137 research outputs found
The Salience of Hegemonic Masculinity
No full textThis article argues that the concept of “hegemonic masculinity” remains highly salient to critical masculinities studies. The author outlines Raewyn Connell\u27s initial formulation of the concept, how that initial model of hegemonic masculinity has been historically misinterpreted, the reformulation of the concept by Connell and Messerschmidt, and the recent scholarly amplification of the concept. The author concludes that Connell’s original emphasis on the legitimation of unequal gender relations remains essential to both the concept and to the field of critical masculinities studies
Charakterisierung der Behandlungsresistenz bei Kopf- und Halskrebs, Lymphomen und Neuroblastomen durch die Analyse von Omics-Daten
No full textIn this thesis, I present my contributions to three publications in the field of translational
precision oncology. What all three presented studies have in common is that they elucidate
mechanisms that influence drug resistance, which is one of the major reasons why cancer
ultimately proves lethal. Through technical and methodical advances, understanding of the
inner workings of cancer cells is continuously improving even after decades of research. This
progress allows for better treatment, tailored specifically for every patient. But as treatment
puts pressure onto a tumor, resistance might eventually develop and the tumor relapses. For
optimal treatment outcome, it is therefore important to use an effective drug while at the
same time monitoring for the emergence of resistance and counteract it.
The first publication, Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC,
is the result of our interest in identifying possible markers for immune checkpoint inhibition
in head and neck tumors, an area of study at Charité Comprehensive Cancer Center. Using
open data from TCGA, we analyzed 496 tumors and evaluated their HPV status, mutational
signatures, gene expression signatures as well as mutational load. We were able to define
a subgroup with a distinct immune profile in HPV-negative tumors that shows increased
inflammation, which correlates with the footprint of APOBEC3-associated single-nucleotide
mutations. Further, in these tumors we observed a higher frequency in mutations that allow
immune-evasion. In a separate single cell expression dataset, we show mRNA expression
of APOBEC3 family members in tumor cells for the first time. Previously, it was not
clear if APOBEC3 was expressed by the tumor cells or only in the surrounding tumor
micro-environment, as APOBEC3 proteins are notoriously difficult to stain with antibodies.
The publication by Akpa et al., Acquired resistance to DZNep-mediated apoptosis is associated
with copy number gains of AHCY in a B-cell lymphoma model, describes how we engineered
a B-cell lymphoma cell line to become resistant against the drug DZnep. By analyzing
whole-exome data and comparing the resistant with sensitive cells, we were able to pinpoint
a gene amplification of the gene AHCY, which is exactly the gene inhibited by DZnep. Thus,
we have shown one possible avenue for development of resistance even before DZnep has been
used in clinical studies.
The final publication by Dorel et al., Neuroblastoma signaling models unveil combination
therapies targeting feedback-mediated resistance, describes our efforts to model Ras/MAPK
pathway activity in a panel of nine cell lines representative of high risk neuroblastoma.
Through molecular characterization and pathway modeling on perturbation-response data we
were able to formulate new treatment strategies that work by vertical inhibition on multiple
pathway targets. By combining targeted drugs in such a deliberate manner, treatment
outcomes will improve in the future.In dieser Arbeit stelle ich meine Beiträge zu drei Veröffentlichungen im Bereich der transla-
tionalen Präzisionsonkologie vor. Allen drei Studien ist gemeinsam, dass sie Mechanismen
aufklären, die Arzneimittelresistenzen beeinflussen. Durch technische und methodische
Fortschritte wird das Wissen über das Innenleben von Krebszellen auch nach Jahrzehnten
der Forschung immer besser. Dieser Fortschritt ermöglicht eine Behandlung, die speziell auf
jeden Patienten zugeschnitten ist. Da die Behandlung jedoch Druck auf den Tumor ausübt,
kann sich schließlich eine Resistenz entwickeln. Für ein optimales Behandlungsergebnis ist es
daher wichtig, ein wirksames Medikament einzusetzen und gleichzeitig die Entstehung von
Resistenzen zu überwachen und ihnen entgegenzuwirken.
Die erste Publikation, Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC,
beschreibt einen möglichen Marker für die Antwort auf Immun-Checkpoint-Inhibition bei
Kopf-Hals-Tumoren. Wir analysierten 496 Tumore und werteten ihren HPV-Status, Muta-
tionssignaturen, Genexpressionssignaturen sowie die Mutationslast aus. Wir definieren eine
Untergruppe mit einem ausgeprägten Immunprofil in HPV-negativen Tumoren, die erhöhte
Entzündungswerte aufweist, welche mit APOBEC3-assoziierten Einzelnukleotidmutationen
korreliert. Außerdem beobachteten wir in diesen Tumoren eine höhere Häufigkeit von Muta-
tionen, die eine Umgehung des Immunsystems ermöglichen. In einem separaten single-cell
Datensatz zeigen wir mRNA-Expression von APOBEC3 in Tumorzellen. Bisher war nicht
klar, ob APOBEC3 von den Tumorzellen oder nur in der Tumorumgebung exprimiert wird,
da APOBEC3-Proteine mit Antikörpern schwer zu färben sind.
Die Veröffentlichung von Akpa et al, Erworbene Resistenz gegen DZNep-vermittelte Apoptose
steht in Verbindung mit Kopienzahlgewinnen von AHCY in einem B-Zell-Lymphom-Modell,
beschreibt, wie wir eine B-Zell-Lymphom-Zelllinie so verändert haben, dass sie gegen das
Medikament DZnep resistent wurde. Durch die Analyse von Whole-Exom-Daten und den
Vergleich der resistenten mit den empfindlichen Zellen konnten wir eine Genamplifikation
des Gens AHCY nachweisen, das genau das Gen ist, das von DZnep gehemmt wird. Damit
haben wir einen möglichen Weg für die Entwicklung einer Resistenz aufgezeigt, noch bevor
DZnep in klinischen Studien eingesetzt wurde.
Die letzte Veröffentlichung von Dorel et al, Neuroblastoma signaling models unveil combination
therapies targeting feedback-mediated resistance, beschreibt unsere Bemühungen, die Aktivität
des Ras/MAPK-Signalwegs in einer Gruppe von neun Zelllinien zu modellieren, die für
das Hochrisiko-Neuroblastom repräsentativ sind. Durch molekulare Charakterisierung und
Modellierung der Signalwege auf der Grundlage von Perturbationsdaten waren wir in der
Lage, neue Behandlungsstrategien zu formulieren, die durch vertikale Hemmung mehrerer
Targets wirken. Durch eine solche gezielte Kombination von Medikamenten werden sich die
Behandlungsergebnisse in Zukunft verbessern
BIOPHYSICAL CONTROLS OF MARSH SOIL SHEAR STRENGTH ALONG AN ESTUARINE SALINITY GRADIENT
No full text© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gillen, M. N., Messerschmidt, T. C., & Kirwan, M. L. Biophysical controls of marsh soil shear strength along an estuarine salinity gradient. Earth Surface Dynamics, 9(3),(2021): 413-421, https://doi.org/10.5194/esurf-9-413-2021.Sea-level rise, saltwater intrusion, and wave erosion threaten coastal marshes, but the influence of salinity on marsh erodibility remains poorly understood. We measured the shear strength of marsh soils along a salinity and biodiversity gradient in the York River estuary in Virginia to assess the direct and indirect impacts of salinity on potential marsh erodibility. We found that soil shear strength was higher in monospecific salt marshes (5–36 kPa) than in biodiverse freshwater marshes (4–8 kPa), likely driven by differences in belowground biomass. However, we also found that shear strength at the marsh edge was controlled by sediment characteristics, rather than vegetation or salinity, suggesting that inherent relationships may be obscured in more dynamic environments. Our results indicate that York River freshwater marsh soils are weaker than salt marsh soils, and suggest that salinization of these freshwater marshes may lead to simultaneous losses in biodiversity and erodibility.This research has been supported by the US National Science Foundation (grant nos. 1654374, 1426981, 1529245, and 1832221)
bihealth/scelvis: v0.4.1
No full text:sparkler: SCelVis - web-based visualization of single-cell data. :arrow_right: :arrow_right: Demo :arrow_right::arrow_right
bihealth/scelvis v0.5.0
No full text:sparkler: SCelVis - web-based visualization of single-cell data. :arrow_right: :arrow_right: Demo :arrow_right::arrow_right
The relationship between parental alcoholism and the emotional coping of their adult children, 1990
No full textThe overall objective of this study was to examine the relationship between alcoholic parents and the emotional coping of their adult children. To attain this objective, theoretical perspectives were addressed in reference to: (a) alcoholism and the dynamics of the alcoholic family, (b) the family roles and rules, (c) characteristics of children reared in an alcoholic family, (d) the implications of these characteristics, and (e) clinical observations of the characteristics of adult children of alcoholics (ACOA's). A correlational research design was used. A descriptive questionnaire, adapted from Woititz (1983) and found to be reliable and valid in identifying personality characteristics among ACOA's, was administered to thirty-two individuals who were identified as ACOA's. The sample was selected from two adult children of alcoholics support groups in Atlanta, Georgia. The study hypothesized that there is no statistical significant relationship between parental alcoholism and the emotional coping of their adult children. With reference to those (84.7%) who identified their father as alcoholic and their emotional coping in adulthood, the contingency table. 2 analysis showed: x = .01678, d.f = 1, and P .05. The null hypothesis was accepted. This study has ramifications for social work professionals to further ascertain the impact that alcoholism has on the family system. Social work literature is limited, especially related to adult children of alcoholics. This study will therefore present as a resource in enhancing the social work literature
Produktie van propeen uit 2-buteen en etheen via disproportionering
No full textDocument(en) uit de collectie Chemische Procestechnologie.DelftChemTechApplied Science
Najstniki, utelesene heteromaskulinosti in spolno nasilje
No full textIn this paper the author summarizes several life history case studies of adolescent boys who were identified at school as “wimps” and who eventually engaged in various forms of sexual violence. Such boys rarely are - if at all - discussed in the childhood, education and feminist literatures on sexual violence. The life stories reveal the interrelationship among in school bullying, reflexivity, embodied structured action, and the social construction of heteromasculinities in the commission of sexual violence by subordinated boys. The author concludes by considering the implications the research has to the evolving discourses on social scientific conceptualizations of reflexive embodiment and heteromasculinities. (DIPF/Orig.
Migrationsgesellschaftliche Geschichtsbeziehungen zum Nationalsozialismus
No full textThis contribution sketches societal conditions for an up-to-date work of remembrance in the context of our current experience in migration societies, and analyses self-images of migration society in the sense of a construction of an ‘us’ as well as phenomena of secondary antisemitism. Also, the memorial practices within a European remembrance of the history of National Socialism are examined within this context. Memorial practices in migration societies are understood as multi-perspective constructs of relational history. The author argues from her own West German context; similarities and differences to the Austrian situation remain to be discussed
bihealth/scelvis: filtering and differential expression
No full textcell filtering
differential expressio
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