Equivariant closure operators and trisp closure maps

A trisp closure map is a special map on the vertices of a trisp T with the property that T collapses onto the subtrisp induced by the image of the map. We study the interaction between trisp closure maps and group operations on the trisp, and give conditions such that the quotient map is again a trisp closure map. Special attention is on the case that the trisp is the nerve of an acyclic category, and the relationship between trisp closure maps and closure operators on posets is studied.Comment: 8 pages, 3 figure

Some necessary conditions for vector space partitions

Some new necessary conditions for the existence of vector space partitions are derived. They are applied to the problem of finding the maximum number of spaces of dimension t in a vector space partition of V(2t,q) that contains m_d spaces of dimension d, where t/2<d<t, and also spaces of other dimensions. It is also discussed how this problem is related to maximal partial t-spreads in V(2t,q). We also give a lower bound for the number of spaces in a vector space partition and verify that this bound is tight.Comment: 19 pages; corrected typos and rewritten introductio

Zervixlängenmessung im ersten Trimenon - Vergleich von drei verschiedenen Messmethoden

Für diese Arbeit wurden drei verschiedene Messmethoden der Zervixlängenmessung im ersten Trimenon verglichen (Eine-Linie, Zwei-Linien, Trace). Hierfür wurden bei 80 Patientinnen zwischen der 11+0 und 13+6 SSW durch vier Untersucher anhand von digital gespeicherten Bildern mithilfe eines Computerprogramms die Zervixlängen durch die drei Messmethoden gemessen. Die Mittelwerte der Zervixlängenmessungen durch die Ein-Linien-Messmethode lagen bei 32,8 mm, durch die Zwei-Linien-Messmethode bei 34,4 mm und durch die Trace-Methode bei 34,5 mm. Ein signifikanter Messunterschied konnte weder zwischen den verschiedenen Messmethoden noch zwischen den Untersuchern aufgezeigt werden. Die Krümmung der Cervix uteri ist unterschiedlich stark ausgeprägt. Bei einer Krümmung der Cervix >5 mm ergab sich ein signifikanter Unterschied in den Messdifferenzen der Ein-Linien- und Zwei-Linien-Messmethode (p <0,0001). Als Goldstandard sollte die Ein-Linien-Methode für die Zervixlängenmessung im ersten Trimenon benutzt weden. In manchen Fällen, vor allem bei sehr stark gebogenen Cervices, kann die Zervixlängenmessung mithilfe der Zwei-Linien- oder Trace-Messung hilfreich sein

Einfluss von außerschulischen Lernorten auf die Gestaltung von technisch geprägten Karrierewegen: Eine empirische Analyse der Effekte des Engagements im Schüler - Institut für Technik und angewandte Informatik (SITI) e.V. auf die Berufswahl

&nbsp;&nbsp;&nbsp

PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization

Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. However, the relationship between hypoxia and PD-L1 regulation in pheochromocytomas and paragangliomas (PPGL), and especially in paragangliomas treated with embolization, is still largely unexplored. We investigated the expression of the hypoxia-marker HIF-2α and of PD-L1 in a PPGL-cohort with and without embolization as potential biomarkers that may predict the response to treatment with HIF-2α and checkpoint inhibitors. A total of 29 tumor samples from 25 patients who were operated at a single center were included and analyzed utilizing immunohistochemistry (IHC) for PD-L1 and HIF-2α. Embolization prior to surgery was performed in seven (24%) tumors. PD-L1 expression in tumor cells of head and neck paragangliomas (HNPGLs) receiving prior embolization (median PD-L1 positivity: 15%) was significantly higher as compared to PD-L1 expression in HNPGLs without prior embolization (median PD-L1 positivity: 0%) (p = 0.008). Consistently, significantly more HNPGLs with prior embolization were positive for HIF-2α (median nuclear HIF-2α positivity: 40%) as compared to HNPGLs without prior embolization (median nuclear HIF-2α positivity: 0%) (p = 0.016). Our results support the hypothesis that embolization with subsequent hypoxia leads to the upregulation of both PD-L1 and HIF-2α in HNPGLs, and could thus facilitate targeted treatment with HIF-2α and checkpoint inhibitors in the case of inoperable, locally advanced, or metastatic disease

Metastatic Pheochromocytoma and Paraganglioma: Somatostatin Receptor 2 Expression, Genetics, and Therapeutic Responses

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors. OBJECTIVE: Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs. METHODS: Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs. RESULTS: Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx). CONCLUSION: SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs

Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer

BACKGROUND: FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. METHODS: Using immunohistochemistry (IHC) we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204) and normal breast tissues (n = 46) on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12) and cancerous (n = 25) breast tissue specimens as well as benign (n = 3) and malignant mammary cell lines (n = 8) were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. RESULTS: FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR). We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P < 0.05). Univariate survival analysis showed a tendency between FOXM1 protein expression and unfavourable prognosis (P = 0.110). CONCLUSION: FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter