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After five years of the Syrian war, we can recognize “four” conflicting parties on the ground – Assad, ISIS, rebel groups and the Kurds. Each one of these conflicting parties has regional and international backers, who ironically do not agree with each other about whom they are fighting for or against. The Syrian regime is backed by Iran, Russia, Hezbollah and Iraqi militias. ISIS is backed by the flood of global Jihadists from all over the world. Rebel groups are backed by Gulf States, Turkey, Jordan and the US. The Kurds are supported by the US. While in the media, we always say “the Syrian conflict, crisis or war”, I wonder what makes this war that much Syrian. It is rather a war on the land of Syria, in which more than 50% of Syria’s population have been displaced, over 220 thousand have been killed, and many more have been injured or imprisoned. According to Amnesty international, more than 12.8 million Syrian people are in “urgent need of humanitarian assistance”. In addition to this humanitarian catastrophe, most of the Syrian land and infrastructure have been destroyed. So what is that Syrian about the Syrian “war”?...
Practicing politics within religious frameworks is more likely to increase states‘ fragility. While employing religious references in political discourses could foster positive outcomes such as avoiding dangerous eruptions of violence under authoritarian regimes, it could also increase the space for political and religious elites to instrumentalise religion for their own interests. Such patterns of instrumentalisation are more common in the Middle East; especially the dominant religion in the region is Islam, which enjoys a decentralised mode of function...
Religion in the Middle East seems to define allies and enemies inside and outside the political borders. On the one hand, Shiite Iran is allies with the Iraqi government, the Houthi rebels in Yemen, Hezbollah in Lebanon, revolutionary forces in Bahrain and the Syrian regime. On the other hand, Sunni Saudi Arabia and other Gulf States, Egypt, Turkey and Sunni elements in the region form an alliance against what they call the expansion of the Iranian influence. There is an unmistaken pattern of alliance in the Middle East, in which states, monarchies and forces seem to define their allies and enemies based on sectarian dimensions, and by which we witness a minority oppressing a majority when it is possible and vice versa across the Middle East including Israel...
When the Iranian revolution embarked against Muhammad Reza Shah’s regime in the late 70s, it wasn’t a social revolution aiming at changing the society, but rather a political one with legitimate demands similar to what Syrians once were looking forward to achieve in 2011. When all this started in Iran, Ayatollah Ruhollah Khomeini, the most central and inspirational figure in the Iranian revolution was still in exile. This is a story that happened 35 years ago and we cannot but see the rhyming of its events with the current Syrian imbroglio...
Using religious frameworks in political contestation and mobilisation processes has become more eminent in recent decades spiralling an intricate debate on the conceptualisation and implementation of such references in the Middle East and North Africa (MENA) region The contradiction, it is argued, mainly lies in the compromising nature of politics and the relatively dogmatic nature of religion. Accentuated by inaccurate media coverage and primordial analytical frameworks, it has become tempting to see religion as responsible for conflicts and underachievement in the MENA region...
Acute myeloid leukemia is a hematopoietic stem cell disorder and a type of acute leukemia which is characterized by clonal proliferation of myeloid precursors with a reduced capacity to differentiate into more mature cellular elements. Clinically AML is characterized by a high degree of heterogeneity with respect to chromosome abnormalities, gene mutations, and changes in expression of multiple genes and microRNAs. Cytogenetic abnormalities can be detected in approximately 50% to 60% of newly diagnosed AML patients. Majority of AML cases are associated with chromosomal aberrations, more specifically translocations that often result in gene arrangements and expression of aberrant fusion proteins. This study was carried out with two fusion proteins: PML/RARα and DEK/CAN which results from the translocations t(15;17) and t (6,9) respectively. PML/RARα is the most common translocation (97%) and the main driver in Acute Promyelocytic Leukemia (APL), a wellcharacterized and well treatable subtype of AML. In contrast, DEK/CAN occurs in 1-5% of AML, associated with poor prognosis and defines a high risk group in AML. The expression of PML/RARα results in a fusion protein that acts as a transcriptional repressor by interfering with gene expression programs involved in differentiation, apoptosis, and selfrenewal. Current therapy focused on the targeting of PML/RARα fusion protien. Success has been achieved by using either ATRA, anthracyclines and Arsenic trioxide or their combinations. These agents induce differentiation in PML/RARα positive AML and hence called differentiation therapy. In comparison with ATRA, ATO and anthracyclines are poor cellular differentiation agents. Despite early promise, several studies have reported that differentiation therapy is unable to target/eradicate leukemic stem cells or eradicate the disease. Therefore current therapeutic focus is to eliminate leukemic stem cells and achieve complete molecular remission not only in APL but also in acute lymphoblastic leukemia and chronic myeloid leukemia as well. Key enzymes of the eicosanoid pathways in the arachidonic acid metabolism, such as COX1/2 as well as the 5-LO have been shown to be good targets for leukemic stem cell therapy approach in AML by interfering with the Wntsignaling which is known to be indispensable for the pathogenesis of AML. Recently it was reported that the third eicosanoid pathway based on the cytochrome P450 (CYP) enzymes interferes with Wnt-signaling as well as with the proliferation and mobilization of hematopoietic stem cells...
Die von J. Wiesehöfer herausgegebene Reihe Oriens et Occidens ist um einen neuen, wissenschaftsgeschichtlich wie kulturhistorisch wertvollen Band bereichert worden, den inzwischen 22. der 2001 begonnenen Reihe. Verfasst hat ihn der emeritierte amerikanische Gelehrte Lawrence J. Baack (* 1943), der sich u.a. durch seine Forschungen zur deutschen Geschichte des frühen 19. Jhs. einen Namen gemacht hat und auch über dänische und schwedische Sprachkenntnisse verfügt. Schon der fünfte Band der Reihe war derselben Thematik gewidmet. Er ist als Begleitband höchst wertvoll mit seinen zahlreichen Spezialbeiträgen, die in dieser Ausführlichkeit vom Vf. nicht behandelt werden konnten. Der Titel darf – auch wenn in der Forschung oft von der „Arabischen Reise“ gesprochen wird – nicht darüber hinwegtäuschen, dass zwar das Hauptziel der von J. D. Michaelis, einem Professor für Philosophie an der damals neu gegründeten Universität Göttingen, angeregten, vom dänischen König Friedrich V. († 1766) finanzierten Expedition von sechs Personen der Jemen war, der am 27.12.1762 mit der Ankunft in al-Luḥayya erreicht wurde. Doch durch den Tod des Philologen und des Botanikers am 25.5. bzw. am 11.7.1763 entschloss man sich bereits am 24.8.1763, nach Indien abzusegeln, aber durch den Tod des Zeichners und des Assistenten nur wenige Tage später kamen nur noch Niebuhr und der Arzt am 11.9.1763 in Bombay in Indien an, und nachdem auch dieser im Februar 1764 verstarb, setzte Niebuhr als Einzelforscher die Reise durch den Vorderen Orient bis zu seiner Rückkehr im Herbst 1767 fort...
Zwei große Theaterzettelsammlungen mit über 100.000 Stück sind seit dem ersten Drittel des 20. Jahrhunderts in der damaligen Stadt- und heutigen Universitätsbibliothek Frankfurt am Main beheimatet und machen sie in dieser Hinsicht zu einer bedeutenden theaterhistorischen Institution im deutschsprachigen Raum: die Sammlung der Städtischen Bühnen Frankfurt am Main und ihrer Vorläufer sowie die Sammlung des Manskopfschen Musik- und Theaterhistorischen Museums...
Innovative Wasserinfrastrukturen, wie sie etwa mit den Neuartigen Sanitärsystemen entwickelt worden sind, versprechen Effizienzgewinne. Ihre Anwendung bedeutet nicht nur, den Einsatz neuer Techniken, sondern auch, dass sich die im konventionellen System erprobten Arbeitsteilungen zwischen verschiedenen Akteuren verändern. Ebenso können sich Beweggründe und Motivationen der beteiligten Akteure wandeln. Die Innovations- und Umsetzungsschritte werden dabei komplexer. Die Konstellationen der verschiedenen (heterogenen) Akteure und ihre Zusammenarbeit haben dabei hohe Relevanz für die Umsetzung innovativer Infrastrukturkonzepte.
Das vorliegende Diskussionspapier zeigt – aufbauend auf Ergebnisse aus zwei BMBFForschungsvorhaben – welcher Koordinationsbedarf bei einer Umsetzung auf der Quartiersebene zu erwarten ist. Zudem werden Hinweise gegeben, wie sich die Koordination zwischen den beteiligten Akteuren optimieren lässt.
Study Design: Survey of 100 worldwide spine surgeons.
Objective: To develop a spine injury score for the AOSpine Thoracolumbar Spine Injury Classification System.
Methods: Each respondent was asked to numerically grade the severity of each variable of the AOSpine Thoracolumbar Spine Injury Classification System. Using the results, as well as limited input from the AOSpine Trauma Knowledge Forum, the Thoracolumbar AOSpine Injury Score was developed.
Results: Beginning with 1 point for A1, groups A, B, and C were consecutively awarded an additional point (A1, 1 point; A2, 2 points; A3, 3 points); however, because of a significant increase in the severity between A3 and A4 and because the severity of A4 and B1 was similar, both A4 and B1 were awarded 5 points. An uneven stepwise increase in severity moving from N0 to N4, with a substantial increase in severity between N2 (nerve root injury with radicular symptoms) and N3 (incomplete spinal cord injury) injuries, was identified. Hence, each grade of neurologic injury was progressively given an additional point starting with 0 points for N0, and the substantial difference in severity between N2 and N3 injuries was recognized by elevating N3 to 4 points. Finally, 1 point was awarded to the M1 modifier (indeterminate posterolateral ligamentous complex injury).
Conclusion: The Thoracolumbar AOSpine Injury Score is an easy-to-use, data-driven metric that will allow for the development of a surgical algorithm to accompany the AOSpine Thoracolumbar Spine Injury Classification System.
Tumour hypoxia plays a pivotal role in cancer therapy for most therapeutic approaches from radiotherapy to immunotherapy. The detailed and accurate knowledge of the oxygen distribution in a tumour is necessary in order to determine the right treatment strategy. Still, due to the limited spatial and temporal resolution of imaging methods as well as lacking fundamental understanding of internal oxygenation dynamics in tumours, the precise oxygen distribution map is rarely available for treatment planing. We employ an agent-based in silico tumour spheroid model in order to study the complex, localized and fast oxygen dynamics in tumour micro-regions which are induced by radiotherapy. A lattice-free, 3D, agent-based approach for cell representation is coupled with a high-resolution diffusion solver that includes a tissue density-dependent diffusion coefficient. This allows us to assess the space- and time-resolved reoxygenation response of a small subvolume of tumour tissue in response to radiotherapy. In response to irradiation the tumour nodule exhibits characteristic reoxygenation and re-depletion dynamics which we resolve with high spatio-temporal resolution. The reoxygenation follows specific timings, which should be respected in treatment in order to maximise the use of the oxygen enhancement effects. Oxygen dynamics within the tumour create windows of opportunity for the use of adjuvant chemotherapeutica and hypoxia-activated drugs. Overall, we show that by using modelling it is possible to follow the oxygenation dynamics beyond common resolution limits and predict beneficial strategies for therapy and in vitro verification. Models of cell cycle and oxygen dynamics in tumours should in the future be combined with imaging techniques, to allow for a systematic experimental study of possible improved schedules and to ultimately extend the reach of oxygenation monitoring available in clinical treatment.
AMP-activated protein kinase (AMPK) maintains energy homeostasis by suppressing cellular ATP-consuming processes and activating catabolic, ATP-producing pathways such as fatty acid oxidation (FAO). The transcription factor peroxisome proliferator-activated receptor δ (PPARδ) also affects fatty acid metabolism, stimulating the expression of genes involved in FAO. To question the interplay of AMPK and PPARδ in human macrophages we transduced primary human macrophages with lentiviral particles encoding for the constitutively active AMPKα1 catalytic subunit, followed by microarray expression analysis after treatment with the PPARδ agonist GW501516. Microarray analysis showed that co-activation of AMPK and PPARδ increased expression of FAO genes, which were validated by quantitative PCR. Induction of these FAO-associated genes was also observed upon infecting macrophages with an adenovirus coding for AMPKγ1 regulatory subunit carrying an activating R70Q mutation. The pharmacological AMPK activator A-769662 increased expression of several FAO genes in a PPARδ- and AMPK-dependent manner. Although GW501516 significantly increased FAO and reduced the triglyceride amount in very low density lipoproteins (VLDL)-loaded foam cells, AMPK activation failed to potentiate this effect, suggesting that increased expression of fatty acid catabolic genes alone may be not sufficient to prevent macrophage lipid overload.
Disturbances in lipid metabolism are responsible for many chronic disorders, such as type 2 diabetes and atherosclerosis. Regulation of lipid metabolism occurs by activated transcription factors peroxisome proliferator-activated receptor δ (PPARδ) and liver X receptor α (LXRα) mediating transcription of different target genes involved in regulation of fatty acid uptake and oxidation or cellular cholesterol homeostasis. This is especially relevant for the macrophages, since pathways regulated by PPARδ and LXRα affect foam cell formation, a process driving the progression of atherosclerotic lesion. AMP-activated protein kinase (AMPK) plays a central role in energy homeostasis in every type of eukaryotic cell, but its role in human macrophages, particularly with regard to lipid metabolism, is not precisely defined yet. Thus, I investigated the impact of AMPK activity on PPARδ and LXRα and the expression of their target genes involved in fatty acid oxidation (FAO) and cholesterol metabolism.
As PPARδ has been described as a potential target for prevention and treatment of several disorders and AMPK as interesting drug target for diabetes and metabolic syndrome, the aim of the first part of my studies was to investigate their interaction in primary human macrophages. Completing the first challenge successfully, I was able to establish a lentiviral transduction system for constitutively active AMPK (consisting of a truncated catalytic AMPKα1 subunit bearing an activating T198D mutation) in primary human macrophages.
Using genome-wide microarray analysis of gene expression, I demonstrate FAO as the strongest affected pathway during combined AMPKα1 overexpression and PPARδ activation.
The most influenced genes were validated by quantitative PCR as well as by Western analysis. I found that AMPK increases the expression of FAO-associated genes targeted by PPARδ. Corroborating the results obtained using AMPKα1 overexpression, PPARδ target gene expression was increased not only by PPARδ agonist GW501516, but also by pharmacological allosteric AMPK activator A-769662. Additional enhancement of target gene mRNA expression was achieved upon co-activation of PPARδ and AMPK. Silencing PPARδ expression increased basal expression of target genes, confirming the repressive nature of ligand-free PPARδ, abolishing the increased target gene expression upon AMPK or PPARδ activation. Measurements of triglyceride contents of human macrophages incubated with VLDL following PPARδ activation demonstrated a reduction of intracellular triglyceride accumulation in cells, which may reflect the enhancement of fat catabolism.
In the second part of my studies, I concentrated on the regulation of cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) expression by AMPK. ABCA1 facilitates
cholesterol efflux from macrophages thus, preventing atherosclerosis progression. For the first time, AMPK implication in the regulation of the ABCA1 pathway could be presented. Both AMPK overexpression and activation lead to significantly increased ABCA1 expression, whereas AMPKα1 knock-down strongly reduced this effect. Besides, I was able to prove an enhanced activity of ABCA1 during AMPK activation in human THP-1 macrophages by measuring cholesterol efflux into apolipoprotein AI-containing medium.
Previous findings showed regulation of ABCA1 by LXRα. I confirmed these results by silencing experiments indicating an essential role of LXRα in ABCA1 regulation pathway.
Here, ABCA1 mRNA as well as protein expression were positively mediated by LXRα. LXRα activation elevated ABCA1 levels, whereas its silencing down-regulated this effect.
Interestingly, ABCA1 was found to be regulated only by LXRα and not through LXRα. At the same time, knock-down of PPARδ, -γ or -δ, which may be also involved in the regulation of LXR/ABCA1 axis, did not influence the activation of ABCA1 expression by an AMPK activator. To confirm that LXRE on Abca1 promoter is essential for ABCA1 regulation, I performed luciferase reporter assay using constructs based on Abca1 promoter with or without LXRE mutation. Mutation of LXRE abolished reporter activity, whereas AMPK activation increased luciferase activity of wild-type LXRE construct. Furthermore, I demonstrate AMPK-dependent LXRα binding to the LXRE site of Abca1 promoter using the method of chromatin immunoprecipitation. AMPK activation significantly increased, whereas silencing of AMPK significantly attenuated LXRα binding, indicating AMPK as one of the most important regulators of ABCA1 expression.
In summary, I provided an evidence for AMPK involvement into lipid and cholesterol metabolism in human macrophages showing the regulation of PPARδ and LXRα target genes. The understanding of AMPK and PPARδ interaction allows the development of new approaches for treatment of metabolic syndrome and related diseases. Increased FAO during the activation of both proteins may exhibit better therapeutic benefit. On the other hand, I have shown the impact of AMPK activation on ABCA1 via LXRα up-regulation leading to increased cholesterol efflux in human macrophages for the first time. These findings thus may impact future improving of anti-atherosclerosis therapies.
Containment problems belong to the classical problems of (convex) geometry. In the proper sense, a containment problem is the task to decide the set-theoretic inclusion of two given sets, which is hard from both the theoretical and the practical perspective. In a broader sense, this includes, e.g., radii or packing problems, which are even harder. For some classes of convex sets there has been strong interest in containment problems. This includes containment problems of polyhedra and balls, and containment of polyhedra, which have been studied in the late 20th century because of their inherent relevance in linear programming and combinatorics.
Since then, there has only been limited progress in understanding containment problems of that type. In recent years, containment problems for spectrahedra, which naturally generalize the class of polyhedra, have seen great interest. This interest is particularly driven by the intrinsic relevance of spectrahedra and their projections in polynomial optimization and convex algebraic geometry. Except for the treatment of special classes or situations, there has been no overall treatment of that kind of problems, though.
In this thesis, we provide a comprehensive treatment of containment problems concerning polyhedra, spectrahedra, and their projections from the viewpoint of low-degree semialgebraic problems and study algebraic certificates for containment. This leads to a new and systematic access to studying containment problems of (projections of) polyhedra and spectrahedra, and provides several new and partially unexpected results.
The main idea - which is meanwhile common in polynomial optimization, but whose understanding of the particular potential on low-degree geometric problems is still a major challenge - can be explained as follows. One point of view towards linear programming is as an application of Farkas' Lemma which characterizes the (non-)solvability of a system of linear inequalities. The affine form of Farkas' Lemma characterizes linear polynomials which are nonnegative on a given polyhedron. By omitting the linearity condition, one gets a polynomial nonnegativity question on a semialgebraic set, leading to so-called Positivstellensaetze (or, more precisely Nichtnegativstellensaetze). A Positivstellensatz provides a certificate for the positivity of a polynomial function in terms of a polynomial identity. As in the linear case, these Positivstellensaetze are the foundation of polynomial optimization and relaxation methods. The transition from positivity to nonnegativity is still a major challenge in real algebraic geometry and polynomial optimization.
With this in mind, several principal questions arise in the context of containment problems: Can the particular containment problem be formulated as a polynomial nonnegativity (or, feasibility) problem in a sophisticated way? If so, how are positivity and nonnegativity related to the containment question in the sense of their geometric meaning? Is there a sophisticated Positivstellensatz for the particular situation, yielding certificates for containment? Concerning the degree of the semialgebraic certificates, which degree is necessary, which degree is sufficient to decide containment?
Indeed, (almost) all containment problems studied in this thesis can be formulated as polynomial nonnegativity problems allowing the application of semialgebraic relaxations. Other than this general result, the answer to all the other questions (highly) depends on the specific containment problem, particularly with regard to its underlying geometry. An important point is whether the hierarchies coming from increasing the degree in the polynomial relaxations always decide containment in finitely many steps.
We focus on the containment problem of an H-polytope in a V-polytope and of a spectrahedron in a spectrahedron. Moreover, we address containment problems concerning projections of H-polyhedra and spectrahedra. This selection is justified by the fact that the mentioned containment problems are computationally hard and their geometry is not well understood.
The three-dimensional quantification of small-scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents the first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe (ESa Sounder Campaign) and TACTS/ESMVal (TACTS: Transport and composition in the upper troposphere/lowermost stratosphere, ESMVal: Earth System Model Validation) aircraft campaigns. The focus of this work is on the so-called dynamics-mode data characterized by a medium-spectral and a very-high-spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3, and CFC-12) and their spatial resolution are discussed. During ESSenCe, high-resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in situ data indicate a good agreement between the data sets. During TACTS/ESMVal, a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere was performed. It was possible to reconstruct this filament at an unprecedented spatial resolution of better than 500 m vertically and 20 × 20 km horizontally.
Ein Vorkommen der nordamerikanischen Adventivart Heterotheca camporum (Asteraceae) wurde im November 2014 in Frankfurt am Main entdeckt. Die Population auf einer städtischen Brachfläche bestand aus mehr als 60 Exemplaren und hatte reichlich Samen gebildet. Die Art und Weise der Einschleppung sowie die taxonomische Identität werden diskutiert. Die Pflanzen sind der var. glandulissima zuzuordnen. Vermutlich geht das Vorkommen auf eine Verwilderung aus Kultur zurück.