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  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 11 ( 2019-11-05), p. 1728-
    In: Cancers, MDPI AG, Vol. 11, No. 11 ( 2019-11-05), p. 1728-
    Abstract: In this review we concentrate on the recent findings describing the oncogenic potential of the protein tyrosine kinase 2 (TYK2). The overview on the current understanding of TYK2 functions in cytokine responses and carcinogenesis focusses on the activation of the signal transducers and activators of transcription (STAT) 3 and 5. Insight gained from loss-of-function (LOF) gene-modified mice and human patients homozygous for Tyk2/TYK2-mutated alleles established the central role in immunological and inflammatory responses. For the description of physiological TYK2 structure/function relationships in cytokine signaling and of overarching molecular and pathologic properties in carcinogenesis, we mainly refer to the most recent reviews. Dysregulated TYK2 activation, aberrant TYK2 protein levels, and gain-of-function (GOF) TYK2 mutations are found in various cancers. We discuss the molecular consequences thereof and briefly describe the molecular means to counteract TYK2 activity under (patho-)physiological conditions by cellular effectors and by pharmacological intervention. For the role of TYK2 in tumor immune-surveillance we refer to the recent Special Issue of Cancers “JAK-STAT Signaling Pathway in Cancer”.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 2
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 14 ( 2022-07-17), p. 7874-
    Abstract: Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1–CCR9, CXCR1–CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4–CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1–CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    In: Lubricants, MDPI AG, Vol. 10, No. 11 ( 2022-10-29), p. 286-
    Abstract: For wet disk clutches, the energy input is strongly influenced by its friction behavior. However, the friction behavior cannot be simulated and therefore is mostly derived from experimental data for specific clutch systems. This paper presents a new approach for the identification and validation of linear friction models using analysis of variance (ANOVA) and stepwise regression. Therefore, we use experimental data of three different friction systems with paper- and carbon-based friction lining. The designed experiments support an efficient parameter-based analysis of the friction behavior. The obtained models can be used as an input for thermal simulations, for example, but can also support a better understanding of the main influencing factors and are applicable to various friction systems. For validation, the obtained models are applied to measured data. A good correspondence between the simulated and measured friction behavior can be shown for speeds in the investigated operating range. The presented procedure can be easily adapted, for different factors and operation modes, as well as other applications.
    Type of Medium: Online Resource
    ISSN: 2075-4442
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704327-7
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