the spleen after CT compared to isotype control treated mice. In contrast, in aCD3 treated mice the T cells were only reduced by 56 % of the frequency of isotype control treated mice. Flow cytometry and immunohistological examinations demonstrated a marked reduction of CD8 T cells in the pancreas of CT treated mice. Importantly, the number of GP-specific CD8 T cells was reduced dramatically by 78 % in the pancreas of CT treated mice, whereas aCD3 treatment led to a less pronounced reduction of the GP-specific CD8 T cell number (23 %). This reduction of infiltration was long lasting since in the pancreas of CT treated mice the _-cells produce insulin and there were almost no infiltrating T cells present at day 182 post-infection. aCD3 treated mice also showed many insulin producing cells after 182 days post-infection. Nevertheless, their pancreas displayed also some infiltrates around the islets.
In order to confirm my data I treated non-obese diabetic (NOD) mice with CT. In contrast to RIP-LCMV-GP mice, NOD mice develop spontaneous T1D within 15 to 30 weeks after birth, due to a mutation in the CTLA-4 gene. Strikingly CT cured 55 % of diabetic NOD mice, whereas only 30 % showed T1D reversion with aCD3 alone and none reverted after isotype control administration.
The impact of CT on GP-specific T cells (Teff) was stronger in the RIP LCMV-GP than in the NOD model. In contrast, regulatory T cells (Tregs) were induced predominantly in NOD mice rather than in RIP-LCMV-GP mice. However, looking at the Treg/Teff ratio and compared to isotype control antibody treated mice, I found a significant 4-fold increase in the pancreas of CT treated RIP LCMV-GP mice and a 17-fold increase in the PDLN of CT treated NOD mice. In addition, a tendency for an increase in Treg/Teff ratio was obtained in the spleen of CT-treated RIP LCMV-GP as well as NOD mice compared to aCD3 and isotype control antibody treated mice.
In the second combination therapy with neutralising aJAM-C, CT-J (51 % reversion) slightly improved the aCD3 therapy (41 % reversion). However, there was no significant difference between CT-J and aCD3 administration in terms of total CD8 and GP-specific CD8 T cells.
JAM-C also interacts with the integrin receptor macrophage-1 antigen (MAC-1), which is among others expressed by neutrophils. Accordingly, JAM-C could be involved in neutrophil transmigration to the pancreas. Indeed, I found a significant reduction for the infiltrating neutrophils into the pancreas of mice after CT-J compared to aCD3 monotherapy.
In summary the addition of aJAM-C to aCD3 monotherapy showed a small improvement, which was associated with a reduced neutrophil migration into the pancreas. However, JAM C seemed to play only a minor role in T1D development and some other adhesion molecules might be more important. Nevertheless, the combination of aCD3 and aCXCL10 resulted in a significant and long lasting reduction of aggressive T cells in the pancreas in two independent mouse models. Furthermore a protective immune balance was obtained. Since both antibodies are available for as well as tested in humans and the therapy is only for a short period of time after disease onset, this combination therapy might kick-start a novel therapy for T1D.
The increasing number of casting shows and talent contests in the media over the past years suggests a public interest in rating the quality of vocal performances. In many of these formats, laymen alongside music experts act as judges. Whereas experts' judgments are considered objective and reliable when it comes to evaluating singing voice, little is known about laymen's ability to evaluate peers. On the one hand, layman listeners–who by definition did not have any formal training or regular musical practice–are known to have internalized the musical rules on which singing accuracy is based. On the other hand, layman listeners' judgment of their own vocal skills is highly inaccurate. Also, when compared with that of music experts, their level of competence in pitch perception has proven limited. The present study investigates laypersons' ability to objectively evaluate melodies performed by untrained singers. For this purpose, laymen listeners were asked to judge sung melodies. The results were compared with those of music experts who had performed the same task in a previous study. Interestingly, the findings show a high objectivity and reliability in layman listeners. Whereas both the laymen's and experts' definition of pitch accuracy overlap, differences regarding the musical criteria employed in the rating task were evident. The findings suggest that the effect of expertise is circumscribed and limited and supports the view that laypersons make trustworthy judges when evaluating the pitch accuracy of untrained singers.
Currently, the structure of the X(3872) meson is unknown. Different competing models of the exotic state X(3872) exist, including the possibilities that this state is either a mesonic molecule with dominating D0D¯ ∗0 + c.c. composition, a tetraquark, or a -gluon hybrid state. It is expected that the X(3872) state is rather strongly coupled to the channel and, therefore, can be produced in and collisions at PANDA. We propose to test the hypothetical molecular structure of by studying the D or D¯⁎ stripping reactions on a nuclear residue.
El artículo, después de haber tratado la cuestión del tiranicidio en Tomás de Aquino y en Bartolo de Sassoferrato, muestra cómo Francisco de Vitoria, consciente de las soluciones que ofrecen los autores anteriores a él, afronta el argumento de forma innovadora, aunque en línea con la tradición anterior. En la base de la solución que propone Vitoria, se encuentra, en efecto, la afirmación de un derecho a la auto-defensa, entendido como derecho natural inalienable que reside en los individuos y en las comunidades; un derecho que siempre lo pueden ejercer los súbditos en relación con un gobernante que se convierte en tirano. Vitoria expresa de este modo el principio de resistencia a la autoridad injusta e ilegal en los términos de un derecho subjetivo, el de la auto-defensa, pero, al mismo tiempo, señala los límites afirmando la necesidad de cada individuo de respetar y someterse a un orden de justicia objetivo. De aquí su prohibición a un particular de matar a un hombre, aunque sea un tirano, sin un justo procedimiento jurídico. Así pues, el artículo muestra, a través del debate sobre la licitud del tiranicidio cómo en la obra de Vitoria se encuentra una teoría sólida de la soberanía juntamente con la afirmación tenaz de derechos naturales individuales. En efecto, Vitoria retoma, por una parte, una tradición de pensamiento para la que la formación de las sociedades políticas era la consecuencia de la sociabilidad natural de los hombres; y por otra, desarrollaba una teoría coherente de los derechos subjetivos a partir de la necesidad misma de los individuos de asociarse los unos con los otros para los fines de una vida éticamente justa y gratificante.
Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients’ outcome in ALL.
The success stories of design-oriented companies like Apple, Audi or Nike have put design on the agenda in many marketing departments. Consumers cannot elude the effect of aesthetics and therefore design is a major factor for business success. Typically consumers choose the product with the best design, all other aspects being equal. Only when the interplay of product characteristics, brand and design is carefully coordinated can successful products be created. This requires an integrated approach to design, one which is applied right at the beginning of the value chain. Product development, marketing and design need to work in close cooperation, communicate well and frequently, and collect feedback from the market. Superior aesthetics are always important but should be a top priority in cases where efficiency-oriented Asian competitors are able to offer functionally similar products at much lower prices.
This thesis develops a conceptual framework for a better understanding of the impact of slow-onset climate and environmental changes on human migration in developing countries. Its regional focus is on the West African Sahel, where the majority of the population depends on agriculture and thus is highly vulnerable to environmental changes. Migration from fragile environments is predominantly considered one of several household strategies to adapt to and minimise the risk of environmental stress. Based on qualitative and quantitative data from two selected rural study areas, Bandiagara in Mali and Linguère in Senegal, this thesis analyses the drivers of migration from the two areas.
The findings illustrate that, even though people highly depend on the natural environment, migration motives are manifold and that migration often is not a household strategy to cope with environmental changes. Although environmental conditions shape migration in the region and the migrants’ support is crucial for most households, environmental stress plays a relatively small role as a driver of migration - at least in Mali, where it is considerably less important than in Senegal. On the contrary, migration is often driven by better opportunities elsewhere rather than by livelihood stressors in the home area. Particularly the migration of young people is often an individual rather than a household decision and influenced by individual aspirations, such as aspirations for consumer goods or a better future, rather than by environmental stress.
This thesis claims that research should consider people’s capabilities to migrate or to stay as well as their individual aspirations and preferences - in addition to the household’s needs and the opportunities elsewhere. This is important in order to explain why some people stay in and others migrate from an area affected by environmental stress, though living under similar conditions. Depending on people’s capabilities to choose freely between staying and migrating and their preferences and aspirations for one or the other activity, people can either be “voluntary migrants”, “voluntary non-migrants”, “forced migrants” or “trapped people”.
Moreover, it is important to consider social trends and transformation processes in the analysis of the linkages between environment change and migration. Higher education levels and aspirations to a “modern” lifestyle among young people, for instance, might decrease the impact of environmental factors on migration, despite worsening environmental conditions.
CLOUD COMPUTING PROMISES ENHANCED FLEXIBILITY AND SUBSTANTIAL ECONOMIC
BENEFITS THROUGH THE ON-DEMAND LEASE OF IT RESOURCES. THESE TWO ASPECTS ARE STRONGLY INFLUENCED BY THE PRICING OF CLOUD RESOURCES. BASED ON A SAMPLE OF 48 INFRASTRUCTURE PROVIDERS, WE EXAMINE CURRENT PRICING SCHEMES IN THE CLOUD MARKET FROM A USER PERSPECTIVE.
This paper explores how banks adjust their risk-based capital ratios and asset allocations following an exogenous shock to their asset quality caused by Hurricane Katrina in 2005. We find that independent banks based in the disaster areas increase their risk-based capital ratios after the hurricane, while those part of a bank holding company do not. The effect on independent banks mainly comes from the subgroup of high-capitalized banks. These banks increase their holdings in government securities and reduce loans to non-financial firms. Hence, banks that become more stable achieve this at the cost of reduced lending.
Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary (H2SO4-H2O) system, and the ternary system involving ammonia (H2SO4-H2O-NH3) may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a Chemical Ionization Mass Spectrometer (CIMS). From these measurements dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4·NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248K. We estimate the thermodynamic properties (dH and dS) of the H2SO4·NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF) mass spectrometry.
Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary (H2SO4–H2O) system and the ternary system involving ammonia (H2SO4–H2O–NH3) may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a chemical ionization mass spectrometer (CIMS). From these measurements, dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4·NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248 K. We estimate the thermodynamic properties (dH and dS) of the H2SO4·NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using chemical ionization–atmospheric pressure interface time-of-flight (CI-APi-TOF) mass spectrometry.
Aerosolteilchen agieren als Kondensationskeime für Wolkentröpfchen (engl. Cloud Condensation Nuclei, CCN) oder Eiskristalle und sind deswegen für die Wolken- und Niederschlagsbildung entscheidend. Sowohl die Aerosolpartikel als auch die Wolken können Sonnenlicht effizient streuen, wodurch ein kühlender Effekt auf das Klima ausgeübt wird. Einige der Teilchen, wie z. B. aufgewirbelter Staub oder Seesalz, werden direkt in die Atmosphäre injiziert; der größte Anteil der Teilchen und etwa die Hälfte der CCN werden allerdings durch die Kondensation gasförmiger Substanzen gebildet. Dieser Prozess wird als Nukleation oder Partikelneubildung (engl. New Particle Formation, NPF) bezeichnet. Trotz intensiver Forschung ist die NPF noch nicht vollständig verstanden, was an der Komplexität der chemischen Abläufe in der Atmosphäre und an der Schwierigkeit liegt, die relevanten Substanzen bei extrem geringen Mischungsverhältnissen (etwa ein Molekül oder Cluster per 1012 bis 1015 Moleküle) zu identifizieren und zu quantifizieren. Neben der Frage nach den bei der Nukleation beteiligten Substanzen ist außerdem noch unklar, ob Ionen-induzierte Nukleation ein wichtiger Prozess für das Klima ist. Das CLOUD-Projekt (Cosmics Leaving OUtdoor Droplets) am CERN soll diesen Fragen nachgehen, indem dort die Partikelbildung in einem Kammer-Experiment unter extrem gut kontrollierten Bedingungen simuliert wird. Die chemischen Systeme, die in dieser Schrift diskutiert werden, umfassen das binäre (H2SO4-H2O), das ternäre Ammoniak (H2SO4-H2O-NH3) und das ternäre Dimethylamin (H2SO4-H2O-(CH3)2NH)-System.
Einige der wesentlichen Ergebnisse von Experimenten an der CLOUD-Kammer werden diskutiert. Diese zeigen, dass das binäre und das ternäre Ammoniak System die atmosphärische Nukleation bei niedrigen Temperaturen erklären können, wohingegen das ternäre Dimethylamin System prinzipiell in der Lage ist, die hohen bodennahen Nukleationsraten bei atmosphärisch relevanten Schwefelsäure-Konzentrationen zu beschreiben. Des Weiteren werden zwei für Nukleationsstudien wesentliche Messmethoden vorgestellt. Das Chemical Ionization Mass Spectrometer (CIMS) wird zur Messung von gasförmiger Schwefelsäure verwendet, da H2SO4 vermutlich die wichtigste Substanz bei der atmosphärischen Nukleation ist. Das Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF) Massenspektrometer misst Schwefelsäure und neutrale Cluster. Beide Geräte wurden für den Einsatz bei CLOUD optimiert und instrumentelle Entwicklungen wurden in Bezug auf die Ionenquelle vorgenommen, die eine Korona-Entladung verwendet. Außerdem wurden eine Kalibrationseinheit zur Bereitstellung definierter Schwefelsäure-Konzentrationen entwickelt und das CI-APi-TOF aufgebaut. In Bezug auf das ternäre Dimethylamin System werden Nukleationsraten und die ersten Messungen von gro en nukleierenden neutralen Clustern präsentiert. Monomer- und Dimer-Konzentrationen der Schwefelsäure, die mit dem CIMS bei tiefen Temperaturen gemessen wurden, dienten der Ableitung der thermodynamischen Eigenschaften bei der Dimer-Bildung im binären und ternären Ammoniak System. Um möglichst exakte Nukleationsraten zu bestimmen, wurde eine neue Methode entwickelt, die es erlaubt, den Effekt der Selbst-Koagulation bei der Nukleation miteinzubeziehen.
Die zusammengefassten Studien tragen signifikant zum Verständnis der Partikelneubildung bei.
Teil VIII unserer Serie zum “Islamischen Staat”: "Blogforum 'Kalifat des Terrors: Interdisziplinäre Perspektiven auf den Islamischen Staat".
Die Kurden feiern in diesen Tagen den Sieg über den Islamischen Staat in Kobane. Die Hauptstadt des Distrikts Ain al-Arab im Gouvernement Aleppo in Syrien liegt nahe der syrisch-türkischen Grenze. Seit Anfang 2014 ist Ain al-Arab Zentrum eines der drei selbstverwalteten Kantone Rojavas. Diese Kantone stehen unter der Kontrolle der kurdischen “Partei der Demokratischen Union” (PYD) und ihrer Verbündeten. Die PYD ist eine Schwesterpartei der PKK, sie erkennt Abdullah Öcalan als ideologischen Führer an...
»In der Praxis läuft nicht alles so glatt, wie man es sich vorstellt …« : »Starker Start« als Tutor
(2015)
Bei den Baustrukturen der Pyramiden des Alten Reiches sind sehr große Unterschiede erkennbar, weist doch jede ein individuelles Inneres auf. Während die Cheops- Pyramide über ein sehr komplexes Kammersystem verfügt, das während des Baus sicherlich größere Komplikationen und damit auch einen höheren Zeitaufwand verursachte, ist bereits unter Chefren eine weitaus weniger komplexe Innenstruktur gewählt worden. In dessen Pyramide befindet sich die Sargkammer in Bodenhöhe, bei Mykerinos sind alle Kammern gänzlich unterhalb des Bodenniveaus. Diese Änderung der Bauweise resultierte sicher aus den Erfahrungen und Problemen beim Bau der Cheopspyramide. Diese ist über einem natürlichen Steinkern unbekannter Größe errichtet, wodurch sehr viel Baumaterial gespart werden konnte. Die Pyramiden der 5. und 6. Dynastie zeichnen sich wiederum durch eine gänzlich andere Bauweise als die der 4. Dynastie aus und sind weitaus kleiner konzipiert. Sehr selten sind Hinweise auf die zeitlichen Abläufe eines Pyramidenbaues zu finden, wie sie z.B. im Verlauf der Grabungen des Deutschen Archäologischen Institutes unter R. Stadelmann an der Roten Pyramide zutage kamen...
Bei dem vorliegenden Werk handelt es sich um die erste längere Monographie zu der Königin Teje überhaupt, wenn auch z.B. ihr Portraitkopf in Berlin des Öfteren in kürzerer Form Beachtung fand. Teje war die Große königliche Gemahlin von Amenophis III., Pharao der 18. Dynastie des Neuen Reiches, sowie die Mutter des Königs Echnaton und Schwiegermutter Nofretetes. Bei ihren Eltern handelt es sich um Juja und Tuja, deren Grab in Theben (KV46) bei der Auffindung 1905 noch mit zahlreichen Objekten versehen war, die heute im Ägyptischen Museum Kairo ausgestellt sind. So wurde z.B. neben den äußeren, mit Schlittenkufen versehenen Sarkophagen, Särgen, Kanopenkästen und vergoldeten Totenmasken einer der überaus wenigen heute vollständig erhaltenen Streitwagen aus pharaonischer Zeit in ihrem Grab gefunden...
Il saggio indaga le connessioni tra l’abolizione della prostituzione legalizzata e i processi di democratizzazione in Germania e Italia, a partire dalla storia dei diritti umani nella sua interazione con il sistema politico. Le fonti principali sono i dibattiti parlamentari e le leggi che portarono alla chiusura dei bordelli e all’abolizione del sistema di sorveglianza nel 1927 in Germania e nel 1958 in Italia. I dibattiti sulla prostituzione pongono anche la questione dell’uguaglianza e della giustizia di genere. In particolare, il problema della regolamentazione della prostituzione, la cui efficienza viene verificata da un numero sempre maggiore di ricercatori nel corso del XX secolo, dispiega fattori di politica sanitaria, di diritti umani e di morale, aspetti di politica sociale e di sicurezza, mettendo in discussione non solo la gerarchia tra i generi, ma anche quella tra gli strati sociali.
Over the last decade, the prospect of improving or maintaining cognitive functioning has provoked a steadily increasing number of cognitive training studies. Central target populations are individuals at risk for a disadvantageous development, such as older adults exhibiting cognitive decline or children with learning impairments. They rely on cognitive resources to meet the challenges of an independent life in old age or requirements at school.
To support daily cognitive functioning, training outcomes need to generalize to other cognitive abilities. Such transfer effects are, however, highly discussed. For example, recent meta-analyses on working memory training differed in the conclusion on the presence (Au et al., 2015; Karbach and Verhaeghen, 2014) or absence of transfer effects (Melby-Lervåg and Hulme, 2013). Usually training-specific design factors such as type, intensity, duration, and feedback routines are discussed as reasons for such inconsistent findings. However, even individuals participating in exactly the same training regime highly differ in their training outcomes. We argue that it is time to study the individual development during trainings to understand these differential outcomes. It is time to have a closer look at the intraindividual training data.
Die vorliegende Dissertation zeigt, dass globale Kohärenz in Lebenserzählungen erst in der Adoleszenz entsteht und sich im Erwachsenenalter weiter entwickelt. Außerdem konnte gezeigt werden, dass die fragmentarische Nutzung der Lebensgeschichte in Form autobiographischen Urteilens in Zeiten tiefgreifender Lebensveränderungen zum Erhalt der Selbst-Kontinuität beiträgt.
Die Arbeit mit Rechnungen bietet den Vorteil, dass es sich dabei fast immer um Originalquellen handelt. Rechnungen wurden üblicherweise nicht in Kompilationen aufgenommen oder nicht in Urkunden inseriert. Wenn sie abgeschrieben wurden, geschah das höchstens im Zuge des Abrechnungsprozesses und nicht, wie etwa bei Chroniken, um für ihre weitere Verbreitung zu sorgen. Unter den schriftlichen Quellen kommen die Rechnungen damit wohl der Definition eines Überrestes am nächsten: Sie wurden für die Mit-, nicht die Nachwelt erstellt. Das bringt allerdings den Nachteil mit sich, dass wir selten genau wissen, zu welchem Zweck eine Rechnung eigentlich verfertigt wurde. Keine Arenga klärt den Forscher über die Vorgeschichte und den Zusammenhang der Niederschrift auf. Erklärende Dokumente sind fast nie überliefert. Die Menschen, die Rechnungen erstellten und mit ihnen arbeiteten, lernten das durch und bei ihrer Arbeit, eventuell unter mündlicher Anleitung. ...
The planned Facility for Antiproton and Ion Research (FAIR) at GSI has to cope with a wide range of beam intensities in its high-energy beam transport systems and in the storage rings. To meet the requirements of a non-intercepting intensity measurement down to nA range, it is planned to install a number of Cryogenic Current Comparator (CCC) units at different locations in the FAIR beamlines. In this work, the first CCC system for intensity measurement of heavy ion beams, which was developed at GSI, was re-commissioned and upgraded to be used as a 'GSI - CCC prototype' for extensive optimization and development of an improved CCC for FAIR. After installation of a new SQUID sensor and related electronics, as well as implementation of improved data acquisition components, successful beam current measurements were performed at a SIS18 extraction line. The measured intensity values were compared with those of a Secondary Electron Monitor (SEM). Furthermore, the spill-structure of a slowly extracted beam was measured and analyzed, investigating its improvement due to bunching during the slow-extraction process. Due to the extreme sensitivity of the superconducting sensor, the determined intensity values as well as the adjustment of the system for optimal performance are strongly influenced by the numerous noise sources of the accelerators environment. For this reason, detailed studies of different effects caused by noise have been carried out, which are presented together with proposals to reduce them. Similarly, studies were performed to increase the dynamic range and overcome slew rate limitations, the results of which are illustrated and discussed as well. By combining the various optimizations and characterizations of the GSI CCC prototype with the experiences made during beam operation, criteria for a more efficient CCC System could be worked out, which are presented in this work. The details of this new design are worked out with respect to the corresponding boundary conditions at FAIR. Larger beam tube diameters, higher radiation resistivity and UHV requirements are of particular importance for the cryostat. At the same time these parameters affect the CCC superconducting magnetic shielding, which again has significant influence on the current resolution of the system. In order to investigate the influence of the geometry of the superconducting magnetic shield on different magnetic field components and to optimize the attenuation, FEM simulations have been performed. Based on the results of these calculations, modifications of the shield geometry for optimum damping behavior are proposed and discussed in the thesis.
This work proposes to employ the (bursty) GLO model from Bingmer et. al (2011) to model the occurrence of tropical cyclones. We develop a Bayesian framework to estimate the parameters of the model and, particularly, employ a Markov chain Monte Carlo algorithm. This also allows us to develop a forecasting framework for future events.
Moreover, we assess the default probability of an insurance company that is exposed to claims that occur according to a GLO process and show that the model is able to substantially improve actuarial risk management if events occur in oscillatory bursts.
Euro crash risk
(2015)
"Mehr Licht!", um die "Seele" der Natur zu erfassen – das verband die Impressionisten mit der vorangegangenen Künstlergeneration um Camille Corot. Claude Monet und seine Kollegen suchten die Wälder und Parks auf, um Licht, Atmosphäre und Farbigkeit in ihrer Malerei festzuhalten. Dabei reagierten sie eher intuitiv auf die in jener Zeit intensiv erforschten optischen Gesetzmäßigkeiten.
n this paper we compute the optimal tax and education policy transition in an economy where progressive taxes provide social insurance against idiosyncratic wage risk, but distort the education decision of households. Optimally chosen tertiary education subsidies mitigate these distortions. We highlight the importance of two different channels through which academic talent is transmitted across generations (persistence of innate ability vs. the impact of parental education) for the optimal design of these policies and model different forms of labor as imperfect substitutes, thereby generating general equilibrium feedback effects from policies to relative wages of skilled and unskilled workers. We show that subsidizing higher education has important redistributive benefits, by shrinking the college wage premium in general equilibrium. We also argue that a full characterization of the transition path is crucial for policy evaluation. We find that optimal education policies are always characterized by generous tuition subsidies, but the optimal degree of income tax progressivity depends crucially on whether transitional costs of policies are explicitly taken into account and how strongly the college premium responds to policy changes in general equilibrium.
Peter Oestmann unterscheidet in seiner Intervention drei Arten der Rechtsgeschichtsschreibung, die er Normen-, Wissenschafts- und Praxisgeschichte nennt. Als bekennender Vertreter der letzten Kategorie setzt er sich für deren Emanzipation von der rechtsdogmatischen "Normenkontrolle" ein. Er bezeichnet es als "unfair, wenn Vertreter der Normengeschichte erwarten, diejenigen, die sich mit der Rechtspraxis beschäftigen, müssten im gleichen Maße die Rechtsliteratur und normative Quellen in ihre Untersuchungen einbeziehen wie andere Rechtshistoriker auch" (8). Zugleich bricht er eine Lanze für die "erheblich unjuristischere" Rechtsgeschichte der Praxis (ebd.). Wir pflichten diesem Anliegen vorbehaltlos bei. Zugleich beobachten wir, dass Oestmanns Kritik an Grundlagen des rechtshistorischen Selbstverständnisses rührt, die zur Diskussion zu stellen im deutschsprachigen Raum erfahrungsgemäß schwer fällt. Auch bleibt Oestmann zu oft in den Kategorien des von ihm Kritisierten befangen. Unsere Replik setzt sich mit den historischen Ursachen dieses strukturellen Unbehagens in der Rechtsgeschichte auseinander.
The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator of the canonical NF-κB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-κB activation; however, there is increasing evidence for NF-κB pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-α-IKKβ-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which ∼1% are regulated up on TNF-α stimulation. We identify various potential novel IKKβ substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKKβ on serine 298. We provide evidence that IKKβ-mediated AEG-1 phosphorylation is essential for IκBα degradation as well as NF-κB-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo.
Dies ist der achte Artikel unseres Blogfokus „Salafismus in Deutschland“.
Die salafistische Propaganda kultiviert ein dichotomisches Weltbild, in dem den Muslimen die Rolle des kollektiven Opfers westlicher Expansionsgelüste zufällt. Die historischen Fakten, die dies untermauern sollen, werden jedoch arg strapaziert und sehr einseitig interpretiert. Die Realität ist sehr viel komplexer, als die salafistische Schwarz-Weiß-Malerei der Öffentlichkeit weismachen will...
Little attention so-far has been paid to the influence of chronobiology on the processes of nanoparticle uptake and transport into the brain, even though this transport appears to be chronobiologically controlled to a significant degree. Nanoparticles with specific surface properties enable the transport across the blood–brain barrier of many drugs that normally cannot cross this barrier. A clear dependence of the central antinociceptive (analgesic) effects of a nanoparticle-bound model drug, i.e., the hexapeptide dalargin, on the time of day was observable after intravenous injection in mice. In addition to the strongly enhanced antinociceptive effect due to the binding to the nanoparticles, the minima and maxima of the pain reaction with the nanoparticle-bound drug were shifted by almost half a day compared to the normal circadian nociception: The maximum in the pain reaction after i.v. injection of the nanoparticle-bound dalargin occurred during the later rest phase of the animals whereas the normal pain reaction and that of a dalargin solution was highest during the active phase of the mice in the night. This important shift could be caused by an enhanced endo- and exocytotic particulates transport activity of the brain capillary endothelial cells or within the brain during the rest phase.
Data-parallel programming is more important than ever since serial performance is stagnating. All mainstream computing architectures have been and are still enhancing their support for general purpose computing with explicitly data-parallel execution. For CPUs, data-parallel execution is implemented via SIMD instructions and registers. GPU hardware works very similar allowing very efficient parallel processing of wide data streams with a common instruction stream.
These advances in parallel hardware have not been accompanied by the necessary advances in established programming languages. Developers have thus not been enabled to explicitly state the data-parallelism inherent in their algorithms. Some approaches of GPU and CPU vendors have introduced new programming languages, language extensions, or dialects enabling explicit data-parallel programming. However, it is arguable whether the programming models introduced by these approaches deliver the best solution. In addition, some of these approaches have shortcomings from a hardware-specific focus of the language design. There are several programming problems for which the aforementioned language approaches are not expressive and flexible enough.
This thesis presents a solution tailored to the C++ programming language. The concepts and interfaces are presented specifically for C++ but as abstract as possible facilitating adoption by other programming languages as well. The approach builds upon the observation that C++ is very expressive in terms of types. Types communicate intention and semantics to developers as well as compilers. It allows developers to clearly state their intentions and allows compilers to optimize via explicitly defined semantics of the type system.
Since data-parallelism affects data structures and algorithms, it is not sufficient to enhance the language's expressivity in only one area. The definition of types whose operators express data-parallel execution automatically enhances the possibilities for building data structures. This thesis therefore defines low-level, but fully portable, arithmetic and mask types required to build a flexible and portable abstraction for data-parallel programming. On top of these, it presents higher-level abstractions such as fixed-width vectors and masks, abstractions for interfacing with containers of scalar types, and an approach for automated vectorization of structured types.
The Vc library is an implementation of these types. I developed the Vc library for researching data-parallel types and as a solution for explicitly data-parallel programming. This thesis discusses a few example applications using the Vc library showing the real-world relevance of the library. The Vc types enable parallelization of search algorithms and data structures in a way unique to this solution. It shows the importance of using the type system for expressing data-parallelism. Vc has also become an important building block in the high energy physics community. Their reliance on Vc shows that the library and its interfaces were developed to production quality.
Zu Beginn dieser Arbeit stand die Vermutung, dass die Klangsprache von Arnold Schönbergs Werk Pierrot lunaire stark durch Albert Girauds gleichnamigen, von Otto Erich Hartleben ins Deutsche übertragenen Gedichtzyklus beeinflusst worden ist.
Um genauer herauszuarbeiten, wie ein Gedichtzyklus die Klangsprache eines Komponisten beeinflussen kann, wurde zuerst Girauds Originaltext mithilfe der symbolistischen Ästhetik sowie der ästhetischen Kategorien des Capriccio und der Groteske analysiert. In einem zweiten Schritt wurde - mithilfe von Walter Benjamins Überlegungen zur Aufgabe des Übersetzers - Otto Erich Hartlebens Übertragung von Girauds Zyklus untersucht. Im Laufe dieser jeweiligen Analysen kristallisierte sich die Rolle des Ephemeren sowohl in der Gestaltung des Originaltextes als auch innerhalb des Vorgangs der Übersetzung heraus.
Das Wirken des Ephemeren im Kunstwerk wurde mithilfe von Theodor W. Adornos Ästhetische Theorie genauer dargestellt und mündete in der Hauptfrage der vorliegenden Untersuchung: Wie gestaltet das Ephemere den Pierrot lunaire bei Albert Giraud, Otto Erich Hartleben und Arnold Schönberg? In Bezug auf Schönbergs Werk wurden dabei in erster Linie der Sprechgesang, die Wechselwirkung von Instrumentation und Klangfarbe sowie einzelne Elemente der Klangsprache behandelt.
Dies ist der vierte Artikel unseres Blogfokus zu Flucht und Migration. Seit einigen Jahren ist ein Anstieg von Feldforschungsprojekten in den Sozialwissenschaften in Deutschland zu verzeichnen. Doch wie finden solche Projekte statt? Werden Flüchtlinge zu reinen Gegenständen der Untersuchungen oder können sie in der Forschung involviert werden?
Viele auf allgemeinen Graphen NP-schwere Probleme (z.B. Hamiltonkreis, k-Färbbarkeit) sind auf Bäumen einfach effizient zu lösen. Baumzerlegungen, Zerlegungen von Graphen in kleine Teilgraphen entlang von Bäumen, erlauben, dies zu effizienten Algorithmen auf baumähnlichen Graphen zu verallgemeinern. Die Baumähnlichkeit wird dabei durch die Baumweite abgebildet: Je kleiner die Baumweite, desto baumähnlicher der Graph.
Die Bedeutung der Baumzerlegungen wurde seit ihrer Verwendung in einer Reihe von 23 Veröffentlichungen von Robertson und Seymour zur Graphminorentheorie allgemein erkannt. Das Hauptresultat der Reihe war der Beweis des Graphminorensatzes, der aussagt, dass die Minorenrelation auf den Graphen Wohlquasiordnung ist. Baumzerlegungen wurden in verschiedenen Bereichen angewandt. So bei probabilistischen Netzen, in der Biologie, bei kombinatorischen Problemen und im Übersetzerbau. Außerdem gibt es algorithmische Metatheoreme, die zeigen, dass sie für weite Problemklassen nützlich sind. Baumzerlegungen sind in dieser Arbeit von zentraler Bedeutung. Die mittels Baumzerlegungen erzielten Erfolge auf baumähnlichen Graphen motivieren Versuche, diese auf größere Graphklassen zu verallgemeinern. Ein erfolgreicher Ansatz beruht auf irrelevanten Knoten und reduziert damit die Probleme auf der größeren Graphklasse auf Probleme auf einer Graphklasse kleiner Baumweite: Wenn der Eingabegraph zu einem Problem kleine Baumweite hat, wird das Problem mittels Baumzerlegungen gelöst. Andernfalls gibt es einen irrelevanten Knoten, so dass das Problem genau dann eine Lösung auf dem ursprünglichen Graphen hat, wenn es auch im Graphen ohne diesen irrelevanten Knoten eine Lösung hat. Es werden solange irrelevante Knoten gefunden und entfernt, bis ein Graph kleiner Baumweite verbleibt.
Ein wichtiges Hilfsmittel zum Finden irrelevanter Knoten ist der Gitterminorensatz: Nach diesem Satz enthalten Graphen großer Baumweite auch große Gitter als Minoren. Die Gitter Baumweite-Dualität ist auch in der Bidimensionalitätstheorie, einem weiteren erfolgreichen Ansatz, um auf größeren Graphklassen, als nur denen kleiner Baumweite, Probleme effizient zu lösen, von zentraler Bedeutung.
This work deals with so-called wh-determination. The notion of D-linking (Discourse-linking) is used to uncover and explain properties of constructions involving wh-determiners. The central claim is that there are two types of wh-determination: Token-whs and Kind-whs. These two forms of wh-determination trigger different syntactic effects. Three structural triggers for the syntactic effects exhibited by D-linked wh-phrases (DWH) are discussed. DWH are argued to be instances of Token-whs since triggers for the syntactic effects of D-linking are identical to the once for the token-reading of a wh-phrase.
In chapter 2, which-phrases are shown to be canonical DWH with a special syntax labelled DL-S(yntax). The five most prominent and frequent DL-S effects are the absence of superiority-effects with DWH, the ability of DWH to be extracted out of weak islands, the fact that DWH licence resumptive elements, the obviation of WCO effects by DWH, and the possibility for DWH to stay in-situ. The syntax of Token-whs and Kind-whs are compared. It is demonstrated that regardless of the actual form of the wh-determiner, there are only these two types of wh-determination. These data support the idea that the DL-S effects observable with DWH are triggered by structural properties of the wh-determiners heading DWH.
In chapter 3, it is demonstrated that although presuppositions projected by the Nominal Restrictor are important for triggering DL-I(nterpretation), they do not directly influence DL-S. The ambiguity of Amount-whs is also examined and the conclusion reached is that there are two #P projections: A NumP and a CardP. The dissertation proceeds with the structurally represented notions of definiteness and specificity and examines how these can help capturing the wh-determiner typology proposed. The idea that D-linking can be explained by recourse to topicality is discussed in detail. Empirical evidence is provided for the existence of wh-topics in general and for the claim that many DWH can be construed as wh-topics.
In chapter 4, the general pattern on which wh-pronouns are built are examined, and it is argued that the results bear directly on the topic of this thesis since wh-determiners are universally derived from pronouns. Wh-pronouns are diachronically built out of an element indicating the function of the proform (wh-morpheme), and an element denoting the range of the proform (Range Restrictor). Among other things, it is argued that the wh-morpheme does not mark interrogativity, leading to the adoption of a version of Q-theory. It is also briefly discussed whether the results are compatible with the hypothesis that wh-determiner phrases are Small Clauses. One claim is that all wh-pronouns are fossilized interrogative sentences, lending further support to the parallelism between sentential and nominal structures. It is then argued that Morphological Restrictors can be subdivided into Formal Features and Functional Nouns (and that elements which can become Functional Nouns are taken from the pool of Basic Ontological Categories). The question answered is how these elements synchronically contribute to the meaning of the wh-determiners. After examining the role of the Nominal Restrictor to the syntax of wh-determiners, the thesis continues investigating how Nominal Restrictor are related to Functional Nouns. Finally, the discussion expands to the structural correlates for DL-S effects. It is demonstrated how the results can formally be applied to wh-split constructions in order to explain differences between empty categories. Then, the results of the section on partitivity support the idea that the occurrences of most of the DL-S effects seem to strongly depend on the presence of a second nominal constituent in the structure of wh-phrases. This second nominal can be either a Functional Noun inside the wh-item used as wh-pronoun or an overt second noun as in wh-partitive phrases.
The contribution of this thesis to linguistic theorizing is not a full-fledged technical analysis of every single DL-S effect, but rather the systemisation proposed. Although a lot of terminology is introduced, the outcome of this proliferation of terms is a sharper picture of the intricate relations between the constituents of the wh-items used as wh-determiners and the Nominal Restrictor. Another main conclusion is that the concept of D-linking is not a basic notion. It is comprised of four components (of which DL-Syntax and Morphological-DL have been scrutinized in this thesis). This assumption explains why DWH do not constitute a homogeneous class. The gradual character of D-linking (i.e. the fact that certain wh-determiner constructions show only a subset of DL-S effects even if they are headed by what could faithfully be classified as a/the Token-wh determiner of the respective language) is argued to be related to the fact that the Token-reading itself can have several triggers.
Mit Blick auf die gescheiterten Verhandlungen mit Griechenland, argumentiert Jan Krahnen im vorliegenden Policy Beitrag, dass eine zielführende Reformagenda nur von der gewählten Regierung Griechenlands formuliert werden kann. Die Euro-Staaten müssten Griechenland für die Zeitdauer einer Restrukturierungszeit eine Grundsicherung zusagen. Die EU-Staaten fordert Krahnen dazu auf, aus der Griechenlandkrise die notwendigen Konsequenzen zu ziehen. Auch die Eurozone brauche eine effektive Reformagenda. Die Verschuldungsdynamik innerhalb der Währungsunion, deren Auswüchse am Beispiel Griechenlands besonders deutlich werden, könne bei fehlendem guten Willen nur durch eine politische Union und eine in sie eingebettete Fiskalunion aufgelöst werden. Krahnen argumentiert, dass ein Weiterverhandeln über Restrukturierungsauflagen aus der derzeitigen verfahrenen Situation nicht herausführen wird. Entscheidend sei, ein mehr oder weniger umfassendes Paket zu schnüren, das Elemente eines teilweisen internationalen Haftungsverbunds mit Elementen eines partiellen nationalen Souveränitätsverzichts verbindet.
In light of the failed negotiations with Greece, Jan Krahnen argues that an effective reform agenda for Greece can only be designed by the elected government. Fundamental reforms will take time to take full effect and euro area member states will, in the meantime, have to offer Greece a basic level of economic security.
Krahnen demands that policy makers and the professional public involved view the Greek crisis as an opportunity to take the next necessary steps to formulate a reform agenda for the European Monetary Union. A community of supranational and non-party researchers and intellectuals could take the initiative and in a structured process develop a trustworthy and realistic concept that drafts the next big step towards a political union of Europe, including elements of a fiscal union.
Plasma fibronectin is a circulating protein that facilitates phagocytosis by connecting bacteria to immune cells. A fibronectin isoform, which includes a sequence of 90 AA called extra-domain B (EDB), is synthesized de novo at the messenger RNA (mRNA) level in immune cells, but the reason for its expression remains elusive. We detected an 80-fold increase in EDB-containing fibronectin in the cerebrospinal fluid of patients with bacterial meningitis that was most pronounced in staphylococcal infections. A role for this isoform in phagocytosis was further suggested by enhanced EDB fibronectin release after internalization of Staphylococcus aureus in vitro. Using transgenic mouse models, we established that immune cell production of fibronectin contributes to phagocytosis, more so than circulating plasma fibronectin, and that accentuated release of EDB-containing fibronectin by immune cells improved phagocytosis. In line with this, administration of EDB fibronectin enhanced in vitro phagocytosis to a larger extent than plasma fibronectin. This enhancement was mediated by αvβ3 integrin as shown using inhibitors or cells from β3 integrin knockout mice. Thus, we identified both a novel function for EDB fibronectin in augmenting phagocytosis over circulating plasma fibronectin, as well as the mediating receptor. Our data also establish for the first time, a direct role for β3 integrin in bacterial phagocytosis in mammals.
We set up and solve a rich life-cycle model of household decisions involving consumption of both perishable goods and housing services, stochastic and unspanned labor income, stochastic house prices, home renting and owning, stock investments, and portfolio constraints. The model features habit formation for housing consumption, which leads to optimal decisions closer in line with empirical observations. Our model can explain (i) that stock investments are low or zero for many young agents and then gradually increasing over life, (ii) that the housing expenditure share is age- and wealth-dependent, (iii) that perishable consumption is more sensitive to wealth and income shocks than housing consumption, and (iv) that non-housing consumption is hump-shaped over life.
Background: Cardiovascular magnetic resonance (CMR) offers quantification of phasic atrial functions based on volumetric assessment and more recently, on CMR feature tracking (CMR-FT) quantitative strain and strain rate (SR) deformation imaging. Inter-study reproducibility is a key requirement for longitudinal studies but has not been defined for CMR-based quantification of left atrial (LA) and right atrial (RA) dynamics.
Methods: Long-axis 2- and 4-chamber cine images were acquired at 9:00 (Exam A), 9:30 (Exam B) and 14:00 (Exam C) in 16 healthy volunteers. LA and RA reservoir, conduit and contractile booster pump functions were quantified by volumetric indexes as derived from fractional volume changes and by strain and SR as derived from CMR-FT. Exam A and B were compared to assess the inter-study reproducibility. Morning and afternoon scans were compared to address possible diurnal variation of atrial function.
Results: Inter-study reproducibility was within acceptable limits for all LA and RA volumetric, strain and SR parameters. Inter-study reproducibility was better for volumetric indexes and strain than for SR parameters and better for LA than for RA dynamics. For the LA, reservoir function showed the best reproducibility (intraclass correlation coefficient (ICC) 0.94–0.97, coefficient of variation (CoV) 4.5–8.2 %), followed by conduit (ICC 0.78–0.97, CoV 8.2–18.5 %) and booster pump function (ICC 0.71–0.95, CoV 18.3–22.7). Similarly, for the RA, reproducibility was best for reservoir function (ICC 0.76–0.96, CoV 7.5–24.0 %) followed by conduit (ICC 0.67–0.91, CoV 13.9–35.9) and booster pump function (ICC 0.73–0.90, CoV 19.4–32.3). Atrial dynamics were not measurably affected by diurnal variation between morning and afternoon scans.
Conclusions: Inter-study reproducibility for CMR-based derivation of LA and RA functions is acceptable using either volumetric, strain or SR parameters with LA function showing higher reproducibility than RA function assessment. Amongst the different functional components, reservoir function is most reproducibly assessed by either technique followed by conduit and booster pump function, which needs to be considered in future longitudinal research studies.
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
Device-related infections in recipients of left ventricular assist devices (LVAD) have been recognized as a major source of morbidity and mortality. They require a high level of diagnostic effort as part of the overall burden resulting from infectious complications in LVAD recipients. We present a multi-allergic patient who was treated for persistent sterile intrathoracic abscess formation and pericardial empyema following minimally invasive LVAD implantation including use of a sheet of e-polytetrafluoroethylene (ePTFE) membrane to restore pericardial integrity. Sterile abscess formation and pericardial empyema recurred after surgical removal until the ePTFE membrane was removed, suggesting that in disposed patients, ePTFE may be related to sterile abscess formation or sterile empyema.
Leben braucht Licht und den täglichen Wechsel von Licht und Dunkel. Das gilt auch für den Menschen. Licht dient unserer Orientierung – nicht nur im Raum, sondern auch in der Zeit. Der Tag-Nacht-Wechsel ist der wichtigste Umweltreiz für die Taktung unserer Inneren Uhr. Zu wenig Licht am Tag und zu viel Licht in der Nacht kann sie aus dem Takt bringen und zu Schlafstörungen und Depressionen führen.
Data supporting the role of the non-glycosylated isoform of MIC26 in determining cristae morphology
(2015)
Membrane architecture is crucially important for mitochondrial function and integrity. The MICOS complex is located at crista junctions and determines cristae membrane morphology and the formation of crista junctions. Here we provide data of the bona fide MICOS subunit MIC26 for determining cristae morphology. MiRNA-mediated downregulation of MIC26 results in higher protein levels of MIC27 and in lower levels of Mic10. Using a miRNA-resistant form to MIC26 we show that this effect is specific to MIC26. Our data further demonstrate that depletion of MIC26 primarily affects the level of the 22 kDa mitochondrial isoform of MIC26 but not the amount of the secreted 55 kDa isoform of MIC26. Depletion of MIC27, however, increases secretion of the latter isoform. Overexpression of a myc-tagged version of MIC26 resulted in altered cristae morphology with swollen and partly vesicular cristae-structures.
Die vorliegende Dissertation mit dem Titel: Ecophysiological monitoring of Oaks in Central Europe, introduced in the framework of proactive climate change mitigation beschäftigt sich mit der Anwendung zerstörungsfreier, radiometrischer Methoden zur Bestimmung von Pigment- und Stickstoffkonzentrationen und der photosynthetischen Funktionalität in Blättern von heimischen und gebietsfremden Eichen und ihre Beeinflussung durch Trocken-, Hitze- und Kältestress.
Die Eichenarten Quercus robur L. (Stieleiche), Q. pubescens Willd. (Flaumeiche), Q. frainetto Ten. (Ungarische Eiche), Q. ilex L. (immergrüne Steineiche) und Q. rubra L. (amerikanische Roteiche) wurden im Frühjahr 2011 auf einer Versuchsfläche im Frankfurter Stadtwald gepflanzt, um ihre Nutzung als potentielle Waldbäume in einem sich ändernden Klima zu untersuchen. Über eine Dauer von zwei Jahren wurden diese Arten mit einem hohen Maß an blattspezifischer Merkmalsvariabilität beobachtet und beprobt. Ziel war es, die interspezifischen Unterschiede und die jahreszeitliche Dynamik von morphologischen und chemischen Blattmerkmalen sowie die Beeinflussung der radiometrischen Bestimmung des Chlorophyllgehaltes (und damit assoziierten Komponenten wie z.B. Blattstickstoffgehalt und Karotinoiden) und der photosynthetischen Funktionalität durch klimatische Umweltbelastungen in Eichen zu untersuchen. Die Analyse der Blattproben zielte neben der Bestimmung der Beziehung zwischen absoluten und optisch ermittelten Pigmentgehalten auf die Ermittlung des Einflusses der Blattstruktur auf die Lichttransmission im roten und infrarotem Bereich des Elektromagnetischen Spektrums ab, sowie auf die artspezifische Korrelation von Blattstickstoff zu Blattchlorophyll zu dessen indirekte Quantifizierung. Des Weiteren wurden Versuche zur Trocken- und Hitzestressanpassung durchgeführt, um eine potentiell artspezifische Stressantwort, sowie eine mögliche Beeinflussung der aufgenommenen radiometrischen Messwerte zu ermitteln. Ein zusätzliches Monitoringprogramm im Winter 2012/2013 mit einer Dauer von sechs Monaten ermöglichte die Überprüfung der Anpassungsfähigkeit der immergrünen Steineiche (Q. ilex) an mitteleuropäische Winterbedingungen und die Veränderung der photosynthetischen Funktionalität unter Kältestress. Messungen im Zusammenhang mit der praktischen Anwendbarkeit der zerstörungsfreien, optischen Methode und zur Bereitstellung von Referenzdaten für zukünftige Evaluierungen komplementieren die Untersuchungen.
Signifikante, artspezifische Unterschiede wurden in den blattmorphologischen Schlüsselmerkmalen in den Quercus-Arten ermittelt. Die artspezifischen Unterschiede in den morphologischen Blattmerkmalen beeinflussten auf signifikante Weise die Beziehung zwischen absoluten, massebasierten Pigment- und Stickstoffgehalten und deren radiometrischen Bestimmung. Wurden die Pigmentgehalte hingegen auf die Blattfläche bezogen und die Stickstoffgehalte mittels des Verhältnisses von Blattfläche zu Trockenmasse korrigiert, zeichnete sich eine Beziehung zwischen absoluten und optisch ermittelten Werten ab, der jegliche jahreszeitliche oder artspezifisch morphologische Variabilität fehlte und die somit für alle Quercus-taxa anwendbar ist. Koeffizienten für die Berechnung von flächenbezogenen Gehalten von Gesamtchlorophyll, Chl a, Chl b und Carotinoiden für die jeweiligen Quercus-taxa, wie auch für ein artübergreifendes Modell wurden ermittelt, um die Bestimmung dieser Gehalte während aller Entwicklungsstufen zu ermöglich. Aus der jahreszeitlichen Entwicklung der Pigmentgehalte konnten drei deutliche Phasen abgeleitet werden: Die Phase der Blattentwicklung im Frühling, einer Plateauphase mit geringen Veränderungen (“core vegetation time”) und die Phase des Pigmentabbaus während der Herbstlaubfärbung. Die Übergänge zwischen diesen Phasen variierten zum Teil erheblich zwischen einzelnen Individuen einer Art sowie zwischen den Arten, was Unterschiede in der potentiellen, jährlichen Kohlenstoffaufnahme nach sich zieht. Stressbedingungen, wie Hitze- Kälte- oder Trockenstress, können zu Veränderung von Fluoreszenzparametern ohne gleichzeitige Änderung des Pigmentgehaltes führen, wie auch die indirekte Bestimmung von mit Chl assoziierten Komponenten (Carotinoide, Chl a, Chl b) mittels optischer Bestimmung (durch die Veränderungen von Pigmentverhältnissen) beeinflussen.
Im Rahmen des Forschungsprojektes konnten, Modelle zur Berechnung von Blattpigmenten und Blattstickstoff aus optischem Messdaten, Veränderungen der photosynthetischen Funktionalität, sowie Referenzdaten für die zukünftig nutzbaren Eichenarten hinsichtlich artspezifischer und jahreszeitlicher Variabilität unter mitteleuropäischen Umweltbedingungen ermittelt werden, die eine Nutzung und Einordnung von zerstörungsfreien, optischen Messwerten zur Ermittlung von Vitalitätsunterschieden in Eichen ermöglichen.
"Die Flüchtlinge", "die Rassisten" und "Wir" – zu den Ambivalenzen im aktuellen Flüchtlingsdiskurs
(2015)
Dies ist der dritte Artikel unseres Blogfokus zu Flucht und Migration. Die vehemente Verurteilung der verbalen und gewaltvollen Übergriffe auf Geflüchtete, die zivilgesellschaftliche Solidarität, mit der Geflüchtete an Bahnhöfen, in Vereinen und Nachbarschaften Willkommen geheißen werden, die kleinen und großen Gesten privater Flüchtlingshilfe – all dies sind wichtige Signale gegen rassistische Hetze und Abschreckungspolitik. Der Flüchtlingshilfediskurs bleibt dennoch ambivalent und lässt sich aktuell an mindestens drei Fragen diskutieren: Wann verfehlen Positionierungen ‚gegen Rechts‘ das Ziel, rassistische Verhältnisse in der Gesellschaft aufzubrechen? Wann läuft das private Engagement im Flüchtlingsbereich Gefahr, politisches Handeln zu ersetzen? Und welche Schwierigkeiten gehen mit der Konjunktur des ‚Helfer-Wirs‘ einher? Eine Gratwanderung.
This report was written by the organizers of the workshop "Accounting for Combat-Related Killings," which took place at the Goethe University Frankfurt in July 2014. Scholars from Israel, the United Kingdom, the United States,, Canada, and Germany came together to present and discuss case studies on the discourse practices involved in accounting for combat-related killings in different national and transnational contexts. Intending to reflect on the methodological skills needed to analyze newly available process data, the workshop brought together scholars using different methodological approaches (here mainly ethnomethodology and critical discourse analysis). In regard to the global trend towards increasing numbers of so called permanent, asymmetric, small, and permanent wars, the report turns to concepts, methods, and empirical findings that foster understandings of the difficulties war generates at social, cultural and political levels as well as the manner in which these predicaments are negotiated, denied, or deflected. The report summarizes the workshop by presenting the papers in a specific order, beginning with accounting in combat, followed by tribunals of accounting, and finally the sedimentation of accounting in cultural representations.
Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling.
Translation elongation factor Tuf of Acinetobacter baumannii is a plasminogen-binding protein
(2015)
Acinetobacter baumannii is an important nosocomial pathogen, causing a variety of opportunistic infections of the skin, soft tissues and wounds, urinary tract infections, secondary meningitis, pneumonia and bacteremia. Over 63% of A. baumannii infections occurring in the United States are caused by multidrug resistant isolates, and pan-resistant isolates have begun to emerge that are resistant to all clinically relevant antibiotics. The complement system represents the first line of defense against invading pathogens. However, many A. baumannii isolates, especially those causing severe bacteremia are resistant to complement-mediated killing, though the underlying mechanisms remain poorly understood. Here we show for the first time that A. baumannii binds host-derived plasminogen and we identify the translation elongation factor Tuf as a moonlighting plasminogen-binding protein that is exposed on the outer surface of A. baumannii. Binding of plasminogen to Tuf is at least partly dependent on lysine residues and ionic interactions. Plasminogen, once bound to Tuf can be converted to active plasmin and proteolytically degrade fibrinogen as well as the key complement component C3b. Thus, Tuf acts as a multifunctional protein that may contribute to virulence of A. baumannii by aiding in dissemination and evasion of the complement system.
In der vorliegenden Arbeit wurde erstmals die Interaktion von A. baumannii mit humanem Plasminogen untersucht. Mit dem Translations-Elongationsfaktor TufAb, dem äußeren Membranprotein OmpW sowie dem Lipoprotein p41 konnten insgesamt drei Plasminogen-bindende Proteine von A. baumannii identifiziert werden. Außerdem wurde ein grundlegender Beitrag zur funktionellen Charakterisierung von TufAb sowie p41 von A. baumannii erbracht.
Es konnte nachgewiesen werden, dass gereinigtes TufAb humanes Plasminogen bindet und diese Interaktion teilweise durch Lysin-Reste vermittelt und von der Ionenstärke beeinflusst ist. An TufAb-gebundenes Plasminogen war für den Plasminogen-Aktivator u-PA zugänglich und konnte zu Plasmin aktiviert werden, welches das chromogene Substrat S-2251, das physiologische Substrat Fibrinogen und die zentrale Komplementkomponente C3b proteolytisch spaltete. Schließlich konnte TufAb als „Moonlighting“-Protein auf der Zelloberfläche von A. baumannii identifiziert werden.
Für das Lipoprotein p41 konnte ebenfalls gezeigt werden, dass dieses an Plasminogen bindet. Die Bindung von Plasminogen an p41 erfolgte ebenfalls über Lysin-Reste, zeigte sich allerdings von der Ionenstärke unbeeinflusst. Im Fall von p41 konnte mit Hilfe von C-terminal verkürzten p41-Konstrukten gezeigt werden, dass C-terminale Lysin-Reste an der Bindung von Plasminogen beteiligt sind. Weitere Versuche mit p41-Proteinen, bei welchen vier C-terminale Lysin-Reste durch Alanin-Reste substituiert wurden, ergaben, dass die beiden Lysin-Reste K368 und K369 essentiell für die Bindung von Plasminogen an p41 sind. Zudem konnte gezeigt werden, dass sowohl Kringle-Domäne 1 als auch Kringle-Domäne 4 von Plasminogen bei der Interaktion mit p41 involviert sind. An p41 gebundenes Plasminogen ließ sich durch u-PA zu Plasmin aktivieren, welches Fibrinogen sowie die zentrale Komplementkomponente C3b degradierte. p41 ist außerdem in der Lage, die Komplementkomponenten C3, C3b und C5 zu binden und den alternativen Weg zu inhibieren. Zudem ergaben Untersuchungen im Rahmen dieser Arbeit erste Hinweise darauf, dass zumindest die Plasminogen-bindende Region auf der Zelloberfläche von A. baumannii lokalisiert ist.
Die Inaktivierung des p41-kodierenden Gens führte zu einer signifikanten Abnahme im Überleben von A. baumannii-Zellen in der Gegenwart von NHS. Zudem zeigte die Mutante Δp41 einen Defekt in der Plasmin-abhängigen Transmigration durch einen Endothelzell-Monolayer. Beide Versuche untermauern die physiologische Relevanz für die Interaktion von A. baumannii mit Plasminogen.
Background: Curcuminoids (curcumin, demethoxycurcumin, bis-demethoxycurcumin) are lipophilic polyphenols thought to be effective in the prevention and treatment of neurodegenerative disorders, of which mitochondrial dysfunction is a prominent feature. In particular, older people may thus benefit from increasing their curcuminoid intake. However until now, it is not investigated if there exist age differences in the bioavailability of curcuminoids and therefore, it is unclear if curcumin doses have to be adjusted to age. Thus, we explored if the tissue concentrations and biological activities of curcuminoids are affected by age.
Methods: We investigated age-differences in the bioavailability and tissue distribution of curcuminoids and mitochondrial function in 3- and 18-months old mice fed a control diet or identical diets fortified with 500 or 2000 mg curcuminoids/kg for 3 weeks. Therefore, we measured curcuminoid concentrations in plasma, liver, kidney, and brain, basal and stress-induced levels of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) in dissociated brain cells and citrate synthase activity of isolated mitochondria.
Results: Plasma but not liver and kidney curcuminoid concentrations were significantly higher in older mice. Age did not affect ATP concentrations and MMP in dissociated brain cells. After damaging cells with nitrosative stress, dissociated brain cells from old mice had a higher MMP than cells from young animals and were therefore more resistant. Furthermore, this effect was enhanced by curcumin.
Conclusion: Our data suggest that age may affect plasma concentrations, but not the tissue distribution of curcuminoids in mice, but has little impact on mitochondrial function in brain cells.
An increasing body of evidences from preclinical as well as epidemiological and clinical studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning. In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and affective disorders is warranted.
The current Review article provides a narrative review about the neurobiological underpinnings and treatment of treatment resistant late-life depression (TRLLD). The manuscript focuses on therapeutic targets of late-life depression, which include pharmacological, psychological, biophysical and exercise treatment approaches. Therefore, we summarize available evidences on that kind of therapies for patients suffering from late-life depression. The search for evidences of therapeutic options of late-life depression were done using searching websites as “pubmed”, and using the searching terms “depression”, “late-life depression”, “treatment”, “biophysical therapy”, “exercise therapy”, “pharmacological therapy” and “psychological therapy”. To the end, we summarize and discuss current data, providing some directions for further research.
Treatment recommendations for elderly depressive patients favour a multimodal approach, containing psychological, pharmacological and secondary biophysical therapeutic options. Particularly, a combination of psychotherapy and antidepressant medication reflects the best therapeutic option. However, mostly accepted and used is the pharmacological treatment although evidence suggests that the drug therapy is not as effective as it is in younger depressive patients. Further studies employing larger samples and longer follow-up periods are necessary and may focus on comparability of study designs and involve novel approaches to establish the validity and reliability of multimodal treatment programs.
Introduction: In this article three research questions are addressed: (1) Is there an association between socioeconomic status (SES) and patient-reported outcomes in a cohort of multimorbid patients? (2) Does the association vary according to SES indicator used (income, education, occupational position)? (3) Can the association between SES and patient-reported outcomes (self-rated health, health-related quality of life and functional status) be (partly) explained by burden of disease?
Methods: Analyses are based on the MultiCare Cohort Study, a German multicentre, prospective, observational cohort study of multimorbid patients from general practice. We analysed baseline data and data from the first follow-up after 15 months (N = 2,729). To assess burden of disease we used the patients’ morbidity data from standardized general practitioner (GP) interviews based on a list of 46 groups of chronic conditions including the GP’s severity rating of each chronic condition ranging from marginal to very severe.
Results: In the cross-sectional analyses SES was significantly associated with the patient-reported outcomes at baseline. Associations with income were more consistent and stronger than with education and occupational position. Associations were partly explained (17% to 44%) by burden of disease. In the longitudinal analyses only income (but not education and occupational position) was significantly related to the patient-reported outcomes at follow-up. Associations between income and the outcomes were reduced by 18% to 27% after adjustment for burden of disease.
Conclusions: Results indicate social inequalities in self-rated health, functional status and health related quality of life among older multimorbid patients. As associations with education and occupational position were inconsistent, these inequalities were mainly due to income. Inequalities were partly explained by burden of disease. However, even among patients with a similar disease burden, those with a low income were worse off in terms of the three patient-reported outcomes under study.
Die aktuelle Debatte um Pornographie stellt sich andere Fragen als in den kämpferischen 70er Jahren. In den interdisziplinären Beiträgen des Sammelbandes wird Pornographie als kulturelles Artefakt behandelt, als Begriff, der in Diskurse über Sexualität und Moderne, über Identität und Jugend verwoben ist. Die Autor_innen arbeiten mit empirisch-sozialwissenschaftlichen Methoden Fragen nach dem Nutzer_innenverhalten von Onlinepornographie und jugendlichem Pornokonsum auf, bieten theoriegeleitete Zugänge zur Unbestimmbarkeit von Pornographie, zu ihrer notwendigen Einbettung in andere gesellschaftliche Kontexte sowie künstlerische Interventionen zu ihrem emanzipatorischen Potential. Die Beiträge bieten einen gelungenen Einblick in den aktuellen Stand der Debatte dieses noch jungen Feldes.
Im Rahmen dieser Dissertation wurden drei bakterielle Enzyme, die Metallo-β-Lactamasen NDM-1 (New Delhi Metallo-β-Lactamase 1), VIM-1 (Verona-Integron Encoded Metallo-β-Lactamase 1) und IMP-7 (Imipenemase 7), sowie ein humanes Enzym, die sEH-Phosphatase, behandelt.
Das Auftreten multiresistenter Bakterien ist eine alarmierende Entwicklung. Dabei ist das vermehrte Erscheinen von Metallo-β-Lactamasen (MBLs) in Gramnegativen Bakterien zu beobachten, die von Inhibitoren anderer β-Lactamasen unbeeinflusst bleiben. MBLs sind Enzyme, die β-Lactam-Antibiotika hydrolysieren und somit unwirksam machen. β-Lactam-Antibiotika hemmen die Zellwandsynthese von Bakterien und haben keinen Einfluss auf menschliche Zellen. Daher sind sie für den Menschen sehr gut verträglich und werden oft eingesetzt. Gerade diese häufige Verwendung und der Fehleinsatz führen vermehrt zur Resistenzbildung. Suche nach neuen Wirkstoffen zur Behandlung von Pathogenen mit Resistenz ist von äußerster Dringlichkeit, da die Resistenzen sich in kürzester Zeit über den kompletten Planeten verbreiten.
NDM-1, VIM-1 und IMP-5 wurden in E.coli überexprimiert und aufgereinigt, um die rekombinanten Enzyme zu erhalten. Damit wurde zunächst ein Fluoreszenz-Intensitäts-Assay entwickelt, um die Wirksamkeit möglicher Inhibitoren zu quantifizieren. Als Testsubstanzen wurden elf zugelassene Wirkstoffe gewählt, die eine Thiol-Gruppe enthalten, da bekannt ist, das Thiole Zink-abhängige Proteine inhibieren. Weiterhin wurden Thermal Shift Assays durchgeführt, um zwischen Liganden, die durch Bindung an die MBL inhibieren, und Liganden, die nur dadurch inhibieren, dass sie der Bindetasche das nötige Zink entziehen, unterscheiden zu können. Substanzen, die Inhibition im Assay zeigten und keine Zink-Chelatoren waren, wurden weiterhin auf Aktivität in bakteriellen Zellen untersucht. Dafür wurden pathogenene Stämme aus Patienten sowie mit den Resistenzplasmiden transfizierte Laborstämme einem Test auf Antibiotikaempfindlichkeit unterzogen. Die Wirksamkeit von Imipenem sollte in Kombination mit den Testsubstanzen wieder hergestellt werden. Insgesamt wurden vier Substanzen mit nicht-antiinfektiösen Indikationen gefunden, die MBLs im niedrig-mikromolaren Bereich inhibieren und die Wirksamkeit von Imipenem in Bakterien partiell wieder herstellen.
In einem zweiten Ansatz wurden Fragmente mittels Docking ausgewählt und ebenfalls im Fluoreszenz-basierten Assay getestet. Die Bestätigung der Bindung erfolgte in diesem Fall mit STD-NMR und die Bestimmung der Dissoziationskonstante des besten Fragments mittels Messung der Chemical Shift Perturbation im NMR. In diesem Projekt wurde leider kein pan-Inhibitor für alle MBLs gefunden, allerdings ein Fragment mit hoher Bindeeffizienz zur NDM-1.
Die lösliche Epoxid-Hydrolase (englisch: soluble Epoxid Hydolase, sEH) katalysiert die Umsetzung von Epoxyeicosatriensäuren (EETs), Lipidmediatoren mit entzündungshemmenden und kardiovaskulär-protektiven Eigenschaften, zu Dihydroxyeicosatriensäuren (DHETs). Diese Reaktion ist ein Bestandteil der Arachidonsäurekaskade. Das Enzym besteht aus zwei Domänen mit unterschiedlichen katalytischen Funktionen, einerseits der viel erforschten Cterminalen Epoxid-Hydrolase-Domäne, aber auch der N-terminalen Domäne, die eine Phosphatase-Eigenschaft zeigt. Die N-terminale Domäne katalysiert die Hydrolyse von Phosphat-Monoestern, Isoprenoid- sowie Lipid-Phosphaten. Die biologische Funktion dieser Domäne ist nicht aufgeklärt, und die Phosphatase Aktivität wird von typischen Phosphatase-Inhibitoren nicht beeinflusst. Daher ist es von Interesse, einen Inhibitor zu entwickeln.
Zunächst wurde ein Aktivitätsassay mit einem fluorogenen Substrat entwickelt und dieser in verschiedene Formate überführt, um in unterschiedlichen Größen testen zu können. Im 96well Format wurden mögliche Inhibitoren getestet, die mittels Docking ausgesucht wurden. Allerdings wurden nur Inhibitoren mit IC50s über 100 μM gefunden oder Inhibitoren, die Sulfonsäure-Strukturen aufweisen. Im 384well Format wurde, in Kollaboration mit dem European ScreeningPort Hamburg, ein High-Throughput Screening von ca. 17000 Substanzen durchgeführt. So wurde Oxaprozin gefunden, ein Inhibitor, der strukturelle Ähnlichkeit zu bereits bekannten Inhibitoren zeigt.
We present in this paper spectral and spatial characteristics of terahertz emission from standard dipole antenna structures used as emitters depending on the substrate material. All antenna structures were lithographically fabricated on low-temperature (LT) grown, few-micrometers-thick gallium arsenide (GaAs) layers. To investigate the effect of the substrate material on the radiation pattern of terahertz beams, either semi-insulating gallium arsenide or high-resistivity silicon substrate wafers have been used. As detector a standard 40 µm long dipole antenna on a semi-insulating GaAs substrate with a low-temperature grown gallium arsenide layer on it has been employed; this configuration allows for broadband detection and is still efficient enough for the characterization purpose. Strong dependence of the radiation pattern on the substrate used for the terahertz source is demonstrated. The measured patterns and differences between the two cases of substrates are well explained by means of classical diffraction.
Previous research on working memory (WM) in children with poor mathematical skills has yielded heterogeneous results, possibly due to inconsistent consideration of the IQ-achievement discrepancy and additional reading and spelling difficulties. To examine the impact of both, the WM of 68 average-achieving and 68 low-achieving third-graders in mathematics was assessed. Preliminary analyses showed that poor mathematical skills were associated with poor WM. Afterwards, children with isolated mathematical difficulties were separated from those with additional reading and spelling difficulties. Half of each group fulfilled the IQ-achievement discrepancy, resulting in a 2 (additional reading and spelling difficulties: yes/no) by 2 (IQ-achievement discrepancy: yes/no) factorial design. Analyses revealed that not fulfilling the IQ achievement discrepancy was associated with poor visual WM, whereas additional reading and spelling difficulties were associated with poor central executive functioning in children fulfilling the IQ-achievement discrepancy. Therefore, WM in children with poor mathematical skills differs according to the IQ-achievement discrepancy and additional reading and spelling difficulties.
Im Zuge der (wieder) zunehmenden Aufmerksamkeit verschiedenster IB-Theorien für postkoloniale Problemlagen hat unter ‚nördlichen‘ IB-Forschern das Interesse an Dialog und Auseinandersetzung mit den IB-Communities des ‚globalen Südens‘ zugenommen. Dieser Beitrag will Möglichkeiten und Hindernisse dieses Dialogs für den Fall der südamerikanischen IB-Communities aufzeigen. Es soll gewissermaßen eine ‚Bedienungsanleitung‘ erstellt werden, um dem interessierten Außenseiter das Verständnis der Interessenlagen, theoretischen Präferenzen und der konkreten Arbeitssituationen südamerikanischer IB-Forscher zu erleichtern. Dies geschieht selbstredend unter Betonung der Unvollständigkeit der Beschreibung sowie der Perspektivenabhängigkeit des Beobachters.
Die bisher nicht lückenlos aufgeklärte, vermutlich aber Gruppen der organisierten Kriminalität zuzurechnende Ermordung von über 40 Lehramtsstudenten in der südmexikanischen Kleinstadt Ayotzinapa Ende 2014 hat ebenso wie die seit dem Abschuss eines Militärhubschraubers im Mai 2015 eskalierende Gewalt im westlichen Bundesstaat Jalisco wieder einmal schmerzlich in Erinnerung gerufen, dass in Mexiko bereits seit fast neun Jahren ein blutiger Gewaltkonflikt im Gange ist, der angesichts der wirtschaftlichen Erfolge des „Aztec tiger“ teils fast schon vergessen schien.
Future FAIR experiments have to deal with very high input rates, large track multiplicities, make full event reconstruction and selection on-line on a large dedicated computer farm equipped with heterogeneous many-core CPU/GPU compute nodes. To develop efficient and fast algorithms, which are optimized for parallel computations, is a challenge for the groups of experts dealing with the HPC computing. Here we present and discuss the status and perspectives of the data reconstruction and physics analysis software of one of the future FAIR experiments, namely, the CBM experiment.