41 research outputs found

    Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

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    Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

    Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

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    Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

    A Critical Examination of Timing of Burning in the Kansas Flint Hills

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    Frequent burning is a crucial ecological and economic component of the Kansas Flint Hills. Although burning is important for the preservation of tallgrass prairie and improving livestock production, it has become a controversial societal issue because of its potential impact on air quality standards. Over the past 80 years, recommendations on burning in Kansas have ranged from total fire exclusion to burning only in late April; and for the past 40 years, the concept that burning should only occur in late spring has become ingrained in the cultural practices of rangeland management. Yet the scientific basis for these recommendations has received little rigorous scrutiny. Herein, we critically review the research on dormant-season burning in the Flint Hills that formed the foundation for modern burn practices in Kansas. Close examination of the historical data does not support the tenet that burning must be limited to a narrow window in late spring. Many conclusions of the research that led to recommending burning only in late spring were ambiguous, not subjected to statistical analysis, or were influenced by an antiburn bias. Current research suggests that timing of a burn is not as critical as ranchers have been led to believe and burning does not have to be restricted to a narrow window in late April. There is an absence of scientific evidence that burning earlier in the spring adversely affects forage production, plant species composition, soil moisture, or cattle weight gain. Although there is a need for research on the consequences of burning grazed pastures at different times of the year, expanding the window for burning earlier in the dormant season should help alleviate air quality issues downwind of the burned areas and potentially be beneficial to ranchers. © 2016 Society for Range Management. Published by Elsevier Inc. All rights reserved.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information

    Evaluation of fly ash reactivity from incineration of hazardous waste in lime pastes

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    The annual global production of fly ash is estimated at about 780 million tons per year and has been used successfully in the cement industry for more than 50 years, mainly as a mineral additive in Portland cement and also as a component of mixed cement. In this work, the ash reactivity from hazardous waste as supplementary cement material was evaluated. For this, the ashes reactivity in lime pastes was analyzed, centered on thermogravimetric tests as a characterization technique to determine the phases present. Part of the ashes of hazardous waste was pretreated, in order to eliminate chlorides and sulfates from the incineration process. The ashes were characterized by means of DRX and FRX, finding low content of SiO2 and Al2O3 in the ashes of hazardous residues. The pastes were prepared according to the ASTM C-305 standard, using a water/lime ratio of 0.4. The hydration process was stopped with acetone at the ages of 1, 3, 7, 14, 28 and 56 days. It can be concluded that only mixtures of untreated hazardous waste ash are more attractive to be used as replacements in the production of construction inputs. Copyright © 2019, AIDIC Servizi S.r.l

    Tecniche di linearizzazione di sistemi di trasmissione IM-DD per migliorare i benefici della equalizzazione elettronica

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    We report two techniques to linearize IM-DD systems in order to better exploit the performance of a linear electronic equalizer. Computer simulations proved that the maximum reachable distance can be greatly extended

    Square root strategy: a novel method to linearize an optical communication system with electronic equalizers

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    We demonstrate a non-linear function after the photodetector that linearizes dispersion-limited IM-DD systems, enhancing the performance of linear electronic equalization. Results showed a clear improvement in terms of chromatic dispersion tolerance
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