2,439 research outputs found
Data fusion techniques for the integration of multi-domain genomic data from uveal melanoma
Full text linkUveal melanoma (UM) is a rare cancer that is well characterized at the molecular level. Two to four classes have been identified by the analyses of gene expression (mRNA, ncRNA), DNA copy number, DNA-methylation and somatic mutations yet no factual integration of these data has been reported. We therefore applied novel algorithms for data fusion, joint Singular Value Decomposition (jSVD) and joint Constrained Matrix Factorization (jCMF), as well as similarity network fusion (SNF), for the integration of gene expression, methylation and copy number data that we applied to the Cancer Genome Atlas (TCGA) UM dataset. Variant features that most strongly impact on definition of classes were extracted for biological interpretation of the classes. Data fusion allows for the identification of the two to four classes previously described. Not all of these classes are evident at all levels indicating that integrative analyses add to genomic discrimination power. The classes are also characterized by different frequencies of somatic mutations in putative driver genes (GNAQ, GNA11, SF3B1, BAP1). Innovative data fusion techniques confirm, as expected, the existence of two main types of uveal melanoma mainly characterized by copy number alterations. Subtypes were also confirmed but are somewhat less defined. Data fusion allows for real integration of multi-domain genomic data
Compendium, oder, Kurtzer Begriff des Massnerischen Processes, welcher von dem Fisco lobl. gmeiner dreyen Pündten vorgenommen im Julio, und zu dem End gebracht und vom lobl. unpartheyischen Special-Land-Gericht besagte dreyen Pündten, etc. darüber die End-Urtel erlassen in Ilantz den 17. Augusti 1711
No full text[Thomas Massner ; Johann Ulrich von Blumenthal et al.
Tractatio Iuris Publici De Serenissimis Potentissimisque Ducibus Brunsvicensibus Et Luneburgensibus / D.O.M.A. Praeside ... Dn. Joh. Ulrico Pregizero ... In Illustri Collegio Ad Diem 10. Decembr. Placido Eruditorum Examini sistit Author Christian Ulrich Blum
Full text linkTRACTATIO IURIS PUBLICI DE SERENISSIMIS POTENTISSIMISQUE DUCIBUS BRUNSVICENSIBUS ET LUNEBURGENSIBUS / D.O.M.A. PRAESIDE ... DN. JOH. ULRICO PREGIZERO ... IN ILLUSTRI COLLEGIO AD DIEM 10. DECEMBR. PLACIDO ERUDITORUM EXAMINI SISTIT AUTHOR CHRISTIAN ULRICH BLUM
Tractatio Iuris Publici De Serenissimis Potentissimisque Ducibus Brunsvicensibus Et Luneburgensibus / D.O.M.A. Praeside ... Dn. Joh. Ulrico Pregizero ... In Illustri Collegio Ad Diem 10. Decembr. Placido Eruditorum Examini sistit Author Christian Ulrich Blum (1)
Titelblatt (1)
Prooemium. (3)
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Identification of a prognostic signature based on the expression of genes related to the insulin pathway in early breast cancer
Full text linkINTRODUCTION: Insulin and the insulin-like growth factor (IGF) family play a key role in breast cancer (BC). OBJECTIVE: In this study, we evaluated on a genomic scale the potential prognostic value of insulin signaling in early BC. METHODS: Candidate genes were selected from the published literature and gene expression profiling experiments. Three publicly available BC datasets, containing gene expression data on 502 cases, were used to test the prognostic ability of the score. The gene signature was developed on GSE1456, containing microarray data from 159 patients, split into a training set (102 breast tumors) and a validation set (n = 57). GSE3494 and GSE2990 (350 patients) were used for external validation. Univariate Mann-Whitney test was used to identify genes differentially expressed between relapsed and nonrelapsed patients. Expression of genes significantly correlated with relapse was combined in a linear score. Patients were classified as low or high risk with respect to the median value. RESULTS: On the training set, 15 genes turned out to be differentially expressed: 8-year disease-free survival (DFS) was 51 and 91% in the high- and low-risk group (p < 0.001), respectively. In the validation set, DFS was 97 and 54% (p = 0.009), respectively. External validation: 8-year DFS was 72 and 61%, respectively, in GSE3494 (p = 0.03) and 74 and 55% in GSE2990 (p = 0.03). By multivariate analyses, the insulin signature was significantly associated with DFS, independently of age, hormone receptor status, nodal status, and grade. CONCLUSIONS: Our findings indicate that the insulin pathway is involved in BC prognosis at a genomic level and provide a window of selectivity for preventive and treatment strategies targeting the insulin/IGF pathway in BC patients
Supplementary movies of the dynamic rupture and tsunami models published in Ulrich et al. (2019)
No full text<p>Supplementary movies of the dynamic rupture and tsunami models published in Ulrich et al. (2019)</p>
<p>movie_Sulawesi_SR-cp.mov: Absolute slip rate (m/s) across the fault network during the earthquake. Author: Thomas Ulrich</p>
<p>movie_Sulawesi_wavefield-cp.mov: Absolute slip rate (m/s) and wavefield (absolute particle velocity in m/s) across the fault network during the earthquake. Author: Thomas Ulrich</p>
<p>SulawesiTanioka.mp4: Sea surface height (m) predicted by the tsunami scenario. Author: Stefan Vater</p>
<p>reference: Ulrich, T., Vater, S., Madden, E. H., Behrens, J., van Dinther, Y., van Zelst, I., Fielding, E. J., Liang, C. & Gabriel, A. A. (2019). Coupled, Physics-based Modeling Reveals Earthquake Displacements are Critical to the 2018 Palu, Sulawesi Tsunami. doi: 10.31223/osf.io/3bwqa.</p>
Identification of a New Cell Population Constitutively Circulating in Healthy Conditions and Endowed with a Homing Ability Toward Injured Sites
No full textStem and progenitor cells are the critical units for tissue maintenance, regeneration, and repair. The activation of regenerative events in response to tissue injury has been correlated with mobilization of tissue-resident progenitor cells, which is functional to the wound healing process. However, until now there has been no evidence for the presence of cells with a healing capacity circulating in healthy conditions. We identified a rare cell population present in the peripheral blood of healthy mice that actively participates in tissue repair. These Circulating cells, with a Homing ability and involved in the Healing process (CH cells), were identified by an innovative flowcytometry strategy as small cells not expressing CD45 and lineage markers. Their transcriptome profile revealed that CH cells are unique and present a high expression of key pluripotency- and epiblast-associated genes. More importantly, CH-labeled cells derived from healthy Red Fluorescent Protein (RFP)-transgenic mice and systemically injected into syngeneic fractured wild-type mice migrated and engrafted in wounded tissues, ultimately differentiating into tissue-specific cells. Accordingly, the number of CH cells in the peripheral blood rapidly decreased following femoral fracture. These findings uncover the existence of constitutively circulating cells that may represent novel, accessible, and versatile effectors of therapeutic tissue regeneration
Air Pollution Monitoring in Street Canyons / Hans-Ulrich Pfeffer, Jürgen Friesel, Gereon Elbers, Reinhold Beier,
No full text
EZH1/2 Inhibitors Favor ILC3 Development from Human HSPC-CD34+ Cells
No full textThe dysregulation of epigenetic modifications has a well-established role in the development and progression of hematological malignancies and of solid tumors. In this context, EZH1/2 inhibitors have been designed to interfere with EZH1/2 enzymes involved in histone methylation (e.g., H3K27me3), leading to tumor growth arrest or the restoration of tumor suppressor gene transcription. However, these compounds also affect normal hematopoiesis, interfering with self-renewal and differentiation of CD34+-Hematopoietic Stem/Progenitor Cells (HSPC), and, in turn, could modulate the generation of potential anti-tumor effector lymphocytes. Given the important role of NK cells in the immune surveillance of tumors, it would be useful to understand whether epigenetic drugs can modulate NK cell differentiation and functional maturation. CD34+-HSPC were cultured in the absence or in the presence of the EZH1/2 inhibitor UNC1999 and EZH2 inhibitor GSK126. Our results show that UNC1999 and GSK126 increased CD56+ cell proliferation compared to the control condition. However, UNC1999 and GSK 126 favored the proliferation of no-cytotoxic CD56+ILC3, according to the early expression of the AHR and ROR-γt transcription factors. Our results describe novel epigenetic mechanisms involved in the modulation of NK cell maturation that may provide new tools for designing NK cell-based immunotherapy
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