907 research outputs found
Independent regulation of P53 stabilisation and activation after Rb deletion in primary epithelial cells
We have previously reported that deletion of the retinoblastoma gene Rb leads to rapid but transient p53 stabilisation. We investigated here the pathways involved. We show that upon Rb-deletion dysregulated E2F activates p19(ARF) expression that localises in the nucleoli. There it interacts with MDM2, leading to P53 stabilisation. At the same time, ATR is activated, activating CHK1 that may phosphorylate P53 but also contribute to inhibition of MnSOD expression leading to accumulation of ROS (reactive oxygen species) and subsequent DNA injury, which in turn maintains ATR/CHK1 activated. However, from 72 h after Rb deletion, NPM interacts with P19ARF and concomitantly the interaction between p19(ARF) and MDM2 decreases leading to a return to P53 degradation. This occurs despite the persistence of the DNA damage response pathways. We therefore observe in primary cells not subjected to exogenous gene expression or exogenous DNA damaging treatment, activation of 2 concomitant pathways of activation of P53 that are dealt with in independent manner: an oncogenic pathway with rapid activation of ARF which is 'switched off' downstream of p19(ARF) activation after 72 h of induction and a DNA damage response pathway keeping a low level of transcriptionally active P53 sufficient to deal with a physiological elevation of oxidative DNA injury. A possible connection between the two pathways is discussed.Publisher PDFPeer reviewe
Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFbeta cell cycle arrest
TGFbeta is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFbeta in disease. We asked how Rb-deficiency would affect responses to TGFbeta-induced cell cycle arrest.Publisher PDFPeer reviewe
The Cyclic Connectivity of Homogeneous Arcwise Connected Continua
A continuum is cyclicly connected provided each pair of its points lie together on some simple closed curve. In 1927, G. T. Whyburn proved that a locally connected plane continuum is cyclicly connected if and only if it contains no separating points. This theorem was fundamental in his original treatment of cyclic element theory. Since then numerous authors have obtained extensions of Whyburn\u27s theorem. In this paper we characterize cyclic connectedness in the class of all Hausdorff continua
Recommended from our members
Cranberry field rot, storage rot, fresh fruit keeping quality and yield in Washington as a function of variety, type of fungicide(s) applied, and the number and timing of applications
Abstract:
Replicated trials were conducted on cranberry beds with high levels of fruit rotting pathogens to assess fungicide effects on field rot, storage rot and yield. There was considerable variability between years, experiments and fungicide treatments. A few patterns emerged. Chlorothalonil applied early to mid-bloom consistently increased yield of marketable fruit (22 ± 9%) and reduced fruit rot (46 ± 8.6%). Similar patterns in fruit rot reduction were noted with combinations of azoxystrobin and prothioconazole and other combinations of groups 11 and 3 fungicides applied during bloom, but the effects on yield were less consistent. In multiple trials comparing the efficacy of single commercial fungicides applied during bloom, carboxamide + fluopyram, prothioconazole, and chlorothalonil all consistently increased yield and reduced fruit rot.
Field and storage rot were assessed in decade-long variety trials in Oregon and Washington. Trials in Washington were fungicide-free. Crimson Queen, Scarlet Knight and BG’s had consistently higher field and storage rot than other new releases and standard comparisons.
2015 and 2016 packout data (% poor, 3 and 6 week keeping quality) from Washington’s fresh fruit growers was analyzed as a function of growers’ fungicide programs. Pre-bloom applications appear to have had little impact on fruit rot. Beds with 5-6 in-bloom fungicides had better quality fruit than beds with fewer fungicide applications. Prothioconazole was the most effective in-bloom fungicide. Post-bloom chlorothalonil applications improved fruit quality
Labrador: Exploring the Limits of Masked Language Modeling for Laboratory Data
In this work we introduce Labrador, a pre-trained Transformer model for
laboratory data. Labrador and BERT were pre-trained on a corpus of 100 million
lab test results from electronic health records (EHRs) and evaluated on various
downstream outcome prediction tasks. Both models demonstrate mastery of the
pre-training task but neither consistently outperform XGBoost on downstream
supervised tasks. Our ablation studies reveal that transfer learning shows
limited effectiveness for BERT and achieves marginal success with Labrador. We
explore the reasons for the failure of transfer learning and suggest that the
data generating process underlying each patient cannot be characterized
sufficiently using labs alone, among other factors. We encourage future work to
focus on joint modeling of multiple EHR data categories and to include
tree-based baselines in their evaluations.Comment: 27 pages, 8 figure
Imágenes continuas de continuos hereditariamente indescomponibles
El teorema demostrado es que todo continuo métrico es imagen continua de algún continuo métrico hereditariamente indescomponible.The theorem proven here is that every compact metric continuum is a continuous image of some hereditarily indecomposable metric continuum
- …