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- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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- Kato, Norihiro, et al.
(author)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Journal article (peer-reviewed)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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- Gross, Sean M., et al.
(author)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Journal article (peer-reviewed)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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- Ramirez Lopez, Pavel Ernesto, et al.
(author)
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A novel approach for coupling slag infiltration to metal flow, solidification and mold oscillation on a 3d model for continuous casting of slabs
- 2012
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In: AISTech - Iron and Steel Technology Conference Proceedings. - 9781935117247 ; , s. 1259-1267
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Conference paper (peer-reviewed)abstract
- This work presents a novel modeling methodology which allows one to predict slag infiltration in a 3D slab model by coupling the slag behavior with the metal flow, heat transfer, oscillation and solidification within the mold. The model is able to describe the dynamic behavior of liquid/solid slag in the shell mold gap and the bed, as well as its effects on heat extraction and shell formation. This paper also illustrates both the application of the model to industrial practice and the challenges faced during its implementation. Furthermore, the model allows one to predict the conditions leading to irregular shell growth, which is likely to generate defects such as cracking and bulging. It also provides, at the same time, a more fundamental understanding of the mechanisms responsible for defect formation.
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- Ramirez Lopez, Pavel Ernesto, et al.
(author)
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Key Lubrication Concepts to Understand the Role of Flow, Heat Transfer and Solidification for Modelling Defect Formation during Continuous Casting
- 2018
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In: ISIJ International. - : IRON STEEL INST JAPAN KEIDANREN KAIKAN. - 0915-1559 .- 1347-5460. ; 58:2, s. 201-210
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Journal article (peer-reviewed)abstract
- Surface defects are recurrent problems during Continuous Casting of steel due to the introduction of new grades that are often difficult to cast, as well as the everlasting pursuit for higher quality and improved yield. Accordingly, numerical modelling has become a ubiquitous tool to analyse the formation mechanisms of such defects. However, industrial application of simulations is often hampered by oversimplifications and omissions of important process details such as variations in material properties, specific casting practices or shortcomings regarding fundamental metallurgical concepts. The present manuscript seeks to create awareness on these issues by visiting key notions such as slag infiltration, interfacial resistance and Lubrication Index. This is done from a conceptual point of view based on industrial observations and numerical modelling experiences. The latter allows a re-formulation of outdated concepts and misconceptions regarding the influence of fluid flow, heat transfer and solidification on lubrication and defect formation. Additionally, the manuscript addresses common challenges and constraints that occur during industrial implementation of numerical models such as the lack of high -temperature material data for slags. Finally, the manuscript provides examples of improvements on product quality and process stability that can be achieved through a holistic approach which combines modelling with laboratory tests, experiences from operators and direct plant measurements.
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