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In the crystal of the title co-crystalline adduct, C8H16N4·C8H9ClO, (I), prepared by solid-state reaction, the molecules are linked by intermolecular O—H⋯N hydrogen bonds, forming a D motif. The azaadamantane structure in (I) is slightly distorted, with N—CH2—CH2—N torsion angles of 10.4 (3) and −9.0 (3)°. These values differ slightly from the corresponding torsion angles in the free aminal cage (0.0°) and in related co-crystalline adducts, which are not far from a planar geometry and consistent with a D2d molecular symmetry in the tetraazatricyclo structure. The structures also differ in that there is a slight elongation of the N—C bond lengths about the N atom that accepts the hydrogen bond in (I) compared with the other N—C bond lengths. In the crystal, the two molecules are not only linked by a classical O—H⋯N hydrogen bond but are further connected by weak C—H⋯π interactions, forming a two-dimensional supramolecular network parallel to the bc plane.
The crystal structure of the title compound, C25H24N2O2, at 173 K has monoclinic (C2/c) symmetry. The molecule is located on a crystallographic twofold rotation axis with only half a molecule in the asymmetric unit. The imidazolidine ring adopts a twist conformation, with a twist about the ring C—C bond. The crystal structure shows the anticlinal disposition of the two (2-hydroxynaphthalen-1-yl)methyl substituents of the imidazolidine ring. The structure displays two intramolecular O—H⋯N hydrogen bonds, each forming an S(6) ring motif.
In the title ternary co-crystalline adduct, C7H14N4·2C6H5NO3, molecules are linked by two intermolecular O—H⋯N hydrogen bonds, forming a tricomponent aggregates in the asymmetric unit. The hydrogen-bond formation to one of the N atoms is enough to induce structural stereoelectronic effects in the normal donor→acceptor direction. In the title adduct, the two independent nitrophenol molecules are essentially planar, with maximum deviations of 0.0157 (13) and 0.0039 (13) Å. The dihedral angles between the planes of the nitro group and the attached benzene rings are 4.04 (17) and 5.79 (17)°. In the crystal, aggregates are connected by C—H⋯O hydrogen bonds, forming a supramolecular dimer enclosing an R66(32) ring motif. Additional C—H⋯O intermolecular hydrogen-bonding interactions form a second supramolecular inversion dimer with an R22(10) motif. These units are linked via C—H⋯O and C—H⋯N hydrogen bonds, forming a three-dimensional network.
The title compound, C21H26Cl2N2O2, was prepared in a solvent-free microwave-assisted synthesis, and crystallizes in the orthorhombic space group Pna21. The imidazolidine ring adopts an envelope conformation and its mean plane is almost perpendicular to the two pendant aromatic rings [dihedral angles = 84.61 (9) and 86.54 (9)°]. The molecular structure shows the presence of two intramolecular O—H⋯N hydrogen bonds between the phenolic hydroxy groups and imidazolidine N atoms. The two 3-chloro-6-hydroxy-2,4-dimethylbenzyl groups are located in a cis orientation with respect to the imidazolidine fragment. As a result, the lone pairs of electrons on the N atoms are presumed to be disposed in a syn conformation. This is therefore the first example of an exception to the `rabbit-ears' effect in such 2,2′-[imidazolidine-1,3-diylbis(methylene)]diphenol derivatives.
Analyzing the relationship between differentiated online sentiment and company-specific stock prices
(2015)
PRACTITIONERS AND RESEARCHERS ALIKE INCREASINGLY USE SOCIAL MEDIA MESSAGES AS AN ADDITIONAL SOURCE OF INFORMATION WHEN DEALING WITH STOCKS. BASED ON EMOTION THEORY AND AN ESTABLISHED SENTIMENT LEXICON, WE DEVELOP AND APPLY AN OPEN SOURCE DICTIONARY FOR THE ANALYSIS OF SEVEN DIFFERENT EMOTIONS IN 5.5 MILLION TWITTER MESSAGES ON 33 S&P 100 COMPANIES. WE FIND VARYING EXPLANATORY POWER OF DIFFERENT EMOTIONS (ESP. HAPPINESS, AND DEPRESSION) FOR COMPANY-SPECIFIC STOCK PRICE MOVEMENTS OVER A PERIOD OF THREE MONTHS.
Introduction: Aim of this study was to reduce blood loss caused by diagnostic blood sampling and to minimize the development of anemia in a high-risk group of mechanically ventilated medical intensive care patients. We therefore implemented a “blood-saving bundle” (BSB) combining a closed-loop arterial blood sampling system, smaller sampling tubes, reduced frequency of blood drawings, and reduced sample numbers.
Methods: The study included all patients from our medical ICU who were ventilated for more than 72 hours. Exclusion criteria were: acute or chronic anemia on admission, bleeding episode(s) during the ICU stay, or end-of-life therapy. The BSB was introduced in 2009 with training and educational support. Patients treated in 2008, before the introduction of the BSB, served as a control group (n = 41, 617 observation days), and were compared with patients treated in 2010 after the introduction of the BSB (BSB group, n = 50, 559 observation days). Primary endpoints were blood loss per day, and development of anemia. Secondary endpoints were numbers of blood transfusions, number of days on mechanical ventilation, and length of the ICU stay.
Results: Mean blood loss per ICU day was decreased from 43.3 ml (95% CI: 41.2 to 45.3 ml) in the controls to 15.0 ml (14.3 to 15.7 ml) in the BSB group (P < 0.001). The introduction of a closed-loop arterial blood sampling system was the major contributor to this effect. Mean hemoglobin concentrations showed no significant differences in both groups during the ICU stay. Hemoglobin values <9 g/dl, however, were recorded in 21.2% of observation days in the controls versus 15.4% in the BSB group (P = 0.01). Units of transfused red blood cells per 100 observation days decreased from 7 to 2.3 (P < 0.001). The mean number of ventilation days was 7.1 days (6.1 to 8.3 days) in the controls and 7.5 days (6.6 to 8.5 days) in the BSB group (P = NS). In total, patients in the BSB group stayed in ICU for a mean of 9.9 days (8.6 to 11.3 days), compared to a mean ICU stay of 13.0 days (10.9 to 15.4 days) in the control group (P = 0.014). Due to the longitudinal study design, however, we cannot exclude uncontrolled confounders affecting the transfusion frequency and mean ICU stay.
Conclusion: Our BSB could be easily implemented and was able to reduce diagnostic blood loss.
Die anhaltende Beliebtheit elektronischer Datenverarbeitung hat dazu geführt, dass Daten uns in unseren Alltag immer wieder unterschiedlich begegnen. Dadurch hat sich ein breites Begriffsfeld entwickelt: Inhaltsdaten, Metadaten, personenbezogene und anonyme Daten, Big Data, Datenklau, Datenschutz und Datenkraken, um nur einige zu nennen. Doch um Daten wird nicht nur wirtschaftlich gekämpft, sondern auch politisch...
Municipal wastewater contains nutrients valuable for a reuse in agriculture and can be the source of a multitude of chemicals used in private households and industry, too. As many of these chemicals are incompletely degraded during wastewater treatment, their residues remain partly in sewage sludge and partly in treated wastewater. Concerns are linked particularly to the so called micropollutants, i.e. anthropogenic organic substances such as personal care products, pharmaceuticals and biocides, for which scarce data on their degradability and environmental fate and particularly on their ecotoxicity are available. Thus, when reusing treated wastewater and sewage sludge for irrigation or as soil amendment for a sustainable land and water management, these wastewater-borne pollutants may enter soil, groundwater and surface water. The present work therefore aimed at assessing potential ecotoxic effects on aquatic and terrestrial organisms of reusing treated wastewater and sewage sludge. To this end, established as well as newly developed experimental approaches were used to investigate the problem on several levels. Individual wastewater-borne substances, samples from field study sites and samples from a soil column experiment simulating prolonged wastewater irrigation were examined.
At the start of the experimental work, the ecotoxicity of climbazole was characterised towards five aquatic and five terrestrial test organisms. Climbazole is an azole antimycotic agent applied in cosmetics and anti-dandruff shampoos and was recently detected in relatively high concentrations in treated wastewater and sewage sludge. In the present work climbazole was found to be particularly toxic towards plants such as water lentils with effective concentrations comparable to those of agricultural azole fungicides. Dwarfism, that is reduced shoot elongation observed in plants, pointed at a specific, phytohormone inhibiting mode of action of climbazole. Furthermore, the expected influence of the soil pH on the phytotoxicity of climbazole was experimentally confirmed.
Based on the findings for climbazole, two additional azole antimycotics, ketoconazole and fluconazole, and the regularly in sewage sludge detected biocide benzyldimethyldodecyl-ammonium chloride (BDDA) were investigated for their toxicity towards plants.
In aqueous medium, an increasing phytotoxicity from fluconazole to BDDA, ketoconazole and climbazole was observed, while in soil, phytotoxicity increased from BDDA to ketoconazole, climbazole and fluconazole. The relatively low terrestrial toxicity of BDDA and ketoconazole probably resulted from their strong binding to soil as well as their good biodegradability. To render the exposure scenario more realistic, sewage sludge was co-applied with the four test substances in a parallel test run. However, as no detectable influence on their effective concentrations was found, it can be assumed that the current practice of assessing sewage sludge borne substances with biotests in standard soil is sufficiently realistic. In a further study, different advanced sludge-treatment technologies were assessed for their efficacy in reducing pollutants. Results from the present work indicated that effects assessed in terrestrial short term biotests only seldom correlated with the concentrations of certain pollutants. Rather, a negative correlation of the stability of the sludges, determined by the ratio of volatile to total solids, to their ecotoxicity was seen.
Another aspect of the present work was the design and performance of an experimental approach to assess the environmental risk of a long-term irrigation with treated wastewater concerning the quality of soil and water in a prospective way, i.e. before the installation at field scale. For the simulation of a continuous irrigation corresponding to approximately 30 years, a percolation apparatus was developed and four different soils were percolated with treated wastewater for three months. Acute and chronic biotests with nine test organisms from different trophic levels (green algae, water lentils and water fleas as well as oilseed rape, oats, bacteria, spring tails, enchytraeids and earthworms) were used to assess the soil percolates as well as the soils with and without percolation. These investigations were accompanied by a comprehensive chemical monitoring conducted by project partners. Results indicated that the soil passage, that is the percolation through the soil, generally improved the quality of the treated wastewater as habitat for aquatic organisms which was visible by a reduction of its phytotoxicity. However, in some cases it deteriorated the water quality, probably resulting from the leaching of metals from pre-contaminated soil. A deteriorated habitat quality of the soil after the percolation with treated wastewater was observed for several test organisms and soils. In the same, mainly peaty soils, the highest accumulation of wastewater-borne micropollutants and of zinc was measured. Yet, their concentrations did not correlate to the observed biological effects. Moreover, data on ecotoxicity were only available for a small fraction of the detected substances so that their concentrations could not successfully be used to predict expected biological effects.
The experimental approach used in the present work demonstrated to be an adequate tool to support the prospective evaluation of environmental risks of treated wastewater irrigation. Overall, it can be concluded that the reuse of treated wastewater on soil can improve the quality of treated wastewater but that this can come at the cost of deteriorating the quality of the soil. As these risks cannot be generalised, a comprehensive biotest battery as well as chemical analysis should be used to assess them on a case-specific basis for each respective wastewater and the respective soil.
In conclusion our data show, that Flightless I function is essential for striated muscle development in zebrafish. Myofibrillar bundling and focal adhesion formation represent the basis for this development, and are ultimately a prerequisite for cardiac trabeculation. Future analysis of Actin polymerization in trabeculation will provide addition knowledge about the sensitivity of the developing and adult heart to a disequilibrium in F-actin versus G-actin availability.
In this study we found a novel ErbB2-dependent cardiomyocyte maturation process which affects both cardiac chambers. It will be of great interest to further study the nature of the Memo1-GFP cell-cell junctions and other junction proteins in order to unravel the significance of this maturation process for heart development.
Interestingly we found, that memo1bns4 homozygous mutant animals, which we generated with CRISPR/Cas9 technology, develop indistinguishable from siblings, suggesting that zygotic memo1 expression is dispensable for zebrafish development. Future studies will address the question if maternal zygotic memo1bns4 mutants will develop a heart or vascular phenotype as reported form Memo1 knockout mice or as observed in memo1 morphants in this study.
In cultured C2 mouse skeletal muscle cells the Golgi-apparatus relocalizes dependent on centrosomal proteins and independent of microtubules. We describe here that zebrafish cardiomyocytes have a similar Golgi-complex distribution suggesting a similar differentiation-dependent reorganization. This striated muscle specific, fragmented Golgi distribution might be an advantage for these cells in order to shuttle vesicles through the densely packed sarcomere structures. Future studies could address the timing of the Golgi-reorganization in cardiomyocytes during development and possibly use this Golgi-zebrafish line as a tool to study cardiomyocyte maturation in disease models and in heart regeneration.
The ancient Egyptians were accustomed to use "travel" and "individualism" as metaphors for the journey of one's life, as an expression of an individual’s aspirations in pursuit of a goal, whether on land or sea. ,A person who exhibits unusual attitudes or deviates from the cultural path of Egyptian society, will face obstacles and serious difficulties such as drowning, drifting, or disaster, while at the same time being tested by the gods, who could integrate him back into society and the Egyptian culture again, or leave him in the depths of darkness. In this context, our paper aims to shed light on the importance of individualism and how it is used as the basis for deviation from the prevalent cultural path. It also examines the relationship between individualism and the Egyptian culture, social identity, and self-representation. It also deals with individualism as an expression of human ambition, and its implications. Additionally, it discusses the issue of determinism and divine fate and their impact on the orientation of humans travelling through life, as opposed to human free will.
O presente artigo busca demonstrar que o individuo padece de uma crise de reconhecimento quando busca a solução dos conflitos no poder Judiciário. Este, porém, pode restabelecer apenas o reconhecimento de um dos indivíduos processuais, deixando o outro em processo de não reconhecimento. Desta forma, busca-se comparar os princípios e ideias da jurisdição estatal com os da mediação, demonstrando que a mediação é um processo resolução de conflitos que melhor coaduna suas ideias e princípios com a teoria do reconhecimento. Assim, aplicando a teoria do reconhecimento de Axel Honneth ao modelo jurisdicional convencional, nota-se que uma parte da demanda acaba insatisfeita com a decisão judicial, enquanto, na mediação, busca-se um equilíbrio de satisfações. Devido a esse equilíbrio e convergência, acredita-se que o processo de afirmação da personalidade de nenhuma das partes processuais, quando a mediação é utilizada, seja desarticulado.
Since few decades there is a broad debate about the so called ecological crisis. The debate had its highlight at the Rio-Conference in 1992. This conference was also the starting point for a wide range of political efforts concerned with a broad spectrum of biodiversity issues. Insofar, the term ‘biodiversity’ is not one of the natural sciences, but one which is inherently connected with questions of good human life. This article argues that the question for the good life predominantly fulfills a heuristic function and is to be answered in light of certain societal relations to nature. Furthermore, in light of these societal relations to nature it is argued for a virtue ethical approach with respect to the individual good life, whereas concerning the scale of societal aspects transdisciplinarity is identified as the appropriate research mode, which addresses both societal and scientific issues.
Seit Oktober 2010 reflektiert im Italienisch-Deutschen Historischen Institut in Trient eine Gruppe von Historikern über ein zentrales Problem der Geschichtswissenschaften, demjenigen der Epochen und der "Transitionen" zwischen diesen. Vom 11.–14. September 2012 veranstaltete das Institut hierzu eine Tagung, auf der erste Ergebnisse und Gedanken vorgestellt wurden. Der Sammelband versammelt die meisten der damaligen Vorträge. ...
Background: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-κB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection.
Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested.
Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-κB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-κB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-κB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-κB phosphorylation after H/R.
Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-κB.
Thought structures of modelling task solutions and their connection to the level of difficulty
(2015)
Although efforts have been made to integrate the concept of mathematical modelling in school, among others PISA and TIMSS revealed weaknesses of not only German students in the field of mathematical modelling. There may be various reasons starting from educational policy via curricular issues to practical instructional concerns. Studies show that mathematical modelling has not been arrived yet in everyday school class (Blum &BorromeoFerri, 2009, p. 47). Thus, the proportion of mathematical modelling in everyday school classes is low (Jordan et al., 2006). When focusing on the teachers’ point of view there are difficulties which may contribute to avoid modelling tasks in class. The development of reasonable modelling tasks, estimating the task space, valuating the task difficulty and assessing the student solutions are difficulties which occur to an increasing degree compared to ordinary mathematics tasks.The project MokiMaS (transl.: modeling competency in math classes of secondary education) aims at providing inter-year modelling tasks, whose task space and level of difficulty is known, together with an evaluation scheme. In particular a theory based method has been developed to determine the level of difficulty of modelling tasks on the basis of thought structures, representing the cognitive load of solution approaches. The current question is whether this method leads to a realistic rating. To go further into that question an evaluation scheme has been developed which is guided by the daily assessment work of teachers, to investigate the relation of task difficulty and student performance.
Von den Realitäten im Cyberwar, oder: Die Bedeutung des Sony-Hacks für zukünftige Cyber-Konflikte
(2015)
Part VI of our series on cyberpeace "Cyberpeace: Dimensionen eines Gegenentwurfs".Ende November des vergangenen Jahres wurde das US-amerikanische Unternehmen Sony Pictures Entertainment (SPE) Opfer einer groß angelegten Hackerkampagne. Dabei wurden Daten von Angestellten und Kooperationspartnern, wie Namen, Adress- und Versicherungsangaben aber auch Finanzinformationen und Verschlüsselungsdaten entwendet und viele Arbeitsplatzrechner des SPE-Netzwerkes durch eine Schadsoftware infiziert. Aussagen hochrangiger Sony-Mitarbeiter zufolge wollten die Angreifer Sony mit den erbeuteten Daten ursprünglich um Geld erpressen. Medial wurde der Vorfall jedoch rasch mit der anstehende Premiere der von SPE produzierten Komödie “The Interview“, die sich satirisch mit der Situation in Nordkorea auseinandersetzt, in Verbindung gesetzt. Jedoch trat erst Mitte Dezember eine Hackergruppe names “Guardians of Peace” mit Forderungen gegen die Ausstrahlung des Films als Urheber der Hacking-Attacke auf und drohte mit der Veröffentlichung der entwendeten Sony-Daten. Kurz darauf wurde der Sony-Hack auch durch das FBI offiziell bestätigt und staatliche Einrichtung Nordkoreas als Urheber der Angriffe beschuldigt. In der Beweisführung bezog sich das FBI auf Erkenntnisse und Ähnlichkeiten zu früheren Vorkommnisse in den USA und Süd-Korea sowie den geografischen Standorten der IP-Adressen einiger, für den Angriff benutzen Computer...
Wenn eine Neuerscheinung von zwei renommierten Verlagen gleich beim Erscheinen angekündigt wird mit dem spektakulären ‚Aufmacher‘ „Das konkurrenzlose Handbuch zu den großen Mythen der Welt“ und mit den plakativen Tops: „Konkurrenzlos umfassend: berücksichtigt alle wichtigen Kulturkreise – Kompakte Einträge zu einzelnen Mythen und ihrer Wirkung – Erklärung von Begriff, Funktion und Deutung von Mythen – Informationen zum Mythos in Wissenschaft und Künsten“, so werden damit beim breiteren Publikum und auch in Fachkreisen einige Erwartungen geweckt. Daher sieht der Rezensent, nach langer ‚Arbeit am Mythos‘ unlängst Verfasser des ersten systematischen Handbuchs zum antiken Mythos (2011) und eines weiteren handbuchartigen Überblickswerks zu Mythen, Sagen und Märchen (2012), seine Aufgabe vor allem in der Beantwortung der Frage, inwieweit die Neuerscheinung diesen Erwartungen gerecht wird...
Das vorliegende Buch behandelt den Kleinhandel in der Stadt Rom und schließt damit eine Lücke in der Erforschung der antiken Wirtschaft. Wie Holleran in ihrer Einleitung mit Recht schreibt, hat die Forschung bisher den überregionalen Handel deutlich umfänglicher in den Blick genommen, während der „retail trade“, auch aufgrund der schwierigen Quellenlage, nur wenig bearbeitet worden ist (4f.)...
Neutron capture cross sections of unstable isotopes are important for neutron-induced nucleosynthesis as well as for technological applications. A combination of a radioactive beam facility, an ion storage ring and a high flux reactor would allow a direct measurement of neutron induced reactions over a wide energy range on isotopes with half lives down to minutes. The idea is to measure neutron-induced reactions on radioactive ions in inverse kinematics. This means, the radioactive ions will pass through a neutron target. In order to efficiently use the rare nuclides as well as to enhance the luminosity, the exotic nuclides can be stored in an ion storage ring. The neutron target can be the core of a research reactor, where one of the central fuel elements is replaced by the evacuated beam pipe of the storage ring. Using particle detectors and Schottky spectroscopy, most of the important neutron-induced reactions, such as (n,γ), (n,p), (n,α), (n,2n), or (n,f), could be investigated.
Au milieu du beau livre d’Anna Karla, le lecteur tombe sur les réflexions du général François-Amédée Doppet qui, dans sa préface aux »Mémoires politiques et militaires«(1797), rapporte les conditions nécessaires pour écrire une histoire véritable de la Révolution française. À son avis, il faudra un écrivain impartial, éloigné du chaos des événements, qui, tout d’abord, rassemblera tous les souvenirs écrits par les protagonistes de la Révolution, jusque-là encore dominés par l’esprit de parti. Seul cet écrivain pourra, avec l’impartialité de l’historien, extraire de ces mémoires une histoire complète des bouleversements révolutionnaires. La vérité sur la Révolution, donc, ne pourra être formulée que longtemps après la fin de celle-ci. ...
Encouraging growth funding
(2015)
The CARIBIC (Civil Aircraft for the Regular Investigation of the Atmosphere Based on an Instrument Container) passenger aircraft observatory performed in situ measurements at 10–12 km altitude in the South Asian summer monsoon anticyclone between June and September 2008. These measurements enable us to investigate this atmospheric region, which so far has mostly been observed from satellites, using the broad suite of trace gases and aerosols measured by CARIBIC. Elevated levels of a range of atmospheric pollutants were recorded e.g. carbon monoxide, total reactive nitrogen oxides, aerosol particles and several volatile organic compounds. The measurements provide detailed information about the chemical composition of air in different parts of the monsoon anticyclone, particularly of ozone precursors. While covering a range of 3500 km inside the monsoon anticyclone, CARIBIC observations show remarkable consistency, i.e. with regular latitudinal patterns of trace gases during the entire monsoon period. Trajectory calculations indicate that these air masses originated mainly from South Asia and Mainland Southeast Asia.
Using the CARIBIC trace gas and aerosol measurements in combination with the Lagrangian particle dispersion model FLEXPART we investigated the characteristics of monsoon outflow and the chemical evolution of air masses during transport. Estimated photochemical ages of the air were found to agree well with transport times from a source region east of 95 ° E. The photochemical ages of the air in the southern part of the monsoon anticyclone were consistently younger (less than 7 days) and the air masses mostly in an ozone forming chemical regime. In its northern part the air masses were older (up to 13 days) and had unclear ozone formation or destruction potential. Based on analysis of forward trajectories several receptor regions were identified. In addition to predominantly westward transport, we found evidence for efficient transport (within 10 days) to the Pacific and North America, particularly during June and September, and also of cross-tropopause exchange, which was strongest during June and July. Westward transport to Africa and further to the Mediterranean was the main pathway during July.
Thermal dilepton radiation from the hot fireballs created in high-energy heavy-ion collisions provides unique insights into the properties of the produced medium. We first show how the predictions of hadronic many-body theory for a melting ρ meson, coupled with quark–gluon plasma emission utilizing a modern lattice-QCD based equation of state, yield a quantitative description of dilepton spectra in heavy-ion collisions at the SPS and the RHIC beam energy scan program. We utilize these results to systematically extract the excess yields and their invariant-mass spectral slopes to predict the excitation function of fireball lifetimes and (early) temperatures, respectively. We thereby demonstrate that future measurements of these quantities can yield unprecedented information on basic fireball properties. Specifically, our predictions quantify the relation between the measured and maximal fireball temperature, and the proportionality of excess yield and total lifetime. This information can serve as a “caloric” curve to search for a first-order QCD phase transition, and to detect non-monotonous lifetime variations possibly related to critical phenomena.
Este trabajo es el resultado de la investigación Capital Humano como factor de crecimiento Económico, en el cual se desarrolla una reflexión crítica sobre la teoría del Capital Humano, el abordaje se hace desde la teoría económica y el análisis tiene como referente los planteamientos de la Escuela de Frankfurt, especialmente en lo que tiene que ver con el uso desde la perspectiva de la racionalidad. Desde el punto de vista metodológico se trata de una investigación cualitativa, basada en un proceso de carácter interpretativo y comprensivo de tipo Histórico Hermenéutico, el método utilizado responde a una finalidad de descripción, interpretación, argumentación, que permitan avanzar hacia la comprensión de las temáticas estudiadas en un proceso dialéctico. Como resultado del proceso investigativo se hace un análisis de la instrumentalización de la educación, la formación, la capacidad de trabajo y el estado de salud del hombre, y aún de su propio ser, las cuales se consideran de la misma naturaleza que una maquina y quedan cosificadas al ser convertidas en mercancías comerciales que se venden en el mercado, lo que determina la posibilidad de colocarle un precio pagado en el mercado a la productividad de un tipo de trabajo determinado, a la acción del propio hombre y el desarrollo de sus capacidades superiores que deberían permitirle contribuir al logro de una sociedad mejor y una vida más digna.
Ribosomes are the central cellular assembly lines for protein synthesis. To cope with the translational needs, a proliferating mammalian cell can produce up to 7500-ribosomes per minute. However, under growth limiting conditions, such as nutrient depletion, ribosome synthesis is rapidly shut down exemplifying the importance of a tight coordination between ribosome supply and cellular energy status. In addition to the quantitative regulation, a strict quality control of ribosome synthesis is equally important, because alterations in the composition or function of ribosomes can lead to a variety of pathologies. To cope with these challenges a highly regulated, multi-step pathway of ribosome biogenesis has evolved. In mammals this pathway generates the mature 80S ribosomes that comprise the large 60S and the small 40S subunits. Together they contain around 80 ribosomal proteins and the 28S, 18S, 5.8S and 5S rRNAs. The 28S, 5.8S and 5S rRNAs are assembled into the large subunit, while the 18S rRNA is part of the small subunit. The pathway of ribosome biogenesis is a multi-step cellular process, where specific stages occur in distinct subcellular compartments. Transcription of the 47S rRNA, which is the precursor for the 28S, 18S and 5.8S species, occurs in the nucleolus. Modification of distinct bases and early processing of this precursor also take place in the nucleolus. Subsequently, the 40S and 60S pre-ribosomes take separate maturation routes through the nucleoplasm before their export and final assembly in the cytoplasm. The various stages of preribosomal maturation require the constant and sequential action of a large number of non-ribosomal proteins, known as trans-acting factors. These factors coordinate the delicate remodeling of the pre-ribosomal intermediates and thereby ensure proper progression of the maturation process. The remodeling events largely depend on the dynamics of post-translational modifications, such as phosphorylation or SUMOylation. This requires that the enzymes controlling these modifications are properly targeted to their sites of activity as they fulfill their functions within specific compartments. Here we studied the regulatory principles that govern the subcellular partitioning of the SUMO-specific isopeptidase SENP3 and its associated factor PELP1. Previous work from our laboratory has delineated the importance of the SUMO system for proper ribosome biogenesis in mammalian cells. In particular, we have shown that SENP3 is critically involved in 28S rRNA formation, which is a key step for pre-60S subunit maturation. A critical involvement of SENP3 at this stage of the maturation process is in agreement with the observed enrichment of SENP3 in the nucleolus, since 28S rRNA processing is considered to occur in the nucleolus. Our subsequent work identified the nucleolar scaffold protein NPM1 and the ribosomal trans-acting factor PELP1 as bona fide substrates of SENP3. For both proteins we could demonstrate modification by SUMO2/3 and define SENP3 as the demodifying enzyme. Depletion of SENP3 enhanced the conjugation of SUMO to both proteins and concomitantly reduced conversion of the 32S pre-rRNA to the mature 28S rRNA. PELP1 is part of a larger protein complex consisting of the core components PELP1, TEX10 and WDR18. We could show that the balanced SUMOylation/deSUMOylation of PELP1 controls the nucleolar/nucleoplasmic distribution of this complex. Enhanced SUMOylation, which is observed in the absence of SENP3, triggers the nucleolar release of the complex suggesting that SENP3-mediated deSUMOylation controls the dynamics of nucleolar trans-acting factors. Based on these findings we first wanted to understand, in which cellular compartment(s) SENP3 exerts its function on 28S maturation. Next, we wanted to tackle the question how the subcellular distribution of SENP3 is controlled. Finally
we addressed the question how the SUMOylation of PELP1 determines the subnuclear distribution of the PELP1 complex. This work initially revealed that the nucleolar localization of SENP3 is crucial for proper 28S rRNA formation and 60S ribosome maturation. Importantly, we could demonstrate that the nucleolar compartmentalization of SENP3 depends on its direct physical interaction with NPM1. Further, we could show that the amino-terminal region of SENP3 is necessary for its binding to NPM1 and nucleolar recruitment. Strikingly, this interaction requires the phosphorylation of SENP3, which is brought about by the mTOR kinase. By in-vitro kinase assays and mass-spectrometric approaches we identified five serine/threonine residues within the amino-terminal region of SENP3 that are targeted by mTOR (S/T 25, 26, 141, 142, 143). We could further demonstrate by mutagenesis that these sites in SENP3 are in fact critical for the phospho-dependent binding of SENP3 to NPM1 and its nucleolar recruitment.
Consistent with these data, we found that chemical inhibitors of the mTOR kinase trigger the nucleolar release of SENP3 and impair its interaction with NPM1. Strikingly, this goes along with severe 28S rRNA maturation defects demonstrating the physiological importance of mTOR signaling in the regulation SENP3 function and rRNA processing. By specifically depleting components of the either mTORC1 or mTORC2, we could attribute the observed effects to signaling by mTORC1 rather than mTORC2. In an attempt to find the negative regulators of SENP3 phosphorylation, we identified PP1-γ as the candidate phosphatase in this pathway. We found a strong physical interaction of SENP3 with PP1-γ and observed a loss of SENP3 nucleolar localization upon ectopic expression of PP1-γ. Thus we could define mTOR/PP1-γ mediated phosphorylation/dephosphorylation of SENP3 as an important
mechanism in the control of ribosome maturation. Given that mTOR activity is controlled by nutrient availability, SENP3 functions as a sensor that couples ribosome synthesis with nutrient availability. The second part of this work delineated the role of SUMOylated PELP1 in nucleoplasmic partitioning of the SENP3-PELP1 complex. It was revealed that the AAA-ATPase MDN1 binds preferentially to SUMO modified PELP1 and likely segregates SUMOylated PELP1 from nucleolar pre-60S particles. We initially found that the PELP1 complex associates with MDN1, a factor known to be involved in the 28S rRNA maturation. Notably, depletion of MDN1 led to an enhanced accumulation of the PELP1 complex in the nucleolus and a strong association of PELP1 with pre-60S particles, suggesting that MDN1 is required for the release of this complex from the pre-ribosomes. Intriguingly, the interaction of PELP1 with MDN1 requires SUMO2/3 and SUMOylated PELP1 shows enhanced binding to MDN1 when compared to unmodified PELP1. Taken together this work provides new insights in the control of the SENP3-PELP1 complex dynamics. We could define several layers for the coordinated spatial regulation of SENP3 and the PELP1 complex. This work therefore underscores the crucial importance of dynamic post-translational modifications for the control of ribosome maturation.
The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic ‘reward’ circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.
Ionizing radiation generates DNA double-strand breaks (DSB) which, unless faithfully repaired, can generate chromosomal rearrangements in hematopoietic stem and/or progenitor cells (HSPC), potentially priming the cells towards a leukemic phenotype. Using an enhanced green fluorescent protein (EGFP)-based reporter system, we recently identified differences in the removal of enzyme-mediated DSB in human HSPC versus mature peripheral blood lymphocytes (PBL), particularly regarding homologous DSB repair (HR). Assessment of chromosomal breaks via premature chromosome condensation or γH2AX foci indicated similar efficiency and kinetics of radiation-induced DSB formation and rejoining in PBL and HSPC. Prolonged persistence of chromosomal breaks was observed for higher LET charged particles which are known to induce more complex DNA damage compared to X-rays. Consistent with HR deficiency in HSPC observed in our previous study, we noticed here pronounced focal accumulation of 53BP1 after X-ray and carbon ion exposure (intermediate LET) in HSPC versus PBL. For higher LET, 53BP1 foci kinetics was similarly delayed in PBL and HSPC suggesting similar failure to repair complex DNA damage. Data obtained with plasmid reporter systems revealed a dose- and LET-dependent HR increase after X-ray, carbon ion and higher LET exposure, particularly in HR-proficient immortalized and primary lymphocytes, confirming preferential use of conservative HR in PBL for intermediate LET damage repair. HR measured adjacent to the leukemia-associated MLL breakpoint cluster sequence in reporter lines revealed dose dependency of potentially leukemogenic rearrangements underscoring the risk of leukemia-induction by radiation treatment.
The hallmark of Philadelphia chromosome positive (Ph+) leukemia is the BCR/ABL kinase, which is successfully targeted by selective ATP competitors. However, inhibition of BCR/ABL alone is unable to eradicate Ph+ leukemia. The t(9;22) is a reciprocal translocation which encodes not only for the der22 (Philadelphia chromosome) related BCR/ABL, but also for der9 related ABL/BCR fusion proteins, which can be detected in 65% of patients with chronic myeloid leukemia (CML) and 100% of patients with Ph+ acute lymphatic leukemia (ALL). ABL/BCRs are oncogenes able to influence the lineage commitment of hematopoietic progenitors. Aim of this study was to further disclose the role of p96ABL/BCR for the pathogenesis of Ph+ ALL. The co-expression of p96ABL/BCR enhanced the kinase activity and as a consequence, the transformation potential of p185BCR/ABL. Targeting p96ABL/BCR by RNAi inhibited growth of Ph+ ALL cell lines and Ph+ ALL patient-derived long-term cultures (PD-LTCs). Our in vitro and in vivo stem cell studies further revealed a functional hierarchy of p96ABL/BCR and p185BCR/ABL in hematopoietic stem cells. Co-expression of p96ABL/BCR abolished the capacity of p185BCR/ABL to induce a CML-like disease and led to the induction of ALL. Taken together our here presented data reveal an important role of p96ABL/BCR for the pathogenesis of Ph+ ALL.
Adult neurogenesis is frequently studied in the mouse hippocampus. We examined the morphological development of adult-born, immature granule cells in the suprapyramidal blade of the septal dentate gyrus over the period of 7–77 days after mitosis with BrdU-labeling in 6-weeks-old male Thy1-GFP mice. As Thy1-GFP expression was restricted to maturated granule cells, it was combined with doublecortin-immunolabeling of immature granule cells. We developed a novel classification system that is easily applicable and enables objective and direct categorization of newborn granule cells based on the degree of dendritic development in relation to the layer specificity of the dentate gyrus. The structural development of adult-generated granule cells was correlated with age, albeit with notable differences in the time course of development between individual cells. In addition, the size of the nucleus, immunolabeled with the granule cell specific marker Prospero-related homeobox 1 gene, was a stable indicator of the degree of a cell's structural maturation and could be used as a straightforward parameter of granule cell development. Therefore, further studies could employ our doublecortin-staging system and nuclear size measurement to perform investigations of morphological development in combination with functional studies of adult-born granule cells. Furthermore, the Thy1-GFP transgenic mouse model can be used as an additional investigation tool because the reporter gene labels granule cells that are 4 weeks or older, while very young cells could be visualized through the immature marker doublecortin. This will enable comparison studies regarding the structure and function between young immature and older matured granule cells.
The ability of hematopoietic stem cells (HSCs) to self-renew is a prerequisite for the establishment of definitive hematopoiesis and life-long blood regeneration. Here, we report the single-stranded DNA-binding transcriptional regulator far upstream element (FUSE)-binding protein 1 (FUBP1) as an essential factor of HSC self-renewal. Functional inactivation of FUBP1 in two different mouse models resulted in embryonic lethal anemia at around E15.5 caused by severely diminished HSCs. Fetal and adult HSCs lacking FUBP1 revealed an HSC-intrinsic defect in their maintenance, expansion, and long-term blood reconstitution, but could differentiate into all hematopoietic lineages. FUBP1-deficient adult HSCs exhibit significant transcriptional changes, including upregulation of the cell-cycle inhibitor p21 and the pro-apoptotic Noxa molecule. These changes caused an increase in generation time and death of HSCs as determined by video-microscopy-based tracking. Our data establish FUBP1 and its recognition of single-stranded genomic DNA as an important element in the transcriptional regulation of HSC self-renewal.
Abstract: The current Ebola outbreak poses a threat to individual and global public health. Although the disease has been of interest to the scientific community since 1976, an effective vaccination approach is still lacking. This fact questions past global public health strategies, which have not foreseen the possible impact of this infectious disease. To quantify the global research activity in this field, a scientometric investigation was conducted. We analyzed the research output of countries, individual institutions and their collaborative networks. The resulting research architecture indicated that American and European countries played a leading role regarding output activity, citations and multi- and bilateral cooperations. When related to population numbers, African countries, which usually do not dominate the global research in other medical fields, were among the most prolific nations. We conclude that the field of Ebola research is constantly progressing, and the research landscape is influenced by economical and infrastructural factors as well as historical relations between countries and outbreak events.
Author Summary: For the first time in the history of the disease, the Ebola virus left its local setting and affected people not only in isolated rural areas, but reached larger towns and cities leading to worldwide repercussions. This development prompted a joint global response to this health threat. This encompassed not only immediate relief efforts, but also an up search in global research work. In this study, the scientific output in Ebola research available in one of the mayor medical search platforms was characterized. We studied among others the origin of research, the collaboration between countries and the research topics. Partly, the obtained data was weighted against economic parameters. We attained a detailed map of the research activities from the discovery of Ebola in 1976 up to today. Our research provides the first overview of the worldwide Ebola research output. It might help stakeholders in Ebola research to better plan investigations with a global perspective.
Correlation functions provide information on the properties of mesons in vacuum and of hot nuclear matter. In this work, we present a new method to derive a well-defined spectral representation for correlation functions. Combining this method with the quark gap equation and the inhomogeneous Bethe–Salpeter equation in the rainbow-ladder approximation, we calculate in-vacuum masses of light mesons and the electrical conductivity of the quark–gluon plasma. The analysis can be extended to other observables of strong-interaction systems.
The metabolome of any live cell consists of several hundred, if not thousands of different molecules at any given moment, be it a relatively small bacterial cell or a whole multicellular organism. Although there are continuous attempts to differentiate between primary and secondary metabolites, the borders often blur in the eye of almost perfect interconvertability of all such matter. With chemistry and physics dominating this domain of biology it is an interdisciplinary endeavor to tackle the questions surrounding the workings of the metabolic pathways involved, searching for answers that ultimately help us to better understand life and find solutions to problems that affect us humans. One area of biochemistry that serves as a formidable example of the intertwined primary and secondary metabolic pathways are fatty acids, essential components of bacterial membranes, sources of energy and carbon but also important building blocks of several natural products. The second area to be mentioned is the metabolism of amino acids, the basic components of proteins and enzymes, which also serve as precursors to a diverse set of metabolites with many biological purposes.
This work focuses on these two areas of biochemistry, as several intermediates of their metabolism serve as building blocks for complex secondary metabolites whence many interesting and bioactive natural products are derived. The powerful and relatively novel tool of click-chemistry is employed to track azide-labeled precursors of primary and secondary metabolism in various bacterial strains to observe biochemistry at work and adds to the knowledge gained through other methods. The methods presented in this work serve the observation of fatty acid biosynthesis, degradation, modification and transport through direct ligation of azido fatty acids with cyclooctynes on one hand, leading to a revision of fatty acid transport in general. On the other hand a cleavable azide-reactive resin is devised to generally track the fate of azidated compounds through the myriads of metabolic pathways offered by entomopathogenic bacteria possessing a rich secondary metabolism. The resulting findings led to the identification of several antimicrobial peptides, amides and other compounds of which many had remained so far undetected in the strains that underwent investigation, underlining the worth of this method for future metabolomic research and beyond.
The metabolome of any live cell consists of several hundred, if not thousands of different molecules at any given moment, be it a relatively small bacterial cell or a whole multicellular organism. Although there are continuous attempts to differentiate between primary and secondary metabolites, the borders often blur in the eye of almost perfect interconvertability of all such matter. With chemistry and physics dominating this domain of biology it is an interdisciplinary endeavor to tackle the questions surrounding the workings of the metabolic pathways involved, searching for answers that ultimately help us to better understand life and find solutions to problems that affect us humans. One area of biochemistry that serves as a formidable example of the intertwined primary and secondary metabolic pathways are fatty acids, essential components of bacterial membranes, sources of energy and carbon but also important building blocks of several natural products. The second area to be mentioned is the metabolism of amino acids, the basic components of proteins and enzymes, which also serve as precursors to a diverse set of metabolites with many biological purposes.
This work focuses on these two areas of biochemistry, as several intermediates of their metabolism serve as building blocks for complex secondary metabolites whence many interesting and bioactive natural products are derived. The powerful and relatively novel tool of click-chemistry is employed to track azide-labeled precursors of primary and secondary metabolism in various bacterial strains to observe biochemistry at work and adds to the knowledge gained through other methods. The methods presented in this work serve the observation of fatty acid biosynthesis, degradation, modification and transport through direct ligation of azido fatty acids with cyclooctynes on one hand, leading to a revision of fatty acid transport in general. On the other hand a cleavable azide-reactive resin is devised to generally track the fate of azidated compounds through the myriads of metabolic pathways offered by entomopathogenic bacteria possessing a rich secondary metabolism. The resulting findings led to the identification of several antimicrobial peptides, amides and other compounds of which many had remained so far undetected in the strains that underwent investigation, underlining the worth of this method for future metabolomic research and beyond.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
Die vorliegende Arbeit befasst sich mit der numerischen Behandlung elasto-plastischer Materialmodelle unter großen Deformationen. Elasto-plastisches Materialverhalten zeichnet sich dadurch aus, dass neben den reversiblen (elastischen) Deformationen auch irreversible (plastische) Deformationen betrachtet werden, die einem Evolutionsgesetz folgen. Ein numerischer Algorithmus der Elasto-Plastizität muss daher dieses plastische Evolutionsgesetz zusammen mit den klassischen Erhaltungsgleichungen der Kontinuumsmechanik lösen und geeignet behandeln. Der prominenteste Vertreter eines elasto-plastischen Algorithmus' ist der sogenannte Return-Mapping-Algorithmus (RMA). Neben seiner Funktionalität werden allerdings auch die einschränkenden Modellannahmen beleuchtet, auf denen der RMA gründet. Diese beschränkte Anwendungsmöglichkeit motiviert die Entwicklung eines neuen Plastizitätsalgorithmus'. Der in dieser Arbeit entwickelte Verallgemeinerte Plastizitätsalgorithmus (GPA: Generalised Plasticity Algorithm) führt eine zusätzliche Linearisierung bezüglich der plastischen Variable ein, in der das plastische Evolutionsgesetz formuliert ist. In der vorliegenden Arbeit ist diese Variable durch den plastischen Deformationstensor gegeben, der die Inverse des plastischen rechten Cauchy-Greenschen Deformationstensors beschreibt. Somit erlaubt der GPA eine Behandlung von allgemeineren und komplexeren elasto-plastischen Modellen als der RMA.
Anhand von bekannten Benchmark-Problemen werden die beiden Algorithmen in dieser Arbeit validiert und verglichen. Ein numerischer Test zur Poroplastizität unter großen Deformationen dient schließlich als Beleg dafür, dass der GPA auf Modelle anwendbar ist, die durch komplexes elasto-plastisches Materialverhalten charakterisiert sind und für die der RMA in seiner klassischen Form nicht als Lösungsstrategie gewählt werden kann.
Neben der Entwicklung des Verallgemeinerten Plastizitätsalgorithmus' hat diese Arbeit das Ziel industrielle Anwendungen effizient zu lösen. Dazu wird für ein Problem der linearen Elastizität der effiziente Einsatz des Mehrgitterlösers bis zu einer viertel Million Prozessoren gezeigt und es werden elasto-plastische Rechnungen für zwei industrielle Beispiele mit einer anspruchsvollen Geometrie durchgeführt.
Den Ausgangspunkt für diese Dissertation bildeten die seit 2010 verstärkt stattfindenden Diskussionen um das Thema Elektromobilität, deren politischer Fokus auf das Elektroautomobil gerichtet ist, was insbesondere in dem Ziel von 1 Mio. Elektroautos, die bis 2020 in Deutschland unterwegs sein sollen, zum Ausdruck kommt. Während die Fortschritte in diesem Bereich aber relativ verhalten waren, hatte sich zu diesem Zeitpunkt bereits die Fahrrad-Elektromobilität aus einem Schattendasein gelöst und in den letzten Jahren erhebliche Zuwächse erzielen können. Nach Erkenntnissen des Zweirad-Industrie-Verbandes (ZIV 2013) hat sich die Anzahl verkaufter Pedelecs zwischen 2009 und 2012 kontinuierlich von 150.000 auf 380.000 erhöht.
Im Rahmen der Dissertation wurde über die Analyse der Akzeptanz, Nutzung und Wirkung von Pedelecs untersucht, ob durch die verstärkte Nutzung dieser technologischen Innovation ein Beitrag zu einem nachhaltigeren und zukunftsfähigen Mobilitätssystem geleistet werden kann. Das Ziel der Untersuchung mit dem Schwerpunkt der berufsbezogenen Mobilität war es, herauszufinden, ob und ggf. wie durch eine Verstärkung der Praxis des Pedelec‐Fahrens ein Wandel innerhalb des Mobilitätssystems erreicht werden kann.
Als Ergebnis der Dissertation kann festgehalten werden, dass die Chancen für einen Wandel des Mobilitätssystems derzeit sehr gut stehen und Pedelecs, als vergleichsweise nachhaltige Fahrzeuge, dazu einen aktiven Beitrag leisten können. Zwar findet die dazu notwendige Nutzung, die insbesondere aber nicht ausschließlich zu einer Reduzierung von Automobilität führt, derzeit noch auf einem relativ niedrigen Niveau statt, so dass von einem systemwirksamen Beitrag noch nicht gesprochen werden kann. Es konnten aber, neben der Substitutionswirkung, noch weitere Wirkungen identifiziert werden, die ebenfalls Beiträge zu einem nachhaltigeren Mobilitätssystem leisten können. Damit wird deutlich, dass eine weitere Förderung von Pedelecs, die als notwendig erachtet wird, nicht nur der Pedelec-Mobilität zugutekommen kann, sondern nachhaltiger Mobilität insgesamt.
Die Dissertation untersucht die posthumen skulpturalen Bildwerke Ludwigs IX. des Heiligen (1226-1270). Seine konkrete Gestaltungsweise wird vor der Folie des französischen Königsbildes im Allgemeinen entwickelt. Vor allem die Zeit von 1270 bis in die 1340er Jahre steht im Fokus der Betrachtung. Diese Zeiteinteilung beruht auf der zentralen Frage, ab wann das Königsbild beginnt lesbar zu werden. Die methodische Voraussetzung dazu ist die bis jetzt noch nicht durchgeführte strikte Distinktion sowohl von Typus und Stil als auch von Typus und Gattung. Hier kristallisiert sich heraus, dass die Bildwerke Ludwigs IX., die nach seiner Kanonisation von 1297 datieren, eine Zäsur darstellen. An ihnen lässt sich erstmals die Präzisierung eines bestimmten Königs in der Gestaltungsweise festhalten. Seine Spezifika werden erarbeitet. Die besondere, zunächst auf Ludwig IX. beschränkte Darstellungsform geht in der unmittelbaren Auseinandersetzung mit den Leiden der Heiligen hervor - wie bei ihnen wird sein Antlitz mimisch belebt, um sein Leiden darzustellen. Ein neuer Königstypus entsteht. Damit sind Bildwerke von Ludwig IX. lesbar – ein Novum innerhalb des französischen Königsbildes.
Diese Entwicklung vollzieht sich vor allem in der Zeit Philipps IV. Zahlreiche Neuerungen sowohl im Herrscherbild als auch in den Bildprogrammen geschehen in seiner Regentschaft. Vor allem die Kanonisation Ludwigs IX. gibt dem Souverän neue Möglichkeiten an die Hand, die besondere Sakralität des französischen Königtums weiter auszubauen. Mit der Darstellung des Heiligen verband sich eine Kultfunktion, die sich in der Gestaltung widerspiegelt und die dem französischen Herrscherbild neue Impulse vermittelt hat. Darüber hinaus erschöpfen sich die Bildstrategin Philipps IV. aber nicht allein in der Indienstnahme des neuen Dynastieheiligen, sondern sie erweitern zudem die politische Ikonografie.
Wie sich das französische Herrscherbild unter welchen formalen sowie historischen Kriterien warum wandelt, ist Untersuchungsgegenstand der Dissertation.
Dieser journalistische Gastbeitrag ist der fünfte Artikel unseres Blogfokus zu Flucht und Migration. Migration ist eine Tatsache in einer Welt, in der Kriege und Globalisierung massenhaft Lebensräume zerstören. Natürlich darf man die Zerstörungen und Verwüstungen nicht als gottgegeben hinnehmen. Im Irak etwa ist ja nicht der liebe Gott einmarschiert, sondern die Amerikaner haben das getan. Natürlich muss man schauen, wie man wieder zu erträglichen Zuständen in Syrien kommt, natürlich muss man alles tun, um Fluchtländer wieder zu Ländern zu machen, in denen Menschen leben können. Man muss etwas tun gegen die Fluchtursachen, auch wenn das sehr schwer ist. Im Fall Syrien heißt das, dass man auch mit Assad reden muss...
Saphenous vein graft disease is a timely problem in coronary artery bypass grafting. Indeed, after exposure of the vein to arterial blood flow, a progressive modification in the wall begins, due to proliferation of smooth muscle cells in the intima. As a consequence, the graft progressively occludes and this leads to recurrent ischemia. In the present study we employed a novel ex vivo culture system to assess the biological effects of arterial-like pressure on the human saphenous vein structure and physiology, and to compare the results to those achieved in the presence of a constant low pressure and flow mimicking the physiologic vein perfusion. While under both conditions we found an activation of Matrix Metallo-Proteases 2/9 and of microRNAs-21/146a/221, a specific effect of the arterial-like pressure was observed. This consisted in a marked geometrical remodeling, in the suppression of Tissue Inhibitor of Metallo-Protease-1, in the enhanced expression of TGF-β1 and BMP-2 mRNAs and, finally, in the upregulation of microRNAs-138/200b/200c. In addition, the veins exposed to arterial-like pressure showed an increase in the density of the adventitial vasa vasorum and of cells co-expressing NG2, CD44 and SM22α markers in the adventitia. Cells with nuclear expression of Sox-10, a transcription factor characterizing multipotent vascular stem cells, were finally found in adventitial vessels. Our findings suggest, for the first time, a role of arterial-like wall strain in the activation of pro-pathologic pathways resulting in adventitial vessels growth, activation of vasa vasorum cells, and upregulation of specific gene products associated to vascular remodeling and inflammation.
Since August 2009, German legislation allows for voluntary Say on Pay Votes (SoPV) during Annual General Meetings (AGMs). We examine 1,169 AGMs of all German listed firms with more than 10,000 agenda items over the period 2010-2013 to identify (1) determinants and approval rates of voluntary SoPVs, (2) the effect of voluntary SoPVs on AGM participation, and (3) the effect of SoP on executive compensation. Our data reveals that in the first four years of the voluntary say on pay regime every second firm in our sample has opted for having a SoPV. The propensity for a SoPV increases with firm size, abnormal executive compensation and free float of shares. Indeed, smaller firms with concentrated ownership do not only have a lower propensity for a SoPV, but also show a higher propensity to opt for only limited disclosure of executive compensation. Approval rates of SoPVs are lower than the approval rate for the average AGM agenda item and this effect is stronger in (i) widely held firms as well as in (ii) firms with abnormal executive compensation. Additionally, SoPVs actually can increase AGM participation; however, this result is particularly evident for widely held firms. Finally, we find stronger pay for performance elements within total executive compensation, particularly when the effect of executive compensation is lagged over the years following the vote. Overall, our results are consistent with the view that firms use voluntary SoPV to gain legitimation for executive remuneration policies in firms with low ownership concentration. This is enforced, where (small) shareholders consider executive compensation a part of the agency problem of listed firms, and where (small) shareholders consider SoPVs as a possibility to actively influence corporate decisions, with these decisions leading to a higher degree of alignment between executive management boards and shareholders.
In der momentanen politischen und medialen Auseinandersetzung um die Flüchtlingsaufnahme in Deutschland scheinen folgende Punkte selbstevident: Die gegenwärtige Flüchtlingsbewegung in die Bundesrepublik sei in ihrer Größe eine seit dem Ende des Zweiten Weltkriegs einzigartige Belastung für die Sozialsysteme. Auch seien für die meisten Skeptiker die ankommenden Flüchtlinge in ihrer kulturellen Eigenart von der deutschen Gesellschaft so verschieden, dass eine Integration quasi aussichtslos erscheine. Schließlich erwachse daraus eine fundamentale Gefahr für die soziale und politische Ordnung in Deutschland. Wobei (paradoxerweise) mit der Berufung auf dieses vermeintliche Bedrohungsszenario dann wiederholt der Ruf nach einer tatsächlichen rechtlichen und politischen Revision der bundesdeutschen Ordnung begründet wird.
In this paper, I examine how maternal myths are deployed in popular development literature. Using critical discourse analysis and working within a feminist postcolonial framework I analyse five texts produced by development organizations for popular consumption. I identify how maternal myths are constructed in each text and conduct a contextual analysis of four myths to identify their ideological significance within the development sector. I conclude that that in their construction of maternal myths, these texts, while intended to elicit support for gender and development interventions, reinforce exploitative gender roles and relations and limit women’s experiences of development.
DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.
Die Geschichte der europäischen Integration wird in der Regel als Erfolgsgeschichte erzählt, vor allem als wirtschaftliche Erfolgsgeschichte, die sich in Folge kluger und aus historischer Erfahrung getroffener Entscheidungen ergeben habe (vgl. Loth 2014; vgl. auch Mittag 2008). Der Zweite Weltkrieg habe endgültig gezeigt, dass das durch zahlreiche Nationalstaaten gekennzeichnete Europa, sollte es nicht zusammenarbeiten, zu verheerenden Konflikten neige. Und die Zusammenarbeit sei nicht nur politisch klug; sie zahle sich zusätzlich wirtschaftlich aus. So seien allen Teilnehmerstaaten auch in einem ganz ordinär materiellen Sinne Profiteure der europäischen Einigung, die in dieser Logik dann auch gar nicht weit genug gehen kann, bedingen sich hiernach doch das politisch Sinnvolle und das ökonomisch Erfolgreiche gegenseitig – und zwar genau in der Form der supranationalen Organisation, die die Europäische Union mittlerweile angenommen hat. Liest man einen Satz der Bundeskanzlerin Angela Merkel so, dann ist die europäische Integration nach Brüsseler Art deshalb alternativlos, weil es kein vergleichbares Erfolgsmodell gibt. Aus der zunächst durch das Leid des Krieges geprägten Bereitschaft zur Zusammenarbeit ist unter der Hand eine Art Sachzwang geworden, denn von der einmal eingeschlagenen Straße der Integration kann man in dieser Sicht nur unter erheblichen Wohlstandsverlusten und politischen Risiken abweichen.
In dieser Sachzwanglogik war allerdings die Euro-Krise nicht vorgesehen. Sie konnte im strengen Sinne auch gar nicht passieren, war doch die weitere Vertiefung der europäischen Union zur Währungsunion in den 1990er Jahren gerade damit begründet worden, dass derartige Krisen zukünftig ausgeschlossen seien (vgl. Tietmeyer 2005). Dass die Politik auf sie zunächst überrascht, fast panisch und dann durch konsequentes Vorantreiben der institutionellen und finanziellen Integration reagiert hat, zeigt auch, dass hier ein Denken vorherrscht, das nach dem Motto funktioniert, es könne doch nicht sein, was nicht sein dürfe. ...
Regionale Kooperation und Integration im Sub-Sahara Afrika – Eine dritte Welle der Regionalisierung?
(2015)
Vor allem seit Mitte der 1990er Jahre ist regionale Kooperation und Integration im sub-saharischen Afrika zu einem Trendphänomen geworden, das immer mehr Politikfelder berührt. Mit der so genannten 2. Welle der Regionalisierung erhofften sich viele afrikanische Staaten nicht nur neue Lösungen für ihre zahlreichen (sicherheits-)politischen, ökonomischen und sozialen Probleme. Vielmehr können die Versuche zur vertieften dauerhaften Kooperation und Integration auf dem Kontinent auch als Antwort auf globale Entwicklungen, Interdependenzen und integrative Erfolgsgeschichten (z.B. EU, ASEAN) betrachtet werden. In die derzeit existierenden 19 Regionalorganisationen in Afrika (davon 14 größere und fünf kleinere), werden demnach sehr viele Hoffnungen und Erwartungen, nicht nur von Seiten der Regierungen, sondern neuerdings auch von Seiten externer und zivilgesellschaftlicher Kräfte gesteckt. Zunehmend sind in verschiedenen Organisationen wie der East African Community (EAC), der Economic Community of West African States (ECOWAS) oder der Southern African Development Community nicht mehr nur kooperative, sondern dezidiert integrative Formen der Zusammenarbeit feststellbar. Befindet sich das sub-saharische Afrika daher auf dem Weg zu einer neuen, einer dritten Welle der Regionalisierung?