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Urn models are simple examples for random growth processes that involve various competing types. In the study of these schemes, one is generally interested in the impact of the specific form of interaction on the allocation of elements to the types. Depending on their reciprocal action, effects of cancellation and self-reinforcement become apparent in the long run of the system. For some urn models, the influencing is of a smoothing nature and the asymptotic allocation to the types is close to being a result of independent and identically distributed growth events. On the contrary, for others, almost sure random tendencies or logarithmically periodic terms emerge in the second growth order. The present thesis is devoted to the derivation of central limit theorems in the latter case. For urns of this kind, we use a "non-classical" normalisation to derive asymptotic joint normality of the types. This normalisation takes random tendencies and phases into account and consequently involves random centering and, also, possibly random scaling.
The linguistic deficit in patients with Alzheimer's Disease: is there a syntactic impairment?
(2017)
The linguistic impairment of patients affected by Alzheimer’s disease (PAD) is defined as a form of fluent aphasia, which is caused by major disruptions in the semantic and lexical domains. Consequently, their discourse is often described as empty, although their speech is fluent. This study aims at enlarging the comprehension of the linguistic deficit in PADs; in particular, it deals with their syntactic competence and it addresses the following questions: 1) Do PADs suffer from syntactic impairment? 2) How can the impairment in PADs be accounted for? 3) At which stage of the disease are PADs affected by syntactic impairment? The syntactic competence of Italian-speaking PADs is investigated under two different perspectives. On one hand, the study considers the syntactic information stored in the lexicon as part of the lexical entry. For this purpose, PADs complete a grammatical gender retrieval task on a list of 100 Italian nouns. On the other hand, the question deals with syntax intended as the capacity to complete the processing of syntactic structures in sentence comprehension and production. The present study focuses on sentence comprehension and includes two sentence-to-picture matching tasks: one on Wh-questions, and one on relative clauses. PADs complete the experiment on grammatical gender retrieval with high accuracy, except for few mistakes on irregular and opaque nouns, thus showing a spared capacity to retrieve the syntactic information, especially when they can rely on the form-driven procedural mechanism, as in the case of regular nouns. Data on the comprehension of Wh-questions and RC reveals that PADs are more sensitive than controls to locality effects. Patients with moderate dementia are impaired at computing dependencies that entail a crossing movement between two arguments whose features are in a relation of inclusion. In contrast, crossing movements are allowed when the involved feature arrays are in a relation of disjunction. In short, patients are spared at using procedural mechanisms for the retrieval of syntactic information, while they are impaired at processing sentences that entail argument extraction. The impairment manifests itself in moderately impaired PADs in the form of enhanced sensitivity to locality effects.
The publication of the Liikanen Group's final report in October 2012 was surrounded by high expectations regarding the implementation of the reform plans through the proposed measures that reacted to the financial and sovereign debt crises. The recommendations mainly focused on introducing a mild version of banking separation and the creation of the preconditions for bail-in measures. In this article, we present an overview of the regulatory reforms, to which the financial sector has been subject over the past years in accordance with the concepts laid out in the Liikanen Report. It becomes clear from our assessment that more specific steps have yet to be taken before the agenda is accomplished. In particular, bail-in rules must be implemented more consistently. Beyond the question of the required minimum, the authors develop the notion of a maximum amount of liabilities subject to bail-in. The combination of both components leads to a three-layer structure of bank capital: a bail-in tranche, a deposit-insured bailout tranche, and an intermediate run-endangered mezzanine tranche. The size and treatment of the latter must be put to a political debate that weighs the costs and benefits of a further increase in financial stability beyond that achieved through loss-bearing of the bail-in tranche.
kurz und kn@pp news : Nr. 41
(2017)
Background: The Aedes (Stegomyia) albopictus subgroup includes 11 cryptic species of which Ae. albopictus is the most widely distributed. Its global expansion associated with a documented vector competence for several emerging arboviruses raise obvious concerns in the recently colonized regions. While several studies have provided important insights regarding medical importance of Ae. albopicus, the investigations of the other sibling species are scarce. In Asia, indigenous populations within the Ae. albopictus subgroup can be found in sympatry. In the present study, we aimed to describe and compare molecular, morphological and bacterial symbionts composition among sympatric individuals from the Ae. albopictus subgroup inhabiting a Vietnamese protected area.
Results: Based on morphological structure of the cibarial armarture, we identified a cryptic species in the forest park at Bù Gia Mập in the south-eastern region of Vietnam. Analysis of nuclear (ITS1-5.8S-ITS2) and mitochondrial (cox1, nad5) markers confirmed the divergence between the cryptic species and Ae. albopictus. Analysis of midgut bacterial microbiota revealed a strong similarity among the two species with a notable difference; contrary to Ae. albopictus, the cryptic species did not harbour any Wolbachia infection.
Conclusions: These results could reflect either a recent invasion of Wolbachia in Ae. albopictus or alternatively a loss of this symbiont in the cryptic species. We argue that neglected species of the Ae. albopictus subgroup are of main importance in order to estimate variation of host-symbionts interactions across evolution.
Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single regulatory mechanism has been proposed for all RCK-regulated channels, involving signal transduction from the RCK domain to the gating area. Here, we present an inactive ADP-bound structure of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy, which, combined with EPR spectroscopy and molecular dynamics simulations, uncovers a novel regulatory mechanism for ligand-induced action at a distance. Exchange of activating ATP to inactivating ADP triggers short helical segments in the K+-translocating KtrB dimer to organize into two long helices that penetrate deeply into the regulatory RCK domains, thus connecting nucleotide-binding sites and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial pathogenicity factors, the discovery of this functionally relevant inactive conformation may advance structure-guided drug development.
SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions. Moreover, SRSF5 is bound to pluripotency-specific transcripts such as Lin28a and Pou5f1/Oct4 in the cytoplasm. SRSF5 depletion reduces and overexpression increases their cytoplasmic mRNA levels, suggesting that enhanced mRNA export by SRSF5 is required for the expression of pluripotency factors. Remarkably, neural differentiation of P19 cells leads to dramatically reduced SRSF5 shuttling. Our findings indicate that posttranslational modification of SR proteins underlies the regulation of their mRNA export activities and distinguishes pluripotent from differentiated cells.
Im Rahmen dieser Arbeit wird darauf eingegangen, welche Anpassungen erforderlich sind, um Protonendichten vergleichbar zu bereits erzeugten Elektronendichten in Gabor-Linsen zu erhalten. Zur Vorbereitung zukünftiger Experimente werden vergleichende Simulationen zum Einschluss der Ladungsträgerdichten durchgeführt und die Strahldynamik bei der Wechselwirkung eines positiven Ionenstrahls mit einem in einer Gabor-Linse eingeschlossenen Protonenplasma untersucht. Die Ergebnisse der Strahldynamiksimulationen werden mit theoretischen Berechnungen vertieft, in dem die Brennweite einer Gabor-Linse, die mit einer beliebigen Teilchensorte gefüllt ist, berechnet und die Drift-Masse eingeführt wird.
Eine weitere analytische Betrachtung ist die Erweiterung der Teilchendynamik in der Gabor-Linse auf beliebige Anfangsbedingungen, in dem die dazugehörige Differentialgleichung entkoppelt und ganz allgemein gelöst wird. Die daraus berechneten Trajektorien der Teilchen führen zu einem besseren Verständnis, das weitere Anwendungen erschließen könnte.
Recently the Universal Linear Accelerator (UNILAC) serves as a powerful high duty factor (25%) heavy ion beam accelerator for the ambitious experiment program at GSI. Beam time availability for SHE (Super Heavy Element)-research will be decreased due to the limitation of the UNILAC providing Uranium beams with an extremely high peak current for FAIR simultaneously. To keep the GSI-SHE program competitive on a high level and even beyond, a standalone superconducting continuous wave (100% duty factor) LINAC in combination with the upgraded GSI High Charge State injector is envisaged. In preparation for this, the first LINAC section (financed by HIM and GSI) will be tested with beam in 2017, demonstrating the future experimental capabilities. Further on the construction of an extended cryo module comprising two shorter Crossbar-H cavities is foreseen to test until end of 2017. As a final R&D step towards an entire LINAC three advanced cryo modules, each comprising two CH cavities, should be built until 2019, serving for first user experiments at the Coulomb barrier.
Die aus Amerika stammende, neophytische Kolumbianische Zwergwasserlinse Wolffia columbiana wurde in Europa erstmals im Jahr 2013 in Deutschland und den Niederlanden nachgewiesen. Daraufhin wurden weitere 11 Freilandvorkommen von Wolffia aus Deutschland (Nordrhein-Westfalen, Hessen und Rheinland-Pfalz), den Niederlanden und Polen überprüft. Bei 10 der insgesamt 13 untersuchten Proben handelte es sich um Wolffia columbiana, darunter alle 8 bislang untersuchten Vorkommen aus Deutschland. Lediglich bei 3 Freilandproben aus den Niederlanden und Polen handelte es sich um die einheimische Wolffia arrhiza. Der Neophyt scheint also durchaus weiter verbreitet zu sein als gedacht. Die Unterscheidung beider Arten ist nicht ganz leicht, die Unterscheidungsmerkmale werden vorgestellt. Die Vorkommen von Wolffia in Europa sollten überprüft werden, um zu klären, wie viele Vorkommen von Wolffia arrhiza es überhaupt noch gibt, und bei wie vielen Vorkommen es sich tatsächlich um die neophytische Wolffia columbiana oder andere neophytische Wolffia-Arten handelt.
Im NSG Emsdettener Venn im Kreis Steinfurt/NRW wächst seit mindestens 2011 Frasers Auenhartheu (Triade-num fraseri), eine Art, die an sumpfigen Standorten in Nord-Amerika heimisch ist. Das Vorkommen breitet sich im Emsdettener Venn weiter aus und ist hier offensichtlich bereits eingebürgert. Da es sich wahrscheinlich um die erste Verwilderung der Art in Deutschland handelt, wird Frasers Auenhartheu mit Fotos vorgestellt und das Vorkommen näher beschrieben.
Es wird über Vorkommen des Rauen Straußgrases Agrostis scabra WILLD. (Poaceae) in Essen und in Nordrhein-Westfalen berichtet. Die Art stammt ursprünglich aus Nordamerika und Ostasien. Sie ist im Ruhrgebiet mindestens seit 1992 eingebürgert und besiedelt offene Standorte auf Zechenbrachen und an Talsperren.
Zwei Funde des Arabischen Schneckenklees (Medicago arabica) in Geseke/Kreis Soest und Köln gaben Anlass, weitere Funde aus NRW zusammenzustellen und den Status der Art im Bundesland zu diskutieren. Angaben von Botanikern des 20. Jahrhunderts legen nahe, dass die Art schon damals an Wegrändern, auf Bahngeländen, auf Geländen von Wollspinnereien und in Gärten eingebürgert war. Zwei aktuelle Vorkommen in Köln und Königs-winter werden hier als eingebürgert betrachtet. Funde im Aachener Raum schließen sich an das niederländische Areal an, wo die Art als indigen betrachtet wird, sodass sogar ein Indigenat der Art in Nordrhein-Westfalen nicht auszuschließen ist.
Im Gemeindegebiet von Holzwickede (Kreis Unna, Nordrhein-Westfalen) wachsen derzeit fünf verschiedene Orchideen-Sippen. Die bei weitem Häufigste ist die Breitblättrige Stendelwurz (Epipactis helleborine), von der mehr als 1300 Pflanzen gefunden wurden und die als typische Orchidee des Siedlungsraums bezeichnet werden kann. Das Fuchs' Knabenkraut (Dactylorhiza fuchsii) wächst heute nicht mehr in der Naturlandschaft, sondern nur noch an zwei Orten in Zierrasen in Privatgärten im Siedlungsraum. Das Hybrid-Knabenkraut (Dactylorhiza maculata agg. x majalis) konnte an drei verschiedenen Stellen in Wiesen gefunden werden und ist offenbar konkurrenzkräftiger als ihre Elternarten. Die Vogelnestwurz (Neottia nidus-avis) war bisher im Gebiet noch nicht gefunden worden, bei dem neu entdeckten Wuchsort handelt es sich möglicherweise um eine Neuansiedlung. Ein Erstfund für Nordrhein-Westfalen gelang mit einer Hybride der Schnepfen-Ragwurz (Ophrys scolopax-Hybride), deren mögliche Herkunft diskutiert wird.
Aktuelle Entwicklungen der Verbreitung und Häufigkeit epiphytischer Moose und Flechten im Stadtgebiet Aachen und in angrenzenden Regionen werden vorgestellt. Speziell besprochen werden die folgenden Arten: Lebermoose: Cololejeunea minutissima, Lejeunea ulicina (= Microlejeunea u.), Metzgeria consanguinea (= M. temperata), M. violacea (= M. fruticulosa); Flechten: Diploicia canescens, Normandina pulchella, Melanohalea exasperata (= Melanelia e.), M. laciniatula (= Melanelia l.), Parmotrema pseudoreticulatum (= Rimelia olivaria), P. reticulatum (= Rimelia r.), Physcia clementei.
Über das Vorkommen stabilisierter Zwischenformen zwischen Geranium purpureum und G. robertianum in Aachen wird berichtet. Sie entsprechen im Habitus, in der Pollengröße sowie in der Farbe der Staubbeutel G. purpureum, unterscheiden sich aber in Kronblattfarbe und -maßen, Kelchfarbe und -behaarung sowie der Fruchtoberfläche. Es handelt sich offenbar um durch introgressive Hybridisation von G. robertianum in G. purpureum entstandene Sippen, die als G. urbanum und G. alboroseum neu beschrieben werden. Aufgrund der Pollengröße ist eine (annähernd) diploide Chromosomenzahl zu erwarten. Selten konnten intermediäre Hybriden G. purpureum × G. robertianum und G. urbanum × G. robertianum beobachtet werden, die heterogen große Pollenkörner ausbilden, keine reifen Früchte bilden und vermutlich triploid sind.
Der erste Teil einer Darstellung der Gattung Echinochloa im Stadtgebiet Aachen und nahe gelegenen Gebieten von Belgien, den Niederlanden und der Städteregion Aachen beschäftigt sich mit der E. muricata-Gruppe. In dieser Gruppe wird neben E. muricata s. str. eine weitere Art, E. wiegandii, unterschieden. Sie vermittelt vom Aussehen der Rispen und Ährchen zu E. crus-galli s. l., gehört aber aufgrund charakteristischer Merkmale der fertilen Deck- und Vorspelzen in die E. muricata-Gruppe. Diagnostische Merkmale von E. wiegandii gegenüber E. muricata s. str. sind ein früherer Blühbeginn, schlankere, schwächer bestachelte, dunkler gefärbte Ährchen sowie eine tendenziell längere Begrannung der Ährchen.
Persicaria x condensata, die Hybride zwischen P. maculosa und P. mitis, konnte an einigen Stellen im Stadtgebiet von Aachen sowie in angrenzenden Gebieten der Städteregion Aachen, Belgien und den Niederlanden an gemeinsamen Wuchsorten der Eltern beobachtet werden, insgesamt in etwa vierhundert Pflanzen. Fast alle sind nahezu steril, morphologisch einheitlich und dürften Primärhybriden sein. Sie vermitteln habituell und in den Merk-malen zwischen den Eltern. Auffallend sind neben der weitgehenden Sterilität die weißen bis hell rosa gefärbten Blütenstände. An einem Fundort in Deutschland konnten deutlich stärker fertile Rückkreuzungen von P. x condensata mit P. maculosa nachgewiesen werden. Sie ähneln P. maculosa. Die Entstehung mehrerer abweichender, recht einheitlicher, wenig fertiler Pflanzen von P. x condensata, die P. mitis stärker ähneln, ist ungeklärt. Sie wuchsen an zwei Stellen in den Niederlanden. An zwei Wuchsorten in Belgien und den Niederlanden konnten sechs Pflanzen von Persicaria x subglandulosa, der Hybride zwischen P. hydropiper und P. minor, und 13 Pflanzen von P. x wilmsii, der Hybride zwischen P. minor und P. mitis, beobachtet werden. P. x subglandulosa bildete keine reifen Früchte und zeigte ebenfalls weißliche Blütenstände. Die Pflanzen vermitteln zwischen den Eltern, ähneln insgesamt eher P. minor, vergrünen im Blütenbereich stärker und sind hier deutlich drüsig. P. x wilmsii ist partiell steril, bildet aber mehr gut ausgebildete Früchte als die anderen Hybriden (außer Rückkreuzungen) aus. Auch bei dieser Hybride sind die Blütenstände weißlich. Sie bildet zwischen den Eltern ansonsten vermittelnde Merkmale aus. Dies betrifft den Habitus sowie die Blüten, Früchte und Blätter. Andere Hybriden zwischen Persicaria hydropiper, P. maculosa, P. minor und P. mitis konnten nicht nachgewiesen werden. Das herausragende Merkmal der beobachteten Hybriden, das auch auf weitere fast sterile Persicaria-Hybriden zutreffen dürfte, sind auffallend helle Blütenstände, die eine einfache Identifizierung von Hybridpflanzen innerhalb von Persicaria-Populationen erlauben.
Hier werden bemerkenswerte floristische Funde aus Nordrhein-Westfalen aus dem Jahr 2016 und einige Nachträge aus 2015 zusammengestellt, die aus Sicht der Schriftleitung von landesweiter Bedeutung sind. Die Funde werden im Laufe des Jahres zunächst chronologisch auf die Homepage des Bochumer Botanischen Vereins gestellt und am Ende des Jahres zu einem Artikel zusammengefasst. Bei der Auswahl der Arten für diese Liste ist nicht an Bestätigung bereits lange bekannter Vorkommen gedacht, die an Ort und Stelle durchgehend vorkommen, sondern z. B. an Neufunde seltener Arten, Wiederfunde seltener Arten, die zwischendurch verschwunden schienen (wie z. B. Ackerunkräuter) oder auch an bekannte Vorkommen, die erloschen sind oder kurz vor dem Erlöschen stehen. Außerdem nehmen Beobachtungen von neophytischen Arten einen großen Raum ein, die entweder auf dem Wege der Einbürgerung sind, deren Einbürgerung noch nicht allgemein bekannt bzw. anerkannt ist oder deren Vorkommen bisher erst selten für Nordrhein-Westfalen veröffentlicht wurden. Ein wichtiges Kriterium für aufgeführte Arten ist die Seltenheit im Bundesland oder der betreffenden Großlandschaft bzw. Region. Die Zuordnung der Arten zu Pflanzenfamilien richtet sich nach Parolly & Rohwer 2016.
Im Folgenden werden für das östliche Ruhrgebiet bemerkenswerte Funde aufgeführt. Das Gebiet umfasst die Städte Gelsenkirchen, Essen, Herne, Bochum, Dortmund, Hagen und Hamm sowie die Kreise Recklinghausen, Unna und den Ennepe-Ruhr-Kreis. Zur besseren Auswertung wurden hinter den Fundorten die MTB-Angaben (Topographische Karte 1:25000) angegeben und ggf. eine Bewertung des Fundes für den hiesigen Raum und der floristische Status hinzugefügt. Funde aus dem östlichen Ruhrgebiet, die von nordrhein-westfälischer Bedeutung sind, sind im Beitrag Bochumer Botanischer Verein 2017 aufgeführt. Die Zuordnung der Arten zu Pflanzenfamilien richtet sich nach Parolly & Rohwer 2016.
Size-resolved measurements of atmospheric aerosol and cloud condensation nuclei (CCN) concentrations and hygroscopicity were conducted at the remote Amazon Tall Tower Observatory (ATTO) in the central Amazon Basin over a full seasonal cycle (Mar 2014–Feb 2015). In a companion part 1 paper, we presented an in-depth CCN characterization based on annually as well as seasonally averaged time intervals and discuss different parametrization strategies to represent the Amazonian CCN cycling in modelling studies (M. Pöhlker et al., 2016b). The present part 2 study analyzes the aerosol and CCN variability in original time resolution and, thus, resolves aerosol advection and transformation for the following case studies, which represent the most characteristic states of the Amazonian atmosphere:
1. Near-pristine (NP) conditions, defined as the absence of detectable black carbon (< 0.01 µg m−3), showed their highest occurrence (up to 30 %) in the wet season (i.e., Mar–May). On average, the NP episodes are characterized by a bimodal aerosol size distribution (strong Aitken mode: DAit = 70 nm, NAit = ~ 200 cm−3 vs. weaker accumulation mode: Dacc = 170 nm, Nacc = ~ 60 cm−3), a mostly organic particle composition, and relatively low hygroscopicity levels (κAit = 0.12 vs. κacc = 0.18). The NP CCN efficiency spectrum shows that the CCN population is sensitive to changes in supersaturation (S) over a wide S range.
2. Long-range transport (LRT) conditions frequently mix Saharan dust, African combustion smoke, and sea spray aerosols into the Amazonian wet season atmosphere. The LRT episodes (i.e., Feb–Apr) are characterized by an accumulation mode dominated size distribution (DAit = 80 nm, NAit = 120 cm−3 vs. Dacc = 180 nm, Nacc = 300 cm−3), a clearly increased abundance of dust and salt compounds, and relatively high hygroscopicity levels (κAit = 0.18, κacc = 0.34). The LRT CCN efficiency spectrum shows that the CCN population is highly sensitive to changes in S in the low S regime.
3. Biomass burning (BB) conditions dominate the Amazonian dry season. A selected characteristic BB episode shows a very strong accumulation mode (DAit = 70 nm, NAit = ~ 140 cm−3 vs. Dacc = 170 nm, Nacc = ~ 3400 cm−3), particles with very high organic fractions (> 90 %), and correspondingly low hygroscopicity levels (κAit = 0.14, κacc = 0.17). The BB CCN efficiency spectrum shows that the CCN population is highly sensitive to changes in S in the low S regime.
4. Mixed pollution conditions show the superposition of African (i.e., volcanic) and Amazonian (i.e., biomass burning) aerosol emissions during the dry season. The African aerosols showed a broad monomodal distribution (D = 130 nm, N = ~ 1300 cm−3), with very high sulfate fractions (20 %), and correspondingly high hygroscopicity (κAit = 0.14, κacc = 0.22). This was superimposed by fresh smoke from nearby fires with one strong mode (D = 113 nm, Nacc = ~ 2800 cm−3), an organic-dominated aerosol, and sharply decreased hygroscopicity (κAit = 0.10, κacc = 0.20). These conditions underline the rapidly changing pollution regimes with clear impacts on the aerosol and CCN properties.
Overall, this study provides detailed insights into the CCN cycling in relation to aerosol-cloud interaction in the vulnerable and climate-relevant Amazon region. The detailed analysis of aerosol and CCN key properties and particularly the extracted CCN efficiency spectra with the associated fit parameters provide a basis for an in-depth analysis of aerosol-cloud interaction in the Amazon and beyond.
The physical housing environment is important to facilitate activities of daily living (ADL) for older people. A hindering environment may lead to ADL dependence and thus increase the need for home services, which is individually restricting and a growing societal burden. This study presents simulations of policy changes with regard to housing accessibility that estimates the potential impact specifically on instrumental activities of daily living (I-ADL), usage of home services, and related costs. The models integrate empirical data to test the hypothesis that a policy providing funding to remove the five most severe environmental barriers in the homes of older people who are at risk of developing dependence in I-ADL, can maintain independence and reduce the need for home services. In addition to official statistics from state agencies in Sweden and Germany, we utilized published results from the ENABLE-AGE and other scientific studies to generate the simulations. The simulations predicted that new policies that remove potentially hindering housing features would improve I-ADL performance among older people and reduce the need for home services. Our findings suggest that a policy change can contribute to positive effects with regard to I-ADL independence among older people and to a reduction of societal burden.
Ein Jahr intensiver Vorbereitungen liegt nun hinter uns. Richtig, ein Jahr Vorbereitung für eine einwöchige Konferenz! Doch auch dieses Jahr hat sich wieder gezeigt wie wichtig diese intensive Vorbereitung ist: Die Studierenden haben sich vertiefte Kenntnisse über die Vereinten Nationen und die zu vertretenden Länder Israel und Frankreich angeeignet und neue Kompetenzen erworben. ...
We developed a coupled regional climate system model based on the CCLM regional climate model. Within this model system, using OASIS3-MCT as a coupler, CCLM can be coupled to two land surface models (the Community Land Model (CLM) and VEG3D), the NEMO-MED12 regional ocean model for the Mediterranean Sea, two ocean models for the North and Baltic seas (NEMO-NORDIC and TRIMNP+CICE) and the MPI-ESM Earth system model.
We first present the different model components and the unified OASIS3-MCT interface which handles all couplings in a consistent way, minimising the model source code modifications and defining the physical and numerical aspects of the couplings. We also address specific coupling issues like the handling of different domains, multiple usage of the MCT library and exchange of 3-D fields.
We analyse and compare the computational performance of the different couplings based on real-case simulations over Europe. The usage of the LUCIA tool implemented in OASIS3-MCT enables the quantification of the contributions of the coupled components to the overall coupling cost. These individual contributions are (1) cost of the model(s) coupled, (2) direct cost of coupling including horizontal interpolation and communication between the components, (3) load imbalance, (4) cost of different usage of processors by CCLM in coupled and stand-alone mode and (5) residual cost including i.a. CCLM additional computations.
Finally a procedure for finding an optimum processor configuration for each of the couplings was developed considering the time to solution, computing cost and parallel efficiency of the simulation. The optimum configurations are presented for sequential, concurrent and mixed (sequential+concurrent) coupling layouts. The procedure applied can be regarded as independent of the specific coupling layout and coupling details.
We found that the direct cost of coupling, i.e. communications and horizontal interpolation, in OASIS3-MCT remains below 7 % of the CCLM stand-alone cost for all couplings investigated. This is in particular true for the exchange of 450 2-D fields between CCLM and MPI-ESM. We identified remaining limitations in the coupling strategies and discuss possible future improvements of the computational efficiency.
National Model United Nations New York 2018 : Delegation der Goethe-Universität Frankfurt am Main
(2017)
Seit ihrer Gründung im Jahr 1945 sind die Vereinten Nationen zur bedeutendsten und einflussreichsten internationalen Organisation avanciert. Mittlerweile arbeiten 193 Mitgliedsstaaten gemeinsam an dem ehrgeizigen Ziel, den Weltfrieden und die internationale Sicherheit zu wahren. Der in der Charta der Vereinten Nationen verankerte Grundsatz des Verzichts auf Gewaltanwendung und der friedlichen Beilegung aller Streitigkeiten macht sie zu einer weltweit einzigartigen Institution.
Die Beschäftigung mit den Vereinten Nationen ist für Studierende der Gesellschaftswissenschaften – insbesondere der Politikwissenschaft – essentiell für den späteren Berufsalltag. Da der Fokus im wissenschaftlichen Universitätsbetrieb häufig auf der Diskussion theoretischer Paradigmen und eher selten auf praktischen Fragestellungen liegt, ist die Teilnahme am National Model United Nations (NMUN) in New York eine willkommene Abwechslung mit einzigartigem Charakter. Innerhalb einer Simulation von UN-Verhandlungen versetzen sich Studierende als Mitglieder einer Delegation in die Lage von Diplomaten und vertreten die Interessen, Werte und Positionen des ihnen zugeteilten Landes. Dabei versuchen sie, dessen Standpunkte in Kooperation mit anderen Delegationen durchzusetzen. ...
Background: As members of the Notothenioidei - the dominant fish taxon in Antarctic waters - the family Bathydraconidae includes 12 genera and 17 species. The knowledge of these species inhabiting an isolated environment is rather fragmentary, including their parasite fauna. Studies on fish hosts and their associated parasites can help gain insights into even remote ecosystems and be used to infer ecological roles in food webs; however, ecological studies on the Bathydraconidae are scarce.
Results: In this study, stomach contents and parasite fauna of the Antarctic dragonfish species Parachaenichthys charcoti (n = 47 specimens) as well as of Gerlachea australis (n = 5), Gymnodraco acuticeps (n = 9) and Racovitzia glacialis (n = 6) were examined. The parasite fauna of P. charcoti consisted of eight genera represented by 11 species, with three of them being new host records. Overall, 24 parasite genera and 26 species were found in the sampled fish, including eleven new host records.
Conclusion: Analyses revealed that the majority of the parasite species found in the different fish hosts are endemic to Antarctic waters and are characterized by a broad host range. These findings are evidence for the current lack of knowledge and the need for further parasitological studies of fish species in this unique habitat.
Background: Treatment of asthma does not always comply with asthma guidelines (AG). This may be rooted in direct or indirect resistance on the doctors’ and/or patients’ side or be caused by the healthcare system. To assess whether patients’ concepts and attitudes are really an implementation barrier for AG, we analysed the patients’ perspective of a “good asthma therapy” and contrasted their wishes with current recommendations.
Methods: Using a qualitative exploratory design, topic centred focus group (FG) discussions were performed until theoretical saturation was reached. Inclusion criteria were an asthma diagnosis and age above 18. FG sessions were recorded audio-visually and analysed via a mapping technique and content analysis performed according to Mayring (supported by MAXQDA®). Participants’ speech times and the proportion of time devoted to different themes were calculated using the Videograph System® and related to the content analysis.
Results: Thirteen men and 24 women aged between 20 and 77 from rural and urban areas attended five FG. Some patients had been recently diagnosed with asthma, others years previously or in childhood. The following topics were addressed: (a) concern about or rejection of therapy components, particularly corticosteroids, which sometimes resulted in autonomous uncommunicated medication changes, (b) lack of time or money for optimal treatment, (c) insufficient involvement in therapy choices and (d) a desire for greater empowerment, (e) suboptimal communication between healthcare professionals and (f) difficulties with recommendations conflicting with daily life. Primarily, (g) participants wanted more time with doctors to discuss difficulties and (h) all aspects of living with an impairing condition.
Conclusions: We identified some important patient driven barriers to implementing AG recommendations. In order to advance AG implementation and improve asthma treatment, the patients’ perspective needs to be considered before drafting new versions of AG. These issues should be addressed at the planning stage.
Trial registration: DRKS00000562 (German Clinical Trials Registry).
To assess the scope of infection control measures for multidrug-resistant bacteria in high-risk settings, a survey among university hospitals was conducted. Fourteen professionals from 8 sites participated. Reported policies varied largely with respect to the types of wards conducting screening, sample types used for screening and implementation of contact precautions. This variability among sites highlights the need for an evidence-based consensus of current infection control policies.
The yeast bc1 complex (complex III) and cytochrome oxidase (complex IV) are mosaics of core subunits encoded by the mitochondrial genome and additional nuclear-encoded proteins imported from the cytosol. Both complexes build in the mitochondrial inner membrane various supramolecular assemblies. The formation of the individual complexes and their supercomplexes depends on the activity of dedicated assembly factors. We identified a so far uncharacterized mitochondrial protein (open reading frame YDR381C-A) as an important assembly factor for complex III, complex IV, and their supercomplexes. Therefore, we named this protein Cox interacting (Coi) 1. Deletion of COI1 results in decreased respiratory growth, reduced membrane potential, and hampered respiration, as well as slow fermentative growth at low temperature. In addition, coi1Δ cells harbour reduced steady-state levels of subunits of complexes III and IV as well as of the assembled complexes and supercomplexes. Interaction of Coi1 with respiratory chain subunits seems transient, as it appears to be a stoichiometric subunit neither of complex III nor of complex IV. Collectively, this work identifies a novel protein that plays a role in the assembly of the mitochondrial respiratory chain.
The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome) based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.
The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model. The disease was less severe if the mice had received rapamycin treatment. Immunohistological analysis revealed that rapamycin not only prevented the activation of mTOR signalling (P-mTOR and P-S6 levels), but almost normalized the expression of epidermal differentiation markers. In addition, the influx of innate immune cells into the draining lymph nodes was partially reduced by rapamycin treatment. These data emphasize the role of mTOR signalling in the pathogenesis of psoriasis, and support the investigation of topical mTOR inhibition as a novel anti-psoriatic strategy.
Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at −80 °C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations (n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment (r = 0.455 to rs = 0.596; p < 0.004). In summary, when considering the acceptable change limit, BDNF was stable in serum and in EDTA-plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations.
Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis
(2017)
Background: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.
Aim: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.
Methods: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.
Results: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.
Conclusions: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions.
The histopathological and molecular heterogeneity of glioblastomas represents a major obstacle for effective therapies. Glioblastomas do not develop autonomously, but evolve in a unique environment that adapts to the growing tumour mass and contributes to the malignancy of these neoplasms. Here, we show that patient-derived glioblastoma xenografts generated in the mouse brain from organotypic spheroids reproducibly give rise to three different histological phenotypes: (i) a highly invasive phenotype with an apparent normal brain vasculature, (ii) a highly angiogenic phenotype displaying microvascular proliferation and necrosis and (iii) an intermediate phenotype combining features of invasion and vessel abnormalities. These phenotypic differences were visible during early phases of tumour development suggesting an early instructive role of tumour cells on the brain parenchyma. Conversely, we found that tumour-instructed stromal cells differentially influenced tumour cell proliferation and migration in vitro, indicating a reciprocal crosstalk between neoplastic and non-neoplastic cells. We did not detect any transdifferentiation of tumour cells into endothelial cells. Cell type-specific transcriptomic analysis of tumour and endothelial cells revealed a strong phenotype-specific molecular conversion between the two cell types, suggesting co-evolution of tumour and endothelial cells. Integrative bioinformatic analysis confirmed the reciprocal crosstalk between tumour and microenvironment and suggested a key role for TGFβ1 and extracellular matrix proteins as major interaction modules that shape glioblastoma progression. These data provide novel insight into tumour-host interactions and identify novel stroma-specific targets that may play a role in combinatorial treatment strategies against glioblastoma.
In Benin, people have a rich ethnobotanical knowledge of plant species, reflecting the cultural and ecological diversity of their environment. Several studies were focused on the question of how valuable are plant species for local communities. However, there has been very little research interest in the orchid species in spite of the importance of orchids in the livelihood of the local people. This study examined the use and differences in knowledge of local people of orchids in the Sudanian zone of Benin. An ethnobotanical study was conducted amongst the four main socio-economic and ethnic groups from six villages around the Pendjari Biosphere Reserve in Benin. One hundred and sixty people participated in this study. Data were gathered using semi-structured individual interviews and analysed using quantitative ethnobotanical methods. 29 different types of use were recorded and can be grouped into four main use categories: medicinal, veterinary, spiritual and food. There were differences in orchid utilization among the ethnic groups, gender and age. The knowledge of orchid uses was significantly affected by the ethnic group and the age of the respondent. Unlike young educated generations, most adults and elders, especially women, had a more comprehensive knowledge of orchid uses. Calyptrochilum christianum, the most used orchid, was mentioned in more than 50% of the types of orchid use. The Gourmantché and Waama tribe had more knowledge on orchid use whereas the Berba tribe had less knowledge. Three orchid species (Habenaria cirrhata, Eulophia horsfallii and Nervilia bicarinata) were reported as food. Orchids had low use value ranging from 0.01 (Eulophia spp) to 0.2 (C. christianum). The controlled access to the biosphere reserve and rural exodus can explain the lack of indigenous knowledge transfer of orchid use and value from elders to the young generation.
Cette étude analyse les stratégies locales de dénomination des espèces végétales par les Mossé des régions du nord, du centre nord, du centre et du Plateau Central du Burkina Faso et leurs perceptions des plantes. A travers des interviews semi directes auprès de 1437 personnes âgées d’au moins 60 ans et des jeunes de moins de 40 ans des différentes localités, l’étude a pu montrer les critères de dénomination, les conceptions que les populations ont des espèces végétales ainsi que l‘impact de ces connaissances dans la conservation de la phytodiversité. 72 espèces au total ont été décrites. Elles sont réparties en 51 genres et 29 familles. Les familles dominantes sont les Commelinaceae et les Fabaceae-Mimosoideae. Dans la taxonomie locale faite sur les plantes en milieu rural Mossé, 16 critères sont utilisés. Les critères les plus cités par la population sont l’usage fait de la plante (94 %), le mysticisme lié à l’espèce (86 %), l’écologie ou le milieu de vie de l’espèce (83 %), la dualité mâle/femelle (83 %), la couleur des organes ou parties de la plante (81 %), l’origine de la plante (80 %), la morphologie foliaire (76 %), la présence d’organes saillants sur la plante (75 %) et le mode de dissémination des fruits ou des graines (74 %). Les noms botaniques attribués aux plantes varient d’une région à une autre. Les populations ont des perceptions vis-à-vis de nombreuses espèces. Ainsi, les espèces comme Stereospermum kunthianum, Calotropis procera, Ozoroa insignis, Faidherbia albida, Maytenus senegalensis et Biophytum umbraculum sont frappées de mysticisme. Elles sont toutes craintes par les populations et sont dans certaines localités à l’abri d’exploitations multiformes humaines. Cela contribue à une meilleure conservation de la biodiversité.
La connaissance du potentiel et de la productivité d'une ressource est une donnée nécessaire à l'élaboration d'une bonne politique de sa gestion. La structure et la productivité des peuplements à Acacia seyal Del. et à Acacia senegal (L) Willd.ont été étudiées dans les formations naturelles de Massenya au Tchad. Sur la base de 32 placeaux de 900 m2 , le diamètre et la hauteur de tous les individus d’espèces ligneuses ont été mesurés. Pour des espèces adultes à port arbustif, le diamètre est mesuré à 50 cm du sol. Les individus juvéniles sont simplement comptés et rangés en classe de hauteur. L’étude de la structure des peuplements et de deux espèces d’Acacia a été réalisée à travers le nombre de tiges à l’hectare et les classes de diamètre. L’Indice de Valeur d’Importance (IVI) a été utilisée pour apprécier la prédominance des espèces sur le site. La productivité des peuplements en gomme a été évaluée en fonction de la production moyenne d’un arbre qui était de 250 g. Les peuplements à Acacia de Massenya sont très denses (619 ± 269 tiges/ha), mais à surface terrière faible (7,10 ± 1,20 m²/ ha) due à un grand nombre d’individus de petit diamètre (11,1 ± 2,2 cm). Ce sont des peuplements généralement arbustif (hauteur de 5,2 ± 0,9 m) avec un bon potentiel de juvéniles (408 ± 267 tiges/ha) pouvant se régénérer naturellement. Toutefois, Acacia seyal semble plus apte à coloniser d’autres milieux qu’Acacia senegal. Sur les sept espèces qui prédominent sur le site, Acacia seyal et Acacia senegal réalisent des IVI plus élevés (respectivement 79 et 54). Les espèces à bon potentiel de régénération sont Acacia seyal (65 ± 8 juv./ha), Acacia senegal (58 ± 10 juv./ha) et Guiera senegalensis (51 ± 8 juv./ha). La production annuelle de gomme est estimée à 56 ± 6 kg/ha de gomme friable (à Acacia seyal) et 41 ± 5 kg/ha de gomme dure (à A. senegal).
Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein.
Self-extracellular RNA (eRNA), released from stressed or injured cells upon various pathological situations such as ischemia-reperfusion-injury, has been shown to act as an alarmin by inducing procoagulatory and proinflammatory responses. In particular, M1-polarization of macrophages by eRNA resulted in the expression and release of a variety of cytokines, including tumor necrosis factor (TNF)-α or interleukin-6 (IL-6). The present study now investigates in which way self-eRNA may influence the response of macrophages towards various Toll-like receptor (TLR)-agonists. Isolated agonists of TLR2 (Pam2CSK4), TLR3 (PolyIC), TLR4 (LPS), or TLR7 (R848) induced the release of TNF-α in a concentration-dependent manner in murine macrophages, differentiated from bone marrow-derived stem cells by mouse colony stimulating factor. Here, the presence of eRNA shifted the dose-response curve for Pam2CSK4 (Pam) considerably to the left, indicating that eRNA synergistically enhanced the cytokine liberation from macrophages even at very low Pam-levels. The synergistic activation of TLR2 by eRNA/Pam was duplicated by other TLR2-agonists such as FSL-1 or Pam3CSK4. In contrast, for TLR4-agonists such as LPS a synergistic effect of eRNA was much weaker, and was not existent for TLR3-, or TLR7-agonists. The synergistic eRNA/Pam action was dependent on the NFκB-signaling pathway as well as on p38MAP- and MEK1/ERK-kinases and was prevented by predigestion of eRNA with RNase1 or by antibodies against TLR2. Thus, the presence of self-eRNA as alarming molecule sensitizes innate immune responses towards pathogen-associated molecular patterns (PAMPs) in a synergistic way and may thereby contribute to the differentiated outcome of inflammatory responses.
Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients
(2017)
Background: Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening performed in a family exhibiting clinical ATS phenotypes unmasked a novel sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to investigate the effect of this variant on Kir2.1 ion channel functionality.
Methods: Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in HEK293 cells. In order to examine the effect of the new variant, electrophysiological measurements were performed using patch clamp technique. Cellular localization of the mutant in comparison to the wild type ion channel was analyzed by confocal laser scanning microscopy.
Results: The currents of cells expressing only mutant channels or a mixture of wild type and mutant were significantly reduced compared to those expressing wild type (WT) channels (p < 0.01). Whereas WT expressing cells exhibited at −120 mV an averaged current of −4.5 ± 1.9 nA, the mutant generates only a current of −0.17 ± 0.07 nA. A co-expression of mutant and WT channel generates only a partial rescue of the WT current. Confocal laser scanning microscopy indicated that the novel variant is not interfering with synthesis and/or protein trafficking.
Conclusions: The detected sequence variant causes loss-of-function of the Kir2.1 channel and explains the clinical phenotypes observed in Andersen-Tawil syndrome patients.
Over recent decades, the global population has been rapidly increasing and human activities have altered terrestrial water fluxes to an unprecedented extent. The phenomenal growth of the human footprint has significantly modified hydrological processes in various ways (e.g. irrigation, artificial dams, and water diversion) and at various scales (from a watershed to the globe). During the early 1990s, awareness of the potential for increased water scarcity led to the first detailed global water resource assessments. Shortly thereafter, in order to analyse the human perturbation on terrestrial water resources, the first generation of large-scale hydrological models (LHMs) was produced. However, at this early stage few models considered the interaction between terrestrial water fluxes and human activities, including water use and reservoir regulation, and even fewer models distinguished water use from surface water and groundwater resources. Since the early 2000s, a growing number of LHMs have incorporated human impacts on the hydrological cycle, yet the representation of human activities in hydrological models remains challenging. In this paper we provide a synthesis of progress in the development and application of human impact modelling in LHMs. We highlight a number of key challenges and discuss possible improvements in order to better represent the human–water interface in hydrological models.
Im Rahmen der vorliegenden Arbeit wurden Inhibitoren der bakteriellen Resistenzproteine New Delhi Metallo-β-Lactamase 1 (NDM-1), die beiden Mutanten der Verona-Integron Encoded Metallo-β-Lactamase 1 und 2 (VIM-1, bzw. -2), sowie die Imipenemase 7 (IMP-7) entwickelt.
Auf Grund natürlicher Selektion, aber vor allem auch bedingt durch den unüberlegten und verschwenderischen Einsatz von β-Lactam-Antibiotika, ist eine weltweite Zunahme an multiresistenten Erregern zu beobachten. Einer der Hauptgründe dieser Resistenzen sind die Metallo- β-Lactamsen (MBL), welche vor allem in Gramnegativen Bakterien vertreten sind und für die Hydrolyse und damit der Desaktivierung der β-Lactam-Wirkstoffe verantwortlich sind. Neben der Suche nach anderweitig wirkenden Antibiotika, ist die Entwicklung von Inhibitoren der MBLs von vordringlicher Bedeutung.
Basierend auf der Grundstruktur des ACE-Hemmers Captopril, wurden trotz synthetischer Herausforderungen erfolgreich mehrere Strukturen mit inhibitorischer Aktivität gegenüber den MBLs synthetisiert. Der Prolinring von Captopril wurde in einer neuen Variante der Captopril-Synthese durch verschiedene Ring- und nicht cyclische Teilstrukturen ersetzt. Durch die Entwicklung einer Schutzgruppenstrategie, konnte die Ringstruktur durch einen Piperazin-Rest ersetzt werden. Dies erlaubt es, die Molekülstruktur auf dieser Seite zu erweitern. Des Weiteren wurde eine neue Syntheseroute etabliert, welche es auf elegante Weise ermöglicht, weitere Derivatisierungen an der Methylgruppe des Captoprils durchzuführen.
In einem proteinbasierten Testsystem wurden die synthetisierten Substanzen auf ihr inhibitorisches Potential hin untersucht. Dabei wurden IC50-Werte im niedrig einstelligen mikromolaren, für drei Verbindungen sogar im sub-mikromolaren Bereich ermittelt. Die erhaltenen Ergebnisse wurden für die drei aktivsten Inhibitoren durch eine Erhöhung des Schmelzpunktes in einem TSA-Testsystem erfolgreich verifiziert. Mittels ITC-Untersuchungen konnte die unterschiedlichen Gewichtungen der entropischen und enthalpischen Beiträge zur Bindung der Inhibitoren an die untersuchten MBLs aufgezeigt werden. Hierdurch konnten die scheinbar widersprüchlichen Ergebnisse der ermittelten IC50-Werte und Schmelzpunktverschiebungen für die Verbindung DBDK48 bezüglich der NDM-1 aufgeklärt werden.
Die Strukturen DB320 konnte erfolgreich mit VIM-2 co-kristallisiert werden. Dies ermöglicht eine genauere Untersuchung und qualifizierte Aussagen über die Bindungsverhältnisse zwischen Protein und Ligand.
Für zwei der synthetisierten Inhibitoren sollte untersucht werden, ob deren Aktivität in vitro auch in Bakterien erhalten bleibt. Dazu wurden pathogene klinische Isolate und Laborstämme, welche mit dem Resistenzplasmid transfiziert wurden, und gegen Imipenem resistent sind, herangezogen. Durch die Zugabe der Inhibitoren konnte die Wirksamkeit von Imipenem wiederhergestellt werden.
Es konnte eine HPLC-Methode etabliert werden, welche eine Abschätzung der Polaritäten in Abhängigkeit der Retentionszeiten erlaubt. Dadurch konnte ein direkter Zusammenhang zwischen der Polarität der Verbindungen und dem Grad der Wirksamkeit im MIC-Testsystem aufgezeigt werden.
Durch die Untersuchung der Inhibitoren auf die Proteine ACE und LTA4H, konnten zwei Ziel-Proteine der Captopril-Grundstruktur als unerwünschte Nebenziele ausgeschlossen werden. Des Weiteren führte die Behandlung von U937-Zellen, selbst bei einer hohen Konzentration von 100 µM, weder zu Auffälligkeiten in einem WST-1 Assay, noch zu einer erhöhten Freisetzung von LDH. Daher kann davon ausgegangen werden, dass die Verbindungen über keine zytotoxischen Eigenschaften verfügen.
In dieser klinischen, randomisierten, doppelverblindeten Vergleichsstudie untersuchten wir, welchen Einfluss auf die Passgenauigkeit von Einzelzahnkronen und dreigliedrigen Brücken aus Vollkeramik zum einen die Anwendung einer intraoralen Digitalisierung mithilfe eines Intraoralscanners (Lava C.O.S Scanner, 3M ESPE, D-Seefeld) und zum anderen der Einsatz einer extraoralen Digitalisierung auf Basis einer konventionellen Abformung (Impregum penta soft, 3M ESPE, D-Seefeld) hat. Als weiteres Prüfkriterium wurde die Effizienz der jeweiligen Abformmethoden untersucht. Die Fragestellung sollte eine Aussage dazu treffen können, ob die digitale Abformung im klinischen Alltag des Zahnarztes einen Vorteil gegenüber der konventionellen Abformung erbringen kann.
In der Studie wurden 25 Patienten eingeschlossen und beide Abformmethoden nach der Zahnpräparation in einer randomisierten Abfolge angewandt. Beim Intraoralscanner waren ein Ganzkieferscan für die Brückenrestaurationen und ein Quadrantenscan für Einzelzahnkronen erforderlich. Die klinischen Arbeitsschritte wurden zeitlich erfasst. Die Kronen- und Brückengerüste aus Zirkoniumdioxidkeramik basierten auf den unterschiedlichen Abformmethoden. Die Gerüste wurden vor der Anprobe verblindet und mit Hilfe von Silikonreplikas die Passgenauigkeit am marginalen Randspalt, an der axialen Wand, am axio-okklusalen Übergang, sowie am okklusalen Messpunkt unter 66x Vergrößerung ermittelt.
Der marginale Randspalt der Restaurationen auf der Basis der konventionellen Abformung betrug 68,64 μm (Medianwert), respektive 60,31 μm bei der digitalen Abformung und unterschied sich statistisch signifikant. Die Passung an der axialen Wand ergab bei der digitalen Abformung 88,27 μm, bei konventioneller 92,13 μm, am axio-okklusalen Übergang 144,78 μm vs. 155,60 μm, am okklusalen Messpunkt 155,57 μm vs. 171,51 μm. Letzter wies einen statistisch signifikanten Unterschied auf (Mann-Whitney U Test, p = 0,05). Die Zeitmessung zeigte eine Ersparnis von 5 min 6 sec beim Quadrantenscan und 1 min 34 sec beim Ganzkieferscan zu Gunsten der digitalen Abformung.
Die Studienergebnisse weisen eine effizientere klinische Arbeitsweise der digitalen gegenüber der konventionellen Abformung nach, die mit einer identischen Passungsqualität einhergeht.
Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein folding and cell-surface thiol-redox control of thrombosis and vascular remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and cytoskeleton organization, however the related underlying mechanisms are unclear. Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2 are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI), known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these three microsyntenic regions reveal their emergence by two successive duplication events of a primordial gene pair in the last common vertebrate ancestor. The arrangement, however, is substantially older, detectable in echinoderms, nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription orientation emerged early in animal evolution and has been largely maintained. PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common cis-regulatory elements. Analysis of gene expression datasets supports evidence for PDI/RhoGDI coexpression in developmental/inflammatory contexts. PDIA1/RhoGDIα were co-induced in endothelial cells upon CRISP-R-promoted transcription activation of each pair component, and also in mouse arterial intima during flow-induced remodeling. We provide evidence for physical interaction between both proteins. These data support strong functional links between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny along > 800-million years of evolution.
This thesis investigated the acquisition of restrictive and appositive interpretations of relative clauses in German-speaking children between the age of 3 and 6 in three experiments.
The theoretical background shows that restrictive relative clauses are semantically less complex than appositive ones. This assumption is supported by observations from a typological overview on the semantic functions attested across languages. It is shown that the existence of appositive relative clauses implies the availability of restrictive readings in a given language. Furthermore, restrictive readings may be favored due to the functioning of general processing principles. Previous research on the acquisition of relative clauses demonstrates that the acquisition of the semantic functions of relative clauses is an understudied area. In contrast, the acquisition of syntactic aspects of relative clauses is well documented. Relative clauses start to be produced in the third year of life and can be interpreted target-like between the age of 4 and 8 depending on their structure. Which semantic interpretation children assign to relative clauses at this age, however, is still an open question.
Based on the formal background and insights from previous studies, three experiments were designed: two picture selection tasks and one acceptability task. The crucial aspect of the experimental design constitutes the interaction of an ordinal number word and the interpretation of the relative clause in sentences like “Take the third car(,) that/which is red”. The scope of the ordinal number reveals whether the relative clause had been attached restrictively at the NP-level or whether it had been attached higher up at the DP shell resulting in an appositive interpretation.
The results of the experiments demonstrate that 4- to 6-year-old German-speaking children and adults prefer restrictive readings over appositive ones. This preference is found within the group data and is mirrored by the results of an individual analysis. In addition, while the majority of children has acquired restrictive readings at the age of 4, appositive interpretations are mastered only by about half of the children between age 4 and 6. Interestingly, 3-year-old children show a different pattern than their older peers. Appositive but not restrictive interpretations seem to be available to these children. Although the results may be taken as evidence that appositivity is acquired before restrictivity in relative clauses by German-speaking children, I propose the contrary. Based on assumptions about the complexity of restrictive and appositive derivations, I argue that the appositive interpretations observed at the age of 3 do not result from a target-like syntactic and semantic representation. I propose that 3-year-old children do not yet identify relative clauses as nominal modifiers. Instead, they are derived from an incorrect attachment of the relative clause higher up in the syntactic tree.
The results of the three experiments are the first to show that neither a prototypical unintegrated prosodic contour nor the presence of a lexical marker, the discourse particle “ja”, or a visual context biasing for appositivity led to an increase of appositive interpretations in the children’s groups. Adults, in contrast, were sensitive to the presence of the discourse particle and the cues from the visual context. As for children, the prosodic format of the relative clauses did not systematically change the interpretation preferences of adults.
The proposed acquisition path may not be specific to German. Instead, it is predicted to hold cross-linguistically and may also be transferred to the interpretation of adjectives. Moreover, the assumptions on how children integrate relative clauses during comprehension may be generalized to other types of subordinate clauses.
Surface water can contain a complex mixture of organic micropollutants (i.e. residues of pharmaceuticals or biocides). Conventional wastewater treatment plants (WWTPs) do not completely remove a broad range of anthropogenic chemicals and therefore represent a leading point source. To upgrade WWTPs, technical solutions based on oxidative and sorptive processes have been developed and successfully implemented. Acknowledging these substantial advances, this thesis focuses on another key topic and aims to investigate whether improved biological treatment processes likewise effectively remove anthropogenic micropollutants from wastewater. The work conducted on this topic was part of two European research projects (ATHENE, ENDETECH).
The ATHENE project aimed to go beyond the state-of-the-art by developing biological wastewater treatment processes that exploit the full potential of biodegradation. With the objective to explore the potential of complementary strictly anaerobic conditions within the biological wastewater treatment, combinations of aerobic and anaerobic treatments on site of a WWTP were implemented. Based on pre-experiments, two promising treatment combinations were selected for a more comprehensive evaluation. An aerobic treatment was paired with an anaerobic pre-treatment under iron-reducing conditions, and an activated sludge treatment was combined with an anaerobic post-treatment under substrate-limiting conditions. For the evaluation of these processes, an effect-based assessment was applied and combined with chemical data of 31 selected target organic micropollutants as well as ten metabolites. To assess the removal of endocrine disrupting chemicals (EDCs), yeast based reporter gene assays covering seven receptor-mediated mechanisms of action including (anti-)estrogenicity, (anti-) androgenicity, retinoid-like, and dioxin-like activity were conducted. Furthermore, the removal of unspecific toxicity (Microtox assay) and oxidative stress response as a marker for reactive toxicity (AREc32 assay) were analyzed to cover micropollutants acting via a non-specific mechanism of action. Moreover, to assess toxicity of the whole effluent in vivo, standardized in vivo bioassays with four aquatic model species (Desmodesmus subspicatus, Daphnia magna, Lumbriculus variegatus, Potamopyrgus antipodarum) were performed.
The combination of aerobic and anaerobic treatments resulted in a low additional removal of the selected target organic micropollutants (by 14-17%). In contrast, the removal of endocrine and dioxin-like activities (by 17-75%) and non-specific in vitro toxicities (by 27-60%) was significantly enhanced. Compared to technical solutions (i.e. ozonation), the combination with an anaerobic pre-treatment under iron-reducing conditions was likewise effective in removing the estrogenic activity as well as the unspecific toxicity, whereas anti-androgenic activity and dioxin-like activity were less effectively removed. Exposure to effluents of the conventional activated sludge treatment did not induce adverse in vivo effects in the investigated aquatic model species. Accordingly, no further improvement in water quality could be observed. In conclusion, the combination of aerobic and anaerobic treatment processes significantly enhanced the removal of specific and non-specific in vitro toxicities. Thus, an optimization of the biological wastewater treatment can lead to a substantially improved detoxification. These capacities of a treatment technology can only be uncovered by complementary effect-based measurements.
The global objective of the ENDETECH project was to develop a biotechnological solution to eliminate recalcitrant pharmaceuticals in wastewater direct from sites, where high loads are expected (i.e. hospitals). For this purpose, laccase, an enzyme mainly found in wood decaying fungi, was immobilized on ceramic membranes for application in bioreactors. In a proof of principle experiment, the performance of immobilized laccase in removing a mixture of 38 antibiotics without and in combination with a natural mediator (syringaldehyde; SYR) was investigated. For the evaluation of the enzymatic membrane bioreactors, chemical data on the elimination of the selected target antibiotics was combined with the outcomes of two in vitro bioassays. Growth inhibition tests with an antibiotic sensitive Bacillus subtilis strain were conducted to assess the residual antibiotic activity of the effluents, and Microtox assays were performed to detect a potential formation of toxic by-products.
The treatment by laccase without SYR did not reduce the load of antibiotics significantly. In contrast, in combination with a SYR concentration of 10 µmol L-1, 26 out of 38 antibiotics were removed by >50% after 24 h treatment. Moreover, increasing the SYR concentration to 1000 µmol L-1 resulted in a further improvement of the antibiotic removal. 32 out of 38 antibiotics were removed by over 50%, whereby 17 were almost completely eliminated (>90%). However, the treatment with laccase in combination with SYR resulted in a time-dependent increase of unspecific toxicity. While SYR alone did not affect B. subtilis, the combination of laccase with SYR led to a strong time-dependent growth inhibition up to 100%. Similar to that, a time-dependent increase of unspecific toxicity in the Microtox assay was observed. In conclusion, the laccase-mediator process successfully degrades a broad spectrum of antibiotics and thus represents a promising technology to treat wastewater from sites, where high loads are expected. However, further research is required to reduce the formation of unspecific toxicity before an implementation of this technology can be considered.
The soluble loop BC region guides, but not dictates, the assembly of the transmembrane cytochrome b6
(2017)
Studying folding and assembly of naturally occurring α-helical transmembrane proteins can inspire the design of membrane proteins with defined functions. Thus far, most studies have focused on the role of membrane-integrated protein regions. However, to fully understand folding pathways and stabilization of α–helical membrane proteins, it is vital to also include the role of soluble loops. We have analyzed the impact of interhelical loops on folding, assembly and stability of the heme-containing four-helix bundle transmembrane protein cytochrome b6 that is involved in charge transfer across biomembranes. Cytochrome b6 consists of two transmembrane helical hairpins that sandwich two heme molecules. Our analyses strongly suggest that the loop connecting the helical hairpins is not crucial for positioning the two protein “halves” for proper folding and assembly of the holo-protein. Furthermore, proteolytic removal of any of the remaining two loops, which connect the two transmembrane helices of a hairpin structure, appears to also not crucially effect folding and assembly. Overall, the transmembrane four-helix bundle appears to be mainly stabilized via interhelical interactions in the transmembrane regions, while the soluble loop regions guide assembly and stabilize the holo-protein. The results of this study might steer future strategies aiming at designing heme-binding four-helix bundle structures, involved in transmembrane charge transfer reactions.
Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic protein misfolding are less clear. Here we show that the mammalian ubiquitin ligase C-terminal Hsp70-interacting protein (CHIP), if freed from chaperones during acute stress, can dock on cellular membranes thus performing a proteostasis sensor function. We reconstituted this process in vitro and found that mainly phosphatidic acid and phosphatidylinositol-4-phosphate enhance association of chaperone-free CHIP with liposomes. HSP70 and membranes compete for mutually exclusive binding to the tetratricopeptide repeat domain of CHIP. At new cellular locations, access to compartment-specific substrates would enable CHIP to participate in the reorganization of the respective organelles, as exemplified by the fragmentation of the Golgi apparatus (effector function).
The formation of secondary particles in the atmosphere accounts for more than half of global cloud condensation nuclei. Experiments at the CERN CLOUD (Cosmics Leaving OUtdoor Droplets) chamber have underlined the importance of ions for new particle formation, but quantifying their effect in the atmosphere remains challenging. By using a novel instrument setup consisting of two nano-particle counters, one of them equipped with an ion filter, we were able to further investigate the ion-related mechanisms of new particle formation. In autumn 2015, we carried out experiments at CLOUD on four systems of different chemical compositions involving monoterpenes, sulfuric acid, nitrogen oxides, and ammonia. We measured the influence of ions on the nucleation rates under precisely controlled and atmospherically relevant conditions. Our results indicate that ions enhance the nucleation process when the charge is necessary to stabilize newly formed clusters, i.e. in conditions where neutral clusters are unstable. For charged clusters that were formed by ion-induced nucleation, we were able to measure, for the first time, their progressive neutralization due to recombination with oppositely charged ions. A large fraction of the clusters carried a charge at 1.2 nm diameter. However, depending on particle growth rates and ion concentrations, charged clusters were largely neutralized by ion–ion recombination before they grew to 2.2 nm. At this size, more than 90 % of particles were neutral. In other words, particles may originate from ion-induced nucleation, although they are neutral upon detection at diameters larger than 2.2 nm. Observations at Hyytiälä, Finland, showed lower ion concentrations and a lower contribution of ion-induced nucleation than measured at CLOUD under similar conditions. Although this can be partly explained by the observation that ion-induced fractions decrease towards lower ion concentrations, further investigations are needed to resolve the origin of the discrepancy.
Einführung: Die höchste Offenheitsrate in der arteriellen Bypasschirurgie der unteren Extremitäten wird mit einem Segment der Vena saphena magna (VSM) von ausreichender Länge und Durchmesser erreicht. Dabei ist der Venendurchmesser der einzige signifikant korrelierende Faktor für das Auftreten einer Transplantatsstenose und damit der beste Prädiktor für die primäre und die sekundäre 2-Jahre-Durchgängigkeitsrates. In 20-40% der Patienten fehlt ein bzgl. des Lumens geeignetes Segment der Vena saphena magna zur Herstellung eines Bypasses bei der primären Operation. Daher wurde eine Technik entwickelt, kleinlumige Vena saphena magna Segmente mittels einer Valvulotomie zu erweitern.
Ziel: Eine zu kleinlumige Vena saphena magna soll VSM für eine spätere Verwendung als autologes Bypassmaterial der unteren Extremität konditioniert werden. Die häufigsten Indikationen für eine derartige Konditionierung sind die Bypassverwendung bei der operativen Therapie der peripheren arteriellen Verschlusskrankheit (pAVK) und beim Aneurysma der Arteria poplitea (PA).
Methoden: Diese prospektive Pilotstudie würde zwischen Juni 2007 und November 2011 durchgeführt. 25 Patienten (26 Fälle) mit einem VSM Durchmesser zwischen 2 und 3mm erhielten eine in situ VSM-Valvulotomie. Die Zerstörung der suffizienten Venenklappen ermöglicht einen retrograden Blutstrom in die Vena saphena magna. Der hierdurch erzeugte Wachstumsreiz soll zu einer Durchmesserzunahme der Vene führen. Nach Erreichen eines Durchmessers von > 3mm für infragenuale Rekonstruktionen und von > 3,5 mm für supragenuale Rekonstruktion wurden die konditionierten Venensegmente als Bypass implantiert. Bei 23 Patienten war die Bypassindikation eine nicht kritische pAVK. Bei 2 Patienten war ein Aneurysma der Arteria poplitea die Indikation. Einschlusskriterium für Teilnahme an der Studie war eine nicht variköse VSM mit einem Querdurchmesser zwischen 2 und 3 mm. Die Venenevaluation erfolgte duplexsonografisch im Stehen durch eine Beurteilung der epifaszialen Vena saphena magna von der Leiste bis zum Innenknöchel. Messpunkte waren: 10 cm unterhalb des Hiatus saphenus, 10 cm oberhalb des Knies, 10 cm unterhalb des Knies und 10 cm oberhalb des Innenknöchels. Um das Venenwachstum zu ermitteln, diente als Messpunkt der kleinste ermittelte Durchmesser über einem Messbereich von 10 mm.
Drei Patienten, bei denen ein femoropoplitealer Bypass oberhalb des Kniegelenkes implantiert wurde, hatten bei der Implantation einen Durchmesser der konditionierten VSM > 3.5 mm. Bei 13 Patienten mit Bypassimplantation unterhalb des Kniegelenkes war die konditionierte VSM > 3mm. Eine Wiederholung der Valvulotomie war in keinem der Patienten nötwendig. Die valvulotomierte VSM wurde bei allen Bypassoperationen offen chirurgisch entnommen. Zur postoperativen Kontrolle erfolgten eine Duplexuntersuchung und eine ABI-Messung 1,3,6,12,18 und 24 Monate nach der Implantation.
Ergebnisse: Durchschnittlich vergrößerte sich der VSM-Durchmesser von initial 2,5±0,18 mm vor Valvulotomie auf 2,8±0,2 mm, 3,0±0,3mm und 3,2±0,4 mm jeweils 30, 60 und 90 Tage nach Valvolutomie. Bei der Entnahme betrug der durchschnittliche Bypassdurchmesser 3.7±0.6 mm. Die primäre 1-Jahres-Offenheitsrate mit der valvulotomierten VSM war 81±9,8% im Vergleich zu in der Literatur publizierten 58,0%±8,4% für alloplastische Transplantate, 51% für kleinkalibrige VSM und 81,6%±3,6% für Armvenentransplantate. Die sekundäre 1-Jahres-Offenheitsrate mit der Valvulotomietechnik betrug 87%±8,3% verglichen mit 82,6% für in der Literatur angegebene Transplantationen mit kleinkalibriger VSM. Die primäre 2-Jahres-Offenheitsrate mit der Valvulotomietechnik betrug 69%±11,8%, verglichen mit 50% in der Literatur angegebener Transplantationen von kleinkalibrige VSM benutzt wurden und 72%, falls Armvenentransplantate benutzt wurden. Die sekundäre 2-Jahres-Offenheitsrate mit der Valvulotomietechnik lag bei 75%±11%.
Fazit: Die Valvulotomie kann zur Zunahme des Venendurchmessers vor Anlage eines femoro-distalen Bypasses verwendet werden, weil sie regelhaft zum Reflux in der valvulotomierten Vene führt und dadurch ein relevantes Venenwachstum verursacht. Zwischen 60 und 90 Tagen nach Valvulotomie wird ein Venenduchmesser > 3.5 mm erreicht und die valvulotomierte VSM kann als femoropoplitealer Bypass oberhalb des Kniegelenkes implantiert werden. Für eine Anastomose unterhalb des Kniegelenkes genügt ein Wachstum bis > 3 mm. Wenn die valvulotomierte Vene einen entsprechenden Durchmesser erreicht, kann die konditionierte VSM benutzt werden, um einen Bypass mit guter Offenheitsprognose zu konstruieren oder einen nicht funktionierenden Bypass zu ersetzen.
The degradation of nonfunctional mitochondrial proteins is of fundamental relevance for maintenance of cellular homeostasis. The heteromeric CLPXP protein complex in the mitochondrial matrix is part of this process. In the fungal aging model Podospora anserina, ablation of CLPXP leads to an increase in healthy lifespan. Here, we report that this counterintuitive increase depends on a functional autophagy machinery. In PaClpXP mutants, autophagy is involved in energy conservation and the compensation of impairments in respiration. Strikingly, despite the impact on mitochondrial function, it is not mitophagy but general autophagy that is constitutively induced and required for longevity. In contrast, in another long-lived mutant ablated for the mitochondrial PaIAP protease, autophagy is neither induced nor required for lifespan extension. Our data provide novel mechanistic insights into the capacity of different forms of autophagy to compensate impairments of specific components of the complex mitochondrial quality control network and about the biological role of mitochondrial CLPXP in the control of cellular energy metabolism.
The study of lattice gauge theories with Monte Carlo simulations is hindered by the infamous sign problem that appears under certain circumstances, in particular at non-zero chemical potential. So far, there is no universal method to overcome this problem. However, recent years brought a new class of non-perturbative Hamiltonian techniques named tensor networks, where the sign problem is absent. In previous work, we have demonstrated that this approach, in particular matrix product states in 1+1 dimensions, can be used to perform precise calculations in a lattice gauge theory, the massless and massive Schwinger model. We have computed the mass spectrum of this theory, its thermal properties and real-time dynamics. In this work, we review these results and we extend our calculations to the case of two flavours and non-zero chemical potential. We are able to reliably reproduce known analytical results for this model, thus demonstrating that tensor networks can tackle the sign problem of a lattice gauge theory at finite density
The widespread application of human stem-cell-derived neurons for functional studies is impeded by complicated differentiation protocols, immaturity, and deficient optogene expression as stem cells frequently lose transgene expression over time. Here we report a simple but precise Cre-loxP-based strategy for generating conditional, and thereby stable, optogenetic human stem-cell lines. These cells can be easily and efficiently differentiated into functional neurons, and optogene expression can be triggered by administering Cre protein to the cultures. This conditional expression system may be applied to stem-cell-derived neurons whenever timed transgene expression could help to overcome silencing at the stem-cell level.
Introduction: DACCORD is an observational, non-interventional study being conducted in German primary and secondary care centres. The study aims to describe the impact of disease (including exacerbations) and treatments over 2 years on ‘real-life’ patients with chronic obstructive pulmonary disease (COPD).
Materials and methods: Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years and, on recruitment, were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and randomised clinical trial participation. Exacerbations data were collected every 3 months. COPD medication, COPD Assessment Test (CAT) and forced expiratory volume in 1 s (FEV1) were recorded at baseline and after 1 and 2 years.
Results: A total of 6122 patients were recruited, 3137 (51.2%) of whom completed the 2-year visit. The mean age of these patients was 65.6 years, 59% were male, 69% had mild or moderate airflow limitation, and their mean COPD Assessment Test (CAT) total score was 20.3. Overall, there was a trend towards decreasing COPD exacerbation rates over the 2-year follow-up period, with rates of 0.390 during Year 1 and 0.347 during Year 2. Rates were lower in patients with no exacerbation during the 6 months prior to entry (0.263 and 0.251 during Years 1 and 2, respectively), with 51.6% of patients having no exacerbation during the 6 months prior to entry and over the 2-year follow-up. Approximately 50% of the overall population experienced a clinically relevant improvement from baseline in CAT total score at Year 1 and 2. When assessed by treatment class (or classes), persistence to medication was high (77.8% in Year 1 and 71.4% in Year 2).
Conclusions: Overall, the 2-year follow-up data from DACCORD suggest that for most patients with COPD exacerbations are a rare event. For the majority of patients, the focus should be on managing symptoms, and the impact that these symptoms have on their daily lives. Even for those patients who do exacerbate, although prevention of exacerbations is an important factor, management of symptoms should be a key consideration. DACCORD also suggests that COPD disease progression is not inevitable – providing patients are receiving pharmacological treatment.
Science Slam zum Thema Nachhaltigkeit +++ Institutsbericht 2017 erschienen +++ Zukunftsstadt: ISOE bei BMBF-Vernetzungskonferenz in Frankfurt am Main +++ Mobiles Baden-Württemberg: Szenarien für eine nachhaltige Mobilität +++ Sustainability Special Issue zur Sozialen Ökologie als Buch erschienen +++ Lebensmittelverpackungen: Alternativen zu Plastik, Alu & Co. +++ Auswirkungen von Mikroplastik auf Umwelt und Gesellschaft +++ UN-Klimagipfel in Bonn: Genderperspektive für eine gerechte Klimaschutzpolitik +++ Ideenwettbewerb Der Blaue Engel: Auszeichnung für Kampagnenkonzepte +++ Aus dem ISOE: Forschungspreis Transformative Wissenschaft für Laura Woltersdorf +++ Termine +++ Publikationen
Verkehrswende braucht neue Mobilitätskultur +++ Urban Farming: Beitrag zur nachhaltigen Entwicklung von Städten? +++ Grundwasser als Quelle der Welternährung in Gefahr +++ Einfamilienhaus: Forschungsergebnisse zur Zukunft eines Wohnideals +++ Wasserbedarf prognostizieren: Planungssicherheit für Wasserversorger +++ Neue Plattform für transdisziplinäre Forschung +++ Ökosystem Savanne bewahren +++ Medikamentenrückstände in der Umwelt: Was Ärzte tun können +++ Energiewende, private Haushalte und nachhaltiger Konsum +++ Umweltgerechtigkeit bei Umwelt- und Naturschutz +++ Aus dem ISOE: Dr. Laura Woltersdorf erhält Forschungspreis "Transformative Wissenschaft" +++ ISOE-Lehrveranstaltungen im Wintersemester +++ Termine +++ Publikationen
Aktuelle Einblicke in die Soziale Ökologie: Special Issue der Zeitschrift Sustainability erschienen +++ Innovative Wohnformen für eine nachhaltige Stadtentwicklung +++ Transportmittel im Trend: Fahrradverkehr in der Zukunftsstadt +++ ISOE Policy Brief zur Biodiversitätsforschung erschienen +++ Zukunftsfähige Wasserinfrastrukturen: Empfehlungen zur Transformation +++ Nachhaltig leben mit Kunststoff? Das Frankfurter Nachhaltigkeitslabor für Schulen geht in die nächste Runde +++ Das ISOE auf der "MS Wissenschaft" +++ Mit dem Rad entlang der Nidda – Exkursion im Forschungsprojekt NiddaMan +++ Termine +++ Publikationen
Nachhaltige Mobilität für alle +++ Welche Rolle spielen die Jüngeren für die Mobilität der Zukunft? +++ Wissenschaftler empfehlen Neuausrichtung der Biodiversitätsforschung +++ A Plastic Ocean – Filmabend und Diskussion mit der Forschungsgruppe PlastX +++ Internationale Konferenz für Meereskunde und Binnengewässer: ISOE-Wissenschaftlerin stellt PlastX vor +++ Wasserressourcen und Klimawandel – Neue Modellierungsmethoden eröffnen Anpassungsstrategien +++ Abwasser als Ressource +++ Wohnraum clever nutzen: Projekt "LebensRäume" gestartet +++ ISOE unterstützt "March for Science" +++ ISOE-Lehrveranstaltungen im Sommersemester +++ Termine +++ Publikationen
Warum in der Schweiz mehr Fairtrade-Produkte als in Deutschland gekauft werden – eine aktuelle Studie gibt Antworten +++ Antibiotika in der Landwirtschaft – Zielkonflikte zwischen Gesundheits- und Umweltschutz +++ Energiearmut in Deutschland: Wie sozialverträglich ist die Energiewende? +++ netWORKS 4 – Was können städtische Versorgungssysteme zur klimagerechten Stadtentwicklung beitragen? +++ Beitrag zu den Sustainable Development Goals – Wasserwiederverwendung in Namibia +++ Energiewende: Wie die Bürgerbeteiligung beim Bau von Windkraft- oder Biogasanlagen verbessert werden kann +++ Wasserressourcen schonen: Aufbereitung von Abwasser für Industrie und Landwirtschaft +++ Aus dem ISOE +++ Termine +++ Publikationen
N-Allyltetramethylpiperidine is readily isomerized to the corresponding enamine by treatment with catalytic amounts of B(C6F5)3. It adds HB(C6F5)2 at the nucleophilic enamine carbon atom to form a C/B Lewis adduct. This reacts with two molar equivalents of carbon monoxide by selective head to tail coupling to give a five-membered C2O2B heterocycle. In contrast the enamine/HB(C6F5)2 Lewis pair reacts with two molar equiv. of nitric oxide by head to head coupling. This reaction probably proceeds via equilibrium with the corresponding vicinal N/B Lewis pair. Most products were characterized by X-ray diffraction.
Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus
(2017)
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro. Although A. fumigatus hyphae increase mRNA levels of IL6 in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte Aspergillus conidia, but phagocytosis of conidia is not associated with an alteration of the cytokine production by MSCs. In addition, human MSCs do not affect activation and function of A. fumigatus specific CD4+ T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our in vitro data indicate that administration of human MSCs is not associated with a negative impact on the host response against A. fumigatus and that the fungus does not stimulate MSCs to increase the release of those cytokines which play a central role in the pathophysiology of GvHD.
New provisioning rules introduced by IFRS 9 are expected to reduce the procyclicality of provisioning. Heterogeneity among banks in the procyclicality of provisioning may not only reflect the formal accounting rules, but also variation in discretionary provisioning policies. This paper presents empirical evidence on the heterogeneity of provisioning procyclicality among significant banks that are directly supervised by the ECB. In particular, this paper finds that provisioning is relatively procyclical at banks that have i) high loans-to-assets ratios, ii) high shares of non-interest income in total operating income, iii) low capitalization rates, and iv) low total assets. Supervisory guidance provided to banks on how to implement IFRS 9 has mostly been of a qualitative nature, and may prove inadequate to prevent an undesirably wide future variation in provisioning among EU banks.
This paper was provided at the request of the Committee on Economic and Monetary Affairs of the European Parliament and commissioned and drafted under the responsibility of the Economic Governance Support Unit (EGOV) of the European Parliament. It was originally published on the European Parliament’s webpage.
Seit 2006 haben die Bundesländer das Recht, den Steuersatz der Grunderwerbsteuer selbst zu bestimmen. Von diesem Recht wurde in den meisten Bundesländern – mit Ausnahme von Bayern und Sachsen – ausgiebig Gebrauch gemacht. Mit dieser Entwicklung sind verschiedene negative Begleiterscheinungen der Steuer weiter in den Vordergrund gerückt. Ausweichreaktionen und Preiseffekte auf dem Immobilienmarkt führten dazu, dass aus jedem Prozent, um das der Steuersatz erhöht wurde, schätzungsweise nur rund 0,6 Prozent zusätzliche Steuereinahmen resultierten, während ohne Ausweichreaktionen und Preiseffekte eine Einnahmenerhöhung um ein Prozent zu erwarten gewesen wäre. Hinter diesem unterproportionalen Aufkommenseffekt sind verschiedene Mechanismen zu vermuten, wie etwa die Umgehung durch den Kauf des Grundvermögens als Teil einer Kapitalgesellschaft.
In Anbetracht der gestiegenen Steuersätze wurde im letzten Bundestagswahlkampf aus CDU sowie FDP der Ruf laut nach einem Freibetrag für Immobilienkäufer, die erworbenes Wohneigentum selbst nutzen möchten. Die Kinderzahl soll den Freibetrag je nach Vorschlag erhöhen.
Der Beitrag diskutiert kritisch die Forderung nach einer Familienkomponente der Grunderwerbssteuer und zeigt darüber hinaus mögliche Alternativen zur Einschränkung der Steuergestaltungen durch Share Deals auf.
Coming (great) events cast their (long) shadow before. As the financial crisis gave birth to the creation of the European System of Financial Supervision (ESFS), the imminent Brexit now serves as an impulse to rather extensively reorganize it. Pursuant to the preferences of the Commission—as revealed in its draft for a regulation amending the regulations founding the European Supervisory Authorities (ESA)—the supervision (and regulation) of the financial sectors should be further centralized and integrated and additional powers should be given to the ESAs. To a large degree these alterations are intended to adjust the competences of the European Securities and Markets Authority (ESMA) to better meet its new objectives under the Capital Markets Union (“CMU”). In view that an equivalent to the CMU or the Banking Union—in the sense of a European Insurance Union—is not yet on the horizon for the insurance sector (or the occupational pensions sector), one could prima vista take the view that insurance supervision and regulation is once again taken captive by the necessity of regulatory reforms stemming from other financial sectors. However, even if that is partially the case, the outcome of the intended reforms might still be advantageous for the insurance sector and an important step in the right direction. Therefore, it needs to be intensively discussed.
At this stage, some of the most prominent envisioned changes to the structure, tasks and powers of the European Insurance and Occupational Pensions Authority (EIOPA) and their necessity, usefulness or counter-productivity still have to be examined.
During the last IAIS Global Seminar in June 2017, IAIS disclosed the agenda for a gradual shift in the systemic risk assessment methodology from the current Entity Based Approach (EBA) to a new Activity Based Approach(ABA). The EBA, which was developed in the aftermath of the 2008/2009 financial crisis, defines a list of Global Systemically Important Insurers (G-SIIs) based on a pre-defined set of criteria related to the size of the institution. These G-SIIs are subject to additional regulatory requirements since their distress or disorderly failure would potentially cause significant disruption to the global financial system and economic activity. Even if size is still a needed element of a systemic risk assessment, the strong emphasis put on the too-big-to-fail approach in insurance, i.e. EBA, might be partially missing the underlying nature of systemic risk in insurance. Not only certain activities, including insurance activities such as life or non-life lines of business, but also common exposures or certain managerial practices such as leverage or funding structures, tend to contribute to systemic risk of insurers but are not covered by the current EBA (Berdin and Sottocornola, 2015). Therefore, we very much welcome the general development of the systemic risk assessment methodology, even if several important questions still need to be answered.
This paper considers the trend towards megaregionalism (TTIP, TPP) that became prominent in the trade domain in the last years of the Obama administration. While megaregionalism has fallen by the wayside since Trump’s inauguration, the underlying rationale for such treaties will most likely reassert itself rather soon. So there are structural issues that need to be discussed from a standpoint of global justice. In all likelihood, megaregionalism is detrimental to global justice. TTIP in particular, or anything like it, might derail any possibility for a trade organization to aid the pursuit of justice at the global level, and any possibility that trade will be used to that end. From the standpoint of global justice one must hope that megaregionalism does not replace WTO multilateralism. The global-justice framework used here is the grounds-of-justice approach offered in the author’s 2012 On Global Justice.
Megaregional trade negotiations have become the subject of heated debate, above all in the context of the Transatlantic Trade and Investment Partnership (TTIP) and the Trans-Pacific Partnership (TPP). In this article, I argue that the justice of the global order suffers from its institutional fragmentation into regime complexes. From a republican perspective, which aspires to non-domination as a guiding principles and idea of global justice, regime complexes raise specific and important challenges in that they open the door to specific forms of domination. I thereby challenge a more optimistic outlook in regime complexes, which paints a positive normative picture of regime complexes, arguing that they enable the enhancement of democracy beyond the state and, consequently, have the potential to reduce the democratic deficit in global governance. By drawing attention to how regime complexes reinforce domination-related injustice, this article contributes an original perspective on megaregionals and to exploring the implications of global justice as non-domination.
Recent trade negotiations such as TTIP include investor protection clauses. Against the background of an analysis of the case for trade, the paper asks whether such clauses can be justified from a normative perspective. More specifically, what is the impact of investor protection on the domestic distribution of the gains from trade between labour and capital, and how should we assess this impact from the perspective of justice? In order to answer this question, the paper develops a series of ideal-type scenarios that reflect the consequences of investor protection on employment on the one hand, and on the distributive conflict between labour and capital on the other. While no claim is made which of these scenarios corresponds to TTIP or other trade agreements, they provide a useful normative framework to analyse such agreements.
nvestor-state-dispute-settlement (ISDS) is an arbitration mechanism to settle disputes between foreign investors and host-states. Seemingly a technical issue in private international law, ISDS procedures have recently become a matter of public concern and the target of political resistance, due to the power they grant to foreign investors in matters of public policies in the countries they invest in. This article examines the practice of ISDS through the lenses of liberal-statist theories of international justice, which value self-determination. It argues that the investor-state arbitration system illustrates how liberal-statist theories of international distributive justice ought to care about relative socioeconomic disadvantage, contra the sufficiency principle that they typically defend. The sufficiency principle draws on a questionable conception of the freedom that self-determination consists in.
Readers of Hannah Arendt’s now classic formulation of the statelessness problem in her 1951 book The Origins of Totalitarianism abound at a moment when the number of stateless peoples worldwide continues to rise exponentially. Along with statelessness, few concepts in Arendt scholarship have spawned such a volume of literature, and perhaps none have provoked as much interest outside of the field of philosophy, as ‘the right to have rights.’ Interpreting this enigmatic term exposes the heart of our beliefs about the nature of the political and has important consequences for how we practice politics on a global scale because it implicitly takes plural human beings, and not the citizen, as its subjects. Arendt’s conceptualization of this problem remains unsurpassed in its diagnosis of the political situation of statelessness, as well as its intimate description of the human cost of what she refers to as ‘world loss,’ a phenomenon that the prevailing human rights and global justice discourse does not take into account. And yet, as an alternative framework for thinking about global politics, the right to have rights resists easy interpretation, let alone practical application.
This Chapter explores how an environment of persistent low returns influences saving, investing, and retirement behaviors, as compared to what in the past had been thought of as more “normal” financial conditions. Our calibrated lifecycle dynamic model with realistic tax, minimum distribution, and Social Security benefit rules produces results that agree with observed saving, work, and claiming age behavior of U.S. households. In particular, our model generates a large peak at the earliest claiming age at 62, as in the data. Also in line with the evidence, our baseline results show a smaller second peak at the (system-defined) Full Retirement Age of 66. In the context of a zero-return environment, we show that workers will optimally devote more of their savings to non-retirement accounts and less to 401(k) accounts, since the relative appeal of investing in taxable versus tax-qualified retirement accounts is lower in a low return setting. Finally, we show that people claim Social Security benefits later in a low interest rate environment.
This paper studies the long-run effects of credit market disruptions on real firm outcomes and how these effects depend on nominal wage rigidities at the firm level. I trace out the long-run investment and growth trajectories of firms which are more adversely affected by a transitory shock to aggregate credit supply. Affected firms exhibit a temporary investment gap for two years following the shock, resulting in a persistent accumulated growth gap. I show that affected firms with a higher degree of wage rigidity exhibit a steeper drop in investment and grow more slowly than affected firms with more flexible wages.
We shed new light on the macroeconomic effects of rising temperatures. In the data, a shock to global temperature dampens expenditures in research and development (R&D). We rationalize this empirical evidence within a stochastic endogenous growth model, featuring temperature risk and growth sustained through innovations. In line with the novel evidence in the data, temperature shocks undermine economic growth via a drop in R&D. Moreover, in our endogenous growth setting temperature risk generates non-negligible welfare costs (i.e., 11% of lifetime utility). An active government, which is committed to a zero fiscal deficit policy, can offset the welfare costs of global temperature risk by subsidizing the aggregate capital investment with one-fifth of total public spending.
After the Lehman-Brothers collapse, the stock index has exceeded its pre-Lehman-Brothers peak by 36% in real terms. Seemingly, markets have been demanding more stocks instead of bonds. Yet, instead of observing higher bond rates, paradoxically, bond rates have been persistently negative after the Lehman-Brothers collapse. To explain this paradox, we suggest that, in the post-Lehman-Brothers period, investors changed their perceptions on disasters, thinking that disasters occur once every 30 years on average, instead of disasters occurring once every 60 years. In our asset-pricing calibration exercise, this rise in perceived market fragility alone can explain the drop in both bond rates and price-dividend ratios observed after the Lehman-Brothers collapse, which indicates that markets mostly demanded bonds instead of stocks.
In the context of the upcoming Brexit, a relocation of the clearing of euro-OTC derivatives for EU-based firms is the subject of controversial discussion. The opponents of a relocation argue that a relocation would cause additional costs for market participants of up to USD 100 bn over a period of 5 years. This paper shows that this cost estimate is fairly unrealistic and that relocation costs would amount to approximately USD 0.6 bn p.a., which translates to cumulative costs of around USD 3.2 bn for a transition period of 5 years. In light of the strategic importance of systemically relevant CCPs for the financial stability of the eurozone, the potential relocation costs should not be a decision criterion.
Das Clearing von Euro-OTC-Derivaten post Brexit – eine Analyse der vorliegenden Kostenschätzungen
(2017)
Im Zusammenhang mit dem Brexit wird über die Kosten einer Relokation des Clearing des Euro-OTC-Derivate-Geschäftes auf ein EU-CCP diskutiert. Das vorliegende Papier zeigt, dass die bislang vorliegenden Kostenschätzungen, die von Kosten in Höhe von bis zu USD 100 Mrd. für einen Zeitraum von fünf Jahren ausgehen, viel zu hoch sind. Die erwarteten Kosten einer Relokation liegen vielmehr bei ca. USD 0,6 Mrd. p.a. bzw. ca. USD 3,2 Mrd. für eine Übergangsphase von fünf Jahren. Angesichts der hohen Bedeutung von systemrelevanten CCPs für die Stabilität der Eurozone sollten diese Kosten nicht entscheidungsrelevant für eine Relokation sein.
We establish a benchmark result for the relationship between the loanable funds and the money-creation approach to banking. In particular, we show that both processes yield the same allocations when there is no uncertainty and thus no bank default. In such cases, using the much simpler loanable funds approach as a shortcut does not imply any loss of generality.
The CLOUD (Cosmics Leaving OUtdoor Droplets) experiment at CERN is studying the nucleation and growth of aerosol particles under atmospheric conditions, and their activation into cloud droplets. A key feature of the CLOUD experiment is precise control of the experimental parameters. Temperature uniformity and stability in the chamber are important since many of the processes under study are sensitive to temperature and also to contaminants that can be released from the stainless steel walls by upward temperature fluctuations. The air enclosed within the 3 m CLOUD chamber is equipped with several arrays (strings) of high precision, fast-response thermometers to measure its temperature. Here we present a study of the air temperature uniformity inside the CLOUD chamber under various experimental conditions. Measurements were performed under calibration conditions and run conditions, which are distinguished by the flow rate of fresh air and trace gases entering the chamber: 20 l/min and up to 210 l/min, respectively. During steady-state calibration runs between −70 °C and +20 °C, the air temperature uniformity is better than +/−0.06 °C in the radial direction and +/−0.1 °C in the vertical direction. Larger non-uniformities are present during experimental runs, depending on the temperature control of the make-up air and trace gases (since some trace gases require elevated temperatures until injection into the chamber). The temperature stability is a few times 0.01 °C over periods of several hours during either calibration or steady-state run conditions. During rapid adiabatic expansions to activate cloud droplets and ice particles, the chamber walls are up to 10 °C warmer than the enclosed air. This results in larger non-uniformities while the air returns to its equilibrium temperature with time constant of about 200 s.
Information theory provides a formal framework within which information processing and its disorders can be described. However, information theory has rarely been applied to modeling aspects of the cognitive neuroscience of schizophrenia. The goal of this article is to highlight the benefits of an approach based on information theory, including its recent extensions, for understanding several disrupted neural goal functions as well as related cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating that foundational concepts from information theory—such as Shannon information, entropy, data compression, block coding, and strategies to increase the signal-to-noise ratio—can be used to provide novel understandings of cognitive impairments in schizophrenia and metrics to evaluate their integrity. We then describe more recent developments in information theory, including the concepts of infomax, coherent infomax, and coding with synergy, to demonstrate how these can be used to develop computational models of schizophrenia-related failures in the tuning of sensory neurons, gain control, perceptual organization, thought organization, selective attention, context processing, predictive coding, and cognitive control. Throughout, we demonstrate how disordered mechanisms may explain both perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we demonstrate that there is consistency between some information-theoretic concepts and recent discoveries in neurobiology, especially involving the existence of distinct sites for the accumulation of driving input and contextual information prior to their interaction. This convergence can be used to guide future theory, experiment, and treatment development.
Auf Grundlage einer interviewbasierten Studie zu heterosexuellen Paaren, in denen die Frau das Haupteinkommen verdient, beschäftigt sich der Beitrag mit milieuspezifischen Bewältigungsmustern prekärer Beschäftigungsverhältnisse. Vor dem Hintergrund der Erosion des Ernährermodells werden dabei Transformationen von Männlichkeit in den Blick genommen. Es wird die These entwickelt, dass sich mit dem Selbstverständnis als "Künstler" im hochqualifizierten individualisierten Milieu des urbanen Raums ein spezifisches Bewältigungsmuster von Prekarität herausgebildet hat.
The inner boundary and the cristae membrane are connected by pore-like structures termed crista junctions (CJs). The MICOS complex is required for CJ formation and enriched at CJs. Here, we address the roles of the MICOS subunits Mic27 and Mic10. We observe a positive genetic interaction between Mic27 and Mic60 and deletion of Mic27 results in impaired formation of CJs and altered cristae membrane curvature. Mic27 acts in an antagonistic manner to Mic60 as it promotes oligomerization of the F1FO-ATP synthase and partially restores CJ formation in cells lacking Mic60. Mic10 impairs oligomerization of the F1FO-ATP synthase similar to Mic60. Applying complexome profiling, we observed that deletion of Mic27 destabilizes the MICOS complex but does not impair formation of a high molecular weight Mic10 subcomplex. Moreover, this Mic10 subcomplex comigrates with the dimeric F1FO-ATP synthase in a Mic27-independent manner. Further, we observed a chemical crosslink of Mic10 to Mic27 and of Mic10 to the F1FO-ATP synthase subunit e. We corroborate the physical interaction of the MICOS complex and the F1FO-ATP synthase. We propose a model in which part of the F1FO-ATP synthase is linked to the MICOS complex via Mic10 and Mic27 and by that is regulating CJ formation.
Background: Computed-tomography-guided interventions are attractive for tissue sampling of paediatric tumor lesions; however, it comes with exposure to ionizing radiation. The aim of this study was to analyse the radiation dose, accuracy and speed of CT-guided interventions in paediatric patient cohort.
Methods: We retrospectively reviewed CT-guided interventions over a 10 -year period in 65 children. The intervention site consisted of bones in 38, chest (lung) in 15 and abdomen (liver, lymph nodes) in 12 cases. Radiation dose and duration of the procedures were analysed. The statistical analysis was performed using dedicated statistical software (BiAS 8.3.6 software, Epsilon Verlag, North Hasted).
Results: All interventions were performed successfully. Mean target access path to lesion within the patients was 6.0 cm (min 3.5 cm, max 11.2 cm). Time duration to complete intervention was 25:15 min (min 17:03 min, max 43:00 min). The dose-length product (DLP) of intervention scan was 29.5 mGy · cm (min 6 mGy · cm, max 85 mGy · cm) with the lowest dose for biopsies in the region of the chest (p = 0.04).
Conclusions: With justified indications, CT-guided paediatric interventions are safe, effective and can be performed both, with short intervention times and low radiation exposure.
Background: To meet the requirements imposed by the time-dependency of acute stroke therapies, it is necessary 1) to initiate structural and cultural changes in the breadth of stroke-ready hospitals and 2) to find new ways to train the personnel treating patients with acute stroke. We aimed to implement and validate a composite intervention of a stroke team algorithm and simulation-based stroke team training as an effective quality initiative in our regional interdisciplinary neurovascular network consisting of 7 stroke units.
Methods: We recorded door-to-needle times of all consecutive stroke patients receiving thrombolysis at seven stroke units for 3 months before and after a 2 month intervention which included setting up a team-based stroke workflow at each stroke unit, a train-the-trainer seminar for stroke team simulation training and a stroke team simulation training session at each hospital as well as a recommendation to take up regular stroke team trainings.
Results: The intervention reduced the network-wide median door-to-needle time by 12 minutes from 43,0 (IQR 29,8–60,0, n = 122) to 31,0 (IQR 24,0–42,0, n = 112) minutes (p < 0.001) and substantially increased the share of patients receiving thrombolysis within 30 minutes of hospital arrival from 41.5% to 59.6% (p < 0.001). Stroke team training participants stated a significant increase in knowledge on the topic of acute stroke care and in the perception of patient safety. The overall course concept was regarded as highly useful by most participants from different professional backgrounds.
Conclusions: The composite intervention of a binding team-based algorithm and stroke team simulation training showed to be well-transferable in our regional stroke network. We provide suggestions and materials for similar campaigns in other stroke networks.
Das Fahren ohne (gültigen) Fahrschein im ÖPNV ist bereits seit den 1960er Jahren ein Problem zahlreicher Verkehrsunternehmen. Auch für die ÖPNV-Nutzenden stellt es ein Problem dar, da Personen, die den ÖPNV ohne (gültiges) Ticket nutzen in Deutschland eine Straftat begehen. In der Wissenschaft wurde das Thema aus unterschiedlichen Perspektiven heraus untersucht (v.a. Rechtswissenschaften, Betriebswirtschaften, Kriminologie sowie einige sozialwissenschaftliche Ansätze), jedoch konzentriert sich die Forschung vorrangig auf sozio-demographische Charakteristika, Marktsegmentierungen und die Folgen des Fahrens ohne (gültigen) Fahrschein für Verkehrsunternehmen und -verbünde. Die Motive und Beweggründe des Fahrens ohne (gültigen) Fahrschein werden in den vorhandenen Studien lediglich objektiv betrachtet. Das Arbeitspapier zeigt die Ergebnisse einer Untersuchung der Motive des Fahrens ohne (gültigen) Fahrschein im Bediengebiet des Rhein-Main-Verkehrsverbundes (RMV), die mithilfe von qualitativen Interviews mit Personen, die bei einer Fahrkartenkontrolle kein (gültiges) Ticket vorzeigen konnten, exploriert wurden.
In recent years, interest in the environmental occurrence and effects of microplastics (MPs) has shifted towards our inland waters, and in this chapter we provide an overview of the issues that may be of concern for freshwater environments. The term ‘contaminant of emerging concern’ does not only apply to chemical pollutants but to MPs as well because it has been detected ubiquitously in freshwater systems. The environmental release of MPs will occur from a wide variety of sources, including emissions from wastewater treatment plants and from the degradation of larger plastic debris items. Due to the chemical makeup of plastic materials, receiving environments are potentially exposed to a mixture of micro- and nano-sized particles, leached additives, and subsequent degradation products, which will become bioavailable for a range of biota. The ingestion of MPs by aquatic organisms has been demonstrated, but the long-term effects of continuous exposures are less well understood. Technological developments and changes in demographics will influence the types of MPs and environmental concentrations in the future, and it will be important to develop approaches to mitigate the input of synthetic polymers to freshwater ecosystems.
The diagnosis that we are living in a world risk society formulated by Ulrich Beck 20 years ago (Beck, Kölner Z Soziol Sozialpsychol 36:119–147, 1996) has lost nothing of its power, especially against the background of the Anthropocene debate. “Global risks” have been identified which are caused by human activities, technology, and modernization processes. Microplastics are a by-product of exactly these modernization processes, being distributed globally by physical processes like ocean currents, and causing effects far from their place of origin. In recent years, the topic has gained great prominence, as microplastics have been discovered nearly everywhere in the environment, raising questions about the impacts on food for human consumption. But are microplastics really a new phenomenon or rather a symptom of an old problem? And exactly what risks are involved? It seems that the phenomenon has accelerated political action—the USA has passed the Microbead-Free Waters Act 2015—and industries have pledged to fade out the use of microbeads in their cosmetic products. At first sight, is it a success for environmentalists and the protection of our planet?
This chapter deals with these questions by adopting a social-ecological perspective, discussing microplastics as a global risk. Taking four main characteristics of global risks, we develop four arguments to discuss (a) the everyday production of risk by societies, (b) scientific risk evaluation of microplastics, (c) social responses, and (d) problems of risk management. To illustrate these four issues, we draw on different aspects of the current scientific and public debate. In doing so, we contribute to a comprehensive understanding of the social-ecological implications of microplastics.
The ubiquitous detection of microplastics in aquatic ecosystems promotes the concern for adverse impacts on freshwater ecosystems. The wide variety of material types, sizes, shapes, and physicochemical properties renders interactions with biota via multiple pathways probable.
So far, our knowledge about the uptake and biological effects of microplastics comes from laboratory studies, applying simplified exposure regimes (e.g., one polymer and size, spherical shape, high concentrations) often with limited environmental relevance. However, the available data illustrates species- and material-related interactions and highlights that microplastics represent a multifaceted stressor. Particle-related toxicities will be driven by polymer type, size, and shape. Chemical toxicity is driven by the adsorption-desorption kinetics of additives and pollutants. In addition, microbial colonization, the formation of hetero-aggregates, and the evolutionary adaptations of the biological receptor further increase the complexity of microplastics as stressors. Therefore, the aim of this chapter is to synthesize and critically revisit these aspects based on the state of the science in freshwater research. Where unavailable we supplement this with data on marine biota. This provides an insight into the direction of future research.
In this regard, the challenge is to understand the complex interactions of biota and plastic materials and to identify the toxicologically most relevant characteristics of the plethora of microplastics. Importantly, as the direct biological impacts of natural particles may be similar, future research needs to benchmark synthetic against natural materials. Finally, given the scale of the research question, we need a multidisciplinary approach to understand the role of microplastics in a multiple-particle world.
"Ihr sollt euch nicht zu den Götzen wenden, und gegossene Götter sollt ihr euch nicht machen [...](Lev 19,4) [...] sollen wir nicht meinen, daß das Göttliche dem Gold und Silber oder Stein, einem Gebilde der Kunst und der Erfindung des Menschen gleich sei. (Acta 17,29) Pfui über euch und über das, was ihr an Gottes Statt verehrt! [...] (Q 21,67)"
Diese drei Sätze stammen nacheinander aus der hebräischen Bibel, dem Neuen Testament und dem Koran. Man kann sie beinahe wie einen Text lesen, an dem sich die These des Ägyptologen Jan Assmann belegen ließe, dass mit der Herausbildung monotheistischer Religionen wie Judentum, Christentum und Islam im Allgemeinen und dem Bilderverbot im Besonderen die Unterscheidung zwischen wahr und falsch in die Götterwelt gekommen sei (Assmann 1998, S. 17). ...
Es wäre eine bessere Welt, würde es diese Bilder nicht geben: Die Rede ist von Darstellungen, die sexuellen Missbrauch von und sexualisierte Gewalt an Kindern und Jugendlichen zeigen. Die physischen und psychischen Verletzungen, die durch den Missbrauch, aber auch durch dessen Perpetuierung in Bildern verursacht werden, sind unermesslich. Daher greift die Gesellschaft zu einem ihrer schärfsten Schwerter – dem Strafrecht.
Mit flexiblen Video-Endoskopen gelingen heute hochaufgelöste Bilder des Magen-Darm-Traktes. Bösartige Tumoren werden früher erkannt und oft auch entfernt, ohne die Bauchdecke aufzuschneiden. Sogar Verengungen der Gallenwege lassen sich mit hochpräziser Endoskopietechnik darstellen und behandeln. Die Medizinische Klinik 1 der Universitätsklinik unter der Leitung von Prof. Dr. Stefan Zeuzem gehört zu den Pionieren auf diesem Gebiet.
Lieblingsbild
(2017)