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Author

Nicholas Thomas

Other affiliations: General Electric
Bio: Nicholas Thomas is an academic researcher from GE Healthcare. The author has contributed to research in topics: Cell cycle & Cell cycle phase. The author has an hindex of 11, co-authored 30 publications receiving 548 citations. Previous affiliations of Nicholas Thomas include General Electric.

Papers
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Journal ArticleDOI
TL;DR: The ability to simultaneously track cell cycle phase and cell motion at the single cell level is demonstrated in a model-based approach to characterize the four phases of the cell cycle G1, S, G2, and M.

151 citations

Journal ArticleDOI
TL;DR: This study is the first to apply multi-parameter phenotypic profiling and clustering techniques commonly used for high-content imaging and microarray data to the analysis of electrophysiology data obtained by multi-electrode array (MEA) analysis of hESC-CM.

137 citations

Journal ArticleDOI
06 Feb 2015-PLOS ONE
TL;DR: A novel approach to rapidly and efficiently down regulate pluripotency genes during initiation of differentiation to DE cells by addition of dimethyl sulfoxide (DMSO) to Activin A-based culture medium is presented and its effects on the downstream differentiation to hepatocyte-like cells are reported.
Abstract: Background Definitive endoderm (DE) is one of the three germ layers which during in vivo vertebrate development gives rise to a variety of organs including liver, lungs, thyroid and pancreas; consequently efficient in vitro initiation of stem cell differentiation to DE cells is a prerequisite for successful cellular specification to subsequent DE-derived cell types [1, 2]. In this study we present a novel approach to rapidly and efficiently down regulate pluripotency genes during initiation of differentiation to DE cells by addition of dimethyl sulfoxide (DMSO) to Activin A-based culture medium and report its effects on the downstream differentiation to hepatocyte-like cells. Materials and Methods Human embryonic stem cells (hESC) were differentiated to DE using standard methods in medium supplemented with 100ng/ml of Activin A and compared to cultures where DE specification was additionally enhanced with different concentrations of DMSO. DE cells were subsequently primed to generate hepatic-like cells to investigate whether the addition of DMSO during formation of DE improved subsequent expression of hepatic markers. A combination of flow cytometry, real-time quantitative reverse PCR and immunofluorescence was applied throughout the differentiation process to monitor expression of pluripotency (POUF5/OCT4 & NANOG), definitive endoderm (SOX17, CXCR4 & GATA4) and hepatic (AFP & ALB) genes to generate differentiation stage-specific signatures. Results Addition of DMSO to the Activin A-based medium during DE specification resulted in rapid down regulation of the pluripotency genes OCT4 and NANOG, accompanied by an increase expression of the DE genes SOX17, CXCR4 and GATA4. Importantly, the expression level of ALB in DMSO-treated cells was also higher than in cells which were differentiated to the DE stage via standard Activin A treatment.

61 citations

Journal ArticleDOI
Nicholas Thomas1
TL;DR: High-content screening has become a highly developed approach to obtaining richly descriptive quantitative phenotypic data using automated microscopy and is now widely recognized as providing an efficient and effective approach to large-scale programs investigating cell biology in situ and in context.
Abstract: In the past decade, high-content screening has become a highly developed approach to obtaining richly descriptive quantitative phenotypic data using automated microscopy. From early use in drug screening, the technique has evolved to embrace a diverse range of applications in both academic and industrial sectors and is now widely recognized as providing an efficient and effective approach to large-scale programs investigating cell biology in situ and in context.

47 citations

Proceedings ArticleDOI
06 Apr 2006
TL;DR: A set of image analysis methods designed to automatically segment nuclei in 2D time-lapse images by segmenting the spatio-temporal volume using level sets is described.
Abstract: Automated analysis of live cells over extended time periods requires both novel assays and automated image analysis algorithms. Among other applications, this is necessary for studying the effect of inhibitor compounds which are designed to block the replication of cancerous cells in a high-throughput environment. Due to their toxicity, fluorescent dyes cannot be used to mark nuclei. Instead, the cell cycle itself may be marked with a fluorescent protein. This paper describes a set of image analysis methods designed to automatically segment nuclei in 2D time-lapse images. Since each nucleus is unstained, it needs to be segmented from the surrounding stained cytoplasm, and since the appearance of each cell depends on its stage in the cell cycle, standard image processing techniques cannot be used for localization. This paper addresses these challenges by segmenting the spatio-temporal volume using level sets. Experimental results show the promise of this approach.

29 citations


Cited by
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Patent
Jong Hwan Kim1
13 Mar 2015
TL;DR: In this article, a mobile terminal including a body; a touchscreen provided to a front and extending to side of the body and configured to display content; and a controller configured to detect one side of a body when it comes into contact with a side of an external terminal, display a first area on the touchscreen corresponding to a contact area of body and the external terminal and a second area including the content.
Abstract: A mobile terminal including a body; a touchscreen provided to a front and extending to side of the body and configured to display content; and a controller configured to detect one side of the body comes into contact with one side of an external terminal, display a first area on the touchscreen corresponding to a contact area of the body and the external terminal and a second area including the content, receive an input of moving the content displayed in the second area to the first area, display the content in the first area, and share the content in the first area with the external terminal.

1,441 citations

Journal ArticleDOI
TL;DR: High-throughput screening (HTS) assays enable the testing of large numbers of chemical substances for activity in diverse areas of biology as mentioned in this paper, including signal transduction pathways and complex networks functioning in cellular environments.
Abstract: High-throughput screening (HTS) assays enable the testing of large numbers of chemical substances for activity in diverse areas of biology. The biological responses measured in HTS assays span isolated biochemical systems containing purified receptors or enzymes to signal transduction pathways and complex networks functioning in cellular environments. This Review addresses factors that need to be considered when implementing assays for HTS and is aimed particularly at investigators new to this field. We discuss assay design strategies, the major detection technologies and examples of HTS assays for common target classes, cellular pathways and simple cellular phenotypes. We conclude with special considerations for configuring sensitive, robust, informative and economically feasible HTS assays.

564 citations

Journal ArticleDOI
TL;DR: A comprehensive summary of the recent state-of-the-art nucleus/cell segmentation approaches on different types of microscopy images including bright-field, phase-contrast, differential interference contrast, fluorescence, and electron microscopies is provided.
Abstract: Digital pathology and microscopy image analysis is widely used for comprehensive studies of cell morphology or tissue structure. Manual assessment is labor intensive and prone to interobserver variations. Computer-aided methods, which can significantly improve the objectivity and reproducibility, have attracted a great deal of interest in recent literature. Among the pipeline of building a computer-aided diagnosis system, nucleus or cell detection and segmentation play a very important role to describe the molecular morphological information. In the past few decades, many efforts have been devoted to automated nucleus/cell detection and segmentation. In this review, we provide a comprehensive summary of the recent state-of-the-art nucleus/cell segmentation approaches on different types of microscopy images including bright-field, phase-contrast, differential interference contrast, fluorescence, and electron microscopies. In addition, we discuss the challenges for the current methods and the potential future work of nucleus/cell detection and segmentation.

430 citations

Journal ArticleDOI
TL;DR: It is demonstrated that a newly developed optical interferometric technique, known as spatial light interference microscopy, can measure the cell dry mass of many individual adherent cells in various conditions, over spatial scales from micrometers to millimeters, temporal scales ranging from seconds to days, and cell types ranging from bacteria to mammalian cells.
Abstract: Determining the growth patterns of single cells offers answers to some of the most elusive questions in contemporary cell biology: how cell growth is regulated and how cell size distributions are maintained. For example, a linear growth in time implies that there is no regulation required to maintain homeostasis; an exponential pattern indicates the opposite. Recently, there has been great effort to measure single cells using microelectromechanical systems technology, and several important questions have been explored. However, a unified, easy-to-use methodology to measure the growth rate of individual adherent cells of various sizes has been lacking. Here we demonstrate that a newly developed optical interferometric technique, known as spatial light interference microscopy, can measure the cell dry mass of many individual adherent cells in various conditions, over spatial scales from micrometers to millimeters, temporal scales ranging from seconds to days, and cell types ranging from bacteria to mammalian cells. We found evidence of exponential growth in Escherichia coli, which agrees very well with other recent reports. Perhaps most importantly, combining spatial light interference microscopy with fluorescence imaging provides a unique method for studying cell cycle-dependent growth. Thus, by using a fluorescent reporter for the S phase, we measured single cell growth over each phase of the cell cycle in human osteosarcoma U2OS cells and found that the G2 phase exhibits the highest growth rate, which is mass-dependent and can be approximated by an exponential.

418 citations

Journal ArticleDOI
TL;DR: This paper presents a fully automated multi-target tracking system that can efficiently cope with these challenges while simultaneously tracking and analyzing thousands of cells observed using time-lapse phase contrast microscopy.

415 citations