University of Coimbra

About: University of Coimbra is a education organization based out in Coimbra, Portugal. It is known for research contribution in the topics: Population & Context (language use). The organization has 14318 authors who have published 43067 publications receiving 994733 citations. The organization is also known as: UC & Universidade dos Estudos Gerais.

Cross-Validation for Imbalanced Datasets: Avoiding Overoptimistic and Overfitting Approaches [Research Frontier]

Abstract: Although cross-validation is a standard procedure for performance evaluation, its joint application with oversampling remains an open question for researchers farther from the imbalanced data topic. A frequent experimental flaw is the application of oversampling algorithms to the entire dataset, resulting in biased models and overly-optimistic estimates.

The Expression of Mitochondrial DNA Transcription Factors during Early Cardiomyocyte In Vitro Differentiation from Human Embryonic Stem Cells

Abstract: Mitochondrial biogenesis and activation of both oxidative phosphorylation, as well as transcription and replication of the mitochondrial genome, are key regulatory events in cell differentiation. Mitochondrial DNA transcription and replication are highly dependent on the interaction with nuclear-encoded transcription factors translocated from the nucleus. Using a human embryonic stem cell line, HSF 6, we analyzed the proliferation of mitochondria and the expression of mtDNA-specific transcription factors in undifferentiated, migratory embryonic stem cells and spontaneously derived cardiomyocytes. Mitochondrial proliferation and mtDNA transcription are initiated in human embryonic stem cells as they undergo spontaneous differentiation in culture into beating cardiomyocytes. Undifferentiated, pluripotent human embryonic stem cells have few mitochondria, and, as they differentiate, they polarize to one extremity of the cell and then bipolarize the differentiating cell. The differentiated cell then adopts the...

Search for dark matter in events with a hadronically decaying W or Z boson and missing transverse momentum in pp collisions at √s = 8 TeV with the ATLAS detector

Abstract: A search is presented for dark matter pair production in association with a W or Z boson in pp collisions representing 20.3 fb(-1) of integrated luminosity at root s = 8 TeV using data recorded with the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet with the jet mass consistent with a W or Z boson, and with large missing transverse momentum are analyzed. The data are consistent with the standard model expectations. Limits are set on the mass scale in effective field theories that describe the interaction of dark matter and standard model particles, and on the cross section of Higgs production and decay to invisible particles. In addition, cross section limits on the anomalous production of W or Z bosons with large missing transverse momentum are set in two fiducial regions.

Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas.

Abstract: Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model). The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies.