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    Coupled dissolution-precipitation and growth processes on calcite, aragonite, and Carrara marble exposed to cadmium-rich aqueous solutions

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    Calcium carbonate and cadmium-rich fluid interactions have been studied at the nano and microscale with fluid flow and static fluid conditions for three forms of CaCO3: calcite in single crystals of Iceland Spar, calcite in a polycrystalline Carrara marble, and aragonite single crystals. Atomic Force Microscopy (AFM) showed the nanoscale effect of cadmium on CaCO3 dissolution and growth underflow-through conditions at ambient temperature, with the modification of calcite dissolution behaviour and simultaneous precipitation of a Cd-rich phase on all the different samples. Hydrothermal experiments at 200°C revealed that the reactivity of single calcite crystals is passivated by epitaxial growth of the less soluble Cd-rich endmember of the (Ca,Cd)CO3 solid-solution on the sample surface due to the similar crystallographic structures of calcite and otavite (CdCO3). Conversely, the presence of grain boundaries in Carrara marble or the change of crystallographic structure and reaction-induced fracturing in aragonite allowed, to some extent, the pseudomorphic replacement of Carrara marble and aragonite samples by a porous (Ca,Cd)CO3 solid-solution phase of variable composition. These phenomena have been observed in solutions undersaturated with respect to all solid phases and are the result of an interface-coupled dissolution-precipitation mechanism where the dissolving CaCO3 provides ions to supersaturate the mineral-fluid interfacial layer, leading to the precipitation of a Cd-containing phase on the samples’ surfaces. This coupled dissolution-precipitation mechanism could potentially be used as a remediation process to sequester cadmium from contaminated effluents.Die Wechselwirkungen zwischen Kalziumkarbonat und cadmiumhaltigen Flüssigkeiten wurden auf der Nano- und Mikroskala unter Strömungs- und statischen Flüssigkeitsbedingungen für drei Formen von CaCO3 untersucht: Kalzit in Einkristallen aus Islandspat, Kalzit in einem polykristallinen Carrara-Marmor und Aragonit-Einkristalle. Die Rasterkraftmikroskopie (AFM) zeigte die nanoskalige Wirkung von Cadmium auf die Auflösung und das Wachstum von CaCO3 unter Durchflussbedingungen bei Raumtemperatur, wobei sich das Auflösungsverhalten von Calcit veränderte und sich gleichzeitig eine Cd-reiche Phase in allen verschiedenen Proben ausbildete. Hydrothermale Experimente bei 200°C zeigten, dass die Reaktivität einzelner Calcitkristalle durch epitaktisches Wachstum des weniger löslichen Cd-reichen Endglieds der (Ca,Cd)CO3-Festkörperlösung auf der Probenoberfläche passiviert wird, was auf die ähnlichen kristallographischen Strukturen von Calcit und Otavit (CdCO3) zurückzuführen ist. Umgekehrt ermöglichten das Vorhandensein von Korngrenzen im Carrara-Marmor oder die Veränderung der kristallographischen Struktur und die reaktionsbedingte Frakturierung im Aragonit bis zu einem gewissen Grad die pseudomorphe Ersetzung von Carrara-Marmor- und Aragonitproben durch eine poröse (Ca,Cd)CO3-Mischkristallphase mit variabler Zusammensetzung. Diese Phänomene wurden in Lösungen beobachtet, die in Bezug auf alle festen Phasen untersättigt waren, und sind das Ergebnis eines grenzflächengekoppelten Auflösungs-/Ausfällungsmechanismus, bei dem das sich auflösende CaCO3 Ionen zur Übersättigung der Mineral-Flüssigkeits-Grenzschicht liefert, was zur Ausfällung einer Cd-haltigen Phase auf den Probenoberflächen führt. Dieser gekoppelte Auflösungs- und Ausfällungsmechanismus könnte möglicherweise als Sanierungsverfahren genutzt werden, um Cadmium aus kontaminierten Abwässern zu binden

    Antioxidants Hydroxytyrosol and Thioredoxin-Mimetic Peptide CB3 Protect Irradiated Normal Tissue Cells

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    Reducing side effects in non-cancerous tissue is a key aim of modern radiotherapy. Here, we assessed whether the use of the antioxidants hydroxytyrosol (HT) and thioredoxin-mimetic peptide CB3 (TMP) attenuated radiation-induced normal tissue toxicity in vitro. We used primary human umbilical vein endothelial cells (HUVECs) and human epidermal keratinocytes (HaCaT) as normal tissue models. Cells were treated with HT and TMP 24 h or immediately prior to irradiation. Reactive oxygen species (ROS) were assessed via luminescent- and fluorescence-based assays, migration was investigated using digital holographic microscopy, and clonogenic survival was quantified by colony formation assays. Angiogenesis and wound healing were evaluated via time-dependent microscopy. Secreted cytokines were validated in quantitative polymerase chain reaction (qPCR) studies. Treatment with HT or TMP was well tolerated by cells. The application of either antioxidant before irradiation resulted in reduced ROS formation and a distinct decrease in cytokines compared to similarly irradiated, but otherwise untreated, controls. Antioxidant treatment also increased post-radiogenic migration and angiogenesis while accelerating wound healing. HT or TMP treatment immediately before radiotherapy increased clonogenic survival after radiotherapy, while treatment 24 h before radiotherapy enhanced baseline proliferation. Both antioxidants may decrease radiation-induced normal tissue toxicity and deserve further pre-clinical investigation

    Formyl peptide receptors as druggable targets in viral infections

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    Diese Studie untersucht die Rolle von alveolären Makrophagen (AMs) und ihren Formylpeptid-Rezeptoren (Fprs) bei viralen Lungeninfektionen mit Influenza-A-Virus (IAV). Eine murine ex vivo Makrophagen-ähnliche Zelllinie (AML), die AMs auf Transkriptom- und Proteom-Ebene ähnelt, wurde etabliert und zeigte Reaktionen auf verschiedene Stimuli. Die AML-Zellen exprimierten Fpr1 und Fpr2, welche die extrazellulär-signalregulierten Kinasen 1/2 aktivierten. Obwohl Fprs keine Wirkung bezüglich der Polarisierung der AMs zeigten, beeinflussten sie die IAV-Infektion stammspezifisch. Die Studie untersuchte auch die Fpr-unabhängigen Eigenschaften des Fpr Liganden Annexin A1 (AnxA1), wessen Bindung an Phosphatidylserin kooperativ durch Cholesterin und Ceramid beeinflusst wurde. Die Ergebnisse dieser Arbeit deuten darauf hin, dass Fprs und ihre Liganden AMs bei viralen Lungenkrankheiten modulieren und potenziell neue, wirtsgerichtete therapeutische Ansätze für IAV-Infektionen sein könnten.This study investigates the role of alveolar macrophages (AMs) and their formyl peptide receptors (Fprs) in viral lung infections, focusing on influenza A virus (IAV). A murine ex vivo alveolar macrophage-like (AML) cell line, resembling AMs at the transcriptomic and proteomic levels, was established and shown to respond to various stimuli. AML cells expressed Fpr1 and Fpr2, signaling through extracellular-signal regulated kinase (ERK) 1/2 and not cyclic adenosine monophosphate. While Fprs were not involved in AM polarization, Fpr-induced ERK signaling influenced IAV infection in a strain-specific manner. The study also explored the Fpr-independent lipid-binding properties of the Fpr ligand Annexin A1 (AnxA1), finding that its binding to phosphatidylserine was cooperatively influenced by cholesterol and ceramide. These results suggest that Fprs and their ligands modulate AMs in viral lung diseases, potentially guiding the development of novel host-targeted therapeutic strategies for IAV infections

    Fitness, functions, and exaptation:a study in philosophical methodology and theoretical and applied philosophy of biology

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    Diese Arbeit widmet sich einem Thema aus dem Bereich der Philosophie der Biologie. Zwei zentrale Begriffe der Biologie werden untersucht: der Begriff der biologischen Fitness und der Funktionsbegriff. Über die Fragen aus diesem speziellen Gebiet hinaus stellt sie methodologische Überlegungen zur philosophischen Reflexion wissenschaftlicher Grundbegriffe an. Insbesondere beschäftigt sich die Arbeit mit der Frage, ob Wissenschaftsphilosophie bei der Erklärung der zu verstehenden Phänomene in Einzelwissenschaften bzw. der Klärung einzelwissenschaftlicher Begriffe dem Ansatz der Begriffsanalyse oder einer anderen Methode folgen sollte. Zum Schluss wird anhand einer Fallstudie aus der Verhaltensbiologie gezeigt, wie die Wissenschaftsphilosophie auch für die experimentelle Biologie fruchtbar gemacht werden kann.This book comprises various areas in the philosophy of science. It begins with a general consideration of philosophical methodology and its significance for the philosophy of science. Applying the methodological framework developed in the first part, it continues to work on some conceptual issues within the philosophy of biology, namely issues concerning the notions of biological fitness and functions. Subsequently, it ends with a case study of the applied philosophy of science suggesting new experiments based on theoretical considerations

    Increase in Income through Studies as an Important Measure

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    Die akademische Qualität der Lehre lässt sich nur schwer messen. Dagegen ist es relativ einfach, die späteren Einkommenszuwächse durch ein Studium zu bestimmen. Das ist für private wie staatliche Allokationsentscheidungen wichtig, etwa ob jemand aus finanziellen Gründen studieren soll, was und wo, während gegebene staatliche Mittel für Studienplätze effizient eingesetzt und zusätzliche Mittel gerechtfertigt werden können, wenn sie mehr bringen als kosten.The academic quality of university teaching is difficult to measure. In comparison, it is easy to determine the later income growth through studying. This is important for both private and state allocation decisions, for example whether someone should study for financial reasons, what and where, while given state funds for study places can be used efficiently and additional funds justified if they bring more than they cost

    Eine Untersuchung zum Effekt von Cafedrin/ Theodrenalin versus Noradrenalin zur Therapie der intraoperativen Hypotension auf renale Stressbiomarker:Eine studienbegleitende Analyse von klinischen Daten zum Vergleich von Theodrenalin/ Cafedrin und Noradrenalin zur Behandlung der intraoperativen Hypotonie bei gefäßchirurgischen Patienten

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    In dieser monozentrischen Substudie wurde der Effekt von Cafedrin/Theodrenalin im Vergleich zu Noradrenalin auf den renalen Stressbiomarker ([TIMP-2][IGFBP7]) bei Patienten mit intraoperativer Hypotension (IOH) untersucht. Die Patienten wurden im Rahmen der HERO-Studie nach Induktion der Allgemeinanästhesie randomisiert entweder mit Cafedrin/Theodrenalin oder Noradrenalin behandelt. Dabei wurden prä- als auch postoperative Messungen der renalen Biomarker analysiert. Die Differenz betrug 0,17 ng/ml in der Cafedrin/Theodrenalin-Gruppe und 0,18 ng/ml in der Noradrenalin-Gruppe, mit einem p-Wert von 0,317. Es zeigte sich kein signifikanter Unterschied zwischen den Gruppen hinsichtlich der prä- und posteroperativer Differenz von [TIMP-2][IGFBP7]. Damit zeigen die Ergebnisse keinen Vorteil von Cafedrin/Theodrenalin gegenüber Noradrenalin in Bezug auf die Reduktion renaler Stressbiomarker

    Efficacy and Low Toxicity of Normo-Fractionated Re-Irradiation with Combined Chemotherapy for Recurrent Glioblastoma—An Analysis of Treatment Response and Failure

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    Background: Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. Methods: A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Results: Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p < 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p < 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm3) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Conclusions: Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well

    Homogeneous Ricci flows and the Dynamical Alekseevskii Conjecture

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    Diese Dissertation befasst sich mit der Ricci-Fluss-Gleichung in der riemannischen Geometrie. Das Hauptziel ist es, unser Verständnis des langfristigen Verhaltens von Ricci-Fluss-Lösungen mit homogenen Anfangsmetriken zu vertiefen. Konkret wird die Dynamische Alekseevskii-Vermutung behandelt, die besagt, dass der universelle Überzug einer unsterblichen homogenen Ricci-Fluss-Lösung zusammenziehbar ist. Zunächst stellen wir ein allgemeines strukturelles Ergebnis für die Isometriengruppe einer homogenen Mannigfaltigkeit auf, die eine unsterbliche Ricci-Fluss-Lösung zulässt, nämlich dass diese keine einfache normale kompakte Untergruppe enthält. Danach zeigen wir, dass die Vermutung für zwei spezielle Mengen homogener Anfangsmetriken gilt: die awesome-Metriken und die awesome-Polarmetriken. Das Testen der Vermutung in diesen Fällen ist von Interesse, weil sie Metriken mit negativer Ricci-Krümmung enthalten und daher komplexere Argumente erfordern, um die anfänglichen Krümmungsschätzungen zu verbessern, was wiederum unser Verständnis des allgemeinen Falls erweitern könnte. Im Fall der awesome-Metriken führen die gewonnenen geometrischen Schätzungen zu einer genaueren Beschreibung der asymptotischen Geometrien der Lösungen, sowohl im unsterblichen als auch im nicht unsterblichen Fall.This dissertation deals with the Ricci flow equation in Riemannian geometry. The main goal is to deepen our understanding of the long-time behavior of Ricci flow solutions with homogeneous initial metrics. Specifically, it addresses the Dynamical Alekseevskii Conjecture, which states that the universal covering of an immortal homogeneous Ricci flow solution is contractible. First, we establish a general structural result for the isometry group of a homogeneous manifold admitting an immortal Ricci flow solution, namely that it does not contain a simple normal compact subgroup. We then show that the conjecture holds for two special sets of homogeneous initial metrics: the awesome metrics and the awesome polar metrics. Testing the conjecture in these cases is of interest because they include metrics with negative Ricci curvature and therefore require more involved arguments to improve the initial curvature estimates, which in turn could expand our understanding of the general case. In the case of awesome metrics, the obtained geometric estimates lead to a more accurate description of the asymptotic geometries of the solutions, both in the immortal and non-immortal cases

    Transcriptomic analysis of Chinese yam (Dioscorea polystachya Turcz.) variants indicates brassinosteroid involvement in tuber development

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    'Dioscorea' is an important but underutilized genus of flowering plants that grows predominantly in tropical and subtropical regions. Several species, known as yam, develop large underground tubers and aerial bulbils that are used as food. The Chinese yam ('D. polystachya' Turcz.) is one of the few 'Dioscorea' species that grows well in temperate regions and has been proposed as a climate-resilient crop to enhance food security in Europe. However, the fragile, club-like tubers are unsuitable for mechanical harvesting, which is facilitated by shorter and thicker storage organs. Brassinosteroids (BRs) play a key role in plant cell division, cell elongation and proliferation, as well as in the gravitropic response. We collected RNA-Seq data from the head, middle and tip of two tuber shape variants: F60 (long, thin) and F2000 (short, thick). Comparative transcriptome analysis of F60 vs. F2000 revealed 30,229 differentially expressed genes (DEGs), 1,393 of which were differentially expressed in the growing tip. Several DEGs are involved in steroid/BR biosynthesis or signaling, or may be regulated by BRs. The quantification of endogenous BRs revealed higher levels of castasterone (CS), 28-norCS, 28-homoCS and brassinolide in F2000 compared to F60 tubers. The highest BR levels were detected in the growing tip, and CS was the most abundant (439.6 ± 196.41 pmol/g in F2000 and 365.6 ± 112.78 pmol/g in F60). Exogenous 24-epi-brassinolide (epi-BL) treatment (20 nM) in an aeroponic system significantly increased the width-to-length ratio (0.045 ± 0.002) compared to the mock-treated plants (0.03 ± 0.002) after 7 weeks, indicating that exogenous epi-BL produces shorter and thicker tubers. In this study we demonstrate the role of BRs in 'D. polystachya' tuber shape, providing insight into the role of plant hormones in yam storage organ development. We found that BRs can influence tuber shape in Chinese yam by regulating the expression of genes involved cell expansion. Our data can help to improve the efficiency of Chinese yam cultivation, which could provide an alternative food source and thus contribute to future food security in Europe

    The soft X-ray and XUV split-and-delay unit at beamlines FL23/24 at FLASH2

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    A split-and-delay unit for the extreme ultraviolet and soft X-ray spectral regions has been built which enables time-resolved experiments at beamlines FL23 and FL24 at the Free-electron LASer in Hamburg (FLASH). Geometric wavefront splitting at a sharp edge of a beam splitting mirror is applied to split the incoming soft X-ray pulse into two beams. Ni and Pt coatings at grazing incidence angles have been chosen in order to cover the whole spectral range of FLASH2 and beyond, up to hν = 1800 eV. In the variable beam path with a grazing incidence angle of ϑd = 1.8°, the total transmission (T) ranges are of the order of 0.48 0.50 for 100 eV 0.06 for hν 0.61 with the Ni coating and T > 0.23 with a Pt coating is achieved. Soft X-ray pump/soft X-ray probe experiments are possible within a delay range of −5 ps < Δt < +18 ps with a nominal time resolution of tr = 66 as and a measured timing jitter of tj = 121 ± 2 as. First experiments with the split-and-delay unit determined the averaged coherence time of FLASH2 to be τc = 1.75 fs at λ = 8 nm, measured at a purposely reduced coherence of the free-electron laser

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