Universitätspublikationen
Refine
Year of publication
- 2015 (1742) (remove)
Document Type
- Article (606)
- Doctoral Thesis (187)
- Working Paper (169)
- Contribution to a Periodical (164)
- Book (159)
- Report (157)
- Part of Periodical (124)
- Review (70)
- Preprint (55)
- Conference Proceeding (22)
- Part of a Book (6)
- Master's Thesis (5)
- Periodical (5)
- Bachelor Thesis (4)
- Magister's Thesis (4)
- magisterthesis (4)
- Habilitation (1)
Language
- English (866)
- German (835)
- Spanish (14)
- Italian (11)
- Portuguese (11)
- French (3)
- Multiple languages (1)
- Russian (1)
Is part of the Bibliography
- no (1742)
Keywords
- Islamischer Staat (34)
- IS (25)
- Terrorismus (23)
- Deutschland (16)
- Dschihadismus (13)
- Syrien (12)
- Terror (11)
- Irak (10)
- Islamismus (10)
- Salafismus (10)
Institute
- Präsidium (336)
- Medizin (252)
- Gesellschaftswissenschaften (230)
- Physik (185)
- Wirtschaftswissenschaften (149)
- Exzellenzcluster Die Herausbildung normativer Ordnungen (116)
- Center for Financial Studies (CFS) (115)
- Biowissenschaften (99)
- Frankfurt Institute for Advanced Studies (FIAS) (97)
- Informatik (96)
In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.
The muscarinic M2 receptor (M2R) acts as a negative feedback regulator in central cholinergic systems. Activation of the M2 receptor limits acetylcholine (ACh) release, especially when ACh levels are increased because acetylcholinesterase (AChE) activity is acutely inhibited. Chronically high ACh levels in the extracellular space, however, were reported to down-regulate M2R to various degrees. In the present study, we used the PRiMA knockout mouse which develops severely reduced AChE activity postnatally to investigate ACh release, and we used microdialysis to investigate whether the function of M2R to reduce ACh release in vivo was impaired in adult PRiMA knockout mice. We first show that striatal and hippocampal ACh levels, while strongly increased, still respond to AChE inhibitors. Infusion or injection of oxotremorine, a muscarinic M2 agonist, reduced ACh levels in wild-type mice but did not significantly affect ACh levels in PRiMA knockout mice or in wild-type mice in which ACh levels were artificially increased by infusion of neostigmine. Scopolamine, a muscarinic antagonist, increased ACh levels in wild-type mice receiving neostigmine, but not in wild-type mice or in PRiMA knockout mice. These results demonstrate that M2R are dysfunctional and do not affect ACh levels in PRiMA knockout mice, likely because of down-regulation and/or loss of receptor-effector coupling. Remarkably, this loss of function does not affect cognitive functions in PRiMA knockout mice. Our results are discussed in the context of AChE inhibitor therapy as used in dementia.
Pharmacology: the pharmacodynamics of nutrients and nutrient interactions in biological functions
(2015)
Epidemiological studies and randomized controlled trials (RCTs) have shown that nutrition and nutritional habits may play a critical role in the optimal functioning of biological systems from conception to old age. Epidemiological studies, due to their methodology, can only provide correlations between consumption of nutrient(s) and biological outcomes, whereas RCTs normally study just one dose of a certain nutrient. Both study types are therefore ill-suited to study the mechanisms by which nutrients exert their benefits. Moreover, the nutrients’ functions may depend on each other. For example, B-vitamins’ functions are known to be interdependent. While the exact mechanisms are unclear, the course and severity of conditions such as obesity, cellular aging, cancer, and neurological disorders can be affected by nutritional approaches. Thus, food and nutrition play an intimate and inextricable role in human health. Despite growing interest in adequate nutrition, the effects of nutrient interaction, the possible varying effects on different organs, and the dependency of such effects on age or health status are complicated topics that deserve careful examination. ...
This article discusses obstacles to overcoming dangerous climate change. It employs an account of dangerous climate change that takes climate change and climate change policy as dangerous if it imposes avoidable costs of poverty prolongation. It then examines plausible accounts of the collective action problems that seem to explain the lack of ambition to mitigate. After criticizing the merits of two proposals to overcome these problems, it discusses the pledge and review process. It argues that pledge and review possesses the virtues of encouraging broad participation and of providing a procedural safeguard for the right of sustainable development. However, given the perceptions of the marginal short term costs of mitigation, pledge and review is unlikely, at least initially, to issue in an agreement to make deep reductions in greenhouse gas emissions. Because there is no rival approach that seems likely to better instantiate the two virtues, pledge and review may be the best available policy for mitigation. Moreover, recent economic research suggests that the co-benefits of mitigation may be greater than previously assumed and that the costs of renewable energy may be less than previously calculated. This would radically undermine claims that the short term mitigation costs necessarily render mitigation irrational and produce collective action problems. Given the circumstances, pledge and review might be our best hope to avoid dangerous climate change.
The upcoming CBM Experiment at FAIR aims at exploring the region of highest net baryonic densities reproducible in energetic heavy ion collisions. Due to the very high beam intensities expected at FAIR, unprecedented data regarding rare observables such as charm quarks and hyperons will be accessible. Open charm mesons are particularly interesting, since they support the reconstruction of the total charm cross-section in order to search for exotic phenomena, e.g. a phase transition towards the quark-gluon plasma which is predicted by several theoretical models. Open charm studies will be performed via secondary vertex reconstruction with a suitable Micro-Vertex Detector (MVD). The CBM-MVD is currently in the development and prototyping phase with primary design goals concentrating on spatial resolution, radiation hardness, material budget, and readout performance. CMOS Monolithic Active Pixel Sensors (MAPS) provide an excellent spatial resolution for the MVD in the order of few um in combination with a low material budget (50 um thickness) and high radiation hardness. The active volume of the devices is formed from the epitaxial layer of standard CMOS wafers. This allows for integration of pixels together with analogue and digital data processing circuits on one single chip. This option was explored with the MIMOSA-26 prototype, which integrates functionalities like pedestal correction, correlated double sampling, discrimination and data sparsification based on zero suppression combined with a small and dense pixel matrix. The pixel array composed of 576 lines of 1152 pixels is read out in a column-parallel rolling shutter mode. One discriminator per column and the digital data processing circuits are located on the same chip in a 3 mm wide area beneath the pixel matrix allowing for binary hit encoding. This area also contains the circuits for pedestal correction and the configuration memory, which is programmed via JTAG. The preprocessed digital data is read out via two 80 Mbit/s LVDS links per sensor, which stream their data continuously based on a low-level protocol.
Within the scope of this thesis, a readout concept of the CBM-MVD is proposed and studied based on the current MIMOSA sensor generation. The backbone of the system is formed by the Readout Controller boards (ROCs) featuring FPGA microchips and optical links. Several ROC prototypes are considered using the synergy with the HADES Experiment. Finally, the TRB3 board is selected as a possible candidate for the initial FAIR experiments. Furthermore, a highly scalable, hardware independent FPGA firmware is implemented in order to steer and read out multiple MIMOSA-26 sensors. The reconfigurable firmware is also designed with the support for future MIMOSA sensor generations. The free-streaming sensor data is deserialized and error-checked, prior to its transmission over a suitable network interface. In order to demonstrate the validity of the concept, a readout network similar to the HADES Data Acquisition (DAQ) system is developed. The ROC is tested on the HADES TRB2 boards and data is acquired using suitable MAPS add-on boards and the TrbNet protocol.
In the context of the CBM-MVD prototype project, a readout network with 12 MIMOSA-26 sensors has been prepared for an in-beam test at the CERN SPS facility. A comprehensive control system is designed comprising customized software tools. The subsequent in-beam test is used to validate the design choices. As a result, the system could be operated synchronously and dead-time free for several days. The readout network behavior in a realistic operating environment has been carefully studied with the outcome the the TrbNet based approach handles the MVD prototype setup without any difficulties. A procedure to keep the sensors synchronous even in case of a data overflow has been pioneered as well. After the beam test, improvements and conceptual changes to the readout systems are being addressed which allow an integration into the global CBM DAQ system.
Background: Recently, we have shown that the ATP-binding cassette (ABC) transporter ABCB1 interferes with the anti-cancer activity of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) but not of the aurora kinase A and B inhibitor alisertib (MLN8237). Preliminary data had suggested tozasertib also to be a substrate of the ABC transporter ABCG2, another ABC transporter potentially involved in cancer cell drug resistance. Here, we studied the effect of ABCG2 on the activity of tozasertib and alisertib.
Results: The tozasertib concentration that reduces cell viability by 50 % (IC50) was dramatically increased in ABCG2-transduced UKF-NB-3ABCG2 cells (48.8-fold) compared to UKF-NB-3 cells and vector-transduced control cells. The ABCG2 inhibitor WK-X-34 reduced tozasertib IC50 to the level of non-ABCG2-expressing UKF-NB-3 cells. Furthermore, ABCG2 depletion from UKF-NB-3ABCG2 cells using another lentiviral vector expressing an shRNA against the bicistronic mRNA of ABCG2 and eGFP largely re-sensitised these cells to tozasertib. In contrast, alisertib activity was not affected by ABCG2 expression.
Conclusions: Tozasertib but not alisertib activity is affected by ABCG2 expression. This should be considered within the design and analysis of experiments and clinical trials investigating these compounds.
The PKCβ inhibitor enzastaurin was tested in parental neuroblastoma and rhabdomyosarcoma cell lines, their vincristine-resistant sub-lines, primary neuroblastoma cells, ABCB1-transduced, ABCG2-transduced, and p53-depleted cells. Enzastaurin IC50s ranged from 3.3 to 9.5 μM in cell lines and primary cells independently of the ABCB1, ABCG2, or p53 status. Enzastaurin 0.3125 μM interfered with ABCB1-mediated drug transport. PKCα and PKCβ may phosphorylate and activate ABCB1 under the control of p53. However, enzastaurin exerted similar effects on ABCB1 in the presence or absence of functional p53. Also, enzastaurin inhibited PKC signalling only in concentrations ≥ 1.25 μM. The investigated cell lines did not express PKCβ. PKCα depletion reduced PKC signalling but did not affect ABCB1 activity. Intracellular levels of the fluorescent ABCB1 substrate rhodamine 123 rapidly decreased after wash-out of extracellular enzastaurin, and enzastaurin induced ABCB1 ATPase activity resembling the ABCB1 substrate verapamil. Computational docking experiments detected a direct interaction of enzastaurin and ABCB1. These data suggest that enzastaurin directly interferes with ABCB1 function. Enzastaurin further inhibited ABCG2-mediated drug transport but by a different mechanism since it reduced ABCG2 ATPase activity. These findings are important for the further development of therapies combining enzastaurin with ABC transporter substrates.
Im Juni spricht der Leipziger Schriftsteller Clemens Meyer im Rahmen der Frankfurter Poetikvorlesungen über den „Untergang der Äkschn GmbH“. Meyers ungewöhnliche Biographie und seine Romane über Leipziger Jugendgangs, Prostituierte und Zuhälter versprechen interessante Vorträge. Wir haben ihm vorab einige Fragen gestellt – seine mitunter forschen Antworten deuten jedenfalls an, dass der Autor sein Publikum bestimmt nicht langweilen wird.
Im Schulunterricht der deutschen Gymnasien hat die Vermittlung poetologischen Wissens im 19. Jahrhundert einen besonderen Platz eingenommen. Dabei wurde das Gebiet der Poetik jedoch sehr unterschiedlich dargestellt. Zum einen war die Poetik, die Lehre der Dichtkunst, seit dem 18. und während des gesamten 19. Jahrhunderts fortlaufend Veränderungen und Repositionierungen unterworfen. Zum anderen formte und entwickelte sich der moderne Deutschunterricht in dieser Zeit, stark beeinflusst durch die zeitgeschichtlichen Tendenzen der Verwissenschaftlichung, der Fächerdifferenzierung und der Nationalideologien. Als Konstante lässt sich jedoch über das gesamte Jahrhundert hinweg eine hohe Wertschätzung der Poetik als Unterrichtsfach erkennen. Daher wurden von Schulbuchverlagen von Beginn des 19. und bis in die 20er Jahre des folgenden Jahrhunderts hinein didaktische Poetiken veröffentlicht, die eine sehr lange und weite schulische Verwendung fanden.
In der hier vorgelegten Arbeit werden anhand einer Auswahl dieser Schulpoetiken die Grundargumente des Diskurses über Poetik herausgearbeitet und untersucht, wie sich diese im Laufe des Jahrhunderts veränderten. Dadurch wird eine Grundlage dafür geschaffen, das als gültig wahrgenommene Wissen über Form und Wesen der Literatur zu rekonstruieren, das sowohl die Leser aber auch die Schriftsteller beeinflusst hat, die aus den Schülergenerationen zwischen 1830 und 1920 stammen.
Nach der Landtagswahl in Bremen 2007 haben sich, nach langjähriger SPD/CDU-Partnerschaft (1995-2007), zwei Parteien zu einer Koalition entschlossen, die in ihren Wahlprogrammen eine „Schule für alle“ (Grüne) bzw. eine „Gemeinsame Schule“ (SPD) von 5 bis 10 angekündigt haben. Die Befürworter einer solchen Schule erwarteten, dass den Ankündigungen im Wahlkampf nun auch Taten folgen. So forderte die GEW von SPD und Grünen die als ersten Schritt versprochenen Maßnahmen: Alle Schulen werden verpflichtet, „die aufgenommenen Schülerinnen und Schüler in ihrer Schule zu einem Abschluss zu führen“ (SPD) und alle Abschlüsse der Sekundarstufe I können „an jeder Schule erworben werden“ (Grüne), womit alle Bildungsgänge, das Gymnasium eingeschlossen, bei der Entwicklung eines integrativen Schulsystems einbezogen waren...