423 research outputs found

    Semantic Bias in the Interpretation of German Personal and Demonstrative Pronouns

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    Contribution to Linguistic Evidence 202

    Association of telomerase activity with radio- and chemosensitivity of neuroblastomas

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    <p>Abstract</p> <p>Background</p> <p>Telomerase activity compensates shortening of telomeres during cell division and enables cancer cells to escape senescent processes. It is also supposed, that telomerase is associated with radio- and chemoresistance. In the here described study we systematically investigated the influence of telomerase activity (TA) and telomere length on the outcome of radio- and chemotherapy in neuroblastoma.</p> <p>Methods</p> <p>We studied the effects on dominant negative (DN) mutant, wild type (WT) of the telomerase catalytic unit (hTERT) using neuroblastoma cell lines. The cells were irradiated with <sup>60</sup>Co and treated with doxorubicin, etoposide, cisplatin and ifosfamide, respectively. Viability was determined by MTS/MTT-test and the GI<sub>50 </sub>was calculated. Telomere length was measured by southernblot analysis and TA by Trap-Assay.</p> <p>Results</p> <p>Compared to the hTERT expressing cells the dominant negative cells showed increased radiosensitivity with decreased telomere length. Independent of telomere length, telomerase negative cells are significantly more sensitive to irradiation. The effect of TA knock-down or overexpression on chemosensitivity were dependent on TA, the anticancer drug, and the chemosensitivity of the maternal cell line.</p> <p>Conclusions</p> <p>Our results supported the concept of telomerase inhibition as an antiproliferative treatment approach in neuroblastomas. Telomerase inhibition increases the outcome of radiotherapy while in combination with chemotherapy the outcome depends on drug- and cell line and can be additive/synergistic or antagonistic. High telomerase activity is one distinct cancer stem cell feature and the here described cellular constructs in combination with stem cell markers like CD133, Aldehyddehydrogenase-1 (ALDH-1) or Side population (SP) may help to investigate the impact of telomerase activity on cancer stem cell survival under therapy.</p

    Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model

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    Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate

    Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo

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    Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironrnent. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-beta II and the subsequent activation of NF-kappa B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-beta knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-beta II-NF-kappa B signaling pathway in the tumor microenvironment. Upregulated stromal PKG-beta II in biopsies from patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies

    Diagnosis of quarantine organisms at the JKI in the National Reference Laboratory for organisms harmful to plants

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    Dem JKI wurde im April 2019 durch das Bundesministerium für Ernährung und Landwirtschaft (BMEL) die Funktion des nationalen Referenzlaboratoriums (NRL) für Schadorganismen der Pflanzen zugewiesen. Mit dieser Funktion des NRL für Deutschland sind bestimmte Zuständigkeiten und Aufgaben verbunden, die in der EU-Verordnung 2017/625 (EU, 2017) geregelt sind. Dazu gehören auch Referenzuntersuchungen bzw. die Diag­nose von Quarantäneschadorganismen (QSO). Das NRL stellt eine übergeordnete Einheit innerhalb des JKI dar. Durch insgesamt 14 Prüflabore der JKI-Institute für Pflanzenschutz in Ackerbau und Grünland (A), nationale und internationale Angelegenheiten der Pflanzengesundheit (AG), Epidemiologie und Pathogendiagnostik (EP), Pflanzenschutz in Gartenbau und Forst (GF), Pflanzenschutz in Obst- und Weinbau (OW) wird die Referenzfunktion bei der Diagnose zu verschiedensten (Quarantäne)-Schadorganismen der Pathogengruppen Bakterien, Insekten, Nematoden, Pilze (einschließlich Oomyceten), Phytoplasmen und Viren wahrgenommen.In April 2019, the JKI was officially designated as the Natio­nal Reference Laboratory (NRL) for organisms harmful to plants by the Federal Ministry of Food and Agri­culture (BMEL). This function as NRL for Germany is associated with certain responsibilities and tasks, which are specified in the EU Regulation 2017/625 (EU, 2017). This also includes reference tests and the diagnosis of quarantine pests, respectively. The NRL represents a super­ordinate unit inside JKI. A total of 14 test laboratories from different JKI institutes, namely for Plant Protection in Field Crops and Grassland (A), for National and International Plant Health (AG), for Epidemiology and Pathogen Diagnostics (EP), Plant Protection in Horti­culture and Forests (GF), and for Plant Protection in Fruit Crops and Viticulture (OW) are in charge to carry out a reference function in the diagnosis of (quarantine) pests in the pathogen groups of bacteria, fungi (including oomycetes), insects, nematodes, phytoplasma und viruses

    MOSAiC-ACA and AFLUX - Arctic airborne campaigns characterizing the exit area of MOSAiC

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    Two airborne field campaigns focusing on observations of Arctic mixed-phase clouds and boundary layer processes and their role with respect to Arctic amplification have been carried out in spring 2019 and late summer 2020 over the Fram Strait northwest of Svalbard. The latter campaign was closely connected to the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition. Comprehensive data sets of the cloudy Arctic atmosphere have been collected by operating remote sensing instruments, insitu probes, instruments for the measurement of turbulent fluxes of energy and momentum, and dropsondes on board the AWI research aircraft Polar 5. In total, 24 flights with 111 flight hours have been performed over open ocean, the marginal sea ice zone, and sea ice. The data sets follow documented methods and quality assurance and are suited for studies on Arctic mixed-phase clouds and their transformation processes, for studies with a focus on Arctic boundary layer processes, and for satellite validation application

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

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    One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

    Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

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    This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good
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