WorldWideScience

Sample records for high-content screening hcs

  1. The development of high-content screening (HCS) technology and its importance to drug discovery.

    Science.gov (United States)

    Fraietta, Ivan; Gasparri, Fabio

    2016-01-01

    High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development. Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology. Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.

  2. HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

    Science.gov (United States)

    Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

    2013-01-01

    High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable

  3. High content screening in microfluidic devices

    Science.gov (United States)

    Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

    2011-01-01

    Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

  4. High Content Screening: Understanding Cellular Pathway

    International Nuclear Information System (INIS)

    Mohamed Zaffar Ali Mohamed Amiroudine; Daryl Jesus Arapoc; Zainah Adam; Shafii Khamis

    2015-01-01

    High content screening (HCS) is the convergence between cell-based assays, high-resolution fluorescence imaging, phase-contrast imaging of fixed- or live-cell assays, tissues and small organisms. It has been widely adopted in the pharmaceutical and biotech industries for target identification and validation and as secondary screens to reveal potential toxicities or to elucidate a drugs mechanism of action. By using the ImageXpress® Micro XLS System HCS, the complex network of key players controlling proliferation and apoptosis can be reduced to several sentinel markers for analysis. Cell proliferation and apoptosis are two key areas in cell biology and drug discovery research. Understanding the signaling pathways in cell proliferation and apoptosis is important for new therapeutic discovery because the imbalance between these two events is predominant in the progression of many human diseases, including cancer. The DNA binding dye DAPI is used to determine the nuclear size and nuclear morphology as well as cell cycle phases by DNA content. Images together with MetaXpress® analysis results provide a convenient and easy to use solution to high volume image management. In particular, HCS platform is beginning to have an important impact on early drug discovery, basic research in systems cell biology, and is expected to play a role in personalized medicine or revealing off-target drug effects. (author)

  5. Automation in high-content flow cytometry screening.

    Science.gov (United States)

    Naumann, U; Wand, M P

    2009-09-01

    High-content flow cytometric screening (FC-HCS) is a 21st Century technology that combines robotic fluid handling, flow cytometric instrumentation, and bioinformatics software, so that relatively large numbers of flow cytometric samples can be processed and analysed in a short period of time. We revisit a recent application of FC-HCS to the problem of cellular signature definition for acute graft-versus-host-disease. Our focus is on automation of the data processing steps using recent advances in statistical methodology. We demonstrate that effective results, on par with those obtained via manual processing, can be achieved using our automatic techniques. Such automation of FC-HCS has the potential to drastically improve diagnosis and biomarker identification.

  6. CellProfiler and KNIME: open source tools for high content screening.

    Science.gov (United States)

    Stöter, Martin; Niederlein, Antje; Barsacchi, Rico; Meyenhofer, Felix; Brandl, Holger; Bickle, Marc

    2013-01-01

    High content screening (HCS) has established itself in the world of the pharmaceutical industry as an essential tool for drug discovery and drug development. HCS is currently starting to enter the academic world and might become a widely used technology. Given the diversity of problems tackled in academic research, HCS could experience some profound changes in the future, mainly with more imaging modalities and smart microscopes being developed. One of the limitations in the establishment of HCS in academia is flexibility and cost. Flexibility is important to be able to adapt the HCS setup to accommodate the multiple different assays typical of academia. Many cost factors cannot be avoided, but the costs of the software packages necessary to analyze large datasets can be reduced by using Open Source software. We present and discuss the Open Source software CellProfiler for image analysis and KNIME for data analysis and data mining that provide software solutions which increase flexibility and keep costs low.

  7. High content screening: science, techniques, and applications

    National Research Council Canada - National Science Library

    Haney, Steven A

    2008-01-01

    ... Workflow - Flexibility is the Key 1.7.6 HCS is Hard - How Do I Learn It and Become Proficient at It? 1.5 1.6 1.7 References 3 4 5 8 9 10 11 11 12 13 13 15 16 18 18 19 20 20 21 21 22 viiviii CONTEN...

  8. Characterization of SPAD Array for Multifocal High-Content Screening Applications

    Directory of Open Access Journals (Sweden)

    Anthony Tsikouras

    2016-10-01

    Full Text Available Current instruments used to detect specific protein-protein interactions in live cells for applications in high-content screening (HCS are limited by the time required to measure the lifetime. Here, a 32 × 1 single-photon avalanche diode (SPAD array was explored as a detector for fluorescence lifetime imaging (FLIM in HCS. Device parameters and characterization results were interpreted in the context of the application to determine if the SPAD array could satisfy the requirements of HCS-FLIM. Fluorescence lifetime measurements were performed using a known fluorescence standard; and the recovered fluorescence lifetime matched literature reported values. The design of a theoretical 32 × 32 SPAD array was also considered as a detector for a multi-point confocal scanning microscope.

  9. Impact of image segmentation on high-content screening data quality for SK-BR-3 cells

    Directory of Open Access Journals (Sweden)

    Li Yizheng

    2007-09-01

    Full Text Available Abstract Background High content screening (HCS is a powerful method for the exploration of cellular signalling and morphology that is rapidly being adopted in cancer research. HCS uses automated microscopy to collect images of cultured cells. The images are subjected to segmentation algorithms to identify cellular structures and quantitate their morphology, for hundreds to millions of individual cells. However, image analysis may be imperfect, especially for "HCS-unfriendly" cell lines whose morphology is not well handled by current image segmentation algorithms. We asked if segmentation errors were common for a clinically relevant cell line, if such errors had measurable effects on the data, and if HCS data could be improved by automated identification of well-segmented cells. Results Cases of poor cell body segmentation occurred frequently for the SK-BR-3 cell line. We trained classifiers to identify SK-BR-3 cells that were well segmented. On an independent test set created by human review of cell images, our optimal support-vector machine classifier identified well-segmented cells with 81% accuracy. The dose responses of morphological features were measurably different in well- and poorly-segmented populations. Elimination of the poorly-segmented cell population increased the purity of DNA content distributions, while appropriately retaining biological heterogeneity, and simultaneously increasing our ability to resolve specific morphological changes in perturbed cells. Conclusion Image segmentation has a measurable impact on HCS data. The application of a multivariate shape-based filter to identify well-segmented cells improved HCS data quality for an HCS-unfriendly cell line, and could be a valuable post-processing step for some HCS datasets.

  10. G protein-coupled receptor internalization assays in the high-content screening format.

    Science.gov (United States)

    Haasen, Dorothea; Schnapp, Andreas; Valler, Martin J; Heilker, Ralf

    2006-01-01

    High-content screening (HCS), a combination of fluorescence microscopic imaging and automated image analysis, has become a frequently applied tool to study test compound effects in cellular disease-modeling systems. This chapter describes the measurement of G protein-coupled receptor (GPCR) internalization in the HCS format using a high-throughput, confocal cellular imaging device. GPCRs are the most successful group of therapeutic targets on the pharmaceutical market. Accordingly, the search for compounds that interfere with GPCR function in a specific and selective way is a major focus of the pharmaceutical industry today. This chapter describes methods for the ligand-induced internalization of GPCRs labeled previously with either a fluorophore-conjugated ligand or an antibody directed against an N-terminal tag of the GPCR. Both labeling techniques produce robust assay formats. Complementary to other functional GPCR drug discovery assays, internalization assays enable a pharmacological analysis of test compounds. We conclude that GPCR internalization assays represent a valuable medium/high-throughput screening format to determine the cellular activity of GPCR ligands.

  11. High-content screening in zebrafish embryos identifies butafenacil as a potent inducer of anemia.

    Directory of Open Access Journals (Sweden)

    Jessica K Leet

    Full Text Available Using transgenic zebrafish (fli1:egfp that stably express enhanced green fluorescent protein (eGFP within vascular endothelial cells, we recently developed and optimized a 384-well high-content screening (HCS assay that enables us to screen and identify chemicals affecting cardiovascular development and function at non-teratogenic concentrations. Within this assay, automated image acquisition procedures and custom image analysis protocols are used to quantify body length, heart rate, circulation, pericardial area, and intersegmental vessel area within individual live embryos exposed from 5 to 72 hours post-fertilization. After ranking developmental toxicity data generated from the U.S. Environmental Protection Agency's (EPA's zebrafish teratogenesis assay, we screened 26 of the most acutely toxic chemicals within EPA's ToxCast Phase-I library in concentration-response format (0.05-50 µM using this HCS assay. Based on this screen, we identified butafenacil as a potent inducer of anemia, as exposure from 0.39 to 3.125 µM butafenacil completely abolished arterial circulation in the absence of effects on all other endpoints evaluated. Butafenacil is an herbicide that inhibits protoporphyrinogen oxidase (PPO--an enzyme necessary for heme production in vertebrates. Using o-dianisidine staining, we then revealed that severe butafenacil-induced anemia in zebrafish was due to a complete loss of hemoglobin following exposure during early development. Therefore, six additional PPO inhibitors within the ToxCast Phase-I library were screened to determine whether anemia represents a common adverse outcome for these herbicides. Embryonic exposure to only one of these PPO inhibitors--flumioxazin--resulted in a similar phenotype as butafenacil, albeit not as severe as butafenacil. Overall, this study highlights the potential utility of this assay for (1 screening chemicals for cardiovascular toxicity and (2 prioritizing chemicals for future hypothesis

  12. Development and Application of High-Content Biological Screening for Modulators of NET Production

    Directory of Open Access Journals (Sweden)

    Ilaria J. Chicca

    2018-03-01

    Full Text Available Neutrophil extracellular traps (NETs are DNA-based antimicrobial web-like structures whose release is predominantly mediated by reactive oxygen species (ROS; their purpose is to combat infections. However, unbalanced NET production and clearance is involved in tissue injury, circulation of auto-antibodies and development of several chronic diseases. Currently, there is lack of agreement regarding the high-throughput methods available for NET investigation. This study, therefore, aimed to develop and optimize a high-content analysis (HCA approach, which can be applied for the assay of NET production and for the screening of compounds involved in the modulation of NET release. A suitable paraformaldehyde fixation protocol was established to enable HCA of neutrophils and NETs. Bespoke and in-built bioinformatics algorithms were validated by comparison with standard low-throughput approaches for application in HCA of NETs. Subsequently, the optimized protocol was applied to high-content screening (HCS of a pharmaceutically derived compound library to identify modulators of NETosis. Of 56 compounds assessed, 8 were identified from HCS for further characterization of their effects on NET formation as being either inducers, inhibitors or biphasic modulators. The effects of these compounds on naïve neutrophils were evaluated by using specific assays for the induction of ROS and NET production, while their modulatory activity was validated in phorbol 12-myristate 13-acetate-stimulated neutrophils. Results indicated the involvement of glutathione reductase, Src family kinases, molecular-target-of-Rapamycin, and mitogen-activated-protein-kinase pathways in NET release. The compounds and pathways identified may provide targets for novel therapeutic approaches for treating NET-associated pathologies.

  13. iScreen: Image-Based High-Content RNAi Screening Analysis Tools.

    Science.gov (United States)

    Zhong, Rui; Dong, Xiaonan; Levine, Beth; Xie, Yang; Xiao, Guanghua

    2015-09-01

    High-throughput RNA interference (RNAi) screening has opened up a path to investigating functional genomics in a genome-wide pattern. However, such studies are often restricted to assays that have a single readout format. Recently, advanced image technologies have been coupled with high-throughput RNAi screening to develop high-content screening, in which one or more cell image(s), instead of a single readout, were generated from each well. This image-based high-content screening technology has led to genome-wide functional annotation in a wider spectrum of biological research studies, as well as in drug and target discovery, so that complex cellular phenotypes can be measured in a multiparametric format. Despite these advances, data analysis and visualization tools are still largely lacking for these types of experiments. Therefore, we developed iScreen (image-Based High-content RNAi Screening Analysis Tool), an R package for the statistical modeling and visualization of image-based high-content RNAi screening. Two case studies were used to demonstrate the capability and efficiency of the iScreen package. iScreen is available for download on CRAN (http://cran.cnr.berkeley.edu/web/packages/iScreen/index.html). The user manual is also available as a supplementary document. © 2014 Society for Laboratory Automation and Screening.

  14. Automated microscopy for high-content RNAi screening

    Science.gov (United States)

    2010-01-01

    Fluorescence microscopy is one of the most powerful tools to investigate complex cellular processes such as cell division, cell motility, or intracellular trafficking. The availability of RNA interference (RNAi) technology and automated microscopy has opened the possibility to perform cellular imaging in functional genomics and other large-scale applications. Although imaging often dramatically increases the content of a screening assay, it poses new challenges to achieve accurate quantitative annotation and therefore needs to be carefully adjusted to the specific needs of individual screening applications. In this review, we discuss principles of assay design, large-scale RNAi, microscope automation, and computational data analysis. We highlight strategies for imaging-based RNAi screening adapted to different library and assay designs. PMID:20176920

  15. Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

    Science.gov (United States)

    Persson, Mikael; Hornberg, Jorrit J

    2016-12-19

    High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

  16. A deep learning and novelty detection framework for rapid phenotyping in high-content screening

    Science.gov (United States)

    Sommer, Christoph; Hoefler, Rudolf; Samwer, Matthias; Gerlich, Daniel W.

    2017-01-01

    Supervised machine learning is a powerful and widely used method for analyzing high-content screening data. Despite its accuracy, efficiency, and versatility, supervised machine learning has drawbacks, most notably its dependence on a priori knowledge of expected phenotypes and time-consuming classifier training. We provide a solution to these limitations with CellCognition Explorer, a generic novelty detection and deep learning framework. Application to several large-scale screening data sets on nuclear and mitotic cell morphologies demonstrates that CellCognition Explorer enables discovery of rare phenotypes without user training, which has broad implications for improved assay development in high-content screening. PMID:28954863

  17. Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells

    Science.gov (United States)

    Nguyen, Minh M.; Dar, Javid A.; Ai, Junkui; Wang, Yujuan; Masoodi, Khalid Z.; Shun, Tongying; Shinde, Sunita; Camarco, Daniel P.; Hua, Yun; Huryn, Donna M.; Wilson, Gabriela Mustata; Lazo, John S.; Nelson, Joel B.; Wipf, Peter

    2016-01-01

    Abstract Patients with castration-resistant prostate cancer (CRPC) can be treated with abiraterone, a potent inhibitor of androgen synthesis, or enzalutamide, a second-generation androgen receptor (AR) antagonist, both targeting AR signaling. However, most patients relapse after several months of therapy and a majority of patients with relapsed CRPC tumors express the AR target gene prostate-specific antigen (PSA), suggesting that AR signaling is reactivated and can be targeted again to inhibit the relapsed tumors. Novel small molecules capable of inhibiting AR function may lead to urgently needed therapies for patients resistant to abiraterone, enzalutamide, and/or other previously approved antiandrogen therapies. Here, we describe a high-throughput high-content screening (HCS) campaign to identify small-molecule inhibitors of AR nuclear localization in the C4-2 CRPC cell line stably transfected with GFP-AR-GFP (2GFP-AR). The implementation of this HCS assay to screen a National Institutes of Health library of 219,055 compounds led to the discovery of 3 small molecules capable of inhibiting AR nuclear localization and function in C4-2 cells, demonstrating the feasibility of using this cell-based phenotypic assay to identify small molecules targeting the subcellular localization of AR. Furthermore, the three hit compounds provide opportunities to develop novel AR drugs with potential for therapeutic intervention in CRPC patients who have relapsed after treatment with antiandrogens, such as abiraterone and/or enzalutamide. PMID:27187604

  18. Development of automatic image analysis methods for high-throughput and high-content screening

    NARCIS (Netherlands)

    Di, Zi

    2013-01-01

    This thesis focuses on the development of image analysis methods for ultra-high content analysis of high-throughput screens where cellular phenotype responses to various genetic or chemical perturbations that are under investigation. Our primary goal is to deliver efficient and robust image analysis

  19. A probabilistic model for cell population phenotyping using HCS data.

    Directory of Open Access Journals (Sweden)

    Edouard Pauwels

    Full Text Available High Content Screening (HCS platforms allow screening living cells under a wide range of experimental conditions and give access to a whole panel of cellular responses to a specific treatment. The outcome is a series of cell population images. Within these images, the heterogeneity of cellular response to the same treatment leads to a whole range of observed values for the recorded cellular features. Consequently, it is difficult to compare and interpret experiments. Moreover, the definition of phenotypic classes at a cell population level remains an open question, although this would ease experiments analyses. In the present work, we tackle these two questions. The input of the method is a series of cell population images for which segmentation and cellular phenotype classification has already been performed. We propose a probabilistic model to represent and later compare cell populations. The model is able to fully exploit the HCS-specific information: "dependence structure of population descriptors" and "within-population variability". The experiments we carried out illustrate how our model accounts for this specific information, as well as the fact that the model benefits from considering them. We underline that these features allow richer HCS data analysis than simpler methods based on single cellular feature values averaged over each well. We validate an HCS data analysis method based on control experiments. It accounts for HCS specificities that were not taken into account by previous methods but have a sound biological meaning. Biological validation of previously unknown outputs of the method constitutes a future line of work.

  20. Active Learning Strategies for Phenotypic Profiling of High-Content Screens.

    Science.gov (United States)

    Smith, Kevin; Horvath, Peter

    2014-06-01

    High-content screening is a powerful method to discover new drugs and carry out basic biological research. Increasingly, high-content screens have come to rely on supervised machine learning (SML) to perform automatic phenotypic classification as an essential step of the analysis. However, this comes at a cost, namely, the labeled examples required to train the predictive model. Classification performance increases with the number of labeled examples, and because labeling examples demands time from an expert, the training process represents a significant time investment. Active learning strategies attempt to overcome this bottleneck by presenting the most relevant examples to the annotator, thereby achieving high accuracy while minimizing the cost of obtaining labeled data. In this article, we investigate the impact of active learning on single-cell-based phenotype recognition, using data from three large-scale RNA interference high-content screens representing diverse phenotypic profiling problems. We consider several combinations of active learning strategies and popular SML methods. Our results show that active learning significantly reduces the time cost and can be used to reveal the same phenotypic targets identified using SML. We also identify combinations of active learning strategies and SML methods which perform better than others on the phenotypic profiling problems we studied. © 2014 Society for Laboratory Automation and Screening.

  1. High-content screening of yeast mutant libraries by shotgun lipidomics

    DEFF Research Database (Denmark)

    Tarasov, Kirill; Stefanko, Adam; Casanovas, Albert

    2014-01-01

    To identify proteins with a functional role in lipid metabolism and homeostasis we designed a high-throughput platform for high-content lipidomic screening of yeast mutant libraries. To this end, we combined culturing and lipid extraction in 96-well format, automated direct infusion...... factor KAR4 precipitated distinct lipid metabolic phenotypes. These results demonstrate that the high-throughput shotgun lipidomics platform is a valid and complementary proxy for high-content screening of yeast mutant libraries....... nanoelectrospray ionization, high-resolution Orbitrap mass spectrometry, and a dedicated data processing framework to support lipid phenotyping across hundreds of Saccharomyces cerevisiae mutants. Our novel approach revealed that the absence of genes with unknown function YBR141C and YJR015W, and the transcription...

  2. Localization-based super-resolution imaging meets high-content screening.

    Science.gov (United States)

    Beghin, Anne; Kechkar, Adel; Butler, Corey; Levet, Florian; Cabillic, Marine; Rossier, Olivier; Giannone, Gregory; Galland, Rémi; Choquet, Daniel; Sibarita, Jean-Baptiste

    2017-12-01

    Single-molecule localization microscopy techniques have proven to be essential tools for quantitatively monitoring biological processes at unprecedented spatial resolution. However, these techniques are very low throughput and are not yet compatible with fully automated, multiparametric cellular assays. This shortcoming is primarily due to the huge amount of data generated during imaging and the lack of software for automation and dedicated data mining. We describe an automated quantitative single-molecule-based super-resolution methodology that operates in standard multiwell plates and uses analysis based on high-content screening and data-mining software. The workflow is compatible with fixed- and live-cell imaging and allows extraction of quantitative data like fluorophore photophysics, protein clustering or dynamic behavior of biomolecules. We demonstrate that the method is compatible with high-content screening using 3D dSTORM and DNA-PAINT based super-resolution microscopy as well as single-particle tracking.

  3. High content screening for G protein-coupled receptors using cell-based protein translocation assays

    DEFF Research Database (Denmark)

    Grånäs, Charlotta; Lundholt, Betina Kerstin; Heydorn, Arne

    2005-01-01

    G protein-coupled receptors (GPCRs) have been one of the most productive classes of drug targets for several decades, and new technologies for GPCR-based discovery promise to keep this field active for years to come. While molecular screens for GPCR receptor agonist- and antagonist-based drugs...... will continue to be valuable discovery tools, the most exciting developments in the field involve cell-based assays for GPCR function. Some cell-based discovery strategies, such as the use of beta-arrestin as a surrogate marker for GPCR function, have already been reduced to practice, and have been used...... as valuable discovery tools for several years. The application of high content cell-based screening to GPCR discovery has opened up additional possibilities, such as direct tracking of GPCRs, G proteins and other signaling pathway components using intracellular translocation assays. These assays provide...

  4. BioSig3D: High Content Screening of Three-Dimensional Cell Culture Models.

    Directory of Open Access Journals (Sweden)

    Cemal Cagatay Bilgin

    Full Text Available BioSig3D is a computational platform for high-content screening of three-dimensional (3D cell culture models that are imaged in full 3D volume. It provides an end-to-end solution for designing high content screening assays, based on colony organization that is derived from segmentation of nuclei in each colony. BioSig3D also enables visualization of raw and processed 3D volumetric data for quality control, and integrates advanced bioinformatics analysis. The system consists of multiple computational and annotation modules that are coupled together with a strong use of controlled vocabularies to reduce ambiguities between different users. It is a web-based system that allows users to: design an experiment by defining experimental variables, upload a large set of volumetric images into the system, analyze and visualize the dataset, and either display computed indices as a heatmap, or phenotypic subtypes for heterogeneity analysis, or download computed indices for statistical analysis or integrative biology. BioSig3D has been used to profile baseline colony formations with two experiments: (i morphogenesis of a panel of human mammary epithelial cell lines (HMEC, and (ii heterogeneity in colony formation using an immortalized non-transformed cell line. These experiments reveal intrinsic growth properties of well-characterized cell lines that are routinely used for biological studies. BioSig3D is being released with seed datasets and video-based documentation.

  5. High-content screening of small compounds on human embryonic stem cells.

    Science.gov (United States)

    Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

    2010-08-01

    Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

  6. A microfluidic array for high-content screening at whole-organism resolution

    Science.gov (United States)

    Migliozzi, D.; Cornaglia, M.; Mouchiroud, L.; Auwerx, J.; Gijs, M. A. M.

    2018-02-01

    A main step for the development and the validation of medical drugs is the screening on whole organisms, which gives the systemic information that is missing when using cellular models. Among the organisms of choice, Caenorhabditis elegansis a soil worm which catches the interest of researchers who study systemic physiopathology (e.g. metabolic and neurodegenerative diseases) because: (1) its large genetic homology with humans supports translational analysis; (2) worms are much easier to handle and grow in large amounts compared to rodents, for which (3) the costs and (4) the ethical concerns are substantial.C. elegansis therefore well suited for large screens, dose-response analysis and target-discovery involving an entire organism. We have developed and tested a microfluidic array for high-content screening, enabling the selection of small populations of its first larval stage in many separated chambers divided into channels for multiplexed screens. With automated protocols for feeding, drug administration and image acquisition, our chip enables the study of the nematodes throughout their entire lifespan. By using a paralyzing agent and a mitochondrial-stress inducer as case studies, we have demonstrated large field-of-view motility analysis, and worm-segmentation/signal-detection for mode-of-action quantification with genetically-encoded fluorescence reporters.

  7. Neuronal models for evaluation of proliferation in vitro using high content screening

    International Nuclear Information System (INIS)

    Mundy, William R.; Radio, Nicholas M.; Freudenrich, Theresa M.

    2010-01-01

    In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity (hazard identification). In order to identify potential developmental neurotoxicants, a battery of in vitro tests for neurodevelopmental processes such as cell proliferation, differentiation, growth, and synaptogenesis has been proposed. The development of in vitro approaches for toxicity testing will require choosing a model system that is appropriate to the endpoint of concern. This study compared several cell lines as models for neuronal proliferation. The sensitivities of neuronal cell lines derived from three species (PC12, rat; N1E-115, mouse; SH-SY5Y, human) to chemicals known to affect cell proliferation were assessed using a high content screening system. After optimizing conditions for cell growth in 96-well plates, proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating DNA during S phase. BrdU-labeled cells were detected by immunocytochemistry and cell counts were obtained using automated image acquisition and analysis. The three cell lines showed approximately 30-40% of the population in S phase after a 4 h pulse of BrdU. Exposure to the DNA polymerase inhibitor aphidicolin for 20 h prior to the 4 h pulse of BrdU significantly decreased proliferation in all three cell lines. The sensitivities of the cell lines were compared by exposure to eight chemicals known to affect proliferation (positive controls) and determination of the concentration inhibiting proliferation by 50% of control (I 50 ). PC12 cells were the most sensitive to chemicals; 6 out of 8 chemicals (aphidicolin, cadmium, cytosine arabinoside, dexamethasone, 5-fluorouracil, and methylmercury) inhibited proliferation at the concentrations tested. SH-SY5Y cells were somewhat less sensitive to chemical effects, with five out of eight chemicals inhibiting proliferation; dexamethasone had no effect, and cadmium

  8. A high content screening assay to predict human drug-induced liver injury during drug discovery.

    Science.gov (United States)

    Persson, Mikael; Løye, Anni F; Mow, Tomas; Hornberg, Jorrit J

    2013-01-01

    Adverse drug reactions are a major cause for failures of drug development programs, drug withdrawals and use restrictions. Early hazard identification and diligent risk avoidance strategies are therefore essential. For drug-induced liver injury (DILI), this is difficult using conventional safety testing. To reduce the risk for DILI, drug candidates with a high risk need to be identified and deselected. And, to produce drug candidates without that risk associated, risk factors need to be assessed early during drug discovery, such that lead series can be optimized on safety parameters. This requires methods that allow for medium-to-high throughput compound profiling and that generate quantitative results suitable to establish structure-activity-relationships during lead optimization programs. We present the validation of such a method, a novel high content screening assay based on six parameters (nuclei counts, nuclear area, plasma membrane integrity, lysosomal activity, mitochondrial membrane potential (MMP), and mitochondrial area) using ~100 drugs of which the clinical hepatotoxicity profile is known. We find that a 100-fold TI between the lowest toxic concentration and the therapeutic Cmax is optimal to classify compounds as hepatotoxic or non-hepatotoxic, based on the individual parameters. Most parameters have ~50% sensitivity and ~90% specificity. Drugs hitting ≥2 parameters at a concentration below 100-fold their Cmax are typically hepatotoxic, whereas non-hepatotoxic drugs typically hit based on nuclei count, MMP and human Cmax, we identified an area without a single false positive, while maintaining 45% sensitivity. Hierarchical clustering using the multi-parametric dataset roughly separates toxic from non-toxic compounds. We employ the assay in discovery projects to prioritize novel compound series during hit-to-lead, to steer away from a DILI risk during lead optimization, for risk assessment towards candidate selection and to provide guidance of safe

  9. Visible-to-near IR quantum dot-based hypermulticolor high-content screening of herbal medicines for the efficacy monitoring of hair growth promotion and hair loss inhibition.

    Science.gov (United States)

    Kim, Min Jung; Lim, Chaeyun; Lee, Jun Young; Im, Kyung Ran; Yoon, Kyung-Sup; Song, Joon Myong

    2013-04-01

    There is a growing interest in alopecia prevention strategies, as the number of alopecia patients is increasing. We examine the efficacy of herbal medicine for hair growth promotion/hair loss inhibition in two cell lines via Western blot and high-content screening (HCS). Nine herbal extracts were obtained from three different herbal medicine mixtures using 3 different extraction methods. Five target proteins-IGF-1 (insulin-like growth factor-1), TGF-β2 (transforming growth factor-β2), VEGF (vascular endothelial growth factor), DKK-1 (Dickkopf-1), and Wnt5α-were observed for the assessment of hair growth promotion/hair loss inhibition efficacy. The efficacies of nine extracts were compared with minoxidil as control. Efficacy was defined as a rise in the expression levels of IGF-1, VEGF, and Wnt5α but a decrease in DKK-1 and TGF-β2. Intracellular concurrent imaging of these proteins was successfully achieved using HCS, employing visible-to-near infrared probing based on quantum-antibody conjugates and hypermulticolor imaging.

  10. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    International Nuclear Information System (INIS)

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian; Ansari, Nariman; Esner, Milan; Bickle, Marc; Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H.; Parczyk, Karsten; Prechtl, Stefan; Steigemann, Patrick

    2014-01-01

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high-content

  11. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Ansari, Nariman [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Esner, Milan; Bickle, Marc [Max Planck Institute of Molecular Cell Biology and Genetics, High-Throughput Technology Development Studio (TDS), Dresden (Germany); Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H. [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Parczyk, Karsten; Prechtl, Stefan [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Steigemann, Patrick, E-mail: Patrick.Steigemann@bayer.com [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany)

    2014-04-15

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high-content

  12. High-content phenotypic screening and triaging strategy to identify small molecules driving oligodendrocyte progenitor cell differentiation.

    Science.gov (United States)

    Peppard, Jane V; Rugg, Catherine A; Smicker, Matthew A; Powers, Elaine; Harnish, Erica; Prisco, Joy; Cirovic, Dragan; Wright, Paul S; August, Paul R; Chandross, Karen J

    2015-03-01

    Multiple Sclerosis is a demyelinating disease of the CNS and the primary cause of neurological disability in young adults. Loss of myelinating oligodendrocytes leads to neuronal dysfunction and death and is an important contributing factor to this disease. Endogenous oligodendrocyte precursor cells (OPCs), which on differentiation are responsible for replacing myelin, are present in the adult CNS. As such, therapeutic agents that can stimulate OPCs to differentiate and remyelinate demyelinated axons under pathologic conditions may improve neuronal function and clinical outcome. We describe the details of an automated, cell-based, morphometric-based, high-content screen that is used to identify small molecules eliciting the differentiation of OPCs after 3 days. Primary screening was performed using rat CG-4 cells maintained in culture conditions that normally support a progenitor cell-like state. From a library of 73,000 diverse small molecules within the Sanofi collection, 342 compounds were identified that increased OPC morphological complexity as an indicator of oligodendrocyte maturation. Subsequent to the primary high-content screen, a suite of cellular assays was established that identified 22 nontoxic compounds that selectively stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This rigorous triaging yielded several chemical series for further expansion and bio- or cheminformatics studies, and their compelling biological activity merits further investigation. © 2014 Society for Laboratory Automation and Screening.

  13. HC StratoMineR: A web-based tool for the rapid analysis of high content datasets

    NARCIS (Netherlands)

    Omta, W.; Heesbeen, R. van; Pagliero, R.; Velden, L. van der; Lelieveld, D.; Nellen, M.; Kramer, M.; Yeong, M.; Saeidi, A.; Medema, R.; Spruit, M.; Brinkkemper, S.; Klumperman, J.; Egan, D.

    2016-01-01

    High-content screening (HCS) can generate large multidimensional datasets and when aligned with the appropriate data mining tools, it can yield valuable insights into the mechanism of action of bioactive molecules. However, easy-to-use data mining tools are not widely available, with the result that

  14. HC StratoMineR : A Web-Based Tool for the Rapid Analysis of High-Content Datasets

    NARCIS (Netherlands)

    Omta, Wienand A; van Heesbeen, Roy G; Pagliero, Romina J; van der Velden, Lieke M; Lelieveld, Daphne; Nellen, Mehdi; Kramer, Maik; Yeong, Marley; Saeidi, Amir M; Medema, Rene H; Spruit, Marco; Brinkkemper, Sjaak; Klumperman, Judith; Egan, David A

    2016-01-01

    High-content screening (HCS) can generate large multidimensional datasets and when aligned with the appropriate data mining tools, it can yield valuable insights into the mechanism of action of bioactive molecules. However, easy-to-use data mining tools are not widely available, with the result that

  15. A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs

    CSIR Research Space (South Africa)

    Kwon, Y-J

    2012-03-01

    Full Text Available was screened against seven agonist-induced GPCR internalization cell models as well as transferrin uptake in human embryonic kidney cells. Molecules acting on a single receptor were identified through excluding pan-specific compounds affecting housekeeping...

  16. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z.

    Directory of Open Access Journals (Sweden)

    Sager J Gosai

    2010-11-01

    Full Text Available The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms.

  17. Adaptive platform for fluorescence microscopy-based high-content screening

    Science.gov (United States)

    Geisbauer, Matthias; Röder, Thorsten; Chen, Yang; Knoll, Alois; Uhl, Rainer

    2010-04-01

    Fluorescence microscopy has become a widely used tool for the study of medically relevant intra- and intercellular processes. Extracting meaningful information out of a bulk of acquired images is usually performed during a separate post-processing task. Thus capturing raw data results in an unnecessary huge number of images, whereas usually only a few images really show the particular information that is searched for. Here we propose a novel automated high-content microscope system, which enables experiments to be carried out with only a minimum of human interaction. It facilitates a huge speed-increase for cell biology research and its applications compared to the widely performed workflows. Our fluorescence microscopy system can automatically execute application-dependent data processing algorithms during the actual experiment. They are used for image contrast enhancement, cell segmentation and/or cell property evaluation. On-the-fly retrieved information is used to reduce data and concomitantly control the experiment process in real-time. Resulting in a closed loop of perception and action the system can greatly decrease the amount of stored data on one hand and increases the relative valuable data content on the other hand. We demonstrate our approach by addressing the problem of automatically finding cells with a particular combination of labeled receptors and then selectively stimulate them with antagonists or agonists. The results are then compared against the results of traditional, static systems.

  18. A High-Content Live-Cell Viability Assay and Its Validation on a Diverse 12K Compound Screen.

    Science.gov (United States)

    Chiaravalli, Jeanne; Glickman, J Fraser

    2017-08-01

    We have developed a new high-content cytotoxicity assay using live cells, called "ImageTOX." We used a high-throughput fluorescence microscope system, image segmentation software, and the combination of Hoechst 33342 and SYTO 17 to simultaneously score the relative size and the intensity of the nuclei, the nuclear membrane permeability, and the cell number in a 384-well microplate format. We then performed a screen of 12,668 diverse compounds and compared the results to a standard cytotoxicity assay. The ImageTOX assay identified similar sets of compounds to the standard cytotoxicity assay, while identifying more compounds having adverse effects on cell structure, earlier in treatment time. The ImageTOX assay uses inexpensive commercially available reagents and facilitates the use of live cells in toxicity screens. Furthermore, we show that we can measure the kinetic profile of compound toxicity in a high-content, high-throughput format, following the same set of cells over an extended period of time.

  19. A novel automatic quantification method for high-content screening analysis of DNA double strand-break response.

    Science.gov (United States)

    Feng, Jingwen; Lin, Jie; Zhang, Pengquan; Yang, Songnan; Sa, Yu; Feng, Yuanming

    2017-08-29

    High-content screening is commonly used in studies of the DNA damage response. The double-strand break (DSB) is one of the most harmful types of DNA damage lesions. The conventional method used to quantify DSBs is γH2AX foci counting, which requires manual adjustment and preset parameters and is usually regarded as imprecise, time-consuming, poorly reproducible, and inaccurate. Therefore, a robust automatic alternative method is highly desired. In this manuscript, we present a new method for quantifying DSBs which involves automatic image cropping, automatic foci-segmentation and fluorescent intensity measurement. Furthermore, an additional function was added for standardizing the measurement of DSB response inhibition based on co-localization analysis. We tested the method with a well-known inhibitor of DSB response. The new method requires only one preset parameter, which effectively minimizes operator-dependent variations. Compared with conventional methods, the new method detected a higher percentage difference of foci formation between different cells, which can improve measurement accuracy. The effects of the inhibitor on DSB response were successfully quantified with the new method (p = 0.000). The advantages of this method in terms of reliability, automation and simplicity show its potential in quantitative fluorescence imaging studies and high-content screening for compounds and factors involved in DSB response.

  20. High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines.

    Science.gov (United States)

    Danovi, Davide; Folarin, Amos A; Baranowski, Bart; Pollard, Steven M

    2012-01-01

    Small molecules with potent biological effects on the fate of normal and cancer-derived stem cells represent both useful research tools and new drug leads for regenerative medicine and oncology. Long-term expansion of mouse and human neural stem cells is possible using adherent monolayer culture. These cultures represent a useful cellular resource to carry out image-based high content screening of small chemical libraries. Improvements in automated microscopy, desktop computational power, and freely available image processing tools, now means that such chemical screens are realistic to undertake in individual academic laboratories. Here we outline a cost effective and versatile time lapse imaging strategy suitable for chemical screening. Protocols are described for the handling and screening of human fetal Neural Stem (NS) cell lines and their malignant counterparts, Glioblastoma-derived neural stem cells (GNS). We focus on identification of cytostatic and cytotoxic "hits" and discuss future possibilities and challenges for extending this approach to assay lineage commitment and differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Screening of siRNA nanoparticles for delivery to airway epithelial cells using high-content analysis

    LENUS (Irish Health Repository)

    Hibbitts, Alan

    2011-08-01

    Aims: Delivery of siRNA to the lungs via inhalation offers a unique opportunity to develop a new treatment paradigm for a range of respiratory conditions. However, progress has been greatly hindered by safety and delivery issues. This study developed a high-throughput method for screening novel nanotechnologies for pulmonary siRNA delivery. Methodology: Following physicochemical analysis, the ability of PEI–PEG–siRNA nanoparticles to facilitate siRNA delivery was determined using high-content analysis (HCA) in Calu-3 cells. Results obtained from HCA were validated using confocal microscopy. Finally, cytotoxicity of the PEI–PEG–siRNA particles was analyzed by HCA using the Cellomics® multiparameter cytotoxicity assay. Conclusion: PEI–PEG–siRNA nanoparticles facilitated increased siRNA uptake and luciferase knockdown in Calu-3 cells compared with PEI–siRNA.

  2. Impedance sensor technology for cell-based assays in the framework of a high-content screening system

    International Nuclear Information System (INIS)

    Schwarzenberger, T; Wolf, P; Brischwein, M; Kleinhans, R; Demmel, F; Becker, B; Wolf, B; Lechner, A

    2011-01-01

    Living cultured cells react to external influences, such as pharmaceutical agents, in an intricate manner due to their complex internal signal processing. Impedance sensing of cells on microelectrodes is a favored label-free technology to indicate cellular events, usually ascribed to morphologic alteration or changes in cellular adhesion, which is usually found in stand-alone systems that do not incorporate life support or additional sensor systems. However, only in symbiosis with metabolic activity sensing and picture documentation may a complete insight into cellular vitality be provided. This complement was created within the framework of an automated high-content screening system previously developed by our group, monitoring 24 cell culture chambers in parallel. The objective of this paper is the development of miniaturized electronics for impedance measurements and its system integration as a modular unit. In addition, it is shown how sensor electrodes were optimized by impedance matching such that spectroscopy and raw data analysis become feasible for every culture well. Undesired mechanical stress on cultured cells may arise from the medium and agent support system of the autonomous screening apparatus. This paper demonstrates how this hazard is treated with the simulation of microfluidics and impedance measurements. Physiological data are subsequently derived from the exemplary tumor cell line MCF-7 both during treatment with the agent doxorubicin and through the impact of natural killer cells. This correlates the information content of complex impedance spectra with cellular respiration as well as data from microscopy

  3. High-content, high-throughput screening for the identification of cytotoxic compounds based on cell morphology and cell proliferation markers.

    Directory of Open Access Journals (Sweden)

    Heather L Martin

    Full Text Available Toxicity is a major cause of failure in drug discovery and development, and whilst robust toxicological testing occurs, efficiency could be improved if compounds with cytotoxic characteristics were identified during primary compound screening. The use of high-content imaging in primary screening is becoming more widespread, and by utilising phenotypic approaches it should be possible to incorporate cytotoxicity counter-screens into primary screens. Here we present a novel phenotypic assay that can be used as a counter-screen to identify compounds with adverse cellular effects. This assay has been developed using U2OS cells, the PerkinElmer Operetta high-content/high-throughput imaging system and Columbus image analysis software. In Columbus, algorithms were devised to identify changes in nuclear morphology, cell shape and proliferation using DAPI, TOTO-3 and phosphohistone H3 staining, respectively. The algorithms were developed and tested on cells treated with doxorubicin, taxol and nocodazole. The assay was then used to screen a novel, chemical library, rich in natural product-like molecules of over 300 compounds, 13.6% of which were identified as having adverse cellular effects. This assay provides a relatively cheap and rapid approach for identifying compounds with adverse cellular effects during screening assays, potentially reducing compound rejection due to toxicity in subsequent in vitro and in vivo assays.

  4. A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

    OpenAIRE

    Lee, Yan Quan; Goh, Amanda S. P.; Ch'ng, Jun Hong; Nosten, François H.; Preiser, Peter Rainer; Pervaiz, Shazib; Yadav, Sanjiv Kumar; Tan, Kevin S. W.

    2014-01-01

    Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of in...

  5. ToxCast Workflow: High-throughput screening assay data processing, analysis and management (SOT)

    Science.gov (United States)

    US EPA’s ToxCast program is generating data in high-throughput screening (HTS) and high-content screening (HCS) assays for thousands of environmental chemicals, for use in developing predictive toxicity models. Currently the ToxCast screening program includes over 1800 unique c...

  6. Step-by-step guide to building an inexpensive 3D printed motorized positioning stage for automated high-content screening microscopy.

    Science.gov (United States)

    Schneidereit, Dominik; Kraus, Larissa; Meier, Jochen C; Friedrich, Oliver; Gilbert, Daniel F

    2017-06-15

    High-content screening microscopy relies on automation infrastructure that is typically proprietary, non-customizable, costly and requires a high level of skill to use and maintain. The increasing availability of rapid prototyping technology makes it possible to quickly engineer alternatives to conventional automation infrastructure that are low-cost and user-friendly. Here, we describe a 3D printed inexpensive open source and scalable motorized positioning stage for automated high-content screening microscopy and provide detailed step-by-step instructions to re-building the device, including a comprehensive parts list, 3D design files in STEP (Standard for the Exchange of Product model data) and STL (Standard Tessellation Language) format, electronic circuits and wiring diagrams as well as software code. System assembly including 3D printing requires approx. 30h. The fully assembled device is light-weight (1.1kg), small (33×20×8cm) and extremely low-cost (approx. EUR 250). We describe positioning characteristics of the stage, including spatial resolution, accuracy and repeatability, compare imaging data generated with our device to data obtained using a commercially available microplate reader, demonstrate its suitability to high-content microscopy in 96-well high-throughput screening format and validate its applicability to automated functional Cl - - and Ca 2+ -imaging with recombinant HEK293 cells as a model system. A time-lapse video of the stage during operation and as part of a custom assembled screening robot can be found at https://vimeo.com/158813199. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. HC StratoMineR: A Web-Based Tool for the Rapid Analysis of High-Content Datasets.

    Science.gov (United States)

    Omta, Wienand A; van Heesbeen, Roy G; Pagliero, Romina J; van der Velden, Lieke M; Lelieveld, Daphne; Nellen, Mehdi; Kramer, Maik; Yeong, Marley; Saeidi, Amir M; Medema, Rene H; Spruit, Marco; Brinkkemper, Sjaak; Klumperman, Judith; Egan, David A

    2016-10-01

    High-content screening (HCS) can generate large multidimensional datasets and when aligned with the appropriate data mining tools, it can yield valuable insights into the mechanism of action of bioactive molecules. However, easy-to-use data mining tools are not widely available, with the result that these datasets are frequently underutilized. Here, we present HC StratoMineR, a web-based tool for high-content data analysis. It is a decision-supportive platform that guides even non-expert users through a high-content data analysis workflow. HC StratoMineR is built by using My Structured Query Language for storage and querying, PHP: Hypertext Preprocessor as the main programming language, and jQuery for additional user interface functionality. R is used for statistical calculations, logic and data visualizations. Furthermore, C++ and graphical processor unit power is diffusely embedded in R by using the rcpp and rpud libraries for operations that are computationally highly intensive. We show that we can use HC StratoMineR for the analysis of multivariate data from a high-content siRNA knock-down screen and a small-molecule screen. It can be used to rapidly filter out undesirable data; to select relevant data; and to perform quality control, data reduction, data exploration, morphological hit picking, and data clustering. Our results demonstrate that HC StratoMineR can be used to functionally categorize HCS hits and, thus, provide valuable information for hit prioritization.

  8. RODENT AND HUMAN NEUROPROGENITOR CELLS FOR HIGH-CONTENT SCREENS OF CHEMICAL EFFECTS ON PROLIFERATION AND APOPTOSIS

    Science.gov (United States)

    The objective of these experiments is to develop high-throughput screens for proliferation and apoptosis in order to compare rodent and human neuroprogenitor cell responses to potential developmental neurotoxicants. Effects of 4 chemicals on proliferation and apoptosis in mouse c...

  9. High-content screening of Aspergillus niger with both increased production and high secretion rate of glucose oxidase.

    Science.gov (United States)

    Zhu, Xudong; Sun, Jingchun; Chu, Ju

    2018-01-01

    To develop a rapid, dual-parameter, plate-based screening process to improve production and secretion rate of glucose oxidase simultaneously in Aspergillus niger. A morphology engineering based on CaCO 3 was implemented, where the yield of GOD by A. niger was increased by up to 50%. Analysis of extracellular GOD activity was achieved in 96-well plates. There was a close negative correlation between the total GOD activity and its residual glucose of the fermentation broth. Based on this, a rapid, plate-based, qualitative analysis method of the total GOD activity was developed. Compared with the conventional analysis method using o-dianisidine, a correlation coefficient of -0.92 by statistical analysis was obtained. Using this dual-parameter screening method, we acquired a strain with GOD activity of 3126 U l -1 , which was 146% higher than the original strain. Its secretion rate of GOD was 83, 32% higher than the original strain.

  10. PeakCaller: an automated graphical interface for the quantification of intracellular calcium obtained by high-content screening.

    Science.gov (United States)

    Artimovich, Elena; Jackson, Russell K; Kilander, Michaela B C; Lin, Yu-Chih; Nestor, Michael W

    2017-10-16

    Intracellular calcium is an important ion involved in the regulation and modulation of many neuronal functions. From regulating cell cycle and proliferation to initiating signaling cascades and regulating presynaptic neurotransmitter release, the concentration and timing of calcium activity governs the function and fate of neurons. Changes in calcium transients can be used in high-throughput screening applications as a basic measure of neuronal maturity, especially in developing or immature neuronal cultures derived from stem cells. Using human induced pluripotent stem cell derived neurons and dissociated mouse cortical neurons combined with the calcium indicator Fluo-4, we demonstrate that PeakCaller reduces type I and type II error in automated peak calling when compared to the oft-used PeakFinder algorithm under both basal and pharmacologically induced conditions. Here we describe PeakCaller, a novel MATLAB script and graphical user interface for the quantification of intracellular calcium transients in neuronal cultures. PeakCaller allows the user to set peak parameters and smoothing algorithms to best fit their data set. This new analysis script will allow for automation of calcium measurements and is a powerful software tool for researchers interested in high-throughput measurements of intracellular calcium.

  11. High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses.

    Directory of Open Access Journals (Sweden)

    Rajini Mudhasani

    2014-08-01

    Full Text Available High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362, which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their

  12. A Novel High Content Imaging-Based Screen Identifies the Anti-Helminthic Niclosamide as an Inhibitor of Lysosome Anterograde Trafficking and Prostate Cancer Cell Invasion.

    Directory of Open Access Journals (Sweden)

    Magdalena L Circu

    Full Text Available Lysosome trafficking plays a significant role in tumor invasion, a key event for the development of metastasis. Previous studies from our laboratory have demonstrated that the anterograde (outward movement of lysosomes to the cell surface in response to certain tumor microenvironment stimulus, such as hepatocyte growth factor (HGF or acidic extracellular pH (pHe, increases cathepsin B secretion and tumor cell invasion. Anterograde lysosome trafficking depends on sodium-proton exchanger activity and can be reversed by blocking these ion pumps with Troglitazone or EIPA. Since these drugs cannot be advanced into the clinic due to toxicity, we have designed a high-content assay to discover drugs that block peripheral lysosome trafficking with the goal of identifying novel drugs that inhibit tumor cell invasion. An automated high-content imaging system (Cellomics was used to measure the position of lysosomes relative to the nucleus. Among a total of 2210 repurposed and natural product drugs screened, 18 "hits" were identified. One of the compounds identified as an anterograde lysosome trafficking inhibitor was niclosamide, a marketed human anti-helminthic drug. Further studies revealed that niclosamide blocked acidic pHe, HGF, and epidermal growth factor (EGF-induced anterograde lysosome redistribution, protease secretion, motility, and invasion of DU145 castrate resistant prostate cancer cells at clinically relevant concentrations. In an effort to identify the mechanism by which niclosamide prevented anterograde lysosome movement, we found that this drug exhibited no significant effect on the level of ATP, microtubules or actin filaments, and had minimal effect on the PI3K and MAPK pathways. Niclosamide collapsed intralysosomal pH without disruption of the lysosome membrane, while bafilomycin, an agent that impairs lysosome acidification, was also found to induce JLA in our model. Taken together, these data suggest that niclosamide promotes

  13. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.

    Science.gov (United States)

    Zhou, Ting; Tan, Lei; Cederquist, Gustav Y; Fan, Yujie; Hartley, Brigham J; Mukherjee, Suranjit; Tomishima, Mark; Brennand, Kristen J; Zhang, Qisheng; Schwartz, Robert E; Evans, Todd; Studer, Lorenz; Chen, Shuibing

    2017-08-03

    Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A high-content phenotypic screen reveals the disruptive potency of quinacrine and 3',4'-dichlorobenzamil on the digestive vacuole of Plasmodium falciparum.

    Science.gov (United States)

    Lee, Yan Quan; Goh, Amanda S P; Ch'ng, Jun Hong; Nosten, François H; Preiser, Peter Rainer; Pervaiz, Shazib; Yadav, Sanjiv Kumar; Tan, Kevin S W

    2014-01-01

    Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca(2+). This assay uses the ImageStream 100, an imaging-capable flow cytometer, to assess the distribution of the fluorescent calcium probe Fluo-4. We obtained two hits from a small library of 25 test compounds, quinacrine and 3',4'-dichlorobenzamil. The ability of these compounds to permeabilize the digestive vacuole in laboratory strains and clinical isolates was validated by confocal microscopy. The hits could induce programmed cell death features in both chloroquine-sensitive and -resistant laboratory strains. Quinacrine was effective at inhibiting field isolates in a 48-h reinvasion assay regardless of artemisinin clearance status. We therefore present as proof of concept a phenotypic screening method with the potential to provide mechanistic insights to the activity of antimalarial drugs.

  15. Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

    Directory of Open Access Journals (Sweden)

    John J. O'Leary

    2013-01-01

    Full Text Available Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9 as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant and A2780 (cisplatin-sensitive ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.

  16. Cytotoxicity evaluation of nanoclays in human epithelial cell line A549 using high content screening and real-time impedance analysis

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Navin K. [Trinity College Dublin, Department of Clinical Medicine, Institute of Molecular Medicine (Ireland); Moore, Edward; Blau, Werner [Trinity College Dublin, School of Physics (Ireland); Volkov, Yuri [Trinity College Dublin, Department of Clinical Medicine, Institute of Molecular Medicine (Ireland); Ramesh Babu, P., E-mail: babup@tcd.ie [Trinity College Dublin, Centre for Research on Adaptive Nanostructures and Nanodevices (Ireland)

    2012-09-15

    Continuously expanding use of products containing nanoclays for wide range of applications have raised public concerns about health and safety. Although the products containing nanoclays may not be toxic, it is possible that nanomaterials may come in contact with humans during handling, manufacture, or disposal, and cause adverse health impact. This necessitates biocompatibility evaluation of the commonly used nanoclays. Here, we investigated the cytotoxic effects of platelet (Bentone MA, ME-100, Cloisite Na{sup +}, Nanomer PGV, and Delite LVF) and tubular (Halloysite, and Halloysite MP1) type nanoclays on cultured human lung epithelial cells A549. For the first time with this aim, we employed a cell-based automated high content screening in combination with real-time impedance sensing. We demonstrate varying degree of dose- and time-dependent cytotoxic effects of both nanoclay types. Overall, platelet structured nanoclays were more cytotoxic than tubular type. A low but significant level of cytotoxicity was observed at 25 {mu}g/mL of the platelet-type nanoclays. A549 cells exposed to high concentration (250 {mu}g/mL) of tubular structured nanoclays showed inhibited cell growth. Confocal microscopy indicated intracellular accumulation of nanoclays with perinuclear localization. Results indicate a potential hazard of nanoclay-containing products at significantly higher concentrations, which warrant their further biohazard assessment on the actual exposure in humans.

  17. Cytotoxicity evaluation of nanoclays in human epithelial cell line A549 using high content screening and real-time impedance analysis

    International Nuclear Information System (INIS)

    Verma, Navin K.; Moore, Edward; Blau, Werner; Volkov, Yuri; Ramesh Babu, P.

    2012-01-01

    Continuously expanding use of products containing nanoclays for wide range of applications have raised public concerns about health and safety. Although the products containing nanoclays may not be toxic, it is possible that nanomaterials may come in contact with humans during handling, manufacture, or disposal, and cause adverse health impact. This necessitates biocompatibility evaluation of the commonly used nanoclays. Here, we investigated the cytotoxic effects of platelet (Bentone MA, ME-100, Cloisite Na + , Nanomer PGV, and Delite LVF) and tubular (Halloysite, and Halloysite MP1) type nanoclays on cultured human lung epithelial cells A549. For the first time with this aim, we employed a cell-based automated high content screening in combination with real-time impedance sensing. We demonstrate varying degree of dose- and time-dependent cytotoxic effects of both nanoclay types. Overall, platelet structured nanoclays were more cytotoxic than tubular type. A low but significant level of cytotoxicity was observed at 25 μg/mL of the platelet-type nanoclays. A549 cells exposed to high concentration (250 μg/mL) of tubular structured nanoclays showed inhibited cell growth. Confocal microscopy indicated intracellular accumulation of nanoclays with perinuclear localization. Results indicate a potential hazard of nanoclay-containing products at significantly higher concentrations, which warrant their further biohazard assessment on the actual exposure in humans.

  18. Effects of defined mixtures of persistent organic pollutants (POPs) on multiple cellular responses in the human hepatocarcinoma cell line, HepG2, using high content analysis screening

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Jodie [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom); Berntsen, Hanne Friis; Zimmer, Karin Elisabeth [Norwegian University of Life Sciences, Oslo (Norway); Frizzell, Caroline [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom); Verhaegen, Steven; Ropstad, Erik [Norwegian University of Life Sciences, Oslo (Norway); Connolly, Lisa, E-mail: l.connolly@qub.ac.uk [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom)

    2016-03-01

    Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential. Most studies focus on single compound effects, however as humans are exposed to several POPs simultaneously, investigating exposure effects of real life POP mixtures on human health is necessary. A defined mixture of POPs was used, where the compound concentration reflected its contribution to the levels seen in Scandinavian human serum (total mix). Several sub mixtures representing different classes of POPs were also constructed. The perfluorinated (PFC) mixture contained six perfluorinated compounds, brominated (Br) mixture contained seven brominated compounds, chlorinated (Cl) mixture contained polychlorinated biphenyls and also p,p’-dichlorodiphenyldichloroethylene, hexachlorobenzene, three chlordanes, three hexachlorocyclohexanes and dieldrin. Human hepatocarcinoma (HepG2) cells were used for 2 h and 48 h exposures to the seven mixtures and analysis on a CellInsight™ NXT High Content Screening platform. Multiple cytotoxic endpoints were investigated: cell number, nuclear intensity and area, mitochondrial mass and membrane potential (MMP) and reactive oxygen species (ROS). Both the Br and Cl mixtures induced ROS production but did not lead to apoptosis. The PFC mixture induced ROS production and likely induced cell apoptosis accompanied by the dissipation of MMP. Synergistic effects were evident for ROS induction when cells were exposed to the PFC + Br mixture in comparison to the effects of the individual mixtures. No significant effects were detected in the Br + Cl, PFC + Cl or total mixtures, which contain the same concentrations of chlorinated compounds as the Cl mixture plus additional compounds; highlighting the need for further exploration of POP mixtures in risk assessment. - Highlights: • High content analysis (HCA) is a novel approach for determining toxicity of

  19. Effects of defined mixtures of persistent organic pollutants (POPs) on multiple cellular responses in the human hepatocarcinoma cell line, HepG2, using high content analysis screening

    International Nuclear Information System (INIS)

    Wilson, Jodie; Berntsen, Hanne Friis; Zimmer, Karin Elisabeth; Frizzell, Caroline; Verhaegen, Steven; Ropstad, Erik; Connolly, Lisa

    2016-01-01

    Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential. Most studies focus on single compound effects, however as humans are exposed to several POPs simultaneously, investigating exposure effects of real life POP mixtures on human health is necessary. A defined mixture of POPs was used, where the compound concentration reflected its contribution to the levels seen in Scandinavian human serum (total mix). Several sub mixtures representing different classes of POPs were also constructed. The perfluorinated (PFC) mixture contained six perfluorinated compounds, brominated (Br) mixture contained seven brominated compounds, chlorinated (Cl) mixture contained polychlorinated biphenyls and also p,p’-dichlorodiphenyldichloroethylene, hexachlorobenzene, three chlordanes, three hexachlorocyclohexanes and dieldrin. Human hepatocarcinoma (HepG2) cells were used for 2 h and 48 h exposures to the seven mixtures and analysis on a CellInsight™ NXT High Content Screening platform. Multiple cytotoxic endpoints were investigated: cell number, nuclear intensity and area, mitochondrial mass and membrane potential (MMP) and reactive oxygen species (ROS). Both the Br and Cl mixtures induced ROS production but did not lead to apoptosis. The PFC mixture induced ROS production and likely induced cell apoptosis accompanied by the dissipation of MMP. Synergistic effects were evident for ROS induction when cells were exposed to the PFC + Br mixture in comparison to the effects of the individual mixtures. No significant effects were detected in the Br + Cl, PFC + Cl or total mixtures, which contain the same concentrations of chlorinated compounds as the Cl mixture plus additional compounds; highlighting the need for further exploration of POP mixtures in risk assessment. - Highlights: • High content analysis (HCA) is a novel approach for determining toxicity of

  20. A NOVEL PIPELINE FOR DRUG DISCOVERY IN NEUROPSYCHIATRIC DISORDERS USING HIGH-CONTENT SINGLE-CELL SCREENING OF SIGNALLING NETWORK RESPONSES EX VIVO

    OpenAIRE

    Lago Cooke, Santiago Guillermo

    2016-01-01

    The current work entails the development of a novel high content platform for the measurement of kinetic ligand responses across cell signalling networks at the single-cell level in distinct PBMC subtypes ex vivo. Using automated sample preparation, fluorescent cellular barcoding and flow cytometry the platform is capable of detecting 21, 840 parallel cell signalling responses in each PBMC sample. We apply this platform to characterize the effects of neuropsychiatric treatments and CNS ligand...

  1. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1.

    Directory of Open Access Journals (Sweden)

    Davide Danovi

    Full Text Available Glioblastoma multiforme (GBM is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS cells and genetically normal neural stem (NS cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101 as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1 (phospho T210, with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364 phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF(-/-, or p53(-/-, as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value.

  2. Phaedra, a protocol-driven system for analysis and validation of high-content imaging and flow cytometry.

    Science.gov (United States)

    Cornelissen, Frans; Cik, Miroslav; Gustin, Emmanuel

    2012-04-01

    High-content screening has brought new dimensions to cellular assays by generating rich data sets that characterize cell populations in great detail and detect subtle phenotypes. To derive relevant, reliable conclusions from these complex data, it is crucial to have informatics tools supporting quality control, data reduction, and data mining. These tools must reconcile the complexity of advanced analysis methods with the user-friendliness demanded by the user community. After review of existing applications, we realized the possibility of adding innovative new analysis options. Phaedra was developed to support workflows for drug screening and target discovery, interact with several laboratory information management systems, and process data generated by a range of techniques including high-content imaging, multicolor flow cytometry, and traditional high-throughput screening assays. The application is modular and flexible, with an interface that can be tuned to specific user roles. It offers user-friendly data visualization and reduction tools for HCS but also integrates Matlab for custom image analysis and the Konstanz Information Miner (KNIME) framework for data mining. Phaedra features efficient JPEG2000 compression and full drill-down functionality from dose-response curves down to individual cells, with exclusion and annotation options, cell classification, statistical quality controls, and reporting.

  3. High content screening in neurodegenerative diseases

    NARCIS (Netherlands)

    Jain, S.; van Kesteren, R.E.; Heutink, P.

    2012-01-01

    The functional annotation of genomes, construction of molecular networks and novel drug target identification, are important challenges that need to be addressed as a matter of great urgency. Multiple complementary 'omics' approaches have provided clues as to the genetic risk factors and pathogenic

  4. User Location Identification for Cooperative Human-Centric Sensing (HCS) Scenario

    DEFF Research Database (Denmark)

    Mihovska, Albena Dimitrova

    – Human-Centric Sensing (HCS) is a newly emerged concept in the context of the Internet of Things (IoT) and the active and assisted living (AAL) scenario. HCS connectivity, also referred to as “smart connectivity” enables applications that are highly personalized and often time...

  5. Fact Sheet: Revisions to the Occupational Safety and Health Administration Hazard Communication Standards (HCS)

    Science.gov (United States)

    On March 26, 2012, Occupational Safety and Health Administration (OSHA) modified its HCS to conform to the United Nations’ (UN) Globally Harmonized System of Classification and Labeling of Chemicals (GHS), to improve consistency and quality of information.

  6. Development Status of the Helium Circulator for the HCS of HCCR-TBS

    International Nuclear Information System (INIS)

    Lee, Eo Hwak; Jin, Hyung Gon; Yoon, Jae Sung; Kim, Suk Kwon; Lee, Dong Won; Lee, Si Woo; Cho, Seung Yon

    2016-01-01

    The calculated eddy current loss on the stainless steel sealing cap of the magnetic coupling device is very high. To solve the eddy current loss problem of the sealing cap, a glass fiber composite, non-conductive and high strength material, is adapted as a material of the sealing cap. The HCCR TBM will be cooled down by HCS (Helium Cooling System), supply high pressure (8 MPa) and temperature (300 .deg. C) helium coolant with 1.15 kg/s of mass flow for nominal operation. The real-scale helium circulator, which is main component of the HCS, has been developed since 2014. In present study, design and manufacture progress of the helium circulator and its verification test plan are described. The real-scale circulator has been developed to provide high temperature and pressure of helium flow as a coolant of the HCCR TBM. To prevent helium leakage, magnetic coupling design was adapted between the shaft and the impeller

  7. Shedding Light on Filovirus Infection with High-Content Imaging

    Directory of Open Access Journals (Sweden)

    Rekha G. Panchal

    2012-08-01

    Full Text Available Microscopy has been instrumental in the discovery and characterization of microorganisms. Major advances in high-throughput fluorescence microscopy and automated, high-content image analysis tools are paving the way to the systematic and quantitative study of the molecular properties of cellular systems, both at the population and at the single-cell level. High-Content Imaging (HCI has been used to characterize host-virus interactions in genome-wide reverse genetic screens and to identify novel cellular factors implicated in the binding, entry, replication and egress of several pathogenic viruses. Here we present an overview of the most significant applications of HCI in the context of the cell biology of filovirus infection. HCI assays have been recently implemented to quantitatively study filoviruses in cell culture, employing either infectious viruses in a BSL-4 environment or surrogate genetic systems in a BSL-2 environment. These assays are becoming instrumental for small molecule and siRNA screens aimed at the discovery of both cellular therapeutic targets and of compounds with anti-viral properties. We discuss the current practical constraints limiting the implementation of high-throughput biology in a BSL-4 environment, and propose possible solutions to safely perform high-content, high-throughput filovirus infection assays. Finally, we discuss possible novel applications of HCI in the context of filovirus research with particular emphasis on the identification of possible cellular biomarkers of virus infection.

  8. A tentative interpretation for the difference in the abundance ratios HCO(+)/CO and HCS(+)/CS in interstellar space

    Science.gov (United States)

    Talbi, D.; Hickman, A. P.; Pauzat, F.; Ellinger, Y.; Berthier, G.

    1989-04-01

    It is shown here that the difference of two orders of magnitude between the values of the abundance ratios HCO(+)/CO and HCS(+)/CS in interstellar clouds can be directly related to the difference in the reaction rates of the dissociative recombination reactions of the positive ions. The potential energy curves of the systems (HCO+ + e-) and (HCS+ + e-) in Rydberg and dissociative valence states, as well as those of the positive ions CHO+ and HCS+, are computed by ab initio quantum chemistry methods. The potential surfaces of the two systems show striking differences, suggesting that the dissociative processes, direct and indirect, should be more efficient for HCO.

  9. A tentative interpretation for the difference in the abundance ratios HCO(+)/CO and HCS(+)/CS in interstellar space

    International Nuclear Information System (INIS)

    Talbi, D.; Hickman, A.P.; Pauzat, F.; Ellinger, Y.; Berthier, G.

    1989-01-01

    It is shown here that the difference of two orders of magnitude between the values of the abundance ratios HCO(+)/CO and HCS(+)/CS in interstellar clouds can be directly related to the difference in the reaction rates of the dissociative recombination reactions of the positive ions. The potential energy curves of the systems (HCO+ + e-) and (HCS+ + e-) in Rydberg and dissociative valence states, as well as those of the positive ions CHO+ and HCS+, are computed by ab initio quantum chemistry methods. The potential surfaces of the two systems show striking differences, suggesting that the dissociative processes, direct and indirect, should be more efficient for HCO. 23 refs

  10. Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis.

    Science.gov (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Wiengkum, Thanatcha

    2016-06-01

    Hemoglobin Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)] is often missed by routine laboratory testing, especially in subjects with co-inheritance of β-thalassemia or β-variants. We reported the case of a 1-year-old female with Hb H-CS disease who was born from a father with heterozygous of α-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [β26 (B8) Glu→Lys, GAG>AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease.

  11. GAMMA-FR and MELCOR Validation using HCS Heat Exchanger Break Accident

    International Nuclear Information System (INIS)

    Jin, Hyung Gon; Hong, Yun Jeong; Cho, Seung Yon

    2016-01-01

    To confirm the HCCR-TBS integrity, enveloped cases from the conceivable events were evaluated and demonstrated compliance with the General Safety Objectives of ITER. In this analysis, amount of discharged helium is the key parameter to examine total tritium ingress to CCWS-1. In this regard, radiation heat transfer and temperature distribution along the pipes did not take account. Due to the same reason, flow network inside of TBM is simplified as one fluid volume (FB1300). In principle, transient of this accident is similar to LOHSA, therefore, TBM temperature is expected to be cool down by passive cooling and isolation valves avoid CCWS-1 pressure build-up during the accident. With relief valve, pressure of CCWS-1 is under 0.43 MPa during LOCA happens. (CCWS-1 max. design pressure: 1MPa). On the other hand, primary concern is tritium concentration increase in CCWS-1 because of tritium contents in HCS coolant. The important point is that CCWS-1 is an ESP device and its ESP level should be confirmed when operating with HCCR-TBS as well. Key parameters, which govern this transient, are relief valve operation, nitrogen in the pressurizer and flow area of the ruptured channels. Relief valve in CCWS-1 pressurizer opens at 0.41 MPa and closes 0.39 MPa, therefore, CCWS-1 pressure is impossible to exceed 0.41 MPa globally. As a comparison, calculation was conducted against CCWS-1 with relief valve (with RV) and without relief valve (without RV)

  12. Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

    KAUST Repository

    Hajjar, Dina A.; Kremb, Stephan Georg; Sioud, Salim; Emwas, Abdul-Hamid M.; Voolstra, Christian R.; Ravasi, Timothy

    2017-01-01

    in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia's traditional medicine. We compared the cytological

  13. Nanoscale high-content analysis using compositional heterogeneities of single proteoliposomes

    DEFF Research Database (Denmark)

    Mathiasen, Signe; Christensen, Sune M.; Fung, Juan José

    2014-01-01

    Proteoliposome reconstitution is a standard method to stabilize purified transmembrane proteins in membranes for structural and functional assays. Here we quantified intrareconstitution heterogeneities in single proteoliposomes using fluorescence microscopy. Our results suggest that compositional...... heterogeneities can severely skew ensemble-average proteoliposome measurements but also enable ultraminiaturized high-content screens. We took advantage of this screening capability to map the oligomerization energy of the β2-adrenergic receptor using ∼10(9)-fold less protein than conventional assays....

  14. Current and high-β sheets in CIR streams: statistics and interaction with the HCS and the magnetosphere

    Science.gov (United States)

    Potapov, A. S.

    2018-04-01

    Thirty events of CIR streams (corotating interaction regions between fast and slow solar wind) were analyzed in order to study statistically plasma structure within the CIR shear zones and to examine the interaction of the CIRs with the heliospheric current sheet (HCS) and the Earth's magnetosphere. The occurrence of current layers and high-beta plasma sheets in the CIR structure has been estimated. It was found that on average, each of the CIR streams had four current layers in its structure with a current density of more than 0.12 A/m2 and about one and a half high-beta plasma regions with a beta value of more than five. Then we traced how and how often the high-speed stream associated with the CIR can catch up with the heliospheric current sheet (HCS) and connect to it. The interface of each fourth CIR stream coincided in time within an hour with the HCS, but in two thirds of cases, the CIR connection with the HCS was completely absent. One event of the simultaneous observation of the CIR stream in front of the magnetosphere by the ACE satellite in the vicinity of the L1 libration point and the Wind satellite in the remote geomagnetic tail was considered in detail. Measurements of the components of the interplanetary magnetic field and plasma parameters showed that the overall structure of the stream is conserved. Moreover, some details of the fine structure are also transferred through the magnetosphere. In particular, the so-called "magnetic hole" almost does not change its shape when moving from L1 point to a neighborhood of L2 point.

  15. Screens

    OpenAIRE

    2016-01-01

    This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

  16. The Study of Implement of HCS Program at Hazardous Chemicals Knowledge and Safety performance in Tehran refinery, s laboratory unit

    Directory of Open Access Journals (Sweden)

    N. Hassanzadeh-Rangi

    2008-10-01

    Full Text Available Background and aims   The HCS standard includes listing of chemicals, labeling of chemical  containers, preparation of material safety data sheets, writing plan and employee training  programs. The aim of this study was to determine the influence of implemented program to enhance the knowledge and safety performance level of employees.   Methods   The knowledge level and unsafe act ratio were measured using both questionnaire  and behavior checklist (with safety sampling method before and after enforcing this interface.   Results   In this study, the mean and standard deviation of the knowledge level of employees  related to chemical safety before enforcing the interface was 46% and 14%. However, after  enforcing the interface, mean and standard deviation was 88% and 12%. The paired-t-test result   in this parameter was significant (p-value <0.0001. The mean and standard deviation of  knowledge level of employees related to warning labels before to enforcing the interface was 29%  and 22%. After enforcing the interface, mean and standard deviation was 80% and 16%. The paired-t-test result in this parameter was significant (p-value <0.0001. The mean and standard  deviation of the knowledge level of employees related to hazard communication methods before enforcing the interface was 25% and 11%. After enforcing the interface, mean and standard deviation was 79% and 16%. The paired-t-test result in this parameter was significant (p-value   <0.001.   Conclusion   The obtained result revealed that enhancement of the knowledge related to chemical safety, hazard communication methods and warning labels was significant. Statistical paired-t-test and control chart methods was used to comparison between unsafe act ratio before  and after enforcing the interface. The mean and standard deviation of unsafe act ratio before implementation of HCS program was 23.6% and 5.49%. However, mean and standard deviation of unsafe act ratio

  17. High content analysis of phagocytic activity and cell morphology with PuntoMorph

    DEFF Research Database (Denmark)

    Al-Ali, Hassan; Gao, Han; Dalby-Hansen, Camilla

    2017-01-01

    methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution. Conclusions We provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package...... with image-based quantification of phagocytic activity. New method We present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs...... content screening. Results We tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial...

  18. Dexterous robotic manipulation of alert adult Drosophila for high-content experimentation.

    Science.gov (United States)

    Savall, Joan; Ho, Eric Tatt Wei; Huang, Cheng; Maxey, Jessica R; Schnitzer, Mark J

    2015-07-01

    We present a robot that enables high-content studies of alert adult Drosophila by combining operations including gentle picking; translations and rotations; characterizations of fly phenotypes and behaviors; microdissection; or release. To illustrate, we assessed fly morphology, tracked odor-evoked locomotion, sorted flies by sex, and dissected the cuticle to image neural activity. The robot's tireless capacity for precise manipulations enables a scalable platform for screening flies' complex attributes and behavioral patterns.

  19. The Proposal Concept of Development and Implementation in Strategy of Sustainable Corporate Social Responsibility in the Context of the HCS Model 3E

    Science.gov (United States)

    Sakál, Peter; Hrdinová, Gabriela

    2016-06-01

    This article is the result of a conceptual design methodology for the development of a sustainable strategy of sustainable corporate social responsibility (SCSR) in the context of the HCS model 3E formed, as a co-author within the stated grants and dissertation. On the basis of the use of propositional logic, the SCSR procedure is proposed for incorporation into the corporate strategy of sustainable development and the integrated management system (IMS) of the industrial enterprise. The aim of this article is the proposal of the concept of development and implementation strategy of SCSR in the context of the HCS model 3E.

  20. High content analysis of phagocytic activity and cell morphology with PuntoMorph.

    Science.gov (United States)

    Al-Ali, Hassan; Gao, Han; Dalby-Hansen, Camilla; Peters, Vanessa Ann; Shi, Yan; Brambilla, Roberta

    2017-11-01

    Phagocytosis is essential for maintenance of normal homeostasis and healthy tissue. As such, it is a therapeutic target for a wide range of clinical applications. The development of phenotypic screens targeting phagocytosis has lagged behind, however, due to the difficulties associated with image-based quantification of phagocytic activity. We present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs statistical modeling to determine the mean fluorescence of individual beads within each image, and uses the information to conduct an accurate count of phagocytosed beads. In addition, the algorithm conducts detailed and sophisticated analysis of cellular morphology, making it a standalone tool for high content screening. We tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial activation, specifically cell body hypertrophy and increased phagocytic activity, are not highly correlated. This novel finding suggests the two phenotypes may be under the control of distinct signaling pathways. We demonstrate that our assay system outperforms preexisting methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution. We provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package, PuntoMorph. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Information management for high content live cell imaging

    Directory of Open Access Journals (Sweden)

    White Michael RH

    2009-07-01

    Full Text Available Abstract Background High content live cell imaging experiments are able to track the cellular localisation of labelled proteins in multiple live cells over a time course. Experiments using high content live cell imaging will generate multiple large datasets that are often stored in an ad-hoc manner. This hinders identification of previously gathered data that may be relevant to current analyses. Whilst solutions exist for managing image data, they are primarily concerned with storage and retrieval of the images themselves and not the data derived from the images. There is therefore a requirement for an information management solution that facilitates the indexing of experimental metadata and results of high content live cell imaging experiments. Results We have designed and implemented a data model and information management solution for the data gathered through high content live cell imaging experiments. Many of the experiments to be stored measure the translocation of fluorescently labelled proteins from cytoplasm to nucleus in individual cells. The functionality of this database has been enhanced by the addition of an algorithm that automatically annotates results of these experiments with the timings of translocations and periods of any oscillatory translocations as they are uploaded to the repository. Testing has shown the algorithm to perform well with a variety of previously unseen data. Conclusion Our repository is a fully functional example of how high throughput imaging data may be effectively indexed and managed to address the requirements of end users. By implementing the automated analysis of experimental results, we have provided a clear impetus for individuals to ensure that their data forms part of that which is stored in the repository. Although focused on imaging, the solution provided is sufficiently generic to be applied to other functional proteomics and genomics experiments. The software is available from: fhttp://code.google.com/p/livecellim/

  2. High-Content Electrophysiological Analysis of Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs).

    Science.gov (United States)

    Kong, Chi-Wing; Geng, Lin; Li, Ronald A

    2018-01-01

    Considerable interest has been raised to develop human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as a model for drug discovery and cardiotoxicity screening. High-content electrophysiological analysis of currents generated by transmembrane cell surface ion channels has been pursued to complement such emerging applications. Here we describe practical procedures and considerations for accomplishing successful assays of hPSC-CMs using an automated planar patch-clamp system.

  3. Cermet anode compositions with high content alloy phase

    Science.gov (United States)

    Marschman, Steven C.; Davis, Norman C.

    1989-01-01

    Cermet electrode compositions comprising NiO-NiFe.sub.2 O.sub.4 -Cu-Ni, and methods for making, are disclosed. Addition of nickel metal prior to formation and densification of a base mixture into the cermet allows for an increase in the total amount of copper and nickel that can be contained in the NiO-NiFe.sub.2 O.sub.4 oxide system. Nickel is present in a base mixture weight concentration of from 0.1% to 10%. Copper is present in the alloy phase in a weight concentration of from 10% to 30% of the densified composition. Such cermet electrodes can be formed to have electrical conductivities well in excess of 100 ohm.sup.-1 cm.sup.-1. Other alloy and oxide system cermets having high content metal phases are also expected to be manufacturable in accordance with the invention.

  4. High content live cell imaging for the discovery of new antimalarial marine natural products

    Directory of Open Access Journals (Sweden)

    Cervantes Serena

    2012-01-01

    Full Text Available Abstract Background The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum. Methods A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope. Results Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts. Conclusion Collectively, our results show that high-content live cell-imaging (HCLCI can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials.

  5. High content live cell imaging for the discovery of new antimalarial marine natural products.

    Science.gov (United States)

    Cervantes, Serena; Stout, Paige E; Prudhomme, Jacques; Engel, Sebastian; Bruton, Matthew; Cervantes, Michael; Carter, David; Tae-Chang, Young; Hay, Mark E; Aalbersberg, William; Kubanek, Julia; Le Roch, Karine G

    2012-01-03

    The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum. A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope. Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts. Collectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials. © 2011 Cervantes et al; licensee BioMed Central Ltd.

  6. IN VITRO SCREENING OF DEVELOPMENTAL NEUROTOXICANTS IN RAT PRIMARY CORTICAL NEURONS USING HIGH CONTENT IMAGE

    Science.gov (United States)

    There is a need for more efficient and cost-effective methods for identifying, characterizing and prioritizing chemicals which may result in developmental neurotoxicity. One approach is to utilize in vitro test systems which recapitulate the critical processes of nervous system d...

  7. Development of a quantitative morphological assessment of toxicant-treated zebrafish larvae using brightfield imaging and high-content analysis.

    Science.gov (United States)

    Deal, Samantha; Wambaugh, John; Judson, Richard; Mosher, Shad; Radio, Nick; Houck, Keith; Padilla, Stephanie

    2016-09-01

    One of the rate-limiting procedures in a developmental zebrafish screen is the morphological assessment of each larva. Most researchers opt for a time-consuming, structured visual assessment by trained human observer(s). The present studies were designed to develop a more objective, accurate and rapid method for screening zebrafish for dysmorphology. Instead of the very detailed human assessment, we have developed the computational malformation index, which combines the use of high-content imaging with a very brief human visual assessment. Each larva was quickly assessed by a human observer (basic visual assessment), killed, fixed and assessed for dysmorphology with the Zebratox V4 BioApplication using the Cellomics® ArrayScan® V(TI) high-content image analysis platform. The basic visual assessment adds in-life parameters, and the high-content analysis assesses each individual larva for various features (total area, width, spine length, head-tail length, length-width ratio, perimeter-area ratio). In developing the computational malformation index, a training set of hundreds of embryos treated with hundreds of chemicals were visually assessed using the basic or detailed method. In the second phase, we assessed both the stability of these high-content measurements and its performance using a test set of zebrafish treated with a dose range of two reference chemicals (trans-retinoic acid or cadmium). We found the measures were stable for at least 1 week and comparison of these automated measures to detailed visual inspection of the larvae showed excellent congruence. Our computational malformation index provides an objective manner for rapid phenotypic brightfield assessment of individual larva in a developmental zebrafish assay. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

    KAUST Repository

    Hajjar, Dina

    2017-06-13

    Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

  9. Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics.

    Science.gov (United States)

    Dhaliwal, Anandika; Brenner, Matthew; Wolujewicz, Paul; Zhang, Zheng; Mao, Yong; Batish, Mona; Kohn, Joachim; Moghe, Prabhas V

    2016-11-01

    materials relies on technologies that can sensitively discern cell response dynamics to biomaterials, while capturing cell-to-cell heterogeneity and preserving cellular native phenotypes. In this study, we illustrate the application of a novel high content image informatics platform to classify emergent human mesenchymal stem cell (hMSC) phenotypes in a diverse range of 3-D biomaterial scaffolds with high sensitivity and precision, and track cell responses to varied external stimuli. A major in silico innovation is the proposed image profiling technology based on unique three dimensional textural signatures of a mechanoreporter protein within the nuclei of stem cells cultured in 3-D scaffolds. This technology will accelerate the pace of high-fidelity biomaterial screening. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. New sunflower seeds with high contents of phytosterols

    Directory of Open Access Journals (Sweden)

    Velasco Leonardo

    2014-11-01

    Full Text Available Dietary phytosterols have a positive nutritional impact because they contribute to reduce cholesterol levels in blood. Accordingly, foods rich in phytosterols are required in a healthy diet. Vegetable oils are the richest source of phytosterols in the diet, though sunflower oil has lower phytosterol content than other seed oils such as rapeseed and corn. Increasing phytosterol content in sunflower oil requires optimizing first selection procedures. In this way, the development of accurate methods for analyzing phytosterol content in seeds instead of oils has opened up recently the way for large-scale screening for this trait. Large variability for seed phytosterol content has been identified in sunflower germplasm, from which we have developed a line, IASP-18, with about twofold seed phytosterol content than conventional sunflower. The trait is expressed across environments. Genetic studies are underway to characterize its inheritance and assess the feasibility of introgressing genes for high phytosterol content into elite sunflower germplasm.

  11. Integration of statistical modeling and high-content microscopy to systematically investigate cell-substrate interactions.

    Science.gov (United States)

    Chen, Wen Li Kelly; Likhitpanichkul, Morakot; Ho, Anthony; Simmons, Craig A

    2010-03-01

    Cell-substrate interactions are multifaceted, involving the integration of various physical and biochemical signals. The interactions among these microenvironmental factors cannot be facilely elucidated and quantified by conventional experimentation, and necessitate multifactorial strategies. Here we describe an approach that integrates statistical design and analysis of experiments with automated microscopy to systematically investigate the combinatorial effects of substrate-derived stimuli (substrate stiffness and matrix protein concentration) on mesenchymal stem cell (MSC) spreading, proliferation and osteogenic differentiation. C3H10T1/2 cells were grown on type I collagen- or fibronectin-coated polyacrylamide hydrogels with tunable mechanical properties. Experimental conditions, which were defined according to central composite design, consisted of specific permutations of substrate stiffness (3-144 kPa) and adhesion protein concentration (7-520 microg/mL). Spreading area, BrdU incorporation and Runx2 nuclear translocation were quantified using high-content microscopy and modeled as mathematical functions of substrate stiffness and protein concentration. The resulting response surfaces revealed distinct patterns of protein-specific, substrate stiffness-dependent modulation of MSC proliferation and differentiation, demonstrating the advantage of statistical modeling in the detection and description of higher-order cellular responses. In a broader context, this approach can be adapted to study other types of cell-material interactions and can facilitate the efficient screening and optimization of substrate properties for applications involving cell-material interfaces. Copyright 2009 Elsevier Ltd. All rights reserved.

  12. Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

    Directory of Open Access Journals (Sweden)

    Albert H Gough

    Full Text Available One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

  13. High content image based analysis identifies cell cycle inhibitors as regulators of Ebola virus infection.

    Science.gov (United States)

    Kota, Krishna P; Benko, Jacqueline G; Mudhasani, Rajini; Retterer, Cary; Tran, Julie P; Bavari, Sina; Panchal, Rekha G

    2012-09-25

    Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

  14. High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Sina Bavari

    2012-09-01

    Full Text Available Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

  15. Advanced Cell Classifier: User-Friendly Machine-Learning-Based Software for Discovering Phenotypes in High-Content Imaging Data.

    Science.gov (United States)

    Piccinini, Filippo; Balassa, Tamas; Szkalisity, Abel; Molnar, Csaba; Paavolainen, Lassi; Kujala, Kaisa; Buzas, Krisztina; Sarazova, Marie; Pietiainen, Vilja; Kutay, Ulrike; Smith, Kevin; Horvath, Peter

    2017-06-28

    High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments. It features methods to mine microscopic image data, discover new phenotypes, and improve recognition performance. We demonstrate that these features substantially expedite the training process, successfully uncover rare phenotypes, and improve the accuracy of the analysis. ACC is extensively documented, designed to be user-friendly for researchers without machine-learning expertise, and distributed as a free open-source tool at www.cellclassifier.org. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The influence of compound admixtures on the properties of high-content slag cement

    Energy Technology Data Exchange (ETDEWEB)

    Dongxu, L.; Xuequan, W.; Jinlin, S.; Yujiang, W.

    2000-01-01

    Based on the activation theory of alkali and sulfate, the influence of compound admixtures on the properties of high-content slag cement was studied by testing the strength, pore structure, hydrates, and microstructure, Test results show that compound admixtures can obviously improve the properties of high-content slag cement. The emphasis of the present research is two-fold: substituting gypsum with anhydrite and calcining gypsum. These both can improve early and later performance.

  17. Integrating high-content imaging and chemical genetics to probe host cellular pathways critical for Yersinia pestis infection.

    Directory of Open Access Journals (Sweden)

    Krishna P Kota

    Full Text Available The molecular machinery that regulates the entry and survival of Yersinia pestis in host macrophages is poorly understood. Here, we report the development of automated high-content imaging assays to quantitate the internalization of virulent Y. pestis CO92 by macrophages and the subsequent activation of host NF-κB. Implementation of these assays in a focused chemical screen identified kinase inhibitors that inhibited both of these processes. Rac-2-ethoxy-3 octadecanamido-1-propylphosphocholine (a protein Kinase C inhibitor, wortmannin (a PI3K inhibitor, and parthenolide (an IκB kinase inhibitor, inhibited pathogen-induced NF-κB activation and reduced bacterial entry and survival within macrophages. Parthenolide inhibited NF-κB activation in response to stimulation with Pam3CSK4 (a TLR2 agonist, E. coli LPS (a TLR4 agonist or Y. pestis infection, while the PI3K and PKC inhibitors were selective only for Y. pestis infection. Together, our results suggest that phagocytosis is the major stimulus for NF-κB activation in response to Y. pestis infection, and that Y. pestis entry into macrophages may involve the participation of protein kinases such as PI3K and PKC. More importantly, the automated image-based screening platform described here can be applied to the study of other bacteria in general and, in combination with chemical genetic screening, can be used to identify host cell functions facilitating the identification of novel antibacterial therapeutics.

  18. A Metric and Workflow for Quality Control in the Analysis of Heterogeneity in Phenotypic Profiles and Screens

    Science.gov (United States)

    Gough, Albert; Shun, Tongying; Taylor, D. Lansing; Schurdak, Mark

    2016-01-01

    Heterogeneity is well recognized as a common property of cellular systems that impacts biomedical research and the development of therapeutics and diagnostics. Several studies have shown that analysis of heterogeneity: gives insight into mechanisms of action of perturbagens; can be used to predict optimal combination therapies; and to quantify heterogeneity in tumors where heterogeneity is believed to be associated with adaptation and resistance. Cytometry methods including high content screening (HCS), high throughput microscopy, flow cytometry, mass spec imaging and digital pathology capture cell level data for populations of cells. However it is often assumed that the population response is normally distributed and therefore that the average adequately describes the results. A deeper understanding of the results of the measurements and more effective comparison of perturbagen effects requires analysis that takes into account the distribution of the measurements, i.e. the heterogeneity. However, the reproducibility of heterogeneous data collected on different days, and in different plates/slides has not previously been evaluated. Here we show that conventional assay quality metrics alone are not adequate for quality control of the heterogeneity in the data. To address this need, we demonstrate the use of the Kolmogorov-Smirnov statistic as a metric for monitoring the reproducibility of heterogeneity in an SAR screen, describe a workflow for quality control in heterogeneity analysis. One major challenge in high throughput biology is the evaluation and interpretation of heterogeneity in thousands of samples, such as compounds in a cell-based screen. In this study we also demonstrate that three heterogeneity indices previously reported, capture the shapes of the distributions and provide a means to filter and browse big data sets of cellular distributions in order to compare and identify distributions of interest. These metrics and methods are presented as a

  19. Challenges and Opportunities to Improve Cervical Cancer Screening Rates in US Health Centers through Patient-Centered Medical Home Transformation

    Directory of Open Access Journals (Sweden)

    Olga Moshkovich

    2015-01-01

    Full Text Available Over the last 50 years, the incidence of cervical cancer has dramatically decreased. However, health disparities in cervical cancer screening (CCS persist for women from racial and ethnic minorities and those residing in rural and poor communities. For more than 45 years, federally funded health centers (HCs have been providing comprehensive, culturally competent, and quality primary health care services to medically underserved communities and vulnerable populations. To enhance the quality of care and to ensure more women served at HCs are screened for cervical cancer, over eight HCs received funding to support patient-centered medical home (PCMH transformation with goals to increase CCS rates. The study conducted a qualitative analysis using Atlas.ti software to describe the barriers and challenges to CCS and PCMH transformation, to identify potential solutions and opportunities, and to examine patterns in barriers and solutions proposed by HCs. Interrater reliability was assessed using Cohen’s Kappa. The findings indicated that HCs more frequently described patient-level barriers to CCS, including demographic, cultural, and health belief/behavior factors. System-level barriers were the next commonly cited, particularly failure to use the full capability of electronic medical records (EMRs and problems coordinating with external labs or providers. Provider-level barriers were least frequently cited.

  20. Synthetic Biomaterials to Rival Nature's Complexity-a Path Forward with Combinatorics, High-Throughput Discovery, and High-Content Analysis.

    Science.gov (United States)

    Zhang, Douglas; Lee, Junmin; Kilian, Kristopher A

    2017-10-01

    Cells in tissue receive a host of soluble and insoluble signals in a context-dependent fashion, where integration of these cues through a complex network of signal transduction cascades will define a particular outcome. Biomaterials scientists and engineers are tasked with designing materials that can at least partially recreate this complex signaling milieu towards new materials for biomedical applications. In this progress report, recent advances in high throughput techniques and high content imaging approaches that are facilitating the discovery of efficacious biomaterials are described. From microarrays of synthetic polymers, peptides and full-length proteins, to designer cell culture systems that present multiple biophysical and biochemical cues in tandem, it is discussed how the integration of combinatorics with high content imaging and analysis is essential to extracting biologically meaningful information from large scale cellular screens to inform the design of next generation biomaterials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery

    Directory of Open Access Journals (Sweden)

    Cervantes Serena

    2009-06-01

    Full Text Available Abstract Background Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes. Results After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells. Conclusion This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.

  2. Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Tolosa, Laia [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Gómez-Lechón, M. José [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Jiménez, Nuria [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Hervás, David [Biostatistics Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Jover, Ramiro [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain); Donato, M. Teresa, E-mail: donato_mte@gva.es [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain)

    2016-07-01

    Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

  3. Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

    International Nuclear Information System (INIS)

    Tolosa, Laia; Gómez-Lechón, M. José; Jiménez, Nuria; Hervás, David; Jover, Ramiro; Donato, M. Teresa

    2016-01-01

    Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

  4. High content analysis platform for optimization of lipid mediated CRISPR-Cas9 delivery strategies in human cells.

    Science.gov (United States)

    Steyer, Benjamin; Carlson-Stevermer, Jared; Angenent-Mari, Nicolas; Khalil, Andrew; Harkness, Ty; Saha, Krishanu

    2016-04-01

    Non-viral gene-editing of human cells using the CRISPR-Cas9 system requires optimized delivery of multiple components. Both the Cas9 endonuclease and a single guide RNA, that defines the genomic target, need to be present and co-localized within the nucleus for efficient gene-editing to occur. This work describes a new high-throughput screening platform for the optimization of CRISPR-Cas9 delivery strategies. By exploiting high content image analysis and microcontact printed plates, multi-parametric gene-editing outcome data from hundreds to thousands of isolated cell populations can be screened simultaneously. Employing this platform, we systematically screened four commercially available cationic lipid transfection materials with a range of RNAs encoding the CRISPR-Cas9 system. Analysis of Cas9 expression and editing of a fluorescent mCherry reporter transgene within human embryonic kidney cells was monitored over several days after transfection. Design of experiments analysis enabled rigorous evaluation of delivery materials and RNA concentration conditions. The results of this analysis indicated that the concentration and identity of transfection material have significantly greater effect on gene-editing than ratio or total amount of RNA. Cell subpopulation analysis on microcontact printed plates, further revealed that low cell number and high Cas9 expression, 24h after CRISPR-Cas9 delivery, were strong predictors of gene-editing outcomes. These results suggest design principles for the development of materials and transfection strategies with lipid-based materials. This platform could be applied to rapidly optimize materials for gene-editing in a variety of cell/tissue types in order to advance genomic medicine, regenerative biology and drug discovery. CRISPR-Cas9 is a new gene-editing technology for "genome surgery" that is anticipated to treat genetic diseases. This technology uses multiple components of the Cas9 system to cut out disease-causing mutations

  5. Seismic Performance Comparison of a High-Content SDA Frame and Standard RC Frame

    OpenAIRE

    van de Lindt, John W.; Rechan, R. Karthik

    2011-01-01

    This study presents the method and results of an experiment to study the seismic behavior of a concrete portal frame with fifty percent of its cement content replaced with a spray dryer ash (SDA). Based on multiple-shake-table tests, the high content SDA frame was found to perform as well as the standard concrete frame for two earthquakes exceeding design-level intensity earthquakes. Hence, from a purely seismic/structural standpoint, it may be possible to replace approximately fifty percen...

  6. Assessing cellular toxicities in fibroblasts upon exposure to lipid-based nanoparticles: a high content analysis approach

    Science.gov (United States)

    Solmesky, Leonardo J.; Shuman, Michal; Goldsmith, Meir; Weil, Miguel; Peer, Dan

    2011-12-01

    Lipid-based nanoparticles (LNPs) are widely used for the delivery of drugs and nucleic acids. Although most of them are considered safe, there is confusing evidence in the literature regarding their potential cellular toxicities. Moreover, little is known about the recovery process cells undergo after a cytotoxic insult. We have previously studied the systemic effects of common LNPs with different surface charge (cationic, anionic, neutral) and revealed that positively charged LNPs ((+)LNPs) activate pro-inflammatory cytokines and induce interferon response by acting as an agonist of Toll-like receptor 4 on immune cells. In this study, we focused on the response of human fibroblasts exposed to LNPs and their cellular recovery process. To this end, we used image-based high content analysis (HCA). Using this strategy, we were able to show simultaneously, in several intracellular parameters, that fibroblasts can recover from the cytotoxic effects of (+)LNPs. The use of HCA opens new avenues in understanding cellular response and nanotoxicity and may become a valuable tool for screening safe materials for drug delivery and tissue engineering.

  7. Assessing cellular toxicities in fibroblasts upon exposure to lipid-based nanoparticles: a high content analysis approach

    International Nuclear Information System (INIS)

    Solmesky, Leonardo J; Weil, Miguel; Shuman, Michal; Goldsmith, Meir; Peer, Dan

    2011-01-01

    Lipid-based nanoparticles (LNPs) are widely used for the delivery of drugs and nucleic acids. Although most of them are considered safe, there is confusing evidence in the literature regarding their potential cellular toxicities. Moreover, little is known about the recovery process cells undergo after a cytotoxic insult. We have previously studied the systemic effects of common LNPs with different surface charge (cationic, anionic, neutral) and revealed that positively charged LNPs ((+)LNPs) activate pro-inflammatory cytokines and induce interferon response by acting as an agonist of Toll-like receptor 4 on immune cells. In this study, we focused on the response of human fibroblasts exposed to LNPs and their cellular recovery process. To this end, we used image-based high content analysis (HCA). Using this strategy, we were able to show simultaneously, in several intracellular parameters, that fibroblasts can recover from the cytotoxic effects of (+)LNPs. The use of HCA opens new avenues in understanding cellular response and nanotoxicity and may become a valuable tool for screening safe materials for drug delivery and tissue engineering.

  8. High-efficient and high-content cytotoxic recording via dynamic and continuous cell-based impedance biosensor technology.

    Science.gov (United States)

    Hu, Ning; Fang, Jiaru; Zou, Ling; Wan, Hao; Pan, Yuxiang; Su, Kaiqi; Zhang, Xi; Wang, Ping

    2016-10-01

    Cell-based bioassays were effective method to assess the compound toxicity by cell viability, and the traditional label-based methods missed much information of cell growth due to endpoint detection, while the higher throughputs were demanded to obtain dynamic information. Cell-based biosensor methods can dynamically and continuously monitor with cell viability, however, the dynamic information was often ignored or seldom utilized in the toxin and drug assessment. Here, we reported a high-efficient and high-content cytotoxic recording method via dynamic and continuous cell-based impedance biosensor technology. The dynamic cell viability, inhibition ratio and growth rate were derived from the dynamic response curves from the cell-based impedance biosensor. The results showed that the biosensors has the dose-dependent manners to diarrhetic shellfish toxin, okadiac acid based on the analysis of the dynamic cell viability and cell growth status. Moreover, the throughputs of dynamic cytotoxicity were compared between cell-based biosensor methods and label-based endpoint methods. This cell-based impedance biosensor can provide a flexible, cost and label-efficient platform of cell viability assessment in the shellfish toxin screening fields.

  9. Workflow for high-content, individual cell quantification of fluorescent markers from universal microscope data, supported by open source software.

    Science.gov (United States)

    Stockwell, Simon R; Mittnacht, Sibylle

    2014-12-16

    Advances in understanding the control mechanisms governing the behavior of cells in adherent mammalian tissue culture models are becoming increasingly dependent on modes of single-cell analysis. Methods which deliver composite data reflecting the mean values of biomarkers from cell populations risk losing subpopulation dynamics that reflect the heterogeneity of the studied biological system. In keeping with this, traditional approaches are being replaced by, or supported with, more sophisticated forms of cellular assay developed to allow assessment by high-content microscopy. These assays potentially generate large numbers of images of fluorescent biomarkers, which enabled by accompanying proprietary software packages, allows for multi-parametric measurements per cell. However, the relatively high capital costs and overspecialization of many of these devices have prevented their accessibility to many investigators. Described here is a universally applicable workflow for the quantification of multiple fluorescent marker intensities from specific subcellular regions of individual cells suitable for use with images from most fluorescent microscopes. Key to this workflow is the implementation of the freely available Cell Profiler software(1) to distinguish individual cells in these images, segment them into defined subcellular regions and deliver fluorescence marker intensity values specific to these regions. The extraction of individual cell intensity values from image data is the central purpose of this workflow and will be illustrated with the analysis of control data from a siRNA screen for G1 checkpoint regulators in adherent human cells. However, the workflow presented here can be applied to analysis of data from other means of cell perturbation (e.g., compound screens) and other forms of fluorescence based cellular markers and thus should be useful for a wide range of laboratories.

  10. An RNA replication-center assay for high content image-based quantifications of human rhinovirus and coxsackievirus infections

    Directory of Open Access Journals (Sweden)

    Lötzerich Mark

    2010-10-01

    Full Text Available Abstract Background Picornaviruses are common human and animal pathogens, including polio and rhinoviruses of the enterovirus family, and hepatits A or food-and-mouth disease viruses. There are no effective countermeasures against the vast majority of picornaviruses, with the exception of polio and hepatitis A vaccines. Human rhinoviruses (HRV are the most prevalent picornaviruses comprising more than one hundred serotypes. The existing and also emerging HRVs pose severe health risks for patients with asthma or chronic obstructive pulmonary disease. Here, we developed a serotype-independent infection assay using a commercially available mouse monoclonal antibody (mabJ2 detecting double-strand RNA. Results Immunocytochemical staining for RNA replication centers using mabJ2 identified cells that were infected with either HRV1A, 2, 14, 16, 37 or coxsackievirus (CV B3, B4 or A21. MabJ2 labeled-cells were immunocytochemically positive for newly synthesized viral capsid proteins from HRV1A, 14, 16, 37 or CVB3, 4. We optimized the procedure for detection of virus replication in settings for high content screening with automated fluorescence microscopy and single cell analysis. Our data show that the infection signal was dependent on multiplicity, time and temperature of infection, and the mabJ2-positive cell numbers correlated with viral titres determined in single step growth curves. The mabJ2 infection assay was adapted to determine the efficacy of anti-viral compounds and small interfering RNAs (siRNAs blocking enterovirus infections. Conclusions We report a broadly applicable, rapid protocol to measure infection of cultured cells with enteroviruses at single cell resolution. This assay can be applied to a wide range of plus-sense RNA viruses, and hence allows comparative studies of viral infection biology without dedicated reagents or procedures. This protocol also allows to directly compare results from small compound or siRNA infection screens

  11. Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi in a myoblastic cell line.

    Directory of Open Access Journals (Sweden)

    Julio Alonso-Padilla

    2015-01-01

    Full Text Available Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, represents a very important public health problem in Latin America where it is endemic. Although mostly asymptomatic at its initial stage, after the disease becomes chronic, about a third of the infected patients progress to a potentially fatal outcome due to severe damage of heart and gut tissues. There is an urgent need for new drugs against Chagas disease since there are only two drugs available, benznidazole and nifurtimox, and both show toxic side effects and variable efficacy against the chronic stage of the disease.Genetically engineered parasitic strains are used for high throughput screening (HTS of large chemical collections in the search for new anti-parasitic compounds. These assays, although successful, are limited to reporter transgenic parasites and do not cover the wide T. cruzi genetic background. With the aim to contribute to the early drug discovery process against Chagas disease we have developed an automated image-based 384-well plate HTS assay for T. cruzi amastigote replication in a rat myoblast host cell line. An image analysis script was designed to inform on three outputs: total number of host cells, ratio of T. cruzi amastigotes per cell and percentage of infected cells, which respectively provides one host cell toxicity and two T. cruzi toxicity readouts. The assay was statistically robust (Z´ values >0.6 and was validated against a series of known anti-trypanosomatid drugs.We have established a highly reproducible, high content HTS assay for screening of chemical compounds against T. cruzi infection of myoblasts that is amenable for use with any T. cruzi strain capable of in vitro infection. Our visual assay informs on both anti-parasitic and host cell toxicity readouts in a single experiment, allowing the direct identification of compounds selectively targeted to the parasite.

  12. Photometric determination of niobium in materials with high content of phosphorus

    International Nuclear Information System (INIS)

    Navrotskaya, V.A.; Aleksandrova, E.I.; Kletenik, Yu.B.

    1982-01-01

    To determine niobium in various samples of niobium concentrates with a high phosphorus content, a photometric method with pyridylazoresorcinol (PAR) is used. It is shown that all the elements indicated (Fe, Si, Ti, Al, Ca) including phosphorus do not interfere with the niobium determination with the use of PAR. The method has been tried on artificial samples with different content of the base components. Variation coefficient constitutes 4.5%. No systematic errors, due to a high content of any concomitant element, are detected. The determination threshold is 10 - 2 %

  13. A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

    Directory of Open Access Journals (Sweden)

    Pei Kan

    2011-01-01

    Full Text Available A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4∘C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40 mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use.

  14. Automated analysis of high-content microscopy data with deep learning.

    Science.gov (United States)

    Kraus, Oren Z; Grys, Ben T; Ba, Jimmy; Chong, Yolanda; Frey, Brendan J; Boone, Charles; Andrews, Brenda J

    2017-04-18

    Existing computational pipelines for quantitative analysis of high-content microscopy data rely on traditional machine learning approaches that fail to accurately classify more than a single dataset without substantial tuning and training, requiring extensive analysis. Here, we demonstrate that the application of deep learning to biological image data can overcome the pitfalls associated with conventional machine learning classifiers. Using a deep convolutional neural network (DeepLoc) to analyze yeast cell images, we show improved performance over traditional approaches in the automated classification of protein subcellular localization. We also demonstrate the ability of DeepLoc to classify highly divergent image sets, including images of pheromone-arrested cells with abnormal cellular morphology, as well as images generated in different genetic backgrounds and in different laboratories. We offer an open-source implementation that enables updating DeepLoc on new microscopy datasets. This study highlights deep learning as an important tool for the expedited analysis of high-content microscopy data. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  15. High-content analysis of single cells directly assembled on CMOS sensor based on color imaging.

    Science.gov (United States)

    Tanaka, Tsuyoshi; Saeki, Tatsuya; Sunaga, Yoshihiko; Matsunaga, Tadashi

    2010-12-15

    A complementary metal oxide semiconductor (CMOS) image sensor was applied to high-content analysis of single cells which were assembled closely or directly onto the CMOS sensor surface. The direct assembling of cell groups on CMOS sensor surface allows large-field (6.66 mm×5.32 mm in entire active area of CMOS sensor) imaging within a second. Trypan blue-stained and non-stained cells in the same field area on the CMOS sensor were successfully distinguished as white- and blue-colored images under white LED light irradiation. Furthermore, the chemiluminescent signals of each cell were successfully visualized as blue-colored images on CMOS sensor only when HeLa cells were placed directly on the micro-lens array of the CMOS sensor. Our proposed approach will be a promising technique for real-time and high-content analysis of single cells in a large-field area based on color imaging. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Depth-resolved incoherent and coherent wide-field high-content imaging (Conference Presentation)

    Science.gov (United States)

    So, Peter T.

    2016-03-01

    Recent advances in depth-resolved wide-field imaging technique has enabled many high throughput applications in biology and medicine. Depth resolved imaging of incoherent signals can be readily accomplished with structured light illumination or nonlinear temporal focusing. The integration of these high throughput systems with novel spectroscopic resolving elements further enable high-content information extraction. We will introduce a novel near common-path interferometer and demonstrate its uses in toxicology and cancer biology applications. The extension of incoherent depth-resolved wide-field imaging to coherent modality is non-trivial. Here, we will cover recent advances in wide-field 3D resolved mapping of refractive index, absorbance, and vibronic components in biological specimens.

  17. DETERMINATION OF STRONTIUM IONS IN WATERS WITH A HIGH CONTENT OF SODIUM IONS

    Directory of Open Access Journals (Sweden)

    Tatiana Mitina

    2015-06-01

    Full Text Available This paper reports on the influence of sodium ions on experimental determination of strontium ions concentration in waters with a high content of sodium ions by using emission flame photometry and atomic absorption spectroscopy. For the method of emission flame photometry it was shown that at a wavelength of 460.7 nm (spectral emission line of strontium the emission is linearly dependent on the concentration of sodium ions. The greatest impact of high concentrations of sodium ions on the result of determination the strontium ions concentration has been registered at low levels of strontium. The influence of nitric acid on the results is also discussed. In the case of using atomic absorption spectroscopy method no influence of sodium ions and nitric acid on the results of determination the strontium ions concentration was revealed. The metrological characteristics of both methods are evaluated.

  18. Method for evaluating building materials with a high content of radioactivity

    International Nuclear Information System (INIS)

    Stranden, E.

    1979-01-01

    In order to avoid increased radiation doses to the population due to the introduction of building materials with an unusually high content of radioactivity, a method for evaluating building materials has been developed. An expression for the gamma radiation due to radium, thorium and potassium 40 has been proposed by a Scandinavian group. When this value for a given material does not exceed 1, then no restriction is placed. Should it exceed 1, then the material is subjected to further investigation. Similarly, since the radon concentration depends on the radium content, an expression for this is proposed. Should this be less than unity the material may be sold freely. Should it exceed unity, further investigations must be made. Measurements have also been made on the exhalation of radon from concrete, and the results are given. An expression including this exhalation rate and the ventilation rate, giving the radon concentration is given. (JIW)

  19. General Staining and Segmentation Procedures for High Content Imaging and Analysis.

    Science.gov (United States)

    Chambers, Kevin M; Mandavilli, Bhaskar S; Dolman, Nick J; Janes, Michael S

    2018-01-01

    Automated quantitative fluorescence microscopy, also known as high content imaging (HCI), is a rapidly growing analytical approach in cell biology. Because automated image analysis relies heavily on robust demarcation of cells and subcellular regions, reliable methods for labeling cells is a critical component of the HCI workflow. Labeling of cells for image segmentation is typically performed with fluorescent probes that bind DNA for nuclear-based cell demarcation or with those which react with proteins for image analysis based on whole cell staining. These reagents, along with instrument and software settings, play an important role in the successful segmentation of cells in a population for automated and quantitative image analysis. In this chapter, we describe standard procedures for labeling and image segmentation in both live and fixed cell samples. The chapter will also provide troubleshooting guidelines for some of the common problems associated with these aspects of HCI.

  20. Seismic Performance Comparison of a High-Content SDA Frame and Standard RC Frame

    Directory of Open Access Journals (Sweden)

    John W. van de Lindt

    2011-01-01

    Full Text Available This study presents the method and results of an experiment to study the seismic behavior of a concrete portal frame with fifty percent of its cement content replaced with a spray dryer ash (SDA. Based on multiple-shake-table tests, the high content SDA frame was found to perform as well as the standard concrete frame for two earthquakes exceeding design-level intensity earthquakes. Hence, from a purely seismic/structural standpoint, it may be possible to replace approximately fifty percent of cement in a concrete mix with SDA for the construction of structural members in high seismic zones. This would help significantly redirect spray dryer ash away from landfills, thus, providing a sustainable greener alternative to concrete that uses only Portland cement, or only a small percentage of SDA or fly ash.

  1. Recent advances in quantitative high throughput and high content data analysis.

    Science.gov (United States)

    Moutsatsos, Ioannis K; Parker, Christian N

    2016-01-01

    High throughput screening has become a basic technique with which to explore biological systems. Advances in technology, including increased screening capacity, as well as methods that generate multiparametric readouts, are driving the need for improvements in the analysis of data sets derived from such screens. This article covers the recent advances in the analysis of high throughput screening data sets from arrayed samples, as well as the recent advances in the analysis of cell-by-cell data sets derived from image or flow cytometry application. Screening multiple genomic reagents targeting any given gene creates additional challenges and so methods that prioritize individual gene targets have been developed. The article reviews many of the open source data analysis methods that are now available and which are helping to define a consensus on the best practices to use when analyzing screening data. As data sets become larger, and more complex, the need for easily accessible data analysis tools will continue to grow. The presentation of such complex data sets, to facilitate quality control monitoring and interpretation of the results will require the development of novel visualizations. In addition, advanced statistical and machine learning algorithms that can help identify patterns, correlations and the best features in massive data sets will be required. The ease of use for these tools will be important, as they will need to be used iteratively by laboratory scientists to improve the outcomes of complex analyses.

  2. Depression Screening

    Science.gov (United States)

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

  3. Development of a data-processing method based on Bayesian k-means clustering to discriminate aneugens and clastogens in a high-content micronucleus assay.

    Science.gov (United States)

    Huang, Z H; Li, N; Rao, K F; Liu, C T; Huang, Y; Ma, M; Wang, Z J

    2018-03-01

    Genotoxicants can be identified as aneugens and clastogens through a micronucleus (MN) assay. The current high-content screening-based MN assays usually discriminate an aneugen from a clastogen based on only one parameter, such as the MN size, intensity, or morphology, which yields low accuracies (70-84%) because each of these parameters may contribute to the results. Therefore, the development of an algorithm that can synthesize high-dimensionality data to attain comparative results is important. To improve the automation and accuracy of detection using the current parameter-based mode of action (MoA), the MN MoA signatures of 20 chemicals were systematically recruited in this study to develop an algorithm. The results of the algorithm showed very good agreement (93.58%) between the prediction and reality, indicating that the proposed algorithm is a validated analytical platform for the rapid and objective acquisition of genotoxic MoA messages.

  4. A Novel High-Content Immunofluorescence Assay as a Tool to Identify at the Single Cell Level γ-Globin Inducing Compounds.

    Directory of Open Access Journals (Sweden)

    Marta Durlak

    Full Text Available The identification of drugs capable of reactivating γ-globin to ameliorate β-thalassemia and Sickle Cell anemia is still a challenge, as available γ-globin inducers still have limited clinical indications. High-throughput screenings (HTS aimed to identify new potentially therapeutic drugs require suitable first-step-screening methods combining the possibility to detect variation in the γ/β globin ratio with the robustness of a cell line. We took advantage of a K562 cell line variant expressing β-globin (β-K562 to set up a new multiplexed high-content immunofluorescence assay for the quantification of γ- and β-globin content at single-cell level. The assay was validated by using the known globin inducers hemin, hydroxyurea and butyric acid and further tested in a pilot screening that confirmed HDACs as targets for γ-globin induction (as proved by siRNA-mediated HDAC3 knockdown and by treatment with HDACs inhibitors entinostat and dacinostat and identified Heme-oxygenases as novel candidate targets for γ-globin induction. Indeed, Heme-oxygenase2 siRNA knockdown as well as its inhibition by Tin protoporphyrin-IX (TinPPIX greatly increased γ-globin expression. This result is particularly interesting as several metalloporphyrins have already been developed for clinical uses and could be tested (alone or in combination with other drugs to improve pharmacological γ-globin reactivation for the treatment of β-hemoglobinopathies.

  5. Search for Internal Cancers in Mice Tattooed with Inks of High Contents of Potential Carcinogens

    DEFF Research Database (Denmark)

    Sepehri, Mitra; Lerche, Catharina M; Hutton Carlsen, Katrina

    2017-01-01

    on the Danish market due to the measured contents of potential carcinogens; benzo(a)pyrene and 2-anisidine, respectively. The mice were housed for 1 year after tattooing, and autopsy study on internal organs was performed. Tissue samples were systematically taken from major organs for screening of subclinical...

  6. High content analysis of differentiation and cell death in human adipocytes.

    Science.gov (United States)

    Doan-Xuan, Quang Minh; Sarvari, Anitta K; Fischer-Posovszky, Pamela; Wabitsch, Martin; Balajthy, Zoltan; Fesus, Laszlo; Bacso, Zsolt

    2013-10-01

    Understanding adipocyte biology and its homeostasis is in the focus of current obesity research. We aimed to introduce a high-content analysis procedure for directly visualizing and quantifying adipogenesis and adipoapoptosis by laser scanning cytometry (LSC) in a large population of cell. Slide-based image cytometry and image processing algorithms were used and optimized for high-throughput analysis of differentiating cells and apoptotic processes in cell culture at high confluence. Both preadipocytes and adipocytes were simultaneously scrutinized for lipid accumulation, texture properties, nuclear condensation, and DNA fragmentation. Adipocyte commitment was found after incubation in adipogenic medium for 3 days identified by lipid droplet formation and increased light absorption, while terminal differentiation of adipocytes occurred throughout day 9-14 with characteristic nuclear shrinkage, eccentric nuclei localization, chromatin condensation, and massive lipid deposition. Preadipocytes were shown to be more prone to tumor necrosis factor alpha (TNFα)-induced apoptosis compared to mature adipocytes. Importantly, spontaneous DNA fragmentation was observed at early stage when adipocyte commitment occurs. This DNA damage was independent from either spontaneous or induced apoptosis and probably was part of the differentiation program. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

  7. Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance.

    Science.gov (United States)

    Lukášová, Ivana; Muselík, Jan; Franc, Aleš; Goněc, Roman; Mika, Filip; Vetchý, David

    2017-11-15

    Warfarin is intensively discussed drug with narrow therapeutic range. There have been cases of bleeding attributed to varying content or altered quality of the active substance. Factor analysis is useful for finding suitable technological parameters leading to high content uniformity of tablets containing low amount of active substance. The composition of tabletting blend and technological procedure were set with respect to factor analysis of previously published results. The correctness of set parameters was checked by manufacturing and evaluation of tablets containing 1-10mg of warfarin sodium. The robustness of suggested technology was checked by using "worst case scenario" and statistical evaluation of European Pharmacopoeia (EP) content uniformity limits with respect to Bergum division and process capability index (Cpk). To evaluate the quality of active substance and tablets, dissolution method was developed (water; EP apparatus II; 25rpm), allowing for statistical comparison of dissolution profiles. Obtained results prove the suitability of factor analysis to optimize the composition with respect to batches manufactured previously and thus the use of metaanalysis under industrial conditions is feasible. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. A Simple and Sensitive High-Content Assay for the Characterization of Antiproliferative Therapeutic Antibodies.

    Science.gov (United States)

    Stengl, Andreas; Hörl, David; Leonhardt, Heinrich; Helma, Jonas

    2017-03-01

    Monoclonal antibodies (mAbs) have become a central class of therapeutic agents in particular as antiproliferative compounds. Their often complex modes of action require sensitive assays during early, functional characterization. Current cell-based proliferation assays often detect metabolites that are indicative of metabolic activity but do not directly account for cell proliferation. Measuring DNA replication by incorporation of base analogues such as 5-bromo-2'-deoxyuridine (BrdU) fills this analytical gap but was previously restricted to bulk effect characterization in enzyme-linked immunosorbent assay formats. Here, we describe a cell-based assay format for the characterization of antiproliferative mAbs regarding potency and mode of action in a single experiment. The assay makes use of single cell-based high-content-analysis (HCA) for the reliable quantification of replicating cells and DNA content via 5-ethynyl-2'-deoxyuridine (EdU) and 4',6-diamidino-2-phenylindole (DAPI), respectively, as sensitive measures of antiproliferative mAb activity. We used trastuzumab, an antiproliferative therapeutic antibody interfering with HER2 cell surface receptor-mediated growth signal transduction, and HER2-overexpressing cell lines BT474 and SKBR3 to demonstrate up to 10-fold signal-to-background (S/B) ratios for treated versus untreated cells and a shift in cell cycle profiles indicating antibody-induced cell cycle arrest. The assay is simple, cost-effective, and sensitive, providing a cell-based format for preclinical characterization of therapeutic mAbs.

  9. Teachable, high-content analytics for live-cell, phase contrast movies.

    Science.gov (United States)

    Alworth, Samuel V; Watanabe, Hirotada; Lee, James S J

    2010-09-01

    CL-Quant is a new solution platform for broad, high-content, live-cell image analysis. Powered by novel machine learning technologies and teach-by-example interfaces, CL-Quant provides a platform for the rapid development and application of scalable, high-performance, and fully automated analytics for a broad range of live-cell microscopy imaging applications, including label-free phase contrast imaging. The authors used CL-Quant to teach off-the-shelf universal analytics, called standard recipes, for cell proliferation, wound healing, cell counting, and cell motility assays using phase contrast movies collected on the BioStation CT and BioStation IM platforms. Similar to application modules, standard recipes are intended to work robustly across a wide range of imaging conditions without requiring customization by the end user. The authors validated the performance of the standard recipes by comparing their performance with truth created manually, or by custom analytics optimized for each individual movie (and therefore yielding the best possible result for the image), and validated by independent review. The validation data show that the standard recipes' performance is comparable with the validated truth with low variation. The data validate that the CL-Quant standard recipes can provide robust results without customization for live-cell assays in broad cell types and laboratory settings.

  10. Thermogravimetric Analysis of Effects of High-Content Limstone Addition on Combustion Characteristics of Taixi Anthracite

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; LI Mei; SUN Min; WEI Xian-yong

    2004-01-01

    Combustion characteristics of Taixi anthracite admixed with high content of limestone addition were investigated with thermogravimetric analysis. The results show that limestone addition has a little promoting effect on the ignition of raw coals as a whole. The addition of limestone is found to significantly accelerate the combustion and burnout of raw coals. The higher the sample mass is, the more significant the effect will be. The results also show that the change of limestone proportion between 45%-80% has little effect on ignition temperatures of coal in the blended samples. Increasing limestone content lowers the temperature corresponding to the maximum weight loss. Although higher maximum mass loss rates are observed with higher limestone content, the effect is found not ascribed to changing limestone addition, but to the decrease of absolute coal mass in the sample. The change of limestone proportion has little effect on its burnout temperature. Mechanism analysis indicates that these phenomena result mainly from improved heat conduction due to limestone addition.

  11. Enhancement of lipid accumulation by oleaginous yeast through phosphorus limitation under high content of ammonia.

    Science.gov (United States)

    Huang, Xiangfeng; Luo, Huijuan; Mu, Tianshuai; Shen, Yi; Yuan, Ming; Liu, Jia

    2018-04-18

    Low concentrations of acetic acid were used as carbon source to cultivate Cryptococcus curvatus MUCL 29819 for lipid production under high content of ammonia. Phosphorus limitation combined with initial pH regulation (pH = 6) weakened inhibition of free ammonia and promoted lipid accumulation. In batch cultivation, the produced lipid content and yield was 30.3% and 0.92 g/L, higher than those under unlimited condition (18.3% and 0.64 g/L). The content of monounsaturated fatty acid also increased from 37.3% (unlimited condition) to 45.8% (phosphorus-limited condition). During sequencing batch cultivation (SBC), the lipid content reached up to 51.02% under phosphorus-limited condition while only 31.88% under unlimited condition, which can be explained by the higher conversion efficiency of the carbon source to lipid. The total energy consumption including lipid extraction, transesterification and purification was 7.47 and 8.33 GJ under phosphorus-limited and unlimited condition, respectively. Copyright © 2018. Published by Elsevier Ltd.

  12. High-content profiling of cell responsiveness to graded substrates based on combinyatorially variant polymers.

    Science.gov (United States)

    Liu, Er; Treiser, Matthew D; Patel, Hiral; Sung, Hak-Joon; Roskov, Kristen E; Kohn, Joachim; Becker, Matthew L; Moghe, Prabhas V

    2009-08-01

    We have developed a novel approach combining high information and high throughput analysis to characterize cell adhesive responses to biomaterial substrates possessing gradients in surface topography. These gradients were fabricated by subjecting thin film blends of tyrosine-derived polycarbonates, i.e. poly(DTE carbonate) and poly(DTO carbonate) to a gradient temperature annealing protocol. Saos-2 cells engineered with a green fluorescent protein (GFP) reporter for farnesylation (GFP-f) were cultured on the gradient substrates to assess the effects of nanoscale surface topology and roughness that arise during the phase separation process on cell attachment and adhesion strength. The high throughput imaging approach allowed us to rapidly identify the "global" and "high content" structure-property relationships between cell adhesion and biomaterial properties such as polymer chemistry and topography. This study found that cell attachment and spreading increased monotonically with DTE content and were significantly elevated at the position with intermediate regions corresponding to the highest "gradient" of surface roughness, while GFP-f farnesylation intensity descriptors were sensitively altered by surface roughness, even in cells with comparable levels of spreading.

  13. A multi-scale convolutional neural network for phenotyping high-content cellular images.

    Science.gov (United States)

    Godinez, William J; Hossain, Imtiaz; Lazic, Stanley E; Davies, John W; Zhang, Xian

    2017-07-01

    Identifying phenotypes based on high-content cellular images is challenging. Conventional image analysis pipelines for phenotype identification comprise multiple independent steps, with each step requiring method customization and adjustment of multiple parameters. Here, we present an approach based on a multi-scale convolutional neural network (M-CNN) that classifies, in a single cohesive step, cellular images into phenotypes by using directly and solely the images' pixel intensity values. The only parameters in the approach are the weights of the neural network, which are automatically optimized based on training images. The approach requires no a priori knowledge or manual customization, and is applicable to single- or multi-channel images displaying single or multiple cells. We evaluated the classification performance of the approach on eight diverse benchmark datasets. The approach yielded overall a higher classification accuracy compared with state-of-the-art results, including those of other deep CNN architectures. In addition to using the network to simply obtain a yes-or-no prediction for a given phenotype, we use the probability outputs calculated by the network to quantitatively describe the phenotypes. This study shows that these probability values correlate with chemical treatment concentrations. This finding validates further our approach and enables chemical treatment potency estimation via CNNs. The network specifications and solver definitions are provided in Supplementary Software 1. william_jose.godinez_navarro@novartis.com or xian-1.zhang@novartis.com. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  14. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.

    Science.gov (United States)

    Romano, Barbara; Borrelli, Francesca; Pagano, Ester; Cascio, Maria Grazia; Pertwee, Roger G; Izzo, Angelo A

    2014-04-15

    Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice. CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer. CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. Colloidal processing of Fe-based metalceramic composites with high content of ceramic reinforcement

    Directory of Open Access Journals (Sweden)

    Escribano, J. A.

    2013-12-01

    Full Text Available Major difficulties of processing metal-matrix composites by means of conventional powder metallurgy techniques are the lack of dispersion of the phases within the final microstructure. In this work, processing through colloidal techniques of the Fe-based metal-matrix composites, with a high content of a ceramic reinforcement (Ti(C,N , is presented for the first time in the literature. The colloidal approach allows a higher control of the powders packing and a better homogenization of phases since powders are mixed in a liquid medium. The chemical stability of Fe in aqueous medium determines the dispersion conditions of the mixture. The Fe slurries were formulated by optimising their zeta potential and their rheology, in order to shape bulk pieces by slip-casting. Preliminary results demonstrate the viability of this procedure, also opening new paths to the microstructural design of fully sintered Fe-based hard metal, with 50 vol. % of Ti(C,N in its composition.Las principales dificultades de procesamiento de materiales compuestos de matriz metálica por medio de técnicas convencionales pulvimetalúrgicas es la falta de dispersión entre fases dentro de la microestructura final. Este trabajo describe por primera vez el procesamiento de materiales compuestos de matriz metálica de Fe, con un alto contenido de un refuerzo cerámico (Ti (C, N, mediante técnicas coloidales. El procesamiento coloidal permite un mayor control sobre el empaquetamiento de polvos y una mejor homogeneización de las fases al mezclarse los polvos en un medio líquido. La estabilidad química del Fe en medio acuoso determina las condiciones de dispersión de la mezcla. Las suspensiones de Fe se formularon mediante la optimización del potencial zeta y de su reología, con el fin de dar forma a piezas compactas por colaje en molde de escayola. Los resultados preliminares mostrados demuestran la viabilidad del proceso, además de abrir nuevas vías al dise

  16. A Photobioreactor System for Precision Cultivation of Photoautotrophic Microorganisms and for High-Content Analysis of Suspension Dynamics

    Czech Academy of Sciences Publication Activity Database

    Nedbal, Ladislav; Trtílek, M.; Červený, Jan; Komárek, Ondřej; Pakrasi, Himadri B.

    2008-01-01

    Roč. 100, č. 5 (2008), s. 902-910 ISSN 0006-3592 R&D Projects: GA ČR GA206/05/0894 Institutional research plan: CEZ:AV0Z60870520 Keywords : algae * cyanobacteria * high-content monitoring * microbial growth * photosynthesis * systems biology Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.936, year: 2008

  17. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    OpenAIRE

    Ester Pagano; Raffaele Capasso; Fabiana Piscitelli; Barbara Romano; Olga Alessandra Parisi; Stefania Finizio; Anna Lauritano; Vincenzo Di Marzo; Angelo A Izzo; Francesca Borrelli

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was ev...

  18. A one-step bioprocess for production of high-content fructo-oligosaccharides from inulin by yeast.

    Science.gov (United States)

    Wang, Da; Li, Fu-Li; Wang, Shi-An

    2016-10-20

    Commercial fructo-oligosaccharides (FOS) are predominantly produced from sucrose by transfructosylation process that presents a maximum theoretical yield below 0.60gFOSgSucrose(-1). To obtain high-content FOS, costly purification is generally employed. Additionally, high-content FOS can be produced from inulin by using endo-inulinases. However, commercial endo-inulinases have not been extensively used in scale-up production of FOS. In the present study, a one-step bioprocess that integrated endo-inulinase production, FOS fermentation, and non-FOS sugars removal into one reactor was proposed to produce high-content FOS from inulin. The bioprocess was implemented by a recombinant yeast strain JZHΔS-TSC, in which a heterologous endo-inulinase gene was expressed and the inherent invertase gene SUC2 was disrupted. FOS fermentation at 40°C from 200g/L chicory inulin presented the maximun titer, yield, and productivity of 180.2±0.8g/L, 0.9gFOSgInulin(-1), and 7.51±0.03g/L/h, respectively. This study demonstrated that the one-step bioprocess was simple and highly efficient. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Dynamic heterogeneity of DNA methylation and hydroxymethylation in embryonic stem cell populations captured by single-cell 3D high-content analysis

    Energy Technology Data Exchange (ETDEWEB)

    Tajbakhsh, Jian, E-mail: tajbakhshj@cshs.org [Chromatin Biology Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Stefanovski, Darko [Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19348 (United States); Tang, George [Chromatin Biology Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Wawrowsky, Kolja [Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Liu, Naiyou; Fair, Jeffrey H. [Department of Surgery and UF Health Comprehensive Transplant Center, University of Florida College of Medicine, Gainesville, FL 32608 (United States)

    2015-03-15

    Cell-surface markers and transcription factors are being used in the assessment of stem cell fate and therapeutic safety, but display significant variability in stem cell cultures. We assessed nuclear patterns of 5-hydroxymethylcytosine (5hmC, associated with pluripotency), a second important epigenetic mark, and its combination with 5-methylcytosine (5mC, associated with differentiation), also in comparison to more established markers of pluripotency (Oct-4) and endodermal differentiation (FoxA2, Sox17) in mouse embryonic stem cells (mESC) over a 10-day differentiation course in vitro: by means of confocal and super-resolution imaging together with 3D high-content analysis, an essential tool in single-cell screening. In summary: 1) We did not measure any significant correlation of putative markers with global 5mC or 5hmC. 2) While average Oct-4 levels stagnated on a cell-population base (0.015 lnIU/day), Sox17 and FoxA2 increased 22-fold and 3-fold faster, respectively (Sox17: 0.343 lnIU/day; FoxA2: 0.046 lnIU/day). In comparison, global DNA methylation levels increased 4-fold faster (0.068 lnIU/day), and global hydroxymethylation declined at 0.046 lnIU/day, both with a better explanation of the temporal profile. 3) This progression was concomitant with the occurrence of distinct nuclear codistribution patterns that represented a heterogeneous spectrum of states in differentiation; converging to three major coexisting 5mC/5hmC phenotypes by day 10: 5hmC{sup +}/5mC{sup −}, 5hmC{sup +}/5mC{sup +}, and 5hmC{sup −}/5mC{sup +} cells. 4) Using optical nanoscopy we could delineate the respective topologies of 5mC/5hmC colocalization in subregions of nuclear DNA: in the majority of 5hmC{sup +}/5mC{sup +} cells 5hmC and 5mC predominantly occupied mutually exclusive territories resembling euchromatic and heterochromatic regions, respectively. Simultaneously, in a smaller subset of cells we observed a tighter colocalization of the two cytosine variants, presumably

  20. Toxicology screen

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

  1. Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis.

    Science.gov (United States)

    Hoffman, Ewelina; Patel, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben; Hutter, Victoria

    2017-12-01

    Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Cell health, morphology and lipid content were comparable (p content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

  2. Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

    Science.gov (United States)

    Smeriglio, Antonella; Giofrè, Salvatore V; Galati, Enza M; Monforte, Maria T; Cicero, Nicola; D'Angelo, Valeria; Grassi, Gianpaolo; Circosta, Clara

    2018-02-07

    Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important. The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes. Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. chemotypes with high content of cannabidiol (CBD)/cannabidiolic acid (CBDA) and cannabigerol (CBG)/cannabigerolic acid (CBGA), respectively, on human recombinant and pig kidney aldose reductase activity in vitro. A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The extracts showed significant dose-dependent aldose reductase inhibitory activity (>70%) and higher than fractions. The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors. The extracts of Cannabis with high content of non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA significantly inhibit aldose reductase activity. These results may have some relevance for the possible use of C. sativa chemotypes based preparations as aldose reductase inhibitors. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. A systematic High-Content Screening microscopy approach reveals key roles for Rab33b, OATL1 and Myo6 in nanoparticle trafficking in HeLa cells

    NARCIS (Netherlands)

    Panarella, Angela; Bexiga, Mariana G; Galea, George; O' Neill, Elaine D; Salvati, Anna; Dawson, Kenneth A; Simpson, Jeremy C

    2016-01-01

    Synthetic nanoparticles are promising tools for imaging and drug delivery; however the molecular details of cellular internalization and trafficking await full characterization. Current knowledge suggests that following endocytosis most nanoparticles pass from endosomes to lysosomes. In order to

  4. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells

    International Nuclear Information System (INIS)

    Carter, Charleata A.; Hamm, Jonathan T.

    2009-01-01

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-κB (NF-κB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-α and NF-κB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30 μg/ml CSC significantly activated PKC-α, while CSC doses above 20 μg/ml CSC significantly activated NF-κB. As NF-κB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30 μg/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30 μg/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-α, NF-κB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

  5. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation.

    Science.gov (United States)

    van Deijk, Anne-Lieke F; Broersen, Laus M; Verkuyl, J Martin; Smit, August B; Verheijen, Mark H G

    2017-01-01

    Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis -docosahexaenoic acid (DHA), uridine and choline- has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro . A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC), improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA), uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium), on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  6. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation

    Directory of Open Access Journals (Sweden)

    Anne-Lieke F. van Deijk

    2017-08-01

    Full Text Available Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis –docosahexaenoic acid (DHA, uridine and choline– has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro. A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC, improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium, on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  7. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  8. ASSESSMENT OF CHEMICAL EFFECTS ON NEURITE OUTGROWTH, NEURONAL POLARIZATION AND SYNAPTOGENESIS IN RAT CORTICAL NEURONS USING HIGH CONTENT IMAGE ANALYSIS

    Science.gov (United States)

    There is a need for efficient, cost-effective methods for screening and prioritization of potential developmental neurotoxicants. One approach uses in vitro cell culture models that can recapitulate the critical processes of nervous system development. In vitro, primary cultures ...

  9. [Development of a high content protein beverage from Chilean mesquite, lupine and quinoa for the diet of pre-schoolers].

    Science.gov (United States)

    Cerezal Mezquita, P; Acosta Barrientos, E; Rojas Valdivia, G; Romero Palacios, N; Arcos Zavala, R

    2012-01-01

    This research was aimed at developing a high content protein beverage from the mixture of liquid extracts of a pseudocereal, quinoa (Chenopodium quinoa Willd) and two legumes: mesquite (Prosopis chilensis (Mol.) Stunz) and lupine (Lupinus albus L.), native from the Andean highlands of the Chilean northern macro-zone, flavored with raspberry pulp, to help in the feeding of children between 2 and 5 years of lower socioeconomic status with nutritional deficiencies. The formulation was defined by linear programming, its composition was determined by proximate analysis and physical, microbiological and sensory acceptance tests were performed. After 90 days of storage time, the beverage got a protein content of 1.36%, being tryptophan the limiting amino acid; for its part, the chromaticity coordinates of CIEL*a*b* color space showed no statistical significant differences (p < 0.05) maintaining the "dark pink" tonality, the viscosity and the sensory evaluation were acceptable for drinking.

  10. Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine.

    Directory of Open Access Journals (Sweden)

    Adam T Szafran

    2009-12-01

    Full Text Available Androgen insensitivity syndrome (AIS is a rare disease associated with inactivating mutations of AR that disrupt male sexual differentiation, and cause a spectrum of phenotypic abnormalities having as a common denominator loss of reproductive viability. No established treatment exists for these conditions, however there are sporadic reports of patients (or recapitulated mutations in cell lines that respond to administration of supraphysiologic doses (or pulses of testosterone or synthetic ligands. Here, we utilize a novel high content analysis (HCA approach to study AR function at the single cell level in genital skin fibroblasts (GSF. We discuss in detail findings in GSF from three historical patients with AIS, which include identification of novel mechanisms of AR malfunction, and the potential ability to utilize HCA for personalized treatment of patients affected by this condition.

  11. Peculiarities of the diffusion of silver and sodium ions in phosphate glasses with a high content of sodium oxide

    International Nuclear Information System (INIS)

    Syutkin, V.M.; Tolkatchev, V.A.

    1996-01-01

    The phosphate glasses with a high content of alkali metal ions are good ionic conductors. Despite active studies, the mechanism of ion diffusion is not so far clear. The present work discusses the characteristics of ion diffusion in phosphate glasses with a high content of sodium oxide. An effective method to study ion transport is the investigation of relaxation processes the kinetics of which depends on ion diffusion. We use the data for two types of relaxation processes the kinetics of which is determined by ion diffusion. This is the conductivity relaxation due to sodium (host) ions and the decay of radiation-induced centers controlled by silver (guest) ion diffusion. Both of the processes being actually the first-order processes display a nonexponential kinetic behavior. The relaxation law can be interpreted either as the inherently nonexponential function or as the weighted sum of exponential decay functions with a distribution of relaxation times. It has been demonstrated that on the molecular level the relaxation function should be interpreted in the frame of the scheme of parallel first-order processes. This fact allows one to formulate a number of features of ion diffusion: (i) the mean square displacement of ions does not exceed several angstrom when transport becomes non-dispersive; (ii) the diffusion coefficient of ions is the function of coordinates. In this case, a characteristic distance at which D(r) noticeably varies is no less than a hundred of angstrom; (iii) the instantaneous concentration of mobile ions is well below the overall concentration ions

  12. Microgrids project. Part 2. Design of an electrification kit with high content of renewable energy sources in Senegal

    Energy Technology Data Exchange (ETDEWEB)

    Alzola, J.A.; Santos, M. [Robotiker Tecnalia, Parque Tecnologico, Edificio 202, 48170 Zamudio (Spain); Vechiu, I. [ESTIA Recherche Technopole Izarbel, 64210 Bidart (France); Camblong, H. [ESTIA Recherche Technopole Izarbel, 64210 Bidart (France); Electrical Engineering Department, University of the Basque Country (E.U.P.-D), Europa Plaza 1, 20018 Donostia - San Sebastian (Spain); Sall, M. [Centre d' Etudes et de Recherches sur les Energies Renouvelables (UCAD) (Senegal); Sow, G. [Laboratoire des Energies Renouvelables (LER), Ecole Sup. Polytechnique, Dakar (Senegal)

    2009-10-15

    Senegal is one of the less developed countries in the world (position 158 in a list of 174 countries). 85% of its rural population does not have access to electricity and there's no doubt that this is an important barrier for socio-economic development. In this context, the project Microgrids aims at contributing to solve this problem. This project is part of the Intelligent Energy - Europe Programme supported by the European Commission. Its objective is the promotion and dissemination of the use of micro-grids with high content of Renewable Energy Sources (RES) for the electrification of villages far away from the grid in Senegal. One of the results of the project was the analysis of rural electrification needs, which is described in another paper [Camblong H, Sarr J, Niang AT, Curea O, Alzola JA, Sylla EH, Santos M. Microgrids project, part 1: analysis of rural electrification with high content of renewable energy sources in Senegal. Renewable Energy, submitted for publication.]. This paper presents the design of an electrification kit based on the information provided by that analysis [Analyse des besoins locaux pour l'electrification de zones rurales au Senegal. Technical report of Microgrids project; 2007. Available from: http://www.microgrids-eie.com.]. After identifying necessary previous conditions for the sustainability of any electrification project, a methodology is proposed for the design of the electrification kit. This methodology is applied to a typical village and results are extended to differently sized villages in the areas of Thies, Fatick and Kaolack. Economic considerations are also included to establish the relationship between electrification costs and paying capability of the communities. Now the Microgrids' consortium hopes to set-up a new project to apply the designed kit on some rural non-electrified villages. (author)

  13. Assessment of 16 chemicals on proliferation and apoptosis in human neuroprogenitor cells using high-content image analysis (HCA).

    Science.gov (United States)

    The need for efficient methods of screening chemicals for the potential to cause developmental neurotoxicity is paramount. We previously described optimization of an HCA assay for proliferation and apoptosis in ReNcell CX cells (ReN), identifying appropriate controls. Utility of ...

  14. Gel spinning of PVA composite fibers with high content of multi-walled carbon nanotubes and graphene oxide hybrids

    International Nuclear Information System (INIS)

    Wei, Yizhe; Lai, Dengpan; Zou, Liming; Ling, Xinlong; Lu, Hongwei; Xu, Yongjing

    2015-01-01

    In this report, poly (vinyl alcohol) (PVA) composite fibers with high content of multi-walled carbon nanotubes and graphene oxide (MWCNTs-GO) hybrids were prepared by gel spinning, and were characterized by TGA, DSC, SEM, XL-2 yarn strength tester and electrical conductivity measurement. The total content of MWCNTs-GO hybrids in the PVA composite fibers, which is up to 25 wt%, was confirmed by TGA analysis. The DSC measurement shows that the melting and crystallization peaks decreased after the addition of nano-fillers. This is due to the reason that the motion of PVA chains is completely confined by strong hydrogen bonding interaction between PVA and nano-fillers. After the addtion of GO, the dispersibility of MWCNTs in composite fibers improved slightly. And the tensile strength and Young's modulus increased by 38% and 67%, respectively. This is caused by the increased hydrogen bonding interaction and synergistic effect through hybridization of MWCNTs and GO. More significantly, the electrical conductivity of PVA/MWCNTs/GO composite fibers enhanced by three orders of magnitude with the addition of GO. (paper)

  15. A high content, high throughput cellular thermal stability assay for measuring drug-target engagement in living cells.

    Science.gov (United States)

    Massey, Andrew J

    2018-01-01

    Determining and understanding drug target engagement is critical for drug discovery. This can be challenging within living cells as selective readouts are often unavailable. Here we describe a novel method for measuring target engagement in living cells based on the principle of altered protein thermal stabilization / destabilization in response to ligand binding. This assay (HCIF-CETSA) utilizes high content, high throughput single cell immunofluorescent detection to determine target protein levels following heating of adherent cells in a 96 well plate format. We have used target engagement of Chk1 by potent small molecule inhibitors to validate the assay. Target engagement measured by this method was subsequently compared to target engagement measured by two alternative methods (autophosphorylation and CETSA). The HCIF-CETSA method appeared robust and a good correlation in target engagement measured by this method and CETSA for the selective Chk1 inhibitor V158411 was observed. However, these EC50 values were 23- and 12-fold greater than the autophosphorylation IC50. The described method is therefore a valuable advance in the CETSA method allowing the high throughput determination of target engagement in adherent cells.

  16. Optimization of conditions to achieve high content of gamma amino butyric acid in germinated black rice, and changes in bioactivities

    Directory of Open Access Journals (Sweden)

    Chaiyavat CHAIYASUT

    Full Text Available Abstract The present study estimated the optimum germination conditions to achieve high content of Gamma-amino butyric acid (GABA and other phytochemicals in Thai black rice cultivar Kum Payao (BR. The Box–Behnken design of response surface methodology was employed to optimize the germination conditions. The changes in the GABA, phytochemical content, impact of salt, and temperature stress variation on phytochemical content, and stability of GABA were studied. The results showed that 12 h of soaking at pH 7, followed by 36 h of germination was the optimum condition to achieve maximum GABA content (0.2029 mg/g of germinated BR (GBR. The temperature (8 and 30 °C, and salt (50-200 mM NaCl content affected the phytochemicals of GBR, especially GABA, and anthocyanins. Obviously, the antioxidant capability, and enzyme (α-amylase and α-glucosidase inhibiting nature of BR was significantly (P < 0.001 increased after germination. The storage of GBR at 4 °C significantly, preserved the GABA content (∼80% for 45 days. Primarily, the current study revealed the changes in phytochemical content, and bioactivity of Thai black rice cr. Kum Payao during germination. More studies should be carried out on pharmacological benefits of GABA-rich GBR.

  17. Automated Slide Scanning and Segmentation in Fluorescently-labeled Tissues Using a Widefield High-content Analysis System.

    Science.gov (United States)

    Poon, Candice C; Ebacher, Vincent; Liu, Katherine; Yong, Voon Wee; Kelly, John James Patrick

    2018-05-03

    Automated slide scanning and segmentation of fluorescently-labeled tissues is the most efficient way to analyze whole slides or large tissue sections. Unfortunately, many researchers spend large amounts of time and resources developing and optimizing workflows that are only relevant to their own experiments. In this article, we describe a protocol that can be used by those with access to a widefield high-content analysis system (WHCAS) to image any slide-mounted tissue, with options for customization within pre-built modules found in the associated software. Not originally intended for slide scanning, the steps detailed in this article make it possible to acquire slide scanning images in the WHCAS which can be imported into the associated software. In this example, the automated segmentation of brain tumor slides is demonstrated, but the automated segmentation of any fluorescently-labeled nuclear or cytoplasmic marker is possible. Furthermore, there are a variety of other quantitative software modules including assays for protein localization/translocation, cellular proliferation/viability/apoptosis, and angiogenesis that can be run. This technique will save researchers time and effort and create an automated protocol for slide analysis.

  18. Screen dealing

    International Nuclear Information System (INIS)

    Barlow, J.W.

    1991-01-01

    The screen dealing system provides a facility whereby buyers and sellers of spot thermal coal can make bids and offers via the medium of the Reuters screen. A sale results when a market participant notifies his acceptance of a price to a central dealing desk. Use of the system is available to all genuine participants in the coal trade. This paper reports that it provides a focus for information and for the visible making of coal prices. For years screen trading has been used successfully to trade other commodities. At last coal is being traded electronically. It makes sense. It works. Users like it

  19. Airport Screening

    Science.gov (United States)

    Health Physics Society Specialists in Radiation Safety Airport Screening Fact Sheet Adopted: May 2011 Photo courtesy of Dan ... a safe level. An American National Standards Institute/Health Physics Society industry standard states that the maxi- mum ...

  20. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  1. Carrier Screening

    Science.gov (United States)

    ... How accurate is carrier screening? No test is perfect. In a small number of cases, test results ... in which an egg is removed from a woman’s ovary, fertilized in a laboratory with the man’s ...

  2. Quality evaluation of four hemoglobin screening methods in a blood donor setting along with their comparative cost analysis in an Indian scenario

    Directory of Open Access Journals (Sweden)

    Tondon Rashmi

    2009-01-01

    Full Text Available Background: Despite the wide range of methods available for measurement of hemoglobin, no single technique has emerged as the most appropriate and ideal for a blood donation setup. Materials and Methods: A prospective study utilizing 1014 blood samples was carried out in a blood donation setting for quality evaluation of four methods of hemoglobin estimation along with cost analysis: Hematology cell analyzer (reference, HCS, CuSO4 method and HemoCue. Results: Mean value of HemoCue (mean ± SD = 14.7 ± 1.49 g/dl was higher by 0.24 compared to reference (mean ± SD = 13.8 ± 1.52 g/dl but not statistically significant ( P > 0.05. HemoCue proved to be the best technique (sensitivity 99.4% and specificity 84.4% whereas HCS was most subjective with 25.2% incorrect estimations. CuSO4 proved to be good with 7.9% false results. Comparative cost analysis of each method was calculated to be 35 INR/test for HemoCue, 0.76 INR /test for HCS and 0.06-0.08 INR /test for CuSO4. Conclusion: CuSO4 method gives accurate results, if strict quality control is applied. HemoCue is too expensive to be used as a primary screening method in an economically restricted country like India.

  3. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    Directory of Open Access Journals (Sweden)

    Ester Pagano

    2016-10-01

    Full Text Available Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD, here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS. Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol. The amounts of CBD in the colon, brain and liver after the oral treatments were measured by HPLC coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion or orally (only at one dose. In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  4. Luminescent screens

    International Nuclear Information System (INIS)

    Lu, C.-I.

    1982-01-01

    Luminescent screens which are useful for such purposes as intensifying screens for radiographs are comprised of a support bearing a layer of finely divided particles of a phosphor dispersed in a cross-linked polymeric matrix formed by heat-curing of a coating composition comprising an unsaturated cross-linkable polymer, a polymerizable acrylic monomer, a thermoplastic polyurethane elastomer, and a heat-activatable polymerization initiator. The phosphor layer includes voids formed by evaporation of an evaporable component which is present in the coating composition from which such layer is formed. (author)

  5. Alcohol Use Screening

    Science.gov (United States)

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  6. Hearing Screening

    Science.gov (United States)

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  7. Vision Screening

    Science.gov (United States)

    ... an efficient and cost-effective method to identify children with visual impairment or eye conditions that are likely to lead ... main goal of vision screening is to identify children who have or are at ... visual impairment unless treated in early childhood. Other problems that ...

  8. Vision Screening

    Science.gov (United States)

    1993-01-01

    The Visi Screen OSS-C, marketed by Vision Research Corporation, incorporates image processing technology originally developed by Marshall Space Flight Center. Its advantage in eye screening is speed. Because it requires no response from a subject, it can be used to detect eye problems in very young children. An electronic flash from a 35 millimeter camera sends light into a child's eyes, which is reflected back to the camera lens. The photorefractor then analyzes the retinal reflexes generated and produces an image of the child's eyes, which enables a trained observer to identify any defects. The device is used by pediatricians, day care centers and civic organizations that concentrate on children with special needs.

  9. A way toward analyzing high-content bioimage data by means of semantic annotation and visual data mining

    Science.gov (United States)

    Herold, Julia; Abouna, Sylvie; Zhou, Luxian; Pelengaris, Stella; Epstein, David B. A.; Khan, Michael; Nattkemper, Tim W.

    2009-02-01

    In the last years, bioimaging has turned from qualitative measurements towards a high-throughput and highcontent modality, providing multiple variables for each biological sample analyzed. We present a system which combines machine learning based semantic image annotation and visual data mining to analyze such new multivariate bioimage data. Machine learning is employed for automatic semantic annotation of regions of interest. The annotation is the prerequisite for a biological object-oriented exploration of the feature space derived from the image variables. With the aid of visual data mining, the obtained data can be explored simultaneously in the image as well as in the feature domain. Especially when little is known of the underlying data, for example in the case of exploring the effects of a drug treatment, visual data mining can greatly aid the process of data evaluation. We demonstrate how our system is used for image evaluation to obtain information relevant to diabetes study and screening of new anti-diabetes treatments. Cells of the Islet of Langerhans and whole pancreas in pancreas tissue samples are annotated and object specific molecular features are extracted from aligned multichannel fluorescence images. These are interactively evaluated for cell type classification in order to determine the cell number and mass. Only few parameters need to be specified which makes it usable also for non computer experts and allows for high-throughput analysis.

  10. Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.

    Science.gov (United States)

    Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G; Ab, Eiso; Heetebrij, Robert J; Irth, Hubertus; Siegal, Gregg

    2010-09-01

    Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited to ligands that bind with K(D) better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

  11. Water screen

    Energy Technology Data Exchange (ETDEWEB)

    Kutepov, A.I.; Fedotov, I.N.; Prokopov, O.I.

    1981-01-01

    The invention refers to ventilation and can be used for repair-fitting operations in a blasting-dangerous gas condition, for example, during elimination of gas-oil gushers, repair of gas-oil pipelines, equipment etc. In order to improve safety of labor, the nozzle adapters of the water collector are oriented towards each other. The collector is installed on a support with the possibility of rotating and vertical movement. The proposed screen excludes the possibility of blasting-dangerous concentrations of gases and guarantees extinguishing of the impact spark during operation of the tool.

  12. RBC Antibody Screen

    Science.gov (United States)

    ... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

  13. Mental Health Screening Center

    Science.gov (United States)

    ... Releases & Announcements Public Service Announcements Partnering with DBSA Mental Health Screening Center These online screening tools are not ... you have any concerns, see your doctor or mental health professional. Depression Screening for Adult Depression Screening for ...

  14. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  15. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse

    OpenAIRE

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A.; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A.; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was ...

  16. An automated wide-field time-gated optically sectioning fluorescence lifetime imaging multiwell plate reader for high-content analysis of protein-protein interactions

    Science.gov (United States)

    Alibhai, Dominic; Kumar, Sunil; Kelly, Douglas; Warren, Sean; Alexandrov, Yuriy; Munro, Ian; McGinty, James; Talbot, Clifford; Murray, Edward J.; Stuhmeier, Frank; Neil, Mark A. A.; Dunsby, Chris; French, Paul M. W.

    2011-03-01

    We describe an optically-sectioned FLIM multiwell plate reader that combines Nipkow microscopy with wide-field time-gated FLIM, and its application to high content analysis of FRET. The system acquires sectioned FLIM images in fluorescent protein. It has been applied to study the formation of immature HIV virus like particles (VLPs) in live cells by monitoring Gag-Gag protein interactions using FLIM FRET of HIV-1 Gag transfected with CFP or YFP. VLP formation results in FRET between closely packed Gag proteins, as confirmed by our FLIM analysis that includes automatic image segmentation.

  17. hcs0614.pdf | jun2007 | jess | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the Three Science Academies of India on the teaching of the theory of evolution more. ... Posted on 21 December 2017. ASTROPHYSICS: An Observational View of the Universe. Math Art and Design: MAD about Math, Math Education and Outreach.

  18. Towards making HCS ear detection robust against rotation

    DEFF Research Database (Denmark)

    Pflug, Anika; Back, Philip Michael; Busch, Christoph

    2012-01-01

    In identity retrieval from crime scene images, the outer ear (auricle) has ever since been regarded as a valuable characteristic. Because of its unique and permanent shape, the auricle also attracted the attention of researches in the field of biometrics over the last years. Since then, numerous...

  19. Experience with Phadebas hCS (HPL)-Test kit

    International Nuclear Information System (INIS)

    Herter, U.

    1976-01-01

    The RIA determination of human placental lactogen (HPL) is described using the Phadebas test kit by Pharmacia, Sweden. The results of the test are shown graphically. The kit was tested over a period of one year and the tests were modified to meet the requirements of clinical examinations. The calibration curve is constant and applicable for a period of 14 days. The Phadebas kit has proved to be advantageous for both scientific research work and for routine clinical examinations. (L.O.)

  20. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  1. Screening for Cancer

    Science.gov (United States)

    Cancer screening is checking for cancer in people who don't have symptoms. Screening tests can help doctors find and treat several types of cancer early, but cancer screening can have harms as well as benefits.

  2. Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  3. Screen time and children

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000355.htm Screen time and children To use the sharing features on ... videos is considered unhealthy screen time. Current Screen Time Guidelines Children under age 2 should have no ...

  4. Stomach (Gastric) Cancer Screening

    Science.gov (United States)

    ... Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is screening? Go ... are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a disease in ...

  5. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

  6. Integrated Automation of High-Throughput Screening and Reverse Phase Protein Array Sample Preparation

    DEFF Research Database (Denmark)

    Pedersen, Marlene Lemvig; Block, Ines; List, Markus

    into automated robotic high-throughput screens, which allows subsequent protein quantification. In this integrated solution, samples are directly forwarded to automated cell lysate preparation and preparation of dilution series, including reformatting to a protein spotter-compatible format after the high......-throughput screening. Tracking of huge sample numbers and data analysis from a high-content screen to RPPAs is accomplished via MIRACLE, a custom made software suite developed by us. To this end, we demonstrate that the RPPAs generated in this manner deliver reliable protein readouts and that GAPDH and TFR levels can...

  7. Vanillin inhibits translation and induces messenger ribonucleoprotein (mRNP) granule formation in saccharomyces cerevisiae: application and validation of high-content, image-based profiling.

    Science.gov (United States)

    Iwaki, Aya; Ohnuki, Shinsuke; Suga, Yohei; Izawa, Shingo; Ohya, Yoshikazu

    2013-01-01

    Vanillin, generated by acid hydrolysis of lignocellulose, acts as a potent inhibitor of the growth of the yeast Saccharomyces cerevisiae. Here, we investigated the cellular processes affected by vanillin using high-content, image-based profiling. Among 4,718 non-essential yeast deletion mutants, the morphology of those defective in the large ribosomal subunit showed significant similarity to that of vanillin-treated cells. The defects in these mutants were clustered in three domains of the ribosome: the mRNA tunnel entrance, exit and backbone required for small subunit attachment. To confirm that vanillin inhibited ribosomal function, we assessed polysome and messenger ribonucleoprotein granule formation after treatment with vanillin. Analysis of polysome profiles showed disassembly of the polysomes in the presence of vanillin. Processing bodies and stress granules, which are composed of non-translating mRNAs and various proteins, were formed after treatment with vanillin. These results suggest that vanillin represses translation in yeast cells.

  8. High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation

    Energy Technology Data Exchange (ETDEWEB)

    Vega, Sebastián L. [Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ (United States); Liu, Er; Arvind, Varun [Department of Biomedical Engineering, Rutgers University, Piscataway, NJ (United States); Bushman, Jared [Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ (United States); School of Pharmacy, University of Wyoming, Laramie, WY (United States); Sung, Hak-Joon [Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Becker, Matthew L. [Department of Polymer Science and Engineering, University of Akron, Akron, OH (United States); Lelièvre, Sophie [Department of Basic Medical Sciences, Purdue University, West Lafayette, IN (United States); Kohn, Joachim [Department of Chemistry and Chemical Biology, New Jersey Center for Biomaterials, Piscataway, NJ (United States); Vidi, Pierre-Alexandre, E-mail: pvidi@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC (United States); Moghe, Prabhas V., E-mail: moghe@rutgers.edu [Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ (United States); Department of Biomedical Engineering, Rutgers University, Piscataway, NJ (United States)

    2017-02-01

    Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative “imaging-derived” parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. - Highlights: • High-content analysis of nuclear shape and organization classify stem and progenitor cells poised for distinct lineages. • Early oncogenic changes in mesenchymal stem cells (MSCs) are also detected with nuclear descriptors. • A new class of cancer-mitigating biomaterials was identified based on image

  9. High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation

    International Nuclear Information System (INIS)

    Vega, Sebastián L.; Liu, Er; Arvind, Varun; Bushman, Jared; Sung, Hak-Joon; Becker, Matthew L.; Lelièvre, Sophie; Kohn, Joachim; Vidi, Pierre-Alexandre; Moghe, Prabhas V.

    2017-01-01

    Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative “imaging-derived” parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. - Highlights: • High-content analysis of nuclear shape and organization classify stem and progenitor cells poised for distinct lineages. • Early oncogenic changes in mesenchymal stem cells (MSCs) are also detected with nuclear descriptors. • A new class of cancer-mitigating biomaterials was identified based on image

  10. USE OF HIGH CONTENT IMAGE ANALYSES TO DETECT CHEMICAL-MEDIATED EFFECTS ON NEURITE SUB-POPULATIONS IN PRIMARY RAT CORTICAL NEURONS

    Science.gov (United States)

    Traditional developmental neurotoxicity tests performed in vivo are costly, time-consuming and utilize a large number of animals. In order to address these inefficiencies, in vitro models of neuronal development have been used in a first tier screening approach for developmenta...

  11. Screening for Glaucoma

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Glaucoma The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Glaucoma . This final recommendation statement ...

  12. Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  13. Hearing Loss: Screening Newborns

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table ... deafness, which account for most cases. Screening Newborns' Hearing Now Standard In 1993, children born in the ...

  14. Cervical Cancer Screening

    Science.gov (United States)

    ... Cancer found early may be easier to treat. Cervical cancer screening is usually part of a woman's health ... may do more tests, such as a biopsy. Cervical cancer screening has risks. The results can sometimes be ...

  15. Screening for Cervical Cancer

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Cervical Cancer The U.S. Preventive Services Task Force (Task Force) has issued final recommendations on Screening for Cervical Cancer . These recommendations are for women ...

  16. Effect of non-homogeneous spatial distributions of surfactants on the stability of high-content bitumen-in-water emulsions

    International Nuclear Information System (INIS)

    Urbina-Villalba, German; Garcia-Sucre, Maximo

    2000-01-01

    In order to study the effects of non-homogeneous spatial distributions of surfactants on the drop size of high-content bitumen-in-water emulsions, a modification of a standard Brownian Dynamics algorithm was employed. The new algorithm is able to simulate the evolution of oil/water emulsions towards flocculation and coalescence. The simulation boxes contain 216 and 125 particles initially distributed in a homogeneous simple cubic arrangement, corresponding to bitumen/water volume fractions of 0.30 and 0.51, respectively. The particles interact through a DLVO potential dependent on the total surfactant concentration, spatial surfactant distribution, and the amount of surfactant adsorbed to the bitumen/water interface. As will be shown in this article, certain combinations of the referred variables can produce a wide variety of repulsive potentials between similar drops. The variation of the total number of drops with time does not obey the usual analytical formalisms developed for more diluted cases, and instead, a simple exponential decrease of the number of drops with time is found. Such behavior has already been confirmed by experiment. Some similarities between the present results and those previously published for more diluted systems are discussed [es

  17. High content of pyridinic- and pyrrolic-nitrogen-modified carbon nanotubes derived from blood biomass for the electrocatalysis of oxygen reduction reaction in alkaline medium

    International Nuclear Information System (INIS)

    Zheng, Jie; Guo, Chaozhong; Chen, Chunyan; Fan, Mingzhi; Gong, Jianping; Zhang, Yanfang; Zhao, Tianxin; Sun, Yuelin; Xu, Xiaofan; Li, Mengmeng; Wang, Ran; Luo, Zhongli; Chen, Changguo

    2015-01-01

    Graphical abstract: Display Omitted -- Highlights: •An ORR electrocatalyst was fabricated from blood biomass and carbon nanotube. •The N-CNT catalyst exhibits good ORR activity, methanol resistance and stability. •The pyrolysis process produces high contents of pyridinic and pyrrolic N species. •The pyridinic-N group may play more important role in the active sites for ORR. -- Abstract: Here we present a facile synthetic route to design nitrogen-doped nanostructured carbon-based electrocatalyst for oxygen reduction reaction (ORR) by the copyrolysis of blood biomass from pig and carbon nanotubes (CNTs) at high temperatures. The nitrogen-doped CNTs obtained at 800 °C not only results in excellent ORR activity with four-electron transfer selectivity in alkaline medium, but also exhibits superior methanol-tolerant property and long-term stability. It is confirmed that high-temperature pyrolysis processes can facilitate to produce higher contents of pyridinic- and pyrrolic-N binding groups in electrocatalysts, contributing to the enhancement of ORR performance in terms of onset potential, half-wave potential, and limited current density. We also propose that the planar-N configuration may be the active site that is responsible for the improved ORR electrocatalytic performance. The straight-forward and cheap synthesis of the active and stable electrocatalyst makes it a promising candidate for electrochemical power sources such as fuel cells or metal-air batteries

  18. High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.

    Science.gov (United States)

    Vega, Sebastián L; Liu, Er; Arvind, Varun; Bushman, Jared; Sung, Hak-Joon; Becker, Matthew L; Lelièvre, Sophie; Kohn, Joachim; Vidi, Pierre-Alexandre; Moghe, Prabhas V

    2017-02-01

    Stem and progenitor cells that exhibit significant regenerative potential and critical roles in cancer initiation and progression remain difficult to characterize. Cell fates are determined by reciprocal signaling between the cell microenvironment and the nucleus; hence parameters derived from nuclear remodeling are ideal candidates for stem/progenitor cell characterization. Here we applied high-content, single cell analysis of nuclear shape and organization to examine stem and progenitor cells destined to distinct differentiation endpoints, yet undistinguishable by conventional methods. Nuclear descriptors defined through image informatics classified mesenchymal stem cells poised to either adipogenic or osteogenic differentiation, and oligodendrocyte precursors isolated from different regions of the brain and destined to distinct astrocyte subtypes. Nuclear descriptors also revealed early changes in stem cells after chemical oncogenesis, allowing the identification of a class of cancer-mitigating biomaterials. To capture the metrology of nuclear changes, we developed a simple and quantitative "imaging-derived" parsing index, which reflects the dynamic evolution of the high-dimensional space of nuclear organizational features. A comparative analysis of parsing outcomes via either nuclear shape or textural metrics of the nuclear structural protein NuMA indicates the nuclear shape alone is a weak phenotypic predictor. In contrast, variations in the NuMA organization parsed emergent cell phenotypes and discerned emergent stages of stem cell transformation, supporting a prognosticating role for this protein in the outcomes of nuclear functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Cationic Copolymerization of 3,3-Bis(hydroxymethyl)oxetane and Glycidol: Biocompatible Hyperbranched Polyether Polyols with High Content of Primary Hydroxyl Groups.

    Science.gov (United States)

    Christ, Eva-Maria; Hobernik, Dominika; Bros, Matthias; Wagner, Manfred; Frey, Holger

    2015-10-12

    The cationic ring-opening copolymerization of 3,3-bis(hydroxymethyl)oxetane (BHMO) with glycidol using different comonomer ratios (BHMO content from 25 to 90%) and BF3OEt2 as an initiator has been studied. Apparent molecular weights of the resulting hyperbranched polyether copolymers ranged from 1400 to 3300 g mol(-1) (PDI: 1.21-1.48; method: SEC, linear PEG standards). Incorporation of both comonomers is evidenced by MALDI-TOF mass spectroscopy. All hyperbranched polyether polyols with high content of primary hydroxyl groups portray good solubility in water, which correlates with an increasing content of glycerol units. Detailed NMR characterization was employed to elucidate the copolymer microstructures. Kinetic studies via FTIR demonstrated a weak gradient-type character of the copolymers. MTT assays of the copolymers (up to 100 μg mL(-1)) on HEK and fibroblast cell lines (3T3, L929, WEHI) as well as viability tests on the fibroblast cells were carried out to assess the biocompatibility of the materials, confirming excellent biocompatibility. Transfection efficiency characterization by flow cytometry and confocal laser microscopy demonstrated cellular uptake of the copolymers. Antiadhesive properties of the materials on surfaces were assessed by adhesion assays with fibroblast cells.

  20. Study and application of new chelating resin to recovery uranium from in-situ leach solution with high content saline chloride ion

    International Nuclear Information System (INIS)

    Zhang Jianguo; Qiu Yueshuang; Feng Yu; Deng Huidong; Zhao Chaoya

    2014-01-01

    Research on the adsorption and elution property of D814 chelating resin was carried out aiming at the difficult separation of uranium from high content saline chloride ion in situ leach liquor and the adsorption mechanism is also discussed. Influence factors such as contact time, pH value, Ca"2"+, Mg"2"+ and Cl"- concentration etc. to the resin adsorption were studied. Experimental results show that adsorption rate is lowly which need 6h to arrive at the adsorption equilibrium. The resin adsorption uranium pH in the solution is from l.33 to 9. When total salinity is over 20 g/L, calcium ion, and magnesium ion is about 3 g/L, there are no big influence on resin adsorption capacity. The resin has good chloride ion resistance. When chloride ion is over 60 g/L, it is no influence on resin adsorption uranium. Column experiment results indicate that ratio of saturation volume to break-through point volume is l.82, resin saturation uranium capacity is 40.5 mg. U/_g_(_∓_)_R. When elution volume bed number is 23, the eluted solution uranium concentration is below 80 mg/L. The elution rate of the uranium is 96.2%. (authors)

  1. Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

    Science.gov (United States)

    Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel

    2017-11-27

    Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

  2. Effect of yeast biomass with high content of carotenoids on erythrocyte deformability, NO production and Na,K-ATPase activity in healthy and LPS treated rats.

    Science.gov (United States)

    Radosinska, J; Mezesova, L; Okruhlicova, L; Frimmel, K; Breierova, E; Bartekova, M; Vrbjar, N

    2016-11-25

    Measurements of red blood cell (RBC) deformability together with estimation of NO-synthase activity and Na,K-ATPase activity were used for characterization of RBC functionality in rats subjected to single dose of Escherichia coli lipopolysaccharides (LPS) at a dose of 1 mg/kg. We hypothesized that LPS might initiate a malfunction of RBC. We also investigated the potential effect of carotenoids (10 mg/kg/day) produced in red yeast biomass of Rhodotorula glutinis on RBC in LPS-challenged rats. LPS significantly reduced the deformability of RBC (by 14%) together with decrease of NO-synthase activity by 20%. Daily supplementation of carotenoids for 10 days attenuated the LPS-induced injury, as observed by 22% increase of RBC deformability and 23% increase of NO-synthase activity. The activity of Na,K-ATPase was also improved probably due to increased number of active enzyme molecules as indicated by 66% enhancement of Vmax value, hence maintaining the activity of erythrocyte Na,K-ATPase to the level even higher as compared with healthy control animals. It may be concluded that administration of yeast biomass with high content of carotenoids resulted in advanced function of erythrocytes as concerns their ability to squeeze through narrow capillaries of the circulation, better intrinsic production of NO and improvement of intracellular homeostasis of sodium.

  3. Between Stage and Screen

    NARCIS (Netherlands)

    Tornqvist, Egil

    1996-01-01

    Ingmar Bergman is worldwide known as a film and stage director. Yet no-one has attempted to compare his stage and screen activities. In Between stage and screen Egil Tornqvist examines formal and thematical correspondences and differences between a number of Bergman's stage, screen, and radio

  4. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.

  5. Screen Practice in Curating

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2014-01-01

    During the past one and a half decade, a curatorial orientation towards "screen practice" has expanded the moving image and digital art into the public domain, exploring alternative artistic uses of the screen. The emergence of urban LED screens in the late 1990s provided a new venue that allowed...... for digital art to expand into public space. It also offered a political point of departure, inviting for confrontation with the Spectacle and with the politics and ideology of the screen as a mass communication medium that instrumentalized spectator positions. In this article I propose that screen practice...... to the dispositif of screen practice in curating, resulting in a medium-based curatorial discourse. With reference to the nomadic exhibition project Nordic Outbreak that I co-curated with Nina Colosi in 2013 and 2014, I suggest that the topos of the defined visual display area, frequently still known as "the screen...

  6. Pilot-scale incineration of wastes with high content of chlorinated and non-halogenated organophosphorus flame retardants used as alternatives for PBDEs.

    Science.gov (United States)

    Matsukami, Hidenori; Kose, Tomohiro; Watanabe, Mafumi; Takigami, Hidetaka

    2014-09-15

    Chlorinated and non-halogenated organophosphorus flame retardants (OPFRs) including tris(2-chloroisopropyl) phosphate (TCIPP), diethylene glycol bis(di(2-chloroisopropyl) phosphate) (DEG-BDCIPP), triphenyl phosphate (TPHP), and bisphenol A bis(diphenyl phosphate) (BPA-BDPP) have been used increasingly as alternatives to polybrominated diphenyl ethers and other brominated flame retardants. For this study, five batches of incineration experiments of wastes containing approximately 1% of TCIPP, DEG-BDCIPP, TPHP, and BPA-BDPP were conducted using a pilot-scale incinerator. Destruction and emission behaviors of OPFRs were investigated along with the effects on behaviors of unintentional persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs), hexachlorobenzene (HCB), pentachlorobenzene (PeCB), and pentachlorophenol (PCP). Incineration conditions were chosen according to current regulations for waste incinerators in Japan and UNEP. The OPFRs in the input materials were mainly destroyed in the primary combustion with destruction efficiencies greater than 99.999%. Concentrations of the OPFRs in the exhaust gases and ash were, respectively, incineration. Inputs of chlorinated OPFRs did not affect the formation markedly. Destruction and emission behaviors of unintentional POPs were investigated. Emissions of such POPs in exhaust gases and the ash were lower than the Japanese and international standards. Results show that even in wastes with high contents of chlorinated and non-halogenated OPFRs, waste incineration by the current regulations for the waste incinerators can control environmental emissions of OPFRs and unintentional POPs. Incineration is regarded as a best available technology (BAT) for waste management systems. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

    Science.gov (United States)

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  8. Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4-ALK fusion.

    Science.gov (United States)

    Smuk, Gábor; Tornóczky, Tamás; Pajor, László; Chudoba, Ilse; Kajtár, Béla; Sárosi, Veronika; Pajor, Gábor

    2018-05-19

    EML4-ALK gene fusion (inv2(p21p23)) of non-small cell lung cancer (NSCLC) predisposes to tyrosine kinase inhibitor treatment. One of the gold standard diagnostics is the dual color (DC) break-apart (BA) FISH technique, however, the unusual closeness of the involved genes has been suggested to raise likelihood of random co-localization (RCL) of signals. Although this is suspected to decrease sensitivity (often to as low as 40-70%), the exact level and effect of RCL has not been revealed thus far. Signal distances were analyzed to the 0.1 µm precision in more than 25,000 nuclei, via automated high content-image cytometry. Negative and positive controls were created using conventional DC BA-, and inv2(p21p23) mimicking probe-sets, respectively. Average distance between red and green signals was 9.72 pixels (px) (±5.14px) and 3.28px (±2.44px), in positives and negatives, respectively; overlap in distribution being 41%. Specificity and sensitivity of correctly determining ALK status was 97% and 29%, respectively. When investigating inv2(p21p23) with DC BA FISH, specificity is high, but seven out of ten aberrant nuclei are inevitably falsely classified as negative, due to the extreme level of RCL. Together with genetic heterogeneity and dilution effect of non-tumor cells in NSCLC, this immense analytical false negativity is the primary cause behind the often described low diagnostic sensitivity. These results convincingly suggest that if FISH is to remain a gold standard for detecting the therapy relevant inv(2), either a modified evaluation protocol, or a more reliable probe-design should be considered than the current DC BA one. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

  9. Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

    Science.gov (United States)

    McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

    2017-07-01

    Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

  10. Automated Groundwater Screening

    International Nuclear Information System (INIS)

    Taylor, Glenn A.; Collard, Leonard B.

    2005-01-01

    The Automated Intruder Analysis has been extended to include an Automated Ground Water Screening option. This option screens 825 radionuclides while rigorously applying the National Council on Radiation Protection (NCRP) methodology. An extension to that methodology is presented to give a more realistic screening factor for those radionuclides which have significant daughters. The extension has the promise of reducing the number of radionuclides which must be tracked by the customer. By combining the Automated Intruder Analysis with the Automated Groundwater Screening a consistent set of assumptions and databases is used. A method is proposed to eliminate trigger values by performing rigorous calculation of the screening factor thereby reducing the number of radionuclides sent to further analysis. Using the same problem definitions as in previous groundwater screenings, the automated groundwater screening found one additional nuclide, Ge-68, which failed the screening. It also found that 18 of the 57 radionuclides contained in NCRP Table 3.1 failed the screening. This report describes the automated groundwater screening computer application

  11. Screening for abdominalt aortaaneurisme

    DEFF Research Database (Denmark)

    Lindholt, J S; Juul, Svend; Henneberg, E W

    1997-01-01

    rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...... on uncertain assumptions concerning prevalence, incidence and risk of rupture. Therefore a randomized trial screening of 65-73 year old males is taking place in the County of Viborg in Denmark. Udgivelsesdato: 1997-Mar-24...

  12. Cathode ray tube screens

    International Nuclear Information System (INIS)

    Cockayne, B.; Robbins, D.J.; Glasper, J.L.

    1982-01-01

    An improved cathode ray tube screen is described which consists of a single- or a poly-crystalline slice of a material such as yttrium aluminium garnet in which dopants such as Tb 3 + , Eu 3 + , Ce 3 + or Tm 3 + are ion implanted to different depths or in different areas of the screen. Annealing the screen removes lattice damage caused by the ion implanting and assists the diffusion of the dopant into the crystal. (U.K.)

  13. Colorectal Cancer Screening

    OpenAIRE

    Quintero, Enrique; Saito, Yutaka; Hassan, Cessare; Senore, Carlo

    2012-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should wo...

  14. Colorectal cancer screening

    OpenAIRE

    Plumb, A. A.; Halligan, S.

    2015-01-01

    Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can...

  15. In-bead screening

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to screening of one-bead-one-compound (OBOC) combinatorial libraries which is useful for the discovery of compounds displaying molecular interactions with a biological or a physicochemical system, such as substrates and inhibitors of enzymes and the like. The invention...... provides a method for screening a library of compounds for their interaction with a physico- chemical or biological system and a corresponding kit for performing the method of screening a one-bead-one-compound library of compounds....

  16. Pilot-scale incineration of wastes with high content of chlorinated and non-halogenated organophosphorus flame retardants used as alternatives for PBDEs

    International Nuclear Information System (INIS)

    Matsukami, Hidenori; Kose, Tomohiro; Watanabe, Mafumi; Takigami, Hidetaka

    2014-01-01

    Chlorinated and non-halogenated organophosphorus flame retardants (OPFRs) including tris(2-chloroisopropyl) phosphate (TCIPP), diethylene glycol bis(di(2-chloroisopropyl) phosphate) (DEG-BDCIPP), triphenyl phosphate (TPHP), and bisphenol A bis(diphenyl phosphate) (BPA-BDPP) have been used increasingly as alternatives to polybrominated diphenyl ethers and other brominated flame retardants. For this study, five batches of incineration experiments of wastes containing approximately 1% of TCIPP, DEG-BDCIPP, TPHP, and BPA-BDPP were conducted using a pilot-scale incinerator. Destruction and emission behaviors of OPFRs were investigated along with the effects on behaviors of unintentional persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs), hexachlorobenzene (HCB), pentachlorobenzene (PeCB), and pentachlorophenol (PCP). Incineration conditions were chosen according to current regulations for waste incinerators in Japan and UNEP. The OPFRs in the input materials were mainly destroyed in the primary combustion with destruction efficiencies greater than 99.999%. Concentrations of the OPFRs in the exhaust gases and ash were, respectively, < 0.01–0.048 μg m −3 and < 0.5–68 μg kg −1 . Almost all of the total phosphorus in the input materials was partitioned into the ash, but less into final exit gases, indicating negligible emissions of volatile phosphorus compounds during incineration. Inputs of chlorinated OPFRs did not affect the formation markedly. Destruction and emission behaviors of unintentional POPs were investigated. Emissions of such POPs in exhaust gases and the ash were lower than the Japanese and international standards. Results show that even in wastes with high contents of chlorinated and non-halogenated OPFRs, waste incineration by the current regulations for the waste incinerators can control environmental emissions of OPFRs and

  17. Pilot-scale incineration of wastes with high content of chlorinated and non-halogenated organophosphorus flame retardants used as alternatives for PBDEs

    Energy Technology Data Exchange (ETDEWEB)

    Matsukami, Hidenori, E-mail: matsukami.hidenori@nies.go.jp [Center for Material Cycles and Waste Management Research, National Institute for Environmental Studies (NIES), 16-2 Onogawa, Tsukuba 305-8506 (Japan); Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa 277-8563 (Japan); Kose, Tomohiro [Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Akiha-ku, Niigata 956-8603 (Japan); Watanabe, Mafumi [Center for Material Cycles and Waste Management Research, National Institute for Environmental Studies (NIES), 16-2 Onogawa, Tsukuba 305-8506 (Japan); Takigami, Hidetaka [Center for Material Cycles and Waste Management Research, National Institute for Environmental Studies (NIES), 16-2 Onogawa, Tsukuba 305-8506 (Japan); Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa 277-8563 (Japan)

    2014-09-15

    Chlorinated and non-halogenated organophosphorus flame retardants (OPFRs) including tris(2-chloroisopropyl) phosphate (TCIPP), diethylene glycol bis(di(2-chloroisopropyl) phosphate) (DEG-BDCIPP), triphenyl phosphate (TPHP), and bisphenol A bis(diphenyl phosphate) (BPA-BDPP) have been used increasingly as alternatives to polybrominated diphenyl ethers and other brominated flame retardants. For this study, five batches of incineration experiments of wastes containing approximately 1% of TCIPP, DEG-BDCIPP, TPHP, and BPA-BDPP were conducted using a pilot-scale incinerator. Destruction and emission behaviors of OPFRs were investigated along with the effects on behaviors of unintentional persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs), hexachlorobenzene (HCB), pentachlorobenzene (PeCB), and pentachlorophenol (PCP). Incineration conditions were chosen according to current regulations for waste incinerators in Japan and UNEP. The OPFRs in the input materials were mainly destroyed in the primary combustion with destruction efficiencies greater than 99.999%. Concentrations of the OPFRs in the exhaust gases and ash were, respectively, < 0.01–0.048 μg m{sup −3} and < 0.5–68 μg kg{sup −1}. Almost all of the total phosphorus in the input materials was partitioned into the ash, but less into final exit gases, indicating negligible emissions of volatile phosphorus compounds during incineration. Inputs of chlorinated OPFRs did not affect the formation markedly. Destruction and emission behaviors of unintentional POPs were investigated. Emissions of such POPs in exhaust gases and the ash were lower than the Japanese and international standards. Results show that even in wastes with high contents of chlorinated and non-halogenated OPFRs, waste incineration by the current regulations for the waste incinerators can control environmental emissions of

  18. Plasma dynamic synthesis and obtaining ultrafine powders of iron oxides with high content of ε-Fe{sub 2}O{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Sivkov, Alexander [Institute of Power Engineering, National Research Tomsk Polytechnic University, Lenin av., 30, Tomsk 634050 (Russian Federation); Naiden, Evgenii [Faculty of Radiophysics, National Research Tomsk State University, Lenin av., 36, Tomsk 634050 (Russian Federation); Ivashutenko, Alexander [Institute of Power Engineering, National Research Tomsk Polytechnic University, Lenin av., 30, Tomsk 634050 (Russian Federation); Shanenkov, Ivan, E-mail: Swordi@list.ru [Institute of Power Engineering, National Research Tomsk Polytechnic University, Lenin av., 30, Tomsk 634050 (Russian Federation)

    2016-05-01

    The ultrafine iron oxide powders were successfully synthesized using the plasma dynamic synthesis method, based on the use of a coaxial magnetoplasma accelerator with the iron electrode system. The synthesis was implemented in the high-speed iron-containing plasma jet, flowing into the space of the sealed chamber, filled with the gaseous mixture of oxygen and argon at different ratios. The XRD investigations showed that the synthesized products were heterophase and consisted of three main phases such as magnetite Fe{sub 3}O{sub 4}, hematite α-Fe{sub 2}O{sub 3} and ε-Fe{sub 2}O{sub 3}. The SEM data confirmed the presence of three particle types: the hollow spheroids with sizes about hundreds of micrometers (magnetite), the particles with sizes up to 100 μm from the porous material of sintered submicron particles (hematite), and nanoscale particles (ε-phase). We found that at the higher oxygen concentration the content of ε-Fe{sub 2}O{sub 3} is increased up to ~50% at the same time with decreasing the Fe{sub 3}O{sub 4} phase. The magnetic properties of the products are mainly determined by magnetite characteristics and are significantly reduced with decreasing its content in the powder. In order to investigate the synthesized ε-Fe{sub 2}O{sub 3} on the ability to absorb the electromagnetic radiation in the millimeter wavelength range, we separated the product with the higher ε-phase concentration. The fraction mainly, consisting of ε-Fe{sub 2}O{sub 3}, showed the occurrence of the natural resonance at frequencies of 8.3 GHz and 130 GHz. - Highlights: • We synthesized iron oxide powder with high content of ε-Fe{sub 2}O{sub 3}. • Synthesis is implemented using iron-containing plasma jet flowing into O{sub 2} atm. • Synthesized powders are heterophase and consist of ε-Fe{sub 2}O{sub 3,} α-Fe{sub 2}O{sub 3} and Fe{sub 3}O{sub 4}. • ε-Fe{sub 2}O{sub 3} content increases up to 50% with increasing the O{sub 2} volume concentration. • We found the

  19. Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis.

    Directory of Open Access Journals (Sweden)

    Walter Georgescu

    Full Text Available Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when

  20. Screening for colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  1. [Overdiagnosis in cancer screening].

    Science.gov (United States)

    Cervera Deval, J; Sentís Crivillé, M; Zulueta, J J

    2015-01-01

    In screening programs, overdiagnosis is defined as the detection of a disease that would have gone undetected without screening when that disease would not have resulted in morbimortality and was treated unnecessarily. Overdiagnosis is a bias inherent in screening and an undesired effect of secondary prevention and improved sensitivity of diagnostic techniques. It is difficult to discriminate a priori between clinically relevant diagnoses and those in which treatment is unnecessary. To minimize the effects of overdiagnosis, screening should be done in patients at risk. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  2. Cancer screening guidelines.

    Science.gov (United States)

    Zoorob, R; Anderson, R; Cefalu, C; Sidani, M

    2001-03-15

    Numerous medical organizations have developed cancer screening guidelines. Faced with the broad, and sometimes conflicting, range of recommendations for cancer screening, family physicians must determine the most reasonable and up-to-date method of screening. Major medical organizations have generally achieved consensus on screening guidelines for breast, cervical and colorectal cancer. For breast cancer screening in women ages 50 to 70, clinical breast examination and mammography are generally recommended every one or two years, depending on the medical organization. For cervical cancer screening, most organizations recommend a Papanicolaou test and pelvic examination at least every three years in patients between 20 and 65 years of age. Annual fecal occult blood testing along with flexible sigmoidoscopy at five-year to 10-year intervals is the standard recommendation for colorectal cancer screening in patients older than 50 years. Screening for prostate cancer remains a matter of debate. Some organizations recommend digital rectal examination and a serum prostate-specific antigen test for men older than 50 years, while others do not. In the absence of compelling evidence to indicate a high risk of endometrial cancer, lung cancer, oral cancer and ovarian cancer, almost no medical organizations have developed cancer screening guidelines for these types of cancer.

  3. Obesity Prevention and Screening.

    Science.gov (United States)

    Mackey, Eleanor R; Olson, Alexandra; DiFazio, Marc; Cassidy, Omni

    2016-03-01

    Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. ScreenOS Cookbook

    CERN Document Server

    Brunner, Stefan; Delcourt, David

    2008-01-01

    In the only book that completely covers ScreenOS, six key members of Juniper Network's ScreenOS development team help you troubleshoot secure networks using ScreenOS firewall appliances. Over 200 recipes address a wide range of security issues, provide step-by-step solutions, and include discussions of why the recipes work, so you can easily set up and keep ScreenOS systems on track. The easy-to-follow format enables you to find the topic and specific recipe you need right away.

  5. Mammography screening in Denmark

    DEFF Research Database (Denmark)

    Vejborg, Ilse; Mikkelsen, Ellen Margrethe; Garne, Jens Peter

    2011-01-01

    Mammography screening is offered healthy women, and a high standard on professional and organizational level is mandatory not only in the screening programme but even in the diagnostic work-up and treatment. The main goal is to achieve a substantial reduction in disease specific mortality......, but it is not possible to evaluate the effect on mortality until several years later, and continuously monitoring of the quality of all aspects of a screening programme is necessary. Based on other European guidelines, 11 quality indicators have been defined, and guidelines concerning organizational requirements...... for a Danish screening programme as well as recommendations for the radiographic and radiological work have been drawn up....

  6. International Cancer Screening Network

    Science.gov (United States)

    The International Cancer Screening Network promotes evidence-based cancer screening implementation and evaluation with cooperation from multilateral organizations around the globe. Learn more about how ICSN aims to reduce the global burden of cancer by supporting research and international collaboration.

  7. Touch screens go optical

    DEFF Research Database (Denmark)

    Hanson, Steen Grüner; Jakobsen, Michael Linde; Pedersen, Henrik Chresten

    2012-01-01

    A simple optical implementation of a touch screen is made possible by disrupting the total internal reflection in a 2D waveguide.......A simple optical implementation of a touch screen is made possible by disrupting the total internal reflection in a 2D waveguide....

  8. EIA screening in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Eskild Holm; Christensen, Per; Kørnøv, Lone

    2005-01-01

    The article points out that EIA screening is effectively a regulatory instrument and it can be a cost-effective instrument with environmental benefits.......The article points out that EIA screening is effectively a regulatory instrument and it can be a cost-effective instrument with environmental benefits....

  9. Substance Abuse Screening

    Science.gov (United States)

    ... information is collected, stored or sent over the Internet. To ensure complete privacy, exit your web browser after completing this screening. ... information is collected, stored or sent over the Internet. To ensure complete privacy, exit your web browser after completing this screening. ...

  10. Screen-film mammography

    International Nuclear Information System (INIS)

    Logan, W.W.; Janus, J.A.

    1987-01-01

    The development of screen-film mammography has resulted in the re-emergence of confidence, rather than fear, in mammography. When screen-film mammography is performed with state-of-the-art dedicated equipment utilizing vigorous breast compression and a ''soft'' x-ray beam for improved contrast, screen-film images are equivalent or superior to those of reduced-dose xeromammography and superior to those of nonscreen film mammography. Technological aids for conversion from xeromammographic or nonscreen film mammographic techniques to screen-film techniques have been described. Screen-film mammography should not be attempted until dedicated equipment has been obtained and the importance of vigorous compression has been understood

  11. Molecular HIV screening.

    Science.gov (United States)

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  12. Screening for abdominalt aortaaneurisme

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Juul, Søren; Henneberg, E W

    1997-01-01

    In spite of increasing number of elective resections of abdominal aortic aneurysms (AAA) the mortality or ruptured AAA is increasing. The advantages of elective operations are obvious; the lethality is 2-6% while the lethality of ruptured AAA is 75-95%. However, AAA seldom causes symptoms before...... rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...

  13. AHCODA-DB: a data repository with web-based mining tools for the analysis of automated high-content mouse phenomics data.

    Science.gov (United States)

    Koopmans, Bastijn; Smit, August B; Verhage, Matthijs; Loos, Maarten

    2017-04-04

    Systematic, standardized and in-depth phenotyping and data analyses of rodent behaviour empowers gene-function studies, drug testing and therapy design. However, no data repositories are currently available for standardized quality control, data analysis and mining at the resolution of individual mice. Here, we present AHCODA-DB, a public data repository with standardized quality control and exclusion criteria aimed to enhance robustness of data, enabled with web-based mining tools for the analysis of individually and group-wise collected mouse phenotypic data. AHCODA-DB allows monitoring in vivo effects of compounds collected from conventional behavioural tests and from automated home-cage experiments assessing spontaneous behaviour, anxiety and cognition without human interference. AHCODA-DB includes such data from mutant mice (transgenics, knock-out, knock-in), (recombinant) inbred strains, and compound effects in wildtype mice and disease models. AHCODA-DB provides real time statistical analyses with single mouse resolution and versatile suite of data presentation tools. On March 9th, 2017 AHCODA-DB contained 650 k data points on 2419 parameters from 1563 mice. AHCODA-DB provides users with tools to systematically explore mouse behavioural data, both with positive and negative outcome, published and unpublished, across time and experiments with single mouse resolution. The standardized (automated) experimental settings and the large current dataset (1563 mice) in AHCODA-DB provide a unique framework for the interpretation of behavioural data and drug effects. The use of common ontologies allows data export to other databases such as the Mouse Phenome Database. Unbiased presentation of positive and negative data obtained under the highly standardized screening conditions increase cost efficiency of publicly funded mouse screening projects and help to reach consensus conclusions on drug responses and mouse behavioural phenotypes. The website is publicly

  14. Screening for skin cancer.

    Science.gov (United States)

    Helfand, M; Mahon, S M; Eden, K B; Frame, P S; Orleans, C T

    2001-04-01

    Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers

  15. Preimplantation genetic screening.

    Science.gov (United States)

    Harper, Joyce C

    2018-03-01

    Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

  16. Phenotypic screening approaches to develop Aurora kinase inhibitors: Drug Discovery perspectives

    Directory of Open Access Journals (Sweden)

    Carlos eMarugán

    2016-01-01

    Full Text Available Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins such as Aurora A and B. Current drugs which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules, have several side effects (neutropenia, alopecia, emesis. Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype.We will briefly describe two multiplexing technologies (high-content imaging, microarrays and flow cytometry and two key processes for drug discovery research (assay development and validation following our own published industry quality standards. We will further focus on high-content imaging as a useful tool for phenotypic screening and will provide a concrete example of high-content imaging assay to detect Aurora A or B selective inhibitors discriminating the off-target effects related to inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

  17. Screening sensitivity theory

    International Nuclear Information System (INIS)

    Oblow, E.M.; Perey, F.G.

    1984-01-01

    A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

  18. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  19. Cervical cancer - screening and prevention

    Science.gov (United States)

    Cancer cervix - screening; HPV - cervical cancer screening; Dysplasia - cervical cancer screening; Cervical cancer - HPV vaccine ... Almost all cervical cancers are caused by HPV (human papilloma virus). HPV is a common virus that spreads through sexual contact. Certain ...

  20. Prostate Cancer Screening

    Science.gov (United States)

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  1. SCREENING FOR CERVICAL CANCER

    African Journals Online (AJOL)

    Enrique

    Cervical cancer remains a major health concern worldwide, especially in devel- ... Important aspects of cervical cancer screening include the age at which .... High-risk types HPV (16,18) are impli- cated in the pathogenesis of cervical cancer.

  2. Breast Cancer Screening

    International Nuclear Information System (INIS)

    Altaf, Fadwa J.

    2004-01-01

    Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

  3. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  4. Breast cancer screening

    International Nuclear Information System (INIS)

    Vandenbroucke, A.

    1987-01-01

    Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

  5. Cell-based DNA demethylation detection system for screening of epigenetic drugs in 2D, 3D, and xenograft models

    Czech Academy of Sciences Publication Activity Database

    Agrawal, K.; Das, V.; Otmar, Miroslav; Krečmerová, Marcela; Džubák, P.; Hajdúch, M.

    91A, č. 2 (2017), s. 133-143 ISSN 1552-4922 R&D Projects: GA MZd(CZ) NV15-31984A; GA MŠk(CZ) LO1304; GA MŠk(CZ) LM2015064; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : DNA methylation * DNA methylation inhibitors * demethylation detection system * epigenetic drugs * high content screening Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.222, year: 2016

  6. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  7. Lung cancer screening: Update

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

    2015-09-15

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

  8. Lung cancer screening: Update

    International Nuclear Information System (INIS)

    Kim, Hyea Young

    2015-01-01

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

  9. Colorectal cancer screening at US community health centers: Examination of sociodemographic disparities and association with patient-provider communication.

    Science.gov (United States)

    Lin, Sue C; McKinley, Duane; Sripipatana, Alek; Makaroff, Laura

    2017-11-01

    Colorectal cancer (CRC) screening rates are low among underserved populations. High-quality patient-physician communication potentially influences patients' willingness to undergo CRC screening. Community health centers (HCs) provide comprehensive primary health care to underserved populations. This study's objectives were to ascertain national CRC screening rates and to explore the relations between sociodemographic characteristics and patient-provider communication on the receipt of CRC screening among HC patients. Using 2014 Health Center Patient Survey data, bivariate and multivariate analyses examined the association of sociodemographic variables (sex, race/ethnicity, age, geography, preferred language, household income, insurance, and employment status) and patient-provider communication with the receipt of CRC screening. Patients between the ages of 65 and 75 years (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.33-4.64) and patients not in the labor force (aOR, 2.32; 95% CI, 1.37-3.94) had higher odds of receiving CRC screening, whereas patients who were uninsured (aOR, 0.33; 95% CI, 0.18-0.61) and patients who were non-English-speaking (aOR, 0.42; 95% CI, 0.18-0.99) had lower odds. Patient-provider communication was not associated with the receipt of CRC screening. The CRC screening rate for HC patients was 57.9%, whereas the rate was 65.1% according to the 2012 Behavioral Risk Factor Surveillance System and 58.2% according to the 2013 National Health Interview Survey. The high ratings of patient-provider communication, regardless of the screening status, suggest strides toward a patient-centered medical home practice transformation that will assist in a positive patient experience. Addressing the lack of insurance, making culturally and linguistically appropriate patient education materials available, and training clinicians and care teams in cultural competency are critical for increasing future CRC screening rates. Cancer 2017

  10. [Organized breast cancer screening].

    Science.gov (United States)

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

    Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to

  11. Physics in Screening Environments

    Science.gov (United States)

    Certik, Ondrej

    In the current study, we investigated atoms in screening environments like plasmas. It is common practice to extract physical data, such as temperature and electron densities, from plasma experiments. We present results that address inherent computational difficulties that arise when the screening approach is extended to include the interaction between the atomic electrons. We show that there may arise an ambiguity in the interpretation of physical properties, such as temperature and charge density, from experimental data due to the opposing effects of electron-nucleus screening and electron-electron screening. The focus of the work, however, is on the resolution of inherent computational challenges that appear in the computation of two-particle matrix elements. Those enter already at the Hartree-Fock level. Furthermore, as examples of post Hartree-Fock calculations, we show second-order Green's function results and many body perturbation theory results of second order. A self-contained derivation of all necessary equations has been included. The accuracy of the implementation of the method is established by comparing standard unscreened results for various atoms and molecules against literature for Hartree-Fock as well as Green's function and many body perturbation theory. The main results of the thesis are presented in the chapter called Screened Results, where the behavior of several atomic systems depending on electron-electron and electron-nucleus Debye screening was studied. The computer code that we have developed has been made available for anybody to use. Finally, we present and discuss results obtained for screened interactions. We also examine thoroughly the computational details of the calculations and particular implementations of the method.

  12. More comprehensive discussion of CRC screening associated with higher screening.

    Science.gov (United States)

    Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

    2013-04-01

    Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

  13. Newborn hearing screening.

    Science.gov (United States)

    Stewart, D L; Pearlman, A

    1994-11-01

    Congenital deafness is a relatively common problem with an incidence of 1/300 to 1/1000. Most states have no mass screening program for hearing loss, but the state of Kentucky compiles a High Risk Registry which is a historical survey of parents relating to risk factors for hearing loss. Unfortunately this survey can miss 50% of those who have a hearing deficit. If not detected prior to discharge, there is often a delay in diagnosis of deafness which prevents early intervention. We report 2 years' experience at Kosair Children's Hospital where 1,987 infants admitted to well baby, intermediate, or intensive care nurseries were screened using the ALGO-1 screener (Natus Medical Inc, Foster City, CA) which is a modified auditory brain stem evoked response (ABR). Our screening of this population led to an 11% incidence of referral for complete audiological evaluation. There were no significant complications. Forty-eight infants were found to have nonspecified, sensorineural, or conductive hearing loss. The positive predictive value of the test was 96%. Therefore, we feel that the use of the modified ABR in the newborn is a timely, cost efficient method of screening for hearing loss and should be used for mass screening of all newborns.

  14. Screening for oral cancer.

    Science.gov (United States)

    Jitender, Solanki; Sarika, Gupta; Varada, Hiremath R; Omprakash, Yadav; Mohsin, Khan

    2016-11-01

    Oral cancer is considered as a serious health problem resulting in high morbidity and mortality. Early detection and prevention play a key role in controlling the burden of oral cancer worldwide. The five-year survival rate of oral cancer still remains low and delayed diagnosis is considered as one of the major reasons. This increases the demand for oral screening. Currently, screening of oral cancer is largely based on visual examination. Various evidence strongly suggest the validity of visual inspection in reducing mortality in patients at risk for oral cancer. Simple visual examination is accompanied with adjunctive techniques for subjective interpretation of dysplastic changes. These include toluidine blue staining, brush biopsy, chemiluminescence and tissue autofluorescence. This review highlights the efficacy of various diagnostic methods in screening of oral cancer. © 2016 Old City Publishing, Inc.

  15. Radiographic intensifying screens

    International Nuclear Information System (INIS)

    Van Landeghem, W.K.; Suys, A.R.

    1979-01-01

    A fluorescent x-ray image intensifying screen is described which comprises discrete particles of fluorescent material dispersed in a binder layer. Intensifying screens are employed to increase the exposure of a photosensitive plate or film without increasing the x-ray exposure dose when struck by x-rays. The screen has an outermost layer containing solid particulate material protruding from a coherent film-forming organic binder medium and having a static friction coefficient at room temperature not higher than 0.50 on steel. The outermost layer may be characterized by micro-unevennesses of at least 3 μm and at least 9 protruding particles per 0.35 sq. cm. These particles have a static friction coefficient less than 0.3 and are made of a solid polystyrene, polyaklylene and/or a solid organic fluorinated polymer. (JTA)

  16. Screening of irradiated food using ESR measurement of paper

    International Nuclear Information System (INIS)

    Goto, Michiko; Yamazaki, Masao

    2005-01-01

    As paper has high content of cellulose, sensibility of ESR measurements of paper should be high. We examined stability of ESR signals in irradiated recycled copying paper, and estimated the possibility to utilize ESR measurement of paper for the detection of irradiated food. Cellulose radicals in paper irradiated at 1kGy and stored at 40degC in water was detected for 20 days. Cellulose radicals in irradiated paper stored at 90degC in water were more stable than that stored in air. ESR measurements of 50mg paper are simple and easy, so ESR measurement of rapping paper or corrugated box is good screening method for the detection of irradiated food. (author)

  17. Screening Risk Evaluation methodology

    International Nuclear Information System (INIS)

    Hopper, K.M.

    1994-01-01

    The Screening Risk Evaluation (SRE) Guidance document is a set of guidelines provided for the uniform implementation of SREs performed on D ampersand D facilities. These guidelines are designed specifically for the completion of the second (semi-quantitative screening) phase of the D ampersand D Risk-Based Process. The SRE Guidance produces screening risk scores reflecting levels of risk through the use of risk ranking indices. Five types of possible risk are calculated from the SRE: current releases, worker exposures, future releases, physical hazards, and criticality. The Current Release Index (CRI) calculates the risk to human health and the environment from ongoing or probable releases within a one year time period. The Worker Exposure Index (WEI) calculates the risk to workers, occupants, and visitors in D ampersand D facilities of contaminant exposure. The Future Release Index (FRI) calculates the risk of future releases of contaminants, after one year, to human health and the environment. The Physical Hazards Index (PHI) calculates the risk-to human health due to factors other than that of contaminants. The index of Criticality is approached as a modifying factor to the entire SRE, due to the fact that criticality issues are strictly regulated under DOE. Screening risk results will be tabulated in matrix form and Total Risk will be calculated (weighted equation) to produce a score on which to base early action recommendations. Other recommendations from the screening risk scores will be made based either on individual index scores or from reweighted Total Risk calculations. All recommendations based on the SRE will be made based on a combination of screening risk scores, decision drivers, and other considerations, determined on a project by project basis. The SRE is the first and most important step in the overall D ampersand D project level decision making process

  18. Newborn screening for galactosaemia.

    Science.gov (United States)

    Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

    2017-12-23

    Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the

  19. Colorectal cancer screening

    OpenAIRE

    McLoughlin, Monica Ramona

    2008-01-01

    Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...

  20. Validation of the haemoglobin colour scale for screening blood ...

    African Journals Online (AJOL)

    blood donors for anaemia, using the WHO Haemoglobin Colour. Scale (HCS) for ... simple alternative for assessing anaemia.3,4 It does not aim to compete with a .... staff to see if similar levels of sensitivity and specificity are obtained. A more ...

  1. Lunar Dust Mitigation Screens

    Science.gov (United States)

    Knutson, Shawn; Holloway, Nancy

    With plans for the United States to return to the moon, and establish a sustainable human presence on the lunar surface many issues must be successfully overcome. Lunar dust is one of a number of issues with the potential to create a myriad of problems if not adequately addressed. Samples of dust brought back from Apollo missions show it to be soft, yet sharp and abrasive. The dust consists of a variety of morphologies including spherical, angular blocks, shards, and a number of irregular shapes. One of the main issues with lunar dust is its attraction to stick to anything it comes in contact with (i.e. astronauts, equipment, habitats, etc.). Ionized radiation from the sun strikes the moon's surface and creates an electrostatic charge on the dust. Further, the dust harbors van der Waals forces making it especially difficult to separate once it sticks to a surface. During the Apollo missions, it was discovered that trying to brush the lunar dust from spacesuits was not effective, and rubbing it caused degradation of the suit material. Further, when entering the lunar module after moonwalks, the astronauts noted that the dust was so prolific inside the cabin that they inhaled and ingested it, causing at least one of them, Harrison "Jack" Schmidt, to report irritation of the throat and lungs. It is speculated that the dust could also harm an astronaut's nervous and cardiovascular systems, especially during an extended stay. In addition to health issues, the dust can also cause problems by scouring reflective coatings off of thermal blankets, and roughening surfaces of windows and optics. Further, panels on solar cells and photovoltaics can also be compromised due to dust sticking on the surfaces. Lunar dust has the capacity to penetrate seals, interfere with connectors, as well as mechanisms on digging machines, all of which can lead to problems and failure. To address lunar dust issues, development of electrostatic screens to mitigate dust on sur-faces is currently

  2. Approaches to virtual screening and screening library selection.

    Science.gov (United States)

    Wildman, Scott A

    2013-01-01

    The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

  3. Screening for Atrial Fibrillation

    DEFF Research Database (Denmark)

    Freedman, Ben; Camm, John; Calkins, Hugh

    2017-01-01

    Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed...

  4. Early Dementia Screening

    Directory of Open Access Journals (Sweden)

    Peter K. Panegyres

    2016-01-01

    Full Text Available As the population of the world increases, there will be larger numbers of people with dementia and an emerging need for prompt diagnosis and treatment. Early dementia screening is the process by which a patient who might be in the prodromal phases of a dementing illness is determined as having, or not having, the hallmarks of a neurodegenerative condition. The concepts of mild cognitive impairment, or mild neurocognitive disorder, are useful in analyzing the patient in the prodromal phase of a dementing disease; however, the transformation to dementia may be as low as 10% per annum. The search for early dementia requires a comprehensive clinical evaluation, cognitive assessment, determination of functional status, corroborative history and imaging (including MRI, FDG-PET and maybe amyloid PET, cerebrospinal fluid (CSF examination assaying Aβ1–42, T-τ and P-τ might also be helpful. Primary care physicians are fundamental in the screening process and are vital in initiating specialist investigation and treatment. Early dementia screening is especially important in an age where there is a search for disease modifying therapies, where there is mounting evidence that treatment, if given early, might influence the natural history—hence the need for cost-effective screening measures for early dementia.

  5. Hazard screening application guide

    International Nuclear Information System (INIS)

    1992-06-01

    The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information

  6. Radiological protective screen

    International Nuclear Information System (INIS)

    Flaugnatti, R.B.

    1976-01-01

    A radiological screen for placing on a patient's skin is discussed, comprising a flat jacket containing a fine particulate filler and a settable resin binder, the fine particulate filler being of a material which absorbs medical radiation, and the jacket including a window to transmit such radiation through the flat jacket. 16 claims, 4 drawing figures

  7. Screening Devices at School

    DEFF Research Database (Denmark)

    Ratner, Helene Gad

    2011-01-01

    ethnographic data from a Danish school, the article explores,first, the script and agencement of the SMTTE and, second, how the screening properties of the SMTTE are achieved, including how these properties challenge management-­‐teacher relations when the SMTTE travels to other networks at the school...

  8. Colorec tal cancer screening

    African Journals Online (AJOL)

    2009-05-12

    May 12, 2009 ... The operator must be skilled in the management of adverse events. • The operator must arrange appropriate follow-up of histopathological results. • The operator must provide appropriate recommendations for follow-up surveil- lance and screening. The average- risk person has a lifetime risk of developing.

  9. [ASCUS in screening].

    Science.gov (United States)

    Caprara, L; Monari, F; De Bianchi, P S; Amadori, A; Bondi, A

    2001-12-01

    The significance and use of the cytological diagnosis "atypical squamous cells of undetermined significance" (ASCUS) remain a major problem in cervical cancer screening. The prevalence of ASCUS by patient age has seldom been investigated. The present paper reports the prevalence of ASCUS in a large series of screening Pap smears from the Italian region of Emilia-Romagna. The study was based on the data collected by the Department of Health of the Emilia-Romagna Region for the first 3-year round (1997-1999) of a population-based screening programme (target age, 25-64 years). The age-specific frequency of ASCUS has been calculated as a prevalence rate per 1000 screened patients. A total of 597,386 women participated in the programme. Women diagnosed with ASCUS (n = 8205 or 13.7 per 1000) accounted for 49% of the recalls for colposcopy (n = 16,871, or 28.2 per 1000). The prevalence of diagnoses of low-grade squamous intraepithelial lesions (LG-SIL) decreased progressively with age while that of high-grade SIL was slightly higher between 30 and 39 years. The prevalence of ASCUS peaked at age 45-49 years (17.3 per 1000 subjects). The observed peak reflects the prevalence of (1) cytological changes closely associated with perimenopausal age and at least compatible with the ASCUS diagnosis, and (2) cytological abnormalities induced by hormone replacement therapy.

  10. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

  11. Screening for asbestbetingede sygdomme?

    DEFF Research Database (Denmark)

    Brauer, Charlotte; Baandrup, Ulrik; Jacobsen, Peter

    2009-01-01

    in asbestos-exposed populations. Data do not currently support implementation of screening programs for asbestos-exposed persons in Denmark. Since mesothelioma is most often an occupational disease, these patients should be admitted to an occupational clinic for aetiological evaluation. Udgivelsesdato: 2009...

  12. Engineering aspects of Passavant screening

    International Nuclear Information System (INIS)

    Siddle, K.R.; Sharma, R.K.

    1978-01-01

    The Passavant screen was developed in Europe almost 30 years ago. The Passavant screen is a vertical traveling screen; however, the basic difference between the conventional vertical traveling screen and the Passavant screen is that in the conventional screen water passes through the front screen belt and then the back screen belt, whereas in the Passavant screen the water enters in between the two belts and passes laterally through either of the belts. Thus, theoretically, the screening surface of the Passavant screen is doubled as compared to the same size conventional vertical traveling screen. Various design and operational modifications of the Passavant screen are possible to yield optimum design and performance characteristics which make it amenable to installation at power plants for safe removal of not only fish but also smaller organisms such as fish eggs and larvae. In this paper, details of the screen design and operational characteristics are discussed with notes on how these features can be modified to suit site- and organism-specific requirements

  13. Chapter 6. Uranium extraction possibilities from natural uranium-bearing waters of complex salt composition. 6.2. Technology for uranium extraction from brine with a high content of ion-chlorine

    International Nuclear Information System (INIS)

    Khakimov, N.; Nazarov, Kh.M.; Mirsaidov, I.U.

    2012-01-01

    Present article is devoted to technology for uranium extraction from brine with a high content of ion-chlorine. The content of basic anions and cations in lake waters of Sasik-Kul deposit was defined. Results of X-ray spectral analysis of salt residual after water evaporation from Sasik-Kul lake was discussed. Investigations revealed that uranium extraction from brines containing ion-chlorine is possible. The developed basic process flow diagram of uranium extraction from Sasik-Kul Lake' brine consists of the following basic stages: evaporation, leaching, catching of formed gases (HCl), sorption, desorption, deposition, drying and tempering.

  14. Chapter 6. Uranium extraction possibilities from natural uranium-bearing waters of complex salt composition. 6.2. Technology for uranium extraction from brine with a high content of ion-chlorine

    International Nuclear Information System (INIS)

    Khakimov, N.; Nazarov, Kh.M.; Mirsaidov, I.U.

    2011-01-01

    Present article is devoted to technology for uranium extraction from brine with a high content of ion-chlorine. The content of basic anions and cations in lake waters of Sasik-Kul deposit was defined. Results of X-ray spectral analysis of salt residual after water evaporation from Sasik-Kul lake was discussed. Investigations revealed that uranium extraction from brines containing ion-chlorine is possible. The developed basic process flow diagram of uranium extraction from Sasik-Kul Lake' brine consists of the following basic stages: evaporation, leaching, catching of formed gases (HCl), sorption, desorption, deposition, drying and tempering.

  15. Screening for chlamydial infection.

    Science.gov (United States)

    Nelson, H D; Helfand, M

    2001-04-01

    To examine data on the effectiveness of screening for chlamydial infection by a physician or other health care professional. Specifically, we examine the evidence that early treatment of chlamydial infection improves health outcomes, as well as evidence of the effectiveness of screening strategies in nonpregnant women, pregnant women, and men, and the accuracy of tests used for screening. This review updates the literature since the last recommendation of the U.S. Preventive Services Task Force published in 1996. We searched the topic of chlamydia in the MEDLINE, HealthSTAR, and Cochrane Library databases from January 1994 to July 2000, supplemented by reference lists of relevant articles and from experts in the field. Articles published prior to 1994 and research abstracts were cited if particularly important to the key questions or to the interpretation of included articles. A single reader reviewed all English abstracts. Articles were selected for full review if they were about Chlamydia trachomatis genitourinary infections in nonpregnant women, pregnant women, or men and were relevant to key questions in the analytic framework. Investigators read the full-text version of the retrieved articles and applied additional eligibility criteria. For all topics, we excluded articles if they did not provide sufficient information to determine the methods for selecting subjects and for analyzing data. We systematically reviewed three types of studies about screening in nonpregnant women that relate to three key questions: (1) studies about the effectiveness of screening programs in reducing prevalence rates of infection, (2) studies about risk factors for chlamydial infection in women, and (3) studies about chlamydial screening tests in women. Our search found too few studies on pregnant women to systematically review, although pertinent studies are described. We systematically reviewed two types of studies about screening in men: (1) studies about prevalence rates and

  16. Screening for Chronic Kidney Disease

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Chronic Kidney Disease The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Chronic Kidney Disease (CKD) . This recommendation ...

  17. Glucose screening tests during pregnancy

    Science.gov (United States)

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... screening test between 24 and 28 weeks of pregnancy. The test may be done earlier if you ...

  18. Risks of Endometrial Cancer Screening

    Science.gov (United States)

    ... Health history and certain medicines can affect the risk of developing endometrial cancer. Anything that increases your ... have abnormal vaginal bleeding, check with your doctor. Risks of Endometrial Cancer Screening Key Points Screening tests ...

  19. Risks of Esophageal Cancer Screening

    Science.gov (United States)

    ... alcohol use, and Barrett esophagus can affect the risk of developing esophageal cancer. Anything that increases the ... tissue gives off less light than normal tissue. Risks of Esophageal Cancer Screening Key Points Screening tests ...

  20. Risks of Cervical Cancer Screening

    Science.gov (United States)

    ... women. Human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Although most women with ... clinical trials is available from the NCI website . Risks of Cervical Cancer Screening Key Points Screening tests ...

  1. Mammographic screening programmes in Europe

    DEFF Research Database (Denmark)

    Giordano, Livia; von Karsa, Lawrence; Tomatis, Mariano

    2012-01-01

    To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe.......To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe....

  2. Exploring Urban Screens

    Directory of Open Access Journals (Sweden)

    Zlatan Krajina

    2009-12-01

    Full Text Available There is a tautological tendency in the widespread claims that urban space is 'me-diated'. Never before has the citizen, it is argued, been confronted with such an unprecedented array of signage. I depart from the rhetoric of 'biggest-ever-saturation' as not necessarily untrue, but as insufficient in exploring the diverse spatial operations of urban screens. I examine some contemporary cases of ani-mated architectural surfaces, informational panels, and advertising billboards, with reference to much longer standing cultural practices of spatial management in modern cities, such as illumination, to suggest that the contemporary display media do not mediate the city anew but re-invent urban space as a field of ubiqui-tous mediation. From that standpoint I suggest exploring urban screens as a both singular visual agents and indivisible items in plural structural assemblages, b complementary forces of public illumination, and c complex perceptual platforms in visual play of scale and distance.

  3. An experience of qualified preventive screening: shiraz smart screening software.

    Science.gov (United States)

    Islami Parkoohi, Parisa; Zare, Hashem; Abdollahifard, Gholamreza

    2015-01-01

    Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.

  4. Ellipticity Weakens Chameleon Screening

    OpenAIRE

    Burrage, Clare; Copeland, Edmund J.; Stevenson, James

    2014-01-01

    The chameleon mechanism enables a long range fifth force to be screened in dense environments when non-trivial self interactions of the field cause its mass to increase with the local density. To date, chameleon fifth forces have mainly been studied for spherically symmetric sources, however the non-linear self interactions mean that the chameleon responds to changes in the shape of the source differently to gravity. In this work we focus on ellipsoidal departures from spherical symmetry and ...

  5. New generation expandable sand screens

    OpenAIRE

    Syltøy, Christer

    2014-01-01

    Master's thesis in Petroleum engineering This thesis aims to give a general insight into sand control and various sorts of sand control measures and applications of sand control tools. Special focus will be given to expandable sand screens – a technology which came about in the late 1990’s through the use of flexible, expandable tubulars as base pipe in sand screens. More specifically Darcy’s Hydraulic Endurance Screens, a compliant sand screen system using hydraulic activation, and the fu...

  6. SCREENING FOR PERSONALITY DISORDERS

    Science.gov (United States)

    Morse, Jennifer Q.; Pilkonis, Paul A.

    2010-01-01

    A brief but valid self-report measure to screen for personality disorders (PDs) would be a valuable tool in making decisions about further assessment and in planning optimal treatments. In psychiatric and nonpsychiatric samples, we compared the validity of three screening measures: the PD scales from the Inventory of Interpersonal Problems, a self-report version of the Iowa Personality Disorder Screen, and the self-directedness scale of the Temperament and Character Inventory. Despite their different theoretical origins, the screeners were highly correlated in a range from .71 to .77. As a result, the use of multiple screeners was not a significant improvement over any individual screener, and no single screener stood out as clearly superior to the others. Each performed modestly in predicting the presence of any PD diagnosis in both the psychiatric and nonpsychiatric groups. Performance was best when predicting a more severe PD diagnosis in the psychiatric sample. The results also highlight the potential value of multiple assessments when relying on self-reports. PMID:17492920

  7. Automated screening for retinopathy

    Directory of Open Access Journals (Sweden)

    A. S. Rodin

    2014-07-01

    Full Text Available Retinal pathology is a common cause of an irreversible decrease of central vision commonly found amongst senior population. Detection of the earliest signs of retinal diseases can be facilitated by viewing retinal images available from the telemedicine networks. To facilitate the process of retinal images, screening software applications based on image recognition technology are currently on the various stages of development.Purpose: To develop and implement computerized image recognition software that can be used as a decision support technologyfor retinal image screening for various types of retinopathies.Methods: The software application for the retina image recognition has been developed using C++ language. It was tested on dataset of 70 images with various types of pathological features (age related macular degeneration, chorioretinitis, central serous chorioretinopathy and diabetic retinopathy.Results: It was shown that the system can achieve a sensitivity of 73 % and specificity of 72 %.Conclusion: Automated detection of macular lesions using proposed software can significantly reduce manual grading workflow. In addition, automated detection of retinal lesions can be implemented as a clinical decision support system for telemedicine screening. It is anticipated that further development of this technology can become a part of diagnostic image analysis system for the electronic health records.

  8. Screening Resonances In Plasmas

    International Nuclear Information System (INIS)

    Winkler, P.

    1998-01-01

    When it was suggested that a new recombination mechanism (Resonant Radiative Recombination (RRR)) which, based on very general physical arguments, should happen in dense plasmas and promises to provide useful information for the local temperature and density diagnostics of plasmas, they assumed the existence of screening resonances. For model potentials the existence of screening resonances has been demonstrated beyond reasonable doubt in a number of calculations. The key question, how well those potentials describe the dominant effects of a real plasma remains open. The relation of theoretical predictions to experimentally measurable effects is an important issue at the present stage of their research. In particular, RRR is expected to account for enhanced recombination rates of low energetic electrons with their ions, since the first stage is the resonant capture of a slow electron by an atom or ion. The mechanism that traps an electron is a combination of complicated many-body interactions of the ions and electrons. For clarity they start here, however, with a discussion in terms of local potential traps the shapes of which are determined predominantly and in an average way by two factors: the degree of screening present at the ionic site and the degree of short-range order in the immediate neighborhood of this ion

  9. Nutrition screening: science behind simplicity

    African Journals Online (AJOL)

    Nutrition screening triggers entry into the nutrition care process.1 Screening has informally been described as simple, quick or low-intensity proxy for more complex procedures. More formal definitions for the nutrition setting have been proposed, describing nutrition screening as a process of identifying patients, clients, or ...

  10. Push for the Second Screen

    DEFF Research Database (Denmark)

    Sørensen, Jannick Kirk; Sørensen, Lene Tolstrup

    Users’ perception of the relation between the TV screen and a secondary screen (e.g. smartphone or tablet) is examined empirically in a pilot project through a low-fi prototype and interviews. Early observations indicate that the user value/acceptance of push-messages delivered to the second screen...

  11. High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

    Science.gov (United States)

    Kaufmann, Markus; Schuffenhauer, Ansgar; Fruh, Isabelle; Klein, Jessica; Thiemeyer, Anke; Rigo, Pierre; Gomez-Mancilla, Baltazar; Heidinger-Millot, Valerie; Bouwmeester, Tewis; Schopfer, Ulrich; Mueller, Matthias; Fodor, Barna D; Cobos-Correa, Amanda

    2015-10-01

    Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention. © 2015 Society for Laboratory Automation and Screening.

  12. Abnormal Cervical Cancer Screening Test Results

    Science.gov (United States)

    ... AQ FREQUENTLY ASKED QUESTIONS FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test ...

  13. Screening diagnostic program breast cancer

    International Nuclear Information System (INIS)

    Portnoj, L.M.; Zhakova, I.I.; Budnikova, N.V.; Rukhlyadko, E.D.

    1995-01-01

    The authors propose their screening program for detection of breast cancer. It includes the entire complex of present-day screening diagnostic methods, starting from an original system for the formation of groups at risk of breast cancer and completed by the direct diagnostic model of detection of the condition, oriented at a differentiated approach to the use of mammographic techniques. The proposed organizational and methodologic screening measures are both economic and diagnostically effective, thus meeting the principal requirements to screening programs. Screening of 8541 risk-groups patients helped detect 867 nodular formations, 244 of which were cancer and 623 benign formations. 8 refs., 3 figs.,

  14. Photon attenuation by intensifying screens

    International Nuclear Information System (INIS)

    Holje, G.

    1983-01-01

    The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

  15. Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, U.; Aalst, C. van der; Jong, P.A. de; Heuvelmans, M.; Scholten, E.T.; Lammers, J.-W.J.; Ooijen, P. van; Nackaerts, K.; Weenink, C.; Groen, H.; Vliegenthart, R.; Haaf, K. Ten; Oudkerk, M.; Koning, H. de

    2016-01-01

    In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  16. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  17. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A.; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  18. Korean Screen Cultures

    DEFF Research Database (Denmark)

    Screen Cultures sets out to redress this imbalance with a broad selection of essays spanning both North and South as well as different methodological approaches, from ethnographic and audience studies to cultural materialist readings. The first section of the book, «The South», highlights popular media...... new approaches to Korean popular culture beyond national borders and includes work on K-pop and Korean television drama. This book is a vital addition to existing scholarship on Korean popular culture, offering a unique view by providing an imaginary unification of the two Koreas negotiated through...

  19. Air-water screen

    Energy Technology Data Exchange (ETDEWEB)

    Prokopov, O.I.; Kutepov, A.I.

    1980-12-08

    The air-water screen based on inventor's certificate No. 577364 contains horizontal water and air lines with water and air nozzles. The air line is situated inside the water line eccentrically and contracts it in the area of the nozzle, whose orifices are situated along the line of contact, while the orifices of the water nozzle are situated symmetrically relative to the air orifices and are located at an acute angle to them. To raise the protective properties, on the end of the water line is a lateral nozzle water distributor is an additional nozzle, connected to this container.

  20. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  1. Molecular screening in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Singh, R.; Fernhoff, P.M. [Emory Univ., Atlanta, GA (United States)] [and others

    1994-09-01

    Classical galactosemia (G/G) is caused by the absence of galactose-1-phosphate uridyl transferase (GALT) activity while the Duarte allele produces partial impairment and a specific biochemical phenotype. Cloning and sequencing of the human GALT gene has enabled the identification of prevalent mutations for both Classical and Duarte alleles. The G allele is caused by a Q188R codon mutation in exon 6 in 70% of a Caucasian population while the D allele is caused by an N134D codon mutation in exon 10. Since the Q188R sequence creates a new Hpa II site and the N314D sequence creates a new Sin I site, it is relatively easy to screen for both mutations by multiplex PCR and restriction digest. Here we describe a method for detection of new mutations producing impaired GALT. Patient DNAs are subjected to SSCP (single strand conformational polymorphism) analysis of their 11 GALT exons. Direct sequencing of the exons targeted by SSCP has revealed many codon changes: IVSC 956 (a splice acceptor site loss), S135L, V151A, E203K, A320T, and Y323D. Two of these codon changes, V151A and S135L, have been confirmed as mutations by finding impaired GALT activity in a yeast expression system. We conclude that molecular screening of GALT DNA will clarify the structural biology of GALT and the pathophysiology of galactosemia.

  2. SUPER-screening

    Energy Technology Data Exchange (ETDEWEB)

    Brax, Philippe, E-mail: Philippe.Brax@cea.fr [Institut de Physique Theorique, CEA, IPhT, CNRS, URA 2306, F-91191Gif/Yvette Cedex (France); Davis, Anne-Christine, E-mail: A.C.Davis@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Sakstein, Jeremy, E-mail: J.A.Sakstein@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

    2013-02-26

    We present a framework for embedding scalar–tensor models of screened modified gravity such as chameleons, symmetrons and environmental dilatons into global supersymmetry. This achieved by secluding the dark sector from both the observable and supersymmetry breaking sectors. We examine the resulting supersymmetric features in a model-independent manner and find that, when the theory follows from an underlying supergravity, the mediation of supersymmetry breaking to the dark sector induces a soft mass for the scalar of order the gravitino mass. This is enough to forbid the construction of supersymmetric symmetrons and ensures that when other screening mechanisms operate, no object in the Universe is unscreened thereby precluding any observable signatures. In view of a possible origin of modified gravity within fundamental physics, we find that only no-scale models can circumvent these features. We also present a novel mechanism where the coupling of the scalar to two other scalars charged under U(1) can dynamically generate a small cosmological constant at late times in the form of a Fayet–Iliopoulos term.

  3. [Primary cervical cancer screening].

    Science.gov (United States)

    Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

    2015-01-01

    Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  4. A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery.

    Science.gov (United States)

    Joslin, John; Gilligan, James; Anderson, Paul; Garcia, Catherine; Sharif, Orzala; Hampton, Janice; Cohen, Steven; King, Miranda; Zhou, Bin; Jiang, Shumei; Trussell, Christopher; Dunn, Robert; Fathman, John W; Snead, Jennifer L; Boitano, Anthony E; Nguyen, Tommy; Conner, Michael; Cooke, Mike; Harris, Jennifer; Ainscow, Ed; Zhou, Yingyao; Shaw, Chris; Sipes, Dan; Mainquist, James; Lesley, Scott

    2018-05-01

    The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.

  5. Consequences of screening in lung cancer: development and dimensionality of a questionnaire.

    Science.gov (United States)

    Brodersen, John; Thorsen, Hanne; Kreiner, Svend

    2010-08-01

    The objective of this study was to extend the Consequences of Screening (COS) Questionnaire for use in a lung cancer screening by testing for comprehension, content coverage, dimensionality, and reliability. In interviews, the suitability, content coverage, and relevance of the COS were tested on participants in a lung cancer screening program. The results were thematically analyzed to identify the key consequences of abnormal and false-positive screening results. Item Response Theory and Classical Test Theory were used to analyze data. Dimensionality, objectivity, and reliability were established by item analysis, examining the fit between item responses and Rasch models. Eight themes specifically relevant for participants in lung cancer screening results were identified: "self-blame,"focus on symptoms,"stigmatization,"introvert,"harm of smoking,"impulsivity,"empathy," and "regretful of still smoking." Altogether, 26 new items for part I and 16 new items for part II were generated. These themes were confirmed to fit a partial-credit Rasch model measuring different constructs including several of the new items. In conclusion, the reliability and the dimensionality of a condition-specific measure with high content validity for persons having abnormal or false-positive lung cancer screening results have been demonstrated. This new questionnaire called Consequences of Screening in Lung Cancer (COS-LC) covers in two parts the psychosocial experience in lung cancer screening. Part I: "anxiety,"behavior,"dejection,"sleep,"self-blame,"focus on airway symptoms,"stigmatization,"introvert," and "harm of smoking." Part II: "calm/relax,"social network,"existential values,"impulsivity,"empathy," and "regretful of still smoking."

  6. Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening.

    Science.gov (United States)

    Wagner, Bridget K; Carrinski, Hyman A; Ahn, Young-Hoon; Kim, Yun Kyung; Gilbert, Tamara J; Fomina, Dina A; Schreiber, Stuart L; Chang, Young-Tae; Clemons, Paul A

    2008-04-02

    A small molecule capable of distinguishing the distinct states resulting from cellular differentiation would be of enormous value, for example, in efforts aimed at regenerative medicine. We screened a collection of fluorescent small molecules for the ability to distinguish the differentiated state of a mouse skeletal muscle cell line. High-throughput fluorescence-based screening of C2C12 myoblasts and myotubes resulted in the identification of six compounds with the desired selectivity, which was confirmed by high-content screening in the same cell states. The compound that resulted in the greatest fluorescence intensity difference between the cell states was used as the screening agent in a pilot screen of 84 kinase inhibitors, each present in four doses, for inhibition of myogenesis. Of the kinase inhibitors, 17 resulted in reduction of fluorescence at one or more concentrations; among the "hits" included known inhibitors of myogenesis, confirming that this compound is capable of detecting the differentiated myotube state. We suggest that the strategy of screening for screening agents reported here may be extended more broadly in the future.

  7. The high throughput biomedicine unit at the institute for molecular medicine Finland: high throughput screening meets precision medicine.

    Science.gov (United States)

    Pietiainen, Vilja; Saarela, Jani; von Schantz, Carina; Turunen, Laura; Ostling, Paivi; Wennerberg, Krister

    2014-05-01

    The High Throughput Biomedicine (HTB) unit at the Institute for Molecular Medicine Finland FIMM was established in 2010 to serve as a national and international academic screening unit providing access to state of the art instrumentation for chemical and RNAi-based high throughput screening. The initial focus of the unit was multiwell plate based chemical screening and high content microarray-based siRNA screening. However, over the first four years of operation, the unit has moved to a more flexible service platform where both chemical and siRNA screening is performed at different scales primarily in multiwell plate-based assays with a wide range of readout possibilities with a focus on ultraminiaturization to allow for affordable screening for the academic users. In addition to high throughput screening, the equipment of the unit is also used to support miniaturized, multiplexed and high throughput applications for other types of research such as genomics, sequencing and biobanking operations. Importantly, with the translational research goals at FIMM, an increasing part of the operations at the HTB unit is being focused on high throughput systems biological platforms for functional profiling of patient cells in personalized and precision medicine projects.

  8. Mass screening in breast cancer

    International Nuclear Information System (INIS)

    Strax, P.

    1977-01-01

    Some questions about mass screening in breast cancer are answered it being concluded that: 1. mass screening for the detection of early breast cancer is the only means with proven potential for lowering the death rate of the disease; 2. mammography is an importante - if not the most important modality in mass screening; 3. new film - screen combinations generally available are capable of producing mammograms of excelent quality with radiation doses down to .1 rad into the body of breast. The risk of malignant changes from such dosage - even when given periodically is negligeable. New equipment, to be available, shortly, will use the new film - screen combinations in an automated manner with must reduce cost in time, filme, personnel and processing - of more than 50%. This would make mass screening more practical. (M.A.) [pt

  9. Current Cervical Carcinoma Screening Guidelines

    Directory of Open Access Journals (Sweden)

    Megan J. Schlichte

    2015-05-01

    Full Text Available A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP and the American Society for Clinical Pathology (ASCP in 2012, and later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG. The 2012 recommendations underscore the utility of molecular testing as an adjunct to cytology screening for certain women and provide guidance to clinicians based on different risk-benefit considerations for different ages. This manuscript will review screening techniques and current recommendations for cervical cancer screening and human papilloma virus (HPV testing, as well as possible future screening strategies.

  10. Luminescence studies on phosphor screens

    International Nuclear Information System (INIS)

    Panayiotakis, G.; Nomikos, C.; Bakas, A.; Proimos, B.

    1994-01-01

    We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors)

  11. Luminescence studies on phosphor screens

    Energy Technology Data Exchange (ETDEWEB)

    Panayiotakis, G; Nomikos, C; Bakas, A; Proimos, B [Medical Physics Department, University of Patras, 265 00 Patras, Greece (Greece)

    1994-12-31

    We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors). 12 refs, 3 figs.

  12. Newborn Screening for Phenylketonuria

    Directory of Open Access Journals (Sweden)

    Gustavo J. C. Borrajo PhD

    2016-12-01

    Full Text Available Newborn screening (NBS for phenylketonuria in Latin America gave its first step in an organized way 3 decades ago when the first national NBS program was implemented in Cuba. From then onward, it experienced a slow but continuous growing, being currently possible to find from countries where no NBS activity is known to several countries with consolidated NBS programs. This complex scenario gave rise to a great diversity in the criteria used for sample collection, selection of analytical methods, and definition of cutoff values. Considering this context, a consensus meeting was held in order to unify such criteria, focusing the discussion in the following aspects—recommended blood specimens and sample collection time; influence of early discharge, fasting, parenteral nutrition, blood transfusions, extracorporeal life support, and antibiotics; main causes of transient hyperphenylalaninemias; required characteristics for methods used in phenylalanine measurement; and finally, criteria to define the more appropriate cutoff values.

  13. Taking place, screening place

    DEFF Research Database (Denmark)

    Hansen, Kim Toft; Waade, Anne Marit

    2019-01-01

    We introduce location studies as a new empirical approach to screen studies. Location studies represent an interdisciplinary perspective, including media, aesthetics and geography, and reflect a growing interest in places in a global media and consumption culture. The chapter analyses two recent......) with one being traditional and the other being commercial; both dramas include discussions of localities and social heritage, and both use local sports as a common metaphor for social cohesion; and both series have been partly funded by a local film Danish commissioner. However, The Legacy is shot...... to a large extent in studios, while Norskov is shot entirely on location. The study is based on interviews with producers, broadcasters, location scouts, production designers and writers, as well as quantitative and qualitative textual analyses of television drama series, the geographical places, and related...

  14. Congenital cataract screening

    Directory of Open Access Journals (Sweden)

    Zhale Rajavi

    2016-01-01

    Full Text Available Congenital cataract is a leading cause of visual deprivation which can damage the developing visual system of a child; therefore early diagnosis, management and long-term follow-up are essential. It is recommended that all neonates be screened by red reflex examination at birth and suspected cases be referred to ophthalmic centers. Early surgery (1 year is highly recommended. After surgery, amblyopia treatment and periodic follow-up examinations should be started as soon as possible to achieve a satisfactory visual outcome. Practitioners should consider the possibility of posterior capsular opacity, elevated intraocular pressure and amblyopia during follow-up, especially in eyes with microphthalmia and/or associated congenital anomalies. All strabismic children should undergo slit lamp examination prior to strabismus surgery to rule out congenital lens opacities. From a social point of view, equal and fair medical care should be provided to all children regardless of gender.

  15. Diabetes screening in the workplace.

    Science.gov (United States)

    Gulley, Tauna; Boggs, Dusta; Mullins, Rebecca; Brock, Emily

    2014-11-01

    The prevalence of diabetes has increased worldwide and the pathophysiological problems associated with diabetes increase the potential for employees' physical disabilities. These complications, including neuropathy, nephropathy, and visual impairment, negatively impact the job performance of employees and compromise workplace safety. Occupational health nurses can provide diabetes screening programs to employees and identify chronic disease risk factors early. This article describes an occupational diabetes screening program at a major corporation in Belize, Central America, defines diabetes, outlines the diabetes teaching plan, and presents the demographics of the participants and results of the screening. Cultural considerations and recommendations for future occupational diabetes screenings are proposed. Copyright 2014, SLACK Incorporated.

  16. Industrial screening programs for workers

    International Nuclear Information System (INIS)

    Lavine, M.P.

    1982-01-01

    Industrial screening efforts to identify classes of workers who are more susceptible to workplace hazards, by virtue of their fertility, genetic, or lifestyle characteristics, represent a relatively new approach to reducing workplace risks. Screening has already raised some important economic, legal, social, medical, and moral questions. Employers, employees, administrative agencies, and the courts are offering different, often conflicting answers. Ultimately the acceptability of various screening schemes rests upon judgments about how a society justifies the distribution of risk. The questions that industrial screening programs raise are only partially answered by empirical evidence; the rest is a matter of values

  17. Advances in cervical screening technology.

    Science.gov (United States)

    Stoler, M H

    2000-03-01

    The Pap smear unquestionably is a successful screening test for cervical cancer. However, recent advances in technology have raised questions regarding whether the conventional Pap smear is still the standard of care. This article relates issues of screening and cost-effectiveness to the state of the art in thin layer preparations, cytology automation, human papillomavirus screening, human papillomavirus vaccines, and other cervical screening adjuncts. Perhaps nowhere in medicine is clinical decision making being more strongly influenced by market and other external forces than in cervical cytopathology.

  18. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of ... at the National Cancer Institute, shared developments in colorectal cancer screening methods with NIH MedlinePlus magazine. What ...

  19. Costs of Colorectal Cancer Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-04

    A health economist talks about studies on figuring out the costs of running a colorectal cancer screening program, and how this can lead to better screening.  Created: 4/4/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/4/2017.

  20. Screening College Students for Hypercholesterolemia.

    Science.gov (United States)

    Faigel, Harris C.

    1992-01-01

    Describes one college's mandatory mass cholesterol screening for new students. Each year, over 30 beginning students with unknown hypercholesterolemia were detected. The program suggests that mass screening efficiently and economically identifies students who would benefit from cholesterol reduction, a modifiable risk in coronary artery disease.…

  1. Overdiagnosis in breast cancer screening

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Beau, Anna-Belle; Christiansen, Peer

    2017-01-01

    Overdiagnosis in breast cancer screening is an important issue. A recent study from Denmark concluded that one in three breast cancers diagnosed in screening areas in women aged 50-69 years were overdiagnosed. The purpose of this short communication was to disentangle the study's methodology...

  2. Prenatal Screening Using Maternal Markers

    Directory of Open Access Journals (Sweden)

    Howard Cuckle

    2014-05-01

    Full Text Available Maternal markers are widely used to screen for fetal neural tube defects (NTDs, chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.

  3. Cervical cancer screening at crossroads

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada

    2014-01-01

    Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark......, screening decreased the incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented...... cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT...

  4. Dysphonia risk screening protocol

    Directory of Open Access Journals (Sweden)

    Katia Nemr

    2016-03-01

    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  5. Data Quality Screening Service

    Science.gov (United States)

    Strub, Richard; Lynnes, Christopher; Hearty, Thomas; Won, Young-In; Fox, Peter; Zednik, Stephan

    2013-01-01

    A report describes the Data Quality Screening Service (DQSS), which is designed to help automate the filtering of remote sensing data on behalf of science users. Whereas this process often involves much research through quality documents followed by laborious coding, the DQSS is a Web Service that provides data users with data pre-filtered to their particular criteria, while at the same time guiding the user with filtering recommendations of the cognizant data experts. The DQSS design is based on a formal semantic Web ontology that describes data fields and the quality fields for applying quality control within a data product. The accompanying code base handles several remote sensing datasets and quality control schemes for data products stored in Hierarchical Data Format (HDF), a common format for NASA remote sensing data. Together, the ontology and code support a variety of quality control schemes through the implementation of the Boolean expression with simple, reusable conditional expressions as operands. Additional datasets are added to the DQSS simply by registering instances in the ontology if they follow a quality scheme that is already modeled in the ontology. New quality schemes are added by extending the ontology and adding code for each new scheme.

  6. Dysphonia risk screening protocol

    Science.gov (United States)

    Nemr, Katia; Simões-Zenari, Marcia; da Trindade Duarte, João Marcos; Lobrigate, Karen Elena; Bagatini, Flavia Alves

    2016-01-01

    OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors) divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children), 29.25 (adult women), 22.75 (adult men), and 27.10 (seniors). CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics. PMID:27074171

  7. Magnetic field screens

    International Nuclear Information System (INIS)

    Mansfield, P.; Turner, R.; Chapman, B.L.W.; Bowley, R.M.

    1990-01-01

    A screen for a magnetic coil, for producing, for example, a homogeneous, gradient or RF field in nuclear magnetic resonance imaging, is described. It is provided by surround the coil with a set of electrical conductors. The currents within the conductors are controlled in such a manner that the field is neutralised in a specific region of space. The current distribution within the conductors is determined by calculating the current within a hypothetical superconductive shield which would have the effect of neutralising the field, the current through the conductors thereby being a substitute for the superconductive shield. The conductors may be evenly spaced and connected in parallel, their resistances being determined by thickness or composition to provide the desired current, or they may carry equal currents but be differently spaced. A further set or sets of controlled conductors outside the first set may ensure that the first set does not upset the field from the NMR coil. The shield may selectively reflect certain fields while transmitting others and may prevent acoustic vibration e.g. when switching gradient fields. An RF coil arrangement may consist of two orthogonal coils, one coil within the other for use as a transmit/receive set or as a double resonance transmitter; a shield between the coils is in series with, and formed from the same winding as, the inner coil. (author)

  8. Touch/Screen

    Directory of Open Access Journals (Sweden)

    Daniel Ross

    2015-12-01

    Full Text Available In 2004 Bernard Stiegler posed “the tragic question of cinema” as that of the germ of regres-­‐‑ sion to television and pornography it has always contained, just as in 1944 Adorno and Hork-­‐‑ heimer argued that Enlightenment reason has always contained a germ of regression making possible a prostitution of theory leading only to the threat of fascism. If comparable threats attend Stiegler’s cinematic question, then this implies the need for an account of this potential for regression, that is, an account of the relationship between desire, technology and knowledge. Tracing the aporias of the origin of desire and trauma in psychoanalysis is one crucial way to pursue this account. Exiting these aporias depends on recognizing that the origin of desire has for human beings always been technical, and hence that the instruments of desire form its conditions and condition its forms. By thus analysing the staging of desire and the setting of fantasy it becomes possible to reflect, for example, on what it means that for Genet fascism was theatre, that for Syberberg Hitler was cinema, and that for Stiegler the new prostitution of the tele-­‐‑visual graphic is digital and algorithmic. Hence arises the potentially tragic question of the possibility or otherwise, in the age of the ubiquitous screen, of a new cinematic invention and a new cinematic practice.

  9. [Toxicologic blood emergency screening].

    Science.gov (United States)

    Cohen, Sabine; Manat, Aurélie; Dumont, Benoit; Bévalot, Fabien; Manchon, Monique; Berny, Claudette

    2010-01-01

    In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.

  10. Efficacious Intestinal Permeation Enhancement Induced by the Sodium Salt of 10-undecylenic Acid, A Medium Chain Fatty Acid Derivative

    OpenAIRE

    Brayden, David J.; Walsh, Edwin

    2014-01-01

    10-undecylenic acid (UA) is an OTC antifungal therapy and a nutritional supplement. It is an unsaturated medium chain fatty acid (MCFA) derivative, so our hypothesis was that its 11-mer sodium salt, uC11, would improve intestinal permeation similar to the established enhancer, sodium caprate (C10), but without the toxicity of the parent saturated MCFA, decylenic acid (C11). MTT assay and high-content screening (HCS) confirmed a cytotoxicity ranking in Caco-2 cells: C11 > C10 = uC11. Five to t...

  11. Domestic violence screening in pregnancy.

    Science.gov (United States)

    Bunn, Mikiko Yazawa; Higa, Nicole A; Parker, Willie J; Kaneshiro, Bliss

    2009-11-01

    Domestic violence is an important health concern that has been shown to have adverse effects on maternal and neonatal outcomes. The objectives of this study were to compare the prevalence of prenatal screening for domestic violence in a hospital-based resident clinic setting with screening practices in private obstetric offices in Honolulu, Hawai'i and to explore physician attitudes towards domestic violence screening during pregnancy. A retrospective chart review was conducted at Queen's Medical Center in Honolulu, Hawai'i in women who delivered between 2003 and 2004. A 6 item written survey was also given to all attending and resident physicians with obstetric privileges. Descriptive statistics including frequency measures were generated and chi square tests were used to compare categorical variables. A total of 270 charts were reviewed. There was a statistically significant difference (p obstetric practices (39.3 percent) that were screened for domestic violence. While the majority of respondents (77.6%) to the domestic violence survey were aware that the American College of Obstetricians and Gynecologists recommends domestic violence screening in pregnancy most respondents (69.0 percent) indicated that they "never or rarely" screened their patients for domestic violence. Despite professional recommendations and an awareness of these recommendations, between 2003 and 2004, routine prenatal screening for domestic violence was markedly lacking for patients in this study population.

  12. Promoting breast screening in Glasgow.

    Science.gov (United States)

    Cohen, L; Dobson, H; McGuire, F

    2000-03-01

    To establish whether there is a role for advertising in the promotion of the Breast Screening Programme and what the role of advertising might be. Four hundred and sixty questionnaires were completed by women attending their breast screening appointment. Quantitative and qualitative data were collected from the static unit at Calder Street and the mobile unit in Govan. The advertising (budget 30,000 Pounds) campaign ran over an eight week period in the Govan, Paisley Road West and Cardonald areas of Glasgow. Media used included press advertising, The Glasgow Underground, adshells, bus advertising (interiors) and poster distribution via local outlets. Forty-two per cent of the sample were aware of the campaign. Ninety-seven per cent liked the campaign images. Eighty eight per cent felt that breast screening should be advertised more. Screening uptake increased in the areas covered by the advertising campaign. Govan -58%-71% and Ibrox (Paisley Road West and Cardonald) -59%-61%. Women were very supportive of the role of advertising for the Breast Screening Programme. In particular they found the campaign images and messages reassuring, supportive and credible. Their views suggest that the role of advertising should be: To raise awareness of the service To make women more conscious of the benefits of screening To change public perceptions of the screening process However, it is recognised that a fully integrated approach is required for the promotion of the service to account for the improvement in uptake, as advertising cannot be expected to work in isolation.

  13. Screening in dense ionic fluids

    International Nuclear Information System (INIS)

    Tosi, M.P.

    1991-01-01

    There has been great progress in recent years in determining and understanding the structure of molten salts. I focus on molten alkali halides and discuss two main points concerning their liquid structure and its relationship with static electrical response in these dense ionic conductors. These are (i) the nature of screening and the related definitions and properties of the screening length and of the dielectric function, and (ii) developments in integral equations techniques for the evaluation of molten salt structure and static screening from given pair potentials. (author). 26 refs, 3 figs, 2 tabs

  14. Virtual screening of compound libraries.

    Science.gov (United States)

    Cerqueira, Nuno M F S A; Sousa, Sérgio F; Fernandes, Pedro A; Ramos, Maria João

    2009-01-01

    During the last decade, Virtual Screening (VS) has definitively established itself as an important part of the drug discovery and development process. VS involves the selection of likely drug candidates from large libraries of chemical structures by using computational methodologies, but the generic definition of VS encompasses many different methodologies. This chapter provides an introduction to the field by reviewing a variety of important aspects, including the different types of virtual screening methods, and the several steps required for a successful virtual screening campaign within a state-of-the-art approach, from target selection to postfilter application. This analysis is further complemented with a small collection important VS success stories.

  15. Intensifying screens in transaxial tomography

    International Nuclear Information System (INIS)

    Debelder, M.H.; Bollen, R.H.

    1981-01-01

    This patent claim by Agfa-Gevaert relates to a method for the production of transaxial tomographs, a combination of materials therefor and X-ray intensifying screens incorporating at least one reflecting element for use in transaxial tomography, wherein the exposure of a photographic silver halide emulsion material proceeds at an angle within the range of 2 0 to 10 0 in conjunction with an X-ray fluorescent intensifying screen including an ultra-violet and/or visible radiation reflective coating or sheet to increase the radiation output of the screen and to reduce the exposure time and radiation dose e.g. in medical X-ray applications. (author)

  16. Newborn Screening: MedlinePlus Health Topic

    Science.gov (United States)

    ... more articles Reference Desk Glossary (National Center for Biotechnology Information) Find an Expert Eunice Kennedy Shriver National ... other than English on Newborn Screening NIH MedlinePlus Magazine Hearing Loss: Screening Newborns Screening Newborns' Hearing Now ...

  17. BREAST CANCER SCREENING IN A RESOURCE POOR ...

    African Journals Online (AJOL)

    al rates of breast cancer, hence screening of asympto- matic, apparently healthy ... screening tools in women who attended free breast cancer screening exercise in a ..... signs of malignancy. www.appliedradiology.mobi/uploadedfiles/Issues/2.

  18. Risk Profiling May Improve Lung Cancer Screening

    Science.gov (United States)

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  19. Inventions on GUI for Touch Sensitive Screens

    OpenAIRE

    Mishra, Umakant

    2014-01-01

    A touch sensitive screen displays the information on the screen and also receives the input by sensing a user's touch on the same screen. This mechanism facilitates system interaction directly through the screen without needing a mouse or keyboard. This method has the advantage to make the system compact by removing keyboard, mouse and similar interactive device. However there are certain difficulties to implement a touch screen interface. The display screens of portable devices are becoming ...

  20. Effectiveness of testis cancer screening

    International Nuclear Information System (INIS)

    Feucht, H.

    1983-04-01

    In the Federal Republic of Germany there are about thousand to two-thousand incidences of testis cancer yearly. The screening (and examination) program currently used for the early detection of cancer includes the screening of malignant tumours of the testis. Since only males 45 years and older are invited to make use of the preventive measures, the most seriously affected age-group between twenty and forty is hereby not considered. The objective of this study is to find out which of the generally conceivable preventive measures could lead to an improvement of the present situation. The analysis shows that, for a diagnostic accuracy of 1 and a participation of 100%, the quantifyable cost of a yearly performed special screening is higher than the quantifyable cost savings achieved. A final judgement of other ways of execution is only possible when the diagnostic accuracy of suitable screening methods and the percentage of the participants of the groups of people concerned are known. (orig.)

  1. RAS - Screens & Assays - Drug Discovery

    Science.gov (United States)

    The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

  2. Screening for Abdominal Aortic Aneurysm

    Science.gov (United States)

    ... benefits. When there is not enough evidence to judge benefits and harms, the Task Force does not ... nurse practitioners, physician assistants, and nurses. selectively offer Decide whether screening is right for a patient on ...

  3. Screening Tests for Birth Defects

    Science.gov (United States)

    ... that best fit your needs. What are the advantages and disadvantages of diagnostic tests compared with screening ... Us Contact Us Copyright Information Privacy Statement RSS Advertising Opportunities Careers at ACOG Sitemap Website Feedback American ...

  4. PHYTOCHEMICAL SCREENING AND THROMBOLYTIC ACTIVITY ...

    African Journals Online (AJOL)

    2014-12-31

    Dec 31, 2014 ... followed by chemical screening, random selection followed by one or more biological ... These were identified by characteristic color changes .... [1] Samuelsson, G. Drugs of Natural Origin: A Textbook of Pharmacognosy.

  5. X-ray screening materials

    International Nuclear Information System (INIS)

    Wardley, R.B.

    1981-01-01

    This invention relates to x-ray screening materials and especially to materials in sheet form for use in the production of, for example, protective clothing such as aprons and lower back shields, curtains, mobile screens and suspended shields. The invention is based on the observation that x-ray screening materials in sheet form having greater flexiblity than the hitherto known x-ray screening materials of the same x-ray absorber content can be produced if, instead of using a single sheet of filled sheet material of increased thickness, one uses a plurality of sheets of lesser thickness together forming a laminar material of the desired thickness and one bonds the individual sheets together at their edges and, optionally, at other spaced apart points away from the edges thereby allowing one sheet to move relative to another. (U.K.)

  6. Risks of Lung Cancer Screening

    Science.gov (United States)

    ... in women. Different factors increase or decrease the risk of lung cancer. Anything that increases your chance ... been studied to see if they decrease the risk of dying from lung cancer. The following screening ...

  7. Breast Cancer Screening in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette

    2017-01-01

    Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Design......) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing...... rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted...

  8. Pennsylvania's experience in mass screening

    International Nuclear Information System (INIS)

    Gerusky, T.M.

    1975-01-01

    A policy statement issued in 1972 by the Assistant Secretary for Health and Scientific Affairs of the Department of Health, Education, and Welfare recommended that community chest x-ray surveys should not be used as a screening procedure for the detection of cardiopulmonary disorders and that when chest x-ray screening programs are justified for selected population groups, the full size photograph, rather than the miniature film, is preferred. A survey conducted in 1974--75 revealed that chest x rays were required for prisoners, prison employees, school employees, food handlers, and students who wished to participate in sports. Meetings were held with medical associations in the hope of stopping the local mass-screening operations. Of 27 groups in Pennsylvania involved in tuberculosis screening, 12 groups refused or were unwilling to phase out their photofluorographic procedures. The problem will be resolved by regulation

  9. Transforming Security Screening With Biometrics

    National Research Council Canada - National Science Library

    Hearnsberger, Brian J

    2003-01-01

    ... and identity theft to dramatically improve physical security. Today, biometric technology could be implemented to transform physical security by enhancing screening procedures currently in use at U.S...

  10. Thermodynamics of H+/Cs+ exchange on amorphous zirconium phosphate in mixed solvents

    International Nuclear Information System (INIS)

    Misak, N.Z.; Mikhail, E.M.

    1983-01-01

    In aqueous, 30% isopropanol and acetone, and up to 90% methanol, the H + /Cs + exchange on zirconium phosphate is entropy directed, while in 60% isopropanol and acetone it is enthalpy directed and a selectivity reversal occurs. ΔF 0 decreases in all cases with increasing addition of the organic solvent. ΔH 0 becomes appreciably negative (ΔH 0 = 0 in aqueous medium) and ΔS 0 decreases appreciably on addition of 30% organic solvent, but they increase with further addition. In presence of methanol, ion-solvent interaction effects are counteracted by effects of solid phase interactions but the former effects predominate and lead to decrease of ΔF 0 . On going from 30 to 90 % methanol, positive enthalpy and entropy changes occur due to solid phase interactions involving probably the dehydration of the ingoing Cs + . In presence of up to 60% acetone, ΔF 0 (or selectively constant) changes mainly due to ion-solvent interactions and can be theoretically calculated from the value in the aqueous medium by use of transfer thermodynamics data. This is probably due to a limited imbibition of acetone. (author)

  11. Mechanistic study and modeling of radionuclides retention by the hydrated calcium silicates (HCS) of cements

    International Nuclear Information System (INIS)

    Pointeau, I.

    2000-09-01

    This work attempts to investigate the modelling of radioisotopes (Cs + , Pb 2+ , Eu 3+ ) immobilization in cement matrix, in the frame of the design of engineered barrier of a deep radwaste repository. The model development concept consists of three major steps: - surface chemistry modelling of the calcium silicate hydrate CSH, used to simulate hydrated cement behaviour; - solid analysis of the batch sorption experiments: identification of the uptake mechanism; - both previous steps are used, with isotherm data, in the modelling of the radioisotopes immobilization in the CSH matrix. Final results: (all modelling are available for all the range of studied Ca/Si ratios and have been validated with predictive calculations). - A thermodynamic modelling of the CSH surface chemistry has been developed. The labile calcium and proton sorption constants on silanol sites (>SiOH) have been extracted. - Cs + is sorbed on two sites. The silanol site (weak site) has a high site density (10 sites.nm -2 ), which accounts for the CSH unsaturation in high [CS + ]. A strong site is also identified. - Pb 2+ immobilization in CSH matrix is modelled with surface equilibria and solubility equilibrium. - Eu 3+ fixation has been investigated with solid analysis: Site-Selective anti Time-Resolved Luminescence Spectroscopy, XPS and SEM-EDS. Eu 3+ thus does not precipitate in CSH water but is sorbed on the CSH surface (high hydroxylated environment). Europium is also (minority site) inserted in the CSH framework. (author)

  12. THE DEVELOPMENT OF SCREEN TRANSLATION

    OpenAIRE

    Sang Ayu Isnu Maharani

    2014-01-01

    Screen translations involve oral translation known as dubbing and revoicing. Re-voicing consists of lip-sync dubbing, free commentary, narration and voice over. The written version is called subtitle. Dubbing and subtitling are two preferred mode used in the screen translation even though various numbers of current options are available nowadays. Dubbing commenced to be used in larger countries in Europe meanwhile smaller countries apply subtitling because it is more...

  13. Industrial radiography with phosphor screens

    International Nuclear Information System (INIS)

    Broadhead, P.

    1981-01-01

    An experimental system that comprises a film of low silver content and a pair of high resolution phosphor intensifying screens and a commercial industrial X-ray film of similar speed are compared for image quality. It is concluded that the use of phosphor screens offers an increase in image quality when the information is limited by the graininess or quantum mottle of a radiograph which is frequently the case in practical radiography. (author)

  14. Fish screens at hydroelectric diversions

    International Nuclear Information System (INIS)

    Ott, R.F.

    1994-01-01

    Preventing downstream migrating fish from entering the turbines at hydroelectric projects is a standard mitigation goal of state and federal fishery management agencies. The object is to minimize the adverse impacts to the fish associated with the exclusion and passage through the bypass water conveyance facilities. In the western United States, most of the fishery management agencies have fish screen design criteria that focus on the approach and transportational velocities, maximum opening dimensions of the screen material, and the cleaning standards. Recently, more attention has been given to fish behavioral traits such as attraction and sustained and darting swimming speed, which has resulted in more attention to the position of the screens to the flow and the length of time the downstream migrants are exposed to the screens. Criteria for length of time of exposure, size and position of bypass, flow and velocities in the bypass entrances, discharge requirements back into the receiving water, and exposure to predation have created unique challenges to the fish screen designer. This paper discusses some of the more recent types of fixed fish screens that are being installed at hydroelectric plants that meet these challenges

  15. Retinopathy of prematurity screening criteria in Iran: new screening guidelines.

    Science.gov (United States)

    Roohipoor, Ramak; Karkhaneh, Reza; Farahani, Afsar; Ebrahimiadib, Nazanin; Modjtahedi, Bobeck; Fotouhi, Akbar; Yaseri, Mehdi; Khodabande, Alireza; Zarei, Mohammad; Imani Fuladi, Marjan; Taheri, Arash; Riazi Esfahani, Mohammad; Loewenstein, John

    2016-07-01

    To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. Both eyes of 1932 infants born ≤37 weeks of gestation and/or weighting ≤3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. Patients with ROP requiring treatment. The mean GA±SD and birth weight (BW)±SD of the screened patients were 32±2.7 weeks and 1713±516 g, respectively. Using criteria of GA≤32 weeks or BW ≤2000 yielded sensitivity and specificity of 100% and 26.7%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4% of ROP and 8.4%ROP requiring treatment in our cohort. Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study

    NARCIS (Netherlands)

    Klompenhouwer, E. G.; Duijm, L. E. M.; Voogd, A. C.; den Heeten, G. J.; Nederend, J.; Jansen, F. H.; Broeders, M. J. M.

    2014-01-01

    Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at

  17. Effect of Blood Collection Tube Type and Time to Processing on the Enumeration and High-Content Characterization of Circulating Tumor Cells Using the High-Definition Single-Cell Assay.

    Science.gov (United States)

    Rodríguez-Lee, Mariam; Kolatkar, Anand; McCormick, Madelyn; Dago, Angel D; Kendall, Jude; Carlsson, Nils Anders; Bethel, Kelly; Greenspan, Emily J; Hwang, Shelley E; Waitman, Kathryn R; Nieva, Jorge J; Hicks, James; Kuhn, Peter

    2018-02-01

    - As circulating tumor cell (CTC) assays gain clinical relevance, it is essential to address preanalytic variability and to develop standard operating procedures for sample handling in order to successfully implement genomically informed, precision health care. - To evaluate the effects of blood collection tube (BCT) type and time-to-assay (TTA) on the enumeration and high-content characterization of CTCs by using the high-definition single-cell assay (HD-SCA). - Blood samples of patients with early- and advanced-stage breast cancer were collected into cell-free DNA (CfDNA), EDTA, acid-citrate-dextrose solution, and heparin BCTs. Time-to-assay was evaluated at 24 and 72 hours, representing the fastest possible and more routine domestic shipping intervals, respectively. - We detected the highest CTC levels and the lowest levels of negative events in CfDNA BCT at 24 hours. At 72 hours in this BCT, all CTC subpopulations were decreased with the larger effect observed in high-definition CTCs and cytokeratin-positive cells smaller than white blood cells. Overall cell retention was also optimal in CfDNA BCT at 24 hours. Whole-genome copy number variation profiles were generated from single cells isolated from all BCT types and TTAs. Cells from CfDNA BCT at 24-hour TTA exhibited the least noise. - Circulating tumor cells can be identified and characterized under a variety of collection, handling, and processing conditions, but the highest quality can be achieved with optimized conditions. We quantified performance differences of the HD-SCA for specific preanalytic variables that may be used as a guide to develop best practices for implementation into patient care and/or research biorepository processes.

  18. Screening_mgmt: a Python module for managing screening data.

    Science.gov (United States)

    Helfenstein, Andreas; Tammela, Päivi

    2015-02-01

    High-throughput screening is an established technique in drug discovery and, as such, has also found its way into academia. High-throughput screening generates a considerable amount of data, which is why specific software is used for its analysis and management. The commercially available software packages are often beyond the financial limits of small-scale academic laboratories and, furthermore, lack the flexibility to fulfill certain user-specific requirements. We have developed a Python module, screening_mgmt, which is a lightweight tool for flexible data retrieval, analysis, and storage for different screening assays in one central database. The module reads custom-made analysis scripts and plotting instructions, and it offers a graphical user interface to import, modify, and display the data in a uniform manner. During the test phase, we used this module for the management of 10,000 data points of various origins. It has provided a practical, user-friendly tool for sharing and exchanging information between researchers. © 2014 Society for Laboratory Automation and Screening.

  19. CLAD DEGRADATION - FEPS SCREENING ARGUMENTS

    International Nuclear Information System (INIS)

    R. Schreiner

    2004-01-01

    The purpose of this report is to evaluate and document the screening of the clad degradation features, events, and processes (FEPs) with respect to modeling used to support the Total System Performance Assessment-License Application (TSPA-LA). This report also addresses the effect of certain FEPs on both the cladding and the commercial spent nuclear fuel (CSNF), DOE-owned spent nuclear fuel (DSNF), and defense high-level waste (DHLW) waste forms, as appropriate to address the effects on multiple materials and both components (FEPs 2.1.09.09.0A, 2.1.09.11.0A, 2.1.11.05.0A, 2.1.12.02.0A, and 2.1.12.03.0A). These FEPs are expected to affect the repository performance during the postclosure regulatory period of 10,000 years after permanent closure. Table 1-1 provides the list of cladding FEPs, including their screening decisions (include or exclude). The primary purpose of this report is to identify and document the analysis, screening decision, and TSPA-LA disposition (for included FEPs) or screening argument (for excluded FEPs) for these FEPs related to clad degradation. In some cases, where a FEP covers multiple technical areas and is shared with other FEP reports, this report may provide only a partial technical basis for the screening of the FEP. The full technical basis for shared FEPs is addressed collectively by the sharing FEP reports. The screening decisions and associated TSPA-LA dispositions or screening arguments from all of the FEP reports are cataloged in a project-specific FEPs database

  20. Development of an image analysis screen for estrogen receptor alpha (ERα) ligands through measurement of nuclear translocation dynamics.

    Science.gov (United States)

    Dull, Angie; Goncharova, Ekaterina; Hager, Gordon; McMahon, James B

    2010-11-01

    We have developed a robust high-content assay to screen for novel estrogen receptor alpha (ERα) agonists and antagonists by quantitation of cytoplasmic to nuclear translocation of an estrogen receptor chimera in 384-well plates. The screen utilizes a green fluorescent protein tagged-glucocorticoid/estrogen receptor (GFP-GRER) chimera which consisted of the N-terminus of the glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER exhibited cytoplasmic localization in the absence of ERα ligands, and translocated to the nucleus in response to stimulation with ERα agonists or antagonists. The BD Pathway 435 imaging system was used for image acquisition, analysis of translocation dynamics, and cytotoxicity measurements. The assay was validated with known ERα agonists and antagonists, and the Library of Pharmacologically Active Compounds (LOPAC 1280). Additionally, screening of crude natural product extracts demonstrated the robustness of the assay, and the ability to quantitate the effects of toxicity on nuclear translocation dynamics. The GFP-GRER nuclear translocation assay was very robust, with z' values >0.7, CVs screening of natural product extracts. This assay has been developed for future primary screening of synthetic, pure natural products, and natural product extracts libraries available at the National Cancer Institute at Frederick. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Screening on urogenital Chlamydia trachomatis

    Directory of Open Access Journals (Sweden)

    Busse, Reinhard

    2005-12-01

    Full Text Available Introduction: Around 92 million urogenital infections are caused yearly by Chlamydia trachomatis worldwide [1]. The overall incidence of sexually transmitted diseases is increasing, as shown by the increases in the number of reported cases of syphilis and gonorrhea [2]. Chlamydia trachomatis infections are associated with various serious diseases in women, men and newborns, which could be, at least partially, avoided by means of early diagnosis and therapy. The Federal Joint Committee - responsible for decision-making concerning the benefit package of the German Social Health Insurance - has publicly announced the starting of deliberations on the issue of screening for Chlamydia trachomatis. Research Questions: The leading question to be answered is whether screening for Chlamydia trachomatis should be included in the German benefit basket. The aim of this report is to provide a summary of the available evidence concerning the issue of screening for Chlamydia trachomatis. Methods: The summary of published scientific evidence, including HTA reports, systematic reviews, guidelines and primary research is represented. The synthesis follows the structure given by the criteria of Wilson and Jungner [3] for the introduction of screening in a population: relevance of the condition, availability of an adequate test, effectiveness of screening, acceptance of the programme, and economical issues. A literature search was conducted for each aspect of the synthesis and the evidence has been summarised in evidence tables. Results: We identified five HTA reports from three European agencies [4], [5], [6], [7] and one from the USA [8]. In addition, we identified four guidelines from Northamerica [9], [10], [11], [12] and one from Europe [13]. A total of 56 primary research publications were included: relevance of the disease (n=26, availability of test (n=1, effectiveness of screening (n=11, acceptance of the programme (n=11, economical issues (n=7. Discussion

  2. 20 CFR 654.408 - Screening.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Screening. 654.408 Section 654.408 Employees... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Housing Standards § 654.408 Screening. (a) All outside openings shall be protected with screening of not less than 16 mesh. (b) All screen doors shall be...

  3. The Diabetic Retinopathy Screening Workflow

    Science.gov (United States)

    Bolster, Nigel M.; Giardini, Mario E.; Bastawrous, Andrew

    2015-01-01

    Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems’ use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound. PMID:26596630

  4. Mass spectrometry for fragment screening.

    Science.gov (United States)

    Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

    2017-11-08

    Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Colour screening and quark confinement

    International Nuclear Information System (INIS)

    Mack, G.

    1978-03-01

    It is proposed that in Quantum Chromodynamics the colour charge of gluons and of anything with zero triality is screened by a dynamical Higgs mechanism with Higgs scalars made out of gluons. The center Z 3 of the gauge group SU(3) is left unbroken in this way, and single quarks, which have nonzero triality, cannot be screened. Long range forces between them persist therefore. Given that the Higgs mechanism produces a mass gap, the most favorable configuration of field lines between e.g. quark and antiquark will be in strings analogous to magnetic field lines in a superconductor. The strings confine the quarks. The screening mechanism, on the other hand, produces not only the mass gap (which leads to string formation) but is also responsible for saturation of forces, i.e. absence of bound states of six quarks etc. (orig.) [de

  6. Colour screening and quark confinement

    International Nuclear Information System (INIS)

    Mack, G.

    1978-01-01

    It is proposed that in quantum chromodynamics the colour charge of gluons and of anything with zero triality is screened by a dynamic Higgs mechanism with Higgs scalars made out of gluons, but the center Z 3 of the gauge group SU(3) is left unbroken, and single quarks, which have nonzero triality, are not screened. Long range forces between them persist therefore. Given that the Higgs mechanism produces a mass gap, the most favourable configuration of field lines between e.g., quark and antiquark will be in strings analogous to magnetic field lines in a superconductor. The string confine the quarks. The screening mechanism, on the other hand, produces not only the mass gap (which leads to string formation) but is also responsible for saturation of forces, i.e. absence of bound states of six quarks, etc. (Auth.)

  7. More misinformation on breast cancer screening

    OpenAIRE

    Kopans, Daniel B.

    2017-01-01

    Unfortunately, a great deal of misinformation has accumulated in the breast cancer screening literature that is based on flawed analyses in an effort to reduce access to screening. Quite remarkably, much of this has come from publications in previously highly respected medical journals. In several papers the intervention (mammography screening) is faulted yet the analyses provided no data on who participated in mammography screening, and which cancers were detected by mammography screening. I...

  8. Histochemical, phytochemical and biological screening of Plinia cauliflora (DC. Kausel, Myrtaceae, leaves

    Directory of Open Access Journals (Sweden)

    Tatiana M. Souza-Moreira

    Full Text Available In this work, chemical and biological activities of crude extracts obtained with 50% ethanol, 70% ethanol, acetone:water (7:3; v/v and chloroform of Plinia cauliflora (DC. Kausel, Myrtaceae, leaves, a native tree from several regions of Brazil, was investigated. Histochemical and phytochemical screenings were done according to characterization reactions and thin layer chromatography. To assist in extracts standardization, total phenol and flavonoids content spectrophotometric was performed. Antioxidant activity was analyzed by percentage of radical scavenging using DPPH solution. Antimicrobial activity was evaluated against Gram-positive, Gram-negative pathogenic bacteria and species of Candida using agar diffusion and minimal inhibitory concentration (MIC determination methods according to standard methods. The leaves presented lipids at secretory cavity and phenols, mainly tannins, in nervures and palisade parenchyma. Polar extracts showed flavonoids, tannins and high content of phenols and flavonoids. The extracts showed great antioxidant activity and antimicrobial activity was better against Candida species than against bacteria.

  9. Premilinary Studies on Phytochemical Screening of Ulam and Fruit from Malaysia

    Directory of Open Access Journals (Sweden)

    Liliwirianis N.

    2011-01-01

    Full Text Available Alkaloids, saponins, steroid, terpenoid, flavonoids, phenolic distribution in 14 Malaysian favourite ulam and fruit belonging to different families were assessed and compared. The plants investigated were parkia speciosa (petai, solanum torvum (terung pipit, pithecellobium bubalinum (kerdas, moringa oleifera (kacang kelor, dryobalanops oblongifolia (keladan, cosmos caudatus (ulam raja, mentha arvensis (pudina, ocimum sp. (selasih, cymbopogon nardus (serai wangi, eugenia polyantha (serai kayu, Barringtonia scortechinii, (Putat, musa sp. (pisang, talinum paniculatum (akar som and phyllanthus acidus (cermai. Moringa oleifera leaf and dryobalanops oblongifolia fruit were found contain positive reactions of alkaloids. All the samples studied also show high content of saponin except in bark and seed of parkia speciosa and stem of phyllanthus acidus. Meanwhile, results of the phytochemical screening on saponins, steroids, terpenoids, phenolic and flavonoids showed that cosmos caudatus, ocimum sp., mentha arvensis, barringtonia scortechinii and moringa oleifera were the active compounds present in the leaves of the plant.

  10. Arvelig hemokromatose - nytten av screening

    Directory of Open Access Journals (Sweden)

    Arne Åsberg

    2009-10-01

    Full Text Available Arvelig hemokromatose fører til jernopphopning i kroppen, men gir sjelden alvorlig helseskade. Nesten alle hemokromatosepasienter i vårt land er homozygote for C282Y-mutasjonen i HFE-genet. Omtrent 7 per 1000 innbyggere har denne genotypen. Alvorlig syke blir bare omkring 5-15% av homozygote menn og nesten ingen kvinner. Likevel er det holdepunkter for at screening for hemokromatose blant friske, yngre menn kan være kostnadseffektivt. Det er relativt lett å påvise om en person er disponert for sykdommen, i god tid før den bryter ut, og forebyggende behandling er billig og effektiv. Imidlertid kan vi ikke forutsi hvilke screeningpositive personer som ubehandlet får alvorlig sykdom. Et kontrollert forsøk med screening bør gjennomføresHereditary hemochromatosis – benefits of screening. Hereditary hemochromatosis leads to iron accumulation in the body; however, serious illness due to hemochromatosis is rare. In Norway, almost all patients with hemochromatosis are homozygous for the C282Ymutation in the HFE-gene, a genotype carried by about 7 per 1000 inhabitants. Serious complications are seen in only about 5-15% of homozygous men and in very few women. Nevertheless, screening young men for hemochromatosis may be cost-effective. Detecting predisposed men is relatively straightforward, and prophylactic treatment is cheap and effective. However, we can not predict, among screen-positive men, the few who untreated will become seriously ill. A controlled screening trial should be conducted.

  11. High Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model

    Science.gov (United States)

    Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E.; Ausubel, Frederick M.

    2009-01-01

    The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen with a mortality rate of up to 37% that is increasingly acquiring resistance to antibiotics. Here, we describe an automated, high throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. The screen uses a robot to accurately dispense live, infected animals into 384-well plates, and automated microscopy and image analysis to generate quantitative, high content data. We identified 28 compounds and extracts that were not previously reported to have antimicrobial properties, including 6 structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use. Our versatile and robust screening system can be easily adapted for other whole animal assays to probe a broad range of biological processes. PMID:19572548

  12. Screening for deformed teeth; Screening for saere taender

    Energy Technology Data Exchange (ETDEWEB)

    Vermeulen, A.; Dall, P.C.; Hansen, F.G.

    1996-04-01

    Water pollution by pesticides and heavy metals causes sublethal effects in larvae of the Chironomidae midges. These effects are particularly noticeable in the deformities of the oral parts and antennae. Possibilities of using these deformities for the purpose of water/sediment biomonitoring are very promising. Here the first results of screening in a Danish stream are presented. (EG) 9 refs.

  13. Nutritional Screening of Children: A Manual for Screening & Followup.

    Science.gov (United States)

    Bureau of Community Health Services (DHHS/PHS), Rockville, MD.

    This manual shows health providers how to perform precisely and expertly each step of several procedures used in screening children for nutritional problems. It is intended for all health providers who are involved in weighing and measuring children, recording and plotting measurements on growth charts, taking blood samples to test for iron…

  14. Faraday screen sputtering on TPX

    International Nuclear Information System (INIS)

    Ehst, D.A.

    1994-12-01

    The TPX design stipulates that the ion-cyclotron resonance frequency (ICRF) antenna must have a Faraday screen (FS). The author considers here possible low Z coatings for the screen, as well as sputtering behavior of the Ni and Ti substrates. The theory of rf-induced sputtering has been developed, and he follows those theoretical approaches. The author's emphasis will be on both impurity generation as a possible source of increased Z eff , and also on actual erosion-lifetime of the materials under worst case conditions

  15. THE DEVELOPMENT OF SCREEN TRANSLATION

    Directory of Open Access Journals (Sweden)

    Sang Ayu Isnu Maharani

    2014-05-01

    Full Text Available Screen translations involve oral translation known as dubbing and revoicing. Re-voicing consists of lip-sync dubbing, free commentary, narration and voice over. The written version is called subtitle. Dubbing and subtitling are two preferred mode used in the screen translation even though various numbers of current options are available nowadays. Dubbing commenced to be used in larger countries in Europe meanwhile smaller countries apply subtitling because it is more economical than dubbing. In Indonesia, the use of dubbing as well as subtitle are found.

  16. RNAi Screening in Spodoptera frugiperda.

    Science.gov (United States)

    Ghosh, Subhanita; Singh, Gatikrushna; Sachdev, Bindiya; Kumar, Ajit; Malhotra, Pawan; Mukherjee, Sunil K; Bhatnagar, Raj K

    2016-01-01

    RNA interference is a potent and precise reverse genetic approach to carryout large-scale functional genomic studies in a given organism. During the past decade, RNAi has also emerged as an important investigative tool to understand the process of viral pathogenesis. Our laboratory has successfully generated transgenic reporter and RNAi sensor line of Spodoptera frugiperda (Sf21) cells and developed a reversal of silencing assay via siRNA or shRNA guided screening to investigate RNAi factors or viral pathogenic factors with extraordinary fidelity. Here we describe empirical approaches and conceptual understanding to execute successful RNAi screening in Spodoptera frugiperda 21-cell line.

  17. Icons and Emoticons: Screen Wars

    OpenAIRE

    Duerfahrd, Lance

    2015-01-01

    The cinema is being upstaged by a device paradoxically meant (in part) to transmit it: the iPhone. How do films change, how is their impact altered, when viewed on these devices? What aspects of the movie screen (and subsequently our movie experience) are lost or threatened when they are displaced by this new technological format? This is not an abstract war: it is going on (in the dark) every time we attend a screening. My paper will explore what is at stake in our decision to illuminate our...

  18. Hierarchical screening for multiple mental disorders.

    Science.gov (United States)

    Batterham, Philip J; Calear, Alison L; Sunderland, Matthew; Carragher, Natacha; Christensen, Helen; Mackinnon, Andrew J

    2013-10-01

    There is a need for brief, accurate screening when assessing multiple mental disorders. Two-stage hierarchical screening, consisting of brief pre-screening followed by a battery of disorder-specific scales for those who meet diagnostic criteria, may increase the efficiency of screening without sacrificing precision. This study tested whether more efficient screening could be gained using two-stage hierarchical screening than by administering multiple separate tests. Two Australian adult samples (N=1990) with high rates of psychopathology were recruited using Facebook advertising to examine four methods of hierarchical screening for four mental disorders: major depressive disorder, generalised anxiety disorder, panic disorder and social phobia. Using K6 scores to determine whether full screening was required did not increase screening efficiency. However, pre-screening based on two decision tree approaches or item gating led to considerable reductions in the mean number of items presented per disorder screened, with estimated item reductions of up to 54%. The sensitivity of these hierarchical methods approached 100% relative to the full screening battery. Further testing of the hierarchical screening approach based on clinical criteria and in other samples is warranted. The results demonstrate that a two-phase hierarchical approach to screening multiple mental disorders leads to considerable increases efficiency gains without reducing accuracy. Screening programs should take advantage of prescreeners based on gating items or decision trees to reduce the burden on respondents. © 2013 Elsevier B.V. All rights reserved.

  19. A new in vivo screening paradigm to accelerate antimalarial drug discovery.

    Directory of Open Access Journals (Sweden)

    María Belén Jiménez-Díaz

    Full Text Available The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR, which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0 of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1 or induce parasite clearance (PRR >1 with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a

  20. A New In Vivo Screening Paradigm to Accelerate Antimalarial Drug Discovery

    Science.gov (United States)

    Jiménez-Díaz, María Belén; Viera, Sara; Ibáñez, Javier; Mulet, Teresa; Magán-Marchal, Noemí; Garuti, Helen; Gómez, Vanessa; Cortés-Gil, Lorena; Martínez, Antonio; Ferrer, Santiago; Fraile, María Teresa; Calderón, Félix; Fernández, Esther; Shultz, Leonard D.; Leroy, Didier; Wilson, David M.; García-Bustos, José Francisco; Gamo, Francisco Javier; Angulo-Barturen, Iñigo

    2013-01-01

    The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR), which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0) of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1) or induce parasite clearance (PRR >1) with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally) in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a feasible task

  1. Newborn screening for MCAD deficiency

    DEFF Research Database (Denmark)

    Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G

    2008-01-01

    . Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second...

  2. Transitivity and partial screening off

    NARCIS (Netherlands)

    Peijnenburg, Jeanne; Atkinson, David

    2013-01-01

    The notion of probabilistic support is beset by well-known problems. In this paper we add a new one to the list: the problem of transitivity. Tomoji Shogenji has shown that positive probabilistic support, or confirmation, is transitive under the condition of screening off. However, under that same

  3. Developments in SPR Fragment Screening.

    Science.gov (United States)

    Chavanieu, Alain; Pugnière, Martine

    2016-01-01

    Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps. In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes. The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices.

  4. Screening Tools for Kindergarten Children

    Directory of Open Access Journals (Sweden)

    Georgia Kokkalia

    2017-12-01

    Full Text Available The current paper review gives a brief and representative description of some of the most used screening tools for kindergarten education. The significant role that early education plays in every child’s academic life is underlined by the importance of tools that give his learning profiles.  Therefore many researchers note that screening tools paly a notable role for the kindergarten teachers, the family and of course for the child in order to offer the appropriate intervention program, the proper support and draw the most suitable teaching method for the child and the class. Thus, the research team of this paper gives the description of some screening tools that are used by kindergarten teachers and specialist’s worldwide-with focus in Greek kindergarten- scoping to underlie strengths and weaknesses of preschoolers. Finally, it is thought worthwhile to say that the screening tools that are presented are used with the traditional way while some of them with the support of new technology.

  5. Disciplining and Screening Top Executives

    NARCIS (Netherlands)

    S. Dominguez Martinez (Silvia); O.H. Swank (Otto); B. Visser (Bauke)

    2006-01-01

    textabstractBoards of directors face the twin task of disciplining and screening executives. To perform these tasks directors do not have detailed information about executives' behaviour, and only infrequently have information about the success or failure of initiated strategies, reorganizations,

  6. Comparative Phytochemical screening and Physicochemical ...

    African Journals Online (AJOL)

    Physicochemical characterization was carried out to determine the saponification value, refractive index, specific gravity, peroxide value and acid value of the oil. The results of the phytochemical screening showed that alkaloid, carbohydrate, saponins, glycosides were present in the sample obtained from Romi New ...

  7. Keuringspanele ("Screening Panels") as Gepaste ...

    African Journals Online (AJOL)

    In this particular article attention is paid to screening panels as pre-trial mechanism with the exclusive purpose to select malpractice disputes, discourage unfounded disputes and to encourage an early settlement in case of a prima facie case. Several objections have been raised by critics in this regard, for instance, ...

  8. Shadows Cast on the Screen?

    DEFF Research Database (Denmark)

    Jensen, Sisse Siggaard

    cast on the screen. This understanding is questioned with reference to a semiotic understanding of avatars if seen as triadic relationships of sign processes—that is, as something that stands for something for someone. This understanding is exemplified by the case of Thomas and his businessman avatar...

  9. Colorectal Cancer Awareness and Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-06

    An oncologist (cancer doctor) shares her medical and personal advice for people between the ages of 50 and 75 about getting screened for colorectal cancer.  Created: 4/6/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/6/2017.

  10. FAST MRI breast screening revisited

    International Nuclear Information System (INIS)

    Jain, Manish; Jain, Arushi; Hyzy, Marek D.; Werth, Graziella

    2017-01-01

    Screening for breast cancer in high-risk women takes about 40 minutes to acquire an MRI scan and is time-intensive to report. There is recent interest in the performance of an abbreviated MRI protocol (FAST) in the screening setting. FAST scans have a reported negative predictive value of 99.8%. This study evaluates the false positive rates (FPR) and recall rates for FAST scans as compared to full diagnostic studies (FD). A database of all screening breast MRI scans performed at our institution between 30 June 2013 and 1 July 2014 (n = 591) was created by one of the researchers, who did not subsequently analyse the MRI scans. The T1W and first post-contrast and subtracted images from each of these scans (FAST protocol) were assessed by experienced breast MRI radiologists, blinded to the final diagnosis. The findings were then compared with the FD result. The recall rates were 6.6% for FAST scans and 5.8% for FD scans. FPR rates were 4.7% and 3.9% respectively. There is no statistically significant difference in the recall rates or FPR of FAST scans in comparison with full diagnostic studies. Given the absence of statistically significant difference in the FPR and recall rates in comparison with FD, FAST scans can replace FD for screening of breast cancer.

  11. Screen violence and youth behavior

    NARCIS (Netherlands)

    Anderson, Craig A.; Bushman, Brad J.; Bartholow, Bruce D.; Cantor, Joanne; Christakis, Dimitri; Coyne, Sarah M.; Donnerstein, Edward; Brockmyer, Jeanne Funk; Gentile, Douglas A.; Green, C. Shawn; Huesmann, Rowell; Hummer, Tom; Krahé, Barbara; Strasburger, Victor C.; Warburton, Wayne; Wilson, Barbara J.; Ybarra, Michele

    2017-01-01

    Violence in screen entertainment media (ie, television, film, video games, and the Internet), defined as depictions of characters (or players) trying to physically harm other characters (or players), is ubiquitous. The Workgroup on Media Violence and Violent Video Games reviewed numerous

  12. Screening for autologous blood transfusions

    DEFF Research Database (Denmark)

    Mørkeberg, J; Belhage, B; Ashenden, M

    2009-01-01

    parameter in the screening for autologous blood doping. Three bags of blood (approximately 201+/-11 g of Hb) were withdrawn from 16 males and stored at either -80 degrees C (-80 T, n=8) or +4 degrees C (+4 T, n=8) and reinfused 10 weeks or 4 weeks later, respectively. Seven subjects served as controls...

  13. Walkthrough screening evaluation field guide

    International Nuclear Information System (INIS)

    Eder, S.J.; Eli, M.W.; Salmon, M.W.

    1993-11-01

    The US Department of Energy (DOE) has a large inventory of existing facilities. Many of these facilities were not designed and constructed to current natural phenomena hazard (NPH) criteria. The NPH events include earthquakes, extreme winds and tornadoes, and floods. DOE Order 5480.28 establishes policy and requirements for NPH mitigation for DOE facilities. DOE is conducting a multiyear project to develop evaluation guidelines for assessing the condition and determining the need for upgrades at DOE facilities. One element of the NPH evaluation guidelines' development involves the existing systems and components at DOE facilities. This effort is described in detail in a cited reference. In the interim period prior to availability of the final guidelines, DOE facilities are encouraged to implement an NPH walk through screening evaluation process by which systems and components that need attention can be rapidly identified. Guidelines for conducting the walk through screening evaluations are contained herein. The result of the NPH walk through screening evaluation should be a prioritized list of systems and components that need further action. Simple and inexpensive fixes for items identified in the walk through as marginal or inadequate should be implemented without further study. By implementing an NPH walk through screening evaluation, DOE facilities may realize significant reduction in risk from NPH in the short term

  14. Review of Autism Screening Tests

    Directory of Open Access Journals (Sweden)

    Farin Soleimani

    2014-10-01

    Full Text Available Background: Autism is a neurodevelopmental disorder that onset in the first 3 years of life and led to lifelong disability.Despite the early onset of symptoms, diagnosis of thissyndromedoes not happenuntil severalyears later, somany childrenlosethe opportunityfor earlyintervention.There arevarious toolsforscreening anddiagnosis, buttheirdesign, strengths and weaknesses aredifferent. The aim of this study was assess these tools from various aspects to provide a comprehensive view. Materials and methods: This study is a narrative literature review on screeningtoolsof autism. Comprehensive searches of the scientific literature were conducted in textbooks and 8 electronic databases(proquest,wiley,google scholar,SID,Scopus, Web of Science ،Science Direct ، and Medline and Pediatric book. language restriction (Persian and English was applied. The search strategy consisted of keywords and medical subject headings for autism and various screening tests. Result: In this study, 28 screening tests were identified from 1992 to 2014. CHAT is oldest test and the most recent test is CAST The minimum age that can perform the screening is six months that related to ITC. Minimum time of testing was 5 minutes  for CHAT and the maximum time was 90-120 minutes for ASIEP-3.RAADS-R test was the highest specificity and specificity (100% and the lowest specificity was 14% in ESAT test Conclusion: The results of this study indicate that any of the autism screening tools consider specific skill and various aspects of the disease, careful evaluation is need to choose proper test.

  15. Rastreo del cáncer colorrectal: Conocimiento y actitud de la población Screening colorectal cancer: Perception and behavior of the population

    Directory of Open Access Journals (Sweden)

    Enrique R. Casal

    2009-02-01

    Full Text Available El rastreo de cáncer colorrectal (CCR cuenta con fuertes evidencias en su favor. Datos preliminares indican que a pesar de ello no se lleva a cabo con la frecuencia adecuada. Se intenta aquí determinar, dentro de un Sistema de Salud que cuenta con los recursos necesarios, los elementos que facilitan o generan barreras para concretar esta práctica preventiva, cuántos individuos lo ponen en práctica y qué predice esta conducta. Se realizó una encuesta telefónica a los afiliados de una Obra Social de empleados de la Universidad de Buenos Aires, de los que 132 completaron el cuestionario (tasa de respuesta 70%. Los elementos considerados facilitadores del rastreo obtuvieron respuestas afirmativas en el 64 a 97%, mientras que los que definían barreras un 11 a 27%. En este último grupo, una categoría diferenciada la constituía el miedo a los efectos adversos: 39%, y el sentimiento de vergüenza relacionado con los procedimientos: 30%. Un 33% de los encuestados tenían hecho un método de rastreo, mayoritariamente de sangre oculta (27, sigmoideoscopía (11 y colonoscopía (20. Una mayoría afirmó que "se haría el procedimiento si el médico se lo recomendara" (95%, o "no se lo haría excepto que su médico se lo aconseje" (87%. Contestar afirmativamente que "los médicos hacen lo mejor para los pacientes" se asoció con haberse hecho un método de rastreo de CCR, OR 1.55 (IC 95%: 1.02-2.37 p: 0.04. El grupo de individuos estudiado parece bien predispuesto para el rastreo del CCR, la recomendación médica sería aquí un determinante prominente para ponerlo en práctica.There is strong evidence favoring colorectal cancer screening. Preliminary data suggests that it is not included in routine practice with the adequate frequency. We intended to recognize in a Health Care System (HCS that provides the needed resources, the facilitators and barriers related with the implementation of this preventive practice, how many individuals have

  16. Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

    Science.gov (United States)

    Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

    2018-04-25

    National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

  17. Chemical compatibility screening test results

    International Nuclear Information System (INIS)

    Nigrey, P.J.; Dickens, T.G.

    1997-12-01

    A program for evaluating packaging components that may be used in transporting mixed-waste forms has been developed and the first phase has been completed. This effort involved the screening of ten plastic materials in four simulant mixed-waste types. These plastics were butadiene-acrylonitrile copolymer rubber, cross-linked polyethylene (XLPE), epichlorohydrin rubber, ethylene-propylene rubber (EPDM), fluorocarbon (Viton or Kel-F), polytetrafluoroethylene, high-density polyethylene (HDPE), isobutylene-isoprene copolymer rubber (butyl), polypropylene, and styrene-butadiene rubber (SBR). The selected simulant mixed wastes were (1) an aqueous alkaline mixture of sodium nitrate and sodium nitrite; (2) a chlorinated hydrocarbon mixture; (3) a simulant liquid scintillation fluid; and (4) a mixture of ketones. The testing protocol involved exposing the respective materials to 286,000 rads of gamma radiation followed by 14-day exposures to the waste types at 60 degrees C. The seal materials were tested using vapor transport rate (VTR) measurements while the liner materials were tested using specific gravity as a metric. For these tests, a screening criterion of 0.9 g/hr/m 2 for VTR and a specific gravity change of 10% was used. Based on this work, it was concluded that while all seal materials passed exposure to the aqueous simulant mixed waste, EPDM and SBR had the lowest VTRs. In the chlorinated hydrocarbon simulant mixed waste, only Viton passed the screening tests. In both the simulant scintillation fluid mixed waste and the ketone mixture simulant mixed waste, none of the seal materials met the screening criteria. For specific gravity testing of liner materials, the data showed that while all materials with the exception of polypropylene passed the screening criteria, Kel-F, HDPE, and XLPE offered the greatest resistance to the combination of radiation and chemicals

  18. Search for Internal Cancers in Mice Tattooed with Inks of High Contents of Potential Carcinogens: A One-Year Autopsy Study of Red and Black Tattoo Inks Banned in the Market.

    Science.gov (United States)

    Sepehri, Mitra; Lerche, Catharina M; Hutton Carlsen, Katrina; Serup, Jørgen

    2017-01-01

    Tattoo ink stock products often contain potential carcinogens, which on large-scale population exposure may be clinically relevant. The aim of this autopsy study in mice was to screen major organs for clinical and subclinical cancers. Mice were tattooed on their backs. In total, 48 mice were included and divided into 4 groups; 11 mice tattooed black, 10 tattooed red, and 5 mice serving as untreated controls. A group of 22 mice with black tattoos and exposed to ultraviolet radiation (UVR) were also studied. The black and red inks were both stock products banned on the Danish market due to the measured contents of potential carcinogens; benzo(a)pyrene and 2-anisidine, respectively. The mice were housed for 1 year after tattooing, and autopsy study on internal organs was performed. Tissue samples were systematically taken from major organs for screening of subclinical changes, not detected by visual examination. Any observed deviation from normal structure was subject to biopsy and light microscopy. All mice survived the 1-year observation period. Autopsy revealed no macroscopic signs of cancer. Microscopic search of internal organs showed no subclinical or clinical cancer. Despite extensive tattoos with 2 banned inks, the long-term observation in mice showed no internal cancers nor was the combination of carcinogen and UVR associated with cancer. Lack of observed malignancy might be explained by the fact that tattooing is only a single dose exposure. Registered data on carcinogens relies on repeated or chronic exposures. The study does not support the hypothesis that tattooing causes cancer. © 2017 S. Karger AG, Basel.

  19. Smoking cessation and lung cancer screening

    DEFF Research Database (Denmark)

    Pedersen, Jesper Johannes Holst; Tønnesen, Philip; Ashraf, Haseem

    2016-01-01

    Smoking behavior may have a substantial influence on the overall effect of lung cancer screening. Non-randomized studies of smoking behavior during screening have indicated that computer tomography (CT) screening induces smoking cessation. Randomized studies have further elaborated that this effect...... and decrease smoking relapse rate. Also low smoking dependency and high motivation to quit smoking at baseline predicted smoking abstinence in screening trials. Lung cancer screening therefore seems to be a teachable moment for smoking cessation. Targeted smoking cessation counselling should be an integrated...... part of future lung cancer screening trials....

  20. Increasing Cervical Cancer Screening in Underserved Populations.

    Science.gov (United States)

    Dorsainvil, Merlyn A

    The incidence of cervical cancer has declined dramatically due to Papanicolaou smear testing. However, some minority populations continue to suffer with high incidences and/or death rates of cervical cancer, due to lack of screening. This article updates on cervical cancer screening and prevention and discusses cultural impacts on screening. Knowledge deficits disproportionately affect ethnic minority groups and contribute to cancer incidence, whereas lack of healthcare coverage and low socioeconomic status contribute to screening disparities. Although minority women have cultural beliefs and practices that influence screening, recommendation and/or education from a provider often lead to screening.

  1. Screening history in women with cervical cancer in a Danish population-based screening program

    DEFF Research Database (Denmark)

    Kirschner, Benny; Poll, Susanne; Rygaard, Carsten

    2011-01-01

    The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer.......The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer....

  2. Screening Sex: revelando e dissimulando o sexo Screening Sex

    Directory of Open Access Journals (Sweden)

    Linda Williams

    2012-06-01

    Full Text Available Neste texto, procura-se contar a história da exibição do sexo em filmes majoritariamente produzidos nos Estados Unidos no período de quase um século. Ao se perguntar quando, porque e como os Estados Unidos se transformaram de uma cultura que não exibia o sexo em uma que o exibe, a autora insiste no duplo significado do verbo screen (tanto como uma revelação quanto uma dissimulação. Exibir é revelar em uma tela. Mas um segundo e igualmente importante significado, como diz o dicionário é "proteger ou esconder atrás de uma tela". Os filmes tanto revelam como escondem. O artigo analisa a forma como mudanças sociais ocorridas nos Estados Unidos, como, por exemplo, a Revolução sexual dos anos 60 e novas visões a respeito da sexualidade, possibilitaram novas maneiras de representação do sexo no cinema, reorganizando a relação entre o público e o privado. O artigo se pergunta também sobre como nossos corpos e sentidos reagem ao encontro com o sexo na tela, introduzindo a ideia de "saber carnal" (carnal knowledge.In this paper, we try to tell the history of the exhibition of sex in movies mainly produced in the United States in almost a century. Asking when, why and how the United States became - from a culture that did not exhibit sex - into a culture that exhibits it, the author insists in the double sense of the verb to screen (as both a revelation and a dissimulation. To exhibit is to reveal in a screen. But another, and important, sense, as says the dictionary, is "to protect or hide behind a screen". Movies show as well as they reveal. The paper analyzes the way social change in the United States, for example the sexual revolution of the sixties and new views on sexuality allowed new ways of representing sex in the movies, creating a new relation between public and private. The paper also asks how our bodies and senses react to sex in the screen, introducing the idea of "carnal knowledge".

  3. Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications

    Directory of Open Access Journals (Sweden)

    John Ong

    2018-03-01

    Full Text Available Summary: Use of hepatocytes derived from induced pluripotent stem cells (i-Heps is limited by their functional differences in comparison with primary cells. Extracellular niche factors likely play a critical role in bridging this gap. Using image-based characterization (high content analysis; HCA of freshly isolated hepatocytes from 17 human donors, we devised and validated an algorithm (Hepatocyte Likeness Index; HLI for comparing the hepatic properties of cells against a physiological gold standard. The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Laminin 411, the top hit, was validated in two additional induced pluripotent stem cell (iPSC lines, primary tissue, and an in vitro model of α1-antitrypsin deficiency. Cumulatively, these data provide a reference method to control and screen for i-Hep differentiation, identify Laminin 411 as a key niche protein, and underscore the importance of combining substrates, soluble factors, and HCA when developing iPSC applications. : Rashid and colleagues demonstrate the utility of a high-throughput imaging platform for identification of physiologically relevant extracellular niche factors to advance i-Heps closer to their primary tissue counterparts. The extracellular matrix (ECM protein screen identified Laminin 411 as an important niche factor facilitating i-Hep-based disease modeling in vitro. Keywords: iPS hepatocytes, extracellular niche, image-based screening, disease modeling, laminin

  4. Screening and classification of ceramic powders

    Science.gov (United States)

    Miwa, S.

    1983-01-01

    A summary is given of the classification technology of ceramic powders. Advantages and disadvantages of the wet and dry screening and classification methods are discussed. Improvements of wind force screening devices are described.

  5. Prostate Cancer Screening Results from PLCO

    Science.gov (United States)

    Learn the results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a large-scale clinical trial to determine whether certain cancer screening tests can help reduce deaths from prostate, lung, colorectal, and ovarian cancer.

  6. Screening for Hepatitis C Infections in Adults

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Hepatitis C Virus Infection in Adults The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Hepatitis C Virus ...

  7. Breast cancer screening: ''reassuring'' the worried well?

    DEFF Research Database (Denmark)

    Brodersen, John; Siersma, Volkert; Ryle, Mette

    2011-01-01

    of women offered screening compared to a population of women not offered screening for breast cancer. METHODS: One thousand women, aged 50-69 years, were randomly drawn from the Danish Civil Registration System to receive part I of the questionnaire Consequences of Screening in Breast Cancer (COS-BC1......): the sample consisted of 500 women living in a geographical area where screening mammography had been offered for more than 10 years and 500 women living in an area where the public health authorities had never invited women to breast cancer screening. RESULTS: A total of 759 women returned the questionnaire....... Those living in areas where screening was not offered reported more negative psychosocial aspects compared to women living in areas where screening was offered. CONCLUSIONS: The results indicate that women tend to perceive breast cancer screening as a reassuring preventive initiative. Alternatively...

  8. Health Screening: MedlinePlus Health Topic

    Science.gov (United States)

    ... I Have an Eye Exam? (Prevent Blindness America) Lipid Panel (American Association for Clinical Chemistry) Lung Cancer Screening (Mayo Foundation for Medical Education and Research) Also in Spanish Skin Cancer Screening (National Cancer ...

  9. Retinopathy of prematurity screening criteria and workload ...

    African Journals Online (AJOL)

    Larger infants require screening to include a few outliers, but they ... Making local screening criteria narrower on the basis of a limited evidence base may be dangerous. Risk factors for CSROP in larger infants need to be researched.

  10. Retinopathy of prematurity screening criteria and workload ...

    African Journals Online (AJOL)

    Larger infants require screening to include a few outliers, but they require ... Making local screening criteria narrower on the basis of a limited evidence base may be dangerous. Risk factors for CSROP in larger infants need to be researched.

  11. Screening candidate systems engineers: a research design

    CSIR Research Space (South Africa)

    Goncalves, DP

    2009-07-01

    Full Text Available engineering screening methodology that could be used to screen potential systems engineers. According to their design, this can be achieved by defining a system engineering profile according to specific psychological attributes, and using this profile...

  12. Sites Pre-Screened for Wind Energy

    Data.gov (United States)

    U.S. Environmental Protection Agency — The RE-Powering Screening Dataset spreadsheet contains detailed site information on over 80,000 contaminated lands, landfills, and mine sites with screening results...

  13. Risks of Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... cancer. Having hepatitis or cirrhosis can increase the risk of developing liver cancer. Anything that increases the ... clinical trials is available from the NCI website . Risks of Liver (Hepatocellular) Cancer Screening Key Points Screening ...

  14. Phytochemical screening and antiproliferative effects of methanol ...

    African Journals Online (AJOL)

    Preliminary Phytochemical screening. Thin layer chromatographic profile (TLC) of methanol crude extract and antiproliferative studies were carried out in this research. Phytochemical screening revealed the presence of carbohydrate, glycoside, anthraquinone, steroid, triterpenes, saponin, tannins, flavonoids and alkaloid.

  15. Sites Pre-Screened for Solar Energy

    Data.gov (United States)

    U.S. Environmental Protection Agency — The RE-Powering Screening Dataset spreadsheet contains detailed site information on over 80,000 contaminated lands, landfills, and mine sites with screening results...

  16. Testing Precision Screening for Breast Cancer

    Science.gov (United States)

    An NCI research article about individualized approaches that could help identify those at risk of breast cancer who need to be screened and testing screening intervals that are appropriate for each person’s level of risk.

  17. Clad Degradation - FEPs Screening Arguments

    International Nuclear Information System (INIS)

    E. Siegmann

    2004-01-01

    The purpose of this report is to document the screening of the cladding degradation features, events, and processes (FEPs) for commercial spent nuclear fuel (CSNF). This report also addresses the effect of some FEPs on both the cladding and the CSNF, DSNF, and HLW waste forms where it was considered appropriate to address the effects on both materials together. This report summarizes the work of others to screen clad degradation FEPs in a manner consistent with, and used in, the Total System Performance Assessment-License Application (TSPA-LA). This document was prepared according to ''Technical Work Plan for Waste Form Degradation Modeling, Testing, and Analyses in Support of LA'' (BSC 2004a [DIRS 167796])

  18. Screening for pulmonary arteriovenous malformations

    DEFF Research Database (Denmark)

    Oxhøj, H; Kjeldsen, A D; Nielsen, G

    2000-01-01

    Pulmonary arteriovenous malformations (PAVM) cause right-to-left shunt and imply risk of paradoxical embolism and cerebral abscess. These complications can be prevented by appropriate treatment. Detection of PAVMs is therefore important, so simple and reliable screening methods are needed...... for this purpose. The aim of this investigation was to compare pulse oximetry and contrast echocardiography as screening tools for detection of pulmonary arteriovenous malformations. Eighty-five hereditary haemorrhagic telangiectasia (HHT) patients and first-degree relatives identified in a comprehensive study...... echocardiography with intravenous injection of echo contrast was performed in all subjects. Outcome measures were oxygen saturation change >2% units on changing body position and echo contrast observed in the left-sided heart chambers. Positive contrast echocardiography indicating the presence of PAVM was found...

  19. Environmental impact assessment screening tool

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    An environmental assessment and impact planning software, SCREENER, was tested at a pilot project at the Cameco site (Port Hope). SCREENER was used to screen the impacts of a new construction project in accordance with the process and reporting requirements laid out in the Canadian Environmental Assessment Act. The software test concentrated on the activities that are directly involved with the structure construction and site preparation activities. In addition, a two and one half day training course was given to three AECB staff using the test case as a hands on example. The conclusion of this project is that an automated tool such as SCREENER (or Calyx, the new generation of environmental assessment tools from ESSA Software Ltd.), will help the AECB to standardize the approach to environmental assessment, assist in project planning, and save resources in the screening process. The new approach could allow to allocate AECB limited resources to the detailed assessments required for maximum impact activities. 2 figs. 7 refs.

  20. Hot Topic: Preimplantation aneuploidy screening

    Directory of Open Access Journals (Sweden)

    Kayhan Yakın

    2009-03-01

    Full Text Available Preimplantation Genetic Screening (PGS is a technique that has been introduced into clinical practice to screen and eliminate aneuploid embryos form transfer with the intention to improve implantation rates and decrease pregnancy wastage. Although practiced widely throughout the world the PGS unfortunately has been adopted without being subjected to rigorous scientific validation. Data from recent prospective randomized trials have shed doubt on the efficacy of the procedure when used in women with advanced age, one of the target populations for PGS. Other purported indications for the application of this complicated technique such as recurrent implantation failure and recurrent spontaneous abortion have not been subjected to randomized controlled trials. For the best interest of patients, we feel it is timely for a debate regarding the efficacy and safety of PGS.

  1. Environmental impact assessment screening tool

    International Nuclear Information System (INIS)

    1995-05-01

    An environmental assessment and impact planning software, SCREENER, was tested at a pilot project at the Cameco site (Port Hope). SCREENER was used to screen the impacts of a new construction project in accordance with the process and reporting requirements laid out in the Canadian Environmental Assessment Act. The software test concentrated on the activities that are directly involved with the structure construction and site preparation activities. In addition, a two and one half day training course was given to three AECB staff using the test case as a hands on example. The conclusion of this project is that an automated tool such as SCREENER (or Calyx, the new generation of environmental assessment tools from ESSA Software Ltd.), will help the AECB to standardize the approach to environmental assessment, assist in project planning, and save resources in the screening process. The new approach could allow to allocate AECB limited resources to the detailed assessments required for maximum impact activities

  2. Profiling, Screening and Criminal Recruitment

    OpenAIRE

    Christopher Cotton; Cheng Li

    2012-01-01

    We model major criminal activity as a game in which a law enforcement officer chooses the rate at which to screen different population groups and a criminal organization (e.g., drug cartel, terrorist cell) chooses the observable characteristics of its recruits. Our model best describes smuggling or terrorism activities at borders, airports and other security checkpoints. When the social costs of crime are high, law enforcement is most-effective when it is unconstrained in its ability to profi...

  3. Film-screen digital radiography

    International Nuclear Information System (INIS)

    Schwenker, R.P.; Eger, H.

    1985-01-01

    The excellent performance of the digital film-screen system as a receptor for projection radiographic data is discussed. An experimental system for obtaining high quality digital radiographic data by laser scanning radiographic films is described. This system is being used to evaluate the clinical utility of various digital image processing algorithms. Future plans include an investigation of quantitative analysis of projection radiographic data. Digital data obtained by film scanning can be used with digital image archiving and communications systems. (author)

  4. Employee Screening : Theory and Evidence

    OpenAIRE

    Fali Huang; Peter Cappelli

    2007-01-01

    Arguably the fundamental problem faced by employers is how to elicit effort from employees. Most models suggest that employers meet this challenge by monitoring employees carefully to prevent shirking. But there is another option that relies on heterogeneity across employees, and that is to screen job candidates to find workers with a stronger work ethic who require less monitoring. This should be especially useful in work systems where monitoring by supervisors is more difficult, such as tea...

  5. Methods for Cervical Cancer Screening

    Directory of Open Access Journals (Sweden)

    Tatiana Vargas-Revilla

    2014-12-01

    This article is divided in three sections: the first one focuses on the general impact of cervical cancer has hadin CostaRica, these condsection gathers information about different methodologies used around the world to detect this cancer and the third one makes reference to the current development of the screening devise in Mexico that works as a monitoring system and can used by women without external assistance.

  6. 3D mosquito screens to create window double screen traps for mosquito control.

    Science.gov (United States)

    Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo

    2017-08-29

    Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and

  7. Bacterial contamination of computer touch screens.

    Science.gov (United States)

    Gerba, Charles P; Wuollet, Adam L; Raisanen, Peter; Lopez, Gerardo U

    2016-03-01

    The goal of this study was to determine the occurrence of opportunistic bacterial pathogens on the surfaces of computer touch screens used in hospitals and grocery stores. Opportunistic pathogenic bacteria were isolated on touch screens in hospitals; Clostridium difficile and vancomycin-resistant Enterococcus and in grocery stores; methicillin-resistant Staphylococcus aureus. Enteric bacteria were more common on grocery store touch screens than on hospital computer touch screens. Published by Elsevier Inc.

  8. Tuberculosis screening in patients with HIV

    DEFF Research Database (Denmark)

    Bjerrum, Stephanie Mia Katrine; Bonsu, Frank; Hanson-Nortey, Nii Nortey

    2016-01-01

    BACKGROUND: Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice...... is scarce. OBJECTIVES: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. DESIGN: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during...

  9. SCREENING FOR EARLY DETECTION OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Rasskazova

    2014-01-01

    Full Text Available The article presents a brief overview of the main methods of breast cancer screening. Proven effectiveness of mammography as a screening method in reducing mortality from breast cancer, specified limits of the method. The main trend of increasing the effectiveness of screening is the transition to digital technologies. Properly organized screening with the active participation of the population reduces mortality from breast cancer by 30%.

  10. Population-based screening versus case detection.

    Directory of Open Access Journals (Sweden)

    Thomas Ravi

    2002-01-01

    Full Text Available India has a large burden of blindness and population-based screening is a strategy commonly employed to detect disease and prevent morbidity. However, not all diseases are amenable to screening. This communication examines the issue of "population-based screening" versus "case detection" in the Indian scenario. Using the example of glaucoma, it demonstrates that given the poor infrastructure, for a "rare" disease, case detection is more effective than population-based screening.

  11. Can economics be applied to prenatal screening?

    OpenAIRE

    Nicholas Phin

    1990-01-01

    This paper is a review of the economics of prenatal screening as seen from a medical point of view. The difficulties and controversies over the economic analysis are examined with specific reference to screening for Down syndrome. The aims and principles of prenatal screening are set out and discussed before reviewing the attempts that have been made to assess the costs and benefits of screening for Down syndrome. The major problem identified is the measurement and valuation of benefits. This...

  12. Absence of micronucleus formation in CHO-K1 cells cultivated in platelet lysate enriched medium.

    Science.gov (United States)

    Bernardi, Martina; Adami, Valentina; Albiero, Elena; Madeo, Domenico; Rodeghiero, Francesco; Astori, Giuseppe

    2014-03-01

    Human platelet lysate (PL) represents an effective substitute of fetal bovine serum (FBS) for mesenchymal stromal cell (MSC) cultivation. Compared to FBS, PL favors MSC proliferation significantly shortening the population doubling time and avoiding the risks related to the use of animal derivatives. Growth factors contained in the platelets are released upon platelet disruption following freezing/thawing cycles or as we have recently described by using ultrasound. We have investigated whether the increased cell proliferation achieved by using PL could induce mitotic stress and whether the potential formation of free radicals during PL production by ultrasound could cause chromosomal instability in mammalian cells. We have applied an image analysis assisted high content screening (HCS) in vitro micronucleus assay in the Chinese Hamster Ovarian K1 (CHO-K1) rodent mammalian cell line. PL was produced by sonication; for the micronucleus assay, CHO-K1 cells were exposed to increasing concentrations of PL. Cytokinesis was blocked by cytochalasin B, nuclei were stained with bisbenzimide and images were acquired and analyzed automatically using an HCS system, both with a 20× and a 10× objective. Our results suggest that growth stimulus induced by the use of PL did not significantly increase micronucleus formation in CHO-K1 cells compared to negative control. Micronucleus testing in conjunction with HCS could represent a valid tool to evaluate the safety of ancillary materials used in the production of cell-based medicinal products. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. An integrated biomedical knowledge extraction and analysis platform: using federated search and document clustering technology.

    Science.gov (United States)

    Taylor, Donald P

    2007-01-01

    High content screening (HCS) requires time-consuming and often complex iterative information retrieval and assessment approaches to optimally conduct drug discovery programs and biomedical research. Pre- and post-HCS experimentation both require the retrieval of information from public as well as proprietary literature in addition to structured information assets such as compound libraries and projects databases. Unfortunately, this information is typically scattered across a plethora of proprietary bioinformatics tools and databases and public domain sources. Consequently, single search requests must be presented to each information repository, forcing the results to be manually integrated for a meaningful result set. Furthermore, these bioinformatics tools and data repositories are becoming increasingly complex to use; typically they fail to allow for more natural query interfaces. Vivisimo has developed an enterprise software platform to bridge disparate silos of information. The platform automatically categorizes search results into descriptive folders without the use of taxonomies to drive the categorization. A new approach to information retrieval for HCS experimentation is proposed.

  14. Computer screens and brain cancer

    International Nuclear Information System (INIS)

    Wood, A.W.

    1995-01-01

    Australia, both in the media and at the federal government level, over possible links between screen-based computer use and cancer, brain tumour in particular. The screen emissions assumed to be the sources of the putative hazard are the magnetic fields responsible for horizontal and vertical scanning of the display. Time-varying fluctuations in these magnetic fields induce electrical current flows in exposed tissues. This paper estimates that the induced current densities in the brain of the computer user are up to 1 mA/m 2 (due to the vertical flyback). Corresponding values for other electrical appliances or installations are in general much less than this. The epidemiological literature shows no obvious signs of a sudden increase in brain tumour incidence, but the widespread use of computers is a relatively recent phenomenon. The occupational use of other equipment based on cathode ray tubes (such as TV repair) has a much longer history and has been statistically linked to brain tumour in some studies. A number of factors make this an unreliable indicator of the risk from computer screens, however. 42 refs., 3 tabs., 2 figs

  15. Celebrity endorsements of cancer screening.

    Science.gov (United States)

    Larson, Robin J; Woloshin, Steven; Schwartz, Lisa M; Welch, H Gilbert

    2005-05-04

    Celebrities often promote cancer screening by relating personal anecdotes about their own diagnosis or that of a loved one. We used data obtained from a random-digit dialing survey conducted in the United States from December 2001 through July 2002 to examine the extent to which adults of screening age without a history of cancer had seen or heard or been influenced by celebrity endorsements of screening mammography, prostate-specific antigen (PSA) testing, or sigmoidoscopy or colonoscopy. The survey response rate was 72% among those known to be eligible and 51% among potentially eligible people accounting for those who could not be contacted. A total of 360 women aged 40 years or older and 140 men aged 50 years or older participated in the survey. Most respondents reported they "had seen or heard a celebrity talk about" mammography (73% of women aged 40 years or older), PSA testing (63% of men aged 50 years or older), or sigmoidoscopy or colonoscopy (52% of adults aged 50 years or older). At least one-fourth of respondents who had seen or heard a celebrity endorsement said that the endorsement made them more likely to undergo mammography (25%), PSA testing (31%), or sigmoidoscopy or colonoscopy (37%).

  16. App Improves Colorectal Cancer Screening Rates

    Science.gov (United States)

    Colorectal cancer screening reduces deaths from the disease, yet about one-third of Americans aren’t up to date with screening. In this Cancer Currents blog post, learn what happened when people waiting for routine checkups could order their own screening test using a computer app.

  17. Design of low cost glaucoma screening

    NARCIS (Netherlands)

    Niessen, A. G.; Langerhorst, C. T.; Geijssen, H. C.; Greve, E. L.

    1997-01-01

    In 1991 the Netherlands Glaucoma Patient Association organized a glaucoma screening survey. This survey was designed to evaluate the effectiveness of a low cost screening setting. During a screening period of 8 days, 1259 subjects over the age of 49 years were examined by a team of

  18. Effectiveness and costeffectiveness of screening immigrants ...

    African Journals Online (AJOL)

    Background: Immigrants to developed countries are a major source of TB. Therefore amongst strategies adopted for TB control in developed countries include; 1) Screening immigrants at ports of entry referred to as “Port of Arrival Screening” (PoA) and 2) Passive screening (PS) for TB which means screening immigrants ...

  19. Breast cancer screening: evidence for false reassurance?

    NARCIS (Netherlands)

    R. de Gelder (Rianne); E. As, van (Elisabeth); M.M.A. Tilanus-Linthorst (Madeleine); C.C.M. Bartels (Carina); R. Boer (Rob); G. Draisma (Gerrit); H.J. de Koning (Harry)

    2008-01-01

    textabstractTumour stage distribution at repeated mammography screening is, unexpectedly, often not more favourable than stage distribution at first screenings. False reassurance, i.e., delayed symptom presentation due to having participated in earlier screening rounds, might be associated with

  20. Screening and Identification in Pediatric Primary Care

    Science.gov (United States)

    Simonian, Susan J.

    2006-01-01

    This article reviews issues related to behavioral screening in pediatric primary care settings. Structural-organizational issues affecting the use of pediatric primary care screening are discussed. This study also reviewed selected screening instruments that have utility for use in the primary care setting. Clinical and research issues related to…

  1. Cancer screening is not only about numbers

    NARCIS (Netherlands)

    Knottnerus, B. J.

    2017-01-01

    In the cancer screening debate, arguments for and against screening are often based on statistics, whereas for individuals personal, non-statistical factors are at least as important when deciding whether to participate in screening. Health care professionals have a responsibility in helping

  2. Radiological mass screening in the Irish Republic

    International Nuclear Information System (INIS)

    O'Donnell, B.

    1987-01-01

    Mass chest screening was first introduced to Ireland in the late 1940's. Routine mammography has never been used in the Irish Republic. For some years it has been customary to carry our routine clinical screening for congenital dislocation of hips on new born babies. Pre-- employment and pre- surgery x-ray screening were also being practiced

  3. Strategies in screening for colon carcinoma

    NARCIS (Netherlands)

    de Wijkerslooth, T. R.; Bossuyt, P. M.; Dekker, E.

    2011-01-01

    Colorectal cancer is the second most common cancer in Europe and meets the criteria for population screening. Population screening should lead to a reduction in CRC-related mortality and incidence. Several options are available for CRC screening, which can be itemised as stool-based tests and

  4. The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

    Energy Technology Data Exchange (ETDEWEB)

    Roman, M., E-mail: Marta.Roman@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Department of Women and Children’s Health, Oslo University Hospital, Oslo (Norway); Skaane, P., E-mail: PERSK@ous-hf.no [Department of Radiology, Oslo University Hospital Ullevaal, University of Oslo, Oslo (Norway); Hofvind, S., E-mail: Solveig.Hofvind@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo (Norway)

    2014-09-15

    Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

  5. The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

    International Nuclear Information System (INIS)

    Roman, M.; Skaane, P.; Hofvind, S.

    2014-01-01

    Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

  6. Influence of a screening navigation program on social inequalities in health beliefs about colorectal cancer screening.

    Science.gov (United States)

    Vallet, Fanny; Guillaume, Elodie; Dejardin, Olivier; Guittet, Lydia; Bouvier, Véronique; Mignon, Astrid; Berchi, Célia; Salinas, Agnès; Launoy, Guy; Christophe, Véronique

    2016-08-01

    The aim of the study was to test whether a screening navigation program leads to more favorable health beliefs and decreases social inequalities in them. The selected 261 noncompliant participants in a screening navigation versus a usual screening program arm had to respond to health belief measures inspired by the Protection Motivation Theory. Regression analyses showed that social inequalities in perceived efficacy of screening, favorable attitude, and perceived facility were reduced in the screening navigation compared to the usual screening program. These results highlight the importance of health beliefs to understand the mechanism of screening navigation programs in reducing social inequalities. © The Author(s) 2014.

  7. European position statement on lung cancer screening

    DEFF Research Database (Denmark)

    Oudkerk, Matthijs; Devaraj, Anand; Vliegenthart, Rozemarijn

    2017-01-01

    Lung cancer screening with low-dose CT can save lives. This European Union (EU) position statement presents the available evidence and the major issues that need to be addressed to ensure the successful implementation of low-dose CT lung cancer screening in Europe. This statement identified...... specific actions required by the European lung cancer screening community to adopt before the implementation of low-dose CT lung cancer screening. This position statement recommends the following actions: a risk stratification approach should be used for future lung cancer low-dose CT programmes...... need to set a timeline for implementing lung cancer screening....

  8. Valuing Equal Protection in Aviation Security Screening.

    Science.gov (United States)

    Nguyen, Kenneth D; Rosoff, Heather; John, Richard S

    2017-12-01

    The growing number of anti-terrorism policies has elevated public concerns about discrimination. Within the context of airport security screening, the current study examines how American travelers value the principle of equal protection by quantifying the "equity premium" that they are willing to sacrifice to avoid screening procedures that result in differential treatments. In addition, we applied the notion of procedural justice to explore the effect of alternative selective screening procedures on the value of equal protection. Two-hundred and twenty-two respondents were randomly assigned to one of three selective screening procedures: (1) randomly, (2) using behavioral indicators, or (3) based on demographic characteristics. They were asked to choose between airlines using either an equal or a discriminatory screening procedure. While the former requires all passengers to be screened in the same manner, the latter mandates all passengers undergo a quick primary screening and, in addition, some passengers are selected for a secondary screening based on a predetermined selection criterion. Equity premiums were quantified in terms of monetary cost, wait time, convenience, and safety compromise. Results show that equity premiums varied greatly across respondents, with many indicating little willingness to sacrifice to avoid inequitable screening, and a smaller minority willing to sacrifice anything to avoid the discriminatory screening. The selective screening manipulation was effective in that equity premiums were greater under selection by demographic characteristics compared to the other two procedures. © 2017 Society for Risk Analysis.

  9. Mathematical Models of the Sinusoidal Screen Family

    Directory of Open Access Journals (Sweden)

    Tajana Koren

    2011-06-01

    Full Text Available In this paper we will define a family of sinusoidal screening elements and explore the possibilities of their application in graphic arts, securities printing and design solutions in photography and typography editing. For this purpose mathematical expressions of sinusoidal families were converted into a Postscript language. The introduction of a random variable results in a countless number of various mutations which cannot be repeated without knowing the programming code itself. The use of the family of screens in protection of securities is thus of great importance. Other possible application of modulated sinusoidal screens is related to the large format color printing. This paper will test the application of sinusoidal screens in vector graphics, pixel graphics and typography. The development of parameters in the sinusoidal screen element algorithms gives new forms defined within screening cells with strict requirements of coverage implementation. Individual solutions include stochastic algorithms, as well as the autonomy of screening forms in regard to multicolor printing channels.

  10. Screening for colorectal cancer: what fits best?

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-06-01

    Colorectal cancer (CRC) screening has been shown to be effective in reducing CRC incidence and mortality. There are currently a number of screening modalities available for implementation into a population-based CRC screening program. Each screening method offers different strengths but also possesses its own limitations as a population-based screening strategy. We review the current evidence base for accepted CRC screening tools and evaluate their merits alongside their challenges in fulfilling their role in the detection of CRC. We also aim to provide an outlook on the demands of a low-risk population-based CRC screening program with a view to providing insight as to which modality would best suit current and future needs.

  11. Breast cancer screening implementation and reassurance

    DEFF Research Database (Denmark)

    Østerø, J; Siersma, Volkert Dirk; Brodersen, John

    2013-01-01

    difference in reported psychosocial aspects had disappeared or been reduced because of the nationwide screening implementation. METHODS: The 1000 women included in the previous survey were posted part I of the questionnaire Consequences of Screening in Breast Cancer (COS-BC1) in August 2011, nearly 5 years......BACKGROUND: Women not offered screening mammography reported higher levels of negative psychosocial aspects than women offered screening. This was demonstrated in a questionnaire survey where 1000 women were included: 500 women living in areas where the public authorities had never offered...... screening mammography and 500 women living in areas where women had been invited to screening mammography for >10 years. After this baseline survey, nationwide screening mammography was implemented. The aim of this follow-up study was to resurvey the 1000 women and to investigate if the identified...

  12. Outcome of breast cancer screening in Denmark

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Bak, Martin; von Euler-Chelpin, My

    2017-01-01

    were node negative and 40% ≤10 mm. False-positive rate was around 2%; higher for North Denmark Region than for the rest of Denmark. Three out of 10 breast cancers in screened women were diagnosed as interval cancers. Conclusions: High coverage by examination and low interval cancer rate are required...... for screening to decrease breast cancer mortality. Two pioneer local screening programs starting in the 1990s were followed by a decrease in breast cancer mortality of 22-25%. Coverage by examination and interval cancer rate of the national program were on the favorable side of values from the pioneer programs...... Region than in the rest of Denmrk. Detection rate was slightly below 1% at first screen, 0.6% at subsequent screens, and one region had some fluctuation over time. Ductal carcinoma in situ (DCIS) constituted 13-14% of screen-detected cancers. In subsequent rounds, 80% of screen-detected invasive cancers...

  13. Empirical study of supervised gene screening

    Directory of Open Access Journals (Sweden)

    Ma Shuangge

    2006-12-01

    Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

  14. Diabetes screening anxiety and beliefs.

    Science.gov (United States)

    Skinner, T C; Davies, M J; Farooqi, A M; Jarvis, J; Tringham, J R; Khunti, K

    2005-11-01

    This study assesses the impact of screening for diabetes on anxiety levels in an ethnically mixed population in the UK, and explores whether beliefs about Type 2 diabetes account for these anxiety levels. This cross-sectional study recruited individuals who were identified at high risk of developing diabetes through general practitioners' (GPs) lists or through public media recruitment. Participants completed an oral glucose tolerance test (OGTT). Between blood tests, participants completed the Spielberger State Anxiety Scale Short Form, the Emotional Stability Scale of the Big Five Inventory 44 and three scales from the Diabetes Illness Representations Questionnaire, revised for this study. Of the 1339 who completed the OGTT and questionnaire booklet, 54% were female, with 21% from an Asian background. Forty-five per cent of participants reported little to moderate amounts of anxiety at screening (mean 35.2; sd = 11.6). There was no significant effect of family history of diabetes, ethnic group or recruitment method on anxiety. The only variable significantly associated (negatively) with anxiety was the personality trait of emotional stability. Of responders, 64% and 61% agreed that diabetes was caused by diet or hereditary factors, respectively. Only 155 individuals (12%) agreed that diabetes was serious, shortens life and causes complications. The results of this study replicate that of previous studies, indicating that screening for diabetes does not induce significant anxiety. Bivariate analysis indicated that individuals who perceived diabetes to be serious, life shortening and resulting in complications had higher anxiety scores, the personality trait of emotional stability being the strongest predictor of anxiety.

  15. Phenotypic Screening Approaches to Develop Aurora Kinase Inhibitors: Drug Discovery Perspectives.

    Science.gov (United States)

    Marugán, Carlos; Torres, Raquel; Lallena, María José

    2015-01-01

    Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins, such as Aurora-A and -B. Current drugs, which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules), have several side effects (neutropenia, alopecia, and emesis). Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype. We will briefly describe two multiplexing technologies [high-content imaging (HCI) and flow cytometry] and two key processes for drug discovery research (assay development and validation) following our own published industry quality standards. We will further focus on HCI as a useful tool for phenotypic screening and will provide a concrete example of HCI assay to detect Aurora-A or -B selective inhibitors discriminating the off-target effects related to the inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

  16. Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

    Science.gov (United States)

    Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

    2012-01-01

    Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

  17. COVARIANCE ASSISTED SCREENING AND ESTIMATION.

    Science.gov (United States)

    Ke, By Tracy; Jin, Jiashun; Fan, Jianqing

    2014-11-01

    Consider a linear model Y = X β + z , where X = X n,p and z ~ N (0, I n ). The vector β is unknown and it is of interest to separate its nonzero coordinates from the zero ones (i.e., variable selection). Motivated by examples in long-memory time series (Fan and Yao, 2003) and the change-point problem (Bhattacharya, 1994), we are primarily interested in the case where the Gram matrix G = X ' X is non-sparse but sparsifiable by a finite order linear filter. We focus on the regime where signals are both rare and weak so that successful variable selection is very challenging but is still possible. We approach this problem by a new procedure called the Covariance Assisted Screening and Estimation (CASE). CASE first uses a linear filtering to reduce the original setting to a new regression model where the corresponding Gram (covariance) matrix is sparse. The new covariance matrix induces a sparse graph, which guides us to conduct multivariate screening without visiting all the submodels. By interacting with the signal sparsity, the graph enables us to decompose the original problem into many separated small-size subproblems (if only we know where they are!). Linear filtering also induces a so-called problem of information leakage , which can be overcome by the newly introduced patching technique. Together, these give rise to CASE, which is a two-stage Screen and Clean (Fan and Song, 2010; Wasserman and Roeder, 2009) procedure, where we first identify candidates of these submodels by patching and screening , and then re-examine each candidate to remove false positives. For any procedure β̂ for variable selection, we measure the performance by the minimax Hamming distance between the sign vectors of β̂ and β. We show that in a broad class of situations where the Gram matrix is non-sparse but sparsifiable, CASE achieves the optimal rate of convergence. The results are successfully applied to long-memory time series and the change-point model.

  18. Machine learning in virtual screening.

    Science.gov (United States)

    Melville, James L; Burke, Edmund K; Hirst, Jonathan D

    2009-05-01

    In this review, we highlight recent applications of machine learning to virtual screening, focusing on the use of supervised techniques to train statistical learning algorithms to prioritize databases of molecules as active against a particular protein target. Both ligand-based similarity searching and structure-based docking have benefited from machine learning algorithms, including naïve Bayesian classifiers, support vector machines, neural networks, and decision trees, as well as more traditional regression techniques. Effective application of these methodologies requires an appreciation of data preparation, validation, optimization, and search methodologies, and we also survey developments in these areas.

  19. Cardiovascular screening in Turner syndrome

    International Nuclear Information System (INIS)

    Dawson, K.L.; Wright, A.M.; Pitlick, P.T.

    1990-01-01

    This paper determines the utility of MR imaging as a cardiovascular screening method in patients with Turner syndrome and to compare its utility with that of echocardiography. Forty females with karytotypically proved Turner syndrome were prospectively evaluated with MR imaging and echocardiography. A 0.38-T resistive magnet was used to obtain ECG-gated axial and off-sagittal oblique images through the thorax with a spin-echo pulse sequence and TR 400--600 msec, TE 15--30 msec. Two-dimensional, M-mode, and Doppler echocardiography were performed and standard echocardiographic views were obtained

  20. X-ray intensifying screens

    International Nuclear Information System (INIS)

    Bossomaier, T.R.J.; Sangway, P.C.

    1979-01-01

    It is claimed that stabilization of X-ray intensifying screens against discolouration and hydrolysis of lanthanum or gadolinium oxyhalide phosphors can be achieved by incorporating into the phosphor/binder formulation a compound containing free epoxy groups. Suitable epoxy compounds include gamma glycidoxy trimethoxy silane and dimethyl di(m-glycidoxy methylphenyl) methane. The oxyhalide may be activated by Tb, Tm or Yb and may be mixed with other phosphors. Plasticisers and organo-tin stabilisers for the formulation are given. Many binders are specified, preferably these should not react with the free epoxy groups. (UK)

  1. Neonatal Hearing screening in tafila

    International Nuclear Information System (INIS)

    Rashed, K.A.

    2007-01-01

    To measure the true prevalence of hearing impairment in neonates in Tafila, Jordan. This retrospective study was carried out at Prince Zeid Hospital, Taflia, Jordan through analysis of data of all births from January 2005 and January 2006. Transient evoked otoacoustic emissions (TEOAE) were measured via the application of echoprobe to both ears. There were two groups of births that were analysed statistically. Hearing impaired neonates were those with two fails or more in each ear. Normal ones were those with 3 pass or more. Of the 1788 babies in the study group, 1622 (90.7%) were enrolled in the study with 9.3% loss rate. 1512 babies were examined on the 2 day of birth, 2 of them had hearing impairment with a rate of 1.2/1000. 110 babies were screened on the day of discharge from the nursery, one of them with hearing defect with a rate of 5.9/1000. Thus, true prevalence of hearing impaiment or failure was 1.7/1000. We conclude that screening for hearing impairment in the neonatal period is easy, informative and the true prevalence of hearing impairment in Tafila is similar to that in different parts of the world. (author)

  2. Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

    International Nuclear Information System (INIS)

    Morrison, B. F.; Aiken, W.; Mayhew, R.; Gordon, Y.; Reid, M.

    2016-01-01

    Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

  3. Breast cancer screening in older women.

    Science.gov (United States)

    Caplan, L S; Haynes, S G

    1996-01-01

    There is currently an epidemic of breast cancer in women 65 years of age and older. The purposes of this paper are to explore the breast cancer screening behaviors of older women and to identify some of the determinants of screening in these women. Data were analyzed from the 1987 National Health Interview Survey, a continuous nationwide household interview survey of the U.S. civilian, noninstitutionalized population. As in other studies, the utilization of breast cancer screening by older women was less in older women than in younger women. This was true for both mammography and clinical breast examination. A number of determinants of screening in older women were identified here. Women with a usual source of care and/or no activity limitation, as well as high school graduates, were the ones most likely to have received a screening mammogram and/or a screening clinical breast exam during the past year. The failure of older women to receive adequate breast cancer screening is an important concern which should be reevaluated, given the breast cancer epidemic in this population. This study identified a number of determinants of breast cancer screening in older women. For the most part, these determinants point to the primary care physician as the key to breast cancer screening in these women. Therefore, the primary care physician must be informed of, and encouraged to follow, the recommendations for periodic breast cancer screening in older women.

  4. Breast cancer screening with digital breast tomosynthesis.

    Science.gov (United States)

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  5. Computer Screen Use Detection Using Smart Eyeglasses

    Directory of Open Access Journals (Sweden)

    Florian Wahl

    2017-05-01

    Full Text Available Screen use can influence the circadian phase and cause eye strain. Smart eyeglasses with an integrated color light sensor can detect screen use. We present a screen use detection approach based on a light sensor embedded into the bridge of smart eyeglasses. By calculating the light intensity at the user’s eyes for different screens and content types, we found only computer screens to have a significant impact on the circadian phase. Our screen use detection is based on ratios between color channels and used a linear support vector machine to detect screen use. We validated our detection approach in three studies. A test bench was built to detect screen use under different ambient light sources and intensities in a controlled environment. In a lab study, we evaluated recognition performance for different ambient light intensities. By using participant-independent models, we achieved an ROC AUC above 0.9 for ambient light intensities below 200 lx. In a study of typical ADLs, screen use was detected with an average ROC AUC of 0.83 assuming screen use for 30% of the time.

  6. Cancer Screening Considerations and Cancer Screening Uptake for Lesbian, Gay, Bisexual, and Transgender Persons.

    Science.gov (United States)

    Ceres, Marc; Quinn, Gwendolyn P; Loscalzo, Matthew; Rice, David

    2018-02-01

    To describe the current state of cancer screening and uptake for lesbian, gay, bisexual, and transgender (LGBT) persons and to propose cancer screening considerations for LGBT persons. Current and historic published literature on cancer screening and LGBT cancer screening; published national guidelines. Despite known cancer risks for members of the LGBT community, cancer screening rates are often low, and there are gaps in screening recommendations for LGBT persons. We propose evidence-based cancer screening considerations derived from the current literature and extant cancer screening recommendations. The oncology nurse plays a key role in supporting patient preventive care and screening uptake through assessment, counseling, education, advocacy, and intervention. As oncology nurses become expert in the culturally competent care of LGBT persons, they can contribute to the improvement of quality of care and overall well-being of this health care disparity population. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Screening and identification of novel biologically active natural compounds [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David Newman

    2017-06-01

    Full Text Available With the advent of very rapid and cheap genome analyses and the linkage of these plus microbial metabolomics to potential compound structures came the realization that there was an immense sea of novel agents to be mined and tested. In addition, it is now recognized that there is significant microbial involvement in many natural products isolated from “nominally non-microbial sources”. This short review covers the current screening methods that have evolved and one might even be tempted to say “devolved” in light of the realization that target-based screens had problems when the products entered clinical testing, with off-target effects being the major ones. Modern systems include, but are not limited to, screening in cell lines utilizing very modern techniques (a high content screen that are designed to show interactions within cells when treated with an “agent”. The underlying principle(s used in such systems dated back to unpublished attempts in the very early 1980s by the pharmaceutical industry to show toxic interactions within animal cells by using automated light microscopy. Though somewhat successful, the technology was not adequate for any significant commercialization. Somewhat later, mammalian cell lines that were “genetically modified” to alter signal transduction cascades, either up or down, and frequently linked to luciferase readouts, were then employed in a 96-well format. In the case of microbes, specific resistance parameters were induced in isogenic cell lines from approximately the mid-1970s. In the latter two cases, comparisons against parent and sibling cell lines were used in order that a rapid determination of potential natural product “hits” could be made. Obviously, all of these assay systems could also be, and were, used for synthetic molecules. These methods and their results have led to a change in what the term “screening for bioactivity” means. In practice, versions of phenotypic screening

  8. Is the tide turning against breast screening?

    DEFF Research Database (Denmark)

    Jørgensen, Karsten Juhl

    2012-01-01

    ABSTRACT: Herein I argue that mammographic screening has not delivered on its fundamental premise: to reduce the incidence of advanced breast cancer. Indeed, achieving this goal is required if screening is to reduce breast cancer mortality or mastectomy use. Rather, screening has caused substantial...... increases in the incidence of in situ and early invasive cancers. Moreover, evidence indicates that these screen-detected cancers are unlikely to be cases that were 'caught early', but instead represent women who would not have been diagnosed in the absence of screening and who, as a result, have received...... harmful, unnecessary treatment. If true, these observations raise the specter that screening creates breast cancer patients and that this practice carries little or no benefit....

  9. Some legal aspects of genetic screening.

    Science.gov (United States)

    Abbing, H R

    2003-01-01

    Screening activities in health care are not always useful and sometimes harmful. The mere offer of a screening test puts the individual's autonomy under constraint. With genetic (predictive and risk assessment) tests, the right to free, informed consent and to protection of privacy and medical confidentiality is even more warranted. Screening evokes many questions from the perspective of the right to health care as well as (in particular with genetic screening) from the perspective of respect for individual human rights. Fear of liability puts pressure on professional restraint not to offer every screening test available. States have to take legislative measures for guaranteeing that only those screening activities become available that can significantly contribute to individual and public health. They also should consider additional rules for protecting individual rights where those that are generally accepted in the "ordinary" medical setting (the individual patient-doctor relationship), offer insufficient protection.

  10. Ethical issues in cancer screening and prevention.

    Science.gov (United States)

    Plutynski, Anya

    2012-06-01

    November 2009's announcement of the USPSTF's recommendations for screening for breast cancer raised a firestorm of objections. Chief among them were that the panel had insufficiently valued patients' lives or allowed cost considerations to influence recommendations. The publicity about the recommendations, however, often either simplified the actual content of the recommendations or bypassed significant methodological issues, which a philosophical examination of both the science behind screening recommendations and their import reveals. In this article, I discuss two of the leading ethical considerations at issue in screening recommendations: respect for patient autonomy and beneficence and then turn to the most significant methodological issues raised by cancer screening: the potential biases that may infect a trial of screening effectiveness, the problem of base rates in communicating risk, and the trade-offs involved in a judgment of screening effectiveness. These issues reach more broadly, into the use of "evidence-based" medicine generally, and have important implications for informed consent.

  11. Prostate cancer screening: and yet it moves!

    Directory of Open Access Journals (Sweden)

    Maciej Kwiatkowski

    2015-06-01

    Full Text Available The debate of prostate cancer (PCa screening has been shaped over decades. There is a plethora of articles in the literature supporting as well as declining prostate-specific antigen (PSA screening. Does screening decrease PCa mortality? With the long-term results of the European Randomized Study of Screening for Prostate (ERSPC the answer is clearly YES. It moves! However, in medicine there are no benefits without any harm and thus, screening has to be performed in targeted and smart way-or in other words-in a risk-adapted fashion when compared with the way it was done in the past. Here, we discuss the main findings of the ERSPC trials and provide insights on how the future screening strategies should be implemented.

  12. Breast Cancer Screening, Mammography, and Other Modalities.

    Science.gov (United States)

    Fiorica, James V

    2016-12-01

    This article is an overview of the modalities available for breast cancer screening. The modalities discussed include digital mammography, digital breast tomosynthesis, breast ultrasonography, magnetic resonance imaging, and clinical breast examination. There is a review of pertinent randomized controlled trials, studies and meta-analyses which contributed to the evolution of screening guidelines. Ultimately, 5 major medical organizations formulated the current screening guidelines in the United States. The lack of consensus in these guidelines represents an ongoing controversy about the optimal timing and method for breast cancer screening in women. For mammography screening, the Breast Imaging Reporting and Data System lexicon is explained which corresponds with recommended clinical management. The presentation and discussion of the data in this article are designed to help the clinician individualize breast cancer screening for each patient.

  13. Epigenetics of prostate cancer and the prospect of identification of novel drug targets by RNAi screening of epigenetic enzymes.

    Science.gov (United States)

    Björkman, Mari; Rantala, Juha; Nees, Matthias; Kallioniemi, Olli

    2010-10-01

    Alterations in epigenetic processes probably underlie most human malignancies. Novel genome-wide techniques, such as chromatin immunoprecipitation and high-throughput sequencing, have become state-of-the-art methods to map the epigenomic landscape of development and disease, such as in cancers. Despite these advances, the functional significance of epigenetic enzymes in cancer progression, such as prostate cancer, remain incompletely understood. A comprehensive mapping and functional understanding of the cancer epigenome will hopefully help to facilitate development of novel cancer therapy targets and improve future diagnostics. The authors have developed a novel cell microarray-based high-content siRNA screening technique suitable to address the putative functional role and impact of all known putative and novel epigenetic enzymes in cancer, including prostate cancer.

  14. Realization of superconductive films by screen printing

    International Nuclear Information System (INIS)

    Baudry, H.

    1988-01-01

    Screen printing is a promising method to manufacture superconductive lines making use of superconductive ceramics. An ink has been realized with YBa 2 Cu 3 0 7-x' and the process conditions defined by thermal analysis. A superconductive transition is observed after screen printing on MgO. The firing of the layer is made at 920 0 C followed by a reoxidation step at 420 0 C. The silver electrical contacts are also screen printed [fr

  15. Mammography with rare earth intensifying screens

    International Nuclear Information System (INIS)

    Maurer, H.J.; Goos, F.

    1987-01-01

    Screens basing on rare earth phosphors with suitable films green or blue sensitive may be used in mammography with grids without diagnostic losses. Highest definition will be obtained with medium densities on film. High-speed screens may reduce dose, but definition is poor. Best compromise between speed and high definition may be reached with relative low thickness of phosphor layers. A system of high definition films (Medichrome) and special rare earth screens give best results. (orig.) [de

  16. High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

    Science.gov (United States)

    Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

    2018-05-15

    Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Breast cancer screening-opportunistic use of registry and linked screening data for local evaluation.

    Science.gov (United States)

    Roder, David; Farshid, Gelareh; Gill, Grantley; Kollias, Jim; Koczwara, Bogda; Karapetis, Chris; Adams, Jacqui; Joshi, Rohit; Keefe, Dorothy; Powell, Kate; Fusco, Kellie; Eckert, Marion; Buckley, Elizabeth; Beckmann, Kerri

    2017-06-01

    Screening has been found to reduce breast cancer mortality at a population level in Australia, but these studies did not address local settings where numbers of deaths would generally have been too low for evaluation. Clinicians, administrators, and consumer groups are also interested in local service outcomes. We therefore use more common prognostic and treatment measures and survivals to gain evidence of screening effects among patients attending 4 local hospitals for treatment. To compare prognostic, treatment, and survival measures by screening history to determine whether expected screening effects are occurring. Employing routine clinical registry and linked screening data to investigate associations of screening history with these measures, using unadjusted and adjusted analyses. Screened women had a 10-year survival from breast cancer of 92%, compared with 78% for unscreened women; and 79% of screened surgical cases had breast conserving surgery compared with 64% in unscreened women. Unadjusted analyses indicated that recently screened cases had earlier tumor node metastasis stages, smaller diameters, less nodal involvement, better tumor differentiation, more oestrogen and progesterone receptor positive lesions, more hormone therapy, and less chemotherapy. Radiotherapy tended to be more common in screening participants. More frequent use of adjunctive radiotherapy applied when breast conserving surgery was used. Results confirm the screening effects expected from the scientific literature and demonstrate the value of opportunistic use of available registry and linked screening data for indicating to local health administrations, practitioners, and consumers whether local screening services are having the effects expected. © 2016 John Wiley & Sons, Ltd.

  18. Diabetes screening anxiety and beliefs

    DEFF Research Database (Denmark)

    Skinner, T. Chas; Davies, M. J.; Farooqi, A. M.

    2005-01-01

    Five Inventory 44 and three scales from the Diabetes Illness Representations Questionnaire, revised for this study. Results: Of the 1339 who completed the OGTT and questionnaire booklet, 54% were female, with 21% from an Asian background. Forty-five per cent of participants reported little to moderate...... amounts of anxiety at screening (mean 35.2; SD = 11.6). There was no significant effect of family history of diabetes, ethnic group or recruitment method on anxiety. The only variable significantly associated (negatively) with anxiety was the personality trait of emotional stability. Of responders, 64...... not induce significant anxiety. Bivariate analysis indicated that individuals who perceived diabetes to be serious, life shortening and resulting in complications had higher anxiety scores, the personality trait of emotional stability being the strongest predictor of anxiety....

  19. X-ray intensifying screens

    International Nuclear Information System (INIS)

    Luckey, G.W.; DeBoer, C.D.

    1982-01-01

    An x-ray intensifying screen comprises a support which has a luminescent composition comprising an isotropic phosphor and a polymer having an index of refraction within 0.02 of that of the phosphor over at least 80 percent of its emission spectrum. The support has an index of refraction up to or equal to 0.05 units higher than that of the phosphor and has a reflection optical density of at least 1.7 to light emitted by the phosphor. A preferred luminescent composition comprises Kl:Tl, Rbl:Tl at BaSrFCl:Eu mixed with two monomers such as 1-naphthylmethylmethacrylate, S(1-naphthylmethyl) thioacrylate, 1-bromo-2-naphthylacrylate, and benzyl methacrylate, coated on black anodised Al and polymerised in situ. The ratio of monomers is adjusted to give the desired refractive index. Other phosphors, polymers and supports are specified together with the preparation of the monomers and polymers. (author)

  20. Screening of Modified RNA duplexes

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Bramsen, Jesper Bertram; Kjems, Jørgen

    protection against a fish pathogenic virus. This protection corresponded with an interferon response in the fish. Here we use this fish model to screen siRNAs containing various chemical modifications of the RNA backbone for their antiviral activity, the overall aim being identification of an siRNA form......Because of sequence specific gene targeting activity siRNAs are regarded as promising active compounds in gene medicine. But one serious problem with delivering siRNAs as treatment is the now well-established non-specific activities of some RNA duplexes. Cellular reactions towards double stranded...... RNAs include the 2´-5´ oligoadenylate synthetase system, the protein kinase R, RIG-I and Toll-like receptor activated pathways all resulting in antiviral defence mechanism. We have previously shown that antiviral innate immune reactions against double stranded RNAs could be detected in vivo as partial...

  1. Market screening of natural gas reformers

    International Nuclear Information System (INIS)

    Themsen, J.; Pagh Nielsen, M.; Knudsen Kaer, S.

    2005-01-01

    This report presents results from the project: Market screening of natural gas reformers. The project objective was to screen the natural gas reformers available on the international market. The technology is developing rapidly, and the results from this project will assist in determining the focus for the future Danish activities and in setting up ambitious and realistic targets. The reformer screening is partly based on AAU and Dantherm's experiences from previous studies, and the screening has been further extended with a number of activities, including seminars and contact with some of the most interesting suppliers. (BA)

  2. PET in cancer screening: a controversial imaging

    International Nuclear Information System (INIS)

    Su Minggang; Tan Tianzhi

    2012-01-01

    Malignancy has been one of the most dangerous threats to human health. Early diagnosis and treatment are key factors for improving prognosis. Cancer screening is an important way to detect early stage cancer and precancerous lesion. PET has been used increasingly in cancer screening in accordance with the requirement of the public. Though a great number of data show that PET can find some subclinical malignancy, yet as a cancer screening modality, PET is still controversial in contemporary medical practice. The aim of this article is to review the application status and existing problem of PET in cancer screening, and to offer some recognition and view about cancer srceening. (authors)

  3. Nuclear clustering and the electron screening puzzle

    Science.gov (United States)

    Bertulani, C. A.; Spitaleri, C.

    2018-01-01

    Electron screening changes appreciably the magnitude of astrophysical nuclear reactions within stars. This effect is also observed in laboratory experiments on Earth, where atomic electrons are present in the nuclear targets. Theoretical models were developed over the past 30 years and experimental measurements have been carried out to study electron screening in thermonuclear reactions. None of the theoretical models were able to explain the high values of the experimentally determined screening potentials. We explore the possibility that the "electron screening puzzle" is due to nuclear clusterization and polarization e_ects in the fusion reactions. We will discuss the supporting arguments for this scenario.

  4. Graphology: A Nontraditional Employment-Screening Technique.

    Science.gov (United States)

    Augustin, Harriet M.; Hinkson, Diana; Halatin, Ted J.

    2001-01-01

    Explains procedures for handwriting analysis (graphology) and the benefits and limitations of its use in employment screening. Presents implications for teaching penmanship in business education. (SK)

  5. Patient-initiated breast cancer screening

    International Nuclear Information System (INIS)

    Chilcote, W.

    1990-01-01

    This paper reviews the results of a breast cancer screening program sponsored by organizations at workplace or community locations. A comprehensive mobile breast cancer screening program, including education, breast physical examination, and mammography, was provided to 89 local organizations at $50.00 per examination over an 18-month period. The examination was patient initiated, following the ACS screening guidelines. Estimates of eligible women were provided by each organization. A total of 5,030 women at 89 organizations were screened for breast cancer. Approximately 25,727 women were eligible

  6. Factors Influencing Colorectal Cancer Screening Participation

    Directory of Open Access Journals (Sweden)

    Antonio Z. Gimeno García

    2012-01-01

    Full Text Available Colorectal cancer (CRC is a major health problem worldwide. Although population-based CRC screening is strongly recommended in average-risk population, compliance rates are still far from the desirable rates. High levels of screening uptake are necessary for the success of any screening program. Therefore, the investigation of factors influencing participation is crucial prior to design and launches a population-based organized screening campaign. Several studies have identified screening behaviour factors related to potential participants, providers, or health care system. These influencing factors can also be classified in non-modifiable (i.e., demographic factors, education, health insurance, or income and modifiable factors (i.e., knowledge about CRC and screening, patient and provider attitudes or structural barriers for screening. Modifiable determinants are of great interest as they are plausible targets for interventions. Interventions at different levels (patient, providers or health care system have been tested across the studies with different results. This paper analyzes factors related to CRC screening behaviour and potential interventions designed to improve screening uptake.

  7. Internet-Based Cervical Cancer Screening Program

    National Research Council Canada - National Science Library

    Wilbur, David C; Crothers, Barbara A; Eichhorn, John H; Ro, Min S; Gelfand, Jeffrey A

    2008-01-01

    This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet...

  8. Internet-Based Cervical Cytology Screening System

    National Research Council Canada - National Science Library

    Wilbur, David C; Crothers, Barbara A; Eichhorn, John H; Ro, Min S; Gelfand, Jeffrey A

    2007-01-01

    This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet...

  9. Internet-Based Cervical Cytology Screening Program

    National Research Council Canada - National Science Library

    Wilbur, David C; Crothers, Barbara A; Eichhorn, John H; Ro, Min S; Gelfand, Jeffrey A

    2006-01-01

    This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet...

  10. Health Screening Behaviour among Female Urban Dwellers

    Directory of Open Access Journals (Sweden)

    Nik Nairan Abdullah

    2016-01-01

    Full Text Available An ageing population is a public health challenge, affects most countries. Health screenings are able to detect diseases at the earliest stage. A cross-sectional study in December 2014 conducted among 643 older women who randomly interviewed using structured questionnaire from two urban governmental health centres in Malaysia. Aims of the study were to describe health screening services behaviour and health care accessibility among women aged 50 and above. Factors such as living arrangement and age played important roles in health screening execution among older female community dwellers. Advocacy on health screening is vital as to reduce the morbidity and mortality among them.

  11. Screening dynamics in doped titanates

    Energy Technology Data Exchange (ETDEWEB)

    Rubensson, J.E.; Luening, J.; Eisebitt, S. [Forschungszentrum Juelich (Germany)] [and others

    1997-04-01

    The time scale for carrier relaxation in semiconductors is on the same order of magnitude as the life time of shallow core hole states (a few femtoseconds). Resonant Inelastic soft X-ray scattering (RIXS) which involves (virtual) excitations of core levels consequently contains information about the time development of the electronic structure on this time scale. In many cases one can treat the scattering in an absorption (SXA) followed-by-emission (SXE) picture, where simply the rates for various processes can be compared with the intermediate core hole state decay rate as an internal {open_quotes}clock{close_quotes}. By variation of x (0 < x < 1) in La{sub x}Sr{sub 1{minus}x}TiO{sub 3}, the amount of Ti d electrons in the system can be controlled. SrTiO{sub 3} (x=0) is an insulator with an empty Ti d band. With increasing x, electrons are doped into the Ti d-band, and LaTiO{sub 3} (x=1) is a Mott Hubbard insulator with a Ti 3d{sup 1} configuration. In this work the authors demonstrate that the rate for Ti 2p core hole screening in La{sub x}Sr{sub 1{minus}x}TiO{sub 3} is doping dependent. The screening rate increases with the availability of Ti 3d electrons, and they estimate it to be 3.8 x 10{sup 13}/sec in La{sub 0.05}Sr{sub 0.95}TiO{sub 3}.

  12. Screen Violence and Youth Behavior.

    Science.gov (United States)

    Anderson, Craig A; Bushman, Brad J; Bartholow, Bruce D; Cantor, Joanne; Christakis, Dimitri; Coyne, Sarah M; Donnerstein, Edward; Brockmyer, Jeanne Funk; Gentile, Douglas A; Green, C Shawn; Huesmann, Rowell; Hummer, Tom; Krahé, Barbara; Strasburger, Victor C; Warburton, Wayne; Wilson, Barbara J; Ybarra, Michele

    2017-11-01

    Violence in screen entertainment media (ie, television, film, video games, and the Internet), defined as depictions of characters (or players) trying to physically harm other characters (or players), is ubiquitous. The Workgroup on Media Violence and Violent Video Games reviewed numerous meta-analyses and other relevant research from the past 60 years, with an emphasis on violent video game research. Consistent with every major science organization review, the Workgroup found compelling evidence of short-term harmful effects, as well as evidence of long-term harmful effects. The vast majority of laboratory-based experimental studies have revealed that violent media exposure causes increased aggressive thoughts, angry feelings, physiologic arousal, hostile appraisals, aggressive behavior, and desensitization to violence and decreases prosocial behavior (eg, helping others) and empathy. Still, to more fully understand the potential for long-term harm from media violence exposure, the field is greatly in need of additional large-sample, high-quality, longitudinal studies that include validated measures of media violence exposure and measures of other known violence risk factors. Also, although several high-quality media violence intervention studies have been conducted, larger-scale studies with more comprehensive and longer-term assessments are needed to fully understand long-term effects and to inform the development of tools that will help to reduce problems associated with aggression and violence. The evidence that violent screen media constitutes a causal risk factor for increased aggression is compelling. Modern social-cognitive theories of social behavior provide useful frameworks for understanding how and why these effects occur. Copyright © 2017 by the American Academy of Pediatrics.

  13. Screening Information - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us JSNP Screening Information Data detail Data name Screening Information DOI 10.18908/lsdba.nb...dc00114-003 Description of data contents Information from polymorphism screening experiments. Derived from E...the sequence for polymorphism screening Screened Position position of the polymorphism in the sequence for polymorphism screeni...ng Screened Symbol gene name related to the sequence for polymorphism screening Screened ...OMIM-ID OMIM ID related to the sequence for polymorphism screening About This Dat

  14. Mammography screening: A major issue in medicine.

    Science.gov (United States)

    Autier, Philippe; Boniol, Mathieu

    2018-02-01

    Breast cancer mortality is declining in most high-income countries. The role of mammography screening in these declines is much debated. Screening impacts cancer mortality through decreasing the incidence of number of advanced cancers with poor prognosis, while therapies and patient management impact cancer mortality through decreasing the fatality of cancers. The effectiveness of cancer screening is the ability of a screening method to curb the incidence of advanced cancers in populations. Methods for evaluating cancer screening effectiveness are based on the monitoring of age-adjusted incidence rates of advanced cancers that should decrease after the introduction of screening. Likewise, cancer-specific mortality rates should decline more rapidly in areas with screening than in areas without or with lower levels of screening but where patient management is similar. These two criteria have provided evidence that screening for colorectal and cervical cancer contributes to decreasing the mortality associated with these two cancers. In contrast, screening for neuroblastoma in children was discontinued in the early 2000s because these two criteria were not met. In addition, overdiagnosis - i.e. the detection of non-progressing occult neuroblastoma that would not have been life-threatening during the subject's lifetime - is a major undesirable consequence of screening. Accumulating epidemiological data show that in populations where mammography screening has been widespread for a long time, there has been no or only a modest decline in the incidence of advanced cancers, including that of de novo metastatic (stage IV) cancers at diagnosis. Moreover, breast cancer mortality reductions are similar in areas with early introduction and high penetration of screening and in areas with late introduction and low penetration of screening. Overdiagnosis is commonplace, representing 20% or more of all breast cancers among women invited to screening and 30-50% of screen

  15. [Generalized neonatal screening based on laboratory tests].

    Science.gov (United States)

    Ardaillou, Raymond; Le Gall, Jean-Yves

    2006-11-01

    Implementation of a generalized screening program for neonatal diseases must obey precise rules. The disease must be severe, recognizable at an early stage, amenable to an effective treatment, detectable with a non expensive and widely applicable test; it must also be a significant public health problem. Subjects with positive results must be offered immediate treatment or prevention. All screening programs must be regularly evaluated. In France, since 1978, a national screening program has been organized by a private association ("Association française pour le dépistage et la prévention des handicaps de l'enfant") and supervised by the "Caisse nationale d'assurance maladie" and "Direction Générale de la Sante". Five diseases are now included in the screening program: phenylketonuria, hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis and sickle cell disease (the latter only in at-risk newborns). Toxoplasmosis is a particular problem because only the children of mothers who were not tested during the pregnancy or who seroconverted are screened. Neonatal screening for phenylketonuria and hypothyrodism is unanimously recommended. Screening for congenital adrenal hyperplasia is approved in most countries. Cases of sickle cell disease and cystic fibrosis are more complex because--not all children who carry the mutations develop severe forms;--there is no curative treatment;--parents may become anxious, even though the phenotype is sometimes mild or even asymptomatic. Supporters of screening stress the benefits of early diagnosis (which extends the life expectancy of these children, particularly in the case of sickle cell disease), the fact that it opens up the possibility of prenatal screening of future pregnancies, and the utility of informing heterozygous carriers identified by familial screening. Neonatal screening for other diseases is under discussion. Indeed, technical advances such as tandem mass spectrometry make it possible to detect about 50

  16. Korean Americans' Beliefs about Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Shin-Young Lee, PhD, RN

    2013-06-01

    Conclusion: Results show the critical need for in-depth understanding of unique health and cultural beliefs about CRC screening in KAs. These beliefs could be useful for future intervention strategies to change health and cultural beliefs in order to increase CRC screening participation in KAs.

  17. Mobile Screens: The Visual Regime of Navigation

    NARCIS (Netherlands)

    Verhoeff, N.

    2012-01-01

    In this book on screen media, space, and mobility I compare synchronically, as well as diachronically, diverse and variegated screen media - their technologies and practices – as sites for virtual mobility and navigation. Mobility as a central trope can be found on the multiple levels that are

  18. Breast cancer screening: An outpatient clinic study

    Directory of Open Access Journals (Sweden)

    Mustafa Girgin

    2017-03-01

    Conclusion: A multidisciplinary cancer screening program should be maintained. With such a process, the aim is to reduce the morbidity and mortality of the disease without adversely affecting the health conditions of asymptomatic individuals based on the screening. Success is brought about by the combination of individual features. [Arch Clin Exp Surg 2017; 6(1.000: 23-27

  19. Screening for Developmental Dysplasia of the Hip

    NARCIS (Netherlands)

    Boere-Boonekamp, Magdalena M.; Verkerk, Paul H.

    1998-01-01

    The success rates of screening programmes for Developmental Dysplasia of the Hip (DDH) vary widely. Studies on screening programmes for DDH based on a Medline search for the years 1966–1997 are reviewed. The percentage treated in most studies, especially those using ultrasound, are high and suggest

  20. Phenylketonuria screening in the Republic of Macedonia.

    Science.gov (United States)

    Kocova, Mirjana; Anastasovska, Violeta

    2016-08-05

    Phenylketonuria is an autosomal recessive inborn error of metabolism which can be prevented by early and continuous treatment. Therefore newborn screening for phenylketonuria has been introduced in many countries. We present here the results of the selective newborn screening for inborn errors of metabolism, including PKU, performed by tandem mass spectrometry which has been introduced in Macedonia since 2011.