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"Die Flüchtlinge", "die Rassisten" und "Wir" – zu den Ambivalenzen im aktuellen Flüchtlingsdiskurs
(2015)
Dies ist der dritte Artikel unseres Blogfokus zu Flucht und Migration. Die vehemente Verurteilung der verbalen und gewaltvollen Übergriffe auf Geflüchtete, die zivilgesellschaftliche Solidarität, mit der Geflüchtete an Bahnhöfen, in Vereinen und Nachbarschaften Willkommen geheißen werden, die kleinen und großen Gesten privater Flüchtlingshilfe – all dies sind wichtige Signale gegen rassistische Hetze und Abschreckungspolitik. Der Flüchtlingshilfediskurs bleibt dennoch ambivalent und lässt sich aktuell an mindestens drei Fragen diskutieren: Wann verfehlen Positionierungen ‚gegen Rechts‘ das Ziel, rassistische Verhältnisse in der Gesellschaft aufzubrechen? Wann läuft das private Engagement im Flüchtlingsbereich Gefahr, politisches Handeln zu ersetzen? Und welche Schwierigkeiten gehen mit der Konjunktur des ‚Helfer-Wirs‘ einher? Eine Gratwanderung.
This report was written by the organizers of the workshop "Accounting for Combat-Related Killings," which took place at the Goethe University Frankfurt in July 2014. Scholars from Israel, the United Kingdom, the United States,, Canada, and Germany came together to present and discuss case studies on the discourse practices involved in accounting for combat-related killings in different national and transnational contexts. Intending to reflect on the methodological skills needed to analyze newly available process data, the workshop brought together scholars using different methodological approaches (here mainly ethnomethodology and critical discourse analysis). In regard to the global trend towards increasing numbers of so called permanent, asymmetric, small, and permanent wars, the report turns to concepts, methods, and empirical findings that foster understandings of the difficulties war generates at social, cultural and political levels as well as the manner in which these predicaments are negotiated, denied, or deflected. The report summarizes the workshop by presenting the papers in a specific order, beginning with accounting in combat, followed by tribunals of accounting, and finally the sedimentation of accounting in cultural representations.
Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling.
Translation elongation factor Tuf of Acinetobacter baumannii is a plasminogen-binding protein
(2015)
Acinetobacter baumannii is an important nosocomial pathogen, causing a variety of opportunistic infections of the skin, soft tissues and wounds, urinary tract infections, secondary meningitis, pneumonia and bacteremia. Over 63% of A. baumannii infections occurring in the United States are caused by multidrug resistant isolates, and pan-resistant isolates have begun to emerge that are resistant to all clinically relevant antibiotics. The complement system represents the first line of defense against invading pathogens. However, many A. baumannii isolates, especially those causing severe bacteremia are resistant to complement-mediated killing, though the underlying mechanisms remain poorly understood. Here we show for the first time that A. baumannii binds host-derived plasminogen and we identify the translation elongation factor Tuf as a moonlighting plasminogen-binding protein that is exposed on the outer surface of A. baumannii. Binding of plasminogen to Tuf is at least partly dependent on lysine residues and ionic interactions. Plasminogen, once bound to Tuf can be converted to active plasmin and proteolytically degrade fibrinogen as well as the key complement component C3b. Thus, Tuf acts as a multifunctional protein that may contribute to virulence of A. baumannii by aiding in dissemination and evasion of the complement system.
In der vorliegenden Arbeit wurde erstmals die Interaktion von A. baumannii mit humanem Plasminogen untersucht. Mit dem Translations-Elongationsfaktor TufAb, dem äußeren Membranprotein OmpW sowie dem Lipoprotein p41 konnten insgesamt drei Plasminogen-bindende Proteine von A. baumannii identifiziert werden. Außerdem wurde ein grundlegender Beitrag zur funktionellen Charakterisierung von TufAb sowie p41 von A. baumannii erbracht.
Es konnte nachgewiesen werden, dass gereinigtes TufAb humanes Plasminogen bindet und diese Interaktion teilweise durch Lysin-Reste vermittelt und von der Ionenstärke beeinflusst ist. An TufAb-gebundenes Plasminogen war für den Plasminogen-Aktivator u-PA zugänglich und konnte zu Plasmin aktiviert werden, welches das chromogene Substrat S-2251, das physiologische Substrat Fibrinogen und die zentrale Komplementkomponente C3b proteolytisch spaltete. Schließlich konnte TufAb als „Moonlighting“-Protein auf der Zelloberfläche von A. baumannii identifiziert werden.
Für das Lipoprotein p41 konnte ebenfalls gezeigt werden, dass dieses an Plasminogen bindet. Die Bindung von Plasminogen an p41 erfolgte ebenfalls über Lysin-Reste, zeigte sich allerdings von der Ionenstärke unbeeinflusst. Im Fall von p41 konnte mit Hilfe von C-terminal verkürzten p41-Konstrukten gezeigt werden, dass C-terminale Lysin-Reste an der Bindung von Plasminogen beteiligt sind. Weitere Versuche mit p41-Proteinen, bei welchen vier C-terminale Lysin-Reste durch Alanin-Reste substituiert wurden, ergaben, dass die beiden Lysin-Reste K368 und K369 essentiell für die Bindung von Plasminogen an p41 sind. Zudem konnte gezeigt werden, dass sowohl Kringle-Domäne 1 als auch Kringle-Domäne 4 von Plasminogen bei der Interaktion mit p41 involviert sind. An p41 gebundenes Plasminogen ließ sich durch u-PA zu Plasmin aktivieren, welches Fibrinogen sowie die zentrale Komplementkomponente C3b degradierte. p41 ist außerdem in der Lage, die Komplementkomponenten C3, C3b und C5 zu binden und den alternativen Weg zu inhibieren. Zudem ergaben Untersuchungen im Rahmen dieser Arbeit erste Hinweise darauf, dass zumindest die Plasminogen-bindende Region auf der Zelloberfläche von A. baumannii lokalisiert ist.
Die Inaktivierung des p41-kodierenden Gens führte zu einer signifikanten Abnahme im Überleben von A. baumannii-Zellen in der Gegenwart von NHS. Zudem zeigte die Mutante Δp41 einen Defekt in der Plasmin-abhängigen Transmigration durch einen Endothelzell-Monolayer. Beide Versuche untermauern die physiologische Relevanz für die Interaktion von A. baumannii mit Plasminogen.
Background: Curcuminoids (curcumin, demethoxycurcumin, bis-demethoxycurcumin) are lipophilic polyphenols thought to be effective in the prevention and treatment of neurodegenerative disorders, of which mitochondrial dysfunction is a prominent feature. In particular, older people may thus benefit from increasing their curcuminoid intake. However until now, it is not investigated if there exist age differences in the bioavailability of curcuminoids and therefore, it is unclear if curcumin doses have to be adjusted to age. Thus, we explored if the tissue concentrations and biological activities of curcuminoids are affected by age.
Methods: We investigated age-differences in the bioavailability and tissue distribution of curcuminoids and mitochondrial function in 3- and 18-months old mice fed a control diet or identical diets fortified with 500 or 2000 mg curcuminoids/kg for 3 weeks. Therefore, we measured curcuminoid concentrations in plasma, liver, kidney, and brain, basal and stress-induced levels of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) in dissociated brain cells and citrate synthase activity of isolated mitochondria.
Results: Plasma but not liver and kidney curcuminoid concentrations were significantly higher in older mice. Age did not affect ATP concentrations and MMP in dissociated brain cells. After damaging cells with nitrosative stress, dissociated brain cells from old mice had a higher MMP than cells from young animals and were therefore more resistant. Furthermore, this effect was enhanced by curcumin.
Conclusion: Our data suggest that age may affect plasma concentrations, but not the tissue distribution of curcuminoids in mice, but has little impact on mitochondrial function in brain cells.
An increasing body of evidences from preclinical as well as epidemiological and clinical studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning. In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and affective disorders is warranted.
The current Review article provides a narrative review about the neurobiological underpinnings and treatment of treatment resistant late-life depression (TRLLD). The manuscript focuses on therapeutic targets of late-life depression, which include pharmacological, psychological, biophysical and exercise treatment approaches. Therefore, we summarize available evidences on that kind of therapies for patients suffering from late-life depression. The search for evidences of therapeutic options of late-life depression were done using searching websites as “pubmed”, and using the searching terms “depression”, “late-life depression”, “treatment”, “biophysical therapy”, “exercise therapy”, “pharmacological therapy” and “psychological therapy”. To the end, we summarize and discuss current data, providing some directions for further research.
Treatment recommendations for elderly depressive patients favour a multimodal approach, containing psychological, pharmacological and secondary biophysical therapeutic options. Particularly, a combination of psychotherapy and antidepressant medication reflects the best therapeutic option. However, mostly accepted and used is the pharmacological treatment although evidence suggests that the drug therapy is not as effective as it is in younger depressive patients. Further studies employing larger samples and longer follow-up periods are necessary and may focus on comparability of study designs and involve novel approaches to establish the validity and reliability of multimodal treatment programs.
Introduction: In this article three research questions are addressed: (1) Is there an association between socioeconomic status (SES) and patient-reported outcomes in a cohort of multimorbid patients? (2) Does the association vary according to SES indicator used (income, education, occupational position)? (3) Can the association between SES and patient-reported outcomes (self-rated health, health-related quality of life and functional status) be (partly) explained by burden of disease?
Methods: Analyses are based on the MultiCare Cohort Study, a German multicentre, prospective, observational cohort study of multimorbid patients from general practice. We analysed baseline data and data from the first follow-up after 15 months (N = 2,729). To assess burden of disease we used the patients’ morbidity data from standardized general practitioner (GP) interviews based on a list of 46 groups of chronic conditions including the GP’s severity rating of each chronic condition ranging from marginal to very severe.
Results: In the cross-sectional analyses SES was significantly associated with the patient-reported outcomes at baseline. Associations with income were more consistent and stronger than with education and occupational position. Associations were partly explained (17% to 44%) by burden of disease. In the longitudinal analyses only income (but not education and occupational position) was significantly related to the patient-reported outcomes at follow-up. Associations between income and the outcomes were reduced by 18% to 27% after adjustment for burden of disease.
Conclusions: Results indicate social inequalities in self-rated health, functional status and health related quality of life among older multimorbid patients. As associations with education and occupational position were inconsistent, these inequalities were mainly due to income. Inequalities were partly explained by burden of disease. However, even among patients with a similar disease burden, those with a low income were worse off in terms of the three patient-reported outcomes under study.
Die aktuelle Debatte um Pornographie stellt sich andere Fragen als in den kämpferischen 70er Jahren. In den interdisziplinären Beiträgen des Sammelbandes wird Pornographie als kulturelles Artefakt behandelt, als Begriff, der in Diskurse über Sexualität und Moderne, über Identität und Jugend verwoben ist. Die Autor_innen arbeiten mit empirisch-sozialwissenschaftlichen Methoden Fragen nach dem Nutzer_innenverhalten von Onlinepornographie und jugendlichem Pornokonsum auf, bieten theoriegeleitete Zugänge zur Unbestimmbarkeit von Pornographie, zu ihrer notwendigen Einbettung in andere gesellschaftliche Kontexte sowie künstlerische Interventionen zu ihrem emanzipatorischen Potential. Die Beiträge bieten einen gelungenen Einblick in den aktuellen Stand der Debatte dieses noch jungen Feldes.
Im Rahmen dieser Dissertation wurden drei bakterielle Enzyme, die Metallo-β-Lactamasen NDM-1 (New Delhi Metallo-β-Lactamase 1), VIM-1 (Verona-Integron Encoded Metallo-β-Lactamase 1) und IMP-7 (Imipenemase 7), sowie ein humanes Enzym, die sEH-Phosphatase, behandelt.
Das Auftreten multiresistenter Bakterien ist eine alarmierende Entwicklung. Dabei ist das vermehrte Erscheinen von Metallo-β-Lactamasen (MBLs) in Gramnegativen Bakterien zu beobachten, die von Inhibitoren anderer β-Lactamasen unbeeinflusst bleiben. MBLs sind Enzyme, die β-Lactam-Antibiotika hydrolysieren und somit unwirksam machen. β-Lactam-Antibiotika hemmen die Zellwandsynthese von Bakterien und haben keinen Einfluss auf menschliche Zellen. Daher sind sie für den Menschen sehr gut verträglich und werden oft eingesetzt. Gerade diese häufige Verwendung und der Fehleinsatz führen vermehrt zur Resistenzbildung. Suche nach neuen Wirkstoffen zur Behandlung von Pathogenen mit Resistenz ist von äußerster Dringlichkeit, da die Resistenzen sich in kürzester Zeit über den kompletten Planeten verbreiten.
NDM-1, VIM-1 und IMP-5 wurden in E.coli überexprimiert und aufgereinigt, um die rekombinanten Enzyme zu erhalten. Damit wurde zunächst ein Fluoreszenz-Intensitäts-Assay entwickelt, um die Wirksamkeit möglicher Inhibitoren zu quantifizieren. Als Testsubstanzen wurden elf zugelassene Wirkstoffe gewählt, die eine Thiol-Gruppe enthalten, da bekannt ist, das Thiole Zink-abhängige Proteine inhibieren. Weiterhin wurden Thermal Shift Assays durchgeführt, um zwischen Liganden, die durch Bindung an die MBL inhibieren, und Liganden, die nur dadurch inhibieren, dass sie der Bindetasche das nötige Zink entziehen, unterscheiden zu können. Substanzen, die Inhibition im Assay zeigten und keine Zink-Chelatoren waren, wurden weiterhin auf Aktivität in bakteriellen Zellen untersucht. Dafür wurden pathogenene Stämme aus Patienten sowie mit den Resistenzplasmiden transfizierte Laborstämme einem Test auf Antibiotikaempfindlichkeit unterzogen. Die Wirksamkeit von Imipenem sollte in Kombination mit den Testsubstanzen wieder hergestellt werden. Insgesamt wurden vier Substanzen mit nicht-antiinfektiösen Indikationen gefunden, die MBLs im niedrig-mikromolaren Bereich inhibieren und die Wirksamkeit von Imipenem in Bakterien partiell wieder herstellen.
In einem zweiten Ansatz wurden Fragmente mittels Docking ausgewählt und ebenfalls im Fluoreszenz-basierten Assay getestet. Die Bestätigung der Bindung erfolgte in diesem Fall mit STD-NMR und die Bestimmung der Dissoziationskonstante des besten Fragments mittels Messung der Chemical Shift Perturbation im NMR. In diesem Projekt wurde leider kein pan-Inhibitor für alle MBLs gefunden, allerdings ein Fragment mit hoher Bindeeffizienz zur NDM-1.
Die lösliche Epoxid-Hydrolase (englisch: soluble Epoxid Hydolase, sEH) katalysiert die Umsetzung von Epoxyeicosatriensäuren (EETs), Lipidmediatoren mit entzündungshemmenden und kardiovaskulär-protektiven Eigenschaften, zu Dihydroxyeicosatriensäuren (DHETs). Diese Reaktion ist ein Bestandteil der Arachidonsäurekaskade. Das Enzym besteht aus zwei Domänen mit unterschiedlichen katalytischen Funktionen, einerseits der viel erforschten Cterminalen Epoxid-Hydrolase-Domäne, aber auch der N-terminalen Domäne, die eine Phosphatase-Eigenschaft zeigt. Die N-terminale Domäne katalysiert die Hydrolyse von Phosphat-Monoestern, Isoprenoid- sowie Lipid-Phosphaten. Die biologische Funktion dieser Domäne ist nicht aufgeklärt, und die Phosphatase Aktivität wird von typischen Phosphatase-Inhibitoren nicht beeinflusst. Daher ist es von Interesse, einen Inhibitor zu entwickeln.
Zunächst wurde ein Aktivitätsassay mit einem fluorogenen Substrat entwickelt und dieser in verschiedene Formate überführt, um in unterschiedlichen Größen testen zu können. Im 96well Format wurden mögliche Inhibitoren getestet, die mittels Docking ausgesucht wurden. Allerdings wurden nur Inhibitoren mit IC50s über 100 μM gefunden oder Inhibitoren, die Sulfonsäure-Strukturen aufweisen. Im 384well Format wurde, in Kollaboration mit dem European ScreeningPort Hamburg, ein High-Throughput Screening von ca. 17000 Substanzen durchgeführt. So wurde Oxaprozin gefunden, ein Inhibitor, der strukturelle Ähnlichkeit zu bereits bekannten Inhibitoren zeigt.
We present in this paper spectral and spatial characteristics of terahertz emission from standard dipole antenna structures used as emitters depending on the substrate material. All antenna structures were lithographically fabricated on low-temperature (LT) grown, few-micrometers-thick gallium arsenide (GaAs) layers. To investigate the effect of the substrate material on the radiation pattern of terahertz beams, either semi-insulating gallium arsenide or high-resistivity silicon substrate wafers have been used. As detector a standard 40 µm long dipole antenna on a semi-insulating GaAs substrate with a low-temperature grown gallium arsenide layer on it has been employed; this configuration allows for broadband detection and is still efficient enough for the characterization purpose. Strong dependence of the radiation pattern on the substrate used for the terahertz source is demonstrated. The measured patterns and differences between the two cases of substrates are well explained by means of classical diffraction.
Previous research on working memory (WM) in children with poor mathematical skills has yielded heterogeneous results, possibly due to inconsistent consideration of the IQ-achievement discrepancy and additional reading and spelling difficulties. To examine the impact of both, the WM of 68 average-achieving and 68 low-achieving third-graders in mathematics was assessed. Preliminary analyses showed that poor mathematical skills were associated with poor WM. Afterwards, children with isolated mathematical difficulties were separated from those with additional reading and spelling difficulties. Half of each group fulfilled the IQ-achievement discrepancy, resulting in a 2 (additional reading and spelling difficulties: yes/no) by 2 (IQ-achievement discrepancy: yes/no) factorial design. Analyses revealed that not fulfilling the IQ achievement discrepancy was associated with poor visual WM, whereas additional reading and spelling difficulties were associated with poor central executive functioning in children fulfilling the IQ-achievement discrepancy. Therefore, WM in children with poor mathematical skills differs according to the IQ-achievement discrepancy and additional reading and spelling difficulties.
Im Zuge der (wieder) zunehmenden Aufmerksamkeit verschiedenster IB-Theorien für postkoloniale Problemlagen hat unter ‚nördlichen‘ IB-Forschern das Interesse an Dialog und Auseinandersetzung mit den IB-Communities des ‚globalen Südens‘ zugenommen. Dieser Beitrag will Möglichkeiten und Hindernisse dieses Dialogs für den Fall der südamerikanischen IB-Communities aufzeigen. Es soll gewissermaßen eine ‚Bedienungsanleitung‘ erstellt werden, um dem interessierten Außenseiter das Verständnis der Interessenlagen, theoretischen Präferenzen und der konkreten Arbeitssituationen südamerikanischer IB-Forscher zu erleichtern. Dies geschieht selbstredend unter Betonung der Unvollständigkeit der Beschreibung sowie der Perspektivenabhängigkeit des Beobachters.
Die bisher nicht lückenlos aufgeklärte, vermutlich aber Gruppen der organisierten Kriminalität zuzurechnende Ermordung von über 40 Lehramtsstudenten in der südmexikanischen Kleinstadt Ayotzinapa Ende 2014 hat ebenso wie die seit dem Abschuss eines Militärhubschraubers im Mai 2015 eskalierende Gewalt im westlichen Bundesstaat Jalisco wieder einmal schmerzlich in Erinnerung gerufen, dass in Mexiko bereits seit fast neun Jahren ein blutiger Gewaltkonflikt im Gange ist, der angesichts der wirtschaftlichen Erfolge des „Aztec tiger“ teils fast schon vergessen schien.
Future FAIR experiments have to deal with very high input rates, large track multiplicities, make full event reconstruction and selection on-line on a large dedicated computer farm equipped with heterogeneous many-core CPU/GPU compute nodes. To develop efficient and fast algorithms, which are optimized for parallel computations, is a challenge for the groups of experts dealing with the HPC computing. Here we present and discuss the status and perspectives of the data reconstruction and physics analysis software of one of the future FAIR experiments, namely, the CBM experiment.
Postface
(2015)
Enfondant l’Académie française en 1635, le cardinal de Richelieu, Premier ministre de Louis XIII, lui avait assigné deux missions : la création d’undictionnaire de langue française etl'élaboration d’une poétique, d’une théorie littéraire analogue à celles qui existaient en Italie. Assurément, il souhaitait soutenir les écrivains français et leur donner une tribune, mais cette initiative n'était cependant pas exempte de considérations politiques. Bien qu'il n'ait pas envisagé la création d’une académie artistique, Richelieu n’excluait guère, de ses préoccupations, l'art : en 1627, il rappela à Paris Simon Vouet, alors à Rome, dans l’idée de développer un art typiquement français, qui serait indépendant des influences italiennes et flamandes. Il estimait qu’un État territorial modernese définissait toutautant par son art et sa littérature que par sa langue. La fondation de l’Académie royale de peinture et de sculpture en 1648, dans le contexte tourmenté de la Fronde, par le cardinal Mazarin, successeur de Richelieu, assignait à la nouvelle institution des tâches plus complexes quoiqu'assez voisines de celles de l’Académie française. Il s'agissait non seulement de témoigner de la noblesse de la peinture et de la sculpture, mais également de prodiguer aux générations successives une formation leur assurant de réelles qualités artistiques. ...
The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is overactivated in malignant glioma and plays a key role in promoting cell survival, thereby increasing the acquired apoptosis resistance of these tumors. Here we investigated the STAT3/myeloid cell leukemia 1 (MCL1) signaling pathway as a target to overcome the resistance of glioma cells to the Bcl-2-inhibiting synthetic BH3 mimetic ABT-737. Stable lentiviral knockdown of MCL1 sensitized LN229 and U87 glioma cells to apoptotic cell death induced by single-agent treatment with ABT-737 which was associated with an early activation of DEVDase activity, cytochrome c release, and nuclear apoptosis. Similar sensitizing effects were observed when ABT-737 treatment was combined with the multikinase inhibitor sorafenib which effectively suppressed levels of phosphorylated STAT3 and MCL1 in MCL1-proficient LN229 and U87 glioma cells. In analogous fashion, these synergistic effects were observed when we combined ABT-737 with the STAT3 inhibitor WP-1066. Lentiviral knockdown of the activating transcription factor 5 combined with subsequent quantitative polymerase chain reaction analysis revealed that sorafenib-dependent suppression of MCL1 occurred at the transcriptional level but did not depend on activating transcription factor 5 which previously had been proposed to be essential for MCL1-dependent glioma cell survival. In contrast, the constitutively active STAT3 mutant STAT3-C was able to significantly enhance MCL1 levels under sorafenib treatment to retain cell survival. Collectively, these data demonstrate that sorafenib targets MCL1 in a STAT3-dependent manner, thereby sensitizing glioma cells to treatment with ABT-737. They also suggest that targeting STAT3 in combination with inducers of the intrinsic pathway of apoptosis may be a promising novel strategy for the treatment of malignant glioma.
Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk) without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk) and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.
Different types of altruistic behavior, namely help-giving, altruistic punishment, and moral courage, are identifiable and distinguishable in the literature, but little is known how they relate to each other. This is significant because understanding altruism and other-regarding behavior is important in the attempt to solve global problems of overpopulation and depletion of natural resources. Understanding the helping forms of altruism (help-giving and sharing) can be helpful, for example, when designing donation collections or recruiting volunteers. Understanding the punitive forms of altruism (moral courage and altruistic punishment) gives valuable insight on individuals participating in campaigns where there is a need to take action, for example, against polluters or governments that violate human rights. The empirical evidence presented in this dissertation demonstrate individual and cultural differences in help-giving, altruistic punishment, and morally courageous behavior. The willingness to engage in the three types of altruistic behaviors relate differently to subjectively preferred thinking style and to personality traits, both in real-life and on the Internet. The divergencies are observable between Eastern (Indian) and Western (German) cultures, where the overlap of oneself and other individuals is experienced in different levels.
The processing of pain undergoes several changes in aging that affect sensory nociceptive fibers and the endogenous neuronal inhibitory systems. So far, it is not completely clear whether age-induced modifications are associated with an increase or decrease in pain perception. In this study, we assessed the impact of age on inflammatory nociception in mice and the role of the hormonal inhibitory systems in this context. We investigated the nociceptive behavior of 12-month-old versus 6–8-week-old mice in two behavioral models of inflammatory nociception. Levels of TRP channels, and cortisol as well as cortisol targets, were measured by qPCR, ELISA, and Western blot in the differently aged mice. We observed an age-related reduction in nociceptive behavior during inflammation as well as a higher level of cortisol in the spinal cord of aged mice compared to young mice, while TRP channels were not reduced. Among potential cortisol targets, the NF-κB inhibitor protein alpha (IκBα) was increased, which might contribute to inhibition of NF-κB and a decreased expression and activity of the inducible nitric oxide synthase (iNOS). In conclusion, our results reveal a reduced nociceptive response in aged mice, which might be at least partially mediated by an augmented inflammation-induced increase in the hormonal inhibitory system involving cortisol.
Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
(2015)
Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e. particles that have grown to diameters of 10 and 15nm following nucleation, and measure their water uptake. Water uptake constrains their chemical composition. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) experiments performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from α-pinene oxidation. The hygroscopicity parameter Κ decreased with increasing particle size indicating decreasing acidity of particles. No clear effect of the sulfuric acid monomer concentrations on the hygroscopicities of 10nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15nm particles sharply decreased with decreasing sulfuric acid monomer concentrations. In 20 particular, when the concentrations of sulfuric acid was 5.1 x 106 molecules cm exp -3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured Κ of 15nm particles was 0.3 ± 0.01 close to the value reported for dimethylamine sulfate (DMAS) (Κ DMAS ~ 0.28). Furthermore, the difference in Κ between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The Κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth already at 10nm sizes.
In den letzten drei Jahrzehnten haben sich die politischen, ökonomischen, sozialen und kulturellen Strukturen unserer Welt auf verschiedenen Ebenen radikal verändert. Das Interesse am Islam ist nicht nur in wissenschaftlichen Arbeiten und Zeitschriften gestiegen, sondern auch in allen anderen westlichen Medien. Dieses Interesse wurde unter Anderem durch die Islamisch-Iranische Revolution von 1979, die Fatwa gegen den Buchautor von „Die satanischen Verse“ Salman Rushdie 1989, die Golfkriege Anfang der 90er Jahre, den Balkankonflikt als auch die Einwanderung von Migranten mit islamischem Hintergrund in Europa gefördert...
The role of social groups in making historical events succeed takes shape according to two important factors: Their ability to change and the kind of their contribution to the development of that change in a way or another. The role of social groups especially emerges at times of revolutions and their subsequent changes on the political, socioeconomic and even intellectual levels. The most active and capable group to achieve change is the group of youth and students. In the revolutionary movements in Latin America, for instance, students prominently contributed to the fall down of long-lasting totalitarian dictatorships such in Chile, Brazil and Argentina. In the Arab uprisings in 2010-2011, students‘ roles varied from one country to another based on three axes of context, networks and contentious practices. This article expands on the role of Egyptian student movement in thriving for change despite the intensified restrictions by the state and how it continued its protest under repressive circumstances as a political actor...
Political rationality as a theory is important in its own right. Government leaders must calculate political costs such as the resources needed to generate support for a policy, the implications of a policy decision for re-election, and the possibility of provoking hostility for decisions not well received. Bounded rationality approach has yielded an enhanced understanding of how government organizations may produce unexpected or even unpredicted policy or program results. With public organizations not operating under full rationality conditions, administrators aspiring toward rationality may nonetheless find their goals undermined by a variety of forces, such as informational uncertainties and non-rational elements of organisational decision-making...
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.