97 research outputs found

    Frankfurt am Main, Deutschland. ClaReNet. Klassifikation und ReprĂ€sentation keltischer MĂŒnzprĂ€gungen im Netz. Das Projekt von 2021 bis 2024

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    The joint project ClaReNet, funded by the Federal Ministry of Education and Research, is testing the possibilities and the limits of new methods of classification and representation on the basis of three Celtic coinages, each selected as an example for specific research questions and problems. Traditional approaches to classification in numismatics and archaeology are compared with classification methods from information technology, including deep learning. An extendable virtual union catalogue, celticcoinage.org, complying with the FAIR principles, will be implemented for the coin series that we are investigating. The work process will be accompanied by a science and technology study, which will contribute to a reflection on the changes in knowledge processes that result from the use of digital tools and algorithms. The aim is to systematically assess in an interdisciplinary dialogue the potential and limits of automation for processes of classification and representation in numismatics and archaeology

    Ding-Editionen. Vom archĂ€ologischen (Be-)Fund ĂŒbers Corpus ins Netz

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    Corpora, thing-editions, are a central epistemic instrument of knowledge generation for archaeology. Due to digitisation attention has turned once more to various strategies and the politics of representation, and in the course of the debate on (post-)factualism and cultures of knowledge and data we are striving to render the production of knowledge more visible and comprehensible. Following B. Latour’s concept of circulating reference, editions are products of a praxeological connection between the world and representations. This is a report on the ongoing discussion of central questions and objectives for digital corpora and research data management following the FAIR (findable, accessible, inter-operable, re-usable) principle

    Missense mutation in the amino terminus of phytochrome A disrupts the nuclear import of the photoreceptor

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    Phytochromes are the red/far-red photoreceptors in higher plants. Among them, phytochrome A (PHYA) is responsible for the far-red high-irradiance response and for the perception of very low amounts of light, initiating the very-low-fluence response. Here, we report a detailed physiological and molecular characterization of the phyA-5 mutant of Arabidopsis (Arabidopsis thaliana), which displays hyposensitivity to continuous low-intensity far-red light and shows reduced very-low-fluence response and high-irradiance response. Red light-induced degradation of the mutant phyA-5 protein appears to be normal, yet higher residual amounts of phyA-5 are detected in seedlings grown under low-intensity far-red light. We show that (1) the phyA-5 mutant harbors a new missense mutation in the PHYA amino-terminal extension domain and that (2) the complex phenotype of the mutant is caused by reduced nuclear import of phyA-5 under low fluences of far-red light. We also demonstrate that impaired nuclear import of phyA-5 is brought about by weakened binding affinity of the mutant photoreceptor to nuclear import facilitators FHY1 (for FAR-RED ELONGATED HYPOCOTYL1) and FHL (for FHY1-LIKE). Finally, we provide evidence that the signaling and degradation kinetics of constitutively nuclear-localized phyA-5 and phyA are identical. Taken together, our data show that aberrant nucleo/cytoplasmic distribution impairs light-induced degradation of this photoreceptor and that the amino-terminal extension domain mediates the formation of the FHY1/FHL/PHYA far-red-absorbing form complex, whereby it plays a role in regulating the nuclear import of phyA

    Coralline Algae in a Changing Mediterranean Sea: How Can We Predict Their Future, if We Do Not Know Their Present?

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    In this review we assess the state of knowledge for the coralline algae of the Mediterranean Sea, a group of calcareous seaweeds imperfectly known and considered highly vulnerable to long-term climate change. Corallines have occurred in the Mediterranean area for ∌140 My and are well-represented in the subsequent fossil record; for some species currently common the fossil documentation dates back to the Oligocene, with a major role in the sedimentary record of some areas. Some Mediterranean corallines are key ecosystem engineers that produce or consolidate biogenic habitats (e.g., coralligenous concretions, Lithophyllum byssoides rims, rims of articulated corallines, maerl/rhodolith beds). Although bioconstructions built by corallines exist virtually in every sea, in the Mediterranean they reach a particularly high spatial and bathymetric extent (coralligenous concretions alone are estimated to exceed 2,700 km2 in surface). Overall, composition, dynamics and responses to human disturbances of coralline-dominated communities have been well-studied; except for a few species, however, the biology of Mediterranean corallines is poorly known. In terms of diversity, 60 species of corallines are currently reported from the Mediterranean. This number, however, is based on morphological assessments and recent studies incorporating molecular data suggest that the correct estimate is probably much higher. The responses of Mediterranean corallines to climate change have been the subject of several recent studies that documented their tolerance/sensitivity to elevated temperatures and pCO2. These investigations have focused on a few species and should be extended to a wider taxonomic set

    Cooperative TRAIL production mediates IFNα/Smac mimetic-induced cell death in TNFα-resistant solid cancer cells

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    Smac mimetics antagonize IAP proteins, which are highly expressed in several cancers. Recent reports indicate that Smac mimetics trigger a broad cytokine response and synergize with immune modulators to induce cell death. Here, we identify a differential requirement of TRAIL or TNFα as mediators of IFNα/Smac mimetic-induced cell death depending on the cellular context. Subtoxic concentrations of Smac mimetics cooperate with IFNα to induce cell death in various solid tumor cell lines in a highly synergistic manner as determined by combination index. Mechanistic studies show that IFNα/BV6 cotreatment promotes the formation of a caspase-8-activating complex together with the adaptor protein FADD and RIP1. Assembly of this RIP1/FADD/caspase-8 complex represents a critical event, since RIP1 silencing inhibits IFNα/BV6-induced cell death. Strikingly, pharmacological inhibition of paracrine/autocrine TNFα signaling by the TNFα scavenger Enbrel rescues HT-29 colon carcinoma cells, but not A172 glioblastoma cells from IFNα/BV6-induced cell death. By comparison, A172 cells are significantly protected against IFNα/BV6 treatment by blockage of TRAIL signaling through genetic silencing of TRAIL or its cognate receptor TRAIL receptor 2 (DR5). Despite this differential requirement of TNFα and TRAIL signaling, mRNA and protein expression is increased by IFNα/BV6 cotreatment in both cell lines. Interestingly, A172 cells turn out to be resistant to exogenously added recombinant TNFα even in the presence of BV6, whereas they display a high sensitivity towards TRAIL/BV6. In contrast, BV6 efficiently sensitizes HT-29 cells to TNFα while TRAIL only had limited efficacy. This demonstrates that a differential sensitivity towards TRAIL or TNFα determines the dependency on either death receptor ligand for IFNα/Smac mimetic-induced cell death. Thus, by concomitant stimulation of both death receptor systems IFNα/Smac mimetic combination treatment is an effective strategy to induce cell death in TNFα- or TRAIL-responsive cancers

    Early Detection of Richter’s Transformation: Stable Disease with Dose-Reduced Gemcitabine and Local Radiation

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    Background: The occurrence of Hodgkin’s lymphoma (HL) as a second aggressive lymphoid malignancy (known as Hodgkin’s disease variant of Richter’s transformation) is rarely observed. Response rates, even with highly aggressive therapy such as stem cell transplantation, are limited, ranging from 4 to 43%, and the medium survival time ranges from 5 to 8 months. Case Report: A 72-year-old patient with a history of chronic lymphatic leukemia (CLL) was admitted with thoracic back pain and assumed progression of the CLL. The patient showed no fever, night sweats or weight loss. A computed tomography (CT) scan confirmed the progression of axillary and cervical lymph nodes. In addition, an intraspinal infiltration at the 8th thoracic vertebra (Th8) was detected. Surprisingly, histology of an extirpated lymph node demonstrated the existence of 2 tumors in the same lymph node. Infiltrates of small lymphocytes representing the pre-existing CLL (CD5-, CD20-, CD23-positive) coexisted with Reed-Sternberg Hodgkin’s cells (CD30-, CD15-positive). Chemotherapy was started, combined with palliative radiation of vertebrae Th7–Th10. 12 months after diagnosis of Richter’s transformation the patient is still alive without any progression of the underlying disease. Conclusion: We present a unique case of a Hodgkin’s disease variant of Richter’s transformation and CLL in the same lymph node, which was detected early because of spinal infiltration and was subsequently stabilized with reduced-dosage gemcitabine and local radiation. Additionally, we show unique pictures of 2 tumors coexisting in the same lymph node.Hintergrund: Das Auftreten eines Hodgkin-Lymphoms als zweite aggressive, bösartige, lymphoidzellige Erkankung (bezeichnet als Hodgkin-Variante einer Richter-Transformation) wird sehr selten beobachtet. Selbst mit Hochdosis- Regimen bewegen sich die Ansprechraten etwa zwischen 4 und 43%. Die mittlere Überlebenszeit betrĂ€gt 5–8 Monate. Case Report: Wir berichten ĂŒber einen 72- jĂ€hrigen Patienten, der bei bekannter chronischer lymphatischer LeukĂ€mie (CLL) aufgrund zunehmender Schmerzen im Bereich des RĂŒckens unter der Annahme eines Progresses der CLL stationĂ€r aufgenommen wurde. Fragen nach Fieber, Nachtschweiß und Gewichtsverlust wurden verneint. Computertomogramm (CT)-Aufnahmen zeigten eine GrĂ¶ĂŸenzunahme axillĂ€rer und zervikaler Lymphknoten. Zudem zeigte sich eine intraspinale Raumforderung in Höhe des achten Brustwirbels (Th8). Histologisch konnten in der durchgefĂŒhrten Lymphknotenbiospie 2 Tumore in ein und demselben Lymphknoten festgestellt werden. Es zeigten sich Infiltrate der vorbestehenden CLL (CD5-, CD20-, CD23-positiv) in Koexistenz mit Reed-Sternberg-Hodgkin-Zellen (CD30-, CD15-positiv). Eine Chemotherapie in Kombination mit lokaler Bestrahlung wurde begonnen. 12 Monate nach der Erstdiagnose einer Richter-Transformation ist der Patient am Leben ohne Zeichen von Progress. Schlussfolgerung: Wir prĂ€sentieren hier das Auftreten eines Morbus Hodgkin mit einer CLL als eine seltene Variante einer Richter-Transformation, die durch die frĂŒhe Diagnosestellung mit subtherapeutischer Dosis von Gemcitabin und lokaler Bestrahlung nun ĂŒber 12 Monate stabilisiert werden konnte. Zudem können wir anhand dieses Falles ein Bild zweier Lymphome in ein und demselben Lymphknoten zeigen
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