86 research outputs found

    SeeBridge Next Generation Bridge Inspection: Overview, Information Delivery Manual and Model View Definition

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    Innovative solutions for rapid and intelligent survey and assessment methods are required in maintenance, repair, retrofit and rebuild of enormous numbers of bridges in service throughout the world. Motivated by this need, a next-generation integrated bridge inspection system, called SeeBridge, has been proposed. An Information Delivery Manual (IDM) was compiled to specify the technical components, activities and information exchanges in the SeeBridge process, and a Model View Definition (MVD) was prepared to specify the data exchange schema to serve the IDM. The MVD was bound to the IFC4 Add2 data schema standard. The IDM and MVD support research and development of the system by rigorously defining the information and data that structure bridge engineers' knowledge. The SeeBridge process is mapped, parts of the data repositories are presented, and the future use of the IDM is discussed. The development underlines the real potential for automated inspection of infrastructure at large, because it demonstrates that the hurdles in the way of automated acquisition of detailed and semantically rich models of existing infrastructure are computational in nature, not instrumental, and are surmountable with existing technologies

    The bone-specific Runx2-P1 promoter displays conserved three-dimensional chromatin structure with the syntenic Supt3h promoter

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    Three-dimensional organization of chromatin is fundamental for transcriptional regulation. Tissue-specific transcriptional programs are orchestrated by transcription factors and epigenetic regulators. The RUNX2 transcription factor is required for differentiation of precursor cells into mature osteoblasts. Although organization and control of the bone-specific Runx2-P1 promoter have been studied extensively, long-range regulation has not been explored. In this study, we investigated higher-order organization of the Runx2-P1 promoter during osteoblast differentiation. Mining the ENCODE database revealed interactions between Runx2-P1 and Supt3h promoters in several non-mesenchymal human cell lines. Supt3h is a ubiquitously expressed gene located within the first intron of Runx2. These two genes show shared synteny across species from humans to sponges. Chromosome conformation capture analysis in the murine pre-osteoblastic MC3T3-E1 cell line revealed increased contact frequency between Runx2-P1 and Supt3h promoters during differentiation. This increase was accompanied by enhanced DNaseI hypersensitivity along with RUNX2 and CTCF binding at the Supt3h promoter. Furthermore, interplasmid-3C and luciferase reporter assays showed that the Supt3h promoter can modulate Runx2-P1 activity via direct association. Taken together, our data demonstrate physical proximity between Runx2-P1 and Supt3h promoters, consistent with their syntenic nature. Importantly, we identify the Supt3h promoter as a potential regulator of the bone-specific Runx2-P1 promoter. Acids Research

    SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells

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    The packaging of DNA into chromatin plays an important role in transcriptional regulation and nuclear processes. Brahma-related gene-1 SMARCA4 (also known as BRG1), the essential ATPase subunit of the mammalian SWI/SNF chromatin remodeling complex, uses the energy from ATP hydrolysis to disrupt nucleosomes at target regions. Although the transcriptional role of SMARCA4 at gene promoters is well-studied, less is known about its role in higher-order genome organization. SMARCA4 knockdown in human mammary epithelial MCF-10A cells resulted in 176 up-regulated genes, including many related to lipid and calcium metabolism, and 1292 down-regulated genes, some of which encode extracellular matrix (ECM) components that can exert mechanical forces and affect nuclear structure. ChIP-seq analysis of SMARCA4 localization and SMARCA4-bound super-enhancers demonstrated extensive binding at intergenic regions. Furthermore, Hi-C analysis showed extensive SMARCA4-mediated alterations in higher-order genome organization at multiple resolutions. First, SMARCA4 knockdown resulted in clustering of intra- and inter-subtelomeric regions, demonstrating a novel role for SMARCA4 in telomere organization. SMARCA4 binding was enriched at topologically associating domain (TAD) boundaries, and SMARCA4 knockdown resulted in weakening of TAD boundary strength. Taken together, these findings provide a dynamic view of SMARCA4-dependent changes in higher-order chromatin organization and gene expression, identifying SMARCA4 as a novel component of chromatin organization

    Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells

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    BACKGROUND: Higher-order chromatin structure is often perturbed in cancer and other pathological states. Although several genetic and epigenetic differences have been charted between normal and breast cancer tissues, changes in higher-order chromatin organization during tumorigenesis have not been fully explored. To probe the differences in higher-order chromatin structure between mammary epithelial and breast cancer cells, we performed Hi-C analysis on MCF-10A mammary epithelial and MCF-7 breast cancer cell lines. RESULTS: Our studies reveal that the small, gene-rich chromosomes chr16 through chr22 in the MCF-7 breast cancer genome display decreased interaction frequency with each other compared to the inter-chromosomal interaction frequency in the MCF-10A epithelial cells. Interestingly, this finding is associated with a higher occurrence of open compartments on chr16-22 in MCF-7 cells. Pathway analysis of the MCF-7 up-regulated genes located in altered compartment regions on chr16-22 reveals pathways related to repression of WNT signaling. There are also differences in intra-chromosomal interactions between the cell lines; telomeric and sub-telomeric regions in the MCF-10A cells display more frequent interactions than are observed in the MCF-7 cells. CONCLUSIONS: We show evidence of an intricate relationship between chromosomal organization and gene expression between epithelial and breast cancer cells. Importantly, this work provides a genome-wide view of higher-order chromatin dynamics and a resource for studying higher-order chromatin interactions in two cell lines commonly used to study the progression of breast cancer

    Malignant melanoma of the stomach presenting in a woman: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Malignant melanoma is reported to metastasize to all organs of the human body. Although it is common for it to metastasize to the gastrointestinal tract, a melanoma located primarily in the gastric mucosa is an uncommon tumor. Gastrointestinal metastases are rarely diagnosed before death with radiological and endoscopic techniques.</p> <p>Case presentation</p> <p>In this case report the clinical course and treatment of a woman with melanoma of the stomach, without any other detectable primary lesion, is presented and discussed. A 55-year-old Turkish woman presented to our clinic with complaints of muscle pain and bone pain in the left side of her chest. During an upper gastrointestinal system endoscopy, dark cherry-colored, light elevated, round-shaped lesions were taken from her gastric fundus and from the first part of her duodenum. Biopsies from these samples were determined to be malignant melanoma by the pathologist.</p> <p>Conclusion</p> <p>Metastatic malignant melanoma cases should be examined through endoscopy for gastrointestinal metastases.</p

    The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

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    Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

    Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C>T polymorphism in non-small cell lung carcinoma

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    Background: Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC.Publisher's Versio

    Effect of Microwave Frying on Acrylamide Generation, Mass Transfer, Color, and Texture in French Fries

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    [EN] The objective of this work was to evaluate the effect of microwave power on acrylamide generation, as well as moisture and oil fluxes and quality attributes of microwave-fried potatoes. Concretely, 25 g of potato strips, in 250 mL of fresh oil (at room temperature), were subjected to three different microwave powers (315, 430, and 600 W) in a conventional microwave oven. Microwave frying resulted in an acrylamide reduction ranged from 37 to 83% compared to deep-oil frying. Microwave-fried French fries presented lower moisture and higher fat content than deep-oil fried potatoes. Concretely, microwave-fried potatoes presented values of moisture and texture more similar to potato chips than French fries, nonetheless with lower fat levels (less than 20 g/100 g wb) and acrylamide content (lower than 100 ¿g/kg wb) at the reference time. This study presents an alternative way of frying to address the production of healthier potato chips.The authors would like to thank the Universitat Politecnica de Valencia for the PhD scholarship given to Mariola Sansano Tomas.Sansano, M.; De Los Reyes Cánovas, R.; Andrés Grau, AM.; Heredia Gutiérrez, AB. (2018). Effect of Microwave Frying on Acrylamide Generation, Mass Transfer, Color, and Texture in French Fries. Food and Bioprocess Technology. 11(10):1934-1939. doi:10.1007/s11947-018-2144-zS193419391110AACC. (1995). Approved methods of the American association of cereal chemists (9th ed.). St. Paul: The Association.Adedeji, A. A., Ngadi, M. O., & Raghavan, G. S. V. (2009). Kinetics of mass transfer in microwave precooked and deep-fat fried chicken nuggets. Journal of Food Engineering, 91(1), 146–153.Ahrné, L., Andersson, C.-G., Floberg, P., Rosén, J., & Lingnert, H. (2007). 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    Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

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    Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer
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