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  • 1
    Online-Ressource
    Online-Ressource
    Getting Noticed by Many: On the Transformations of the Popular
    MDPI AG ; 2023
    In:  Arts Vol. 12, No. 1 ( 2023-02-17), p. 39-
    Details
    In: Arts, MDPI AG, Vol. 12, No. 1 ( 2023-02-17), p. 39-
    Kurzfassung: This article argues that the transformations of the popular, which began in Europe around 1800 and introduced the powerful distinction between low culture and high culture, have established a competitive distinction between the popular and the non-popular that has become dominant over the course of the 20th century. As a result, the popular is no longer either the culture of the ‘lower classes’ or the inclusion of the ‘people’ in the service of higher goals. The popular today is hardly the object of desired transgressions (Leslie Fiedler’s “cross the border, close the gap”) or an expression of felt or feared “massification” or “flattening”. Rather, being popular now means getting noticed by many. Popularity is measured as well as staged, as rankings and charts provide information on what is popular while vying for popularity themselves. These quantifying formats do not speak to the quality or originality of the popular, only to its evident success across different scales of evaluation. People do not buy good products, they buy popular ones; they do not listen to the best music, but to popular music; they do not share, like, or retweet important, but popular news. Even the ‘unpopular’ can be popular: a despised politician, a hated jingle, an unpopular measure. The popular modifies whatever it affords with attention. Its quantitatively and hierarchically comparative terms (‘bestseller,’ ‘outperformer,’ ‘high score,’ ‘viral’) generate valences that do not inhere in the objects themselves. Conversely, the non-popular, which does not find any measurable resonance in these terms, risks being dismissed as irrelevant or worthless simply because it does not appear in any rankings or ratings. This can be observed particularly with artefacts whose relevance as part of high culture may be taken for granted even when they do not achieve mass resonance. The purpose of this article is to outline a theory of the popular that does justice to these developments by identifying two decisive transformations: 1. the popularization of quantifying methods to measure attention in popular culture around 1950; 2. the popularization of the internet around 2000, whereby the question of what can and cannot become popular is partially removed from the gatekeepers of the established mass media, educational institutions, and cultural elites and is increasingly decided via social media.
    Materialart: Online-Ressource
    ISSN: 2076-0752
    URL: Article
    DOI: 10.3390/arts12010039
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2704221-2
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 2
    Online-Ressource
    Online-Ressource
    Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation “MSC-FFM”—Outcome Report of 92 Patients
    MDPI AG ; 2019
    In:  Cells Vol. 8, No. 12 ( 2019-12-05), p. 1577-
    Details
    In: Cells, MDPI AG, Vol. 8, No. 12 ( 2019-12-05), p. 1577-
    Kurzfassung: (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
    Materialart: Online-Ressource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells8121577
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2019
    ZDB Id: 2661518-6
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Novel FGFR4-Targeting Single-Domain Antibodies for Multiple Targeted Therapies against Rhabdomyosarcoma
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 11 ( 2020-11-10), p. 3313-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 11 ( 2020-11-10), p. 3313-
    Kurzfassung: The fibroblast growth factor receptor 4 (FGFR4) is overexpressed in rhabdomyosarcoma (RMS) and represents a promising target for treatments based on specific and efficient antibodies. Despite progress, there is an urgent need for targeted treatment options to improve survival rates, and to limit long-term side effects. From phage display libraries we selected FGFR4-specific single-domain antibodies (sdAb) binding to recombinant FGFR4 and validated them by flow cytometry, surface plasmon resonance, and fluorescence microscopy. The specificity of the selected sdAb was verified on FGFR4-wild type and FGFR4-knock out cells. FGFR4-sdAb were used to decorate vincristine-loaded liposomes and to generate chimeric antigen receptor (CAR) T cells. First, incubation of RMS cells with FGFR4-sdAb revealed that FGFR4-sdAb can block FGF19-FGFR4 signaling via the MAPK pathway and could therefore serve as therapeutics for FGFR4-dependent cancers. Second, FGFR4-targeted vincristine-loaded liposomes bound specifically to RMS cells and were internalized by the receptor, demonstrating the potential for active drug delivery to the tumor. Third, FGFR4-CAR T cells, generated with one sdAb candidate, demonstrated strong and specific cytotoxicity against FGFR4 expressing RMS cells. We selected novel FGFR4-sdAb with high specificity and nano- to picomolar affinities for FGFR4 which have the potential to enable multiple FGFR4-targeted cancer therapy approaches.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12113313
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    A Smart Imaging Workflow for Organ-Specific Screening in a Cystic Kidney Zebrafish Disease Model
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 6 ( 2019-03-14), p. 1290-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 6 ( 2019-03-14), p. 1290-
    Kurzfassung: The zebrafish is being increasingly used in biomedical research and drug discovery to conduct large-scale compound screening. However, there is a lack of accessible methodologies to enable automated imaging and scoring of tissue-specific phenotypes at enhanced resolution. Here, we present the development of an automated imaging pipeline to identify chemical modifiers of glomerular cyst formation in a zebrafish model for human cystic kidney disease. Morpholino-mediated knockdown of intraflagellar transport protein Ift172 in Tg(wt1b:EGFP) embryos was used to induce large glomerular cysts representing a robustly scorable phenotypic readout. Compound-treated embryos were consistently aligned within the cavities of agarose-filled microplates. By interfacing feature detection algorithms with automated microscopy, a smart imaging workflow for detection, centring and zooming in on regions of interests was established, which enabled the automated capturing of standardised higher resolution datasets of pronephric areas. High-content screening datasets were processed and analysed using custom-developed heuristic algorithms implemented in common open-source image analysis software. The workflow enables highly efficient profiling of entire compound libraries and scoring of kidney-specific morphological phenotypes in thousands of zebrafish embryos. The demonstrated toolset covers all the aspects of a complex whole organism screening assay and can be adapted to other organs, specimens or applications.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20061290
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2019
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 5
    Online-Ressource
    Online-Ressource
    Efficacy and Toxicity of Different Chemotherapy Protocols for Concurrent Chemoradiation in Non-Small Cell Lung Cancer—A Secondary Analysis of the PET Plan Trial
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 11 ( 2020-11-13), p. 3359-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 11 ( 2020-11-13), p. 3359-
    Kurzfassung: (1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician’s discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12113359
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
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