359 research outputs found

    Martial\u27s Materials: Materiality In The Literary Epigram

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    Originating from inscribed epigram, concerning itself with occasional and satirical matters, and being written during the Flavian period, a time marked by efforts to catalogue and reframe Roman thought and tradition, Martial’s Epigrams understandably so are obsessed with the material world. Material objects, animate or inanimate, are at the center of interest of Martial’s poetry so much, that this dissertation suggests materiality as a fruitful lens through which Martial’s oeuvre as a whole can be approached. To do so, this study is structured into three avenues of investigation: sense perception, the (imagined) transformations of objects that are evoked through word plays, and a play with the representation of books and poets in poetry. This study finds that Martial often calls the very concept of materiality into question. This can occur e.g., when the poet portrays things that are not material, such as a smell, as palpable within his poetry. Elsewhere, the poet implicitly suggests a transformation of the legs of an individual by juxtaposing them with similarly shaped objects. Finally, the poet imagines concepts such as the greatness of an author as a material presence that can take up an entire room. Likewise, Martial alludes to an ubiquitous, dematerialized presence when he claims that “all of Rome reads me” or “I am in everyone’s pocket,” imagining himself as one with his book. The three chapters of my dissertation in conjunction shed light on how Martial’s material worldmaking suggests a coexistence of physical and conceptual materials that can both be captured by literary epigram. Literary epigram, thus, is fruitful for a reflection on matters of materiality: originating from being inscribed in stone, turned into ephemeral entertainment-pieces which lack coherency with one another and can be fragmented by the reader at will, literary epigram comes across as an anti-genre in which the material and the abstract lie close together

    Neutrophil-Platelet Interactions as Novel Treatment Targets in Cardiovascular Disease

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    Neutrophils and platelets are among the most abundant cell types in peripheral blood and characterized by high plasticity and a readily available reservoir of surface proteins and secretable granule contents. Receptor-mediated activation and granule release predispose both cell types for rapid responses to various stimuli. While neutrophils provide the first line of defense to microbial infections and platelets are known for their aggregatory functions in hemostasis and thrombosis, research of the past decade has highlighted that both cell types jointly shape local and systemic immune responses and clot formation alike. Concomitant activation of neutrophils and platelets has been observed in a variety of cardiovascular diseases, including arterial and venous thrombosis, atherosclerosis as well as myocardial infarction and ischemia-reperfusion injury. In this review, we describe the mechanisms by which neutrophils and platelets interact physically, how release of granule contents and soluble molecules by either cell type affects the other and how this mutual activation supports the efficacy of immune responses. We go on to describe how activated platelets contribute to host defense by triggering neutrophil extracellular trap (NET) formation in a process termed immunothrombosis, which in turn promotes local platelet activation and coagulation. Further, we review current evidence of hazardous overactivation of either cell type and their respective role in cardiovascular disease, with a focus on thrombosis, myocardial infarction and ischemia-reperfusion injury, and describe how neutrophils and platelets shape thromboinflammation in COVID-19. Finally, we provide an overview of therapeutic approaches targeting neutrophil-platelet interactions as novel treatment strategy in cardiovascular disease

    Nonperturbative dynamics of reheating after inflation: A review

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    Our understanding of the state of the universe between the end of inflation and big bang nucleosynthesis (BBN) is incomplete. The dynamics at the end of inflation are rich and a potential source of observational signatures. Reheating, the energy transfer between the inflaton and Standard Model fields (possibly through intermediaries) and their subsequent thermalization, can provide clues to how inflation fits in with known high-energy physics. We provide an overview of our current understanding of the nonperturbative, nonlinear dynamics at the end of inflation, some salient features of realistic particle physics models of reheating, and how the universe reaches a thermal state before BBN. In addition, we review the analytical and numerical tools available in the literature to study preheating and reheating and discuss potential observational signatures from this fascinating era.Kavli Institute for Cosmology, CambridgeUnited States. Dept. of Energy (Contract Number DE-SC00012567)Massachusetts Institute of Technology. Center for Theoretical Physic

    AATF/Che-1-An RNA Binding Protein at the Nexus of DNA Damage Response and Ribosome Biogenesis

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    The DNA damage response (DDR) is a complex signaling network that is activated upon genotoxic stress. It determines cellular fate by either activating cell cycle arrest or initiating apoptosis and thereby ensures genomic stability. The Apoptosis Antagonizing Transcription Factor (AATF/Che-1), an RNA polymerase II-interacting transcription factor and known downstream target of major DDR kinases, affects DDR signaling by inhibiting p53-mediated transcription of pro-apoptotic genes and promoting cell cycle arrest through various pathways instead. Specifically, AATF was shown to inhibit p53 expression at the transcriptional level and repress its pro-apoptotic activity by direct binding to p53 protein and transactivation of anti-apoptotic genes. Solid and hematological tumors of various organs exploit this function by overexpressing AATF. Both copy number gains and high expression levels of AATF were associated with worse prognosis or relapse of malignant tumors. Recently, a number of studies have enabled insights into the molecular mechanisms by which AATF affects both DDR and proliferation. AATF was found to directly localize to sites of DNA damage upon laser ablation and interact with DNA repair proteins. In addition, depletion of AATF resulted in increased DNA damage and decrease of both proliferative activity and genotoxic tolerance. Interestingly, considering the role of ribosomal stress in the regulation of p53, more recent work established AATF as ribosomal RNA binding protein and enabled insights into its role as an important factor for rRNA processing and ribosome biogenesis. This Mini Review summarizes recent findings on AATF and its important role in the DDR, malignancy, and ribosome biogenesis

    Insulin receptor activation and down-regulation by cationic lipid transfection reagents

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    BACKGROUND: Transfection agents comprised of cationic lipid preparations are widely used to transfect cell lines in culture with specific recombinant complementary DNA molecules. We have found that cells in culture are often resistant to stimulation with insulin subsequent to treatment with transfection agents such as LipofectAMINE 2000™ and FuGENE-6™. This is seen with a variety of different readouts, including insulin receptor signalling, glucose uptake into muscle cells, phosphorylation of protein kinase B and reporter gene activity in a variety of different cell types RESULTS: We now show that this is due in part to the fact that cationic lipid agents activate the insulin receptor fully during typical transfection experiments, which is then down-regulated. In attempts to circumvent this problem, we investigated the effects of increasing concentrations of LipofectAMINE 2000™ on insulin receptor phosphorylation in Chinese hamster ovary cells expressing the human insulin receptor. In addition, the efficiency of transfection that is supported by the same concentrations of transfection reagent was studied by using a green fluorescent protein construct. Our data indicate that considerably lower concentrations of LipofectAMINE 2000™ can be used than are recommended by the manufacturers. This is without sacrificing transfection efficiency markedly and avoids the problem of reducing insulin receptor expression in the cells. CONCLUSION: Widely-used cationic lipid transfection reagents cause a state of insulin unresponsiveness in cells in culture due to fully activating and subsequently reducing the expression of the receptor in cells. This phenomenon can be avoided by reducing the concentration of reagent used in the transfection process

    Alterations of peripheral blood T cell subsets following donor lymphocyte infusion in patients after allogeneic stem cell transplantation

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    Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) is an established method to enhance the Graft-versus-Leukemia (GvL) effect. However, alterations of cellular subsets in the peripheral blood of DLI recipients have not been studied. We investigated the changes in lymphocyte subpopulations in 16 patients receiving DLI after successful alloSCT. Up to three DLIs were applied in escalating doses, prophylactically for relapse prevention in high-risk disease (n = 5), preemptively for mixed chimerism and/or a molecular relapse/persistence (n = 8), or as part of treatment for hematological relapse (n = 3). We used immunophenotyping to measure the absolute numbers of CD4+, CD8+, NK, and CD56+ T cells and their respective subsets in patients’ peripheral blood one day before DLI (d-1) and compared the results at day + 1 and + 7 post DLI to the values before DLI. After the administration of 1 × 106 CD3+ cells/kg body weight, we observed an overall increase in the CD8+ and CD56+ T cell counts. We determined significant changes between day − 1 compared to day + 1 and day + 7 in memory and activated CD8+ subsets and CD56+ T cells. Applying a higher dose of DLI (5 × 106 CD3+ cells/kg) led to a significant increase in the overall counts and subsets of CD8+, CD4+, and NK cells. In conclusion, serial immune phenotyping in the peripheral blood of DLI recipients revealed significant changes in immune effector cells, in particular for various CD8+ T cell subtypes, indicating proliferation and differentiation

    Schulische Bildung unter Berücksichtigung von Digitalität – in Präsenz und Distanz

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    Wie kann schulische Bildung in einer digitalisierten Welt in der Sekundarstufe I der Laborschule verstanden werden? Wie ordnen sich Kritik- und Demokratiefähigkeit sowie Mündigkeit in einer digitalisierten Welt in dieses Verständnis ein? Wie sollen vor diesem Hintergrund digitale Medien in den Unterrichts- und Schulalltag integriert werden? Mit diesen Fragen hat das Forschungs- und Entwicklungsprojekt „Bildung in einer digitalisierten Welt im Unterrichts- und Schulalltag der Sekundarstufe I der Laborschule“ Anfang 2020 die Arbeit aufgenommen und sich auf den Weg gemacht, das Medienkonzept der Laborschule Bielefeld (weiter) zu entwickeln. Dieser Beitrag zeichnet nach, wie die COVID-19-Pandemie den Forschungszugang der Gruppe verändert und wie die Ergebnisse aus den in den Pandemiejahren durchgeführten Studien für das ursprüngliche Ziel, die Weiterentwicklung des Medienkonzeptes, nutzbar gemacht werden

    On-Surface Carbon Nitride Growth from Polymerization of 2,5,8-Triazido-s-heptazine

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    Carbon nitrides have recently come into focus for photo- and thermal catalysis, both as support materials for metal nanoparticles as well as photocatalysts themselves. While many approaches for the synthesis of three-dimensional carbon nitride materials are available, only top-down approaches by exfoliation of powders lead to thin film flakes of this inherently two-dimensional material. Here, we describe an in situ on-surface synthesis of monolayer 2D carbon nitride films, as a first step towards precise combination with other 2D materials. Starting with a single monomer precursor, we show that 2,5,8-triazido-s-heptazine (TAH) can be evaporated intact, deposited on a single crystalline Au(111) or graphite support, and activated via azide decomposition and subsequent coupling to form a covalent polyheptazine network. We demonstrate that the activation can occur in three pathways, via electrons (X-ray illumination), photons (UV illumination) and thermally. Our work paves the way to coat materials with extended carbon nitride networks which are, as we show, stable under ambient conditions

    Cerebrovascular risk factors in cerebral amyloid angiopathy – modifier or bystander?

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    Goal: Cerebral amyloid angiopathy (CAA) is a frequent cause of atypical intracerebral hemorrhage (ICH) in the elderly. Stroke risk factors such as arterial hypertension (AHT), atrial fibrillation (AFib), diabetes mellitus (DM), and renal dysfunction (RD) are increasingly apparent in these patients. In this retrospective study, we analyzed the presence of these stroke risk factors in different initial CAA presentations comprising cerebral microbleeds (CMB), acute ischemic stroke (AIS), cortical superficial hemosiderosis (cSS), or lobar ICH (LICH) and evaluated their influence on the initial clinical presentation of patients with CAA. Material and Methods: We identified patients with at least possible CAA defined by the modified Boston criteria admitted to the Department of Neurology or Neurosurgery from 2002 to 2018. Findings: In the overall cohort of 209 patients, we analyzed the correlation between the number of stroke risk factors and the initial clinical presentation of patients with CAA and could show the high multimorbidity of the collective. There are large differences between the subgroups with different initial clinical presentations, e.g., patients with CMB as initial CAA presentation have the highest number of cerebrovascular risk factors and recurrent AIS, whereas AFib is more frequent in the Neurosurgery Department. Conclusion: There is a distinct overlap between the subgroups of CAA manifestations and stroke risk factors that need to be verified in larger patient collectives. Since these comorbidities are likely to influence the clinical course of CAA, they represent possible targets for secondary prevention until specific treatment for CAA becomes available

    The Conformational Equilibrium of the Neuropeptide Y2 Receptor in Bilayer Membranes

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    Dynamic structural transitions within the seven-transmembrane bundle represent the mechanism by which G-protein-coupled receptors convert an extracellular chemical signal into an intracellular biological function. Here, the conformational dynamics of the neuropeptide Y receptor type 2 (Y2R) during activation was investigated. The apo, full agonist-, and arrestin-bound states of Y2R were prepared by cell-free expression, functional refolding, and reconstitution into lipid membranes. To study conformational transitions between these states, all six tryptophans of Y2R were(13)C-labeled. NMR-signal assignment was achieved by dynamic-nuclear-polarization enhancement and the individual functional states of the receptor were characterized by monitoring(13)C NMR chemical shifts. Activation of Y2R is mediated by molecular switches involving the toggle switch residue Trp281(6.48)of the highly conserved SWLP motif and Trp327(7.55)adjacent to the NPxxY motif. Furthermore, a conformationally preserved "cysteine lock"-Trp116(23.50)was identified
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