Sample records for cell-based screening system

  1. Adaptation of a Cell-Based High Content Screening System for the In-Depth Analysis of Celiac Biopsy Tissue. (United States)

    Cooper, Sarah E J; Mohamed, Bashir M; Elliott, Louise; Davies, Anthony Mitchell; Feighery, Conleth F; Kelly, Jacinta; Dunne, Jean


    The IN Cell Analyzer 1000 possesses several distinguishing features that make it a valuable tool in research today. This fully automated high content screening (HCS) system introduced quantitative fluorescent microscopy with computerized image analysis for use in cell-based analysis. Previous studies have focused on live cell assays, where it has proven to be a powerful and robust method capable of providing reproducible, quantitative data. Using HCS as a tool to investigate antigen expression in duodenal biopsies, we developed a novel approach to tissue positioning and mapping. We adapted IN Cell Analyzer 1000's image acquisition and analysis software for the investigation of tissue transglutaminase (tTG) and smooth muscle alpha-actin (SM α-actin) staining in paraffin-embedded duodenal tissue sections from celiac patients and healthy controls. These innovations allowed a quantitative analysis of cellular structure and protein expression. The results from routine biopsy material indicated the intensity of protein expression was altered in celiac disease compared to normal biopsy material.

  2. Cell based assay for hypoglycemic drugs screening

    Institute of Scientific and Technical Information of China (English)

    LiZHANG; Juan-juanHU; Guan-huaDU


    OBJECTIVE: To establish a cell based assay for hypoglyc emicdrugs. METHODS: The five cell lines, BALB/c3T3, HepG2, NIH3T3, Be17402, and L929 were incubated with insulin (0-125n mol/L) for 48 h. Their sensitivities to insulin were studied by detecting glucose consumption. The dose-response and time-response relationship between the sensitive cell line (BALB/c 3T3)

  3. Development and validation of a high-throughput cell-based screen to identify activators of a bacterial two-component signal transduction system. (United States)

    van Rensburg, Julia J; Fortney, Kate R; Chen, Lan; Krieger, Andrew J; Lima, Bruno P; Wolfe, Alan J; Katz, Barry P; Zhang, Zhong-Yin; Spinola, Stanley M


    CpxRA is a two-component signal transduction system (2CSTS) found in many drug-resistant Gram-negative bacteria. In response to periplasmic stress, CpxA autophosphorylates and donates a phosphoryl group to its cognate response regulator, CpxR. Phosphorylated CpxR (CpxR-P) upregulates genes involved in membrane repair and downregulates multiple genes that encode virulence factors, which are trafficked across the cell membrane. Mutants that constitutively activate CpxRA in Salmonella enterica serovar Typhimurium and Haemophilus ducreyi are avirulent in mice and humans, respectively. Thus, the activation of CpxRA has high potential as a novel antimicrobial/antivirulence strategy. Using a series of Escherichia coli strains containing a CpxR-P-responsive lacZ reporter and deletions in genes encoding CpxRA system components, we developed and validated a novel cell-based high-throughput screen (HTS) for CpxRA activators. A screen of 36,000 compounds yielded one hit compound that increased reporter activity in wild-type cells. This is the first report of a compound that activates, rather than inhibits, a 2CSTS. The activity profile of the compound against CpxRA pathway mutants in the presence of glucose suggested that the compound inhibits CpxA phosphatase activity. We confirmed that the compound induced the accumulation of CpxR-P in treated cells. Although the hit compound contained a nitro group, a derivative lacking this group retained activity in serum and had lower cytotoxicity than that of the initial hit. This HTS is amenable for the screening of larger libraries to find compounds that activate CpxRA by other mechanisms, and it could be adapted to find activators of other two-component systems.

  4. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation. (United States)

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios


    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

  5. Mammalian Cell-Based Sensor System (United States)

    Banerjee, Pratik; Franz, Briana; Bhunia, Arun K.

    Use of living cells or cellular components in biosensors is receiving increased attention and opens a whole new area of functional diagnostics. The term "mammalian cell-based biosensor" is designated to biosensors utilizing mammalian cells as the biorecognition element. Cell-based assays, such as high-throughput screening (HTS) or cytotoxicity testing, have already emerged as dependable and promising approaches to measure the functionality or toxicity of a compound (in case of HTS); or to probe the presence of pathogenic or toxigenic entities in clinical, environmental, or food samples. External stimuli or changes in cellular microenvironment sometimes perturb the "normal" physiological activities of mammalian cells, thus allowing CBBs to screen, monitor, and measure the analyte-induced changes. The advantage of CBBs is that they can report the presence or absence of active components, such as live pathogens or active toxins. In some cases, mammalian cells or plasma membranes are used as electrical capacitors and cell-cell and cell-substrate contact is measured via conductivity or electrical impedance. In addition, cytopathogenicity or cytotoxicity induced by pathogens or toxins resulting in apoptosis or necrosis could be measured via optical devices using fluorescence or luminescence. This chapter focuses mainly on the type and applications of different mammalian cell-based sensor systems.

  6. Cell-based bioassays in microfluidic systems (United States)

    Itle, Laura J.; Zguris, Jeanna C.; Pishko, Michael V.


    The development of cell-based bioassays for high throughput drug screening or the sensing of biotoxins is contingent on the development of whole cell sensors for specific changes in intracellular conditions and the integration of those systems into sample delivery devices. Here we show the feasibility of using a 5-(and-6)-carboxy SNARF-1, acetoxymethyl ester, acetate, a fluorescent dye capable of responding to changes in intracellular pH, as a detection method for the bacterial endotoxin, lipopolysaccharide. We used photolithography to entrap cells with this dye within poly(ethylene) glyocol diacrylate hydrogels in microfluidic channels. After 18 hours of exposure to lipopolysaccharide, we were able to see visible changes in the fluorescent pattern. This work shows the feasibility of using whole cell based biosensors within microfluidic networks to detect cellular changes in response to exogenous agents.

  7. Computer-aided screening system for cervical precancerous cells based on field emission scanning electron microscopy and energy dispersive x-ray images and spectra (United States)

    Jusman, Yessi; Ng, Siew-Cheok; Hasikin, Khairunnisa; Kurnia, Rahmadi; Osman, Noor Azuan Bin Abu; Teoh, Kean Hooi


    The capability of field emission scanning electron microscopy and energy dispersive x-ray spectroscopy (FE-SEM/EDX) to scan material structures at the microlevel and characterize the material with its elemental properties has inspired this research, which has developed an FE-SEM/EDX-based cervical cancer screening system. The developed computer-aided screening system consisted of two parts, which were the automatic features of extraction and classification. For the automatic features extraction algorithm, the image and spectra of cervical cells features extraction algorithm for extracting the discriminant features of FE-SEM/EDX data was introduced. The system automatically extracted two types of features based on FE-SEM/EDX images and FE-SEM/EDX spectra. Textural features were extracted from the FE-SEM/EDX image using a gray level co-occurrence matrix technique, while the FE-SEM/EDX spectra features were calculated based on peak heights and corrected area under the peaks using an algorithm. A discriminant analysis technique was employed to predict the cervical precancerous stage into three classes: normal, low-grade intraepithelial squamous lesion (LSIL), and high-grade intraepithelial squamous lesion (HSIL). The capability of the developed screening system was tested using 700 FE-SEM/EDX spectra (300 normal, 200 LSIL, and 200 HSIL cases). The accuracy, sensitivity, and specificity performances were 98.2%, 99.0%, and 98.0%, respectively.

  8. A sandwiched microarray platform for benchtop cell-based high throughput screening (United States)

    Wu, Jinhui; Wheeldon, Ian; Guo, Yuqi; Lu, Tingli; Du, Yanan; Wang, Ben; He, Jiankang; Hu, Yiqiao; Khademhosseini, Ali


    The emergence of combinatorial chemistries and the increased discovery of natural compounds have led to the production of expansive libraries of drug candidates and vast numbers of compounds with potentially interesting biological activities. Despite broad interest in high throughput screening (HTS) across varied fields of biological research, there has not been an increase in accessible HTS technologies. Here, we present a simple microarray sandwich system suitable for screening chemical libraries in cell-based assays at the benchtop. The microarray platform delivers chemical compounds to isolated cell cultures by ‘sandwiching’ chemical-laden arrayed posts with cell-seeded microwells. In this way, an array of sealed cell-based assays was generated without cross-contamination between neighboring assays. After chemical exposure, cell viability was analyzed by fluorescence detection of cell viability indicator assays on a per microwell basis in a standard microarray scanner. We demonstrate the efficacy of the system by generating four hits from toxicology screens towards MCF-7 human breast cancer cells. Three of the hits were identified in a combinatorial screen of a library of natural compounds in combination with verapamil, a P-glycoprotein inhibitor. A fourth hit, 9-methoxy-camptothecin, was identified by screening the natural compound library in the absence of verapamil. The method developed here miniaturizes existing HTS systems and enables the screening of a wide array of individual or combinatorial libraries in a reproducible and scalable manner. We anticipate broad application of such a system as it is amenable to combinatorial drug screening in a simple, robust and portable platform. PMID:20965560

  9. A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Yashiroda, Yoko, E-mail: [Chemical Genomics Research Group/Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Okamoto, Reika [Chemical Genomics Research Group/Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Japan Biological Informatics Consortium (JBIC), Koto-ku, Tokyo 135-8073 (Japan); Hatsugai, Kaori [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550 (Japan); Division of Chemotherapy, Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo 105-8512 (Japan); Takemoto, Yasushi [Chemical Genomics Research Group/Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Goshima, Naoki [National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo 135-0064 (Japan); Saito, Tamio [Chemical Biology Core Facility/Antibiotics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Hamamoto, Makiko [Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571 (Japan); Sugimoto, Yoshikazu [Division of Chemotherapy, Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo 105-8512 (Japan); Osada, Hiroyuki [Chemical Biology Core Facility/Antibiotics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Seimiya, Hiroyuki [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550 (Japan); Yoshida, Minoru [Chemical Genomics Research Group/Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); CREST Research Project, Japan Science and Technology Corporation, Saitama 332-0012 (Japan)


    The telomere-associated protein tankyrase 1 is a poly(ADP-ribose) polymerase and is considered to be a promising target for cancer therapy, especially for BRCA-associated cancers. However, an efficient assay system for inhibitor screening has not been established, mainly due to the difficulty of efficient preparation of the enzyme and its substrate. Here, we report a cell-based assay system for detecting inhibitory activity against tankyrase 1. We found that overexpression of the human tankyrase 1 gene causes a growth defect in the fission yeast Schizosaccharomyces pombe. Chemicals that restore the growth defect phenotype can be identified as potential tankyrase 1 inhibitors. We performed a high-throughput screen using this system, and identified flavone as a compound that restores the growth of yeast cells overexpressing tankyrase 1. Indeed, flavone inhibited poly(ADP-ribosyl)ation of proteins caused by overexpression of tankyrase 1 in yeast cells. This system allows rapid identification of inhibitory activity against tankyrase 1 and is amenable to high-throughput screening using robotics.

  10. A Cell-based High-throughput Screening Assay for Farnesoid X Recepter Agonist

    Institute of Scientific and Technical Information of China (English)


    Objective To develop a high-throughput screening assay for Farnesoid X receptor (FXR) agonists based on mammalian one-hybrid system (a chimera receptor gene system) for the purpose of identifying new lead compounds for dyslipidaemia drug from the chemical library. Methods cDNA encoding the human FXR ligand binding domain (LBD) was amplified by RT-PCR from a human liver total mRNA and fused to the DNA binding domain (DBD) of yeast GAL4 of pBIND to construct a GAL4-FXR (LBD) chimera expression plasmid. Five copies of the GAL4 DNA binding site were synthesized and inserted into upstream of the SV40 promoter of pGL3-promoter vector to construct a reporter plasmid pG5-SV40 Luc. The assay was developed by transient co-transfection with pG5-SV40 Luc reporter plasmid and pBIND-FXR-LBD (189-472) chimera expression plasmid. Results After optimization, CDCA, a FXR natural agonist, could induce expression of the luciferase gene in a dose-dependent manner, and had a signal/noise ratio of 10 and Z'factor value of 0.65. Conclusion A stable and sensitive cell-based high-throughput screening model can be used in high-throughput screening for FXR agonists from the synthetic and natural compound library.

  11. Suitability of Cell-Based Label-Free Detection for Cytotoxicity Screening of Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Claudia Meindl


    Full Text Available Cytotoxicity testing of nanoparticles (NPs by conventional screening assays is often complicated by interference. Carbon nanotubes (CNTs are particularly difficult to assess. To test the suitability of cell-based label-free techniques for this application, a panel of CNTs with different diameters and surface functionalizations was assessed by impedance-based technique (xCELLigence RTCA and automated microscopy (Cell-IQ compared to formazan bioreduction (MTS assay. For validation of the label-free systems different concentrations of ethanol and of amine (AMI polystyrene NPs were used. CNTs were evaluated in various cell lines, but only endothelial EAhy926 cells and L929 and V79 fibroblasts could be evaluated in all systems. Polystyrene particles obtained similar results in all assays. All systems identified thin (20 nm CNTs, but detection by xCELLigence system was less sensitive to CNT-induced cytotoxicity. Despite advantages, such as continuous monitoring and more detailed analysis of cytotoxic effects, label-free techniques cannot be generally recommended for cytotoxicity screening of NPs.

  12. A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia.


    Serbus, Laura R.; Frederic Landmann; Bray, Walter M.; Pamela M White; Jordan Ruybal; R Scott Lokey; Alain Debec; William Sullivan


    Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targe...

  13. Development of a cell-based, high-throughput screening assay for ATM kinase inhibitors. (United States)

    Guo, Kexiao; Shelat, Anang A; Guy, R Kiplin; Kastan, Michael B


    The ATM (ataxia-telangiectasia, mutated) protein kinase is a major regulator of cellular responses to DNA double-strand breaks (DSBs), DNA lesions that can be caused by ionizing irradiation (IR), oxidative damage, or exposure to certain chemical agents. In response to DSBs, the ATM kinase is activated and subsequently phosphorylates numerous downstream substrates, including p53, Chk2, BRCA1, and KAP1, which affect processes such as cell cycle progression and DNA repair. Numerous studies have demonstrated that loss of ATM function results in enhanced sensitivity to ionizing irradiation in clinically relevant dose ranges, suggesting that ATM kinase is an attractive therapeutic target for enhancing tumor cell kill with radiotherapy. Previously identified small-molecule ATM kinase inhibitors, such as CP466722 and Ku55933, were identified using in vitro kinase assays carried out with recombinant ATM kinase isolated from mammalian cells. Since it has not been feasible to express full-length recombinant ATM in bacterial or baculovirus systems, a robust in vitro screening tool has been lacking. We have developed a cell-based assay that is robust, straightforward, and sensitive. Using this high-throughput assay, we screened more than 7000 compounds and discovered additional small molecules that inhibit the ATM kinase and further validated these hits by secondary assays.

  14. 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


    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...... 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...... the capability to probe GPCR function at the cellular level with better resolution than has previously been possible, and offer practical strategies for more definitive selectivity evaluation and counter-screening in the early stages of drug discovery. The potential of cell-based translocation assays for GPCR...

  15. Microfluidics for cell-based high throughput screening platforms - A review. (United States)

    Du, Guansheng; Fang, Qun; den Toonder, Jaap M J


    In the last decades, the basic techniques of microfluidics for the study of cells such as cell culture, cell separation, and cell lysis, have been well developed. Based on cell handling techniques, microfluidics has been widely applied in the field of PCR (Polymerase Chain Reaction), immunoassays, organ-on-chip, stem cell research, and analysis and identification of circulating tumor cells. As a major step in drug discovery, high-throughput screening allows rapid analysis of thousands of chemical, biochemical, genetic or pharmacological tests in parallel. In this review, we summarize the application of microfluidics in cell-based high throughput screening. The screening methods mentioned in this paper include approaches using the perfusion flow mode, the droplet mode, and the microarray mode. We also discuss the future development of microfluidic based high throughput screening platform for drug discovery.

  16. Adapting Cell-Based Assays to the High Throughput Screening Platform: Problems Encountered and Lessons Learned. (United States)

    Maddox, Clinton B; Rasmussen, Lynn; White, E Lucile


    In recent years, cell-based phenotypic assays have emerged as an effective and robust addition to the array of assay technologies available for drug discovery in the high throughput screening arena. Previously, biochemical target-based assays have been the technology of choice. With the emergence of stem cells as a basis for a new screening technology, it is important to keep in mind the lessons that have been learned from the adaptation of existing stable cell lines onto the high throughput screening drug discovery platform, with special consideration being given to assay miniaturization, liquid handling complications and instrument-introduced artifacts. We present an overview of the problems encountered with the implementation of multiple cell-based assays at the High Throughput Screening Center at Southern Research Institute as well as empirically defined effective solutions to these problems. These include examples of artifacts induced by temperature differences throughout the screening campaign, cell plating conditions including the effect of room temperature incubation on assay consistency, DMSO carry-over, and incubator induced artifacts.

  17. Establishment of a cell-based assay to screen regulators for Klotho gene promoter

    Institute of Scientific and Technical Information of China (English)

    Zhi-liang XU; Hong GAO; Ke-qing OU-YANG; Shao-xi CAI; Ying-he HU


    AIM: To discover compounds which can regulate Klotho promoter activity. Klotho is an aging suppressor gene. A defect in Klotho gene expression in the mouse results in the phenotype similar to human aging. Recombinant Klotho protein improves age-associated diseases in animal models. It has been proposed that up-regulation of Klotho gene expression may have anti-aging effects. METHODS: Klotho promoter was cloned into a vector containing luciferase gene, and the reporter gene vector was transfected into HEK293 cells to make a stable cell line (HEK293/KL). A model for cellular aging was established by treating HEK293/KL cells with H2O2. These cells were treated with extracts from Traditional Chinese Medicines (TCMs). The luciferase activity was detected to identify compounds that can regulate Klotho promoter. RESULTS:The expression of luciferase in these cells was under control of Klotho promoter and down-regulated after H2O2 treatment The down-regulation of luciferase expression was H2O2 concentration-dependent with an IC50 at approximately 0.006 %. This result demonstrated that the Klotho gene promoter was regulated by oxidative stress. Using the cell-based reporter gene assay, we screened natural product extracts for regulation of Klotho gene promoter. Several extracts were identified that could rescue the H2O2effects and up-regulated Klotho promoter activity. CONCLUSION: A cell -based assay for high-throughput drug screening was established to identify compounds that regulate Klotho promoter activity, and several hits were discovered from natural products. Further characterization of these active extracts could help to investigate Klotho function and aging mechanisms.

  18. A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia. (United States)

    Serbus, Laura R; Landmann, Frederic; Bray, Walter M; White, Pamela M; Ruybal, Jordan; Lokey, R Scott; Debec, Alain; Sullivan, William


    Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts.

  19. A cell-based method for screening RNA-protein interactions: identification of constitutive transport element-interacting proteins.

    Directory of Open Access Journals (Sweden)

    Robert L Nakamura

    Full Text Available We have developed a mammalian cell-based screening platform to identify proteins that assemble into RNA-protein complexes. Based on Tat-mediated activation of the HIV LTR, proteins that interact with an RNA target elicit expression of a GFP reporter and are captured by fluorescence activated cell sorting. This "Tat-hybrid" screening platform was used to identify proteins that interact with the Mason Pfizer monkey virus (MPMV constitutive transport element (CTE, a structured RNA hairpin that mediates the transport of unspliced viral mRNAs from the nucleus to the cytoplasm. Several hnRNP-like proteins, including hnRNP A1, were identified and shown to interact with the CTE with selectivity in the reporter system comparable to Tap, a known CTE-binding protein. In vitro gel shift and pull-down assays showed that hnRNP A1 is able to form a complex with the CTE and Tap and that the RGG domain of hnRNP A1 mediates binding to Tap. These results suggest that hnRNP-like proteins may be part of larger export-competent RNA-protein complexes and that the RGG domains of these proteins play an important role in directing these binding events. The results also demonstrate the utility of the screening platform for identifying and characterizing new components of RNA-protein complexes.

  20. Cell-based microfluidic platform for mimicking human olfactory system. (United States)

    Lee, Seung Hwan; Oh, Eun Hae; Park, Tai Hyun


    Various attempts have been made to mimic the human olfactory system using human olfactory receptors (hORs). In particular, OR-expressed cell-based odorant detection systems mimic the smell sensing mechanism of humans, as they exploit endogenous cellular signaling pathways. However, the majority of such cell-based studies have been performed in the liquid phase to maintain cell viability, and liquid odorants were used as detection targets. Here, we present a microfluidic device for the detection of gaseous odorants which more closely mimics the human olfactory system. Cells expressing hOR were cultured on a porous membrane. The membrane was then flipped over and placed between two compartments. The upper compartment is the gaseous part where gaseous odorants are supplied, while the lower compartment is the aqueous part where viable cells are maintained in the liquid medium. Using this simple microfluidic device, we were able to detect gaseous odorant molecules by a fluorescence signal. The fluorescence signal was generated by calcium influx resulting from the interaction between odorant molecules and the hOR. The system allowed detection of gaseous odorant molecules in real-time, and the findings showed that the fluorescence responses increased dose-dependently in the range of 0-2 ppm odorant. In addition, the system can discriminate among gaseous odorant molecules. This microfluidic system closely mimics the human olfactory system in the sense that the submerged cells detect gaseous odorants.

  1. A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening. (United States)

    Chi, Taiyun; Park, Jong Seok; Butts, Jessica C; Hookway, Tracy A; Su, Amy; Zhu, Chengjie; Styczynski, Mark P; McDevitt, Todd C; Wang, Hua


    In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, cellular impedance mapping, optical detection with shadow imaging and bioluminescence sensing, and thermal monitoring. The sensor array consists of nine parallel pixel groups and nine corresponding signal conditioning blocks. Each pixel group comprises one temperature sensor and 16 tri-modality sensor pixels, while each tri-modality sensor pixel can be independently configured for extracellular voltage recording, cellular impedance measurement (voltage excitation/current sensing), and optical detection. This sensor array supports multi-modality cellular sensing at the pixel level, which enables holistic cell characterization and joint-modality physiological monitoring on the same cellular sample with a pixel resolution of 80 μm × 100 μm. Comprehensive biological experiments with different living cell samples demonstrate the functionality and benefit of the proposed multi-modality sensing in cell-based assay and drug screening.

  2. NSC23925, identified in a high-throughput cell-based screen, reverses multidrug resistance.

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    Zhenfeng Duan

    Full Text Available BACKGROUND: Multidrug resistance (MDR is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically. METHODOLOGY/PRINCIPAL FINDINGS: To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1 but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors. CONCLUSIONS/SIGNIFICANCE: The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients.

  3. Identification of novel radiosensitizers in a high-throughput, cell-based screen for DSB repair inhibitors. (United States)

    Goglia, Alexander G; Delsite, Robert; Luz, Antonio N; Shahbazian, David; Salem, Ahmed F; Sundaram, Ranjini K; Chiaravalli, Jeanne; Hendrikx, Petrus J; Wilshire, Jennifer A; Jasin, Maria; Kluger, Harriet M; Glickman, J Fraser; Powell, Simon N; Bindra, Ranjit S


    Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved to repair these lesions, and successful DSB repair is essential for tumor cell survival after exposure to ionizing radiation (IR) and other DNA-damaging agents. As such, inhibition of DNA repair is a potentially efficacious strategy for chemo- and radiosensitization. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. Here, we report the design and execution of a high-throughput, cell-based small molecule screen for novel DSB repair inhibitors. We miniaturized our recently developed dual NHEJ and HR reporter system into a 384-well plate-based format and interrogated a diverse library of 20,000 compounds for molecules that selectively modulate NHEJ and HR repair in tumor cells. We identified a collection of novel hits that potently inhibit DSB repair, and we have validated their functional activity in a comprehensive panel of orthogonal secondary assays. A selection of these inhibitors was found to radiosensitize cancer cell lines in vitro, which suggests that they may be useful as novel chemo- and radio sensitizers. Surprisingly, we identified several FDA-approved drugs, including the calcium channel blocker mibefradil dihydrochloride, that demonstrated activity as DSB repair inhibitors and radiosensitizers. These findings suggest the possibility for repurposing them as tumor cell radiosensitizers in the future. Accordingly, we recently initiated a phase I clinical trial testing mibefradil as a glioma radiosensitizer.

  4. Photonic crystal enhanced silicon cell based thermophotovoltaic systems. (United States)

    Yeng, Yi Xiang; Chan, Walker R; Rinnerbauer, Veronika; Stelmakh, Veronika; Senkevich, Jay J; Joannopoulos, John D; Soljacic, Marin; Čelanović, Ivan


    We report the design, optimization, and experimental results of large area commercial silicon solar cell based thermophotovoltaic (TPV) energy conversion systems. Using global non-linear optimization tools, we demonstrate theoretically a maximum radiative heat-to-electricity efficiency of 6.4% and a corresponding output electrical power density of 0.39 W cm(-2) at temperature T = 1660 K when implementing both the optimized two-dimensional (2D) tantalum photonic crystal (PhC) selective emitter, and the optimized 1D tantalum pentoxide - silicon dioxide PhC cold-side selective filter. In addition, we have developed an experimental large area TPV test setup that enables accurate measurement of radiative heat-to-electricity efficiency for any emitter-filter-TPV cell combination of interest. In fact, the experimental results match extremely well with predictions of our numerical models. Our experimental setup achieved a maximum output electrical power density of 0.10W cm(-2) and radiative heat-to-electricity efficiency of 1.18% at T = 1380 K using commercial wafer size back-contacted silicon solar cells.

  5. T cell-based functional cDNA library screening identified SEC14-like 1a carboxy-terminal domain as a negative regulator of human immunodeficiency virus replication. (United States)

    Urano, Emiko; Ichikawa, Reiko; Morikawa, Yuko; Yoshida, Takeshi; Koyanagi, Yoshio; Komano, Jun


    Genome-wide screening of host factors that regulate HIV-1 replication has been attempted using numerous experimental approaches. However, there has been limited success using T cell-based cDNA library screening to identify genes that regulate HIV-1 replication. We have established a genetic screening strategy using the human T cell line MT-4 and a replication-competent HIV-1. With this system, we identified the C-terminal domain (CTD) of SEC14-like 1a (SEC14L1a) as a novel inhibitor of HIV-1 replication. Our T cell-based cDNA screening system provides an alternative tool for identifying novel regulators of HIV-1 replication.

  6. An efficient strategy for cell-based antibody library selection using an integrated vector system

    Directory of Open Access Journals (Sweden)

    Yoon Hyerim


    Full Text Available Abstract Background Cell panning of phage-displayed antibody library is a powerful tool for the development of therapeutic and imaging agents since disease-related cell surface proteins in native complex conformation can be directly targeted. Here, we employed a strategy taking advantage of an integrated vector system which allows rapid conversion of scFv-displaying phage into scFv-Fc format for efficient cell-based scFv library selection on a tetraspanin protein, CD9. Results A mouse scFv library constructed by using a phagemid vector, pDR-D1 was subjected to cell panning against stable CD9 transfectant, and the scFv repertoire from the enriched phage pool was directly transferred to a mammalian cassette vector, pDR-OriP-Fc1. The resulting constructs enabled transient expression of enough amounts of scFv-Fcs in HEK293E cells, and flow cytometric screening of binders for CD9 transfectant could be performed simply by using the culture supernatants. All three clones selected from the screening showed correct CD9-specificity. They could immunoprecipitate CD9 molecules out of the transfectant cell lysate and correctly stain endogenous CD9 expression on cancer cell membrane. Furthermore, competition assay with a known anti-CD9 monoclonal antibody (mAb suggested that the binding epitopes of some of them overlap with that of the mAb which resides within the large extracellular loop of CD9. Conclusions This study demonstrates that scFv-Fc from mammalian transient expression can be chosen as a reliable format for rapid screening and validation in cell-based scFv library selection, and the strategy described here will be applicable to efficient discovery of antibodies to diverse cell-surface targets.

  7. Modeling and control of fuel cell based distributed generation systems (United States)

    Jung, Jin Woo

    This dissertation presents circuit models and control algorithms of fuel cell based distributed generation systems (DGS) for two DGS topologies. In the first topology, each DGS unit utilizes a battery in parallel to the fuel cell in a standalone AC power plant and a grid-interconnection. In the second topology, a Z-source converter, which employs both the L and C passive components and shoot-through zero vectors instead of the conventional DC/DC boost power converter in order to step up the DC-link voltage, is adopted for a standalone AC power supply. In Topology 1, two applications are studied: a standalone power generation (Single DGS Unit and Two DGS Units) and a grid-interconnection. First, dynamic model of the fuel cell is given based on electrochemical process. Second, two full-bridge DC to DC converters are adopted and their controllers are designed: an unidirectional full-bridge DC to DC boost converter for the fuel cell and a bidirectional full-bridge DC to DC buck/boost converter for the battery. Third, for a three-phase DC to AC inverter without or with a Delta/Y transformer, a discrete-time state space circuit model is given and two discrete-time feedback controllers are designed: voltage controller in the outer loop and current controller in the inner loop. And last, for load sharing of two DGS units and power flow control of two DGS units or the DGS connected to the grid, real and reactive power controllers are proposed. Particularly, for the grid-connected DGS application, a synchronization issue between an islanding mode and a paralleling mode to the grid is investigated, and two case studies are performed. To demonstrate the proposed circuit models and control strategies, simulation test-beds using Matlab/Simulink are constructed for each configuration of the fuel cell based DGS with a three-phase AC 120 V (L-N)/60 Hz/50 kVA and various simulation results are presented. In Topology 2, this dissertation presents system modeling, modified space

  8. A novel cell-based duplex high-throughput screening assay combining fluorescent Ca(2+) measurement with homogeneous time-resolved fluorescence technology. (United States)

    Kiss, László; Cselenyák, Attila; Varga, Ágnes; Visegrády, András


    Cell-based assays for G-protein-coupled receptor (GPCR) activation applied in high-throughput screening (HTS) monitor various readouts for second messengers or intracellular effectors. Recently, our understanding of diverging signaling pathways downstream of receptor activation and the capability of small molecules to selectively modulate signaling routes has increased substantially, underlining the importance of selecting appropriate readouts in cellular functional screens. To minimize the rate of false negatives in large-scale screening campaigns, it is crucial to maximize the chance of a ligand being detected, and generally applicable methods for detecting multiple analytes from a single well might serve this purpose. The few assays developed so far based on multiplexed GPCR readouts are limited to only certain applications and usually rely on genetic manipulations hindering screening in native or native-like cellular systems. Here we describe a more generally applicable and HTS-compatible homogeneous assay based on the combination of fluorometric detection of [Ca(2+)] with subsequent homogeneous time-resolved fluorescence (HTRF) cAMP readout in the same well. Besides describing development and validation of the assay, using a cell line recombinantly expressing the human PTH1 receptor screening of a small library is also presented, demonstrating the robustness and HTS compatibility of the novel paradigm.

  9. 1Click1View: Interactive Visualization Methodology for RNAi Cell-Based Microscopic Screening

    Directory of Open Access Journals (Sweden)

    Lukasz Zwolinski


    Full Text Available Technological advancements are constantly increasing the size and complexity of data resulting from large-scale RNA interference screens. This fact has led biologists to ask complex questions, which the existing, fully automated analyses are often not adequate to answer. We present a concept of 1Click1View (1C1V as a methodology for interactive analytic software tools. 1C1V can be applied for two-dimensional visualization of image-based screening data sets from High Content Screening (HCS. Through an easy-to-use interface, one-click, one-view concept, and workflow based architecture, visualization method facilitates the linking of image data with numeric data. Such method utilizes state-of-the-art interactive visualization tools optimized for fast visualization of large scale image data sets. We demonstrate our method on an HCS dataset consisting of multiple cell features from two screening assays.

  10. Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents. (United States)

    Wang, Tong; Sepulveda, Mario; Gonzales, Paul; Gately, Stephen


    A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models.

  11. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier (United States)

    Claveria-Gimeno, Rafael; Vega, Sonia; Grazu, Valeria; de la Fuente, Jesús M; Lanas, Angel; Velazquez-Campoy, Adrian; Abian, Olga


    In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with γ-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while γ-cyclodextrin did not show antiviral activity by itself). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solution, but its γ-cyclodextrin complex exhibited a 50% effective concentration of 5 μM. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using γ-cyclodextrin as carrier molecule. PMID:25834436

  12. High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling

    Directory of Open Access Journals (Sweden)

    Du Peige


    Full Text Available Abstract Background Estrogen receptor α (ERα is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ERα, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE with a reporter gene. This allowed the cellular activity of ERα, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2. Results From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131 as a repressor of ERα mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ERα in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERα interrupts or prevents ERα binding to the estrogen response element (ERE. In addition, ZNF131 was able to suppress the expression of pS2, an ERα target gene. Conclusion We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ERα-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ERα regulation in mammalian cells.

  13. Demonstration of a visual cell-based assay for screening glucose transporter 4 translocation modulators in real time

    Indian Academy of Sciences (India)

    Maleppillil Vavachan Vijayakumar; Amrendra Kumar Ajay; Manoj Kumar Bhat


    Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to cell membrane leading to glucose uptake is the rate-limiting step in diabetes. It is also a defined target of antidiabetic drug research. Existing GLUT4 translocation assays are based on time-consuming immunoassays and are hampered by assay variability and low sensitivity. We describe a real-time, visual, cell-based qualitative GLUT4 translocation assay using CHO-HIRc-myc-GLUT4eGFP cells that stably express myc- and eGFP-tagged GLUT4 in addition to human insulin receptor (HIRc). GLUT4 translocation is visualized by live cell imaging based on GFP fluorescence by employing a cooled charge-coupled device camera attached to a fluorescent microscope. This video imaging method and further quantitative analysis of GLUT4 on the cell membrane provide rapid and foolproof visual evidence that this method is suitable for screening GLUT4 translocation modulators.

  14. Screening in quantum charged systems (United States)

    Martin, Ph. A.; Gruber, Ch.


    For stationary states of quantum charged systems in ν dimensions, ν>=2, it is proven that the reduced-density matrices satisfy a set of sum rules whenever the clustering is faster than |x|-(ν+l). These sum rules, describing the screening properties, are analogous to those previously derived for classical systems. For neutral quantum fluids, it is shown that the clustering cannot be faster than the decay of the force.

  15. Cell-Based Screen Identifies Human Interferon-Stimulated Regulators of Listeria monocytogenes Infection (United States)

    Eitson, Jennifer L.; Chen, Didi; Jimenez, Alyssa; Mettlen, Marcel; Schoggins, John W.; Alto, Neal M.


    The type I interferon (IFN) activated transcriptional response is a critical antiviral defense mechanism, yet its role in bacterial pathogenesis remains less well characterized. Using an intracellular pathogen Listeria monocytogenes (Lm) as a model bacterial pathogen, we sought to identify the roles of individual interferon-stimulated genes (ISGs) in context of bacterial infection. Previously, IFN has been implicated in both restricting and promoting Lm growth and immune stimulatory functions in vivo. Here we adapted a gain-of-function flow cytometry based approach to screen a library of more than 350 human ISGs for inhibitors and enhancers of Lm infection. We identify 6 genes, including UNC93B1, MYD88, AQP9, and TRIM14 that potently inhibit Lm infection. These inhibitors act through both transcription-mediated (MYD88) and non-transcriptional mechanisms (TRIM14). Further, we identify and characterize the human high affinity immunoglobulin receptor FcγRIa as an enhancer of Lm internalization. Our results reveal that FcγRIa promotes Lm uptake in the absence of known host Lm internalization receptors (E-cadherin and c-Met) as well as bacterial surface internalins (InlA and InlB). Additionally, FcγRIa-mediated uptake occurs independently of Lm opsonization or canonical FcγRIa signaling. Finally, we established the contribution of FcγRIa to Lm infection in phagocytic cells, thus potentially linking the IFN response to a novel bacterial uptake pathway. Together, these studies provide an experimental and conceptual basis for deciphering the role of IFN in bacterial defense and virulence at single-gene resolution. PMID:28002492

  16. Immune cell-based screening assay for response to anticancer agents: applications in pharmacogenomics

    Directory of Open Access Journals (Sweden)

    Frick A


    Full Text Available Amber Frick,1 Yuri Fedoriw,2 Kristy Richards,3,4 Blossom Damania,3,5 Bethany Parks,6 Oscar Suzuki,1 Cristina S Benton,1 Emmanuel Chan,1 Russell S Thomas,7 Tim Wiltshire1,3 1Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, 2Department of Pathology and Laboratory Medicine, School of Medicine, 3Lineberger Comprehensive Cancer Center, School of Medicine, 4Department of Genetics, School of Medicine, 5Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA; 6The Hamner Institutes for Health Sciences, 7Environmental Protection Agency, Research Triangle Park, NC, USA Background: Interpatient variability in immune and chemotherapeutic cytotoxic responses is likely due to complex genetic differences and is difficult to ascertain in humans. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at examining interstrain differences in viability on normal, noncancerous immune cells following chemotherapeutic cytotoxic insult. Drug effects were investigated by comparing selective chemotherapeutic agents, such as BEZ-235 and selumetinib, against conventional cytotoxic agents targeting multiple pathways, including doxorubicin and idarubicin. Methods: Splenocytes were isolated from 36 isogenic strains of mice using standard procedures. Of note, the splenocytes were not stimulated to avoid attributing responses to pathways involved with cellular stimulation rather than toxicity. Cells were incubated with compounds on a nine-point logarithmic dosing scale ranging from 15 nM to 100 µM (37°C, 5% CO2. At 4 hours posttreatment, cells were labeled with antibodies and physiological indicator dyes and fixed with 4% paraformaldehyde. Cellular phenotypes (eg, viability were collected and analyzed using flow cytometry. Dose-response curves with response normalized to the zero dose as a function of log concentration

  17. Cell Based GIS as Cellular Automata for Disaster Spreading Predictions and Required Data Systems

    Directory of Open Access Journals (Sweden)

    Kohei Arai


    Full Text Available A method for prediction and simulation based on the Cell Based Geographic Information System(GIS as Cellular Automata (CA is proposed together with required data systems, in particular metasearch engine usage in an unified way. It is confirmed that the proposed cell based GIS as CA has flexible usage of the attribute information that is attached to the cell in concert with location information and does work for disaster spreading simulation and prediction.

  18. Research on Software-Cell-Based Software System

    Institute of Scientific and Technical Information of China (English)


    The aim of research on software architecture is to improve the quality attributes of software sys tems, such as security, reliability, maintainability, testability , reassembility , evolvability. However, a sin gle running system is hard to achieve all these goals. In this paper, software-cell is introduced as the basic u nit throughout developing process. Then it is further advanced that a robust, safe and high-quality software system is composed of a running system and four supportive systems. This paper especially discusses the structure of software-cell, the construction of the five systems, and the relations between them.

  19. Iterative Cellular Screening System for Nanoparticle Safety Testing

    Directory of Open Access Journals (Sweden)

    Franziska Sambale


    Full Text Available Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimic in vivo conditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

  20. A Reconfigurable Logic Cell Based on a Simple Dynamical System

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    Lixiang Li


    Full Text Available This paper introduces a new scheme to achieve a dynamic logic gate which can be adjusted flexibly to obtain different logic functions by adjusting specific parameters of a dynamical system. Based on graphical tools and the threshold mechanism, the distribution of different logic gates is studied, and a transformation method between different logics is given. Analyzing the performance of the dynamical system in the presence of noise, we discover that it is resistant to system noise. Moreover, we find some part of the system can be considered as a leaky integrator which has been already widely applied in engineering. Finally, we provide a proof-of-principle hardware implementation of the proposed scheme to illustrate its effectiveness. With the proposed scheme in hand, it is convenient to build the flexible, robust, and general purpose computing devices such as various network coding routers, communication encoders or decoders, and reconfigurable computer chips.

  1. Rescue the failed half-ZFN by a sensitive mammalian cell-based luciferase reporter system.

    Directory of Open Access Journals (Sweden)

    Weifeng Zhang

    Full Text Available ZFN technology is a powerful research tool and has been used for genome editing in cells lines, animals and plants. The generation of functional ZFNs for particular targets in mammalian genome is still challenging for an average research group. The modular-assembly method is relatively fast, easy-to-practice but has a high failure rate. Some recent studies suggested that a ZFP with low binding activity might be able to form a working ZFN pair with another binding active half-ZFP. In order to unveil the potential ZFP candidates among those with low binding activities, this paper established a highly sensitive mammalian cell-based transcriptional reporter system to assess the DNA binding activities of ZFPs by inserting multiple copies of ZFN target sequence fragment (TSF of an interested gene (e. g., hPGRN or hVEGF. Our results showed that this system increased the screening sensitivity up to 50-fold and markedly amplified the differences in the binding activities between different ZFPs. We also found that the targeted chromosomal gene repair efficiency of each hPGRN or hVEGF ZFN pair was in proportion with the combination of the binding activities of the ZFL (Left zinc finger and ZFR (Right zinc finger. A hPGRN ZFR with low binding ability was able to form a biological active ZFN if combined with a hPGRN ZFL with relatively high binding ability. Lastly, site-specific genome editing by hPGRN ZFNs generated by this system was confirmed by sequencing, and the PGRN knock-out cell line showed significantly decreased cell growth compared with the control. Our system will provide a valuable tool for further optimizing the nucleases with regard to specificity and cytotoxicity.

  2. A cell-based model system links chromothripsis with hyperploidy

    DEFF Research Database (Denmark)

    Mardin, Balca R; Drainas, Alexandros P; Waszak, Sebastian M;


    A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has...... remained elusive. We developed an integrative method termed "complex alterations after selection and transformation (CAST)," enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively...... parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular...

  3. Photoelectrochemical cells based on photosynthetic systems: a review

    Directory of Open Access Journals (Sweden)

    Roman A. Voloshin


    Full Text Available Photosynthesis is a process which converts light energy into energy contained in the chemical bonds of organic compounds by photosynthetic pigments such as chlorophyll (Chl a, b, c, d, f or bacteriochlorophyll. It occurs in phototrophic organisms, which include higher plants and many types of photosynthetic bacteria, including cyanobacteria. In the case of the oxygenic photosynthesis, water is a donor of both electrons and protons, and solar radiation serves as inexhaustible source of energy. Efficiency of energy conversion in the primary processes of photosynthesis is close to 100%. Therefore, for many years photosynthesis has attracted the attention of researchers and designers looking for alternative energy systems as one of the most efficient and eco-friendly pathways of energy conversion. The latest advances in the design of optimal solar cells include the creation of converters based on thylakoid membranes, photosystems, and whole cells of cyanobacteria immobilized on nanostructured electrode (gold nanoparticles, carbon nanotubes, nanoparticles of ZnO and TiO2. The mode of solar energy conversion in photosynthesis has a great potential as a source of renewable energy while it is sustainable and environmentally safety as well. Application of pigments such as Chl f and Chl d (unlike Chl a and Chl b, by absorbing the far red and near infrared region of the spectrum (in the range 700-750 nm, will allow to increase the efficiency of such light transforming systems. This review article presents the last achievements in the field of energy photoconverters based on photosynthetic systems.

  4. Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay

    Directory of Open Access Journals (Sweden)

    Atsuya Yamashita


    Full Text Available The current treatments of chronic hepatitis B (CHB face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV. We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95% and low cytotoxicity (66% to 77%. Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy-phenol (compound 1 and 3,4,5-tribromo-2-(2,4-dibromophenoxy-phenol (compound 2, which are classified as polybrominated diphenyl ethers (PBDEs, were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 µM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs.

  5. Microfluidic cell culture systems with integrated sensors for drug screening (United States)

    Grist, Samantha; Yu, Linfen; Chrostowski, Lukas; Cheung, Karen C.


    Cell-based testing is a key step in drug screening for cancer treatments. A microfluidic platform can permit more precise control of the cell culture microenvironment, such as gradients in soluble factors. These small-scale devices also permit tracking of low cell numbers. As a new screening paradigm, a microscale system for integrated cell culture and drug screening promises to provide a simple, scalable tool to apply standardized protocols used in cellular response assays. With the ability to dynamically control the microenvironment, we can create temporally varying drug profiles to mimic physiologically measured profiles. In addition, low levels of oxygen in cancerous tumors have been linked with drug resistance and decreased likelihood of successful treatment and patient survival. Our work also integrates a thin-film oxygen sensor with a microfluidic oxygen gradient generator which will in future allow us to create spatial oxygen gradients and study effects of hypoxia on cell response to drug treatment. In future, this technology promises to improve cell-based validation in the drug discovery process, decreasing the cost and increasing the speed in screening large numbers of compounds.

  6. Establishment of a cell-based assay system for hepatitis C virus serine protease and its primary applications

    Institute of Scientific and Technical Information of China (English)

    Hong-Xia Mao; Shui-Yun Lan; Yun-Wen Hu; Li Xiang; Zheng-Hong Yuan


    AIM: To establish an efficient, sensitive, cell-based assay system for NS3 serine protease in an effort to study further the property of hepatitis C virus (HCV) and develop new antiviral agents.METHOOS: We constructed pCI-neo-NS3/4A-SEAP chimeric plasmid, in which the secreted alkaline phosphatase (SEAP) was fused in-frame to the downstream of NS4A/4B cleavage site. The protease activity of NS3 was reflected by the activity of SEAP in the culture media of transient or stable expression cells. Stably expressing cell lines were obtained by G418 selection. Pefabloc SC, a potent irreversible serine protease inhibitor, was used to treat the stably expressing cell lines to assess the system for screening NS3 inhibitors. To compare the activity of serine proteases from 1b and 1a, two chimeric clones were constructed and introduced into both transient and stable expression systems.RESULTS: The SEAP activity in the culture media could be detected in both transient and stable expression systems,and was apparently decreased after Pefabloc SC treatment.In both transient and stable systems, NS3/4A-SEAP chimeric gene from HCV genotype 1b produced higher SEAP activity in the culture media than that from 1a.CONCLUSION: The cell-based system is efficient and sensitive enough for detection and comparison of NS3 protease activity, and screening of anti-NS3 inhibitors. The functional difference between NS3/4A from 1a and 1b subtypes revealed by this system provides a clue for further investigations.

  7. Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening (United States)

    Chen, Shuai; Zhou, Jinfeng; Cai, Yingying; Zheng, Xinyuan; Xie, Sirong; Liao, Yuhan; Zhu, Yu; Qin, Chaoyan; Lai, Weiming; Yang, Cuixia; Xie, Xin; Du, Changsheng


    Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs’ cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1β during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy. PMID:28272439

  8. Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening. (United States)

    Chen, Shuai; Zhou, Jinfeng; Cai, Yingying; Zheng, Xinyuan; Xie, Sirong; Liao, Yuhan; Zhu, Yu; Qin, Chaoyan; Lai, Weiming; Yang, Cuixia; Xie, Xin; Du, Changsheng


    Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs' cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1β during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy.

  9. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Directory of Open Access Journals (Sweden)

    Claveria-Gimeno R


    Full Text Available Rafael Claveria-Gimeno,1–3 Sonia Vega,3 Valeria Grazu,4 Jesús M de la Fuente,4–6 Angel Lanas,2,8–10 Adrian Velazquez-Campoy,2,3,7 Olga Abian1–3,8 1Instituto Aragonés de Ciencias de la Salud (IACS, Zaragoza, Spain; 2IIS Aragón, Zaragoza, Spain; 3Institute of Biocomputation and Physics of Complex Systems (BIFI, Joint Unit IQFR-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain; 4Instituto de Nanociencia de Aragon (INA, Universidad de Zaragoza, Zaragoza, Spain; 5Instituto de Ciencia de Materiales de Aragón (ICMA, CSIC-Universidad de Zaragoza, Zaragoza, Spain; 6Institute NanoBiomedicine and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Fundacion ARAID, Government of Aragon, Spain; 8Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd, Barcelona, Spain; 9Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; 10Department of Medicine, University of Zaragoza, Zaragoza, Spain Abstract: In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction

  10. Cell-Based Screening: Cellular Assays with a Molecular Endpoint Measured by SAMDI Mass Spectrometry (Small 28/2016). (United States)

    Berns, Eric J; Cabezas, Maria D; Mrksich, Milan


    On page 3811, M. Mrksich and co-workers culture cells using self-assembled monolayers presenting cell adhesion ligands and enzyme substrates. A lysis buffer disrupts the cell membranes, releasing enzymes that modify the immobilized substrates. These modifications can be measured with SAMDI mass spectrometry, giving a high-throughput, cell-based assay.

  11. Intelligent Screening Systems for Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Yessi Jusman


    Full Text Available Advent of medical image digitalization leads to image processing and computer-aided diagnosis systems in numerous clinical applications. These technologies could be used to automatically diagnose patient or serve as second opinion to pathologists. This paper briefly reviews cervical screening techniques, advantages, and disadvantages. The digital data of the screening techniques are used as data for the computer screening system as replaced in the expert analysis. Four stages of the computer system are enhancement, features extraction, feature selection, and classification reviewed in detail. The computer system based on cytology data and electromagnetic spectra data achieved better accuracy than other data.

  12. Cell-based screening identifies the active ingredients from Traditional Chinese Medicine formula Shixiao San as the inhibitors of atherosclerotic endothelial dysfunction.

    Directory of Open Access Journals (Sweden)

    Xiaofan Wang

    Full Text Available In this study, we performed a phenotypic screening in human endothelial cells exposed to oxidized low density lipoprotein (an in vitro model of atherosclerotic endothelial dysfunction to identify the effective compounds in Shixiao San. After investigating the suitability and reliability of the cell-based screening method using atorvastatin as the positive control drug, this method was applied in screening Shixiao San and its extracts. The treatment of n-butanol fraction on endothelial cells exhibited stronger healing effects against oxidized low density lipoprotein-induced insult when compared with other fractions. Cell viability, the level of nitric oxide, endothelial nitric oxide synthase and endothelin-1 were measured, respectively. The assays revealed n-butanol fraction significantly elevated the survival ratio of impaired cells in culture. In parallel, n-butanol fraction exhibited the highest inhibition of inflammation. The generation of prostaglandin-2 and adhesion molecule (soluble intercellular adhesion molecule-1 was obviously declined. Furthermore, n-butanol fraction suppressed the production of reactive oxygen species and malondialdehyde, and restored the activity of superoxide dismutase. Compounds identification of the n-butanol fraction was carried out by ultra high liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The active ingredients including quercetin-3-O-(2G-α-l-rhamnosyl-rutinoside, quercetin-3-O-neohesperidoside, isorhamnetin-3-O-neohesperidoside and isorhamnetin-3-O-rutinoside revealed the ability of anti-atherosclerosis after exposing on endothelial cells. The current work illustrated the pharmacology effect of Shixiao San and clearly indicated the major active components in Shixiao San. More importantly, the proposed cell-based screening method might be particularly suitable for fast evaluating the anti-atherosclerosis efficacy of Traditional Chinese Medicines and screening out the


    Institute of Scientific and Technical Information of China (English)



    In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.


    Institute of Scientific and Technical Information of China (English)



    In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.``

  15. A Cell-Based Approach for the Biosynthesis/Screening of Cyclic Peptide Libraries against Bacterial Toxins

    Energy Technology Data Exchange (ETDEWEB)

    Camarero, J A; Kimura, R; Woo, Y; Cantor, J; Steenblock, E


    Available methods for developing and screening small drug-like molecules able to knockout toxins or pathogenic microorganisms have some limitations. In order to be useful, these new methods must provide high-throughput analysis and identify specific binders in a short period of time. To meet this need, we are developing an approach that uses living cells to generate libraries of small biomolecules, which are then screened inside the cell for activity. Our group is using this new, combined approach to find highly specific ligands capable of disabling anthrax Lethal Factor (LF) as proof of principle. Key to our approach is the development of a method for the biosynthesis of libraries of cyclic peptides, and an efficient screening process that can be carried out inside the cell.

  16. A small molecule screen for enhanced homing of systemically infused cells (United States)

    Tong, Zhixiang; Perrault, Christelle; Benhamou, Brigitte; Zhang, Jidong; Stratton, Tara; Han, Edward; Safaee, Helia; Musabeyezu, Juliet; Yang, Zijiang; Multon, Marie-Christine; Rothblatt, Jonathan; Deleuze, Jean-Francois; Lin, Charles P.; Karp, Jeffrey M.


    SUMMARY Poor homing of systemically infused cells to disease sites may limit the success of exogenous cell-based therapy. In this study, we screened 9,000 signal transduction modulators to identify hits that increase mesenchymal stromal cell (MSC) surface expression of homing ligands that bind to ICAM-1, such as CD11a. Pretreatment of MSCs with Ro-31-8425, an identified hit from this screen, increased MSC firm adhesion to an ICAM-1-coated substrate in-vitro, and enabled targeted delivery of systemically administered MSCs to inflamed sites in-vivo in a CD11a (and other ICAM-1-binding domains)-dependent manner. This resulted in a heightened anti-inflammatory response. This represents a new strategy for engineering cell homing to enhance therapeutic efficacy and validates CD11a/ICAM-1 as potential targets. Altogether, this multi-step screening process may significantly improve clinical outcomes of cell-based therapies. PMID:25732817

  17. Updating Interconnection Screens for PV System Integration

    Energy Technology Data Exchange (ETDEWEB)

    Coddington, M.; Mather, B.; Kroposki, B.; Lynn, K.; Razon, A.; Ellis, A.; Hill, R.; Key, T.; Nicole, K.; Smith, J.


    This white paper evaluates the origins and usefulness of the capacity penetration screen, offer short-term solutions which could effectively allow fast-track interconnection to many PV system applications, and considers longer-term solutions for increasing PV deployment levels in a safe and reliable manner while reducing or eliminating the emphasis on the penetration screen. Short-term and longer-term alternatives approaches are offered as examples; however, specific modifications to screening procedures should be discussed with stakeholders and must ultimately be adopted by state and federal regulatory bodies.

  18. Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen

    Directory of Open Access Journals (Sweden)

    Mark S. McClain


    Full Text Available The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for countering the cytotoxic activity of the toxin in exposed individuals. Using a robust cell-based high-throughput screening (HTS assay, we screened a 151,616-compound library for the ability to inhibit e-toxin-induced cytotoxicity. Survival of MDCK cells exposed to the toxin was assessed by addition of resazurin to detect metabolic activity in surviving cells. The hit rate for this screen was 0.6%. Following a secondary screen of each hit in triplicate and assays to eliminate false positives, we focused on three structurally-distinct compounds: an N-cycloalkylbenzamide, a furo[2,3-b]quinoline, and a 6H-anthra[1,9-cd]isoxazol. None of the three compounds appeared to inhibit toxin binding to cells or the ability of the toxin to form oligomeric complexes. Additional assays demonstrated that two of the inhibitory compounds inhibited ε-toxin-induced permeabilization of MDCK cells to propidium iodide. Furthermore, the two compounds exhibited inhibitory effects on cells pre-treated with toxin. Structural analogs of one of the inhibitors identified through the high-throughput screen were analyzed and provided initial structure-activity data. These compounds should serve as the basis for further structure-activity refinement that may lead to the development of effective anti-ε-toxin therapeutics.

  19. Smart Screening System (S3) In Taconite

    Energy Technology Data Exchange (ETDEWEB)

    Daryoush Allaei


    The conventional screening machines used in processing plants have had undesirable high noise and vibration levels. They also have had unsatisfactorily low screening efficiency, high energy consumption, high maintenance cost, low productivity, and poor worker safety. These conventional vibrating machines have been used in almost every processing plant. Most of the current material separation technology uses heavy and inefficient electric motors with an unbalanced rotating mass to generate the shaking. In addition to being excessively noisy, inefficient, and high-maintenance, these vibrating machines are often the bottleneck in the entire process. Furthermore, these motors, along with the vibrating machines and supporting structure, shake other machines and structures in the vicinity. The latter increases maintenance costs while reducing worker health and safety. The conventional vibrating fine screens at taconite processing plants have had the same problems as those listed above. This has resulted in lower screening efficiency, higher energy and maintenance cost, and lower productivity and workers safety concerns. The focus of this work is on the design of a high performance screening machine suitable for taconite processing plants. SmartScreens{trademark} technology uses miniaturized motors, based on smart materials, to generate the shaking. The underlying technologies are Energy Flow Control{trademark} and Vibration Control by Confinement{trademark}. These concepts are used to direct energy flow and confine energy efficiently and effectively to the screen function. The SmartScreens{trademark} technology addresses problems related to noise and vibration, screening efficiency, productivity, and maintenance cost and worker safety. Successful development of SmartScreens{trademark} technology will bring drastic changes to the screening and physical separation industry. The final designs for key components of the SmartScreens{trademark} have been developed. The key

  20. Discovery of novel BRD4 inhibitors by high-throughput screening, crystallography, and cell-based assays. (United States)

    Sun, Zhongya; Zhang, Hao; Chen, Zhifeng; Xie, Yiqian; Jiang, Hao; Chen, Limin; Ding, Hong; Zhang, Yuanyuan; Jiang, Hualiang; Zheng, Mingyue; Luo, Cheng


    As an epigenetic reader, BRD4 regulates the transcription of important downstream genes that are essential for the survival of tumor cells. Small molecular inhibitors targeting the first bromodomain of BRD4 (BRD4-BD1) have showed promising potentials in the therapies of BRD4-related cancers. Through AlphaScreen-based high-throughput screening assay, a novel small molecular inhibitor was identified, and named DCBD-005, which inhibited the binding between BRD4-BD1 and acetylated lysines with an IC50 value of 0.81±0.03μM. The compound DCBD-005 effectively inhibited the viability, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Moreover, the crystal structure of compound DCBD-005 with the BRD4-BD1 was determined at 1.72Å resolution, which revealed the binding mechanism of the leading compound, and also provided solid basis for further structure-based optimization. These results indicated that this novel BRD4-BD1 inhibitor DCBD-005 is promising to be developed into a drug candidate in the treatment of BRD4-related diseases.

  1. Establishment and validation of whole-cell based fluorescence assays to identify anti-mycobacterial compounds using the Acanthamoeba castellanii-Mycobacterium marinum host-pathogen system.

    Directory of Open Access Journals (Sweden)

    Sébastien Kicka

    Full Text Available Tuberculosis is considered to be one of the world's deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority of the hits discovered by traditional target-based screening showed low efficiency in vivo. Therefore, there is heightened demand for whole-cell based approaches directly using host-pathogen systems. The phenotypic host-pathogen assay described here is based on the monitoring of GFP-expressing Mycobacterium marinum during infection of the amoeba Acanthamoeba castellanii. The assay showed straight-forward medium-throughput scalability, robustness and ease of manipulation, demonstrating its qualities as an efficient compound screening system. Validation with a series of known antitubercular compounds highlighted the advantages of the assay in comparison to previously published macrophage-Mycobacterium tuberculosis-based screening systems. Combination with secondary growth assays based on either GFP-expressing D. discoideum or M. marinum allowed us to further fine-tune compound characterization by distinguishing and quantifying growth inhibition, cytotoxic properties and antibiotic activities of the compounds. The simple and relatively low cost system described here is most suitable to detect anti-infective compounds, whether they present antibiotic activities or not, in which case they might exert anti-virulence or host defense boosting activities, both of which are largely overlooked by classical screening approaches.

  2. Establishment and validation of whole-cell based fluorescence assays to identify anti-mycobacterial compounds using the Acanthamoeba castellanii-Mycobacterium marinum host-pathogen system. (United States)

    Kicka, Sébastien; Trofimov, Valentin; Harrison, Christopher; Ouertatani-Sakouhi, Hajer; McKinney, John; Scapozza, Leonardo; Hilbi, Hubert; Cosson, Pierre; Soldati, Thierry


    Tuberculosis is considered to be one of the world's deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority of the hits discovered by traditional target-based screening showed low efficiency in vivo. Therefore, there is heightened demand for whole-cell based approaches directly using host-pathogen systems. The phenotypic host-pathogen assay described here is based on the monitoring of GFP-expressing Mycobacterium marinum during infection of the amoeba Acanthamoeba castellanii. The assay showed straight-forward medium-throughput scalability, robustness and ease of manipulation, demonstrating its qualities as an efficient compound screening system. Validation with a series of known antitubercular compounds highlighted the advantages of the assay in comparison to previously published macrophage-Mycobacterium tuberculosis-based screening systems. Combination with secondary growth assays based on either GFP-expressing D. discoideum or M. marinum allowed us to further fine-tune compound characterization by distinguishing and quantifying growth inhibition, cytotoxic properties and antibiotic activities of the compounds. The simple and relatively low cost system described here is most suitable to detect anti-infective compounds, whether they present antibiotic activities or not, in which case they might exert anti-virulence or host defense boosting activities, both of which are largely overlooked by classical screening approaches.

  3. A cell-based luciferase assay amenable to high-throughput screening of inhibitors of arenavirus budding. (United States)

    Capul, Althea A; de la Torre, Juan Carlos


    Several arenaviruses cause hemorrhagic fever (HF) disease in humans for which there are no licensed vaccines, and current therapy is limited to the use of ribavirin (Rib) that is only partially effective and associated with significant side effects. In addition, compelling evidence indicates that the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Therefore, it is important to develop novel and effective anti-arenaviral drugs. The arenavirus Z protein is the driving force of arenavirus budding, and PPPY and PTAP late (L) domain motifs within Z are critical for Z-mediated budding, which involves the interaction of Z with a variety of host cellular factors. Compounds capable of inhibiting these virus-host cell interactions represent candidate anti-arenaviral drugs. The identification of these candidate compounds would be facilitated by the availability of a Z budding assay amenable to high-throughput screens (HTS). To this end, we have developed a novel assay that allows for rapid and quantitative assessment of Z-mediated budding. We provide evidence that this novel assay is amenable to HTS to identify small molecule inhibitors of Z-mediated budding, as well as to uncover cellular genes contributing to arenavirus budding.

  4. MAS-based production scheduling system for manufacturing cell-based workshop

    Institute of Scientific and Technical Information of China (English)

    CHU Hong-yan; CAO Quan-jun; FEI Ren-yuan


    The task of production scheduling is to determine the detailed machining path,time,machine tool,etc.,for every work piece,according to the production objective and constraints.It is also an important part of the manufacturing system.In this paper,the manufacturing cell-based workshop is described and its scheduling system structure is established based on MAS (multi-agent system) technology.Through the negotiation and communication of each agent,the machining path is determined and the machining sequence and start time are calculated by GA (genetics algorithm).The communication among agents uses the CORBA (common object request broker architecture) technology of the OMG (Object Management Group).The CORBA-based architecture of the communication is designed and some interfaces for the communication are listed.For the genetics algorithm,chromosome coding,fitness function,parameters selection,and the basic genetics operation including selection,crossover and aberrance,are described.The scheduling system also can deal with some abnormal conditions,such as machine tool failure and urgent tasks.Finally,two scheduling examples are given.

  5. Solar cells based on the poly(N-vinylcarbazole):porphyrin:tris(8-hydroxyquinolinato) aluminium blend system

    Institute of Scientific and Technical Information of China (English)

    Zhang Tian-Hui; Zhao Su-Ling; Piao Ling-Yu; Xu Zheng; Ju Si-Ting; Liu Xiao-Dong; Kong Chao; Xu Xu-Rong


    Organic solar cells based on poly(N-vinylcarbazole) (PVK): porphyrin: tris (8-hydroxyquinolinato) aluminium (Alq3) blend p-n junction systems have been fabricated in this work. The roles of the different components in the blend system and of the amount of porphyrin have been investigated. The 5, 10, 15, 20-tetraphenylporphyrin (TPP) and 5, 10, 15, 20-tetra(o-chloro)phenylporphyrinato-copper (CuTCIPP) are used in the solar cells. The results show that TPP is better than CuTClPP in enhancing the performance of PVK:Alq3 solar cells. When the weight ratio of PVK:TPP:Alq3 is 1:1.5:1, the best performance of solar cell is obtained. The open circuit voltage (Voc) is 0.87 V, and the short circuit current (Jsc) is 17.5 μA·cm-2. In the ternary bulk hereojunction system, the device may be regarded as a cascade of three devices of PVK:TPP, TPP:Alq3 and PVK:Alq3. PVK, TPP and Alq3 can improve the hole mobility, light absorption intensity and electron mobility of the ternary bulk hereojunction system, respectively.

  6. Unit cell-based computer-aided manufacturing system for tissue engineering. (United States)

    Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo


    Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering.

  7. Stem and Progenitor Cell-Based Therapy of the Central Nervous System

    DEFF Research Database (Denmark)

    Goldman, Steven A.


    A variety of neurological disorders are attractive targets for stem and progenitor cell-based therapy. Yet many conditions are not, whether by virtue of an inhospitable disease environment, poorly understood pathophysiology, or poor alignment of donor cell capabilities with patient needs. Moreove...

  8. Desulfurization of jet fuel for fuel cell-based APU systems in aircraft

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.; Pasel, J.; Peters, R.; Stolten, D. [Forschungszentrum Juelich GmbH (Germany)


    To prevent the catalysts in fuel cell systems from poisoning by sulfur containing substances the fuel to be used must be desulfurized to a maximum of 10 ppmw of sulfur. Since the conventional hydrodesulfurization process employed in the refinery industry is not suitable for mobile fuel cell applications (e.g. auxiliary power units, APUs), the present study aims at developing an alternative process and determining its technical feasibility. A large number of processes were assessed with respect to their application in fuel cell APUs. The results revealed that a two-step process combining pervaporation and adsorption is a suitable process for the on-board desulfurization of jet fuel. The investigations to evaluate this process are presented in this paper. Seven different membrane materials and ten sorbent materials were screened to choose the most suitable candidates. Further laboratory experiments were conducted to optimize the operating conditions and to collect data for a pilot plant design. Different jet fuel qualities with up to 1650 ppmw of sulfur can be desulfurized to a level of 10 ppmw. (orig.)

  9. A Small-Molecule Screen for Enhanced Homing of Systemically Infused Cells

    Directory of Open Access Journals (Sweden)

    Oren Levy


    Full Text Available Poor homing of systemically infused cells to disease sites may limit the success of exogenous cell-based therapy. In this study, we screened 9,000 signal-transduction modulators to identify hits that increase mesenchymal stromal cell (MSC surface expression of homing ligands that bind to intercellular adhesion molecule 1 (ICAM-1, such as CD11a. Pretreatment of MSCs with Ro-31-8425, an identified hit from this screen, increased MSC firm adhesion to an ICAM-1-coated substrate in vitro and enabled targeted delivery of systemically administered MSCs to inflamed sites in vivo in a CD11a- (and other ICAM-1-binding domains-dependent manner. This resulted in a heightened anti-inflammatory response. This represents a new strategy for engineering cell homing to enhance therapeutic efficacy and validates CD11a and ICAM-1 as potential targets. Altogether, this multi-step screening process may significantly improve clinical outcomes of cell-based therapies.

  10. EyeScreen: A Vision-Based Gesture Interaction System

    Institute of Scientific and Technical Information of China (English)

    LI Shan-qing; XU Yi-hua; JIA Yun-de


    EyeScreen is a vision-based interaction system which provides a natural gesture interface for human-computer interaction (HCI) by tracking human fingers and recognizing gestures. Multi-view video images are captured by two cameras facing a computer screen, which can be used to detect clicking actions of a fingertip and improve the recognition rate. The system enables users to directly interact with rendered objects on the screen. Robustness of the system has been verified by extensive experiments with different user scenarios. EyeScreen can be used in many applications such as intelligent interaction and digital entertainment.

  11. Mimer: an automated spreadsheet-based crystallization screening system. (United States)

    Brodersen, Ditlev Egeskov; Andersen, Gregers Rom; Andersen, Christian Brix Folsted


    In this paper, a simple low-cost alternative to large commercial systems for preparing macromolecular crystallization conditions is described. Using an intuitive spreadsheet-based approach, the system allows the rapid calculation of relevant pipetting volumes given known stock-solution concentrations and incorporates the automatic design of custom crystallization screens via the incomplete-factorial and grid-screen approaches. Automated dispensing of the resulting crystallization screens is achieved using a generic and relatively inexpensive liquid handler.

  12. Screening of Aptamers on Microfluidic Systems for Clinical Applications


    Gwo-Bin Lee; Chao-Jyun Huang; Chen-Hsun Weng


    The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can be used as promising candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer screening protocol has been conducted with microfluidic-based devices. Furthermore, aptamer affinity screening...

  13. Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms.

    Directory of Open Access Journals (Sweden)

    Alan E Bilsland


    Full Text Available Cancer cells depend on transcription of telomerase reverse transcriptase (TERT. Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3'-oxime (BIO predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several

  14. Quantum dot-based screening system for discovery of g protein-coupled receptor agonists. (United States)

    Lee, Junghan; Kwon, Yong-Jun; Choi, Youngseon; Kim, Hi Chul; Kim, Keumhyun; Kim, JinYeop; Park, Sun; Song, Rita


    Cellular imaging has emerged as an important tool to unravel biological complexity and to accelerate the drug-discovery process, including cell-based screening, target identification, and mechanism of action studies. Recently, semiconductor nanoparticles known as quantum dots (QDs) have attracted great interest in cellular imaging applications due to their unique photophysical properties such as size, tunable optical property, multiplexing capability, and photostability. Herein, we show that QDs can also be applied to assay development and eventually to high-throughput/content screening (HTS/HCS) for drug discovery. We have synthesized QDs modified with PEG and primary antibodies to be used as fluorescent probes for a cell-based HTS system. The G protein-coupled receptor (GPCR) family is known to be involved in most major diseases. We therefore constructed human osteosarcoma (U2OS) cells that specifically overexpress two types of differently tagged GPCRs: influenza hemagglutinin (HA) peptide-tagged κ-opioid receptors (κ-ORs) and GFP-tagged A3 adenosine receptors (A3AR). In this study, we have demonstrated that 1) anti-HA antibody-conjugated QDs could specifically label HA-tagged κ-ORs, 2) subsequent treatment of QD-tagged GPCR agonists allowed agonist-induced translocation to be monitored in real time, 3) excellent emission spectral properties of QD permitted the simultaneous detection of two GPCRs in one cell, and 4) the robust imaging capabilities of the QD-antibody conjugates could lead to reproducible quantitative data from high-content cellular images. These results suggest that the present QD-based GPCR inhibitor screening system can be a promising platform for further drug screening applications.

  15. Successful identification of novel agents to control infectious diseases from screening mixture-based peptide combinatorial libraries in complex cell-based bioassays. (United States)

    Boggiano, César; Reixach, Natàlia; Pinilla, Clemencia; Blondelle, Sylvie E


    Mixture-based peptide synthetic combinatorial libraries (SCLs) represent a valuable source for the development of novel agents to control infectious diseases. Indeed, a number of studies have now proven the ability of identifying active peptides from libraries composed of thousands to millions of peptides in cell-based biosystems of varying complexity. Furthermore, progressing knowledge on the importance of endogenous peptides in various immune responses lead to a regain in importance for peptides as potential therapeutic agents. This article is aimed at providing recent studies in our laboratory for the development of antimicrobial or antiviral peptides derived from mixture-based SCLs using cell-based assays, as well as a short review of the importance of such peptides in the control of infectious diseases. Furthermore, the use of positional scanning (PS) SCL-based biometrical analyses for the identification of native optimal epitopes specific to HIV-1 proteins is also presented.

  16. A magnetic cell-based sensor. (United States)

    Wang, Hua; Mahdavi, Alborz; Tirrell, David A; Hajimiri, Ali


    Cell-based sensing represents a new paradigm for performing direct and accurate detection of cell- or tissue-specific responses by incorporating living cells or tissues as an integral part of a sensor. Here we report a new magnetic cell-based sensing platform by combining magnetic sensors implemented in the complementary metal-oxide-semiconductor (CMOS) integrated microelectronics process with cardiac progenitor cells that are differentiated directly on-chip. We show that the pulsatile movements of on-chip cardiac progenitor cells can be monitored in a real-time manner. Our work provides a new low-cost approach to enable high-throughput screening systems as used in drug development and hand-held devices for point-of-care (PoC) biomedical diagnostic applications.

  17. Screening of aptamers on microfluidic systems for clinical applications. (United States)

    Weng, Chen-Hsun; Huang, Chao-Jyun; Lee, Gwo-Bin


    The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can be used as promising candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer screening protocol has been conducted with microfluidic-based devices. Furthermore, aptamer affinity screening by a microfluidic-based method has demonstrated remarkable advantages over competing traditional methods. In this paper, we first reviewed microfluidic systems which demonstrated efficient and rapid screening of a specific aptamer. Then, the clinical applications of screened aptamers, also performed by microfluidic systems, are further reviewed. These automated microfluidic systems can provide advantages over their conventional counterparts including more compactness, faster analysis, less sample/reagent consumption and automation. An aptamer-based compact microfluidic system for diagnosis may even lead to a point-of-care device. The use of microfluidic systems for aptamer screening and diagnosis is expected to continue growing in the near future and may make a substantial impact on biomedical applications.

  18. Screening of Aptamers on Microfluidic Systems for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Gwo-Bin Lee


    Full Text Available The use of microfluidic systems for screening of aptamers and their biomedical applications are reviewed in this paper. Aptamers with different nucleic acid sequences have been extensively studied and the results demonstrated a strong binding affinity to target molecules such that they can be used as promising candidate biomarkers for diagnosis and therapeutics. Recently, the aptamer screening protocol has been conducted with microfluidic-based devices. Furthermore, aptamer affinity screening by a microfluidic-based method has demonstrated remarkable advantages over competing traditional methods. In this paper, we first reviewed microfluidic systems which demonstrated efficient and rapid screening of a specific aptamer. Then, the clinical applications of screened aptamers, also performed by microfluidic systems, are further reviewed. These automated microfluidic systems can provide advantages over their conventional counterparts including more compactness, faster analysis, less sample/reagent consumption and automation. An aptamer-based compact microfluidic system for diagnosis may even lead to a point-of-care device. The use of microfluidic systems for aptamer screening and diagnosis is expected to continue growing in the near future and may make a substantial impact on biomedical applications.

  19. Transcript annotation prioritization and screening system (TrAPSS) for mutation screening. (United States)

    O'Leary, Brian M; Davis, Steven G; Smith, Michael F; Brown, Bartley; Kemp, Mathew B; Almabrazi, Hakeem; Grundstad, Jason A; Burns, Thomas; Leontiev, Vladimir; Andorf, Jeaneen; Clark, Abbot F; Sheffield, Val C; Casavant, Thomas L; Scheetz, Todd E; Stone, Edwin M; Braun, Terry A


    When searching for disease-causing mutations with polymerase chain reaction (PCR)-based methods, candidate genes are usually screened in their entirety, exon by exon. Genomic resources (i.e.,, and largely support this paradigm for mutation screening by making it easy to view and access sequence data associated with genes in their genomic context. However, the administrative burden of conducting mutation screening in potentially hundreds of genes and thousands of exons in thousands of patients is significant, even with the use of public genome resources. For example, the manual design of oligonucleotide primers for all exons of the 10 Leber's congenital amaurosis (LCA) genes (149 exons) represents a significant information management challenge. The Transcript Annotation Prioritization and Screening System (TrAPSS) is designed to accelerate mutation screening by (1) providing a gene-based local cache of candidate disease genes in a genomic context, (2) automating tasks associated with optimizing candidate disease gene screening and information management, and (3) providing the implementation of an algorithmic technique to utilize large amounts of heterogeneous genome annotation (e.g. conserved protein functional domains) so as to prioritize candidate genes.

  20. Cell-based galactosemia diagnosis system based on a galactose assay using a bioluminescent Escherichia coli array. (United States)

    Woo, Min-Ah; Kim, Moon Il; Cho, Daeyeon; Park, Hyun Gyu


    A new cell-based galactose assay system, which is comprised of two bioluminescent Escherichia coli strains immobilized within an agarose gel arrayed on a well plate, has been developed. For this purpose, a galT knockout strain [galT(-) cell] of E. coli was genetically constructed so that cell growth is not promoted by galactose but rather by glucose present in a sample. Another E. coli W strain (normal cell), which grows normally in the presence of either glucose or galactose, was employed. A luminescent reporter gene, which produces luminescence as cells grow, was inserted into both of the E. coli strains, so that cell growth could be monitored in a facile manner. The two strains were separately grown for 4 h on gel arrays to which test samples were individually supplied. The relative luminescence unit (RLU) values caused by cell growth were determined for each array, one of which is resulted by glucose only and the other of which is resulted by both glucose and galactose present in the sample. By employing this protocol, galactose concentrations present in the test sample are reflected in the differences between the RLU values for each array. The practical utility of the new assay system was demonstrated by its use in determining galactose levels in clinical blood spot specimens coming from newborn babies. Because it can be employed to diagnosis of galactosemia in newborn babies in a more rapid, convenient, and cost-effective manner, this cell-based solid-phase galactose assay system should become a powerful alternative to conventional methods, which require labor-intensive and time-consuming procedures and/or complicated and expensive equipment.

  1. Smart Screening System (S3) In Taconite Processing

    Energy Technology Data Exchange (ETDEWEB)

    Daryoush Allaei; Angus Morison; David Tarnowski; Asim Syed Mohammed


    components include smart motor and associated electronics, resonators, and supporting structural elements. It is shown that the smart motors have an acceptable life and performance. Resonator (or motion amplifier) designs are selected based on the final system requirement and vibration characteristics. All the components for a fully functional prototype are fabricated. The development program is on schedule. The last semi-annual report described the process of FE model validation and correlation with experimental data in terms of dynamic performance and predicted stresses. It also detailed efforts into making the supporting structure less important to system performance. Finally, an introduction into the dry application concept was presented. Since then, the design refinement phase was completed. This has resulted in a Smart Screen design that meets performance targets both in the dry condition and with taconite slurry flow using PZT motors. Furthermore, this system was successfully demonstrated for the DOE and partner companies at the Coleraine Mineral Research Laboratory in Coleraine, Minnesota.

  2. Imaging of blood cells based on snapshot Hyper-Spectral Imaging systems (United States)

    Robison, Christopher J.; Kolanko, Christopher; Bourlai, Thirimachos; Dawson, Jeremy M.


    Snapshot Hyper-Spectral imaging systems are capable of capturing several spectral bands simultaneously, offering coregistered images of a target. With appropriate optics, these systems are potentially able to image blood cells in vivo as they flow through a vessel, eliminating the need for a blood draw and sample staining. Our group has evaluated the capability of a commercial Snapshot Hyper-Spectral imaging system, the Arrow system from Rebellion Photonics, in differentiating between white and red blood cells on unstained blood smear slides. We evaluated the imaging capabilities of this hyperspectral camera; attached to a microscope at varying objective powers and illumination intensity. Hyperspectral data consisting of 25, 443x313 hyperspectral bands with ~3nm spacing were captured over the range of 419 to 494nm. Open-source hyper-spectral data cube analysis tools, used primarily in Geographic Information Systems (GIS) applications, indicate that white blood cells features are most prominent in the 428-442nm band for blood samples viewed under 20x and 50x magnification over a varying range of illumination intensities. These images could potentially be used in subsequent automated white blood cell segmentation and counting algorithms for performing in vivo white blood cell counting.

  3. The Multiscale Systems Immunology project: software for cell-based immunological simulation

    Directory of Open Access Journals (Sweden)

    Kepler Thomas B


    Full Text Available Abstract Background Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response to vaccination by an agent based immune response simulation that incorporates realistic biophysics and intracellular dynamics, and which is sufficiently flexible to accurately model the multi-scale nature and complexity of the immune system, while maintaining the high performance critical to scientific computing. Results The Multiscale Systems Immunology (MSI simulation framework is an object-oriented, modular simulation framework written in C++ and Python. The software implements a modular design that allows for flexible configuration of components and initialization of parameters, thus allowing simulations to be run that model processes occurring over different temporal and spatial scales. Conclusion MSI addresses the need for a flexible and high-performing agent based model of the immune system.

  4. Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems. (United States)

    Ackova, Darinka Gjorgieva; Kanjevac, Tatjana; Rimondini, Lia; Bosnakovski, Darko


    Understanding and apprehension of the characteristics and circumstances in which mesenchymal stem cells (MSCs) affect and make alterations (enhance or reduce) to the growth of tumors and metastasis spread is pivotal, not only for reaching the possibility to employ MSCs as drug delivery systems, but also for making forward movement in the existing knowledge of involvement of major factors (tumor microenvironment, soluble signaling molecules, etc.) in the process of carcinogenesis. This capability is reliable because MSCs present a great basis for engineering and constructions of new systems to target cancers, intended to secrete therapeutic proteins in the tumor region, or for delivering of oncolytic viruses' directly at the tumor site (targeted chemotherapy with enzyme prodrug conversion or induction of tumor cell apoptosis). MSCs as a crucial segment of the tumor surroundings and their confirmed tumor tropism, are assumed to be an open gateway for the design of promising drug delivery systems. The presented paper reviews current publications in this fieldwork, searches out the most recent patents that were published after 2012 (WO2014066122, US20140017787, WO2015100268, US20150086515), and tries to present the current progress and future prospective on the design and development in anti-cancer drug delivery systems based on MSCs.

  5. Nanog reporter system in mouse embryonic stem cells based on highly efficient BAC homologous recombination

    Institute of Scientific and Technical Information of China (English)


    Nanog is a novel transcription factor specifically expressed in mouse embryonic stem cells (mES cells). It has been reported that Nanog plays an essential role in maintaining multi-potency of ES cells. The expression of Nanog is very sensitive to ES cells differentiation, making Nanog one of the best markers to indicate the status of ES cells. In this study, we developed an efficient method to construct Nanog promoter driven EGFP reporter system based on the BAC homologous recombination. We further generated a Nanog-EGFP reporter mES cell line. This reporter mES cell line exhibited features similar to those of normal mES cells, and the EGFP reporter efficiently reflected the expression of Nanog, indicating the differentiation status of mES cells. We achieved a reliable experimental reporter system to research self-renewal and differentiation of mES cells. The system could facilitate research on culture system of mES cells and researches on the expression and regulation of Nanog and other related factors in mES cells.

  6. Development of a robust cell-based high-throughput screening assay to identify targets of HIV-1 viral protein R dimerization

    Directory of Open Access Journals (Sweden)

    Zych C


    Full Text Available Courtney Zych,1 Alexander Domling,2 Velpandi Ayyavoo11Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; 2Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USAAbstract: Targeting protein–protein interactions (PPI is an emerging field in drug discovery. Dimerization and PPI are essential properties of human immunodeficiency virus (HIV-1 proteins, their mediated functions, and virus biology. Additionally, dimerization is required for the functional interaction of HIV-1 proteins with many host cellular components. In this study, a bimolecular fluorescence complementation (BiFC-based screening assay was developed that can quantify changes in dimerization, using HIV-1 viral protein R (Vpr dimerization as a "proof of concept." Results demonstrated that Venus Vpr (generated by BiFC Vpr constructs could be competed off in a dose-dependent manner using untagged, full-length Vpr as a competitor molecule. The change in signal intensity was measured quantitatively through flow cytometry and fluorescence microscopy in a high content screening assay. High content imaging was used to screen a library of small molecules for an effect on Vpr dimerization. Among the tested molecules, a few of the small molecules demonstrate an effect on Vpr dimerization in a dose-dependent manner.Keywords: BiFC, protein–protein interaction, HIV-1 Vpr, dimerization, drug targets

  7. Managing System of Systems Requirements with a Requirements Screening Group

    Energy Technology Data Exchange (ETDEWEB)

    Ronald R. Barden


    Figuring out an effective and efficient way to manage not only your Requirement’s Baseline, but also the development of all your individual requirements during a Program’s/Project’s Conceptual and Development Life Cycle Stages can be both daunting and difficult. This is especially so when you are dealing with a complex and large System of Systems (SoS) Program with potentially thousands and thousands of Top Level Requirements as well as an equal number of lower level System, Subsystem and Configuration Item requirements that need to be managed. This task is made even more overwhelming when you have to add in integration with multiple requirements’ development teams (e.g., Integrated Product Development Teams (IPTs)) and/or numerous System/Subsystem Design Teams. One solution for tackling this difficult activity on a recent large System of Systems Program was to develop and make use of a Requirements Screening Group (RSG). This group is essentially a Team made up of co-chairs from the various Stakeholders with an interest in the Program of record that are enabled and accountable for Requirements Development on the Program/Project. The RSG co-chairs, often with the help of individual support team, work together as a Program Board to monitor, make decisions on, and provide guidance on all Requirements Development activities during the Conceptual and Development Life Cycle Stages of a Program/Project. In addition, the RSG can establish and maintain the Requirements Baseline, monitor and enforce requirements traceability across the entire Program, and work with other elements of the Program/Project to ensure integration and coordination.

  8. On-line experimental results of an argon gas cell-based laser ion source (KEK Isotope Separation System) (United States)

    Hirayama, Y.; Watanabe, Y. X.; Imai, N.; Ishiyama, H.; Jeong, S. C.; Jung, H. S.; Miyatake, H.; Oyaizu, M.; Kimura, S.; Mukai, M.; Kim, Y. H.; Sonoda, T.; Wada, M.; Huyse, M.; Kudryavtsev, Yu.; Van Duppen, P.


    KEK Isotope Separation System (KISS) has been developed at RIKEN to produce neutron rich isotopes with N = 126 to study the β -decay properties for application to astrophysics. The KISS is an element-selective mass-separation system which consists of an argon gas cell-based on laser ion source for atomic number selection and an ISOL mass-separation system. The argon gas cell of KISS is a key component to stop and collect the unstable nuclei produced in a multi-nucleon transfer reaction, where the isotopes of interest will be selectively ionized using laser resonance ionization. We have performed off- and on-line experiments to study the basic properties of the gas cell as well as of the KISS. We successfully extracted the laser-ionized stable 56Fe (direct implantation of a 56Fe beam into the gas cell) atoms and 198Pt (emitted from the 198Pt target by elastic scattering with a 136Xe beam) atoms from the KISS during the commissioning on-line experiments. We furthermore extracted laser-ionized unstable 199Pt atoms and confirmed that the measured half-life was in good agreement with the reported value.

  9. Investigation of Mesh Choosing Parameters in Screen Printing System

    Directory of Open Access Journals (Sweden)

    Ahmet AKGÜL


    Full Text Available The mesh, which is made by weaving of natural silk, plastic, or metal fibers, is basic material for screen-printing. Image is created on stretched on a frame in screen-printing. Mesh should be selected correctly for a high quality printing. Therefore, substrates, types of print job and mesh parameters have importance. Need to know more about to mesh, yarn type, yarn thickness, frequency of weaving, stretching tension, the kind of weaving, etc. In this study, for a high quality screen-printing, mesh variables examined in detail and optimum conditions indicated, with the aim of increase productivity, minimize to losses time, material and labor. As a result, this information’s for obtaining a high quality printing with screen-printing system have importance as a guide. Also resolution of the image, amount of print run and viscosity of the printing ink, factors affecting the selection of mesh.

  10. Fuel Cell Power Model Version 2: Startup Guide, System Designs, and Case Studies. Modeling Electricity, Heat, and Hydrogen Generation from Fuel Cell-Based Distributed Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Steward, D.; Penev, M.; Saur, G.; Becker, W.; Zuboy, J.


    This guide helps users get started with the U.S. Department of Energy/National Renewable Energy Laboratory Fuel Cell Power (FCPower) Model Version 2, which is a Microsoft Excel workbook that analyzes the technical and economic aspects of high-temperature fuel cell-based distributed energy systems with the aim of providing consistent, transparent, comparable results. This type of energy system would provide onsite-generated heat and electricity to large end users such as hospitals and office complexes. The hydrogen produced could be used for fueling vehicles or stored for later conversion to electricity.

  11. Optimization of cell line development in the GS-CHO expression system using a high-throughput, single cell-based clone selection system. (United States)

    Nakamura, Tsuyoshi; Omasa, Takeshi


    Therapeutic antibodies are commonly produced by high-expressing, clonal and recombinant Chinese hamster ovary (CHO) cell lines. Currently, CHO cells dominate as a commercial production host because of their ease of use, established regulatory track record, and safety profile. CHO-K1SV is a suspension, protein-free-adapted CHO-K1-derived cell line employing the glutamine synthetase (GS) gene expression system (GS-CHO expression system). The selection of high-producing mammalian cell lines is a crucial step in process development for the production of therapeutic antibodies. In general, cloning by the limiting dilution method is used to isolate high-producing monoclonal CHO cells. However, the limiting dilution method is time consuming and has a low probability of monoclonality. To minimize the duration and increase the probability of obtaining high-producing clones with high monoclonality, an automated single cell-based clone selector, the ClonePix FL system, is available. In this study, we applied the high-throughput ClonePix FL system for cell line development using CHO-K1SV cells and investigated efficient conditions for single cell-based clone selection. CHO-K1SV cell growth at the pre-picking stage was improved by optimizing the formulation of semi-solid medium. The efficiency of picking and cell growth at the post-picking stage was improved by optimization of the plating time without decreasing the diversity of clones. The conditions for selection, including the medium formulation, were the most important factors for the single cell-based clone selection system to construct a high-producing CHO cell line.

  12. Evaluation of a new screening system for enteric pathogens. (United States)

    Hinrichs, J; Gauthier, A; Keating, M; Murray, P


    The two-hour Rapid SST strip (DMS Laboratories, Inc.) was compared with our standard screening system (triple sugar iron agar, lysine iron agar, and urea) for enteric pathogens. We tested 50 stock cultures of enteric pathogens and 213 stool cultures received in the Barnes Hospital Clinical Microbiology Laboratory over a two-month period. All enteric pathogens from the stock cultures and clinical specimens were identified correctly with the Rapid SST system. More false-positive reactions were observed with the Rapid SST system (34%) than with the conventional system (23%). However, the costs associated with using both systems were equivalent and the test results were available one day faster with the Rapid SST system. Thus, the Rapid SST is a rapid, accurate, and cost-effective method for screening stool specimens for enteric pathogens.

  13. Cell-Based Sensor System Using L6 Cells for Broad Band Continuous Pollutant Monitoring in Aquatic Environments

    Directory of Open Access Journals (Sweden)

    Evamaria Stütz


    Full Text Available Pollution of drinking water sources represents a continuously emerging problem in global environmental protection. Novel techniques for real-time monitoring of water quality, capable of the detection of unanticipated toxic and bioactive substances, are urgently needed. In this study, the applicability of a cell-based sensor system using selected eukaryotic cell lines for the detection of aquatic pollutants is shown. Readout parameters of the cells were the acidification (metabolism, oxygen consumption (respiration and impedance (morphology of the cells. A variety of potential cytotoxic classes of substances (heavy metals, pharmaceuticals, neurotoxins, waste water was tested with monolayers of L6 cells (rat myoblasts. The cytotoxicity or cellular effects induced by inorganic ions (Ni2+ and Cu2+ can be detected with the metabolic parameters acidification and respiration down to 0.5 mg/L, whereas the detection limit for other substances like nicotine and acetaminophen are rather high, in the range of 0.1 mg/L and 100 mg/L. In a close to application model a real waste water sample shows detectable signals, indicating the existence of cytotoxic substances. The results support the paradigm change from single substance detection to the monitoring of overall toxicity.

  14. Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study

    DEFF Research Database (Denmark)

    Schledermann, Doris; Hyldebrandt, Tina; Ejersbo, Dorthe;


    The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening ...

  15. A new system for electroanalytical mass screening

    Directory of Open Access Journals (Sweden)

    Jaromir Zak


    Full Text Available The work deals with n–channel system enabling many sampleanalysis at sort time from sensor array using electrochemicalmethods. The 8x12 sensor array is formed from 3–electrodes systemcreated on PCB (Printed Circuit Board with combination ofgalvanic deposition and screen–printing special paste on theelectrodes which can be used for heavy metal analysis and alsobiomolecular complexes and organic toxic substancesdetermination. The control unit switches each 3–electrode sensor to8–channel precise potentiostat which was designed forelectrochemical analysis with current sensitivity below 1 pA. Thepotentiostat can synchronize with control unit to depress time foranalysis to minimum. Measured data are sent to user–friendlyapplication in computer and analyzed or saved consequently.


    Energy Technology Data Exchange (ETDEWEB)

    McNeany, Karen I [ORNL


    The Random Drug Screening System (RDSS) is a desktop computing application designed to assign nongameable drug testing dates to each member in a population of employees, within a specific time line. The program includes reporting capabilities, test form generation, unique test ID number assignment, and the ability to flag high-risk employees for a higher frequency of drug testing than the general population.

  17. A note on the gravity screening in quantum systems

    CERN Document Server

    Gregori, Andrea


    We discuss how, in the theoretical scenario presented in [1], the gravity screening and the gravity impulse which seem to be produced under certain conditions by high temperature superconductors are expected to be an entropic response to the flow of part of the system into a deeper quantum regime.

  18. Screening for pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry


    Full Text Available The onset and progression of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc can be particularly aggressive; however, effective treatments are available. Therefore, early identification of patients with suspected PAH, confirmation of diagnosis, and intervention is essential. PAH may be challenging to diagnose in its earliest stages, particularly in populations that have multiple causes of breathlessness, and, therefore, screening is required. The optimal screening tools and methodology are, as yet, unknown, and this is confounded by a lack of consensus over which patients to screen. Current practice favours annual screening of all SSc patients using Doppler echocardiography to detect elevated right heart pressures. This will typically identify most patients with the various forms of pulmonary hypertension found in SSc. The optimum thresholds for Doppler echocardiography are still subject to investigation, especially for patients with mild pulmonary hypertension, and this technique may, therefore, yield a significant number of false-positives and a currently unknown number of false-negatives. Confirmatory right heart catheterisation remains necessary in all suspected cases. Further research is needed to identify the optimal tools and the screening approach with greatest specificity and selectivity.

  19. Network-based reading system for lung cancer screening CT (United States)

    Fujino, Yuichi; Fujimura, Kaori; Nomura, Shin-ichiro; Kawashima, Harumi; Tsuchikawa, Megumu; Matsumoto, Toru; Nagao, Kei-ichi; Uruma, Takahiro; Yamamoto, Shinji; Takizawa, Hotaka; Kuroda, Chikazumi; Nakayama, Tomio


    This research aims to support chest computed tomography (CT) medical checkups to decrease the death rate by lung cancer. We have developed a remote cooperative reading system for lung cancer screening over the Internet, a secure transmission function, and a cooperative reading environment. It is called the Network-based Reading System. A telemedicine system involves many issues, such as network costs and data security if we use it over the Internet, which is an open network. In Japan, broadband access is widespread and its cost is the lowest in the world. We developed our system considering human machine interface and security. It consists of data entry terminals, a database server, a computer aided diagnosis (CAD) system, and some reading terminals. It uses a secure Digital Imaging and Communication in Medicine (DICOM) encrypting method and Public Key Infrastructure (PKI) based secure DICOM image data distribution. We carried out an experimental trial over the Japan Gigabit Network (JGN), which is the testbed for the Japanese next-generation network, and conducted verification experiments of secure screening image distribution, some kinds of data addition, and remote cooperative reading. We found that network bandwidth of about 1.5 Mbps enabled distribution of screening images and cooperative reading and that the encryption and image distribution methods we proposed were applicable to the encryption and distribution of general DICOM images via the Internet.

  20. High-throughput screening in the C. elegans nervous system. (United States)

    Kinser, Holly E; Pincus, Zachary


    The nematode Caenorhabditis elegans is widely used as a model organism in the field of neurobiology. The wiring of the C. elegans nervous system has been entirely mapped, and the animal's optical transparency allows for in vivo observation of neuronal activity. The nematode is also small in size, self-fertilizing, and inexpensive to cultivate and maintain, greatly lending to its utility as a whole-animal model for high-throughput screening (HTS) in the nervous system. However, the use of this organism in large-scale screens presents unique technical challenges, including reversible immobilization of the animal, parallel single-animal culture and containment, automation of laser surgery, and high-throughput image acquisition and phenotyping. These obstacles require significant modification of existing techniques and the creation of new C. elegans-based HTS platforms. In this review, we outline these challenges in detail and survey the novel technologies and methods that have been developed to address them.

  1. Calculation of electromagnetic fields in inductor-screen-ingot systems

    Energy Technology Data Exchange (ETDEWEB)

    Getselev, Z.N.; Martynov, G.I.


    The method proposed is used for designing complex electromagnetic ''inductor-screen-ingot'' systems with non-uniform boundary conditions which are encountered in electromagnetic formation and induction heating. As a result of using the approximate Fourier transformation, the original system of integral equations is replaced by a system of linear algebraic equations with known coefficients and which is numerically solved on a computer. The vector potential in regional boundaries is calculated in the first stage, and the potential within the region is computed in the second stage. The method is analyzed in detail by solving five specific problems.

  2. Cell-based Assays to Identify Inhibitors of Viral Disease (United States)

    Green, Neil; Ott, Robert D.; Isaacs, Richard J.; Fang, Hong


    Background Antagonizing the production of infectious virus inside cells requires drugs that can cross the cell membrane without harming host cells. Objective It is therefore advantageous to establish intracellular potency of anti-viral drug candidates early in the drug-discovery pipeline. Methods To this end, cell-based assays are being developed and employed in high-throughput drug screening, ranging from assays that monitor replication of intact viruses to those that monitor activity of specific viral proteins. While numerous cell-based assays have been developed and investigated, rapid counter screens are also needed to define the specific viral targets of identified inhibitors and to eliminate nonspecific screening hits. Results/Conclusions Here, we describe the types of cell-based assays being used in antiviral drug screens and evaluate the equally important counter screens that are being employed to reach the full potential of cell-based high-throughput screening. PMID:19750206

  3. Application of a Decomposition Strategy to the Optimal Synthesis/Design and Operation of a Fuel Cell Based Total Energy System



    A decomposition methodology based on the concept of â thermoeconomic isolationâ applied to the synthesis/design and operational optimization of a stationary cogeneration proton exchange membrane fuel cell (PEMFC) based total energy system (TES) for residential/commercial applications is the focus of this work. A number of different configurations for the fuel cell based TES were considered. The most promising set based on an energy integration analysis of candidate configurations was devel...

  4. Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study. (United States)

    Schledermann, Doris; Hyldebrandt, Tina; Ejersbo, Dorthe; Hoelund, Berit


    The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening procedure was timed for each of the 11,354 slides included. In every slide 22 fields of view were reviewed, and the samples that contained potentially abnormal cells were fully screened. The screening time was reduced by 42% (mean) (p < 0.001). By manual rescreening of the negative TIS samples, abnormal cells were found in 10 samples (false negative rate 0.14%). In every case the abnormal cells had been identified by the scanner, but misinterpreted by the cytotechnologist. These findings stressed the importance of carefulness in the interpretation of the marked fields and beyond that helped the cytotechnologists and pathologists to have more confidence in the automated system.

  5. 全细胞高通量筛选α-氨基酸酯水解酶突变体的方法%Cell-based high throughput screening of α-amino acid ester hydrolase variants

    Institute of Scientific and Technical Information of China (English)

    叶丽娟; 王佳珉; 王辂; 曹毅


    [Objective] The study aimed to develop an efficient and sensitive high-throughput method to obtain alpha-amino acid ester hydrolase (AEH) with improved activity or thermo-stability. [Methods] Standard curve was made based on the fact that hydrolysis of cefaclor in alkaline buffer yields a derivate which has specific absorbance at 340 nm. Whole cell-based ultra-violet spectrophotometric method was applied to screen the cefaclor synthesis activity of AEH variants at a high-throughput scale. [Results] Beer's Law is obeyed in the range of (0.1-0.6)xl0~3 mol/L cefaclor. The average recovery is 99.8%-101.3%. 2 300 Clones obtained by one round of site-directed saturated mutagenesis were screened by this method. Three variants with more than 1.4-fold kcat and 4 variants with T50 5 ℃ more than wild type were obtained. [Conclusion] The screening method was precise and reliable. The screen capacity can be up to 2 000 samples per day, which was in the scale of high-throughput screening.%[目的]建立高效敏感的高通量筛选方法,用于筛选头孢克洛合成活性提高或热稳定性提高的α-氨基酸酯水解酶.[方法]根据头孢克洛在碱性条件下水解生成的衍生物在340 nm处有特征吸收峰的原理,制作出标准曲线.采用全细胞96孔板紫外分光光度法高通量测定α-氨基酸酯水解酶突变体的头孢克洛合成活性.[结果]头孢克洛含量与△A340-405在(0.1-0.6)×10-3 mol/L浓度范围内有良好的线性关系,服从朗伯-比尔定律,平均回收率为99.8%-101.3%.一轮定点饱和突变产生的2 300个克隆经该方法的筛选,获得3株Kcat提高40%以上,4株半失活温度较野生型提高5℃以上的突变体酶.[结论]该方法准确可靠,每天筛选量可达到2 000个反应,达到高通量筛选的要求.

  6. Continuous Membrane-Based Screening System for Biocatalysis

    Directory of Open Access Journals (Sweden)

    Matthias Kraume


    Full Text Available The use of membrane reactors for enzymatic and co-factor regenerating reactions offers versatile advantages such as higher conversion rates and space-time-yields and is therefore often applied in industry. However, currently available screening and kinetics characterization systems are based on batch and fed-batch operated reactors and were developed for whole cell biotransformations rather than for enzymatic catalysis. Therefore, the data obtained from such systems has only limited transferability for continuous membrane reactors. The aim of this study is to evaluate and to improve a novel screening and characterization system based on the membrane reactor concept using the enzymatic hydrolysis of cellulose as a model reaction. Important aspects for the applicability of the developed system such as long-term stability and reproducibility of continuous experiments were very high. The concept used for flow control and fouling suppression allowed control of the residence time with a high degree of precision (±1% accuracy in a long-term study (>100 h.

  7. Hypoxia-sensitive reporter system for high-throughput screening. (United States)

    Tsujita, Tadayuki; Kawaguchi, Shin-ichi; Dan, Takashi; Baird, Liam; Miyata, Toshio; Yamamoto, Masayuki


    The induction of anti-hypoxic stress enzymes and proteins has the potential to be a potent therapeutic strategy to prevent the progression of ischemic heart, kidney or brain diseases. To realize this idea, small chemical compounds, which mimic hypoxic conditions by activating the PHD-HIF-α system, have been developed. However, to date, none of these compounds were identified by monitoring the transcriptional activation of hypoxia-inducible factors (HIFs). Thus, to facilitate the discovery of potent inducers of HIF-α, we have developed an effective high-throughput screening (HTS) system to directly monitor the output of HIF-α transcription. We generated a HIF-α-dependent reporter system that responds to hypoxic stimuli in a concentration- and time-dependent manner. This system was developed through multiple optimization steps, resulting in the generation of a construct that consists of the secretion-type luciferase gene (Metridia luciferase, MLuc) under the transcriptional regulation of an enhancer containing 7 copies of 40-bp hypoxia responsive element (HRE) upstream of a mini-TATA promoter. This construct was stably integrated into the human neuroblastoma cell line, SK-N-BE(2)c, to generate a reporter system, named SKN:HRE-MLuc. To improve this system and to increase its suitability for the HTS platform, we incorporated the next generation luciferase, Nano luciferase (NLuc), whose longer half-life provides us with flexibility for the use of this reporter. We thus generated a stably transformed clone with NLuc, named SKN:HRE-NLuc, and found that it showed significantly improved reporter activity compared to SKN:HRE-MLuc. In this study, we have successfully developed the SKN:HRE-NLuc screening system as an efficient platform for future HTS.

  8. Rapid Color Test Identification System for Screening of Counterfeit Fluoroquinolone

    Directory of Open Access Journals (Sweden)

    B. K. Singh


    Full Text Available The protocol of rapid identification system consists of three chemical color reactions; two group tests for fluoroquinolone class and a compound specific test each for norfloxacin, ciprofloxacin, gatifloxacin, ofloxacin, levofloxacin and sparfloxacin. The group color reactions are based on (a Oxidizing behavior of quinolone and (b Fluorine functional groups, both of which are characteristic of fluoroquinolone class. The compound specific color reactions are developed taking into consideration unique chemical behavior of each compound. The proposed chemical color tests have high selectivity⁄specificity, are ideal for screening purpose. The color of each test was defined by two standard color systems namely CIE lab and Munsell color. A suspected counterfeit tablet of any of the above mentioned drugs can be identified within 10-15 min using this rapid identification system.

  9. Thermal Protection System Aerothermal Screening Tests in HYMETS Facility (United States)

    Szalai, Christine E.; Beck, Robin A. S.; Gasch, Matthew J.; Alumni, Antonella I.; Chavez-Garcia, Jose F.; Splinter, Scott C.; Gragg, Jeffrey G.; Brewer, Amy


    The Entry, Descent, and Landing (EDL) Technology Development Project has been tasked to develop Thermal Protection System (TPS) materials for insertion into future Mars Entry Systems. A screening arc jet test of seven rigid ablative TPS material candidates was performed in the Hypersonic Materials Environmental Test System (HYMETS) facility at NASA Langley Research Center, in both an air and carbon dioxide test environment. Recession, mass loss, surface temperature, and backface thermal response were measured for each test specimen. All material candidates survived the Mars aerocapture relevant heating condition, and some materials showed a clear increase in recession rate in the carbon dioxide test environment. These test results supported subsequent down-selection of the most promising material candidates for further development.

  10. Screening Systems and Decision Making at the Preschool Level: Application of a Comprehensive Validity Framework (United States)

    Kettler, Ryan J.; Feeney-Kettler, Kelly A.


    Universal screening is designed to be an efficient method for identifying preschool students with mental health problems, but prior to use, screening systems must be evaluated to determine their appropriateness within a specific setting. In this article, an evidence-based validity framework is applied to four screening systems for identifying…

  11. A novel screening system for claudin binder using baculoviral display.

    Directory of Open Access Journals (Sweden)

    Hideki Kakutani

    Full Text Available Recent progress in cell biology has provided new insight into the claudin (CL family of integral membrane proteins, which contains more than 20 members, as a target for pharmaceutical therapy. Few ligands for CL have been identified because it is difficult to prepare CL in an intact form. In the present study, we developed a method to screen for CL binders by using the budded baculovirus (BV display system. CL4-displaying BV interacted with a CL4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE, but it did not interact with C-CPE that was mutated in its CL4-binding region. C-CPE did not interact with BV and CL1-displaying BV. We used CL4-displaying BV to select CL4-binding phage in a mixture of a scFv-phage and C-CPE-phage. The percentage of C-CPE-phage in the phage mixture increased from 16.7% before selection to 92% after selection, indicating that CL-displaying BV may be useful for the selection of CL binders. We prepared a C-CPE phage library by mutating the functional amino acids. We screened the library for CL4 binders by affinity to CL4-displaying BV, and we found that the novel CL4 binders modulated the tight-junction barrier. These findings indicate that the CL-displaying BV system may be a promising method to produce a novel CL binder and modulator.

  12. Why screening rates vary between Korea and Japan--differences between two national healthcare systems. (United States)

    Goto, Rei; Hamashima, Chisato; Mun, Sunghyun; Lee, Won-Chul


    Both Japan and Korea provide population-based screening programs. However, screening rates are much higher in Korea than in Japan. To clarify the possible factors explaining the differences between these two countries, we analyzed the current status of the cancer screening and background healthcare systems. Population- based cancer screening in Korea is coordinated well with social health insurance under a unified insurer system. In Japan, there are over 3,000 insurers and coordinating a comprehensive strategy for cancer screening promotion has been very difficult. The public healthcare system also has influence over cancer screening. In Korea, public healthcare does not cover a wide range of services. Almost free cancer screening and subsidization for medical cost for cancers detected in population-screening provides high incentive to participation. In Japan, on the other hand, a larger coverage of medical services, low co-payment, and a lenient medical audit enables people to have cancer screening under public health insurance as well as the broad range of cancer screening. The implementation of evidence-based cancer screening programs may be largely dependent on the background healthcare system. It is important to understand the impacts of each healthcare system as a whole and to match the characteristics of a particular health system when designing an efficient cancer screening system.

  13. Screening portal, system and method of using same (United States)

    Linker, Kevin L.; Hunter, John A.; Brusseau, Charles A.


    A portal, system and method for screening an object for a target substance is provided. The portal includes an inflatable bladder expandable to form a test space for receiving the object and a plurality of nozzles positioned about the inflatable bladder. The nozzles are in fluid communication with a fluid source for directing air over the object whereby samples are removed from the object for examination. A collector is operatively connected to the inflatable bladder for collecting the samples removed from the object. A detector is operatively connected to the collector for examining the removed samples for the presence of the target substance. At least one preconcentrator may be operatively connected to the collector for concentrating the samples collected thereby.

  14. $ND$ and $NB$ systems in quark delocalization color screening model

    CERN Document Server

    Zhao, Lifang; Ping, Jialun


    The $ND$ and $NB$ systems with $I=0$ and $1$, $J^{P}=\\frac{1}{2}^{\\pm}$, $\\frac{3}{2}^{\\pm}$, and $\\frac{5}{2}^{\\pm}$ are investigated within the framework of quark delocalization color screening model. The results show that all the positive parity states are unbound. By coupling to the $ND^{*}$ channel, the state $ND$ with $I=0,~J^{P}=\\frac{1}{2}^{-}$ can form a bound state, which can be invoked to explain the observed $\\Sigma(2800)$ state. The mass of the $ND^{*}$ with $I=0,~J^{P}=\\frac{3}{2}^{-}$ is close to that of the reported $\\Lambda_{c}(2940)^{+}$, which indicates that $\\Lambda_{c}(2940)^{+}$ can be explained as a $ND^{*}$ molecular state in QDCSM. Besides, the $\\Delta D^{*}$ with $I=1,~J^{P}=\\frac{5}{2}^{-}$ is also a possible resonance state. The results of the bottom case of $NB$ system are similar to those of the $ND$ system. Searching for these states will be a challenging subject of experiments.

  15. Microfluidic liquid chromatography system for proteomic applications and biomarker screening. (United States)

    Lazar, Iulia M; Trisiripisal, Phichet; Sarvaiya, Hetal A


    A microfluidic liquid chromatography (LC) system for proteomic investigations that integrates all the necessary components for stand-alone operation, i.e., pump, valve, separation column, and electrospray interface, is described in this paper. The overall size of the LC device is small enough to enable the integration of two fully functional separation systems on a 3 in. x 1 in. glass microchip. A multichannel architecture that uses electroosmotic pumping principles provides the necessary functionality for eluent propulsion and sample valving. The flow rates generated within these chips are fully consistent with the requirements of nano-LC platforms that are routinely used in proteomic applications. The microfluidic device was evaluated for the analysis of a protein digest obtained from the MCF7 breast cancer cell line. The cytosolic protein extract was processed according to a shotgun protocol, and after tryptic digestion and prefractionation using strong cation exchange chromatography (SCX), selected sample subfractions were analyzed with conventional and microfluidic LC platforms. Using similar experimental conditions, the performance of the microchip LC was comparable to that obtained with benchtop instrumentation, providing an overlap of 75% in proteins that were identified by more than two unique peptides. The microfluidic LC analysis of a protein-rich SCX fraction enabled the confident identification of 77 proteins by using conventional data filtering parameters, of 39 proteins with p screening applications.

  16. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases. (United States)

    Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong


    This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  17. A tetra-layer microfluidic system for peptide affinity screening through integrated sample injection. (United States)

    Wang, Weizhi; Huang, Yanyan; Jin, Yulong; Liu, Guoquan; Chen, Yi; Ma, Huimin; Zhao, Rui


    A novel integrated microfluidic system was designed and fabricated for affinity peptide screening with in situ detection. A tetra-layer microfluidic hybrid chip containing two top eccentric diffluent layers, an inter-layer and a bottom screening layer, was developed as the core device of the system. The eccentric diffluent layers were ingeniously invented for the vertical sample delivery from 2 top-inlets into 12 bottom-inlets, which eliminated the use of excessive accessories and complicated pipelines currently used in other systems. By using six pH gradient generators, the magnetic bead-based screening in 36 parallel chambers was simultaneously carried out under 6 different pH conditions from 5.4 to 8.2. This allowed simultaneous screening of 6 compounds and each under 6 different pH conditions. The fabricated chip system was applied to screening of affinity peptides towards β-endorphin antibody. The affinities of the peptide ligands to the antibody were assessed by on-chip confocal detection. The results from the screening study using this system indicated that the pentapeptide with the sequence of YGGFL had the highest affinity towards β-endorphin antibody at pH 7.1, which was further confirmed by the ELISA assay using a 96-well plate format. This microfluidic screening system is automatic, low-cost and reusable for not only peptide screening but also other bioactive compounds screening towards target molecules.

  18. Control and load management of a fuel cell based hybrid system; Steuerung und Lademanagement eines brennstoffzellen-basierten Hybridsystems

    Energy Technology Data Exchange (ETDEWEB)

    Klausmann, Andreas


    Objective of this work is the development of a control for a hybrid electric power train. Initial point is an electric drive powered by a rechargeable battery. This battery shall be recharged during operation by a methanol-driven fuel cell. At this point it is not intended to deploy a direct methanol fuel cell but a combination of a methanol reformer generating hydrogen-rich gas and a high-temperature fuel cell (HTPEM-FC). This work covers the general strategy of operation like load cycles, standby phases etc., the reformer control and the fuel cell operation with a newly developed charge concept. While the basic research is done on a rapid prototyping system this work aims on porting the control system to an embedded platform. Here emphasis is put on the hardware independency of the control. The development of the reformer control contains the strategy for heating up the system with a minimum of electrical energy consumption, since this energy has to be supplied from the battery during the system start-up, increasing the minimum charge level of the battery required for an autarkic recharge. Unlike in common systems the reformer will be modulated according to the electric load and not vice versa, though the fuel cell serves as load sensor. Beside start-up and shutdown strategies the fuel cell control covers particularly the charge control. The electric load is assumed to be unknown, non-influenceable and unsteady. The charge control handles the charging of the battery under optimal utilization of the available hydrogen while avoiding an overload of the fuel cell caused by sudden load changes like powering up the drive. Therefore the common step-down circuit will be advanced so that all huge and heavy electronic components can be minimized or substituted by internal effects of battery and fuel cell. The fuel utilization will be feed back to the reformer control. After coupling of reformer and fuel cell control the system will be ported to an embedded control system

  19. A cell-based systems biology assessment of human blood to monitor immune responses after influenza vaccination. (United States)

    Hoek, Kristen L; Samir, Parimal; Howard, Leigh M; Niu, Xinnan; Prasad, Nripesh; Galassie, Allison; Liu, Qi; Allos, Tara M; Floyd, Kyle A; Guo, Yan; Shyr, Yu; Levy, Shawn E; Joyce, Sebastian; Edwards, Kathryn M; Link, Andrew J


    Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses.

  20. Advanced cathode materials for polymer electrolyte fuel cells based on pt/ metal oxides: from model electrodes to catalyst systems. (United States)

    Fabbri, Emiliana; Pătru, Alexandra; Rabis, Annett; Kötz, Rüdiger; Schmidt, Thomas J


    The development of stable catalyst systems for application at the cathode side of polymer electrolyte fuel cells (PEFCs) requires the substitution of the state-of-the-art carbon supports with materials showing high corrosion resistance in a strongly oxidizing environment. Metal oxides in their highest oxidation state can represent viable support materials for the next generation PEFC cathodes. In the present work a multilevel approach has been adopted to investigate the kinetics and the activity of Pt nanoparticles supported on SnO2-based metal oxides. Particularly, model electrodes made of SnO2 thin films supporting Pt nanoparticles, and porous catalyst systems made of Pt nanoparticles supported on Sb-doped SnO2 high surface area powders have been investigated. The present results indicate that SnO2-based supports do not modify the oxygen reduction reaction mechanism on the Pt nanoparticle surface, but rather lead to catalysts with enhanced specific activity compared to Pt/carbon systems. Different reasons for the enhancement in the specific activity are considered and discussed.

  1. Biosensors and Biofuel Cells based on Vertically Aligned Carbon Nanotubes for Integrated Energy Sensing, Generation, and Storage (SGS) Systems (United States)

    Pandey, Archana; Prasad, Abhishek; Khin Yap, Yoke


    Diabetes is a growing health issue in the nation. Thus in-situ glucose sensors that can monitor the glucose level in our body are in high demand. Furthermore, it will be exciting if the excessive blood sugar can be converted into usable energy, and be stored in miniature batteries for applications. This will be the basis for an integrated energy sensing, generation, and storage (SGS) system in the future. Here we report the use of functionalized carbon nanotubes arrays as the glucose sensors as well as fuel cells that can convert glucose into energy. In principle, these devices can be integrated to detect excessive blood glucose and then convert the glucose into energy. They are also inline with our efforts on miniature 3D microbatteries using CNTs [1]. All these devices will be the basis for future SGS systems. Details of these results will be discussed in the meeting. [1] Wang et al., in 206^th Meeting of the Electrochemical Society, October 3-8, Honolulu, Hawaii (2004), Symposium Q1, abstract 1492. Y. K. Yap acknowledges supports from DARPA (DAAD17-03-C-0115), USDA (2007-35603-17740), and the Multi-Scale Technologies Institute (MuSTI) at MTU.

  2. Screensaver: an open source lab information management system (LIMS for high throughput screening facilities

    Directory of Open Access Journals (Sweden)

    Nale Jennifer


    Full Text Available Abstract Background Shared-usage high throughput screening (HTS facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. Results We have developed Screensaver, a free, open source, web-based lab information management system (LIMS, to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. Conclusions The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

  3. Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities (United States)


    Background Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. Results We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. Conclusions The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities. PMID:20482787

  4. Multidimensional single cell based STAT phosphorylation profiling identifies a novel biosignature for evaluation of systemic lupus erythematosus activity.

    Directory of Open Access Journals (Sweden)

    Xinfang Huang

    Full Text Available INTRODUCTION: Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE, a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE. METHODS: Phospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA patients and 13 healthy donors (HDs. A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10 were also monitored. RESULTS: We observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF, and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells. CONCLUSIONS: The basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE.

  5. Using a geographic information system to improve childhood lead-screening efforts. (United States)

    Graff, Robert


    The Idaho Division of Public Health conducted a pilot study to produce a lead-exposure-risk map to help local and state agencies better target childhood lead-screening efforts. Priority lead-screening areas, at the block group level, were created by using county tax assessor data and geographic information system software. A series of maps were produced, indicating childhood lead-screening prevalence in areas in which there was high potential for exposure to lead. These maps could enable development of more systematically targeted and cost-effective childhood lead-screening efforts.


    The report is a user's manual that describes Version 1.0 of EPA's STate Acid Rain Research and Screening System (STARRSS), developed to assist utility regulatory commissions in reviewing utility acid rain compliance plans. It is a screening tool that is based on scenario analysis...

  7. Functional Movement Screen (FMS) - kompleksowy system oceny funkcjonalnej pacjenta = Functional Movement Screen (FMS) - a comprehensive system for the functional evaluation of the patient


    Kochański, Bartosz; Plaskiewicz, Anna; Kałużny, Krystian; Dylewska, Monika; Płoszaj, Ola; Hagner-Derengowska, Magdalena; Zukow, Walery


    Kochański Bartosz, Plaskiewicz Anna, Kałużny Krystian, Dylewska Monika, Płoszaj Ola, Hagner-Derengowska Magdalena, Zukow Walery. Functional Movement Screen (FMS) - kompleksowy system oceny funkcjonalnej pacjenta = Functional Movement Screen (FMS) - a comprehensive system for the functional evaluation of the patient. Journal of Education, Health and Sport. 2015;5(4):90-101. ISSN 2391-8306. DOI: 10.5281/zenodo.16626

  8. Toxicological screening in urine: comparison of two automated HPLC screening systems, toxicological identification system (TOX.I.S.*) versus REMEDI-HS. (United States)

    Schönberg, Lena; Grobosch, Thomas; Lampe, Dagmar; Kloft, Charlotte


    In this paper, the comparison of two automated high-performance liquid chromatography (HPLC) screening systems, a newly developed toxicological identification system (TOX.I.S.) versus the commercially available Remedi-HS (Bio-Rad), is presented. Urine samples from 405 cases screened positive for amphetamines, cocaine, and opiates by immunological assays and confirmed by GC-MS were analyzed with both systems. In more than 80% (TOX.I.S.) and 78% (Remedi-HS) of the cases (except for cocaine), the results obtained by both HPLC methods showed agreement with the earlier obtained results by immunoassay prescreening and gas chromatography-mass spectrometry (GC-MS). The evaluation showed that both automated HPLC methods led to comparable results and can be used alternatively. As the confirmation results for cocaine were rather poor (45% TOX.I.S., 54% Remedi-HS) in comparison to GC-MS, the TOX.I.S. was further optimized for the detection of the cocaine metabolite benzoylecgonine (BEC). The BEC method improved the detectability of BEC from 45% to 80%. Besides confirmation screening, the use of both systems in cases of acute intoxications was investigated. Information about basic compounds was obtained from urine screening by both systems, which therefore were useful as complementary techniques in the toxicological laboratory. The TOX.I.S. offers advantages such as common equipment, modern software, and higher versatility with the opportunity to establish additional methods in the system.

  9. Evaluation of Lifestyle Criminality Screening from in Croatian Prison System


    Buđanovac, Aleksandar; Jandrić, Anita


    This paper examines metric characteristics and factor structure of Lifestyle Criminality Screening Form (LCSF). Also, the correlation between LCSF and Level of Service Inventory- Revised (LSI-R) is analysed. The sample consists of 399 male prisoners, placed in the Department of Diagnostics and Treatment Programming in Zagreb Prison between March 2004 and June 2005. Analysis of the metric characteristics suggested that the LCSF questionnaire requires some improvements. Reliability meas...

  10. A screening system for smear-negative pulmonary tuberculosis using artificial neural networks

    Directory of Open Access Journals (Sweden)

    João B. de O. Souza Filho


    Conclusions: In settings with a high prevalence of smear-negative PTB, the system can be useful for screening and also to aid clinical practice in expediting complementary tests for higher risk patients.

  11. A Novel Volumetric 3D Display System with Static Screen Project (United States)

    National Aeronautics and Space Administration — The physical world around us is three-dimensional (3D), yet most existing display systems with flat screens can handle only two-dimensional (2D) flat images that...

  12. In Vitro Testing of Scaffolds for Mesenchymal Stem Cell-Based Meniscus Tissue Engineering—Introducing a New Biocompatibility Scoring System

    Directory of Open Access Journals (Sweden)

    Felix P. Achatz


    Full Text Available A combination of mesenchymal stem cells (MSCs and scaffolds seems to be a promising approach for meniscus repair. To facilitate the search for an appropriate scaffold material a reliable and objective in vitro testing system is essential. This paper introduces a new scoring for this purpose and analyzes a hyaluronic acid (HA gelatin composite scaffold and a polyurethane scaffold in combination with MSCs for tissue engineering of meniscus. The pore quality and interconnectivity of pores of a HA gelatin composite scaffold and a polyurethane scaffold were analyzed by surface photography and Berliner-Blau-BSA-solution vacuum filling. Further the two scaffold materials were vacuum-filled with human MSCs and analyzed by histology and immunohistochemistry after 21 days in chondrogenic media to determine cell distribution and cell survival as well as proteoglycan production, collagen type I and II content. The polyurethane scaffold showed better results than the hyaluronic acid gelatin composite scaffold, with signs of central necrosis in the HA gelatin composite scaffolds. The polyurethane scaffold showed good porosity, excellent pore interconnectivity, good cell distribution and cell survival, as well as an extensive content of proteoglycans and collagen type II. The polyurethane scaffold seems to be a promising biomaterial for a mesenchymal stem cell-based tissue engineering approach for meniscal repair. The new score could be applied as a new standard for in vitro scaffold testing.

  13. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial (United States)

    Samir, Parimal; Galassie, Allison; Allos, Tara M.; Niu, Xinnan; Gordy, Laura E.; Creech, C. Buddy; Prasad, Nripesh; Jensen, Travis L.; Hill, Heather; Levy, Shawn E.; Joyce, Sebastian; Link, Andrew J.; Edwards, Kathryn M.


    Background Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. Objective and Methods We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18–49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Results Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Conclusions Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. Trial Registration NCT

  14. Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice (United States)

    Contreras, Amanda; Sen, Siddhartha; Tatar, Andrew J.; Mahvi, David A.; Meyers, Justin V.; Srinand, Prakrithi; Suresh, Marulasiddappa


    Adoptive cell transfer (ACT) melanoma immunotherapy typically employs acutely activated effector CD8+ T cells for their ability to rapidly recognize and clear antigen. We have previously observed that effector CD8+ T cells are highly susceptible to melanoma-induced suppression, whereas memory CD8+ T cells are not. Although memory T cells have been presumed to be potentially advantageous for ACT, the kinetics of local and systemic T cell responses after effector and memory ACT have not been compared. B16F10 melanoma cells stably transfected to express very low levels of the lymphocytic choriomeningitis virus (LCMV) peptide GP33 (B16GP33) were inoculated into syngeneic C57BL/6 mice. Equal numbers of bona fide naïve, effector, or memory phenotype GP33-specific CD8+ T cells were adoptively transferred into mice 1 day after B16GP33 inoculation. The efficacy of ACT immunotherapy was kinetically assessed using serial tumor measurements and flow cytometric analyses of local and systemic CD8+ T cell responses. Control of B16GP33 tumor growth, persistence of adoptively transferred CD8+ cells, intratumoral infiltration of CD8+ T cells, and systemic CD8+ T cell responsiveness to GP33 were strongest after ACT of memory CD8+ T cells. Following surgical tumor resection and melanoma tumor challenge, only mice receiving memory T cell-based ACT immunotherapy exhibited durable tumor-specific immunity. These findings demonstrate how the use of non-expanded memory CD8+ T cells may enhance ACT immunotherapeutic efficacy. PMID:27011014

  15. The screening effects of the screened exchange hybrid functional in surface systems: A case study on the CO/Pt(111) problem (United States)

    Li, H.; Gillen, R.; Robertson, J.


    The screened exchange (sX) hybrid functional has been widely used in computational material science. Although it has widely been studied in bulk systems, less is known about its functional behavior in surface systems which are crucial to many technologies such as materials synthesis and nano-electronic devices. Assessing the screening dependent functional behaviors in the surface systems is therefore important for its application in such systems. In this work, we investigate the screening effects of the sX in CO adsorption on Pt(111) surface. The differences between the sX and Heyd-Scuseria-Ernzerhof (HSE06) hybrid functionals, and the effects of screening parameters are studied. The screening has two effects: first, the HOMO-LUMO gap is screening dependent. This affects the site preference most significantly. In this work, atop adsorption of CO/Pt(111) is predicted by the hybrid functionals with screened exchange potential. The sX(1.44) gives the largest HOMO-LUMO gap for the isolated CO molecule. The adsorption energy difference between the atop and fcc site is also the largest by the sX(1.44) which is explained by the reduced metal d states to the CO 2π* state back-donation, with stronger effect for the fcc adsorption than for the atop adsorption; second, the adsorption energy is screening dependent. This can be seen by comparing the sX(2.38) and HSE06 which have different screening strengths. They show similar surface band structures for the CO adsorption but different adsorption energies, which is explained by the stronger CO 5σ state to the metal d states donation or the effectively screened Pauli repulsion. This work underlines the screening strength as a main difference between sX and HSE06, as well as an important hybrid functional parameter for surface calculation.

  16. A comparison of the performance of modern screen-film and digital mammography systems

    Energy Technology Data Exchange (ETDEWEB)

    Monnin, P [Institut Universitaire de Radiophysique Appliquee (IRA), CH-1007 Lausanne (Switzerland); Gutierrez, D [Institut Universitaire de Radiophysique Appliquee (IRA), CH-1007 Lausanne (Switzerland); Bulling, S [Institut Universitaire de Radiophysique Appliquee (IRA), CH-1007 Lausanne (Switzerland); Lepori, D [Department of Radiology, University Hospital Center (CHUV), CH-1011 Lausanne (Switzerland); Valley, J-F [Institut Universitaire de Radiophysique Appliquee (IRA), CH-1007 Lausanne (Switzerland); Verdun, F R [Institut Universitaire de Radiophysique Appliquee (IRA), CH-1007 Lausanne (Switzerland)


    This work compares the detector performance and image quality of the new Kodak Min-R EV mammography screen-film system with the Fuji CR Profect detector and with other current mammography screen-film systems from Agfa, Fuji and Kodak. Basic image quality parameters (MTF, NPS, NEQ and DQE) were evaluated for a 28 kV Mo/Mo (HVL = 0.646 mm Al) beam using different mAs exposure settings. Compared with other screen-film systems, the new Kodak Min-R EV detector has the highest contrast and a low intrinsic noise level, giving better NEQ and DQE results, especially at high optical density. Thus, the properties of the new mammography film approach those of a fine mammography detector, especially at low frequency range. Screen-film systems provide the best resolution. The presampling MTF of the digital detector has a value of 15% at the Nyquist frequency and, due to the spread size of the laser beam, the use of a smaller pixel size would not permit a significant improvement of the detector resolution. The dual collection reading technology increases significantly the low frequency DQE of the Fuji CR system that can at present compete with the most efficient mammography screen-film systems.

  17. Telescope Array Control System Based on Wireless Touch Screen Platform (United States)

    Fu, X. N.; Huang, L.; Wei, J. Y.


    GWAC (Ground-based Wide Angle Cameras) are the ground-based observational instruments of the Sino-French cooperation SVOM (Space Variable Objects Monitor) astronomical satellite, and Mini-GWAC is a pathfinder and supplement of GWAC. In the context of the Mini-GWAC telescope array, this paper introduces the design and implementation of a kind of telescope array control system, which is based on wireless serial interface module to communicate. We describe the development and implementation of the system in detail in terms of control system principle, system hardware structure, software design, experiment, and test. The system uses the touch-control PC which is based on the Windows CE system as the upper-computer, the wireless transceiver module and PLC (Programmable Logic Controller) as the core. It has the advantages of low cost, reliable data transmission, and simple operation. So far, the control system has been applied to Mini-GWAC successfully.

  18. Development of a screening system for the evaluation of soybean volatiles. (United States)

    Kakumyan, Pattana; Kato, Marie; Hajika, Makita; Matsui, Kenji


    Flavor properties are important factors of soybean seeds in their utilization as food materials. In order to isolate novel varieties and mutants of soybean having preferable flavor properties, a simple and efficient screening system was established using an automated headspace sampler coupled to gas chromatography. With this system, five major volatile compounds were analyzed within 12 min. By applying this screening system to 626 soybean varieties collected worldwide, we isolated four soybean varieties that showed unique compositions of volatile compounds. Through biochemical analysis, it was found that the uniqueness of three of them was possibly independent of lipoxygenase enzyme, and thus perhaps this screening system can expand the subject of flavor properties beyond lipoxygenase and thus be useful in discovering new types of soybeans.

  19. Efficacy of screening immune system function in at-risk newborns. (United States)

    Pavlovski, Christopher J


    This paper explores the introduction of a screening test to highlight impaired immune system status for newborn infants and its efficacy as a preventative clinical measure. Moreover, it is suggested that screening of the infantile immune system has the potential to highlight susceptibility to a range of infant and childhood diseases, bestowing an opportunity to introduce early intervention to reduce the incidence of these diseases. Development of the neonatal immune system is an important health issue, implicated in many childhood problems such as allergies, infection, and autoimmunity. The neonate has a limited immune system and ability to combat bacteria. Depleted levels of the tripeptide reduced glutathione (GSH) have been linked to numerous conditions and its intracellular level is acknowledged as an indicator of immune system function. Introduction of an immune system screening programme for infants is formally reviewed and assessed. Several benefits are reported in the treatment of impaired immune systems, a trial screening programme is proposed for at-risk infants to gather further evidence as to its efficacy. Infants at risk of impaired immune system function include cystic fibrosis, premature infants, and low birth weight infants. The interventions include breastfeeding, milk banks, and appropriate formula to support the immune system.

  20. Factor Structure of the BASC-2 Behavioral and Emotional Screening System Student Form (United States)

    Dowdy, Erin; Twyford, Jennifer M.; Chin, Jenna K.; DiStefano, Christine A.; Kamphaus, Randy W.; Mays, Kristen L.


    The BASC-2 Behavioral and Emotional Screening System (BESS) Student Form (Kamphaus & Reynolds, 2007) is a recently developed youth self-report rating scale designed to identify students at risk for behavioral and emotional problems. The BESS Student Form was derived from the Behavior Assessment System for Children-Second Edition Self-Report of…

  1. Prototype of Microwave Imaging System for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Zhurbenko, Vitaliy


    Microwave imaging for breast-cancer detection has received the attention of a large number of research groups in the last decade. In this paper, the imaging system currently being developed at the Technical university of Denmark is presented. This includes a description of the antenna system......, the microwave hardware, and the imaging algorithm....

  2. Microfluidic chip-based analytical system for rapid screening of photocatalysts. (United States)

    Zhang, Hao; Wang, Jing-Jing; Fan, Jie; Fang, Qun


    A simple and efficient microfluidic chip-based analytical system for rapid screening of photocatalysts was developed. The catalyst screening system consisted of a microchip with multiple channels for parallel reactions, a UV light source, and a CCD camera-based photometric detection system for monitoring the photocatalytic reaction. A novel microfluidic introduction method for loading particle samples into chip microchannels was established using dry sample powders and wedge-structure channel design. With this method, multiple different photocatalyst samples could be quickly introduced into the microchip with good reproducibility without the need of additional pumps or valves. We applied the present system in the rapid screening of doping TiO2 photocatalysts in terms of their activity for methylene blue (MB) degradation under UV light irradiation. Ten parallel photocatalyst screening reactions were achieved within 15 min in the multi-channel chip. We also examined nine element doped TiO2 materials to investigate the doping effects of different elements on TiO2. Compared with conventional systems, the photocatalyst consumption (0.1mg) in the present system was significantly reduced at least 100 times. High reaction rate in chip microreactors was obtained with an increase of two orders of magnitude over bulk reactors. The miniaturization of the photocatalytic reaction on the microchip significantly improves the reaction rates, reduces the sample and reagent consumptions, and increases the throughput of screening for multiple catalyst samples in parallel. The present work provides a novel application for microfluidic chip-based analytical systems, as well as a rapid, highly-efficient and low-consumption method for screening of photocatalysts.

  3. Cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry for screening bioactive capilliposide C metabolites generated by rat intestinal microflora. (United States)

    Cheng, Zhongzhe; Huang, Meilin; Chen, Guiying; Yang, Guangjie; Zhou, Xin; Chen, Chang; Zhang, Yang; Xu, Yong; Feng, Yulin; Zhang, Lin; Jiang, Hongliang


    Many plant-derived glycosides are used as medications. It is common that these glycosides show poor intestinal absorption but their metabolites generated by intestinal microflora demonstrate strong bioactivity. Hence, it is crucial to develop a method for the identification and characterization of the metabolites, and consequently reveal the pathway in which the glycosides are processed in gut. In this study, cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) were developed for rapid discovery and evaluation of the metabolites of a glycoside compound, capilliposide C (LC-C). 92.7% of LC-C was biotransformed by rat intestinal microflora after 36-h incubation at 37°C. Human cancer cell lines HepG2, PC-3 and A549 was treated with metabolites pool, respectively, which was followed by cell viability assays and characterization of metabolites using UHPLC-QTOF-MS/MS. As a result, significant cytotoxicity was observed for the metabolites pool, from which six metabolites were identified. Based on the metabolites identified, deglycosylation and esterolysis were proposed as the major metabolic pathways of LC-C in rat intestinal microflora. In addition, M4, an esterolysis product of LC-C, was obtained and evaluated for its bioactivity in vitro. As a result, M4 exhibited a reduction in cell viability in HepG2 with an IC50 value of 17.46±1.55μg/mL.

  4. Integrated remote analytical screening system for hostile environments (United States)

    Addleman, Shane R.; Crawford, Beverly A.; Keele, B. D.; Kohlasch, Frank L.; Rebagay, Teofila V.; Troyer, Gary L.


    An integrated analytical measurement system is being assembled for application to remote analysis in chemically and radiologically harsh environments. A single, compact, integrated probe will be the only section of the system in the hostile environment. The instrument array initially composed of a fiber optic Raman spectrophotometer, a fiber optic FTIR, gamma radiation spectrometer, beta radiation detector, and a CCD camera. Within the hostile region, a robotic positioning system or remote manipulators will provide mobility for the multisensor probe. The application of this array will be to characterize multiphase nuclear waste.

  5. A new screening method to identify inhibitors of the Lol (localization of lipoproteins) system, a novel antibacterial target. (United States)

    Ito, Hideaki; Ura, Atsushi; Oyamada, Yoshihiro; Yoshida, Hiroaki; Yamagishi, Jun-Ichi; Narita, Shin-Ichiro; Matsuyama, Shin-Ichi; Tokuda, Hajime


    As the Lol system, which is involved in localization of lipoproteins, is essential for Escherichia coli growth and widely conserved among gram-negative bacteria, it is considered to be a promising target for the development of anti-gram-negative bacterial agents. However, no high-throughput screening method has so far been developed to screen for Lol system inhibitors. By combining three assay systems (anucleate cell blue assay, Lpp assay, and LolA-dependent release inhibition assay) and a drug susceptibility test, we have successfully developed a new screening method for identification of compounds that inhibit the Lol system. Using this new screening method, we screened 23,600 in-house chemical compounds and found 2 Lol system inhibitors. We therefore conclude that our new screening method can efficiently identify new antibacterial agents that target the Lol system.

  6. Online fault location on AC cables in underground transmission systems using screen currents

    DEFF Research Database (Denmark)

    Jensen, Christian Flytkjær; Nanayakkara, O.M.K.K; Rajapakse, Athula

    This paper studies online travelling wave methods for fault location on a crossbonded cable system using screen currents. During the construction of the electrical connection to the 400 MW off shore wind farm Anholt, it was possible to perform measurements on a 38.4 km crossbonded cable system...... coils if the screen currents contain the necessary information for accurate fault location. In this paper, this is examined by analysis of field measurements and through a study of simulations. The wavelet transform and visual inspection methods are used and the accuracy is compared. Field measurements...... and simulations are compared for testing the reliability of using simulations for studying fault location methods....

  7. Dynamic screening and electron electron scattering in low-dimensional metallic systems (United States)

    Silkin, V. M.; Quijada, M.; Muiño, R. Díez; Chulkov, E. V.; Echenique, P. M.


    The modification of dynamic screening in the electron-electron interaction in systems with reduced dimensionality and tunable one-particle electronic structure is studied. Two examples of such systems are considered, namely, the adsorbate-induced quantum well states at the Na adlayer covered Cu(1 1 1) surface, and metal clusters of sizes up to few nanometers. The dependence of the electron-electron decay rates on the Na coverage in the former case and on the cluster size in the latter is investigated. The role played by the dynamical screened interaction in such processes is addressed as well.

  8. Realization of Intelligent Measurement and Control System for Limb Rehabilitation Based on PLC and Touch Screen (United States)

    Liu, Xiangquan

    According to the treatment needs of patients with limb movement disorder, on the basis of the limb rehabilitative training prototype, function of measure and control system are analyzed, design of system hardware and software is completed. The touch screen which is adopt as host computer and man-machine interaction window is responsible for sending commands and training information display; The PLC which is adopt as slave computer is responsible for receiving control command from touch screen, collecting the sensor data, regulating torque and speed of motor by analog output according to the different training mode, realizing ultimately active and passive training for limb rehabilitation therapy.

  9. The criteria for metabolic syndrome and the national health screening and education system in Japan. (United States)

    Yamagishi, Kazumasa; Iso, Hiroyasu


    Two major definitions of metabolic syndrome have been proposed. One focuses on the accumulation of risk factors, a measure used by the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI); the other focuses on abdominal obesity, a measure used by the International Diabetes Federation (IDF) and the Japanese government. The latter definition takes waist circumference (WC) into consideration as an obligatory component, whereas the former does not. In 2009, the IDF, NHLBI, AHA, and other organizations attempted to unify these criteria; as a result, WC is no longer an obligatory component of those systems, while it remains obligatory in the Japanese criteria. In 2008, a new Japanese cardiovascular screening and education system focused on metabolic syndrome was launched. People undergoing screening are classified into three groups according to the presence of abdominal obesity and the number of metabolic risk factors, and receive health educational support from insurers. This system has yielded several beneficial outcomes: the visibility of metabolic syndrome at the population level has drastically improved; preventive measures have been directed toward metabolic syndrome, which is expected to become more prevalent in future generations; and a post-screening education system has been established. However, several problems with the current system have been identified and are under debate. In this review, we discuss topics related to metabolic syndrome, including (1) the Japanese criteria for metabolic syndrome; (2) metabolic syndrome and the universal health screening and education system; and (3) recent debates about Japanese criteria for metabolic syndrome.

  10. Processing of nanolitre liquid plugs for microfluidic cell-based assays

    Directory of Open Access Journals (Sweden)

    Junji Fukuda, Shintaro Takahashi, Tatsuya Osaki, Naoto Mochizuki and Hiroaki Suzuki


    Full Text Available Plugs, i.e. droplets formed in a microchannel, may revolutionize microfluidic cell-based assays. This study describes a microdevice that handles nanolitre-scale liquid plugs for the preparation of various culture setups and subsequent cellular assays. An important feature of this mode of liquid operation is that the recirculation flow generated inside the plug promotes the rapid mixing of different solutions after plugs are merged, and it keeps cell suspensions homogeneous. Thus, serial dilutions of reagents and cell suspensions with different cell densities and cell types were rapidly performed using nanolitres of solution. Cells seeded through the plug processing grew well in the microdevice, and subsequent plug processing was used to detect the glucose consumption of cells and cellular responses to anticancer agents. The plug-based microdevice may provide a useful platform for cell-based assay systems in various fields, including fundamental cell biology and drug screening applications.

  11. Nuclear Material Monitoring System (NMMS) for security screens

    Energy Technology Data Exchange (ETDEWEB)

    Hyun Kim, Kwang, E-mail: [Faculty of Biomedical Engineering, Jungwon University, 5 Goesan-eup, Goesan-gun, Chungcheongbuk-do 367-805 (Korea, Republic of); Hong Chang, Ji [Faculty of Biomedical Engineering, Jungwon University, 5 Goesan-eup, Goesan-gun, Chungcheongbuk-do 367-805 (Korea, Republic of); Hyun Jung, Young [Department of Radiological Science, Yonsei University, Wonju (Korea, Republic of)


    As a Nuclear Material Monitoring System (NMMS), two large-volume plastic detectors and a NaI detector for gamma-ray sources and two He-3 tubes for neutron sources were integrated in a mobile box that can be mounted on a vehicle. Custom-made preamplifiers, shapers, and a MCA (Multi-Channel Analyzer) for each detector were conceived of and built on a compact circuit board to collect and integrate different types of data from each detector. The collected data, counts rates and spectra of the detected radiation, were continually monitored and plotted on several user-friendly display windows on a laptop computer. The system performance in the vehicle-mounted condition was tested for Co-60, Cs-137, and Cf-252 sources at various distances and speeds.

  12. Performance of Implementing Guideline Driven Cervical Cancer Screening Measures in an Inner City Hospital System (United States)

    Wieland, Daryl L.; Reimers, Laura L.; Wu, Eijean; Nathan, Lisa M.; Gruenberg, Tammy; Abadi, Maria; Einstein, Mark H.


    Objective In 2006, the American Society for Colposcopy and Cervical Pathology (ASCCP) updated evidence based guidelines recommending screening intervals for women with abnormal cervical cytology. In our low-income inner city population, we sought to improve performance by uniformly applying the guidelines to all patients. We report the prospective performance of a comprehensive tracking, evidence-based algorithmically driven call-back and appointment scheduling system for cervical cancer screening in a resource-limited inner city population. Materials and Methods Outreach efforts were formalized with algorithm-based protocols for triage to colposcopy, with universal adherence to evidence-based guidelines. During implementation from August 2006 through July 2008, we prospectively tracked performance using the electronic medical record with administrative and pathology reports to determine performance variables such as the total number of Pap tests, colposcopy visits, and the distribution of abnormal cytology and histology results, including all CIN 2,3 diagnoses. Results 86,257 gynecologic visits and 41,527 Pap tests were performed system-wide during this period of widespread and uniform implementation of standard cervical cancer screening guidelines. The number of Pap tests performed per month varied little. The incidence of CIN 1 significantly decreased from 117/171 (68.4%) the first tracked month to 52/95 (54.7%) the last tracked month (p=0.04). The monthly incidence rate of CIN 2,3, including incident cervical cancers did not change. The total number of colposcopy visits declined, resulting in a 50% decrease in costs related to colposcopy services and approximately a 12% decrease in costs related to excisional biopsies. Conclusions Adherence to cervical cancer screening guidelines reduced the number of unnecessary colposcopies without increasing numbers of potentially missed CIN 2,3 lesions, including cervical cancer. Uniform implementation of administrative

  13. Controllable 3D Display System Based on Frontal Projection Lenticular Screen (United States)

    Feng, Q.; Sang, X.; Yu, X.; Gao, X.; Wang, P.; Li, C.; Zhao, T.


    A novel auto-stereoscopic three-dimensional (3D) projection display system based on the frontal projection lenticular screen is demonstrated. It can provide high real 3D experiences and the freedom of interaction. In the demonstrated system, the content can be changed and the dense of viewing points can be freely adjusted according to the viewers' demand. The high dense viewing points can provide smooth motion parallax and larger image depth without blurry. The basic principle of stereoscopic display is described firstly. Then, design architectures including hardware and software are demonstrated. The system consists of a frontal projection lenticular screen, an optimally designed projector-array and a set of multi-channel image processors. The parameters of the frontal projection lenticular screen are based on the demand of viewing such as the viewing distance and the width of view zones. Each projector is arranged on an adjustable platform. The set of multi-channel image processors are made up of six PCs. One of them is used as the main controller, the other five client PCs can process 30 channel signals and transmit them to the projector-array. Then a natural 3D scene will be perceived based on the frontal projection lenticular screen with more than 1.5 m image depth in real time. The control section is presented in detail, including parallax adjustment, system synchronization, distortion correction, etc. Experimental results demonstrate the effectiveness of this novel controllable 3D display system.

  14. 采用磁微粒分离酶联免疫法构建基于KGN细胞的雌激素生物合成筛选模型%Establishment of a Cell-based Screen Platform for Estrogen Biosynthesis Using Magnetic Particle-based Enzyme-linked immunosorbent Assay

    Institute of Scientific and Technical Information of China (English)

    鲁丹枫; Azimova Bahtigul Jovliqizi; 张国林; 王飞


    Estrogens play important roles in the growth and development of human,and the disorders of estrogen biosynthesis and metabolism can lead to occurrence of many diseases such as breast cancer and osteoporosis. Currently, the cell-based screen models for estrogen biosynthesis need the use of radioactive substances, which cause environmental pollution and the cost for screening too high to be affordable,thus severely restrict the finding of new drugs to modulate estrogen biosynthesis in a tissue-specific manner. By using human granulosa-like KGN cells which express high amount of aromatase.we found that the 17β-estradiol magnetic particle-based enzyme-linked imminosorbent assay (ELISA) was more stable and sensitive than conventional polystyrene-based ELJSA in quantification of 17β-estradiol by comparing the cross-reactivity and sensitivity of the two different 17β-estradiol ELJSA methods. After further examining the effects of phenol red in cell culture medium and testosterone substance concentration on the quantitative detection of 17β-estradi-ol.we successfully established a human granulosa-like KGN cell-based screen platform for estrogen biosynthesis by using magnetic particle-based ELJSA.%雌激素在机体生长发育中发挥着重要作用,其合成代谢紊乱会导致乳腺癌和骨质疏松等疾病发生.目前,基于细胞的雌激素合成筛选模型需用到放射性底物,对环境污染大,成本较高,限制了具有组织特异性调控雌激素合成的药物筛选.我们以高表达芳香化酶的KGN细胞为检测对象,比较基于聚苯乙烯酶联免疫法和磁微粒分离酶联免疫法的雌二醇ELISA试剂盒的交叉反应和灵敏度,发现相对于聚苯乙烯酶联免疫法,磁微粒分离酶联免疫法能够稳定高效的检测雌激素合成.进一步比较培养基中酚红和底物睾酮对雌二醇检测的影响,成功建立通过磁微粒酶联免疫法检测KGN细胞雌二醇合成的筛选模型.

  15. ANN expert system screening for illicit amphetamines using molecular descriptors (United States)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.


    The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

  16. Experience with the European quality assurance guidelines for digital mammography systems in a national screening programme. (United States)

    McCullagh, J; Keavey, E; Egan, G; Phelan, N


    The transition to a fully digital breast screening programme, utilising three different full-field digital mammography (FFDM) systems has presented many challenges to the implementation of the European guidelines for physico-technical quality assurance (QA) testing. An analysis of the QA results collected from the FFDM systems in the screening programme over a 2-y period indicates that the three different systems have similar QA performances. Generally, the same tests were failed by all systems and failure rates were low. The findings provide some assurance that the QA guidelines are being correctly implemented. They also suggest that there is more scope for the development of the relevance of the guidelines with respect to modern FFDM systems. This study has also shown that a summary review of the QA data can be achieved by simple organisation of the QA data storage and by automation of data query and retrieval using commonly available software.

  17. Adapting the Australian system: is an organized screening program feasible in Malaysia?--an overview of cervical cancer screening in both countries. (United States)

    Rashid, Rima Ma; Dahlui, Maznah; Mohamed, Majdah; Gertig, Dorota


    Cervical cancer is the third most common form of cancer that strikes Malaysian women. The National Cancer Registry in 2006 and 2007 reported that the age standardized incidence (ASR) of cervical cancer was 12.2 and 7.8 per 100,000 women, respectively. The cumulative risk of developing cervical cancer for a Malaysian woman is 0.9 for 74 years. Among all ethnic groups, the Chinese experienced the highest incidence rate in 2006, followed by Indians and Malays. The percentage cervical cancer detected at stage I and II was 55% (stage I: 21.0%, stage II: 34.0%, stage III: 26.0% and stage IV: 19.0%). Data from Ministry of Health Malaysia (2006) showed a 58.9% estimated coverage of pap smear screening conducted among those aged 30-49 years. Only a small percentage of women aged 50-59 and 50-65 years old were screened, 14% and 13.8% coverage, respectively. Incidence of cervical cancer was highest (71.6%) among those in the 60-65 age group (MOH, 2003). Currently, there is no organized population-based screening program available for the whole of Malaysia. A pilot project was initiated in 2006, to move from opportunistic cervical screening of women who attend antenatal and postnatal visits to a population based approach to be able to monitor the women through the screening pathway and encourage women at highest risk to be screened. The project was modelled on the screening program in Australia with some modifications to suit the Malaysian setting. Substantial challenges have been identified, particularly in relation to information systems for call and recall of women, as well as laboratory reporting and quality assurance. A cost-effective locally-specific approach to organized screening, that will provide the infrastructure for increasing participation in the cervical cancer screening program, is urgently required.

  18. Improved benzodiazepine radioreceptor assay using the MultiScreen (R) Assay System

    NARCIS (Netherlands)

    Janssen, MJ; Ensing, K; de Zeeuw, RA


    In this article, an improved benzodiazepine radioreceptor assay is described, which allows substantial reduction in assay time, The filtration in this method was performed by using the MultiScreen(R) Assay System. The latter consists of a 96-well plate with glass fibre filters sealed at the bottom,

  19. Screening of Aspergillus nidulans metabolites from habitat mimicking media using LC-DAD-TOFMS system

    DEFF Research Database (Denmark)

    Klitgaard, Andreas; Holm, Dorte Koefoed; Frisvad, Jens Christian;


    cultured on a range of different habitat mimicking media. Extracts from the fungi were analyzed using a LC-DAD-TOFMS system, and by screening the extracts using an in-house database of known fungal metabolites. Using this database we were able to easily select unknown compounds, and dereplicate these using...

  20. Development and applicability of a ready-to-use PCR system for GMO screening. (United States)

    Rosa, Sabrina F; Gatto, Francesco; Angers-Loustau, Alexandre; Petrillo, Mauro; Kreysa, Joachim; Querci, Maddalena


    With the growing number of GMOs introduced to the market, testing laboratories have seen their workload increase significantly. Ready-to-use multi-target PCR-based detection systems, such as pre-spotted plates (PSP), reduce analysis time while increasing capacity. This paper describes the development and applicability to GMO testing of a screening strategy involving a PSP and its associated web-based Decision Support System. The screening PSP was developed to detect all GMOs authorized in the EU in one single PCR experiment, through the combination of 16 validated assays. The screening strategy was successfully challenged in a wide inter-laboratory study on real-life food/feed samples. The positive outcome of this study could result in the adoption of a PSP screening strategy across the EU; a step that would increase harmonization and quality of GMO testing in the EU. Furthermore, this system could represent a model for other official control areas where high-throughput DNA-based detection systems are needed.

  1. Natural and Unnatural Parity Resonance States in the Positron-Hydrogen System with Screened Coulomb Interactions

    Directory of Open Access Journals (Sweden)

    Ye Ning


    Full Text Available In the present work, we report calculations of resonances in the positron-hydrogen system interacting with screened Coulomb potentials using the method of complex scaling together with employing correlated Hylleraas wave functions. Resonances with natural and unnatural parities are investigated. For the natural parity case, resonance parameters (energy and width for D-wave resonance states with even parity lying below various positronium and hydrogen thresholds up to the H(N = 4 level are determined. For the unnatural parity case, results for P-even and D-odd resonance states with various screened Coulomb interaction strengths are located below different lower-lying Ps and H thresholds.

  2. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine Lydia


    different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after...... tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts...

  3. ScreenRecorder: A Utility for Creating Screenshot Video Using Only Original Equipment Manufacturer (OEM) Software on Microsoft Windows Systems (United States)


    ScreenRecorder: A Utility for Creating Screenshot Video Using Only Original Equipment Manufacturer (OEM) Software on Microsoft Windows Systems...ScreenRecorder: A Utility for Creating Screenshot Video Using Only Original Equipment Manufacturer (OEM) Software on Microsoft Windows Systems 5a...Ground, MD 21005-5069 ARL-TN-0658 January 2015 ScreenRecorder: A Utility for Creating Screenshot Video Using Only Original Equipment

  4. An Active Learning Classifier for Further Reducing Diabetic Retinopathy Screening System Cost

    Directory of Open Access Journals (Sweden)

    Yinan Zhang


    Full Text Available Diabetic retinopathy (DR screening system raises a financial problem. For further reducing DR screening cost, an active learning classifier is proposed in this paper. Our approach identifies retinal images based on features extracted by anatomical part recognition and lesion detection algorithms. Kernel extreme learning machine (KELM is a rapid classifier for solving classification problems in high dimensional space. Both active learning and ensemble technique elevate performance of KELM when using small training dataset. The committee only proposes necessary manual work to doctor for saving cost. On the publicly available Messidor database, our classifier is trained with 20%–35% of labeled retinal images and comparative classifiers are trained with 80% of labeled retinal images. Results show that our classifier can achieve better classification accuracy than Classification and Regression Tree, radial basis function SVM, Multilayer Perceptron SVM, Linear SVM, and K Nearest Neighbor. Empirical experiments suggest that our active learning classifier is efficient for further reducing DR screening cost.

  5. Systems analysis of quantitative shRNA-library screens identifies regulators of cell adhesion

    Directory of Open Access Journals (Sweden)

    Huang XiaoDong


    Full Text Available Abstract Background High throughput screens with RNA interference technology enable loss-of-function analyses of gene activities in mammalian cells. While the construction of genome-scale shRNA libraries has been successful, results of large-scale screening of those libraries can be difficult to analyze because of the relatively high noise levels and the fact that not all shRNAs in a library are equally effective in silencing gene expression. Results We have screened a library consisting of 43,828 shRNAs directed against 8,500 human genes for functions that are necessary in cell detachment induced by a constitutively activated c-Abl tyrosine kinase. To deal with the issues of noise and uncertainty of knockdown efficiencies, we employed an analytical strategy that combines quantitative data analysis with biological knowledge, i.e. Gene Ontology and pathway information, to increase the power of the RNAi screening technique. Using this strategy we found 16 candidate genes to be involved in Abl-induced disruption of cell adhesion, and verified that the knockdown of IL6ST is associated with enhanced cell attachment. Conclusion Our results suggest that the power of genome-wide quantitative shRNA screens can be significantly increased when analyzed using a systems biology-based approach to identify functional gene networks.

  6. Automatic Glass-Slide Capturing System for Cervical Cancer Pre-Screening Program

    Directory of Open Access Journals (Sweden)

    Nor R.M. Noor


    Full Text Available Clinical glass-slide capturing system is becoming an important part of telemedicine, medical database and diagnostic system that involves of microscope and image acquisition device which is digital camera. One of the areas of interest is slide capturing system for cervical cancer pre-screening program. An automated microscope with FireWire digital camera will be used to acquire the image and store in digital lossless format. The capturing procedure involves of 100X and 400 X magnifications that are necessary for further diagnosis actions. The system that comes with software and hardware parts also provides image retrieval or displaying facilities for ease of user who are pathologist and cytologist to perform the screening program.

  7. High-throughput screens in mammalian cells using the CRISPR-Cas9 system. (United States)

    Peng, Jingyu; Zhou, Yuexin; Zhu, Shiyou; Wei, Wensheng


    As a powerful genome-editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR)-clustered regularly interspaced short palindromic repeats-associated protein 9 (Cas9) system has been quickly developed into a large-scale function-based screening strategy in mammalian cells. This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. Compared with RNA interference screening, the CRISPR-Cas9 system demonstrates much higher levels of effectiveness and reliability with respect to both loss-of-function and gain-of-function screening. Unlike the RNA interference strategy, a CRISPR-Cas9 library can target both protein-coding sequences and regulatory elements, including promoters, enhancers and elements transcribing microRNAs and long noncoding RNAs. This powerful genetic tool will undoubtedly accelerate the mechanistic discovery of various biological processes. In this mini review, we summarize the general procedure of CRISPR-Cas9 library mediated functional screening, system optimization strategies and applications of this new genetic toolkit.

  8. Cell-based biosensors: Towards the development of cellular monitoring

    Institute of Scientific and Technical Information of China (English)


    Cell-based biosensors (CBBs), a research hotspot of biosensors, which treat living cells as sensing elements, can detect the functional information of biologically active analytes. They characterize with high sensitivity, excellent selectivity and rapid response, and have been applied in many fields, such as biomedicine, environmental monitoring and pharmaceutical screening. Recently cell-cultured technology, silicon microfabrication technology and genetic technology have promoted exploration of CBBs dramatically. To elucidate the novel research findings and applications of cell- based biosensors, this paper summarizes various research approaches, presents some challenges and proposes the research trends.

  9. Design of a breath analysis system for diabetes screening and blood glucose level prediction. (United States)

    Yan, Ke; Zhang, David; Wu, Darong; Wei, Hua; Lu, Guangming


    It has been reported that concentrations of several biomarkers in diabetics' breath show significant difference from those in healthy people's breath. Concentrations of some biomarkers are also correlated with the blood glucose levels (BGLs) of diabetics. Therefore, it is possible to screen for diabetes and predict BGLs by analyzing one's breath. In this paper, we describe the design of a novel breath analysis system for this purpose. The system uses carefully selected chemical sensors to detect biomarkers in breath. Common interferential factors, including humidity and the ratio of alveolar air in breath, are compensated or handled in the algorithm. Considering the intersubject variance of the components in breath, we build subject-specific prediction models to improve the accuracy of BGL prediction. A total of 295 breath samples from healthy subjects and 279 samples from diabetic subjects were collected to evaluate the performance of the system. The sensitivity and specificity of diabetes screening are 91.51% and 90.77%, respectively. The mean relative absolute error for BGL prediction is 21.7%. Experiments show that the system is effective and that the strategies adopted in the system can improve its accuracy. The system potentially provides a noninvasive and convenient method for diabetes screening and BGL monitoring as an adjunct to the standard criteria.

  10. Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems. (United States)

    Woehrling, E K; Hill, E J; Coleman, M D


    Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.

  11. Screening system of blocking agents of the receptor for advanced glycation endproducts in cells using fluorescence. (United States)

    Jung, Dong Ho; Kim, Young Sook; Kim, Jin Sook


    Activation of the receptor for advanced glycation endproducts (RAGE) triggers cellular responses implicated in the pathogenesis of diabetic complications; blockade of RAGE has been shown to inhibit the development of diabetic complications. To develop a screening system to identify novel disruptors of advanced glycation endproducts (AGE)-RAGE binding, we used an AGE-RAGE binding system in RAGE-overexpressing cells; test compounds were screened using this system. To construct human RAGE-overexpressing cells, mouse mesangial cells (MMCs) were stably transfected with the pcDNA-human RAGE (hRAGE) vector and selected under 1 mg/mL gentamicin (G418). RAGE expression in hRAGE-overexpressing MMCs was analyzed by Western blotting with specific RAGE antibody. To identify novel disruptors of AGE-RAGE binding, 50 single compounds and AGE-bovine serum albumin (BSA)-Alexa 488 (AGE-BSA labeled with Alexa 488) were treated to the hRAGE-overexpressing MMCs. Nonbinding AGE-BSA-Alexa 488 was washed and fluorescence measured by microtiter plate reader (excitation wavelength, 485 nm; emission wavelength, 528 nm). In hRAGE-overexpressing cells, only treatment with AGE-BSA-Alexa 488 significantly increased fluorescence intensity in a dose-dependent manner. Of 50 compounds tested, genistein disrupted AGE-RAGE binding in a dose-dependent manner. This AGE-RAGE binding system using AGE-BSA-Alexa 488 in hRAGE-overexpressing cells was suitable for screening of agents that disrupt AGE-hRAGE binding.

  12. Microfabricated Electrochemical Cell-Based Biosensors for Analysis of Living Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Jun Wang


    Full Text Available Cellular biochemical parameters can be used to reveal the physiological and functional information of various cells. Due to demonstrated high accuracy and non-invasiveness, electrochemical detection methods have been used for cell-based investigation. When combined with improved biosensor design and advanced measurement systems, the on-line biochemical analysis of living cells in vitro has been applied for biological mechanism study, drug screening and even environmental monitoring. In recent decades, new types of miniaturized electrochemical biosensor are emerging with the development of microfabrication technology. This review aims to give an overview of the microfabricated electrochemical cell-based biosensors, such as microelectrode arrays (MEA, the electric cell-substrate impedance sensing (ECIS technique, and the light addressable potentiometric sensor (LAPS. The details in their working principles, measurement systems, and applications in cell monitoring are covered. Driven by the need for high throughput and multi-parameter detection proposed by biomedicine, the development trends of electrochemical cell-based biosensors are also introduced, including newly developed integrated biosensors, and the application of nanotechnology and microfluidic technology.

  13. Calculations of properties of screened He-like systems using correlated wave functions. (United States)

    Dai, S T; Solovyova, A; Winkler, P


    The purpose of the present study is twofold. First, the techniques of correlated wave functions for two-electron systems have been extended to obtain results for P and D states in a screening environment, and in particular for Debye screening. In these calculations, the satisfaction of both the quantum virial theorem and a related sum rule has been enforced and found to provide a high degree of stability of the solutions. Second, in order to facilitate the general use of correlated wave functions in combination with sum rule stability criteria, a rather systematic computational approach to this notoriously cumbersome method has been developed and thoroughly discussed here. Accurate calculations for few-electron systems are of interest to plasma diagnostics; in particular, when inaccuracies in binding energies are drastically magnified as they occur in exponents of Boltzmann factors.

  14. Quantitative Population Epigenetics in Screening and Development of Regulator-Active Factors of the Farming System


    Stauss, R.


    Likewise, index selection based on statistical genetic theory in plant and animal breeding the methodology "Quantitative Population Epigenetics" can be appropriated to improve efficiency in screening and development of regulator-active factors of the farming system for potential to enhance quantitative characters such as yield, standability and resistance to unfavorable environmental influences (e.g., water stress, cold temperatures, disease resistance). For example, as was shown for an ef...

  15. Dielectric screening in extended systems using the self-consistent Sternheimer equation and localized basis sets



    We develop a first-principles computational method for investigating the dielectric screening in extended systems using the self-consistent Sternheimer equation and localized non-orthogonal basis sets. Our approach does not require the explicit calculation of unoccupied electronic states, only uses two-center integrals, and has a theoretical scaling of order O(N^3). We demonstrate this method by comparing our calculations for silicon, germanium, diamond, and LiCl with reference planewaves cal...

  16. Evaluation of the effects of the screen based on an analytical solution of a simplified MIT system (United States)

    Yin, W.; Dekdouk, B.; Ktistis, C.; Peyton, A. J.


    Magnetic induction tomography (MIT) is a technology that reconstructs cross sectional conductivity distribution of an object from mutual impedance measurements of coils distributed around the object. In high frequency and low conductivity applications, an outer screen is generally used to confine the magnetic fields and to prevent electromagnetic interference from outside. However, the screen will alter the sensing and excitation field, hence the sensitivity distribution of the coil array. Therefore, the design parameters of the screen (thickness, distance to coil, materials) are important to the performance of the sensor system. This paper presents a simple method based on an analytical solution for the evaluation of the effects of the screen. The advantage of the approach includes efficient modelling of thin screens and physical insights into the effects of the screen.

  17. Avicequinone C Isolated from Avicennia marina Exhibits 5α-Reductase-Type 1 Inhibitory Activity Using an Androgenic Alopecia Relevant Cell-Based Assay System

    Directory of Open Access Journals (Sweden)

    Ruchy Jain


    Full Text Available Avicennia marina (AM exhibits various biological activities and has been traditionally used in Egypt to cure skin diseases. In this study, the methanolic heartwood extract of AM was evaluated for inhibitory activity against 5α-reductase (5α-R [E.C.], the enzyme responsible for the over-production of 5α-dihydrotestosterone (5α-DHT causing androgenic alopecia (AGA. An AGA-relevant cell-based assay was developed using human hair dermal papilla cells (HHDPCs, the main regulator of hair growth and the only cells within the hair follicle that are the direct site of 5α-DHT action, combined with a non-radioactive thin layer chromatography (TLC detection technique. The results revealed that AM is a potent 5α-R type 1 (5α-R1 inhibitor, reducing the 5α-DHT production by 52% at the final concentration of 10 µg/mL. Activity-guided fractionation has led to the identification of avicequinone C, a furanonaphthaquinone, as a 5α-R1 inhibitor with an IC50 of 9.94 ± 0.33 µg/mL or 38.8 ± 1.29 µM. This paper is the first to report anti-androgenic activity through 5α-R1 inhibition of AM and avicequinone C.

  18. [Cell based therapy for COPD]. (United States)

    Kubo, Hiroshi


    To develop a new cell based therapy for chronic obstructive pulmonary disease (COPD), we need to understand 1) the role of tissue-specific and bone marrow-derived stem cells, 2) extracellular matrix, and 3) growth factors. Recently, bronchioalveolar stem cells were identified in murine distal lungs. Impairment of these stem cells may cause improper lung repair after inflammation, resulting in pulmonary emphysema. Bone marrow-derived cells are necessary to repair injured lungs. However, the long term role of these cells is not understood yet. Although we need more careful analysis and additional experiments, growth factors, such as hepatocyte growth factor, are good candidates for the new cell based therapy for COPD. Lung was believed as a non-regenerative organ. Based on these recent reports about lung regeneration and stem cells, however, new strategies to treat COPD and a new point of view to understand the pathophysiology of COPD are rising.

  19. Study on the Holdup and Mass Transfer Performances for Gas-Liquid-Liquid System in a Screen Plate Column

    Institute of Scientific and Technical Information of China (English)


    The gas and dispersed phase holdups and mass transfer coefficients of liquid-iquid were determined for gas-liquid-liquid three phase system in a screen plate column. The flow pattern of gas-liquid-liquid three phase system was studied under different gas velocities. The shape factors showed the geometric properties of screen plates and the corrected drop characteristic velocities were introduced. The phase holdup in two phases was correlated. The research results indicated that mass transfer coefficient for liquid-liquid system in a column with screen plates and gas agitation was found to increase apparently.

  20. In Vivo RNAi-Based Screens: Studies in Model Organisms

    Directory of Open Access Journals (Sweden)

    Miki Yamamoto-Hino


    Full Text Available RNA interference (RNAi is a technique widely used for gene silencing in organisms and cultured cells, and depends on sequence homology between double-stranded RNA (dsRNA and target mRNA molecules. Numerous cell-based genome-wide screens have successfully identified novel genes involved in various biological processes, including signal transduction, cell viability/death, and cell morphology. However, cell-based screens cannot address cellular processes such as development, behavior, and immunity. Drosophila and Caenorhabditis elegans are two model organisms whose whole bodies and individual body parts have been subjected to RNAi-based genome-wide screening. Moreover, Drosophila RNAi allows the manipulation of gene function in a spatiotemporal manner when it is implemented using the Gal4/UAS system. Using this inducible RNAi technique, various large-scale screens have been performed in Drosophila, demonstrating that the method is straightforward and valuable. However, accumulated results reveal that the results of RNAi-based screens have relatively high levels of error, such as false positives and negatives. Here, we review in vivo RNAi screens in Drosophila and the methods that could be used to remove ambiguity from screening results.

  1. Glutathione transferases immobilized on nanoporous alumina: flow system kinetics, screening, and stability. (United States)

    Kjellander, Marcus; Mazari, Aslam M A; Boman, Mats; Mannervik, Bengt; Johansson, Gunnar


    The previously uncharacterized Drosophila melanogaster Epsilon-class glutathione transferases E6 and E7 were immobilized on nanoporous alumina. The nanoporous anodized alumina membranes were derivatized with 3-aminopropyl-triethoxysilane, and the amino groups were activated with carbonyldiimidazole to allow coupling of the enzymes via ε-amino groups. Kinetic analyses of the immobilized enzymes were carried out in a circulating flow system using CDNB (1-chloro-2,4-dinitrobenzene) as substrate, followed by specificity screening with alternative substrates. A good correlation was observed between the substrate screening data for immobilized enzyme and corresponding data for the enzyme in solution. A limited kinetic study was also carried out on immobilized human GST S1-1 (also known as hematopoietic prostaglandin D synthase). The stability of the immobilized enzymes was virtually identical to that of enzymes in solution, and no leakage of enzyme from the matrix could be observed.

  2. Identification of human dopamine D1-like receptor agonist using a cell-based functional assay

    Institute of Scientific and Technical Information of China (English)

    Nan JIANG; Ke-qing OU-YANG; Shao-xi CAI; Ying-he HU; Zhi-liang XU


    Aim: To establish a cell-based assay to screen human dopamine D1 and D5 receptor agonists against compounds from a natural product compound library.Methods: Synthetic responsive elements 6×cAMP response elements (CRE) and a mini promoter containing a TATA box were inserted into the pGL3 basic vector to generate the reporter gene construct pCRE/TA/Luci. CHO cells were co-transfected with the reporter gene construct and human D1 or D5 receptor cDNA in mammalian expression vectors. Stable cell lines were established for agonist screening. A natural product compound library from over 300 herbs has been established. The extracts from these herbs were used for human D1 and D5 receptor agonist screenings. Results: A number of extracts were identified that activated both D1 and D5 receptors. One of the herb extracts, SBG492, demonstrated distinct pharmacological characteristics with human D1 and D5 receptors.The EC50 values of SBG492 were 342.7 μg/mL for the D1 receptor and 31.7 μg/mL for the D5 receptor. Conclusion: We have established a cell-based assay for high-throughput drug screening to identify D 1-like receptor agonists from natural products. Several extracts that can active D1-like receptors were discovered.These compounds could be useful tools for studies on the functions of these receptors in the brain and could potentially be developed into therapeutic drugs for the treatment of central nervous system diseases.

  3. Automated screening system for retinal health using bi-dimensional empirical mode decomposition and integrated index. (United States)

    Acharya, U Rajendra; Mookiah, Muthu Rama Krishnan; Koh, Joel E W; Tan, Jen Hong; Bhandary, Sulatha V; Rao, A Krishna; Fujita, Hamido; Hagiwara, Yuki; Chua, Chua Kuang; Laude, Augustinus


    Posterior Segment Eye Diseases (PSED) namely Diabetic Retinopathy (DR), glaucoma and Age-related Macular Degeneration (AMD) are the prime causes of vision loss globally. Vision loss can be prevented, if these diseases are detected at an early stage. Structural abnormalities such as changes in cup-to-disc ratio, Hard Exudates (HE), drusen, Microaneurysms (MA), Cotton Wool Spots (CWS), Haemorrhages (HA), Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in PSED can be identified by manual examination of fundus images by clinicians. However, manual screening is labour-intensive, tiresome and time consuming. Hence, there is a need to automate the eye screening. In this work Bi-dimensional Empirical Mode Decomposition (BEMD) technique is used to decompose fundus images into 2D Intrinsic Mode Functions (IMFs) to capture variations in the pixels due to morphological changes. Further, various entropy namely Renyi, Fuzzy, Shannon, Vajda, Kapur and Yager and energy features are extracted from IMFs. These extracted features are ranked using Chernoff Bound and Bhattacharyya Distance (CBBD), Kullback-Leibler Divergence (KLD), Fuzzy-minimum Redundancy Maximum Relevance (FmRMR), Wilcoxon, Receiver Operating Characteristics Curve (ROC) and t-test methods. Further, these ranked features are fed to Support Vector Machine (SVM) classifier to classify normal and abnormal (DR, AMD and glaucoma) classes. The performance of the proposed eye screening system is evaluated using 800 (Normal=400 and Abnormal=400) digital fundus images and 10-fold cross validation method. Our proposed system automatically identifies normal and abnormal classes with an average accuracy of 88.63%, sensitivity of 86.25% and specificity of 91% using 17 optimal features ranked using CBBD and SVM-Radial Basis Function (RBF) classifier. Moreover, a novel Retinal Risk Index (RRI) is developed using two significant features to distinguish two classes using single number. Such a system helps to reduce eye

  4. A cell-based computational modeling approach for developing site-directed molecular probes.

    Directory of Open Access Journals (Sweden)

    Jing-Yu Yu

    Full Text Available Modeling the local absorption and retention patterns of membrane-permeant small molecules in a cellular context could facilitate development of site-directed chemical agents for bioimaging or therapeutic applications. Here, we present an integrative approach to this problem, combining in silico computational models, in vitro cell based assays and in vivo biodistribution studies. To target small molecule probes to the epithelial cells of the upper airways, a multiscale computational model of the lung was first used as a screening tool, in silico. Following virtual screening, cell monolayers differentiated on microfabricated pore arrays and multilayer cultures of primary human bronchial epithelial cells differentiated in an air-liquid interface were used to test the local absorption and intracellular retention patterns of selected probes, in vitro. Lastly, experiments involving visualization of bioimaging probe distribution in the lungs after local and systemic administration were used to test the relevance of computational models and cell-based assays, in vivo. The results of in vivo experiments were consistent with the results of in silico simulations, indicating that mitochondrial accumulation of membrane permeant, hydrophilic cations can be used to maximize local exposure and retention, specifically in the upper airways after intratracheal administration.

  5. Juvenile idiopathic arthritis (JIA): a screening study to measure class II skeletal pattern, TMJ PDS and use of systemic corticosteroids.

    LENUS (Irish Health Repository)

    Mandall, Nicky A


    To screen patients with oligoarticular and polyarticular forms of Juvenile Idiopathic Arthritis (JIA) to determine (i) the severity of their class II skeletal pattern; (ii) temporomandibular joint signs and symptoms and (iii) use of systemic corticosteroids.

  6. Risk factors associated with pulmonary arterial hypertension in patients with systemic sclerosis and implications for screening

    Directory of Open Access Journals (Sweden)

    C.P. Denton


    Full Text Available Pulmonary arterial hypertension (PAH is a relatively common complication of systemic sclerosis (SSc affecting 5–12% of patients, and its development is associated with significant morbidity and a particularly poor prognosis. Deaths associated with other complications of SSc, such as renal crisis, have fallen significantly in recent years in line with improvements in their treatment and management. However, mortality due to PAH in this population, although improved, has shown a less dramatic decline. The early diagnosis of PAH in SSc would allow for earlier treatment, before functional and haemodynamic impairment becomes severe; this may further improve outcome, and evidence suggests that screening of SSc patients for PAH is associated with improved survival. In addition, patients with PAH associated with SSc are not a homogeneous population and they differ in terms of disease haemodynamic severity, functional capacity and rate of disease progression. Likewise, management strategies may differ, and the ability to stratify patients may help optimise screening and treatment. A number of patient-, clinical- and disease-specific risk factors associated with the development and prognosis of PAH in SSc have been identified, but their optimal use, alone or in combination, in screening and stratification of patients remains to be established.

  7. Contribution of the Unified Health Care System to mammography screening in Brazil, 2013* (United States)

    Freitas-Junior, Ruffo; Rodrigues, Danielle Cristina Netto; Corrêa, Rosangela da Silveira; Peixoto, João Emílio; de Oliveira, Humberto Vinícius Carrijo Guimarães; Rahal, Rosemar Macedo Sousa


    Objective To estimate the coverage of opportunistic mammography screening performed via the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System), at the state and regional level, in 2013. Materials and Methods This was an ecological study in which coverage was estimated by determining the ratio between the number of mammograms performed and the expected number of mammograms among the population of females between 50 and 69 years of age. The number of mammograms performed in the target population was obtained from the Outpatient Database of the Information Technology Department of the SUS. To calculate the expected number of mammograms, we considered 58.9% of the target population, the proportion that would be expected on the basis of the recommendations of the Brazilian National Cancer Institute. Results In 2013, the estimated national coverage of mammography screening via the SUS was 24.8%. The mammography rate ranged from 12.0% in the northern region to 31.3% in the southern region. When stratified by state, coverage was lowest in the state of Pará and highest in the state of Santa Catarina (7.5% and 35.7%, respectively). Conclusion The coverage of mammography screening performed via the SUS is low. There is a significant disparity among the Brazilian states (including the Federal District of Brasília) and among regions, being higher in the south/southeast and lower in the north/northeast. PMID:27818544

  8. Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization

    Directory of Open Access Journals (Sweden)

    Branko Stefanovic


    Full Text Available Fibroproliferative diseases are one of the leading causes of death worldwide. They are characterized by reactive fibrosis caused by uncontrolled synthesis of type I collagen. There is no cure for fibrosis and development of therapeutics that can inhibit collagen synthesis is urgently needed. Collagen α1(I mRNA and α2(I mRNA encode for type I collagen and they have a unique 5' stem-loop structure in their 5' untranslated regions (5'SL. Collagen 5'SL binds protein LARP6 with high affinity and specificity. The interaction between LARP6 and the 5'SL is critical for biosynthesis of type I collagen and development of fibrosis in vivo. Therefore, this interaction represents is an ideal target to develop antifibrotic drugs. A high throughput system to screen for chemical compounds that can dissociate LARP6 from 5'SL has been developed. It is based on fluorescence polarization and can be adapted to screen for inhibitors of other protein-RNA interactions. Screening of 50,000 chemical compounds yielded a lead compound that can inhibit type I collagen synthesis at nanomolar concentrations. The development, characteristics, and critical appraisal of this assay are presented.

  9. A versatile knowledge-based clinical imaging annotation system for breast cancer screening (United States)

    Gemo, Monica; Gouze, Annabelle; Debande, Benoît; Grivegnée, André; Mazy, Gilbert; Macq, Benoît


    Medical information is evolving towards more complex multimedia data representation, as new imaging modalities are made available by sophisticated devices. Features such as segmented lesions can now be extracted through analysis techniques and need to be integrated into clinical patient data. The management of structured information extracted from multimedia has been addressed in knowledge based annotation systems providing methods to attach interpretative semantics to multimedia content. Building on these methods, we develop a new clinical imaging annotation system for computer aided breast cancer screening. The proposed system aims at more consistent, efficient and standardised data mark-up of digital and digitalised radiology images. The objective is to provide detailed characterisation of abnormalities as an aid in the diagnostic task through integrated annotation management. The system combines imaging analysis results and radiologist diagnostic information about suspicious findings by mapping well-established visual and low-level descriptors into pathology specific profiles. The versatile characterisation allows differentiating annotation descriptors for different types of findings. Our approach of semi-automatic integrated annotations supports increased quality assurance in screening practice. This is achieved through detailed and objective patient imaging information while providing user-friendly means for their manipulation that is oriented to relieving the radiologist's workload.

  10. An opto-electronic joint detection system based on DSP aiming at early cervical cancer screening (United States)

    Wang, Weiya; Jia, Mengyu; Gao, Feng; Yang, Lihong; Qu, Pengpeng; Zou, Changping; Liu, Pengxi; Zhao, Huijuan


    The cervical cancer screening at a pre-cancer stage is beneficial to reduce the mortality of women. An opto-electronic joint detection system based on DSP aiming at early cervical cancer screening is introduced in this paper. In this system, three electrodes alternately discharge to the cervical tissue and three light emitting diodes in different wavelengths alternately irradiate the cervical tissue. Then the relative optical reflectance and electrical voltage attenuation curve are obtained by optical and electrical detection, respectively. The system is based on DSP to attain the portable and cheap instrument. By adopting the relative reflectance and the voltage attenuation constant, the classification algorithm based on Support Vector Machine (SVM) discriminates abnormal cervical tissue from normal. We use particle swarm optimization to optimize the two key parameters of SVM, i.e. nuclear factor and cost factor. The clinical data were collected on 313 patients to build a clinical database of tissue responses under optical and electrical stimulations with the histopathologic examination as the gold standard. The classification result shows that the opto-electronic joint detection has higher total coincidence rate than separate optical detection or separate electrical detection. The sensitivity, specificity, and total coincidence rate increase with the increasing of sample numbers in the training set. The average total coincidence rate of the system can reach 85.1% compared with the histopathologic examination.

  11. LiSIs: An Online Scientific Workflow System for Virtual Screening. (United States)

    Kannas, Christos C; Kalvari, Ioanna; Lambrinidis, George; Neophytou, Christiana M; Savva, Christiana G; Kirmitzoglou, Ioannis; Antoniou, Zinonas; Achilleos, Kleo G; Scherf, David; Pitta, Chara A; Nicolaou, Christos A; Mikros, Emanuel; Promponas, Vasilis J; Gerhauser, Clarissa; Mehta, Rajendra G; Constantinou, Andreas I; Pattichis, Constantinos S


    Modern methods of drug discovery and development in recent years make a wide use of computational algorithms. These methods utilise Virtual Screening (VS), which is the computational counterpart of experimental screening. In this manner the in silico models and tools initial replace the wet lab methods saving time and resources. This paper presents the overall design and implementation of a web based scientific workflow system for virtual screening called, the Life Sciences Informatics (LiSIs) platform. The LiSIs platform consists of the following layers: the input layer covering the data file input; the pre-processing layer covering the descriptors calculation, and the docking preparation components; the processing layer covering the attribute filtering, compound similarity, substructure matching, docking prediction, predictive modelling and molecular clustering; post-processing layer covering the output reformatting and binary file merging components; output layer covering the storage component. The potential of LiSIs platform has been demonstrated through two case studies designed to illustrate the preparation of tools for the identification of promising chemical structures. The first case study involved the development of a Quantitative Structure Activity Relationship (QSAR) model on a literature dataset while the second case study implemented a docking-based virtual screening experiment. Our results show that VS workflows utilizing docking, predictive models and other in silico tools as implemented in the LiSIs platform can identify compounds in line with expert expectations. We anticipate that the deployment of LiSIs, as currently implemented and available for use, can enable drug discovery researchers to more easily use state of the art computational techniques in their search for promising chemical compounds. The LiSIs platform is freely accessible (i) under the GRANATUM platform at: and (ii) directly at:

  12. Systemic QSAR and phenotypic virtual screening: chasing butterflies in drug discovery. (United States)

    Cruz-Monteagudo, Maykel; Schürer, Stephan; Tejera, Eduardo; Pérez-Castillo, Yunierkis; Medina-Franco, José L; Sánchez-Rodríguez, Aminael; Borges, Fernanda


    Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final outcomes and consequently prioritize those events, leading to a desired effect. Here, we introduce a new concept, 'Systemic Chemogenomics/Quantitative Structure-Activity Relationship (QSAR)'. To elaborate on the concept, relevant information surrounding it is addressed. The concept is challenged by implementing a systemic QSAR approach for phenotypic virtual screening (VS) of candidate ligands acting as neuroprotective agents in Parkinson's disease (PD). The results support the suitability of the approach for the phenotypic prioritization of drug candidates.

  13. Enzyme- and affinity biomolecule-mediated polymerization systems for biological signal amplification and cell screening. (United States)

    Malinowska, Klara H; Nash, Michael A


    Enzyme-mediated polymerization and polymerization-based signal amplification have emerged as two closely related techniques that are broadly applicable in the nanobio sciences. We review recent progress on polymerization systems mediated by biological molecules (e.g., affinity molecules and enzymes), and highlight newly developed formats and configurations of these systems to perform such tasks as non-instrumented biodetection, synthesis of core-shell nanomaterials, isolation of rare cells, and high-throughput screening. We discuss useful features of biologically mediated polymerization systems, such as multiple mechanisms of amplification (e.g., enzymatic, radical chain propagation), and the ability to localize structures at interfaces and at cell surfaces with microscopic spatial confinement. We close with a perspective on desirable improvements that need to be addressed to adapt these molecular systems to future applications.

  14. Challenges in small screening laboratories: implementing an on-demand laboratory information management system. (United States)

    Lemmon, Vance P; Jia, Yuanyuan; Shi, Yan; Holbrook, S Douglas; Bixby, John L; Buchser, William


    The Miami Project to Cure Paralysis, part of the University of Miami Miller School of Medicine, includes a laboratory devoted to High Content Analysis (HCA) of neurons. The goal of the laboratory is to uncover signaling pathways, genes, compounds, or drugs that can be used to promote nerve growth. HCA permits the quantification of neuronal morphology, including the lengths and numbers of axons. HCA of various libraries on primary neurons requires a team-based approach, a variety of process steps and complex manipulations of cells and libraries to obtain meaningful results. HCA itself produces vast amounts of information including images, well-based data and cell-based phenotypic measures. Documenting and integrating the experimental workflows, library data and extensive experimental results is challenging. For academic laboratories generating large data sets from experiments involving thousands of perturbagens, a Laboratory Information Management System (LIMS) is the data tracking solution of choice. With both productivity and efficiency as driving rationales, the Miami Project has equipped its HCA laboratory with an On Demand or Software As A Service (SaaS) LIMS to ensure the quality of its experiments and workflows. The article discusses how the system was selected and integrated into the laboratory. The advantages of a SaaS based LIMS over a client-server based system are described.

  15. A comparison of high-speed flywheels, batteries, and ultracapacitors on the bases of cost and fuel economy as the energy storage system in a fuel cell based hybrid electric vehicle (United States)

    Doucette, Reed T.; McCulloch, Malcolm D.

    Fuel cells aboard hybrid electric vehicles (HEVs) are often hybridized with an energy storage system (ESS). Batteries and ultracapacitors are the most common technologies used in ESSs aboard HEVs. High-speed flywheels are an emerging technology with traits that have the potential to make them competitive with more established battery and ultracapacitor technologies in certain vehicular applications. This study compares high-speed flywheels, ultracapacitors, and batteries functioning as the ESS in a fuel cell based HEV on the bases of cost and fuel economy. In this study, computer models were built to simulate the powertrain of a fuel cell based HEV where high-speed flywheels, batteries, and ultracapacitors of a range of sizes were used as the ESS. A simulated vehicle with a powertrain using each of these technologies was run over two different drive cycles in order to see how the different ESSs performed under different driving patterns. The results showed that when cost and fuel economy were both considered, high-speed flywheels were competitive with batteries and ultracapacitors.

  16. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay. (United States)

    Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine


    Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.

  17. Toward an objective indexing system for ADHD-screening using children's activity monitoring. (United States)

    Kam, Hye Jin; Choi, Jong Pil; Park, Rae Woong


    Signs of ADHD are discernible in specific situations, and usually assessed according to subjective impressions. We performed a preliminary comparative study from children's activity at a natural classroom environment with 3-axis accelerator for a feasible objective index. From a total of 157 children (7-9 yrs) and clinically diagnosed 24 children out of them, variances in 1-min epoch mean activity had shown significant differences among the subgroups: (1) ADHD=.0194, Other Diseases=.0080, Normal=.0009; (2) ADHD=.0194, non-ADHD=.0057(p1.6G) features among subgroups with the same order (pindexing system for screening ADHD patients.

  18. Dielectric screening in extended systems using the self-consistent Sternheimer equation and localized basis sets (United States)

    Hübener, Hannes; Pérez-Osorio, Miguel A.; Ordejón, Pablo; Giustino, Feliciano


    We develop a first-principles computational method for investigating the dielectric screening in extended systems using the self-consistent Sternheimer equation and localized nonorthogonal basis sets. Our approach does not require the explicit calculation of unoccupied electronic states, uses only two-center integrals, and has a theoretical scaling of order O(N3). We demonstrate this method by comparing our calculations for silicon, germanium, diamond, and LiCl with reference plane-wave calculations. We show that accuracy comparable to that of plane-wave calculations can be achieved via a systematic optimization of the basis set.


    Directory of Open Access Journals (Sweden)

    Yulia yulia


    Full Text Available Disk is a very useful device to a computer to save data file. For that, is much needed to have a program that has a capability to represent, navigate, and operate that files. There are many computer programs that used to present, navigate, and operate disk files in text form with a lot of facilities, but only a few programs that can represent files in a graphic form and have special feature, like capability to find the biggest files that use disk space. This capability is very useful in disk file management. This software use split screen system method and tree map algorithm. Split screen system is used to navigate, where the monitor screen divided into two parts to visualize files in a disk, the small part (map navigator visualize the whole content of a drive or directory and the big part visualize the detail of a part according to focus box in the map navigator. A mouse can move focus box in the map navigator and the box size is the comparison between map navigator sizes with map view size. Tree map algorithm is used to calculate the size of box picture of the represented file. This algorithm needs a complete tree structure from a drive or directory that will be painted. The software to make this windows based program is Borland Delphi 5.0. Abstract in Bahasa Indonesia : Disk merupakan alat yang sangat bermanfaat bagi sebuah sistem komputer untuk menyimpan data berupa file. Untuk itu sangat dibutuhkan program yang dapat merepresentasikan, menavigasi dan mengoperasikan file-file tersebut. Banyak program komputer yang digunakan untuk merepresentasikan, menavigasi dan mengoperasikan file-file pada media penyimpanan disk dalam bentuk teks dengan berbagai macam fasilitas, tetapi sangat sedikit program yang merepresentasikan file-file dalam bentuk grafik atau secara visual serta mampu memberikan kelebihan-kelebihan tersendiri, seperti kemampuan untuk merepresentasikan file-file yang paling banyak menggunakan ruang media penyimpanan disk. Kemampuan

  20. Comparative evaluation of the sensitometric properties of screen-film systems and conventional dental receptors for intraoral radiography

    Energy Technology Data Exchange (ETDEWEB)

    Kircos, L.T.; Staninec, M.; Chou, L.


    This investigation determined the sensitometric properties of 27 rare-earth screen-film combinations and compared them to E- and D-speed films and xeroradiography, the current standards for intraoral radiography. A series of exposures from base plus fog to film saturation were made to determine the Hurter and Driffield curve of each image receptor. The base plus fog, film saturation, speed, gamma, average gradient, and resolution were determined. When dental receptors and screen-film systems are compared on the basis of radiographic quality (contrast and resolution), many screen-film systems have similar resolution (greater than 10 line pairs/mm), significantly greater contrast (greater than 2.0), and a substantial speed advantage (greater than 10). Thus selected screen-film systems may be an alternative to conventional dental receptors for intraoral radiography.

  1. Computer-assisted lesion detection system for stomach screening using stomach shape and appearance models (United States)

    Midoh, Y.; Nakamura, M.; Takashima, M.; Nakamae, K.; Fujioka, H.


    In Japan, stomach cancer is one of the three most common causes of death from cancer. Since periodic health checks of stomach X-rays have become more widely carried out, the physicians' burdens have been increasing in the mass screening to detect initial symptoms of a disease. For the purpose of automatic diagnosis, we try to develop a computer-assisted lesion detection system for stomach screening. The proposed system has two databases. One is the stomach shape database that consists of the computer graphics stomach 3D models based on biomechanics simulation and their projected 2D images. The other is the normal appearance database that is constructed by learning patterns in a normal patient training set. The stomach contour is extracted from an X-ray image including a barium filled region by the following steps. Firstly, the approximated stomach region is obtained by nonrigid registration based on mutual information. We define nonrigid transformation as one that includes translations, rotations, scaling, air-barium interface and weights of eigenvectors determined by principal components analysis in the stomach shape database. Secondly, the accurate stomach contour is extracted from the gradient of an image by using the Dynamic Programming. After then, stomach lesions are detected by inspecting whether the Mahalanobis distance from the mean in the normal appearance database is longer than a suitable value on the extracted stomach contour. We applied our system to 75 X-ray images of barium-filled stomach to show its validity.

  2. Policy Analysis Screening System (PASS) demonstration: sample queries and terminal instructions

    Energy Technology Data Exchange (ETDEWEB)



    This document contains the input and output for the Policy Analysis Screening System (PASS) demonstration. This demonstration is stored on a portable disk at the Environmental Impacts Division. Sample queries presented here include: (1) how to use PASS; (2) estimated 1995 energy consumption from Mid-Range Energy-Forecasting System (MEFS) data base; (3) pollution projections from Strategic Environmental Assessment System (SEAS) data base; (4) diesel auto regulations; (5) diesel auto health effects; (6) oil shale health and safety measures; (7) water pollution effects of SRC; (8) acid rainfall from Energy Environmental Statistics (EES) data base; 1990 EIA electric generation by fuel type; sulfate concentrations by Federal region; forecast of 1995 SO/sub 2/ emissions in Region III; and estimated electrical generating capacity in California to 1990. The file name for each query is included.

  3. Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator (United States)

    Okada, Jun-ichi; Yoshinaga, Takashi; Kurokawa, Junko; Washio, Takumi; Furukawa, Tetsushi; Sawada, Kohei; Sugiura, Seiryo; Hisada, Toshiaki


    To save time and cost for drug discovery, a paradigm shift in cardiotoxicity testing is required. We introduce a novel screening system for drug-induced arrhythmogenic risk that combines in vitro pharmacological assays and a multiscale heart simulator. For 12 drugs reported to have varying cardiotoxicity risks, dose-inhibition curves were determined for six ion channels using automated patch clamp systems. By manipulating the channel models implemented in a heart simulator consisting of more than 20 million myocyte models, we simulated a standard electrocardiogram (ECG) under various doses of drugs. When the drug concentrations were increased from therapeutic levels, each drug induced a concentration-dependent characteristic type of ventricular arrhythmia, whereas no arrhythmias were observed at any dose with drugs known to be safe. We have shown that our system combining in vitro and in silico technologies can predict drug-induced arrhythmogenic risk reliably and efficiently. PMID:26601174

  4. Discovery of bile salt hydrolase inhibitors using an efficient high-throughput screening system.

    Directory of Open Access Journals (Sweden)

    Katie Smith

    Full Text Available The global trend of restricting the use of antibiotic growth promoters (AGP in animal production necessitates the need to develop valid alternatives to maintain productivity and sustainability of food animals. Previous studies suggest inhibition of bile salt hydrolase (BSH, an intestinal bacteria-produced enzyme that exerts negative impact on host fat digestion and utilization, is a promising approach to promote animal growth performance. To achieve the long term goal of developing novel alternatives to AGPs, in this study, a rapid and convenient high-throughput screening (HTS system was developed and successfully used for identification of BSH inhibitors. With the aid of a high-purity BSH from a chicken Lactobacillus salivarius strain, we optimized various screening conditions (e.g. BSH concentration, reaction buffer pH, incubation temperature and length, substrate type and concentration and establish a precipitation-based screening approach to identify BSH inhibitors using 96-well or 384-well microplates. A pilot HTS was performed using a small compound library comprised of 2,240 biologically active and structurally diverse compounds. Among the 107 hits, several promising and potent BSH inhibitors (e.g. riboflavin and phenethyl caffeate were selected and validated by standard BSH activity assay. Interestingly, the HTS also identified a panel of antibiotics as BSH inhibitor; in particular, various tetracycline antibiotics and roxarsone, the widely used AGP, have been demonstrated to display potent inhibitory effect on BSH. Together, this study developed an efficient HTS system and identified several BSH inhibitors with potential as alternatives to AGP. In addition, the findings from this study also suggest a new mode of action of AGP for promoting animal growth.

  5. Discovery of Bile Salt Hydrolase Inhibitors Using an Efficient High-Throughput Screening System (United States)

    Smith, Katie; Zeng, Ximin; Lin, Jun


    The global trend of restricting the use of antibiotic growth promoters (AGP) in animal production necessitates the need to develop valid alternatives to maintain productivity and sustainability of food animals. Previous studies suggest inhibition of bile salt hydrolase (BSH), an intestinal bacteria-produced enzyme that exerts negative impact on host fat digestion and utilization, is a promising approach to promote animal growth performance. To achieve the long term goal of developing novel alternatives to AGPs, in this study, a rapid and convenient high-throughput screening (HTS) system was developed and successfully used for identification of BSH inhibitors. With the aid of a high-purity BSH from a chicken Lactobacillus salivarius strain, we optimized various screening conditions (e.g. BSH concentration, reaction buffer pH, incubation temperature and length, substrate type and concentration) and establish a precipitation-based screening approach to identify BSH inhibitors using 96-well or 384-well microplates. A pilot HTS was performed using a small compound library comprised of 2,240 biologically active and structurally diverse compounds. Among the 107 hits, several promising and potent BSH inhibitors (e.g. riboflavin and phenethyl caffeate) were selected and validated by standard BSH activity assay. Interestingly, the HTS also identified a panel of antibiotics as BSH inhibitor; in particular, various tetracycline antibiotics and roxarsone, the widely used AGP, have been demonstrated to display potent inhibitory effect on BSH. Together, this study developed an efficient HTS system and identified several BSH inhibitors with potential as alternatives to AGP. In addition, the findings from this study also suggest a new mode of action of AGP for promoting animal growth. PMID:24454844

  6. Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System.

    Directory of Open Access Journals (Sweden)

    Yoichiro Ito

    Full Text Available Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering.

  7. A comparison between molten carbonate fuel cells based hybrid systems using air and supercritical carbon dioxide Brayton cycles with state of the art technology (United States)

    Sánchez, D.; Muñoz de Escalona, J. M.; Chacartegui, R.; Muñoz, A.; Sánchez, T.

    A proposal for high efficiency hybrid systems based on molten carbonate fuel cells is presented in this paper. This proposal is based on adopting a closed cycle bottoming gas turbine using supercritical carbon dioxide as working fluid as opposed to open cycle hot air turbines typically used in this type of power generators. First, both bottoming cycles are compared for the same operating conditions, showing that their performances do not differ as much as initially expected, even if the initial objective of reducing compression work is accomplished satisfactorily. In view of these results, a profound review of research and industrial literature is carried out in order to determine realistic specifications for the principal components of the bottoming systems. From this analysis, it is concluded that an appropriate set of specifications must be developed for each bottoming cycle as the performances of compressor, turbine and recuperator differ significantly from one working fluid to another. Thus, when the operating conditions are updated, the performances of the resulting systems show a remarkable advantage of carbon dioxide based systems over conventional air units. Actually, the proposed hybrid system shows its capability to achieve 60% net efficiency, what represents a 10% increase with respect to the reference system.

  8. Development of an Expert System as a Diagnostic Support of Cervical Cancer in Atypical Glandular Cells, Based on Fuzzy Logics and Image Interpretation

    Directory of Open Access Journals (Sweden)

    Karem R. Domínguez Hernández


    Full Text Available Cervical cancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC. The expert system consists of 3 phases: (1 risk diagnosis which consists of the interpretation of a patient’s clinical background and the risks for contracting CN according to specialists; (2 cytology images detection which consists of image interpretation (IM and the Bethesda system for cytology interpretation, and (3 determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN.

  9. Development of droplets‐based microfluidic systems for single­‐cell high‐throughput screening

    DEFF Research Database (Denmark)

    Chen, Jun; Jensen, Thomas Glasdam; Godina, Alexei


    High-throughput screening (HTS) plays an important role in the development of microbial cell factories. One of the most popular approaches is to use microplates combined with the application of robotics, liquid handling and sophisticated detection methods. However, these workstations require larg...... picoliter aqueous droplets surround by an immiscible fluorinated oil phase. Our aim is to use this system to facilitate the screening process for both the biotechnology and food industry....

  10. Rapid antioxidant capacity screening in herbal extracts using a simple flow injection-spectrophotometric system. (United States)

    Mrazek, Nookrai; Watla-iad, Kanchana; Deachathai, Suwanna; Suteerapataranon, Siripat


    A simple flow injection (FI)-spectrophotometric system for the screening of antioxidant capacity in herbal extracts was developed. The analysis was based on the color disappearance due to the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by antioxidant compounds. DPPH and ascorbic acid were used as reagent and antioxidant standard, respectively. Effects of the DPPH concentration, DPPH flow rate, and reaction coil length on sensitivity were studied. The optimized condition provided the linear range of 0.010-0.300mM ascorbic acid with less than 5%RSD(n=10). Detection limit and quantitation limit were 0.004 and 0.013mM, respectively. Comparison of antioxidant capacity in some herbal extracts determined by the FI system and a standard method was carried out and no significant difference was obtained.

  11. Creating electronic screens in a hospital information system using nursing classifications

    Directory of Open Access Journals (Sweden)

    Dorothea Maria Beckers Marques de Almeida


    Full Text Available Electronic health records aim at providing greater readability and safety in documenting nursing actions. Using the nursing classifications of an information system organizes, standardizes and retrieves the data considered essential to plan individualized care and the results evaluation from the interventions. The objective was to describe the development of the Nursing Care Systematization stages using Nursing Classifications in a Hospital Information System. Cross-mapping was performed of the care plan content and the printed version, at a Semi-Intensive Care Unit. Excel spreadsheets were included according to the systematization stage and electronic screens permitted to record the nurses’ clinical evaluation. The electronic documentation permitted faster data input and retrieval, in addition to stimulating diagnosis accuracy and evaluating the interventions by means of result indicators. Descriptors: Nursing Diagnosis; Nursing Process; Nursing Care; Nursing Informatics.

  12. Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect.

    Directory of Open Access Journals (Sweden)

    Anna Pereira-Fernandes

    Full Text Available Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds, were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA. PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound.

  13. A digital microfluidic method for multiplexed cell-based apoptosis assays. (United States)

    Bogojevic, Dario; Chamberlain, M Dean; Barbulovic-Nad, Irena; Wheeler, Aaron R


    Digital microfluidics (DMF), a fluid-handling technique in which picolitre-microlitre droplets are manipulated electrostatically on an array of electrodes, has recently become popular for applications in chemistry and biology. DMF devices are reconfigurable, have no moving parts, and are compatible with conventional high-throughput screening infrastructure (e.g., multiwell plate readers). For these and other reasons, digital microfluidics has been touted as being a potentially useful new tool for applications in multiplexed screening. Here, we introduce the first digital microfluidic platform used to implement parallel-scale cell-based assays. A fluorogenic apoptosis assay for caspase-3 activity was chosen as a model system because of the popularity of apoptosis as a target for anti-cancer drug discovery research. Dose-response profiles of caspase-3 activity as a function of staurosporine concentration were generated using both the digital microfluidic method and conventional techniques (i.e., pipetting, aspiration, and 96-well plates.) As expected, the digital microfluidic method had a 33-fold reduction in reagent consumption relative to the conventional technique. Although both types of methods used the same detector (a benchtop multiwell plate reader), the data generated by the digital microfluidic method had lower detection limits and greater dynamic range because apoptotic cells were much less likely to de-laminate when exposed to droplet manipulation by DMF relative to pipetting/aspiration in multiwell plates. We propose that the techniques described here represent an important milestone in the development of digital microfluidics as a useful tool for parallel cell-based screening and other applications.

  14. A systems wide mass spectrometric based linear motif screen to identify dominant in-vivo interacting proteins for the ubiquitin ligase MDM2. (United States)

    Nicholson, Judith; Scherl, Alex; Way, Luke; Blackburn, Elizabeth A; Walkinshaw, Malcolm D; Ball, Kathryn L; Hupp, Ted R


    Linear motifs mediate protein-protein interactions (PPI) that allow expansion of a target protein interactome at a systems level. This study uses a proteomics approach and linear motif sub-stratifications to expand on PPIs of MDM2. MDM2 is a multi-functional protein with over one hundred known binding partners not stratified by hierarchy or function. A new linear motif based on a MDM2 interaction consensus is used to select novel MDM2 interactors based on Nutlin-3 responsiveness in a cell-based proteomics screen. MDM2 binds a subset of peptide motifs corresponding to real proteins with a range of allosteric responses to MDM2 ligands. We validate cyclophilin B as a novel protein with a consensus MDM2 binding motif that is stabilised by Nutlin-3 in vivo, thus identifying one of the few known interactors of MDM2 that is stabilised by Nutlin-3. These data invoke two modes of peptide binding at the MDM2 N-terminus that rely on a consensus core motif to control the equilibrium between MDM2 binding proteins. This approach stratifies MDM2 interacting proteins based on the linear motif feature and provides a new biomarker assay to define clinically relevant Nutlin-3 responsive MDM2 interactors.

  15. A Novel High-Throughput 3D Screening System for EMT Inhibitors: A Pilot Screening Discovered the EMT Inhibitory Activity of CDK2 Inhibitor SU9516 (United States)

    Eguchi, Takanori; Rahman, M. Mamunur; Sakamoto, Ruriko; Masuda, Norio; Nakatsura, Tetsuya; Calderwood, Stuart K.; Kozaki, Ken-ichi; Itoh, Manabu


    Epithelial-mesenchymal transition (EMT) is a crucial pathological event in cancer, particularly in tumor cell budding and metastasis. Therefore, control of EMT can represent a novel therapeutic strategy in cancer. Here, we introduce an innovative three-dimensional (3D) high-throughput screening (HTS) system that leads to an identification of EMT inhibitors. For the establishment of the novel 3D-HTS system, we chose NanoCulture Plates (NCP) that provided a gel-free micro-patterned scaffold for cells and were independent of other spheroid formation systems using soft-agar. In the NCP-based 3D cell culture system, A549 lung cancer cells migrated, gathered, and then formed multiple spheroids within 7 days. Live cell imaging experiments showed that an established EMT-inducer TGF-β promoted peripheral cells around the core of spheroids to acquire mesenchymal spindle shapes, loss of intercellular adhesion, and migration from the spheroids. Along with such morphological change, EMT-related gene expression signatures were altered, particularly alteration of mRNA levels of ECAD/CDH1, NCAD/CDH2, VIM and ZEB1/TCF8. These EMT-related phenotypic changes were blocked by SB431542, a TGF-βreceptor I (TGFβR1) inhibitor. Inside of the spheroids were highly hypoxic; in contrast, spheroid-derived peripheral migrating cells were normoxic, revealed by visualization and quantification using Hypoxia Probe. Thus, TGF-β-triggered EMT caused spheroid hypoplasia and loss of hypoxia. Spheroid EMT inhibitory (SEMTIN) activity of SB431542 was calculated from fluorescence intensities of the Hypoxia Probe, and then was utilized in a drug screening of EMT-inhibitory small molecule compounds. In a pilot screening, 9 of 1,330 compounds were above the thresholds of the SEMTIN activity and cell viability. Finally, two compounds SB-525334 and SU9516 showed SEMTIN activities in a dose dependent manner. SB-525334 was a known TGFβR1 inhibitor. SU9516 was a cyclin-dependent kinase 2 (CDK2) inhibitor

  16. Comparative assessment of lipid based nano-carrier systems for dendritic cell based targeting of tumor re-initiating cells in gynecological cancers. (United States)

    Bhargava, Arpit; Mishra, Dinesh K; Jain, Subodh K; Srivastava, Rupesh K; Lohiya, Nirmal K; Mishra, Pradyumna K


    We aimed to identify an optimum nano-carrier system to deliver tumor antigen to dendritic cells (DCs) for efficient targeting of tumor reinitiating cells (TRICs) in gynecological malignancies. Different lipid based nano-carrier systems i.e. liposomes, ethosomes and solid lipid nanoparticles (SLNPs) were examined for their ability to activate DCs in allogeneic settings. Out of these three, the most optimized formulation was subjected for cationic and mannosylated surface modification and pulsed with DCs for specific targeting of tumor cells. In both allogeneic and autologous trials, SLNPs showed a strong ability to activate DCs and orchestrate specific immune responses for targeting TRICs in gynecological malignancies. Our findings suggest that the mannosylated form of SLNPs is a suitable molecular vector for DC based therapeutics. DCs pulsed with mannosylated SLNPs may be utilized as adjuvant therapy for specific removal of TRICs to benefit patients from tumor recurrence.

  17. Novel protein kinase signaling systems regulating lifespan identified by small molecule library screening using Drosophila.

    Directory of Open Access Journals (Sweden)

    Stephen R Spindler

    Full Text Available Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay system which allowed screening using the small amounts of materials normally present in commercial chemical libraries. The studies identified 17 inhibitors, the majority of which targeted tyrosine kinases associated with the epidermal growth factor receptor (EGFR, platelet-derived growth factor (PDGF/vascular endothelial growth factor (VEGF receptors, G-protein coupled receptor (GPCR, Janus kinase (JAK/signal transducer and activator of transcription (STAT, the insulin and insulin-like growth factor (IGFI receptors. Comparison of the protein kinase signaling effects of the inhibitors in vitro defined a consensus intracellular signaling profile which included decreased signaling by p38MAPK (p38, c-Jun N-terminal kinase (JNK and protein kinase C (PKC. If confirmed, many of these kinases will be novel additions to the signaling cascades known to regulate metazoan longevity.

  18. Novel protein kinase signaling systems regulating lifespan identified by small molecule library screening using Drosophila. (United States)

    Spindler, Stephen R; Li, Rui; Dhahbi, Joseph M; Yamakawa, Amy; Sauer, Frank


    Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay system which allowed screening using the small amounts of materials normally present in commercial chemical libraries. The studies identified 17 inhibitors, the majority of which targeted tyrosine kinases associated with the epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) receptors, G-protein coupled receptor (GPCR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the insulin and insulin-like growth factor (IGFI) receptors. Comparison of the protein kinase signaling effects of the inhibitors in vitro defined a consensus intracellular signaling profile which included decreased signaling by p38MAPK (p38), c-Jun N-terminal kinase (JNK) and protein kinase C (PKC). If confirmed, many of these kinases will be novel additions to the signaling cascades known to regulate metazoan longevity.

  19. Screening of BRD7 interacting proteins by yeast two-hybrid system

    Institute of Scientific and Technical Information of China (English)

    余鹰; 朱诗国; 张必成; 周鸣; 李小玲; 李桂源


    BRD7 gene is low or undetectably expressed in nasopharyngeal carcinoma tissue (NPC) and can obviously suppress the growth of NPC cell line HNE1. In this study, the proteins that interacted with BRD7 coding protein were screened by yeast two-hybrid system. The complete reading frame of BRD7 gene was subcloned into pAS2 vector (BRD7-BD). Then the human embryo brain cDNA library was screened by BRD7-BD bait. Eleven positive clones were obtained from 4.8×106 transformed clones. By sequencing directly, 6 interacting proteins of BRD7 coding protein were isolated (Bromodomain-containing 3 protein (BRD3), Bromodomain-containing 2 protein (BRD2), IκB kinase-beta, KIAA1375 protein, interleukin 7 and adaptor-related protein complex 3δ-1 subunit). These results suggest BRD7 protein might form heterogenous dimer or triplex polymer with BRD2 and/or BRD3 to participate in transcriptional regulation.

  20. Proposal to institutionalize criteria and quality standards for cervical cancer screening within a health care system

    Directory of Open Access Journals (Sweden)

    Salmerón-Castro Jorge


    Full Text Available The uterine cervix is the most common cancer site for females. Approximately 52,000 new cases occur annually in Latin America, thus the need to improve efficiency and effectiveness of Cervical Cancer Screening Programs (CCSP is mandatory to decrease the unnecessary suffering women must bear. This paper is addressing essential issues to revamp the CCSP as proposed by the Mexican official norm. A general framework for institutionaling CCSP is outlined. Furthermore, strategies to strengthen CCSP performance through managerial strategies and quality assurance activities are described. The focus is on the following activities: 1 improving coverage; 2 implementing smear-taking quality control; 3 improving quality in interpretation of Pap test; 4 guaranteeing treatment for women for whom abnormalities are detected; 5 improving follow-up; 6 development of quality control measures and 7 development of monitoring and epidemiological surveillance information systems. Changes within the screening on cervical cancer may be advocated as new technologies present themselves and shortcomings in the existing program appear. It is crucial that these changes should be measured through careful evaluation in order to tally up potential benefits.

  1. Comparison of absolute speed of screen-film systems measured in seven institutions

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ken-ichi [Yamaguchi Univ., Ube (Japan). Hospital; Murakami, Yasunori; Asahara, Masaki; Nakamura, Satoru; Honda, Mitsugi; Morishita, Junji; Higashida, Yoshiharu; Otsuka, Akiyoshi; Yoshida, Akira


    We compared the differences in absolute speed of four screen-film systems in seven institutions. Four different screens (HR-4, Fuji; Lanex Medium, Kodak; Lanex 250, Kodak; and HR-12, Fuji) combined with super HRS-30 (Fuji) film and a beam quality of 80 kV tube voltage with a 20 mm aluminum filter were employed. Absolute speeds of the HR-4, Lanex Medium, Lanex 250, and HR-12 in combination with super HRS-30 were 1.83 mR{sup -1}, 2.72 mR{sup -1}, 2.79 mR{sup -1}, and 5.35 mR{sup -1} (average of seven institutions), respectively. The variation in speed was about {+-}10% for the seven institutions. Two factors (film processor and densitometer) affecting absolute speed were analyzed. The absolute speed measured in seven institutions varied {+-}14% depending on the film processor (development conditions) and {+-}3% depending on the densitometer employed in each institution. (author)

  2. Construction of the Application Systems for Universal Education in Architectural Heritage – Multimedia Touch Screen Desk System

    Directory of Open Access Journals (Sweden)

    Sato Reika


    Full Text Available The importance of popular education in architectural heritage is well known. It is an effective method for public education to develop applications that utilize digital copy of architectural heritage. We provide a case study focusing on the historical buildings of Toji Temple in Kyoto, Japan. We digitize the historical buildings in both overall construction and detailed structures. We build a demonstration and operating system using multimedia technologies such as multimedia touch screen desk system. The system will produce 3D digital models of architectural heritage with high resolution and use advanced technology to develop a variety of demonstration applications that can enhance your presentation and ease operation. The users can also have more opportunities and ways to improve their interests in learning and understanding about the architectural heritage knowledge, hence finding new ways to further improve the methodology of architectural heritage education with the application of multimedia interactive technologies and digital copy of historical buildings.

  3. Improvement of light collection efficiency of lens-coupled YAG screen TV system for a high-voltage electron microscope. (United States)

    Yamamoto, K; Tanji, T; Hibino, M; Schauer, P; Autrata, R


    A new lens coupling television (TV) system using a YAG (Yttrium Aluminum Garnet: Y(3)Al(5)O(12) : Ce(3+)) single crystal screen has been developed for a high-voltage electron microscope (HVEM), and its performance is examined. The system, using a combination of YAG and lenses, is less damaged by high-energy electron irradiation and reduces the influence of X-rays on the image. YAG screens have not been used for lens-coupling systems, because the high refractive index (n = 1.84) of YAG results in a low light collection efficiency for emitted light. This disadvantage is overcome by combining a thin YAG disk screen (thickness; 100 microm) with a glass hemisphere whose refractive index is 1.81. We found that the light intensity is almost the same as that obtained with a conventional P22 powder screen and lenses system. The resolution is about 55 microm on the YAG screen, and this value is 1.3 times higher than that measured by the conventional system. Shading and distortion do not affect TV observation. Detection quantum efficiency, obtained after correction of the channel mixing effect, is about 0.1.

  4. Screening of sustainable groundwater sources for integration into a regional drought-prone water supply system

    Directory of Open Access Journals (Sweden)

    H. Lucas


    Full Text Available This paper reports on the qualitative and quantitative screening of groundwater sources for integration into the public water supply system of the Algarve, Portugal. The results are employed in a decision support system currently under development for an integrated water resources management scheme in the region. Such a scheme is crucial for several reasons, including the extreme seasonal and annual variations in rainfall, the effect of climate change on more frequent and long-lasting droughts, the continuously increasing water demand and the high risk of a single-source water supply policy. The latter was revealed during the severe drought of 2004 and 2005, when surface reservoirs were depleted and the regional water demand could not be met, despite the drilling of emergency wells.

    For screening and selection, quantitative criteria are based on aquifer properties and well yields, whereas qualitative criteria are defined by water quality indices. These reflect the well's degree of violation of drinking water standards for different sets of variables, including toxicity parameters, nitrate and chloride, iron and manganese and microbiological parameters. Results indicate the current availability of at least 1100 l s−1 of high quality groundwater (55% of the regional demand, requiring only disinfection (900 l s−1 or basic treatment, prior to human consumption. These groundwater withdrawals are sustainable when compared to mean annual recharge, considering that at least 40% is preserved for ecological demands. A more accurate and comprehensive analysis of sustainability is performed with the help of steady-state and transient groundwater flow simulations, which account for aquifer geometry, boundary conditions, recharge and discharge rates, pumping activity and seasonality. They permit an advanced analysis of present and future scenarios and show that increasing water demands and decreasing rainfall will make

  5. Screening of sustainable groundwater sources for integration into a regional drought-prone water supply system

    Directory of Open Access Journals (Sweden)

    T. Y. Stigter


    Full Text Available This paper reports on the qualitative and quantitative screening of groundwater sources for integration into the public water supply system of the Algarve, Portugal. The results are employed in a decision support system currently under development for an integrated water resources management scheme in the region. Such a scheme is crucial for several reasons, including the extreme seasonal and annual variations in rainfall, the effect of climate change on more frequent and long-lasting droughts, the continuously increasing water demand and the high risk of a single-source water supply policy. The latter was revealed during the severe drought of 2004 and 2005, when surface reservoirs were depleted and the regional water demand could not be met, despite the drilling of emergency wells.

    For screening and selection, quantitative criteria are based on aquifer properties and well yields, whereas qualitative criteria are defined by water quality indices. These reflect the well's degree of violation of drinking water standards for different sets of variables, including toxicity parameters, nitrate and chloride, iron and manganese and microbiological parameters. Results indicate the current availability of at least 1100 l s−1 of high quality groundwater (55% of the regional demand, requiring only disinfection (900 l s−1 or basic treatment, prior to human consumption. These groundwater withdrawals are sustainable when compared to mean annual recharge, considering that at least 40% is preserved for ecological demands. A more accurate and comprehensive analysis of sustainability is performed with the help of steady-state and transient groundwater flow simulations, which account for aquifer geometry, boundary conditions, recharge and discharge rates, pumping activity and seasonality. They permit an advanced analysis of present and future scenarios and show that increasing water demands and decreasing rainfall will make

  6. Screening of sustainable groundwater sources for integration into a regional drought-prone water supply system (United States)

    Stigter, T. Y.; Monteiro, J. P.; Nunes, L. M.; Vieira, J.; Cunha, M. C.; Ribeiro, L.; Nascimento, J.; Lucas, H.


    This paper reports on the qualitative and quantitative screening of groundwater sources for integration into the public water supply system of the Algarve, Portugal. The results are employed in a decision support system currently under development for an integrated water resources management scheme in the region. Such a scheme is crucial for several reasons, including the extreme seasonal and annual variations in rainfall, the effect of climate change on more frequent and long-lasting droughts, the continuously increasing water demand and the high risk of a single-source water supply policy. The latter was revealed during the severe drought of 2004 and 2005, when surface reservoirs were depleted and the regional water demand could not be met, despite the drilling of emergency wells. For screening and selection, quantitative criteria are based on aquifer properties and well yields, whereas qualitative criteria are defined by water quality indices. These reflect the well's degree of violation of drinking water standards for different sets of variables, including toxicity parameters, nitrate and chloride, iron and manganese and microbiological parameters. Results indicate the current availability of at least 1100 l s-1 of high quality groundwater (55% of the regional demand), requiring only disinfection (900 l s-1) or basic treatment, prior to human consumption. These groundwater withdrawals are sustainable when compared to mean annual recharge, considering that at least 40% is preserved for ecological demands. A more accurate and comprehensive analysis of sustainability is performed with the help of steady-state and transient groundwater flow simulations, which account for aquifer geometry, boundary conditions, recharge and discharge rates, pumping activity and seasonality. They permit an advanced analysis of present and future scenarios and show that increasing water demands and decreasing rainfall will make the water supply system extremely vulnerable, with a high

  7. Hypertension Screening and Follow-up Management by Primary Health Care System among Chinese Population Aged 35 Years and Above

    Institute of Scientific and Technical Information of China (English)

    FENG Ya Jing; WANG Hui Cheng; LI Yi Chong; ZHAO Wen Hua


    Objective To describe hypertension screening and follow-up management among Chinese population aged 35 years and above within the primary health care system. Methods Data from 2010 China Chronic Disease and Risk Factor Surveillance System were used. We investigated previous hypertension diagnosis, screening, and follow-up assessments within the primary health care system. The prevalence of self-reported and criterion-based hypertension, screening rates, demographic and socioeconomic characteristics associated with screening, and patterns of follow-up assessments were recorded. The SAS software system was used for statistical analyses. Results About 17.1% reported a previous hypertension diagnosis. The rate difference between the two measures of prevalence was 27.2%. Among those without self-reported hypertension, 27.7%reported never visiting a clinic during the past 1 year and 60.4%of those attending a clinic reported ever being screened. Younger age group was associated with lower screening proportion;odds ratios of 35-, 45-, 55-, and≥65 years were 1.7 (95%CI:1.5-1.9), 1.5 (95%CI:1.3-1.7), 1.3 (95%CI:1.2-1.4), and 1.0, respectively. About 35.1% of the patients had undergone follow-up assessments four or more times during the past 1 year. Conclusion Majority of the Chinese population aged 35 years and above, particularly the less educated, elderly population, and rural residents were unaware of that they were suffering from hypertension. Most patients did not receive enough management services by the primary health care system. Thus, strengthening both the screening and follow-up management is needed.

  8. Performance of a microbial fuel cell-based biosensor for online monitoring in an integrated system combining microbial fuel cell and upflow anaerobic sludge bed reactor. (United States)

    Jia, Hui; Yang, Guang; Wang, Jie; Ngo, Huu Hao; Guo, Wenshan; Zhang, Hongwei; Zhang, Xinbo


    A hybrid system integrating a microbial fuel cell (MFC)-based biosensor with upflow anaerobic sludge blanket (UASB) was investigated for real-time online monitoring of the internal operation of the UASB reactor. The features concerned were its rapidity and steadiness with a constant operation condition. In addition, the signal feedback mechanism was examined by the relationship between voltage and time point of changed COD concentration. The sensitivity of different concentrations was explored by comparing the signal feedback time point between the voltage and pH. Results showed that the electrical signal feedback was more sensitive than pH and the thresholds of sensitivity were S=3×10(-5)V/(mg/L) and S=8×10(-5)V/(mg/L) in different concentration ranges, respectively. Although only 0.94% of the influent COD was translated into electricity and applied for biosensing, this integrated system indicated great potential without additional COD consumption for real-time monitoring.

  9. Establishment of a system based on universal multiplex-PCR for screening genetically modified crops. (United States)

    Lu, I-Jen; Lin, Chih-Hui; Pan, Tzu-Ming


    The rapid development of many genetically modified (GM) crops in the past two decades makes it necessary to introduce an alternative strategy for routine screening and identification. In this study, we established a universal multiplex PCR detection system which will effectively reduce the number of reactions needed for sample identification. The PCR targets of this system include the six most frequently used transgenic elements: cauliflower mosaic virus (CaMV) 35S promoter, Agrobacterium tumefaciens nopaline synthase (nos) promoter, Agrobacterium tumefaciens nopaline synthase (nos) terminator, the neomycin phosphotransferase II (nptII) gene, the 5-enolpyruvylshikimate-3-phosphate synthase (CP4 epsps) gene of Agrobacterium tumefaciens strain CP4, and the phosphinothricin N-acetyltransferase (pat) gene. According to the AGBIOS database, the coverage of this detection system is 93% of commercial GM crops. This detection system could detect all certified reference materials (CRMs) at the 1.0% level. The correct combination of all the CRM amplicon patterns proved the specificity of this multiplex PCR system. Furthermore, the amplicon patterns of this multiplex PCR detection system could be used as an index of classification which will narrow the range of possible GM products. The simulation result of this multiplex PCR detection system on all commercialized 139 GM products in the AGBIOS database showed that the maximum number of PCR reactions needed to identify an unknown sample can be reduced to 13. In this study, we established a high-throughput multiplex PCR detection system with feasible sensitivity, specificity, and cost. By incorporating this detection system, the routine GM crop-detection process will meet the challenges resulting from a rapid increase in the number of GM crops in the future.

  10. Digital I&C Systems in Nuclear Power Plants. Risk-Screening of Environmental Stressors and a Comparison of Hardware Unavailability With an Existing Analog System (United States)


    NUREG /CR-6579 BNL- NUREG -52536 Digital I&C Systems in Nuclear Power Plants Risk-Screening of Environmental Stressors and a Comparison of Hardware...13.2.3 NUREG /CR-6579 BNL- NUREG -52536 Digital I&C Systems in Nuclear Power Plants Risk-Screening of Environmental Stressors and a Comparison of...licensee documents and correspondence. The following documents in the NUREG series are available for purchase from the Government Printing Office: formal

  11. Establishment of a transgenic yeast screening system for estrogenicity and identification of the anti-estrogenic activity of malachite green. (United States)

    Jiao, Baowei; Yeung, Eric K C; Chan, Chi Bun; Cheng, Christopher H K


    Endocrine disruptors refer to chemical compounds in the environment which interfere with the endocrine systems of organisms. Among them, environmental estrogens pose serious problems to aquatic organisms, in particular fish. It is therefore important and necessary to have a fast and low-cost system to screen the large number of different chemical compounds in the aquatic environment for their potential endocrine disrupting actions. In this study, a screening platform was developed to detect xenoestrogens in the aquatic environment using the fission yeast Schizosaccharomyces pombe, and applied for compound screening. The aim was to demonstrate any significant potential differences between the fish screening system and the human screening system. To this end, a yeast expression vector harboring a fish estrogen receptor alpha and a reporter vector containing the estrogen responsive element fused with the Escherichia coli LacZ gene were constructed. After transformation with these two vectors, the transformed yeast clones were confirmed by Western blotting and selected on the basis of the beta-galactosidase activity. In this transgenic yeast system, the natural estrogen (estradiol) and other known xenoestrogens such as diethylstilbestrol, bisphenol A, genistein and dichloro-diphenyl-trichloroethane exhibited dose-dependent activities. Using this system, more than 40 putative endocrine disruptors including phytoestrogens, pesticides, herbicides, industrial dyes and other industrial chemicals were screened. Ten of them were demonstrated to exhibit estrogenic actions. Industrial dyes such as malachite green (MG) that disrupt thyroid hormone synthesis are extensively used and are widely distributed in the aquatic environment. Using this system, MG did not show any estrogenic action, but was demonstrated to exhibit anti-estrogenic activity.

  12. NOD/scid IL-2Rgnull mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo

    Directory of Open Access Journals (Sweden)

    Spranger Stefani


    Full Text Available Abstract Background To date very few systems have been described for preclinical investigations of human cellular therapeutics in vivo. However, the ability to carry out comparisons of new cellular vaccines in vivo would be of substantial interest for design of clinical studies. Here we describe a humanized mouse model to assess the efficacy of various human dendritic cell (DC preparations. Two reconstitution regimes of NOD/scid IL2Rgnull (NSG mice with adult human peripheral blood mononuclear cells (PBMC were evaluated for engraftment using 4-week and 9-week schedules. This led to selection of a simple and rapid protocol for engraftment and vaccine evaluation that encompassed 4 weeks. Methods NSG recipients of human PBMC were engrafted over 14 days and then vaccinated twice with autologous DC via intravenous injection. Three DC vaccine formulations were compared that varied generation time in vitro (3 days versus 7 days and signals for maturation (with or without Toll-like receptor (TLR3 and TLR7/8 agonists using MART-1 as a surrogate antigen, by electroporating mature DC with in vitro transcribed RNA encoding full length protein. After two weekly vaccinations, the splenocyte populations containing human lymphocytes were recovered 7 days later and assessed for MART-1-specific immune responses using MHC-multimer-binding assays and functional assessment of specific killing of melanoma tumor cell lines. Results Human monocyte-derived DC generated in vitro in 3 days induced better MART-1-specific immune responses in the autologous donor T cells present in the humanized NSG mice. Moreover, consistent with our in vitro observations, vaccination using mature DC activated with TLR3 and TLR7/8 agonists resulted in enhanced immune responses in vivo. These findings led to a ranking of the DC vaccine effects in vivo that reflected the hierarchy previously found for these mature DC variations in vitro. Conclusions This humanized mouse model system enables

  13. An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer drugs.

    Directory of Open Access Journals (Sweden)

    Young-Ki Bae

    Full Text Available The epidermal growth factor receptor (EGFR is a well-established target for cancer treatment. EGFR tyrosine kinase (TK inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK, a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R], or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R] in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor and U0126 (a MEK inhibitor were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs.

  14. Designing Capital-Intensive Systems with Architectural and Operational Flexibility Using a Screening Model (United States)

    Lin, Jijun; de Weck, Olivier; de Neufville, Richard; Robinson, Bob; MacGowan, David

    Development of capital intensive systems, such as offshore oil platforms or other industrial infrastructure, generally requires a significant amount of capital investment under various resource, technical, and market uncertainties. It is a very challenging task for development co-owners or joint ventures because important decisions, such as system architectures, have to be made while uncertainty remains high. This paper develops a screening model and a simulation framework to quickly explore the design space for complex engineering systems under uncertainty allowing promising strategies or architectures to be identified. Flexibility in systems’ design and operation is proposed as a proactive means to enable systems to adapt to future uncertainty. Architectural and operational flexibility can improve systems’ lifecycle value by mitigating downside risks and capturing upside opportunities. In order to effectively explore different flexible strategies addressing a view of uncertainty which changes with time, a computational framework based on Monte Carlo simulation is proposed in this paper. This framework is applied to study flexible development strategies for a representative offshore petroleum project. The complexity of this problem comes from multi-domain uncertainties, large architectural design space, and structure of flexibility decision rules. The results demonstrate that architectural and operational flexibility can significantly improve projects’ Expected Net Present Value (ENPV), reduce downside risks, and improve upside gains, compared to adopting an inflexible strategy appropriate to the view of uncertainty at the start of the project. In this particular case study, the most flexible strategy improves ENPV by 85% over an inflexible base case.

  15. Cell-Based Biosensors Principles and Applications

    CERN Document Server

    Wang, Ping


    Written by recognized experts the field, this leading-edge resource is the first book to systematically introduce the concept, technology, and development of cell-based biosensors. You find details on the latest cell-based biosensor models and novel micro-structure biosensor techniques. Taking an interdisciplinary approach, this unique volume presents the latest innovative applications of cell-based biosensors in a variety of biomedical fields. The book also explores future trends of cell-based biosensors, including integrated chips, nanotechnology and microfluidics. Over 140 illustrations hel

  16. 缺氧诱导因子-1抑制剂细胞筛选模型的建立及抑制剂研究%Identification of two small molecule inhibitors of hypoxia-inducible factor 1 with different cell-based screening model

    Institute of Scientific and Technical Information of China (English)

    郎立伟; 唐克; 李燕; 刘晓宇; 王超; 陈晓光


    sensitive inhibition activity of HIF-1 on manassantin A than that of detected by U251-HRE model. The IC50 of manassantin A on HIF-1 activity was (2. 4 ±0. 6)× 10 -8 mol · L-1. HIF-1 target gene VEGF was also inhibited by test compounds on protein level in T47D cells. Manasaantin A showed selective inhibition on the growth of human solid cancer cell lines, especially on breast cancer and pancreatic cancer cells. Meanwhile, triplotide showed strong proliferation inhibition activity on all tested cell lines. Conclusion: It is very important to select a suitable cell-based report gene assay of HIF-1 for screening of different kinds of inhibitor.


    Directory of Open Access Journals (Sweden)

    E.A. Chaplygin


    Full Text Available Introduction. Developments in the field of magnetic-pulse treatment of metals (MPTM are increasingly used in the modern technologies of production and repair of the aviation, automotive and other machinery, as they are environmentally friendly and energy-efficient in comparison with classical approaches. One of the main components of the device MPTM is a tool – inductor or the inductor system with an attractive screen (ISAS. The calculated dependences to calculate the inductor system with an attractive screen were taken from previous works. The ratios were obtained for the low-frequency mode of the excited fields, when is place their significant penetration through a thin-walled metal screen and a deformed workpiece. As it was shown earlier this mode is the most efficient from point of view of a force action on the object of a processing. Purpose. The theoretical analysis of the spatial-temporal distributions of the induced currents and forces of an attraction in the inductor system with an attractive screen excited by a flat circular solenoid located on the outside of the auxiliary screen. Methodology. The calculations are shown that the induced currents both in the screen and the workpiece are unidirectional and their interaction, in accordance with the law of Ampere determines the amplitudes of excited forces of attraction. Let’s note the effective validity of the considered inductor system excited by an external circular solenoid. With sufficient simplicity of the design take place rather high values of the developed forces of attraction and their averages. Results. Physically, a higher power efficiency of the system with an «external» coil in comparison with a system where coil is located in the internal cavity, can be accounted for lade of «failure» in the radial distribution of the excited forces. This «failure» in the design with a coil between the sheet metal is caused by its screening action against the forces of attraction

  18. On the Development of a Web-Based M-Learning System for Dual Screen Handheld Game Consoles

    Directory of Open Access Journals (Sweden)

    Hend S. Al-Khalifa


    Full Text Available This paper presents our experience on the design and development of an M-Learning web-based system for the Nintendo DSi game console. The paper starts by addressing the difficulties that emerged from the lack of resources on design guidelines for dual screen devices also the absence of adequate techniques and methods to support the design decisions. Then it explains how we overcame these challenges by adopting a design decision suitable for the screen requirements of the Nintendo DSi console. Finally, we present the components of our M-Learning system and the results of a preliminary usability evaluation.

  19. Research and fabrication of image-forming system of the cell based on LIFD%基于激光诱导的细胞荧光成像系统研制

    Institute of Scientific and Technical Information of China (English)

    柳葆; 张思祥; 周围; 常银霞


    分析了激光诱导荧光法检测钙离子浓度的原理.并利用微流控芯片在细胞培养和检测上的独特优越性,设计实现了基于微流控芯片的测量细胞内钙离子浓度变化的显微荧光成像系统.在对微流控芯片技术研究的基础上设计制作了微流控芯片,并设计了显微系统、快速波长切换系统、CCD成像系统等.利用这套显微荧光成像系统对活体细胞的荧光图像进行采集.本系统的设计为微流控芯片开辟了新的应用领域,同时提供了一种活体细胞离子检测的新手段.%Theory of laser-induced fluorescence detection (LIFD) method for concentration of calcium ion detection is analyzed. Because of superiority in cells development and detection, an image-forming system for concentration detecting of calcium ion in cells based on microfiuidic chip using the technology of LIFD is built. On the basis of studies of the technology of microfiuidic chips, a microfiuidic chip has been designed and manufactured for the detection of calcium concentration. A microscope system, a fast wavelength switching system and a CCD image forming system have also been designed. The images of fluorescence are collected by the imageforming system. Based on this new image-forming system, a new application domain is opened for microfiuidic chip and a new method is provided for detecting ion in cells.

  20. Screening and genetic manipulation of green organisms for establishment of biological life support systems in space. (United States)

    Saei, Amir Ata; Omidi, Amir Ali; Barzegari, Abolfazl


    Curiosity has driven humankind to explore and conquer space. However, today, space research is not a means to relieve this curiosity anymore, but instead has turned into a need. To support the crew in distant expeditions, supplies should either be delivered from the Earth, or prepared for short durations through physiochemical methods aboard the space station. Thus, research continues to devise reliable regenerative systems. Biological life support systems may be the only answer to human autonomy in outposts beyond Earth. For construction of an artificial extraterrestrial ecosystem, it is necessary to search for highly adaptable super-organisms capable of growth in harsh space environments. Indeed, a number of organisms have been proposed for cultivation in space. Meanwhile, some manipulations can be done to increase their photosynthetic potential and stress tolerance. Genetic manipulation and screening of plants, microalgae and cyanobacteria is currently a fascinating topic in space bioengineering. In this commentary, we will provide a viewpoint on the realities, limitations and promises in designing biological life support system based on engineered and/or selected green organism. Special focus will be devoted to the engineering of key photosynthetic enzymes in pioneer green organisms and their potential use in establishment of transgenic photobioreactors in space.

  1. Deployment and Validation of a Smart System for Screening of Language Disorders in Primary Care

    Directory of Open Access Journals (Sweden)

    Iván Pau de la Cruz


    Full Text Available Neuro-evolutive development from birth until the age of six years is a decisive factor in a child’s quality of life. Early detection of development disorders in early childhood can facilitate necessary diagnosis and/or treatment. Primary-care pediatricians play a key role in its detection as they can undertake the preventive and therapeutic actions requested to promote a child’s optimal development. However, the lack of time and little specific knowledge at primary-care avoid to applying continuous early-detection anomalies procedures. This research paper focuses on the deployment and evaluation of a smart system that enhances the screening of language disorders in primary care. Pediatricians get support to proceed with early referral of language disorders. The proposed model provides them with a decision-support tool for referral actions to trigger essential diagnostic and/or therapeutic actions for a comprehensive individual development. The research was conducted by starting from a sample of 60 cases of children with language disorders. Validation was carried out through two complementary steps: first, by including a team of seven experts from the fields of neonatology, pediatrics, neurology and language therapy, and, second, through the evaluation of 21 more previously diagnosed cases. The results obtained show that therapist positively accepted the system proposal in 18 cases (86% and suggested system redesign for single referral to a speech therapist in three remaining cases.

  2. Development of a Drosophila cell-based error correction assay

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Salemi


    Full Text Available Accurate transmission of the genome through cell division requires microtubules from opposing spindle poles to interact with protein super-structures called kinetochores that assemble on each sister chromatid. Most kinetochores establish erroneous attachments that are destabilized through a process called error correction. Failure to correct improper kinetochore-microtubule (kt-MT interactions before anaphase onset results in chromosomal instability (CIN, which has been implicated in tumorigenesis and tumor adaptation. Thus, it is important to characterize the molecular basis of error correction to better comprehend how CIN occurs and how it can be modulated. An error correction assay has been previously developed in cultured mammalian cells in which incorrect kt-MT attachments are created through the induction of monopolar spindle assembly via chemical inhibition of kinesin-5. Error correction is then monitored following inhibitor wash out. Implementing the error correction assay in Drosophila melanogaster S2 cells would be valuable because kt-MT attachments are easily visualized and the cells are highly amenable to RNAi and high-throughput screening. However, Drosophila kinesin-5 (Klp61F is unaffected by available small molecule inhibitors. To overcome this limitation, we have rendered S2 cells susceptible to kinesin-5 inhibitors by functionally replacing Klp61F with human kinesin-5 (Eg5. Eg5 expression rescued the assembly of monopolar spindles typically caused by Klp61F depletion. Eg5-mediated bipoles collapsed into monopoles due to the activity of kinesin-14 (Ncd when treated with the kinesin-5 inhibitor S-trityl-L-cysteine (STLC. Furthermore, bipolar spindles reassembled and error correction was observed after STLC wash out. Importantly, error correction in Eg5-expressing S2 cells was dependent on the well-established error correction kinase Aurora B. This system provides a powerful new cell-based platform for studying error correction and

  3. Development of a Drosophila cell-based error correction assay. (United States)

    Salemi, Jeffrey D; McGilvray, Philip T; Maresca, Thomas J


    Accurate transmission of the genome through cell division requires microtubules from opposing spindle poles to interact with protein super-structures called kinetochores that assemble on each sister chromatid. Most kinetochores establish erroneous attachments that are destabilized through a process called error correction. Failure to correct improper kinetochore-microtubule (kt-MT) interactions before anaphase onset results in chromosomal instability (CIN), which has been implicated in tumorigenesis and tumor adaptation. Thus, it is important to characterize the molecular basis of error correction to better comprehend how CIN occurs and how it can be modulated. An error correction assay has been previously developed in cultured mammalian cells in which incorrect kt-MT attachments are created through the induction of monopolar spindle assembly via chemical inhibition of kinesin-5. Error correction is then monitored following inhibitor wash out. Implementing the error correction assay in Drosophila melanogaster S2 cells would be valuable because kt-MT attachments are easily visualized and the cells are highly amenable to RNAi and high-throughput screening. However, Drosophila kinesin-5 (Klp61F) is unaffected by available small molecule inhibitors. To overcome this limitation, we have rendered S2 cells susceptible to kinesin-5 inhibitors by functionally replacing Klp61F with human kinesin-5 (Eg5). Eg5 expression rescued the assembly of monopolar spindles typically caused by Klp61F depletion. Eg5-mediated bipoles collapsed into monopoles due, in part, to kinesin-14 (Ncd) activity when treated with the kinesin-5 inhibitor S-trityl-L-cysteine (STLC). Furthermore, bipolar spindles reassembled and error correction was observed after STLC wash out. Importantly, error correction in Eg5-expressing S2 cells was dependent on the well-established error correction kinase Aurora B. This system provides a powerful new cell-based platform for studying error correction and CIN.

  4. A high throughput screening assay system for the identification of small molecule inhibitors of gsp.

    Directory of Open Access Journals (Sweden)

    Nisan Bhattacharyya

    Full Text Available Mis-sense mutations in the α-subunit of the G-protein, Gsα, cause fibrous dysplasia of bone/McCune-Albright syndrome. The biochemical outcome of these mutations is constitutively active Gsα and increased levels of cAMP. The aim of this study was to develop an assay system that would allow the identification of small molecule inhibitors specific for the mutant Gsα protein, the so-called gsp oncogene. Commercially available Chinese hamster ovary cells were stably transfected with either wild-type (WT or mutant Gsα proteins (R201C and R201H. Stable cell lines with equivalent transfected Gsα protein expression that had relatively lower (WT or higher (R201C and R201H cAMP levels were generated. These cell lines were used to develop a fluorescence resonance energy transfer (FRET-based cAMP assay in 1536-well microplate format for high throughput screening of small molecule libraries. A small molecule library of 343,768 compounds was screened to identify modulators of gsp activity. A total of 1,356 compounds with inhibitory activity were initially identified and reconfirmed when tested in concentration dose responses. Six hundred eighty-six molecules were selected for further analysis after removing cytotoxic compounds and those that were active in forskolin-induced WT cells. These molecules were grouped by potency, efficacy, and structural similarities to yield 22 clusters with more than 5 of structurally similar members and 144 singleton molecules. Seven chemotypes of the major clusters were identified for further testing and analyses.

  5. Training set optimization and classifier performance in a top-down diabetic retinopathy screening system (United States)

    Wigdahl, J.; Agurto, C.; Murray, V.; Barriga, S.; Soliz, P.


    Diabetic retinopathy (DR) affects more than 4.4 million Americans age 40 and over. Automatic screening for DR has shown to be an efficient and cost-effective way to lower the burden on the healthcare system, by triaging diabetic patients and ensuring timely care for those presenting with DR. Several supervised algorithms have been developed to detect pathologies related to DR, but little work has been done in determining the size of the training set that optimizes an algorithm's performance. In this paper we analyze the effect of the training sample size on the performance of a top-down DR screening algorithm for different types of statistical classifiers. Results are based on partial least squares (PLS), support vector machines (SVM), k-nearest neighbor (kNN), and Naïve Bayes classifiers. Our dataset consisted of digital retinal images collected from a total of 745 cases (595 controls, 150 with DR). We varied the number of normal controls in the training set, while keeping the number of DR samples constant, and repeated the procedure 10 times using randomized training sets to avoid bias. Results show increasing performance in terms of area under the ROC curve (AUC) when the number of DR subjects in the training set increased, with similar trends for each of the classifiers. Of these, PLS and k-NN had the highest average AUC. Lower standard deviation and a flattening of the AUC curve gives evidence that there is a limit to the learning ability of the classifiers and an optimal number of cases to train on.

  6. Control system design of the CERN/CMS tracker thermal screen

    CERN Document Server

    Carrone, E


    The Tracker is one of the CMS (Compact Muon Solenoid experiment) subdetectors to be installed at the LHC (Large Hadron Collider) accelerator, scheduled to start data taking in 2007 at CERN (European Organization for Nuclear Research). The tracker will be operated at a temperature of -10 degree C in order to reduce the radiation damage on the silicon detectors; hence, an insulated environment has to be provided by means of a screen that introduces a thermal separation between the Tracker and the neighboring detection systems. The control system design includes a formal description of the process by means of a thermodynamic model; then, the electrical equivalence is derived. The transfer function is inferred by the ratio of the voltage on the outer skin and the voltage input, i.e. the ratio of the temperature outside the tracker and the heat generated (which is the controlled variable). A PID (Proportional Integral Derivative) controller has been designed using MatLab. The results achieved so far prove that thi...

  7. MOLA: a bootable, self-configuring system for virtual screening using AutoDock4/Vina on computer clusters

    Directory of Open Access Journals (Sweden)

    Abreu Rui MV


    Full Text Available Abstract Background Virtual screening of small molecules using molecular docking has become an important tool in drug discovery. However, large scale virtual screening is time demanding and usually requires dedicated computer clusters. There are a number of software tools that perform virtual screening using AutoDock4 but they require access to dedicated Linux computer clusters. Also no software is available for performing virtual screening with Vina using computer clusters. In this paper we present MOLA, an easy-to-use graphical user interface tool that automates parallel virtual screening using AutoDock4 and/or Vina in bootable non-dedicated computer clusters. Implementation MOLA automates several tasks including: ligand preparation, parallel AutoDock4/Vina jobs distribution and result analysis. When the virtual screening project finishes, an open-office spreadsheet file opens with the ligands ranked by binding energy and distance to the active site. All results files can automatically be recorded on an USB-flash drive or on the hard-disk drive using VirtualBox. MOLA works inside a customized Live CD GNU/Linux operating system, developed by us, that bypass the original operating system installed on the computers used in the cluster. This operating system boots from a CD on the master node and then clusters other computers as slave nodes via ethernet connections. Conclusion MOLA is an ideal virtual screening tool for non-experienced users, with a limited number of multi-platform heterogeneous computers available and no access to dedicated Linux computer clusters. When a virtual screening project finishes, the computers can just be restarted to their original operating system. The originality of MOLA lies on the fact that, any platform-independent computer available can he added to the cluster, without ever using the computer hard-disk drive and without interfering with the installed operating system. With a cluster of 10 processors, and a

  8. Quality assurance for screening mammography data collection systems in 22 countries.

    NARCIS (Netherlands)

    Klabunde, C.N.; Sancho-Garnier, H.; Broeders, M.E.A.C.; Thoresen, S.; Rodrigues, V.J.; Ballard-Barbash, R.


    OBJECTIVES: To document the mammography data that are gathered by the organized screening programs participating in the International Breast Cancer Screening Network (IBSN), the nature of their procedures for data quality assurance, and the measures used to assess program performance and impact. MET

  9. COSMO-RS-based extractant screening for phenol extraction as model system

    NARCIS (Netherlands)

    Burghoff, B.; Goetheer, E.L.V.; Haan, A.B. de


    The focus of this investigation is the development of a fast and reliable extractant screening approach. Phenol extraction is selected as the model process. A quantum chemical conductor-like screening model for real solvents (COSMO-RS) is combined with molecular design considerations. For this purpo

  10. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem... (United States)


    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Newborn screening test system for amino acids... carnitine, and acyl-carnitine metabolism. (b) Classification. Class II (special controls). The...

  11. Assessment of radiographic screen-film systems: a comparison between the use of a microdensitometer and a drum film digitiser. (United States)

    Verdun, F R; Pachoud, M; Bergmann, D; Buhr, E


    A high-end drum film digitiser (Tango, Germany) and a calibrated linear microdensitometer developed by PTB were used to assess the modulation transfer function (MTF) and the noise power spectra (NPS) of 3 mammographic screen film systems at optical density levels of 0.8, 1.5 and 2.5. The use of a drum scanner to assess MTF and NPS data appears to be adequate but requires an appropriate characterisation of the scanner to verify its internal noise level and its MTF. It is further necessary to calibrate the scanner output in terms of visual diffuse optical densities. Processing of two-dimensional digital data of grating images need to be more strictly defined for accurate MTF measurements of screen-film systems. Nevertheless, even now it seems to be feasible to use commercially available high-end and well calibrated scanners to assess screen film systems. This is especially important for quality assurance purposes because important parameters of screen film systems such like MTF and NPS can now be determined without using sophisticated microdensitometers which are not commercially available.

  12. Economic Screening of Geologic Sequestration Options in the United States with a Carbon Management Geographic Information System

    Energy Technology Data Exchange (ETDEWEB)

    Dahowski, Robert T.(BATTELLE (PACIFIC NW LAB)); Dooley, James J.(BATTELLE (PACIFIC NW LAB)); Brown, Daryl R.(BATTELLE (PACIFIC NW LAB)); Stephan, Alex J.(BATTELLE (PACIFIC NW LAB)); Badie I. Morsi


    Developing a carbon management strategy is a formidable task for nations as well as individual companies. It is often difficult to understand what options are available, let alone determine which may be optimal. In response to the need for a better understanding of complex carbon management options, Battelle has developed a state-of-the-art Geographic Information System (GIS) model with economic screening capability focused on carbon capture and geologic sequestration opportunities in the United States. This paper describes the development of this GIS-based economic screening model and demonstrates its use for carbon management analysis.

  13. Use of a geographic information system (GIS) for targeting radon screening programs in South Dakota. (United States)

    Kearfott, Kimberlee J; Whetstone, Zachary D; Rafique Mir, Khwaja M


    Because (222)Rn is a progeny of (238)U, the relative abundance of uranium may be used to predict the areas that have the potential for high indoor radon concentration and therefore determine the best areas to conduct future surveys. Geographic Information System (GIS) mapping software was used to construct maps of South Dakota that included levels of uranium concentrations in soil and stream water and uranium deposits. Maps of existing populations and the types of land were also generated. Existing data about average indoor radon levels by county taken from a databank were included for consideration. Although the soil and stream data and existing recorded average indoor radon levels were sparse, it was determined that the most likely locations of elevated indoor radon would be in the northwest and southwest corners of the state. Indoor radon levels were only available for 9 out of 66 counties in South Dakota. This sparcity of data precluded a study of correlation of radon to geological features, but further motivates the need for more testing in the state. Only actual measurements should be used to determine levels of indoor radon because of the strong roles home construction and localized geology play in radon concentration. However, the data visualization method demonstrated here is potentially useful for directing resources relating to radon screening campaigns.

  14. Characteristics of Screen Mesh Wick Heat Pipe with Nanofluid as Passive Cooling System

    Directory of Open Access Journals (Sweden)

    W.N. Septiadi


    Full Text Available The heat pipe is one of the cooling media which is potential to be developed for the passive cooling system for nuclear reactors. To enhance the performance of the heat pipe, nanofluids have been used as the working fluid for the heat pipe. This paper studies the characteristics of nanofluids as the working fluid of heat pipe with screen mesh wick, which was the mixture of nano-sized particles (Al2O3 and TiO2 with water as the base fluid. The nanoparticles have average diameter of 20 nm, made with 1% to 5% volume fraction. The heat pipe thermal performance was tested using heater with different heat load. The experimental result shows the use of 5% Al2O3-water improve the thermal performance by reducing the temperature at evaporator side as much as 23.7% and the use of TiO2-water reduce the temperature at evaporator side as much as 20.2% compared to the use of water. The use of nanofluid also decreases the thermal resistance of heat pipe. As the use of nanofluid improves thermal performance of heat pipe, it has a potential for applications along with heat pipes at nuclear reactors

  15. Use of electronic personal health record systems to encourage HIV screening: an exploratory study of patient and provider perspectives

    Directory of Open Access Journals (Sweden)

    McInnes D Keith


    Full Text Available Abstract Background When detected, HIV can be effectively treated with antiretroviral therapy. Nevertheless in the U.S. approximately 25% of those who are HIV-infected do not know it. Much remains unknown about how to increase HIV testing rates. New Internet outreach methods have the potential to increase disease awareness and screening among patients, especially as electronic personal health records (PHRs become more widely available. In the US Department of Veterans' Affairs medical care system, 900,000 veterans have indicated an interest in receiving electronic health-related communications through the PHR. Therefore we sought to evaluate the optimal circumstances and conditions for outreach about HIV screening. In an exploratory, qualitative research study we examined patient and provider perceptions of Internet-based outreach to increase HIV screening among veterans who use the Veterans Health Administration (VHA health care system. Findings We conducted two rounds of focus groups with veterans and healthcare providers at VHA medical centers. The study's first phase elicited general perceptions of an electronic outreach program to increase screening for HIV, diabetes, and high cholesterol. Using phase 1 results, outreach message texts were drafted and then presented to participants in the second phase. Analysis followed modified grounded theory. Patients and providers indicated that electronic outreach through a PHR would provide useful information and would motivate patients to be screened for HIV. Patients believed that electronic information would be more convenient and understandable than information provided verbally. Patients saw little difference between messages about HIV versus about diabetes and cholesterol. Providers, however, felt patients would disapprove of HIV-related messages due to stigma. Providers expected increased workload from the electronic outreach, and thus suggested adding primary care resources and devising

  16. Application effect of TruScreen system in cervical cancer screening%TruScreen系统在宫颈癌筛查中的应用效果

    Institute of Scientific and Technical Information of China (English)

    李佩; 王金声; 康媛


    Objective To investigate the effect of TruScreen (TS) system as applied in cervical cancer screening. Method 368 patients were included in the retrospective analysis, and were randomized into TS group or TCT group, with 184 cases in each. The TS group was tested with TS detection, while the TCT group was administered with Thin Prep cytology test (TCT), and the effect of the two tests were compared with histopathology as the diagnostic standard. Result The detection sensitivity, specificity and the positive rate of the TS and TCT group were 93.2%and 100%, 76.0%and 75.0%, 64.7% and 55.7%, respectively. Conclusion TS detection is as good as TCT detection in cervical cancer screening, which is clinically applicable.%目的:探讨宫颈癌筛查系统TruScreen(TS)在宫颈癌筛查中的应用效果。方法回顾性分析368例检查者,分为TS检测组和TCT检测组,每组184例,TS检测组行TS检测,TCT检测组行液基薄层细胞学(TCT)检测,以组织病理学为诊断标准,比较TS与TCT检查在宫颈癌筛查中的应用效果。结果 TS检测组与TCT检测组检测敏感度分别为93.2%、100%,特异度分别为76.0%、75.0%,阳性符合率分别为64.7%、55.7%。结论 TS检测与TCT检测在宫颈癌筛查中具有相似的检测效果,值得临床推广和运用。

  17. Phosphorus Uptake and Utilisation Efficiencies of Different Wheat Cultivars Based on a Sand-Culture Screening System

    Institute of Scientific and Technical Information of China (English)


    A sand-based culture system using rock phosphate (P) was developed to simulate the situation in alkalinesoils, with respect to the dominant P form, and five wheat cultivars (Excalibur, Brookton, Krichauff, Westoniaand Sunco) were tested in this screening system to compare their P uptake and utilisation efficiencies. Resultsshowed that these cultivars differed significantly in their ability to acquire P from the sparingly available form(rock phosphate in this case). The accumulation of P by Brookton was three times that by Krichauff. Pconcentrations in plant tissues did not differ significantly, indicating that all cultivars were similar in Putilisation efficiency. A further experiment showed that the greater ability of a cultivar to take up P fromsparingly available form was related to the ability of a cultivar to acidify the rhizosphere. Seed P content wasa confounding factor in this system, and the use of relatively uniform seed with similar P content, preferablylow, was conducive to a successful outcome of the screening process.

  18. Cell based assays for anti-Plasmodium activity evaluation. (United States)

    Mokgethi-Morule, Thabang; N'Da, David D


    Malaria remains one of the most common and deadly infectious diseases worldwide. The severity of this global public health challenge is reflected by the approximately 198 million people, who were reportedly infected in 2013 and by the more than 584,000 related deaths in that same year. The rising emergence of drug resistance towards the once effective artemisinin combination therapies (ACTs) has become a serious concern and warrants more robust drug development strategies, with the objective of eradicating malaria infections. The intricate biology and life cycle of Plasmodium parasites complicate the understanding of the disease in such a way that would enhance the development of more effective chemotherapies that would achieve radical clinical cure and that would prevent disease relapse. Phenotypic cell based assays have for long been a valuable approach and involve the screening and analysis of diverse compounds with regards to their activities towards whole Plasmodium parasites in vitro. To achieve the Millennium Development Goal (MDG) of malaria eradication by 2020, new generation drugs that are active against all parasite stages (erythrocytic (blood), exo-erythrocytic (liver stages and gametocytes)) are needed. Significant advances are being made in assay development to overcome some of the practical challenges of assessing drug efficacy, particularly in the liver and transmission stage Plasmodium models. This review discusses primary screening models and the fundamental progress being made in whole cell based efficacy screens of anti-malarial activity. Ongoing challenges and some opportunities for improvements in assay development that would assist in the discovery of effective, safe and affordable drugs for malaria treatments are also discussed.

  19. A High-Throughput Screening System for Arabidopsis Transcription Factors and Its Application to Med25-Dependent Transcriptional Regulation

    Institute of Scientific and Technical Information of China (English)

    Bin Ou; Minami Matsui; Hong-Ya Gu; Li-Jia Qu; Kang-Quan Yin; Sai-Nan Liu; Yan Yang; Tren Gu; Jennifer Man Wing Hui; Li Zhang; Jin Miao; Youichi Kondou


    T The activities of transcription factors (TFs) require interactions with specific DNA sequences and other regulatory proteins. To detect such interactions in Arabidopsis, we developed a high-throughput screening system with a Gateway-compatible Gal4-AD-TF library of 1589 Arabidopsis TFs, which can be easily screened by mating-based yeast-one-hybrid (Y1H) and yeast-two-hybrid (Y2H) methods. The efficiency of the system was validated by examining two well-characterized TF-DNA and TF-protein interactions: the CHE-CCA1 promoter interaction by Y1H and NPR1-TGAs interactions by Y2H. We used this system to identify eight TFs that interact with a Mediator subunit, Med25, a key regulator in JA signaling. We identified five TFs that interacted with the GCC-box cis-element in the promoter of PDF1.2, a downstream gene of Med25. We found that three of these TFs, all from the AP2-EREBP family, interact directly both with Med25 and the GCC-box of PDF1.2, suggesting that Med25 regulates PDF1.2 expression through these three TFs.These results demonstrate that this high-throughput Y1H/Y2H screening system is an efficient tool for studying transcriptional regulation networks in Arabidopsis. This system will be available for other Arabidopsis researchers, and thus it provides a vital resource for the Arabidopsis community.

  20. Screening and expression of genes from metagenomes. (United States)

    Leis, Benedikt; Angelov, Angel; Liebl, Wolfgang


    Microorganisms are the most abundant and widely spread organisms on earth. They colonize a huge variety of natural and anthropogenic environments, including very specialized ecological niches and even extreme habitats, which are made possible by the immense metabolic diversity and genetic adaptability of microbes. As most of the organisms from environmental samples defy cultivation, cultivation-independent metagenomics approaches have been applied since more than one decade to access and characterize the phylogenetic diversity in microbial communities as well as their metabolic potential and ecological functions. Thereby, metagenomics has fully emerged as an own scientific field for mining new biocatalysts for many industrially relevant processes in biotechnology and pharmaceutics. This review summarizes common metagenomic approaches ranging from sampling, isolation of nucleic acids, construction of metagenomic libraries and their evaluation. Sequence-based screenings implement next-generation sequencing platforms, microarrays or PCR-based methods, while function-based analysis covers heterologous expression of metagenomic libraries in diverse screening setups. Major constraints and advantages of each strategy are described. The importance of alternative host-vector systems is discussed, and in order to underline the role of phylogenetic and physiological distance from the gene donor and the expression host employed, a case study is presented that describes the screening of a genomic library from an extreme thermophilic bacterium in both Escherichia coli and Thermus thermophilus. Metatranscriptomics, metaproteomics and single-cell-based methods are expected to complement metagenomic screening efforts to identify novel biocatalysts from environmental samples.

  1. New approaches to screening infrastructure investments in multi-reservoir systems- Evaluating proposed dams in Ethiopia and Kenya (United States)

    Harou, J. J.; Geressu, R. T.; Hurford, A. P.


    Two approaches have been used traditionally to screen infrastructure investments in multi-reservoir systems: scenario analysis of a few simulated designs and deterministic optimization, sometimes using hydro-economic models or screening optimization models. Simulation models realistically represent proposed water systems and can easily include multiple performance metrics; however each prospective system operating rules need to be formulated and simulated for each proposed design (time consuming. Optimization models have been used to overcome this burden. Screening optimization models use integer or non-linear programming and can be challenging to apply to large and/or multi-objective systems. Hydro-economic models that use deterministic (implicit stochastic) optimization must be modified to examine each different plan and they cannot always reproduce realistic or politically acceptable system operations. In this presentation we demonstrate the application of a new screening approach to multi-reservoir systems where operating rules and new assets (dams) are simultaneously optimized in a multi-criteria context. Results are not least cost investment plans that satisfy reliability or other engineering constraints, but rather Pareto-optimal sets of asset portfolios that work well under historical and/or future scenarios. This is achieved by using stakeholder-built simulation models linked to multi-criteria search algorithms (e.g. many objective evolutionary algorithms, MOEA). Typical output is demonstrated through two case-studies on the Tana and Blue Nile rivers where operating rules and reservoir assets are efficiently screened together considering stakeholder-defined metrics. The focus on the Tana system is how reservoir operating rules and new irrigation schemes should be co-managed to limit ecological damages. On the Nile system, we identify Blue Nile river reservoir capacities that least negatively impact downstream Nile nations. Limitations and new directions of

  2. Cell-Based Genotoxicity Testing (United States)

    Reifferscheid, Georg; Buchinger, Sebastian

    Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970s, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, e.g., due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). Deeper knowledge of the ­mutation events allows a mechanistic understanding of the induced DNA-damage by the utilization of base specific tester strains. Collections of such specific tester strains were extended by genetic engineering. Beside the reversion assays, test systems utilizing the bacterial SOS-response were invented. These methods are based on the fusion of various SOS-responsive promoters with a broad variety of reporter genes facilitating numerous methods of signal detection. A very important aspect of genotoxicity testing is the bioactivation of ­xenobiotics to DNA-damaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. Again, genetic engineering allows the construction of highly sophisticated bacterial tester strains with significantly enhanced sensitivity due to overexpression of enzymes that are involved in the metabolism of xenobiotics. This provides mechanistic insights into the toxification and detoxification pathways of xenobiotics and helps explaining the chemical nature of hazardous substances in unknown mixtures. In summary, beginning with "natural" tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective

  3. Simple and fast screening of G-quadruplex ligands with electrochemical detection system. (United States)

    Fan, Qiongxuan; Li, Chao; Tao, Yaqin; Mao, Xiaoxia; Li, Genxi


    Small molecules that may facilitate and stabilize the formation of G-quadruplexes can be used for cancer treatments, because the G-quadruplex structure can inhibit the activity of telomerase, an enzyme over-expressed in many cancer cells. Therefore, there is considerable interest in developing a simple and high-performance method for screening small molecules binding to G-quadruplex. Here, we have designed a simple electrochemical approach to screen such ligands based on the fact that the formation and stabilization of G-quadruplex by ligand may inhibit electron transfer of redox species to electrode surface. As a proof-of-concept study, two types of classical G-quadruplex ligands, TMPyP4 and BRACO-19, are studied in this work, which demonstrates that this method is fast and robust and it may be applied to screen G-quadruplex ligands for anticancer drugs testing and design in the future.

  4. [Comparative radiography of the respiratory tract of snakes using conventional high-resolution film-screen-system and a digital detector system]. (United States)

    Pees, Michael; Bochmann, Monika; Krautwald-Junghanns, Maria-Elisabeth; Schmidt, Volker; Ludewig, Eberhard


    A conventional high-resolution screen-film-system (film Kodak MIN-R S, screen Kodak MIN-R 2000) was compared to a digital detector system (Varian PaxScan 4030E) for the evaluation of the respiratory tract in snakes. Digital radiographs were taken with the same dose as well as with half the dose used for the conventional radiographs. A total of 20 Burmese pythons (Python molurus) were examined in dorsoventral and lateral projection. Four criteria (three features, one overall assessment) were defined for each of the anatomical structures lung, trachea and spinal column and assessed by five veterinarians in a semi-blinded study using a score system. Comparison of the ratings between the techniques used was done using a visual grading analysis. For the lung, two of the three features as well as the overall assessment were rated significantly superior using the digital system. The trachea was rated significantly superior using the conventional system for the overall assessment as well as for one feature. For the spinal column, the overall assessment was significantly superior using the digital system with the full dose. Conventional radiography as well as digital radiography using half the dose was rated significantly inferior for one feature each. The of the relatively low-contrast respiratory tract. A limiting factor is the demonstration of particularly small structures. Generally, a dose reduction (compared to a conventional high-resolution film-screen-system) is possible for the evaluation of the respiratory system.

  5. Emulsion culture: a miniaturized library screening system based on micro-droplets in an emulsified medium. (United States)

    Kojima, Takaaki; Nagao, Nobuhito; Ando, Daisuke; Ojima, Teruyo; Kawarasaki, Yasuaki; Kobayashi, Isao; Nakajima, Mitsutoshi; Nakano, Hideo


    A typical library screen in directed evolution primarily requires physical separation of the clones on agar plates followed by detection of clones with improved properties; using this method only limited numbers of clones relative to the number of potential variations can be assessed. In particular, screening for a secretory enzyme is difficult to perform at high clone density, because of diffusion of the signal or unfavorable utilization of the reaction product by neighboring clones. In this study, we have developed a novel method of enrichment culture: "Emulsion Culture", i.e., segregated replication of clones in an emulsified culture medium. Clones expressing enzyme-variants are separately distributed to small (up to 50 μm in diameter), segregated compartments composed of a droplet of medium to form several tens of millions of microcolonies in a milliliter of medium, which allows a miniaturized, in-bulk screening of clones. We applied this culture method to yeast clones expressing secretory beta-galactosidase to analyze the enrichment factor achieved. A high-density screen for a signal peptide sequence that maximizes extracellular production of the enzyme was also performed to demonstrate the practicability of this culture method. In addition, micro-channel emulsification was tested as a method of forming uniformly-sized compartments in the emulsion.

  6. Levels of Evidence: Universal Newborn Hearing Screening (UNHS) and Early Hearing Detection and Intervention Systems (EHDI) (United States)

    Yoshinaga-Itano, Christine


    Levels of evidence differ according to the audience addressed. Implementation of universal newborn hearing screening requires responses to a complex myriad of diverse groups: the general public, families with children who are deaf or hard of hearing, the deaf and hard of hearing communities, hospital administrators, physicians (pediatricians,…

  7. Evaluation of clinical features scoring system as screening tool for influenza A (H1N1 in epidemic situations

    Directory of Open Access Journals (Sweden)

    P Ranjan


    Full Text Available Background: Influenza A (H1N1 hit the headlines in recent times and created mass hysteria and general panic. The high cost and non-availability of diagnostic laboratory tests for swine flu, especially in the developing countries underlines the need of having a cheaper, easily available, yet reasonably accurate screening test. Aims: This study was carried out to develop a clinical feature-based scoring system (CFSS for influenza A (H1N1 and to evaluate its suitability as a screening tool when large numbers of influenza-like illness cases are suspect. Settings and Design: Clinical-record based study, carried out retrospectively in post-pandemic period on subject′s case-sheets who had been quarantined at IG International Airport′s quarantine center at Delhi. Materials and Methods: Clinical scoring of each suspected case was done by studying their case record sheet and compared with the results of RT-PCR. RT-PCR was used to confirm the diagnosis (Gold Standard. Statistical Analysis: We calculated sensitivity, specificity, positive and negative predictive values of the clinical feature-based scoring system (the proposed new screening tool at different cut-off values. The most discriminant cut-off value was determined by plotting the ROC curve. Results: Of the 638 suspected cases, 127 (20% were confirmed to have H1N1 by RT-PCR examination. On the basis of ROC, the most discriminant clinical feature score for diagnosing Influenza A was found to be 7, which yielded sensitivity, specificity, positive, and negative predictive values of 86%, 88%, 64%, and 96%, respectively. Conclusion: The clinical features scoring system (CFSS can be used as a valid and cost-effective tool for screening swine flu (influenza A (H1N1 cases from large number of influenza-like illness suspects.

  8. Comparison of the image quality of a high-resolution screen-film system and a digital flat panel detector system in avian radiography. (United States)

    Bochmann, Monika; Ludewig, Eberhard; Krautwald-Junghanns, Maria-Elisabeth; Pees, Michael


    A conventional high-resolution screen-film system was compared with a digital detector system. A total of 20 birds (14 pigeons and six psittacine birds) with an average body mass of 533g were examined in dorsoventral as well as lateral projections. Digital radiographs were acquired with the same mAs as well as half the mAs used for the conventional radiographs. Three criteria and one overall assessment were defined for each of four anatomic regions and assessed by five veterinarians using a score system. Comparison of the ratings was done by visual grading analysis. For the majority of criteria, there was no significant difference regarding image quality between the digital and screen-film projections. However, for certain criteria the quality of the digital images was significantly superior. Using the same mAs as for the conventional radiographs, the humeral joint surfaces and the honeycomb structure of the lung were assessed as superior with the digital imaging system. The tracheal rings and the delineation of the trachea from the surrounding tissue were also superior with the digital system. Assessment of the trabecular structure of the humerus was superior when the full mAs was used compared with the reduced mAs. In conclusion the digital technique is equal or superior to the conventional screen-film high-resolution system for pet birds of a medium size. With some limitations, a dose reduction is possible with the digital system.

  9. The health system and population health implications of large-scale diabetes screening in India: a microsimulation model of alternative approaches.

    Directory of Open Access Journals (Sweden)

    Sanjay Basu


    Full Text Available Like a growing number of rapidly developing countries, India has begun to develop a system for large-scale community-based screening for diabetes. We sought to identify the implications of using alternative screening instruments to detect people with undiagnosed type 2 diabetes among diverse populations across India.We developed and validated a microsimulation model that incorporated data from 58 studies from across the country into a nationally representative sample of Indians aged 25-65 y old. We estimated the diagnostic and health system implications of three major survey-based screening instruments and random glucometer-based screening. Of the 567 million Indians eligible for screening, depending on which of four screening approaches is utilized, between 158 and 306 million would be expected to screen as "high risk" for type 2 diabetes, and be referred for confirmatory testing. Between 26 million and 37 million of these people would be expected to meet international diagnostic criteria for diabetes, but between 126 million and 273 million would be "false positives." The ratio of false positives to true positives varied from 3.9 (when using random glucose screening to 8.2 (when using a survey-based screening instrument in our model. The cost per case found would be expected to be from US$5.28 (when using random glucose screening to US$17.06 (when using a survey-based screening instrument, presenting a total cost of between US$169 and US$567 million. The major limitation of our analysis is its dependence on published cohort studies that are unlikely fully to capture the poorest and most rural areas of the country. Because these areas are thought to have the lowest diabetes prevalence, this may result in overestimation of the efficacy and health benefits of screening.Large-scale community-based screening is anticipated to produce a large number of false-positive results, particularly if using currently available survey-based screening

  10. Disposable amperometric biosensors based on xanthine oxidase immobilized in the Prussian blue modified screen-printed three-electrode system

    Institute of Scientific and Technical Information of China (English)


    The screen-printed three-electrode system was applied to fabricate a new type of disposable amperometric xanthine oxidase biosensor.Carbon-working,carbon-counter and Ag/AgCl reference electrodes were all manually printed on the polyethylene terephthalate substrate forming the screen-printed three-electrode system by the conventional screen-printing process.As a mediator,Prussian blue could not only catalyze the electrochemical reduction of hydrogen peroxide produced from the enzyme reaction,but also keep the favorable potential around 0 V.The optimum operational conditions,including pH,potential and temperature,were investigated.The sensitivities of xanthine and hypoxanthine detections were 13.83 mA/M and 25.56 mA/M,respectively.A linear relationship was obtained in the concentration range between 0.10μM and 4.98μM for xanthine and between 0.50μM and 3.98μM for hypoxanthine.The small Michaelis-menten constant value of the xanthine oxidase biosensor was calculated to be 3.90 μM.The results indicate that the fabricated xanthine oxidase biosensor is effective and sensitive for the detection of xanthine and hypoxanthine.

  11. Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells. (United States)

    Tabata, Yoshikuni; Murai, Norio; Sasaki, Takeo; Taniguchi, Sachie; Suzuki, Shuichi; Yamazaki, Kazuto; Ito, Masashi


    Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology.

  12. Cell-Based Therapies for Diabetic Complications (United States)

    Bernardi, Stella; Severini, Giovanni Maria; Zauli, Giorgio; Secchiero, Paola


    In recent years, accumulating experimental evidence supports the notion that diabetic patients may greatly benefit from cell-based therapies, which include the use of adult stem and/or progenitor cells. In particular, mesenchymal stem cells and the circulating pool of endothelial progenitor cells have so far been the most studied populations of cells proposed for the treatment of vascular complications affecting diabetic patients. We review the evidence supporting their use in this setting, the therapeutic benefits that these cells have shown so far as well as the challenges that cell-based therapies in diabetic complications put out. PMID:21822425

  13. Cell-Based Therapies for Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Stella Bernardi


    Full Text Available In recent years, accumulating experimental evidence supports the notion that diabetic patients may greatly benefit from cell-based therapies, which include the use of adult stem and/or progenitor cells. In particular, mesenchymal stem cells and the circulating pool of endothelial progenitor cells have so far been the most studied populations of cells proposed for the treatment of vascular complications affecting diabetic patients. We review the evidence supporting their use in this setting, the therapeutic benefits that these cells have shown so far as well as the challenges that cell-based therapies in diabetic complications put out.

  14. Identification of Small Molecule Modulators of MicroRNA by Library Screening. (United States)

    Xiao, Zhangang; Chen, Yangchao


    MicroRNAs (miRNAs) function as oncogenes or tumor suppressors and are dysregulated in cancer. miRNAs therefore represent promising therapeutic targets for cancer. Small molecules that could modulate the expression of miRNAs would thus have potential as anticancer agents. Library screening of small molecules targeting miRNAs is a useful technology platform for anticancer drug development. Here, we describe a hepatocellular carcinoma (HCC) cell-based luciferase reporter system which could be used to screen for small molecule modulators of tumor suppressor microRNA-34a.

  15. Screening of proteins that interact with human thrombopoietin receptor c-Mpl using yeast two-hybrid system

    Institute of Scientific and Technical Information of China (English)


    Thrombopoietin(TPO) is the major cytokine involved in platelet production and exerts its effects via the receptor c-Mpl.The yeast two-hybrid system has been used to screen the proteins interacting with c-Mpl.First,the cDNA fragment of c-Mpl intracellular domain was cloned into two-hybrid vector pAS2,and the resulting plasmid is designated as pASMM.Then a human placenta cDNA library was screened using the pASMM as a target plasmid.Seven positive clones were isolated from 150 000 independent transformants.Sequence analysis of one of the positive clones demonstrates that a part of coding sequence of vimentin from 611 bp to 3'end and flanking non-translation region was obtained.Therefore,there is an interaction between vimentin and TPO receptor.The results suggest that cytoskeletal protein may play an important role in TPO signal transduction pathway.

  16. Screening of proteins that interact with human thrombopoietin receptor c-Mpl using yeast two-hybrid system

    Institute of Scientific and Technical Information of China (English)

    赵新燕[1; 冯丽冰[2; 周伟国[3; 戴卫列[4; 李昌本[5; 赵寿元[6


    Thrombopoietin (TPO) is the major cytokine involved in platelet production and exerts its effects via the receptor c-Mpl. The yeast two-hybrid system has been used to screen the proteins interacting with c-Mpl. First, the cDNA fragment of c-Mpl intracellular domain was cloned into two-hybrid vector pAS2, and the resulting plasmid is designated as pASMM. Then a human placenta cDNA library was screened using the pASMM as a target plasmid. Seven positive clones were isolated from 150 000 independent transformants. Sequence analysis of one of the positive clones demonstrates that a part of coding sequence of vimentin from 611 bp to 3’ end and flanking non-translation region was obtained. Therefore, there is an interaction between vimentin and TPO receptor. The results suggest that cytoskeletal protein may play an important role in TPO signal transduction pathway.

  17. Statistical processes limiting the noise of a screen-film system: II (United States)

    Beutel, Jacob; Shaw, Rodney; Yampolsky, Michael


    In a recent publication we demonstrated that the increase in image noise which results from exposing a film via a phosphor screen can be attributed entirely to the increased extent of the autocorrelation interval introduced by the screen, and not to any change in the shape or scale of the probability distribution function which governs the fluctuations about the mean level. This result implies that the (0,0)-value of the autocovariance function is independent of the degree of so-called quantum mottle and since the autocovariance function, ACV(x,y), and the Wiener Spectrum, WS(u,v), are Fourier transform pairs, it follows that the integral of the Wiener Spectrum over all spatial frequencies (u,v) must share this independence. Since this result was counterintuitive to existing assumptions of the role of screen and film in defining the Wiener Spectrum (i.e., a simple additive combination of quantum mottle and film grain), we now investigate this relationship in more detail in order to provide a more complete insight. For this purpose we have simulated a set of controlled images which correspond to a wide range of screen correlation intervals, from 192 micrometers down to uncorrelated film noise. Included in this simulation we have also explored the role of the overall amplification factor, i.e., the average number of image grains associated with an x-ray quantum. The results of these simulations are presented here, and confirm our previous findings, by establishing the invariance of the scale (0,0) value of the ACV.

  18. Evaluations of cirrus contamination and screening in ground aerosol observations using collocated lidar systems (United States)

    Huang, Jingfeng; Hsu, N. Christina; Tsay, Si-Chee; Holben, Brent N.; Welton, Ellsworth J.; Smirnov, Alexander; Jeong, Myeong-Jae; Hansell, Richard A.; Berkoff, Timothy A.; Liu, Zhaoyan; Liu, Gin-Rong; Campbell, James R.; Liew, Soo Chin; Barnes, John E.


    Cirrus clouds, particularly subvisual high thin cirrus with low optical thickness, are difficult to screen in operational aerosol retrieval algorithms. Collocated aerosol and cirrus observations from ground measurements, such as the Aerosol Robotic Network (AERONET) and the Micro-Pulse Lidar Network (MPLNET), provide us with an unprecedented opportunity to systematically examine the susceptibility of operational aerosol products to cirrus contamination. Quality assured aerosol optical thickness (AOT) measurements were also tested against the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical feature mask (VFM) and the Moderate Resolution Imaging Spectroradiometer (MODIS) thin cirrus screening parameters for the purpose of evaluating cirrus contamination. Key results of this study include: (1) quantitative evaluations of data uncertainties in AERONET AOT retrievals are conducted; although AERONET cirrus screening schemes are successful in removing most cirrus contamination, strong residuals displaying strong spatial and seasonal variability still exist, particularly over thin cirrus prevalent regions during cirrus peak seasons; (2) challenges in matching up different data for analysis are highlighted and corresponding solutions proposed; and (3) estimates of the relative contributions from cirrus contamination to aerosol retrievals are discussed. The results are valuable for better understanding and further improving ground aerosol measurements that are critical for aerosol-related climate research.

  19. Screening Analysis : Volume 2, Impact Results (Columbia River System Operation Review).

    Energy Technology Data Exchange (ETDEWEB)


    Detailed results from all of the work groups are presented in this chapter. Ninety alternatives were analyzed during the screening process. Three of the alternative represent various base cases and are used for comparison purposes. The other 87 alternatives represent a wide variety of operational possibilities ranging from current operations to emphasizing a single river use to compromise operations that attempt to accommodate the multiple uses. Every possible alternative suggested during the screening phase was considered. Each alternative was given an abbreviated name, a number and assigned by ROSE to either the Corps (C) or BPA (B) for hydroregulation modeling. A list of the alternatives with its number and hydroregulation assignment is given below. The results in this chapter are presented in numerical order. The first 3 letters in the name identify which work group suggested the alternative. The format for the results includes a brief description of each alternative, a tabulation of the screening calculations organized by work group, and observations/comments on the alternative by the work groups. The description summarizes the key operational requirements for the alternative and was taken directly from the instructions given to the hydroregulation modelers.

  20. Formalize clinical processes into electronic health information systems: Modelling a screening service for diabetic retinopathy. (United States)

    Eguzkiza, Aitor; Trigo, Jesús Daniel; Martínez-Espronceda, Miguel; Serrano, Luis; Andonegui, José


    Most healthcare services use information and communication technologies to reduce and redistribute the workload associated with follow-up of chronic conditions. However, the lack of normalization of the information handled in and exchanged between such services hinders the scalability and extendibility. The use of medical standards for modelling and exchanging information, especially dual-model based approaches, can enhance the features of screening services. Hence, the approach of this paper is twofold. First, this article presents a generic methodology to model patient-centered clinical processes. Second, a proof of concept of the proposed methodology was conducted within the diabetic retinopathy (DR) screening service of the Health Service of Navarre (Spain) in compliance with a specific dual-model norm (openEHR). As a result, a set of elements required for deploying a model-driven DR screening service has been established, namely: clinical concepts, archetypes, termsets, templates, guideline definition rules, and user interface definitions. This model fosters reusability, because those elements are available to be downloaded and integrated in any healthcare service, and interoperability, since from then on such services can share information seamlessly.

  1. Screening for colorectal cancer. (United States)

    He, Jin; Efron, Jonathan E


    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.

  2. Drug activity screening based on microsomes-hydrogel system in predicting metabolism induced antitumor effect of oroxylin A. (United States)

    Yang, Huiying; Li, Jianfeng; Zheng, Yuanting; Zhou, Lu; Tong, Shanshan; Zhao, Bei; Cai, Weimin


    A novel microsomes-hydrogel added cell culture system (MHCCS) was employed in the antitumor activity screening of natural compounds, aiming to achieve drug screening with better in vivo correlation, higher initiative to explore the potential active metabolites, and investigation of the antitumor mechanism from the perspective of metabolism. MTT assay and cell apoptosis detection showed that test drug oroxylin A (OA) had enhanced cytotoxicity and wogonin (W) with reduced cytotoxicity on MCF-7 cell line upon MHCCS incubation. In vivo antitumor evaluations also demonstrated that OA induced higher tumor inhibition than W at the same dosage. To explore the reasons, nine major metabolites of OA were separated and collected through UPLC-Q-TOF and semi-preparative HPLC. Metabolites M318 exhibited higher cytotoxicity than OA and other metabolites by MTT assay. (1)H NMR spectrums, HPLC and TOF MS/MS results revealed that OA was catalyzed into its active metabolite M318 via a ring-opening reaction. M318 induced significant cell apoptosis and S-phase arrest through affecting tumor survival related genes after mechanism study. In conclusion, our MHCCS could be a useful tool for drug activity screening from a perspective of metabolism.

  3. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer. (United States)

    Rad, Roland; Rad, Lena; Wang, Wei; Strong, Alexander; Ponstingl, Hannes; Bronner, Iraad F; Mayho, Matthew; Steiger, Katja; Weber, Julia; Hieber, Maren; Veltkamp, Christian; Eser, Stefan; Geumann, Ulf; Öllinger, Rupert; Zukowska, Magdalena; Barenboim, Maxim; Maresch, Roman; Cadiñanos, Juan; Friedrich, Mathias; Varela, Ignacio; Constantino-Casas, Fernando; Sarver, Aaron; Ten Hoeve, Jelle; Prosser, Haydn; Seidler, Barbara; Bauer, Judith; Heikenwälder, Mathias; Metzakopian, Emmanouil; Krug, Anne; Ehmer, Ursula; Schneider, Günter; Knösel, Thomas; Rümmele, Petra; Aust, Daniela; Grützmann, Robert; Pilarsky, Christian; Ning, Zemin; Wessels, Lodewyk; Schmid, Roland M; Quail, Michael A; Vassiliou, George; Esposito, Irene; Liu, Pentao; Saur, Dieter; Bradley, Allan


    Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse model and correlates with lymph node metastasis in human patients with pancreatic cancer. The propensity of piggyBac for open chromatin also enabled genome-wide screening for cancer-relevant noncoding DNA, which pinpointed a Cdkn2a cis-regulatory region. Histologically, we observed different tumor subentities and discovered associated genetic events, including Fign insertions in hepatoid pancreatic cancer. Our studies demonstrate the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis, such as downstream targets of commonly mutated human cancer genes. These piggyBac resources are universally applicable in any tissue context and provide unique experimental access to the genetic complexity of cancer.

  4. Characterization of film-converter screens systems for neutron radiography; Caracterizacao de sistemas filme-conversor para radiografia com neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Marcos Leandro Garcia


    In general a good quality radiography is that one able to furnish high contrast and sharp edge images. Technically 'high contrast' means high capability to discern material thickness and 'sharp edges', high resolution power. In the present work the optimal conditions to obtain neutron radiography images by using the following film-converter screen systems, Kodak-AA/Gd vaporated; Kodak-AA/Gd metallic; Kodak-AA/LiF; Min-R/GdS{sub 2}O{sub 4}, have been determined. The irradiations were performed in a radiographic facility which was designed and constructed by the neutron radiography working group and is installed at the beamhole 08 of the IEA-R1 nuclear research reactor of the IPEN-CNEN/SP. In order to determine such conditions, the start point was to evaluate the neutron exposure interval for which the optical contrast is maximal and so quantify the sensitivity or capability to discern material thickness, as well as the spatial resolution achieved in the radiographic image, for these systems. The best results have been obtained for the Kodak-AA/Gd vaporated system which is able to discern, for example, 0,024 cm of lucite, with a maximal resolution of 22{mu}m. The radiography images presently obtained in IPEN-CNEN/SP have similar quality when compared to the ones from several other research centers, around the world, whose making use of the same film-converter screens systems. (author)

  5. Evaluating factors influencing screening for pulmonary hypertension in systemic sclerosis: does disparity between available guidelines influence clinical practice? (United States)

    Pauling, John D; McHugh, Neil J


    Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in systemic sclerosis (SSc). We audited adherence with available recommendations regarding cardiopulmonary screening for PAH in SSc and explored potential factors influencing clinical practice. A retrospective case note review of 108 patients with SSc who had attended outpatient clinic over the previous year was undertaken. Records were scrutinised for evidence of previous assessment with trans-thoracic echocardiography (TTE) and pulmonary function tests (PFT), along with information regarding clinical phenotype and serological subset. The proportion of patients for whom screening had been undertaken within the previous 12 months was low, with significantly fewer having TTE compared with PFT assessment (34.7% vs. 53.1%, p = 0.014). The majority of patients had undergone TTE and PFT assessment within the previous 2 years, but a lower proportion had undergone TTE compared with PFT (69.4% vs. 82.7%, p = 0.044). There were strong trends for more frequent PFT assessment in younger patients, limited cutaneous SSc and worse previous PFT results. In contrast, the frequency of TTE assessment was not associated with previous investigation results or disease subtype. Serological profile did not influence the frequency of either TTE or PFT assessments. Disparity between available published guidelines may influence both the frequency and preference of PAH screening in SSc in clinical practice. The higher frequency of PFT assessment might reflect a perceived superiority amongst clinicians of PFT over TTE in the early identification of SSc-PAH. SSc-specific guidelines, possibly incorporating additional independent risk factors, may improve the cost-effectiveness and clinical efficacy of screening recommendations designed to ensure the early identification of PAH in patients with SSc.

  6. Screening of Potential HIV-1 Inhibitors/Replication Blockers Using Secure Lentiviral in Vitro System. (United States)

    Prokofjeva, M M; Spirin, P V; Yanvarev, D V; Ivanov, A V; Novikov, M S; Stepanov, O A; Gottikh, M B; Kochetkov, S N; Fehse, B; Stocking, C; Prassolov, V S


    The development and usage of safe cell systems for testing agents which possess anti-HIV activity is a very important factor in the design of new drugs. We have described in detail a system we designed that is based on lentiviral vectors (Prokofjeva et. al.,Antiviral Therapy,in print) for swift and completely safe screening of potential HIV-1 replication inhibitors. The system enables one to test the efficiency of the inhibitory activity of compounds whose action is directed towards either wild-type HIV-1 reverse transcriptase or integrase, or mutant enzymes corresponding to the drug-resistant virus form. Testing results of a number of already known drugs, which correlate well with published data as well as data on newly synthesized compounds, were obtained. Application of this system substantially broadens the possibilities of preclinical anti-HIV drugs testing.

  7. Predicting Behavior Assessment System for Children-Second Edition Self-Report of Personality Child Form Results Using the Behavioral and Emotional Screening System Student Form: A Replication Study with an Urban, Predominantly Latino/a Sample (United States)

    Kiperman, Sarah; Black, Mary S.; McGill, Tia M.; Harrell-Williams, Leigh M.; Kamphaus, Randy W.


    This study assesses the ability of a brief screening form, the Behavioral and Emotional Screening System-Student Form (BESS-SF), to predict scores on the much longer form from which it was derived: the Behavior Assessment System for Children-Second Edition Self-Report of Personality-Child Form (BASC-2-SRP-C). The present study replicates a former…

  8. Modified inverse square sensitometry for the determination of the characteristic curve of radiographic screen/film systems.

    Directory of Open Access Journals (Sweden)



    Full Text Available To determine the characteristic curve of the radiographic screen/film systems in a short focal spot-film distance, the inverse square sensitometric method was modified by changing the radiation intensity with two kinds of filters. The characteristic curves obtained in the two exposure series with these two kinds of filters were overlapped to obtain a complete one. The characteristic curve thus obtained was almost the same as the one obtained by the original inverse square sensitometric method. The accuracy of the characteristic curves obtained by the modified method was well-reflected in the clinical radiographs.

  9. Debye screening (United States)

    Brydges, David C.; Federbush, Paul


    The existence and exponential clustering of correlation functions for a classical coulomb system at low density or high temperature are proven using methods from constructive quantum field theory, the sine gordon transformation and the Glimm, Jaffe, Spencer expansion about mean field theory. This is a vindication of a belief of long standing among physicists, known as Debye screening. That is, because of special properties of the coulomb potential, the configurations of significant probability are those in which the long range parts of r -1 are mostly cancelled, leaving an effective exponentially decaying potential acting between charge clouds. This paper generalizes a previous paper of one of the authors in which these results were obtained for a special lattice system. The present treatment covers the continuous mechanics situation, with essentially arbitrary short range forces and charge species. Charge symmetry is not assumed.

  10. Efficacy of Allium cepa test system for screening cytotoxicity and genotoxicity of industrial effluents originated from different industrial activities. (United States)

    Pathiratne, Asoka; Hemachandra, Chamini K; De Silva, Nimal


    Efficacy of Allium cepa test system for screening cytotoxicity and genotoxicity of treated effluents originated from four types of industrial activities (two textile industries, three rubber based industries, two common treatment plants of industrial zones, and two water treatment plants) was assessed. Physico-chemical parameters including the heavy metal/metalloid levels of the effluents varied depending on the industry profile, but most of the measured parameters in the effluents were within the specified tolerance limits of Sri Lankan environmental regulations for discharge of industrial effluents into inland surface waters. In the A. cepa test system, the undiluted effluents induced statistically significant root growth retardation, mitosis depression, and chromosomal aberrations in root meristematic cells in most cases in comparison to the dilution water and upstream water signifying effluent induced cytotoxicity and genotoxicity. Ethyl methane sulphonate (a mutagen, positive control) and all the effluents under 1:8 dilution significantly induced total chromosomal aberrations in root meristematic cells in comparison to the dilution water and upstream water indicating inadequacy of expected 1:8 dilutions in the receiving waters for curtailing genotoxic impacts. The results support the use of a practically feasible A. cepa test system for rapid screening of cytotoxicity and genotoxicity of diverse industrial effluents discharging into inland surface waters.

  11. Effectiveness of diagnostic screening tests in mass screening for COPD using a cooperative regional system in a region with heavy air pollution: a cross-sectional study (United States)

    Kotaki, Kenji; Ikeda, Hisao; Fukuda, Takeshi; Yuki, Fumiko; Hasuo, Kanehiro; Kawano, Yuhei; Kawasaki, Masayuki


    Objectives This study aimed to evaluate the effectiveness of a cooperative healthcare model for early detection and diagnosis of chronic obstructive pulmonary disease (COPD). Methods This was a cross-sectional observational study. We performed diagnosis of COPD at 4 public health centres in Ōmuta, Japan from March 2015 to March 2016, by adding screening for COPD at the time of routine medical evaluations. All patients aged over 40 years were eligible to participate. Among 397 eligible patients, 293 agreed to participate in the study. Results The estimated prevalence of COPD in Ōmuta was 10% among patients aged over 40 years and was 17% among smokers. Among those who were screened, over half of them had questionnaire scores over the cut-off of 17 points and decreased FEV1/FVC%, indicating COPD (p>0.05). 30 patients with suspected COPD were referred for further investigation at a local central hospital, but only 6 underwent further medical examinations. Conclusions The combination of a COPD questionnaire and medical examination is effective as a COPD screening tool. Future research should investigate behavioural interventions for smoking cessation that can be offered in a cooperative model, as well as for improving participation in COPD screening and for encouraging early presentation for treatment in those suspected of having COPD. PMID:28082365

  12. A simple technique for reducing edge effect in cell-based assays. (United States)

    Lundholt, Betina Kerstin; Scudder, Kurt M; Pagliaro, Len


    Several factors are known to increase the noise and variability of cell-based assays used for high-throughput screening. In particular, edge effects can result in an unacceptably high plate rejection rate in screening runs. In an effort to minimize these variations, the authors analyzed a number of factors that could contribute to edge effects in cell-based assays. They found that pre-incubation of newly seeded plates in ambient conditions (air at room temperature) resulted in even distribution of the cells in each well. In contrast, when newly seeded plates were placed directly in the CO(2) incubator, an uneven distribution of cells occurred in wells around the plate periphery, resulting in increased edge effect. Here, the authors show that the simple, inexpensive approach of incubating newly seeded plates at room temperature before placing them in a 37 degrees C CO(2) incubator yields a significant reduction in edge effect.

  13. Cell-based detection of microbial biomaterial contaminations. (United States)

    Roch, Toralf; Ma, Nan; Kratz, Karl; Lendlein, Andreas


    A major challenge in biomaterial synthesis and functionalization is the prevention of microbial contaminations such as endotoxins (lipopolysaccharides (LPS)). In addition to LPS, which are exclusively expressed by Gram negative bacteria, also other microbial products derived from fungi or Gram positive bacteria can be found as contaminations in research laboratories. Typically, the Limulus amebocyte lysate (LAL)-test is used to determine the endotoxin levels of medical devices. However, this test fails to detect material-bound LPS and other microbial contaminations and, as demonstrated in this study, detects LPS from various bacterial species with different sensitivities.In this work, a cell-based assay using genetically engineered RAW macrophages, which detect not only soluble but also material-bound microbial contaminations is introduced.The sensitivity of this cell-line towards different LPS species and different heat-inactivated microbes was investigated. As proof of principle a soft hydrophobic poly(n-butyl acrylate) network (cPnBA), which may due to adhesive properties strongly bind microbes, was deliberately contaminated with heat-inactivated bacteria. While the LAL-test failed to detect the microbial contamination, the cell-based assay clearly detected material-bound microbial contaminations. Our data demonstrate that a cell-based detection system should routinely be used as supplement to the LAL-test to determine microbial contaminations of biomaterials.

  14. Depression Screening (United States)

    ... Centers Diseases + Condition Centers Mental Health Medical Library 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 ...

  15. Droplet Microfluidic System with On-Demand Trapping and Releasing of Droplet for Drug Screening Applications. (United States)

    Courtney, Matthew; Chen, Xiaoming; Chan, Sarah; Mohamed, Tarek; Rao, Praveen P N; Ren, Carolyn L


    96-Well plate has been the traditional method used for screening drug compounds libraries for potential bioactivity. Although this method has been proven successful in testing dose-response analysis, the microliter consumption of expensive reagents and hours of reaction and analysis time call for innovative methods for improvements. This work demonstrates a droplet microfluidic platform that has the potential to significantly reduce the reagent consumption and shorten the reaction and analysis time by utilizing nanoliter-sized droplets as a replacement of wells. This platform is evaluated by applying it to screen drug compounds that inhibit the tau-peptide aggregation, a phenomena related to Alzheimer's disease. In this platform, sample reagents are first dispersed into nanolitre-sized droplets by an immiscible carrier oil and then these droplets are trapped on-demand in the downstream of the microfluidic device. The relative decrease in fluorescence through drug inhibition is characterized using an inverted epifluorescence microscope. Finally, the trapped droplets are released on-demand after each test by manipulating the applied pressures to the channel network which allows continuous processing. The testing results agree well with that obtained from 96-well plates with much lower sample consumption (∼200 times lower than 96-well plate) and reduced reaction time due to increased surface volume ratio (2.5 min vs 2 h).

  16. Optical oxygen sensing systems for drug discovery applications: Respirometric Screening Technology (RST) (United States)

    Papkovsky, Dmitri B.; Hynes, James; Fernandes, Richard


    Quenched-fluorescence oxygen sensing allows non-chemical, reversible, real-time monitoring of molecular oxygen and rates of oxygen consumption in biological samples. Using this approach we have developed Respirometric Screening Technology (RST); a platform which facilitates the convenient analysis of cellular oxygen uptake. This in turn allows the investigation of compounds and processes which affect respiratory activity. The RST platform employs soluble phosphorescent oxygen-sensitive probes, which may be assessed in standard microtitter plates on a fluorescence plate reader. New formats of RST assays and time-resolved fluorescence detection instrumentation developed by Luxcel provide improvements in assay sensitivity, miniaturization and overall performance. RST has a diverse range of applications in drug discovery area including high throughput analysis of mitochondrial function; studies of mechanisms of toxicity and apoptosis; cell and animal based screening of compound libraries and environmental samples; and, sterility testing. RST has been successfully validated with a range of practical targets and adopted by several leading pharmaceutical companies.

  17. Long Term Implementation of a 100 Percent Checked Baggage Screening System: A Value Focused Thinking Approach (United States)


    baggage checking system. The checked baggage system in place at Dayton International Airport is an interim solution. EDS and explosive trace detection machines...system will include detection equipment such as Explosive Trace Detection (ETD) systems, EDS machines, conveyor systems, and operators necessary to run...4.1.1 Terminal Floor System – Interim as of 31 December 2002 This interim system consists of the placement of EDS and Explosive Trace Detection machines

  18. An hourly based performance comparison of an integrated micro-structural perforated shading screen with standard shading systems

    DEFF Research Database (Denmark)

    Appelfeld, David; McNeil, Andrew; Svendsen, Svend


    gains and heat transfer through the transparent parts of the fenestration systems. MSPSS is angular-dependent shading device that provides an effective strategy in the control of daylight, solar gains and overheating through windows. The study focuses on using direct experimental methods to determine bi......This article evaluates the performance of an integrated micro structural perforated shading screen (MSPSS). Such a system maintains a visual connection with the outdoors while imitating the shading functionality of a venetian blind. Building energy consumption is strongly influenced by the solar....... The bi-directional description of the systems was used throughout the article. The simulations were validated against outdoor measurements of solar and light transmittance....

  19. Cancer Screening

    Directory of Open Access Journals (Sweden)

    Krishna Prasad


    Full Text Available Cancer screening is a means to detect cancer early with the goal of decreasing morbidity and mortality. At present, there is a reasonable consensus regarding screening for breast, cervical and colorectal cances and the role of screening is under trial in case of cancers of the lung,  ovaries and prostate. On the other hand, good screening tests are not available for some of the commonest cancers in India like the oral, pharyngeal, esophageal and stomach cancers.

  20. Establishment of health clinics as mass screening and referral systems for chronic non-communicable diseases in primary health care

    Directory of Open Access Journals (Sweden)

    Kamal Heidari


    Full Text Available Background: This study aimed to establish a comprehensive screening and referral system for chronic non-communicable diseases (CNCD in the routine primary health care, and to determine the prevalence of diabetes, pre-diabetes, metabolic syndrome, and dyslipidemia in adult population invited by public announcement to the Health clinics in Isfahan, Iran. Methods: This survey was conducted from March 2010, and the current paper presents data obtained until November 2011. To provide health services for prevention and control of CNCDs, with priority of type2 diabetes mellitus, Health clinics were established in different parts of Isfahan city with a population of approximately 2,100,000 in Iran. The general populations aged 30 years and above were invited to the Health clinics by public announcement. Results: A total of 198972 participants were screened. The mean age of participants was 47.8 years (48.5 men, 47.3 women, with a range of 1 to 95 years old and standard deviation of 12.3 years (12.7 men, 12.1 women. Overall, 22% of participants had impaired fasting glucose, 25% had hypercholesterolemia, 31% had hypertriglyceridemia, and 20% had metabolic syndrome. Conclusion: The high prevalence of dysglycemia and diabetes in our survey may serve as confirmatory evidence about the importance of mass screening and early diagnosis of CNCDs′ risk factors. Our model of establishing Health clinics, as a comprehensive referral system in the routine primary health care can be adopted by Middle Eastern countries, where CNCDs notably diabetes are an emerging health problem.

  1. ScreenOS Cookbook

    CERN Document Server

    Brunner, Stefan; Delcourt, David


    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.

  2. Stem cell-based approaches in dentistry


    Mitsiadis, T A; Orsini, G.; Jimenez-Rojo, L


    Repair of dental pulp and periodontal lesions remains a major clinical challenge. Classical dental treatments require the use of specialised tissue-adapted materials with still questionable efficacy and durability. Stem cell-based therapeutic approaches could offer an attractive alternative in dentistry since they can promise physiologically improved structural and functional outcomes. These therapies necessitate a sufficient number of specific stem cell populations for implantation. Dental m...

  3. Ontology for cell-based geographic information (United States)

    Zheng, Bin; Huang, Lina; Lu, Xinhai


    Inter-operability is a key notion in geographic information science (GIS) for the sharing of geographic information (GI). That requires a seamless translation among different information sources. Ontology is enrolled in GI discovery to settle the semantic conflicts for its natural language appearance and logical hierarchy structure, which are considered to be able to provide better context for both human understanding and machine cognition in describing the location and relationships in the geographic world. However, for the current, most studies on field ontology are deduced from philosophical theme and not applicable for the raster expression in GIS-which is a kind of field-like phenomenon but does not physically coincide to the general concept of philosophical field (mostly comes from the physics concepts). That's why we specifically discuss the cell-based GI ontology in this paper. The discussion starts at the investigation of the physical characteristics of cell-based raster GI. Then, a unified cell-based GI ontology framework for the recognition of the raster objects is introduced, from which a conceptual interface for the connection of the human epistemology and the computer world so called "endurant-occurrant window" is developed for the better raster GI discovery and sharing.

  4. A two-host fosmid system for functional screening of (meta)genomic libraries from extreme thermophiles. (United States)

    Angelov, Angel; Mientus, Markus; Liebl, Susanne; Liebl, Wolfgang


    A new cloning system is described, which allows the construction of large-insert fosmid libraries in Escherichia coli and the transfer of the recombinant libraries to the extreme thermophile Thermus thermophilus via natural transformation. Libraries are established in the thermophilic host by site-specific chromosomal insertion of the recombinant fosmids via single crossover or double crossover recombination at the T. thermophilus pyr locus. Comparative screening of a fosmid library constructed from genomic DNA from the thermophilic spirochaete, Spirochaeta thermophila, for clones expressing thermoactive xylanase activity revealed that 50% of the fosmids that conferred xylanase activity upon the corresponding T. thermophilus transformants did not give rise to xylanase-positive E. coli clones, indicating that significantly more S. thermophila genes are functionally expressed in T. thermophilus than in E. coli. The novel T. thermophilus host/vector system may be of value for the construction and functional screening of recombinant DNA libraries from individual thermophilic or extremely thermophilic organisms as well as from complex metagenomes isolated from thermophilic microbial communities.

  5. A strategy for integrating essential three-dimensional microphysiological systems of human organs for realistic anticancer drug screening. (United States)

    Heylman, Christopher; Sobrino, Agua; Shirure, Venktesh S; Hughes, Christopher Cw; George, Steven C


    Cancer is one of the leading causes of morbidity and mortality around the world. Despite some success, traditional anticancer drugs developed to reduce tumor growth face important limitations primarily due to undesirable bone marrow and cardiovascular toxicity. Many drugs fail in clinical development after showing promise in preclinical trials, suggesting that the available in vitro and animal models are poor predictors of drug efficacy and toxicity in humans. Thus, novel models that more accurately mimic the biology of human organs are necessary for high-throughput drug screening. Three-dimensional (3D) microphysiological systems can utilize induced pluripotent stem cell technology, tissue engineering, and microfabrication techniques to develop tissue models of human tumors, cardiac muscle, and bone marrow on the order of 1 mm(3) in size. A functional network of human capillaries and microvessels to overcome diffusion limitations in nutrient delivery and waste removal can also nourish the 3D microphysiological tissues. Importantly, the 3D microphysiological tissues are grown on optically clear platforms that offer non-invasive and non-destructive image acquisition with subcellular resolution in real time. Such systems offer a new paradigm for high-throughput drug screening and will significantly improve the efficiency of identifying new drugs for cancer treatment that minimize cardiac and bone marrow toxicity.

  6. A three-dimensional collagen scaffold cell culture system for screening anti-glioma therapeutics (United States)

    Lv, Donglai; Yu, Shi-cang; Ping, Yi-fang; Wu, Haibo; Zhao, Xilong; Zhang, Huarong; Cui, Youhong; Chen, Bing; Zhang, Xia; Dai, Jianwu


    Three-dimensional (3D) culture, which can simulate in vivo microenvironments, has been increasingly used to study tumor cell biology. Since most preclinical anti-glioma drug tests still rely on conventional 2D cell culture, we established a collagen scaffold for 3D glioma cell culture. Glioma cells cultured on these 3D scaffolds showed greater degree of dedifferentiation and quiescence than cells in 2D culture. 3D-cultured cells also exhibited enhanced resistance to chemotherapeutic alkylating agents, with a much higher proportion of glioma stem cells and upregulation of O6-methylguanine DNA methyltransferase (MGMT). Importantly, tumor cells in 3D culture showed chemotherapy resistance patterns similar to those observed in glioma patients. Our results suggest that 3D collagen scaffolds are promising in vitro research platforms for screening new anti-glioma therapeutics. PMID:27486877

  7. Landau damping in finite regularity for unconfined systems with screened interactions

    CERN Document Server

    Bedrossian, Jacob; Mouhot, Clement


    We prove Landau damping for the collisionless Vlasov equation with a class of $L^1$ interaction potentials (including the physical case of screened Coulomb interactions) on $\\mathbb R^3_x \\times \\mathbb R^3_v$ for localized disturbances of an infinite, homogeneous background. Unlike the confined case $\\mathbb T^3_x \\times \\mathbb R_v^3$, results are obtained for initial data in Sobolev spaces (as well as Gevrey and analytic classes). For spatial frequencies bounded away from zero, the Landau damping of the density is similar to the confined case. The finite regularity is possible due to an additional dispersive mechanism available on $\\mathbb R_x^3$ which reduces the strength of the plasma echo resonance.

  8. Rapid construction and screening of artificial microRNA systems in Chlamydomonas reinhardtii. (United States)

    Hu, Jinlu; Deng, Xuan; Shao, Ning; Wang, Gaohong; Huang, Kaiyao


    The unicellular green algae Chlamydomonas reinhardtii is a classic model for the study of flagella/cilia and photosynthesis, and it has recently been exploited for producing biopharmaceuticals and biofuel. Due to the low frequency of homologous recombination, reverse genetic manipulation in Chlamydomonas relies mainly on miRNA- and siRNA-based knockdown methods. However, the difficulty in constructing artificial miRNA vectors, laborious screening of knockdown transformants, and undesired epigenetic silencing of exogenous miRNA constructs limit their application. We have established a one-step procedure to construct an artificial miRNA precursor by annealing eight oligonucleotides of approximately 40 nucleotides. In the final construct, the Gaussia princeps luciferase gene (G-Luc) is positioned between the promoter and the artificial miRNA precursor so that knockdown strains may quickly be screened by visualizing luciferase luminescence using a photon-counting camera. Furthermore, the luciferase activity of transformants correlates with the knockdown level of two test target proteins: the chloroplast protein VIPP1 (vesicle inducing protein in plastids 1) and the flagellar protein CDPK3 (calcium-dependent protein kinase 3). Adding an intron from RBCS2 (ribulose bisphosphate carboxylase/oxygenase small subunit 2) to the miRNA construct enhanced both the luciferase activity and the miRNA knockdown efficiency. A second miRNA vector incorporated the promoter of the nitrate reductase gene to allow inducible expression of the artificial miRNA. These vectors will facilitate application of the artificial miRNA and provide tools for studying the mechanism of epigenetics in Chlamydomonas, and may also be adapted for use in other model organisms.

  9. Digital I&C systems in nuclear power plants. Risk-screening of environmental stressors and a comparison of hardware unavailability with an existing analog system

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, M.; Vesely, W.E.


    In this report, we present a screening study to identify environmental stressors for digital instrumentation and control (I&C) systems in a nuclear power plant (NPP) which can be potentially risk-significant, and compare the hardware unavailability of such a system with that of its existing analog counterpart. The stressors evaluated are temperature, humidity, vibration, radiation, electro-magnetic interference (EMI), and smoke. The results of risk-screening for an example plant, subject to some bounding assumptions and based on relative changes in plant risk (core damage frequency impacts of the stressors), indicate that humidity, EMI from lightning, and smoke can be potentially risk-significant. Risk from other sources of EMI could not be evaluated for a lack of data. Risk from temperature appears to be insignificant as that from the assumed levels of vibrations. A comparison of the hardware unavailability of the existing analog Safety Injection Actuation System (SIAS) in the example plant with that of an assumed digital upgrade of the system indicates that system unavailability may be more sensitive to the level of redundancy in elements of the digital system than to the environmental and operational variations involved. The findings of this study can be used to focus activities relating to the regulatory basis for digital I&C upgrades in NPPs, including identification of dominant stressors, data-gathering, equipment qualification, and requirements to limit the effects of environmental stressors. 30 refs., 8 figs., 26 tabs.

  10. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. (United States)

    Skardal, Aleksander; Shupe, Thomas; Atala, Anthony


    In recent years, advances in tissue engineering and microfabrication technologies have enabled rapid growth in the areas of in vitro organoid development as well as organoid-on-a-chip platforms. These 3D model systems often are able to mimic human physiology more accurately than traditional 2D cultures and animal models. In this review, we describe the progress that has been made to generate organ-on-a-chip platforms and, more recently, more complex multi-organoid body-on-a-chip platforms and their applications. Importantly, these systems have the potential to dramatically impact biomedical applications in the areas of drug development, drug and toxicology screening, disease modeling, and the emerging area of personalized precision medicine.

  11. Screening Analysis for the Environmental Risk Evaluation System Fiscal Year 2011 Report Environmental Effects of Offshore Wind Energy

    Energy Technology Data Exchange (ETDEWEB)

    Copping, Andrea E.; Hanna, Luke A.


    Potential environmental effects of offshore wind (OSW) energy development are not well understood, and yet regulatory agencies are required to make decisions in spite of substantial uncertainty about environmental impacts and their long-term consequences. An understanding of risks associated with interactions between OSW installations and avian and aquatic receptors, including animals, habitats, and ecosystems, can help define key uncertainties and focus regulatory actions and scientific studies on interactions of most concern. During FY 2011, Pacific Northwest National Laboratory (PNNL) scientists adapted and applied the Environmental Risk Evaluation System (ERES), first developed to examine the effects of marine and hydrokinetic energy devices on aquatic environments, to offshore wind development. PNNL scientists conducted a risk screening analysis on two initial OSW cases: a wind project in Lake Erie and a wind project off the Atlantic coast of the United States near Atlantic City, New Jersey. The screening analysis revealed that top-tier stressors in the two OSW cases were the dynamic effects of the device (e.g., strike), accidents/disasters, and effects of the static physical presence of the device, such as alterations in bottom habitats. Receptor interactions with these stressors at the highest tiers of risk were dominated by threatened and endangered animals. Risk to the physical environment from changes in flow regime also ranked high. Peer review of this process and results will be conducted during FY 2012. The ERES screening analysis provides an assessment of the vulnerability of environmental receptors to stressors associated with OSW installations; a probability analysis is needed to determine specific risk levels to receptors. As more data become available that document effects of offshore wind farms on specific receptors in U.S. coastal and Great Lakes waters, probability analyses will be performed.

  12. Colon cancer screening (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 ...

  13. Direct comparison of highly efficient solution- and vacuum-processed organic solar cells based on merocyanine dyes

    Energy Technology Data Exchange (ETDEWEB)

    Kronenberg, Nils M.; Steinmann, Vera; Hertel, Dirk; Meerholz, Klaus [Department fuer Chemie, Universitaet Koeln, Luxemburger Strasse 116, 50939 Koeln (Germany); Buerckstuemmer, Hannah; Wuerthner, Frank [Institut fuer Organische Chemie and Roentgen Research Center for Complex Material Systems, Universitaet Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany); Hwang, Jaehyung [BASF SE, Carl-Bosch-Strasse 38, 67056 Ludwigshafen (Germany)


    Identically configured bulk heterojunction organic solar cells based on merocyanine dye donor and fullerene acceptor compounds are manufactured either from solution or by vacuum deposition, to enable a direct comparison. Whereas the former approach is more suitable for screening purposes, the latter approach affords higher short-circuit current density and power conversion efficiency. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  14. Direct comparison of highly efficient solution- and vacuum-processed organic solar cells based on merocyanine dyes. (United States)

    Kronenberg, Nils M; Steinmann, Vera; Bürckstümmer, Hannah; Hwang, Jaehyung; Hertel, Dirk; Würthner, Frank; Meerholz, Klaus


    Identically configured bulk heterojunction organic solar cells based on merocyanine dye donor and fullerene acceptor compounds (see figure) are manufactured either from solution or by vacuum deposition, to enable a direct comparison. Whereas the former approach is more suitable for screening purposes, the latter approach affords higher short-circuit current density and power conversion efficiency.

  15. Implementation of Line Stability Index for Contingency Analysis and Screening in Power Systems

    Directory of Open Access Journals (Sweden)

    Vivek Kumar


    Full Text Available Problem statement: Estimating the margin in the loadability of the power system is essential in the real time voltage stability assessment. Voltage stability is currently one of the most important research areas in the field of electrical power system. In power system operation unpredictable events is termed as contingency and may be caused by line outage in the system which could lead to entire system instability. Voltage stability analysis and contingency analysis are would be performed in a power system by evaluating the derived voltage stability index. Approach: Voltage Stability Index Lmn can be useful for estimating the distance from the current operating point to voltage collapse point. The index can either reveal the critical bus of a power system or the stability of each line connected between two buses in an interconnected network or evaluate the voltage stability margins of a system. Results: Flexible Alternating Current Transmission Systems (FACTS devices have been proposed as an effective solution for controlling power flow and regulating bus voltage in electrical power systems, resulting in an increased transfer capability, low system losses and improved stability. However to what extent the performance of FACTS devices can be brought out highly depends upon the location and the parameters of these devices. Unified Power Flow Controller (UPFC is the most promising FACTS device for power flow control. Conclusion/Recommendations: The performance of this index is presented and the effectiveness of the analyzed methods is demonstrated through simulation studies in IEEE 14 bus reliability test systems.

  16. Dendritic cell-based cancer immunotherapy for colorectal cancer. (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo


    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.

  17. Inventions on GUI for Touch Sensitive Screens


    Mishra, Umakant


    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 ...

  18. Development of a Novel Anti-HIF-1α Screening System Coupled with Biochemical and Biological Validation for Rapidly Selecting Potent Anti-Cancer Compounds. (United States)

    Lu, Yi; Madu, Chikezie; Masters, Jordan; Lu, Andrew; Li, Liyuan


    Breast cancer (BCa) is the most diagnosed cancer and the second leading cause of cancer death in the American women. Adaptation to the hypoxic environment seen in solid tumors is critical for tumor cell survival and growth. The activation of hypoxia inducible factor-1 alpha (HIF-1α), an important master transcriptional factor that is induced and stabilized by intratumoral hypoxia, stimulates a group of HIF-1α-regulated genes including vascular endothelial growth factor (VEGF), leading tumor cells towards malignant progression. Therefore, a promising therapeutic approach to cancer treatment is to target HIF-1α. The goal of this project was to develop and validate a screening system coupled with secondary screen/validation process that has the capability to screen large numbers of potential anti-cancer small-molecule compounds based on their anti-HIF-1α activities. Breast cancer MDA-231 cells were used as the model to select potent anti-HIF-1α compounds by their abilities to inhibit transactivation of a VEGF promoter fused to a luciferase reporter gene under hypoxia. Positive compounds were then validated by a series of assays that confirm compounds' anti-HIF-1α activities including measurement of HIF-1α downstream VEGF gene expression and angiogenic ability of BCa cells. Results of our pilot screening demonstrate that this prototype screening coupled with validation system can effectively select highly potent anti-HIF-1α agents from the compound library, suggesting that this prototype screen system has the potential to be developed into a high-throughput screen (HTS) coupled with automated validation process for the screening and identification of novel and effective anti-cancer drugs based on anti-HIF-1α mechanism.

  19. Adaptive Neuro-Fuzzy Inference System Approach for the Automatic Screening of Diabetic Retinopathy in Fundus Images

    Directory of Open Access Journals (Sweden)

    S. Kavitha


    Full Text Available Problem statement: Diabetic retinopathy is one of the most significant factors contributing to blindness and so early diagnosis and timely treatment is particularly important to prevent visual loss. Approach: An integrated approach for extraction of blood vessels and exudates detection was proposed to screen diabetic retinopathy. An automated classifier was developed based on Adaptive Neuro-Fuzzy Inference System (ANFIS to differentiate between normal and nonproliferative eyes from the quantitative assessment of monocular fundus images. Feature extraction was performed on the preprocessed fundus images. Structure of Blood vessels was extracted using Multiscale analysis. Hard Exudates were detected using CIE Color channel transformation, Entropy Thresholding and Improved Connected Component Analysis from the fundus images. Features like Wall to Lumen ratio in blood vessels, Texture, Homogeneity properties and area occupied by Hard Exudates, were given as input to ANFIS.ANFIS was trained with Back propagation in combination with the least squares method. Proposed method was evaluated on 200 real time images comprising 70 normal and 130 retinopathic eyes. Results and Conclusion: All of the results were validated with ground truths obtained from expert ophthalmologists. Quantitative performance of the method, detected exudates with an accuracy of 99.5%. Receiver operating characteristic curve evaluated for real time images produced better results compared to the other state of the art methods. ANFIS provides best classification and can be used as a screening tool in the analysis and diagnosis of retinal images.

  20. Screening of hepatocyte proteins binding to NS5ABP37 protein by yeast-two hybrid system

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Qing-yong Ma; Xian-kui Meng; Kang Li; Jun Cheng


    Objective To investigate the biological function of NS5ABP37 and to look for proteins interacting with NS5ABP37 protein in hepatocytes. Methods We constructed bait plasmid expressing NS5ABP37 protein of hepatitis C virus (HCV) by cloning the gene of NS5ABP37 protein into pGBKT7, then the recombinant plasmid DNA was transformed into yeast AH109 (α type). The transformed yeast AH109 was mated with yeast Y187 (α type) containing liver cDNA library plasmid in 2×YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing X-α-gal for selection and screening. After extracting and sequencing of plasmids from positive (blue) colonies, we made a sequence analysis by bioinformatics. Results We screened twenty-five proteins binding to NS5ABP37, including Homo sapiens cyclin Ⅰ (CCNI) gene, Homo sapiens matrix metallopeptidase 25 (MMP25) and Homo sapiens talin 1. Conclusion The yeast-two hybrid system is an effective method for identifying hepatocyte proteins interacting with NS5ABP37 of HCV. And the biological function of NS5ABP37 may be associated with glycometabolism, lipid metabolism and apoptosis.

  1. Evaluation of PCR Systems for Field Screening of Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Ozanich, Richard M.; Colburn, Heather A.; Victry, Kristin D.; Bartholomew, Rachel A.; Arce, Jennifer S.; Heredia-Langner, Alejandro; Jarman, Kristin; Kreuzer, Helen W.; Bruckner-Lea, Cynthia J.


    There is little published data on the performance of hand-portable polymerase chain reaction (PCR) instruments that could be used by first responders to determine if a suspicious powder contains a potential biothreat agent. We evaluated five commercially available hand-portable PCR instruments for detection of Bacillus anthracis (Ba). We designed a cost-effective, statistically-based test plan that allows instruments to be evaluated at performance levels ranging from 0.85-0.95 lower confidence bound (LCB) on the probability of detection (POD) at confidence levels of 80-95%. We assessed specificity using purified genomic DNA from 13 Ba strains and 18 Bacillus near neighbors, interference with 22 common hoax powders encountered in the field, and PCR inhibition when Ba spores were spiked into these powders. Our results indicated that three of the five instruments achieved >0.95 LCB on the POD with 95% confidence at test concentrations of 2,000 genome equivalents/mL (comparable to 2,000 spores/mL), displaying more than sufficient sensitivity for screening suspicious powders. These instruments exhibited no false positive results or PCR inhibition with common hoax powders, and reliably detected Ba spores spiked into common hoax powders, though some issues with instrument controls were observed. Our testing approach enables efficient instrument performance testing to a statistically rigorous and cost-effective test plan to generate performance data that will allow users to make informed decisions regarding the purchase and use of biodetection equipment in the field.

  2. Screening and determination of sulphonamide residues in bovine milk samples using a flow injection system. (United States)

    Fernandes, Flávio Cesar Bedatty; Silva, Aline Santana; Rufino, José Luiz; Pezza, Helena Redigolo; Pezza, Leonardo


    A new, simple, rapid and sensitive flow injection spectrophotometric method was developed for the screening and determination of sulphonamides in bovine milk samples. The method is based on the condensation of sulphathiazole, sulphamethazine, and sulphadimethoxine with p-dimethylaminobenzaldehyde (p-DAB) in acid medium, in the presence of sodium dodecyl sulphate (SDS), producing a yellow compound (λmax=465 nm). Optimisation of the experimental parameters was performed using a multivariate methodology. The linear range was 90-500 μg/L and the limits of detection and quantification were in the ranges 25-29 μg/L and 84-88 μg/L, respectively. The procedure was applied for the determination of sulphonamide antibiotics in bovine milk samples submitted to a prior extraction procedure based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) methodology. Recoveries of 60.5-70.5% were achieved for milk samples spiked with 0.09, 0.1, 0.2, and 0.3 μg/g of each sulphonamide.

  3. Establishment of a functional secretory IgA transcytosis model system in vitro for functional food screening. (United States)

    Zuo, Tao; Feng, Xianqi; Zhang, Na; Xue, Changhu; Tang, Qing-Juan


    A characteristic mucosal immune response involves the production of antigen-specific secretory immunoglobulin A (SIgA) antibodies. In order to study transcytosis by mimicking the SIgA secretion and to screen for SIgA secretion-promoting substances, we developed a model system of a transfected Madin-Darby canine kidney (MDCK) cell line that expresses the human polymeric immunoglobulin receptor (pIgR). We thus isolated the human dIgA (dimeric IgA)/pIgA (polymeric IgA) complex as the binding ligands. In the present study, a recombinant vector encoding the human pIgR gene was constructed and infected into MDCK cells. Following reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunofluorescence staining, we confirmed that pIgR was expressed in the transfectant MDCK-pIgR cells and was located at the basolateral side of the cell surface. We also confirmed the coexistence of the dIgA/pIgA complex in the IgA myeloma serum. The covalent dIgA/pIgA complex was then isolated from the serum of an IgA multiple myeloma patient using an ÄKTA purifier operation system with a HiPrep 16/60 Sephacryl S-300 HR column, in order to utilize the complex as transcytosis ligands for human pIgR. Finally, we confirmed the uptake of the isolated human dIgA/pIgA complex into MDCK-pIgR cells. We demonstrated that the human dIgA/pIgA complex was transcytosed into the apical side of the monolayer cells. Therefore, our MDCK-human pIgR cell transcytosis model is an operational system and can be used for screening functional food components that promote dIgA/pIgR transcytosis as well as SIgA secretion.

  4. Non-target screening analyses of organic contaminants in river systems as a base for monitoring measures (United States)

    Schwarzbauer, J.


    Organic contaminants discharged to the aquatic environment exhibit a high diversity with respect to their molecular structures and the resulting physico-chemical properties. The chemical analysis of anthropogenic contamination in river systems is still an important feature, especially with respect to (i) the identification and structure elucidation of novel contaminants, (ii) to the characterisation of their environmental behaviour and (iii) to their risk for natural systems. A huge proportion of riverine contamination is caused by low-molecular weight organic compounds, like pesticides plasticizers, pharmaceuticals, personal care products, technical additives etc. Some of them, like PCB or PAH have already been investigated thoroughly and, consequently, their behaviour in aqueous systems is very well described. Although analyses on organic substances in river water traditionally focused on selected pollutants, in particular on common priority pollutants which are monitored routinely, the occurrence of further contaminants, e.g. pharmaceuticals, personal care products or chelating agents has received increasing attention within the last decade. Accompanied, screening analyses revealing an enormous diversity of low-molecular weight organic contaminants in waste water effluents and river water become more and more noticed. Since many of these substances have been rarely noticed so far, it will be an important task for the future to study their occurrence and fate in natural environments. Further on, it should be a main issue of environmental studies to provide a comprehensive view on the state of pollution of river water, in particular with respect to lipophilic low molecular weight organic contaminants. However, such non-target-screening analyses has been performed only rarely in the past. Hence, we applied extended non-target screening analyses on longitudinal sections of the rivers Rhine, Rur and Lippe (Germany) on the base of GC/MS analyses. The investigations

  5. Urine drug screen (United States)

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

  6. Cervical Cancer Screening (United States)

    ... are at increased risk for HPV infections. Other risk factors for cervical cancer include: Giving birth to many children. Smoking cigarettes. Using oral contraceptives ("the Pill"). Having a weakened immune system . Cervical Cancer Screening ...

  7. Design of linear anti-scatter grid geometry with optimum performance for screen-film and digital mammography systems. (United States)

    Khodajou-Chokami, H; Sohrabpour, M


    A detailed 3D Monte Carlo simulation of the grid geometrical parameters in screen-film mammography (SFM) and digital mammography (DM) systems has been performed. A combination of IEC 60627:2013 international standard conditions and other more clinically relevant parameters were used for this simulation. Accuracy of our results has been benchmarked with previously published data and good agreement has been obtained. Calculations in a wide range of linear anti-scatter grid geometries have been carried out. The evaluated parameters for the SFM system were the Bucky factor (BF) and contrast improvement factor (CIF) and for the DM system it was signal difference-to-noise ratio improvement factor (SIF). The CIF parameter was chosen to be nearly the same as the commercial grade, the BF and SIF were significantly improved compared to commercial grids in use today. Our optimized grid parameters for the SFM system were lead strip thickness d = 12 µm, grid ratio r = 5 and strip density N = 65 lines/cm. And for the DM system these parameters were d = 5 µm, r = 3 and N = 100 lines/cm. Both optimized grid sets have thinner d and higher N compared to the commercial grids.

  8. Development of a system for receiving, crushing and screening recycled fuel (REF) material; Kierraetyspolttoaineen vastaanotto-, murskaus- ja seulontajaerjestelmaen kehittaeminen

    Energy Technology Data Exchange (ETDEWEB)

    Nurmi, A. [VTT Energy, Jyvaeskylae (Finland)


    The goal of this project is to develop a system to which source sorted combustible industrial, office and municipal waste material can be taken and where it is then processed in such way that it can be burnt in modern fluidized bed and circulating bed boilers. The project started in the end of year 1995. The main stages of the project are: (1) Study and analysis of existing technology and equipment, (2) Development of system components, (3) Development of the system, (4) Building a pilot/demonstration plant, (5) Tests and results analysis and (6) Decisions on further actions. In the year 1996 the main stage was development of system components; especially crushing. Results of running slow-speed big crushers were collected, analysed and the main development details determined. Additionally, particle size distribution from different crushing methods were analyzed using also primary and secondary crushing. Development of a heavy-duty 2-rotor ECO-Crusher and a crushing screen was started. Regarding to the development of the REF-system, different alternatives have been analyzed and possible demonstration places have been searched. The first multi-crushing line will be demonstrated in Sweden. (orig.)

  9. Employer-Based Screening for Diabetes and Prediabetes in an Integrated Health Care Delivery System: A Natural Experiments for Translation in Diabetes (NEXT-D) Study (United States)

    Adams, Sara R.; Wiley, Deanne M.; Fargeix, Andromache; George, Victoria; Neugebauer, Romain S.; Schmittdiel, Julie A.


    OBJECTIVE To evaluate an employer-based diabetes/prediabetes screening intervention that invited at-risk employees via letters, secure emails, and automated voice messages to complete blood glucose testing at a health plan facility. METHODS Quasi-experimental cohort study among health plan members insured by two employers that received the intervention and three employers that were selected as control sites. RESULTS The proportion of at-risk members that completed a screening was higher in the intervention group than in the control group (36% vs. 13%, P < .001, adjusted for patient characteristics). Among those screened in the intervention group, the presence of obesity, hypertension, hyperlipidemia, and tobacco use were significant predictors of having a result which indicated diabetes or prediabetes (P < .05, all comparisons). CONCLUSIONS A low-intensity, employer-based intervention conducted in collaboration with a health care delivery system effectively increased screening for diabetes/prediabetes. PMID:26539761

  10. Urinary Glycosaminoglycan Electrophoresis With Optimized Keratan Sulfate Separation Using Peltier System for the Screening of Mucopolysaccharidoses

    Directory of Open Access Journals (Sweden)

    Mihriban Tijen Tanyalcin MD, PhD


    Full Text Available The purpose of this communication is to indicate a simple and rapid method with a small volume of urine sample to detect urine glycosaminoglycan (GAG and serve as a screening procedure for mucopolysaccharidoses (MPSs. Total GAG measurement for patients with MPS disorders is considered to be the first step in diagnosis of those heterogeneous group of lysosomal storage disorders presenting clinical phenotype. In this study, modified 9-dimethylmethylene blue method is used for total GAG measurement. Following GAG quantitation, the procedure described here allows GAG isolation from a very a small volume of urine sample and subjected to high-resolution GAG electrophoresis, which can be easily performed in routine clinical diagnostic laboratories. Glycosaminoglycan precipitation is a modified method based on total GAG concentration in the urine. For optimized isolation of total GAG for electrophoresis, instead of considering the urine creatinine concentration, 300 μg/mL GAG containing urine is considered to be the target concentration for the best precipitation with 1000 μL cetylpyridinium chloride (CPC/citrate buffer. Glycosaminoglycan concentration-based precipitation of urine with CPC allows the laboratory to be able to work with a small volume of urine sample by keeping the precipitating ratio with CPC constant for samples that contain GAG less than 300 μg/mL. Based on the effect of cold buffer using low voltage, GAGs high-resolution electrophoresis banding patterns described here enable a clear separation of keratan sulfate from chondroitin sulfate as well as dermatan sulfate (DS1 and DS2 and heparan sulfate. By this procedure, GAG patterns are more clear, easily identified, and provide a guide for the enzyme analysis deficient in the MPS disorders.

  11. Phantom experiments with a microwave imaging system for breast-cancer screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Zhurbenko, Vitaliy


    Microwave imaging is emerging as a promising technique for breast-cancer detection. In this paper, the microwave imaging system currently being developed at the Technical University of Denmark is introduced. This system consists of 32 antennas positioned in a cylindrical setup, each equipped...

  12. A novel screening system for secretion of heterologous proteins in Bacillus subtilis

    NARCIS (Netherlands)

    Trip, Hein; van der Veek, Patricia J.; Renniers, Ton C.; Meima, Rob; Sagt, Cees M.; Mohrmann, Lisette; Kuipers, Oscar P.


    High-level production of secretory proteins in Bacillus subtilis leads to a stress response involving the two-component system CssRS and its target genes htrA and htrB. Here, we used this sensing system in a reporter strain in which gfp is under control of P(htrA), the secretion stress responsive pr

  13. Automated high-performance cIMT measurement techniques using patented AtheroEdge™: a screening and home monitoring system. (United States)

    Molinari, Filippo; Meiburger, Kristen M; Suri, Jasjit


    The evaluation of the carotid artery wall is fundamental for the assessment of cardiovascular risk. This paper presents the general architecture of an automatic strategy, which segments the lumen-intima and media-adventitia borders, classified under a class of Patented AtheroEdge™ systems (Global Biomedical Technologies, Inc, CA, USA). Guidelines to produce accurate and repeatable measurements of the intima-media thickness are provided and the problem of the different distance metrics one can adopt is confronted. We compared the results of a completely automatic algorithm that we developed with those of a semi-automatic algorithm, and showed final segmentation results for both techniques. The overall rationale is to provide user-independent high-performance techniques suitable for screening and remote monitoring.

  14. Design, construction and commissioning of the Thermal Screen Control System for the CMS Tracker detector at CERN

    CERN Document Server

    Carrone, E; Tsirou, A

    The CERN (European Organization for Nuclear Research) laboratory is currently building the Large Hadron Collider (LHC). Four international collaborations have designed (and are now constructing) detectors able to exploit the physics potential of this collider. Among them is the Compact Muon Solenoid (CMS), a general purpose detector optimized for the search of Higgs boson and for physics beyond the Standard Model of fundamental interactions between elementary particles. This thesis presents, in particular, the design, construction, commissioning and test of the control system for a screen that provides a thermal separation between the Tracker and ECAL (Electromagnetic CALorimeter) detector of CMS (Compact Muon Solenoid experiment). Chapter 1 introduces the new challenges posed by these installations and deals, more in detail, with the Tracker detector of CMS. The size of current experiments for high energy physics is comparable to that of a small industrial plant: therefore, the techniques used for controls a...

  15. Cancer screening and health system resilience: keys to protecting and bolstering preventive services during a financial crisis. (United States)

    Martin-Moreno, Jose M; Anttila, Ahti; von Karsa, Lawrence; Alfonso-Sanchez, Jose L; Gorgojo, Lydia


    The aim of this paper is to elucidate the rationale for sustaining and expanding cost-effective, population-based screening services for breast, cervical and colorectal cancers in the context of the current financial crisis. Our objective is not only to promote optimal delivery of high-quality secondary cancer prevention services, but also to underline the importance of strengthening comprehensive cancer control, and with it, health system response to the complex care challenges posed by all chronic diseases. We focus primarily on issues surrounding planning, organisation, implementation and resources, arguing that given the growing cancer burden, policymakers have ample justification for establishing and expanding population-based programmes that are well-organised, well-resourced and well-executed. In a broader economic context of rescue packages, deficits and cutbacks to government entitlements, health professionals must intensify their advocacy for the protection of vital preventive health services by fighting for quality services with clear benefits for population health outcomes.

  16. Sensitive-cell-based fish chromatophore biosensor (United States)

    Plant, Thomas K.; Chaplen, Frank W.; Jovanovic, Goran; Kolodziej, Wojtek; Trempy, Janine E.; Willard, Corwin; Liburdy, James A.; Pence, Deborah V.; Paul, Brian K.


    A sensitive biosensor (cytosensor) has been developed based on color changes in the toxin-sensitive colored living cells of fish. These chromatophores are highly sensitive to the presence of many known and unknown toxins produced by microbial pathogens and undergo visible color changes in a dose-dependent manner. The chromatophores are immobilized and maintained in a viable state while potential pathogens multiply and fish cell-microbe interactions are monitored. Low power LED lighting is used to illuminate the chromatophores which are magnified using standard optical lenses and imaged onto a CCD array. Reaction to toxins is detected by observing changes is the total area of color in the cells. These fish chromatophores are quite sensitive to cholera toxin, Staphococcus alpha toxin, and Bordatella pertussis toxin. Numerous other toxic chemical and biological agents besides bacterial toxins also cause readily detectable color effects in chromatophores. The ability of the chromatophore cell-based biosensor to distinguish between different bacterial pathogens was examined. Toxin producing strains of Salmonella enteritis, Vibrio parahaemolyticus, and Bacillus cereus induced movement of pigmented organelles in the chromatophore cells and this movement was measured by changes in the optical density over time. Each bacterial pathogen elicited this measurable response in a distinctive and signature fashion. These results suggest a chromatophore cell-based biosensor assay may be applicable for the detection and identification of virulence activities associated with certain air-, food-, and water-borne bacterial pathogens.

  17. Identification of active Plasmodium falciparum calpain to establish screening system for Pf-calpain-based drug development

    Directory of Open Access Journals (Sweden)

    Soh Byoung


    Full Text Available Abstract Background With the increasing resistance of malaria parasites to available drugs, there is an urgent demand to develop new anti-malarial drugs. Calpain inhibitor, ALLN, is proposed to inhibit parasite proliferation by suppressing haemoglobin degradation. This provides Plasmodium calpain as a potential target for drug development. Pf-calpain, a cysteine protease of Plasmodium falciparum, belongs to calpain-7 family, which is an atypical calpain not harboring Ca2+-binding regulatory motifs. In this present study, in order to establish the screening system for Pf-calpain specific inhibitors, the active form of Pf-calpain was first identified. Methods Recombinant Pf-calpain including catalytic subdomain IIa (rPfcal-IIa was heterologously expressed and purified. Enzymatic activity was determined by both fluorogenic substrate assay and gelatin zymography. Molecular homology modeling was carried out to address the activation mode of Pf-calpain in the aspect of structural moiety. Results Based on the measurement of enzymatic activity and protease inhibitor assay, it was found that the active form of Pf-calpain only contains the catalytic subdomain IIa, suggesting that Pf-calpain may function as a monomeric form. The sequence prediction indicates that the catalytic subdomain IIa contains all amino acid residues necessary for catalytic triad (Cys-His-Asn formation. Molecular modeling suggests that the Pf-calpain subdomain IIa makes an active site, holding the catalytic triad residues in their appropriate orientation for catalysis. The mutation analysis further supports that those amino acid residues are functional and have enzymatic activity. Conclusion The identified active form of Pf-calpain could be utilized to establish high-throughput screening system for Pf-calpain inhibitors. Due to its unique monomeric structural property, Pf-calpain could be served as a novel anti-malarial drug target, which has a high specificity for malaria parasite

  18. Screened spin-1 and -1/2 Kondo effect in a triangular quantum dot system with interdot Coulomb repulsion (United States)

    Xiong, Yong-Chen; Wang, Wei-Zhong; Luo, Shi-Jun; Yang, Jun-Tao; Huang, Hai-Ming


    By means of the numerical renormalization group (NRG) technique, we study the low temperature transport property and the phase transition for a triangular triple quantum dot system, including two centered dots (dot 1 and 2) and one side dot (dot 3). We focus on the effect of interdot repulsion V between two centered dots in a wide range of the interdot hopping tij (i,j = 1,2,3). When the hoppings between the centered dot and the side dot are symmetric, i.e., t13 = t23, and that between two centered dots t12 is small, two centered dots form a spin triplet when V is absent, and a totally screened spin-1 Kondo effect is observed. In this case, one has a spin 1 that is partially screened by the leads as in the usual spin-1 Kondo model, and the remaining spin 1/2 degree of freedom forms a singlet with the side dot. As V is large enough, one of the centered dots is singly occupied, while the other one is empty. The spin-1/2 Kondo effect is found when t13 is small. For large t12, two centered dots form a spin singlet when V = 0, leading to zero conductance. As V is large enough, the spin-1/2 Kondo effect is recovered in the case of small t13. For asymmetric t13≠t23 and small t12, a crossover is found as V increases in comparison with a first order quantum phase transition for the symmetric case. In the regime of large V, the spin-1/2 Kondo effect could also be found when both t13 and t23 are small. We demonstrate the present model is similar to the side-coupled double dot system in some appropriate regimes, and it appears as a possible realization of side-controllable molecular electronics and spintronics devices.

  19. A semiconductor gas sensor system for high throughput screening of heterogeneous catalysts for the production of benzene derivatives (United States)

    Yamada, Yusuke; Ueda, Atsushi; Shioyama, Hiroshi; Maekawa, Toru; Kanda, Keisen; Suzuki, Kengo; Kobayashi, Tetsuhiko


    We used a semiconductor gas sensor system developed for odour discrimination for a rapid quantification of benzene derivatives which can be formed as the product of a catalytic reaction. Phenol can be obtained by the selective oxidation of benzene. The sensor system shows higher sensitivity to phenol than benzene. In particular, a SnO2 sensor sensitized with ZrO2 responds selectively to phenol. Aniline is provided as a reaction product between ammonia and benzene. The output signal of the gas sensor system increases when it is exposed to air containing aniline at the ppm level; on the other hand, the sensor output resulting from 1% ammonia in air does not increase so much. Cumene formation can be observed by the reaction of propane and benzene. The sensitivity of a SnO2 sensor sensitized with 12%SiO2-Al2O3 to cumene was about ten times higher than that to benzene. These results indicate that the semiconductor gas sensor system is useful for rapid screening of the catalyst for benzene functionalization.

  20. CKD screening and management in the Veterans Health Administration: the impact of system organization and an innovative electronic record. (United States)

    Patel, Thakor G; Pogach, Leonard M; Barth, Robert H


    At the beginning of this decade, Healthy People 2010 issued a series of objectives to "reduce the incidence, morbidity, mortality and health care costs of chronic kidney disease." A necessary feature of any program to reduce the burden of kidney disease in the US population must include mechanisms to screen populations at risk and institute early the aspects of management, such as control of blood pressure, management of diabetes, and, in patients with advanced chronic kidney disease (CKD), preparation for dialysis therapy and proper vascular access management, that can retard CKD progression and improve long-term outcome. The Department of Veterans Affairs and the Veterans Health Administration is a broad-based national health care system that is almost uniquely situated to address these issues and has developed a number of effective approaches using evidence-based clinical practice guidelines, performance measures, innovative use of a robust electronic medical record system, and system oversight during the past decade. In this report, we describe the application of this systems approach to the prevention of CKD in veterans through the treatment of risk factors, identification of CKD in veterans, and oversight of predialysis and dialysis care. The lessons learned and applicability to the private sector are discussed.

  1. Development of a system for receiving, crushing and screening recycled fuel (REF) material; Kierraetyspolttoaineen vastaanotto-, murskaus- ja seulontajaerjestelmaen kehittaeminen

    Energy Technology Data Exchange (ETDEWEB)

    Nurmi, A.; Kurki, T.; Wrang, T. [BMH Wood Technology Oy, Rauma (Finland)


    The goal of this project is to develop a system to which source sorted combustible industrial, office and municipal waste material can be dumped to be handled in such way that it can be burnt in modern fluidized bed and circulating bed boilers. One drawback of present handling systems is the fact that most of them are more or less inapplicable for handling plastic materials, especially thin plastic films and sheets. Reducing plastic waste into a particle size of 50 mm required by modern fluidized bed boilers has proved to be very difficult. An essential part of this project is the development of waste material screening after primary and/or secondary crushing. The idea is to separate plastic particles larger than the maximum allowable size from the crushed material and then feed them to a separate low-capacity plastic crusher. The main stages of the project are: (1) Study and analysis on existing technology and equipment, (2) Development of system components, (3) Development of the system, (4) Building a pilot/demonstration plant, (5) Tests and analysis and (6) Decisions on further actions

  2. Assessment of human multi-potent hematopoietic stem/progenitor cell potential using a single in vitro screening system.

    Directory of Open Access Journals (Sweden)

    Julien Calvo

    Full Text Available Hematopoietic stem cells are responsible for the generation of the entire blood system through life. This characteristic relies on their ability to self renew and on their multi-potentiality. Thus quantification of the number of hematopoietic stem cells in a given cell population requires to show both properties in the studied cell populations. Although xenografts models that support human hematopoietic stem cells have been described, such in vivo experimental systems remain restrictive for high throughput screening purposes for example. In this work we developed a conditional tetracycline inducible system controlling the expression of the human NOTCH ligand Delta-like 1 in the murine stromal MS5 cells. We cultured hematopoietic immature cells enriched in progenitor/stem cells in contact with MS5 cells that conditionally express Delta-like 1, in conditions designed to generate multipotential lineage differentiation. We show that upon induction or repression of DL1 expression during co-culture, human immature CD34(+CD38(-/low(CD45RA(-CD90(+ cells can express their B, T, NK, granulo/monocytic and erythroid potentials in a single well, and at the single cell level. We also document the interference of low NOTCH activation with human B and myelo/erythroid lymphoid differentiation. This system represents a novel tool to precisely quantify human hematopoietic immature cells with both lymphoid and myeloid potentials.

  3. [Use of the Helkimo Index as screening of dysfunctions of the stomatognathic system]. (United States)

    von Majewsky, I; Simm, R


    The Helkimo index was used on 130 subjects to identify dysfunctions of the stomatognathic system. There were no significant discrepancies between the results obtained by two investigators except in the case of occlusal interference.

  4. Screening reservoir systems by considering the efficient trade-offs—informing infrastructure investment decisions on the Blue Nile (United States)

    Geressu, Robel T.; Harou, Julien J.


    Multi-reservoir system planners should consider how new dams impact downstream reservoirs and the potential contribution of each component to coordinated management. We propose an optimized multi-criteria screening approach to identify best performing designs, i.e., the selection, size and operating rules of new reservoirs within multi-reservoir systems. Reservoir release operating rules and storage sizes are optimized concurrently for each separate infrastructure design under consideration. Outputs reveal system trade-offs using multi-dimensional scatter plots where each point represents an approximately Pareto-optimal design. The method is applied to proposed Blue Nile River reservoirs in Ethiopia, where trade-offs between total and firm energy output, aggregate storage and downstream irrigation and energy provision for the best performing designs are evaluated. This proof-of concept study shows that recommended Blue Nile system designs would depend on whether monthly firm energy or annual energy is prioritized. 39 TWh/yr of energy potential is available from the proposed Blue Nile reservoirs. The results show that depending on the amount of energy deemed sufficient, the current maximum capacities of the planned reservoirs could be larger than they need to be. The method can also be used to inform which of the proposed reservoir type and their storage sizes would allow for the highest downstream benefits to Sudan in different objectives of upstream operating objectives (i.e., operated to maximize either average annual energy or firm energy). The proposed approach identifies the most promising system designs, reveals how they imply different trade-offs between metrics of system performance, and helps system planners asses the sensitivity of overall performance to the design parameters of component reservoirs.

  5. Screening of mixed surfactant systems: Phase behavior studies and CT imaging of surfactant-enhanced oil recovery experiments

    Energy Technology Data Exchange (ETDEWEB)

    Llave, F.M.; Gall, B.L.; Lorenz, P.B.; Cook, I.M.; Scott, L.J.


    A systematic chemical screening study was conducted on selected anionic-nonionic and nonionic-nonionic systems. The objective of the study was to evaluate and determine combinations of these surfactants that would exhibit favorable phase behavior and solubilization capacity. The effects of different parameters including (a) salinity, (b) temperature, (c) alkane carbon number, (c) hydrophilic/lipophilic balance (HLB) of nonionic component, and (d) type of surfactant on the behavior of the overall chemical system were evaluated. The current work was conducted using a series of ethoxylated nonionic surfactants in combinations of several anionic systems with various hydrocarbons. Efforts to correlate the behavior of these mixed systems led to the development of several models for the chemical systems tested. The models were used to compare the different systems and provided some guidelines for formulating them to account for variations in salinity, oil hydrocarbon number, and temperature. The models were also evaluated to determine conformance with the results from experimental measurements. The models provided good agreement with experimental results. X-ray computed tomography (CT) was used to study fluid distributions during chemical enhanced oil recovery experiments. CT-monitored corefloods were conducted to examine the effect of changing surfactant slug size injection on oil bank formation and propagation. Reducing surfactant slug size resulted in lower total oil production. Oil recovery results, however, did not correlate with slug size for the low-concentration, alkaline, mixed surfactant system used in these tests. The CT measurements showed that polymer mobility control and core features also affected the overall oil recovery results.

  6. Screening CO

    NARCIS (Netherlands)

    Ramírez, A.; Hagedoorn, S.; Kramers, L.; Wildenborg, T.; Hendriks, C.


    This paper describes the development and application of a methodology to screen and rank Dutch reservoirs suitable for long-term large scale CO2 storage. The screening focuses on off- and on-shore individual aquifers, gas and oil fields. In total 176 storage reservoirs have been taken int

  7. Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode

    Directory of Open Access Journals (Sweden)

    Liang Qiong-Lin


    Full Text Available Abstract Background Shuanglong formula (SLF, a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF. Method In this study, we present a "system to system" (S2S mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6 while maintaining its curative effect for MI. Results Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage. Conclusions The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.

  8. Computational Validation of a 3-D Microwave Imaging System for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Kim, Oleksiy S.; Meincke, Peter


    -of-moments solution of the associated forward scattering problem. A cylindrical multistatic antenna setup with 32 horizontally oriented antennas is used for collecting the data. It has been found that formulating the imaging algorithm in terms of the logarithm of the amplitude and the unwrapped phase of the measured......The microwave imaging system currently being developed at the Technical University of Denmark is described and its performance tested on simulated data. The system uses an iterative Newton-based imaging algorithm for reconstructing the images in conjunction with an efficient method...... in the measurement system is shown by imaging the same breast model using a measurement setup in which the antennas are vertically oriented....

  9. High-throughput system for screening of high L-lactic acid-productivity strains in deep-well microtiter plates. (United States)

    Lv, Xiangyun; Song, Jiali; Yu, Bo; Liu, Huilan; Li, Chao; Zhuang, Yingping; Wang, Yonghong


    For strain improvement, robust and scalable high-throughput cultivation systems as well as simple and rapid high-throughput detection methods are crucial. However, most of the screening methods for lactic acid bacteria (LAB) strains were conducted in shake flasks and detected by high-performance liquid chromatography (HPLC), making the screening program laborious, time-consuming and costly. In this study, an integrated strategy for high-throughput screening of high L-lactic acid-productivity strains by Bacillus coagulans in deep-well microtiter plates (MTPs) was developed. The good agreement of fermentation results obtained in the MTPs platform with shake flasks confirmed that 24-well U-bottom MTPs could well alternate shake flasks for cell cultivation as a scale-down tool. The high-throughput pH indicator (bromocresol green) and L-lactate oxidase (LOD) assays were subsequently developed to qualitatively and quantitatively analyze L-lactic acid concentration. Together with the color halos method, the pH indicator assay and LOD assay, the newly developed three-step screening strategy has greatly accelerated the screening process for LAB strains with low cost. As a result, two high L-lactic acid-productivity mutants, IH6 and IIIB5, were successfully screened out, which presented, respectively, 42.75 and 46.10 % higher productivities than that of the parent strain in a 5-L bioreactor.

  10. Audio-Visual Attractors for Capturing Attention to the Screens When Walking in CAVE Systems


    Grani, Francesco; Argelaguet Sanz, Ferran; Gouranton, Valérie; Badawi, Marwan; Gaugne, Ronan; Serafin, Stefania; Lécuyer, Anatole


    International audience; In four-sided CAVE-like VR systems, the absence of the rear wall has been shown to decrease the level of immersion and can introduce breaks in presence. In this paper it is investigated to which extent user's attention can be driven by visual and auditory stimuli in a four-sided CAVE-like system. An experiment was conducted in order to analyze how user attention is diverted while physically walking in a virtual environment, when audio and/or visual attractors are prese...

  11. System for rapid biohydrogen phenotypic screening of microorganisms using a chemochromic sensor (United States)

    Seibert, Michael; Benson, David K.; Flynn, Timothy Michael


    Provided is a system for identifying a hydrogen gas producing organism. The system includes a sensor film having a first layer comprising a transition metal oxide or oxysalt and a second layer comprising a hydrogen-dissociative catalyst metal, the first and second layers having an inner and an outer surface wherein the inner surface of the second layer is deposited on the outer surface of the first layer, and a substrate adjacent to the outer surface of the second layer, the organism isolated on the substrate.

  12. 基于超声波的筛分系统电路设计%Screening system circuit design based on the ultrasonic

    Institute of Scientific and Technical Information of China (English)

    高同辉; 李树伟


    针对常规的振动筛分机产生会有堵塞筛孔、噪声污染大、筛分细度级别低等不足,研究设计出采用超声波传感器(换能器)产生的振动波附加整个筛网上,实现物料微小颗粒筛分的电路。给出了超声波的筛分系统硬件电路设计方案及单元等进行了详细的设计,并采用单片机从而实现了脉宽和功率的跟踪调节。通过应用到药物筛分机上实验,取得了很好的筛分效果。%Aiming to solving the disadvantage of vibrating screen classifier,such as screen blinding,serious noise pollution,low fineness level screening etc,a circuit which using the ultrasonic sensor(energy conversion device)to produce oscillation wave attached to the whole screen mesh is designed,making the micro particle of material screened.The design shows the plan and unit of the screening system hardware circuit in detail,and carries out the follow-up accommodation of pulse width and power by using the MCU.Through the experiment of applying to the medicine screen classifier,an excellent screening effect has been acquired.

  13. Screening of willow species for resistance to heavy metals: comparison of performance in a hydroponics system and field trials. (United States)

    Watson, C; Pulford, I D; Riddell-Black, D


    The aim of this study was to ascertain whether metal resistance in willow (Salix) clones grown in a hydroponics screening test correlated with data from the same clones grown independently in a field trial. If so, results from a short-term, glasshouse-based system could be extrapolated to the field, allowing rapid identification of willows suitable for planting in metal-contaminated substrates without necessitating longterm field trials. Principal Components Analysis was used to show groups of clones and to assess the relative importance of the parameters measured in both the hydroponics system and the field; including plant response factors such as increase in stem height, as well as metal concentrations in plant tissues. The clones tested fell into two distinct groups. Salix viminalis clones and the basket willow Black Maul (S. triandra) were less resistant to elevated concentrations of heavy metals than a group of hardier clones, including S. burjatica 'Germany,' S.x dasyclados, S. candida and S. spaethii. The more resistant clones produced more biomass in the glasshouse and field, and had higher metal concentrations in the wood. The less resistant clones had greater concentrations of Cu and Ni in the bark, and produced less biomass in the glasshouse and field. Significant relationships were found between the response of the same clones grown the in short-term glasshouse hydroponics system and in the field.

  14. Stereoscopic uncooled thermal imaging with autostereoscopic 3D flat-screen display in military driving enhancement systems (United States)

    Haan, H.; Münzberg, M.; Schwarzkopf, U.; de la Barré, R.; Jurk, S.; Duckstein, B.


    Thermal cameras are widely used in driver vision enhancement systems. However, in pathless terrain, driving becomes challenging without having a stereoscopic perception. Stereoscopic imaging is a well-known technique already for a long time with understood physical and physiological parameters. Recently, a commercial hype has been observed, especially in display techniques. The commercial market is already flooded with systems based on goggle-aided 3D-viewing techniques. However, their use is limited for military applications since goggles are not accepted by military users for several reasons. The proposed uncooled thermal imaging stereoscopic camera with a geometrical resolution of 640x480 pixel perfectly fits to the autostereoscopic display with a 1280x768 pixels. An eye tracker detects the position of the observer's eyes and computes the pixel positions for the left and the right eye. The pixels of the flat panel are located directly behind a slanted lenticular screen and the computed thermal images are projected into the left and the right eye of the observer. This allows a stereoscopic perception of the thermal image without any viewing aids. The complete system including camera and display is ruggedized. The paper discusses the interface and performance requirements for the thermal imager as well as for the display.

  15. Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis (United States)

    Wang, Jingbo; Liu, Rui; Liu, Baoxiu; Yang, Yan; Xie, Jun; Zhu, Naishuo


    Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in many subjects. Animal and cellular experiments finally validated that the new vaccine simultaneously improves the humoral and cellular immunity of BALB/c mice without side effects. All this results demonstrate that cordycepin could work as adjuvant to hepatitis b vaccine and systems-pharmacology analysis could be used as a new method to select adjuvants. PMID:28317886

  16. Adaptable Holders for Arc-Jet Screening Candidate Thermal Protection System Repair Materials (United States)

    Riccio, Joe; Milhoan, Jim D.


    Reusable holders have been devised for evaluating high-temperature, plasma-resistant re-entry materials, especially fabrics. Typical material samples tested support thermal-protection-system damage repair requiring evaluation prior to re-entry into terrestrial atmosphere. These tests allow evaluation of each material to withstand the most severe predicted re-entry conditions.

  17. A novel sensitive cell-based Love Wave biosensor for marine toxin detection. (United States)

    Zhang, Xi; Fang, Jiaru; Zou, Ling; Zou, Yingchang; Lang, Lang; Gao, Fan; Hu, Ning; Wang, Ping


    A novel HepG2 cell-based biosensor using Love Wave sensor was developed to implement the real-time and sensitive detection of a diarrheic shellfish poisoning (DSP) toxin, Okadaic acid (OA). Detachable Love Wave sensor unit and miniaturized 8-channel recording instrument were designed for the convenient experimental preparation and sensor response signal measurement. The Love Wave sensor, whose synchronous frequency is around 160 MHz, was fabricated with ST-cut quartz substrate. To establish a cell-based biosensor, HepG2 cells as sensing elements were cultured onto the Love Wave sensor surface, and the cell attachment process was recorded by this biosensor. Results showed this sensor could monitor the cell attachment process in real time and response signals were related to the initial cell seeding densities. Furthermore, cell-based Love Wave sensor was treated with OA toxin. This biosensor presented a good performance to various OA concentrations, with a wide linear detection range (10-100 μg/L). Based on the ultrasensitive acoustic wave platform, this cell-based biosensor will be a promising tool for real-time and convenient OA screening.

  18. Feature, Event, and Process Screening and Scenario Development for the Yucca Mountain Total System Performance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Barnard, R.; Barr, G.; Burch, P.; Freeze, G.; Rechard, R.; Schenker, A.; Swift, P.


    Scenario development has two primary purposes in the design and documentation of post-closure performance assessments in a regulatory setting. First, scenario development ensures a sufficiently comprehensive consideration of the possible future states of the system. Second, scenario development identifies the important scenarios that must be considered in quantitative analyses of the total system performance assessment (TSPA). Section 2.0 of this report describes the scenario development process. Steps in the process are described in Section 2.1, and terms introduced in this section are defined in Section 2.2. The electronic database used to document the process is described in Section 3, and Section 4 provides a summary of the current status of the YMP scenario development work. Section 5 contains acknowledgments, and Section 6 contains a list of the references cited.

  19. Real-time detection of undersea mines: a complete screening and acoustic fusion processing system (United States)

    Sacramone, Anthony; Desai, Mukund N.


    A complete mine detection/classification (D/C) system has been specified and implemented, which runs in real-time, and has been exercised on the latest available dual-frequency side-scan sonar acoustic image sets. The compete DC system is comprised of a collection of algorithms that has been developed and evolved at Draper Laboratory over the past decade. The detection process consists of image normalization, enhancement, segmentation, and feature extraction algorithms. The enhancement algorithm is a variant of a Markov Random Field based anomaly screener developed in FY-94. The feature that were extracted were those derived in FY-93. A distance constrained matching algorithm, which was developed in FY-95, is used to generate a list of high and low frequency fused tokens. The classification process involves the evaluation of a hierarchy of three multi-layer perceptron neural networks: HF, LF, and HF/LF fused. Research performed in FY-95 also concentrated on the development of several variants of information fusion with hierarchical neural networks. The 'discriminant-combining' variant of fusion was selected as part of this DC system. In addition, a classification post- processing and decision node statistic modification step, which was developed in FY-96, was included. This paper will describe the algorithm that were implemented. However, the emphasis will be on the performance results of processing the latest available side-scan imagery, comparison of single sensor vs dual-frequency sensor results, and the issues that were encountered while exercising the DC system on the new data set.

  20. A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system


    Schlecht, Ulrich; Suresh, Sundari; Xu, Weihong; Aparicio, Ana Maria; Chu, Angela; Proctor, Michael J; Davis, Ronald W.; Scharfe, Curt; St.Onge, Robert P.


    Background Copper is essential for the survival of aerobic organisms. If copper is not properly regulated in the body however, it can be extremely cytotoxic and genetic mutations that compromise copper homeostasis result in severe clinical phenotypes. Understanding how cells maintain optimal copper levels is therefore highly relevant to human health. Results We found that addition of copper (Cu) to culture medium leads to increased respiratory growth of yeast, a phenotype which we then system...

  1. Colorectal cancer screening

    Institute of Scientific and Technical Information of China (English)

    Ramona M McLoughlin; Colm A O'Morain


    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 be accommodated within individual health care systems.

  2. Screening for Pancreatic Cancer. (United States)

    Wada, Keita; Takaori, Kyoichi; Traverso, L William


    Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection.

  3. Using the pER8:GUS reporter system to screen for phytoestrogens from Caesalpinia sappan. (United States)

    Lai, Wan-Chun; Wang, Hui-Chun; Chen, Guan-Yu; Yang, Juan-Cheng; Korinek, Michal; Hsieh, Chia-Jung; Nozaki, Hiroshi; Hayashi, Ken-Ichiro; Wu, Chih-Chung; Wu, Yang-Chang; Chang, Fang-Rong


    Arabidopsis thaliana pER8:GUS, a low-cost, highly efficient, and convenient transgenic plant system, was used to assay the estrogen-like activity of 30 traditional Chinese medicines. The MeOH extract of Caesalpinia sappan exhibited significant bioactivity in this assay, and subsequent bioactivity-guided fractionation of the extract led to the isolation of one new compound, (S)-3,7-dihydroxychroman-4-one (1), and 10 known compounds. Both the plant pER8:GUS and in vitro estrogen response element reporter assays were used to evaluate the estrogenic activity of the isolated compounds, and these two systems produced comparable results. Compounds 6, 8, and 11 showed significant estrogenic activity comparable to genistein. These active compounds were determined to be nontoxic new sources of phytoestrogens. In addition, compounds 2 and 3 inhibited ERE transcription induced by 17β-estradiol. A docking model revealed that compounds 6, 8, and 11 showed high affinity to the estrogen receptor. The pER8:GUS reporter system was demonstrated to be a useful and effective technique in phytoestrogen discovery.

  4. The P1 vector system for the preparation and screening of genomic libraries. (United States)

    Shepherd, N S; Smoller, D


    In retrospect, it is remarkable how swiftly the P1 cloning system has progressed in only a few years from a novel cloning system to one now widely used for the production of recombinant libraries and the building of physical maps. As the libraries become larger, better characterized and more widely distributed, we certainly will see a blossoming of research articles and techniques based on the use of P1 recombinant clones. Specifically, we can look forward to scanning P1 clones for expressed sequences (N. Sternberg, personal communication), routine retrofitting of P1 clones with a combination of transposon and P1 transduction techniques (3), the random or loxP-directed (68,69) insertion of P1 clones into host genomes and the subsequent production of transgenic animals (63), a further use of P1 clones in the building of contigs and physical maps, an a higher in vitro cloning efficiency due to the purification of the P1 pacase proteins used during in vitro packaging (70). In summary, P1 bacteriophage cloning is favorably impacting research today and will continue to fill an important niche as a genomic cloning system.

  5. Very low cost stand-off suicide bomber detection system using human gait analysis to screen potential bomb carrying individuals (United States)

    Greneker, Gene, III


    Individuals who carry bombs on their bodies and detonate those bombs in public places are a security problem. There is belief that suicide bombings currently used in the mid-east may spread to the United States if the organized terrorist groups operating in the United States are not identified and the cell members arrested. While bombs in vehicles are the primary method currently used to spread terror in Iraq, U. S. warfighters are starting to face suicide bombers. This may become more of the situation if a stand-off detection capability is developed for the vehicle bomb case. This paper presents a concept, that if developed and commercialized, could provide an inexpensive suicide bomber screening system that could be used to screen individuals approaching a checkpoint while the individual is still 500 to 1,000 feet from the checkpoint. The proposed system measures both the radar cross-section of the individual and the radar derived gait characteristics that are associated with individuals carrying a bomb on their body. GTRI researchers propose to use human gait characteristics, as detected by radar, to determine if a human subject who is carrying no visible load on the body is actually carrying a concealed load under their clothes. The use of radar gait as a metric for the detection (as opposed to a video system) of a suicide bomber is being proposed because detection of gait characteristics are thought to be less sensitive to where the bomb is located on the body, lighting conditions, and the fact that the legs may be shrouded in a robe. The detection of a bomb using radar gait analysis may also prove to be less sensitive to changing tactics regarding where the bomb is placed on the body. An inert suicide bomb vest was constructed using water pipes to simulate the explosive devices. Wiring was added to simulated detonators. The vest weighs approximately 35 pounds. Radar data was taken on the volunteer subject wearing the vest that simulated the suicide bomb. This

  6. Phantom-less QCT BMD system as screening tool for osteoporosis without additional radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Dirk K., E-mail: [Philips GmbH, Healthcare Division, Luebeckertordamm 5, 20099 Hamburg (Germany); Kutscherenko, Alex; Bartel, Hans [Kaiserswerther Diakonie, Florence-Nightingale Hospital, Kreuzbergstrasse 79, 40489 Duesseldorf (Germany); Vlassenbroek, Alain [Philips Healthcare, Bruxelles, Rue des Deux Gares 80, 1070 Bruxelles (Belgium); Ourednicek, Petr [Philips Czech Republic, Safrankova 1, 15500 Prague 5 (Czech Republic); Erckenbrecht, Joachim [Kaiserswerther Diakonie, Florence-Nightingale Hospital, Kreuzbergstrasse 79, 40489 Duesseldorf (Germany)


    Purpose: Phantom-less bone mineral density (PLBMD) systems are easily integrated into the CT workflow for non-dedicated Quantitative CT (QCT) BMD measurements in thoracic and abdominal scans. This in vivo retrospective study aims to determine accuracy and precision of the PLBMD option located on the Extended Brilliance Workspace (Philips Medical Systems, Cleveland, OH, US) from both cross-sectional and longitudinal image data. Materials and methods: The cross-sectional comparison with phantom-based QCT BMD was performed for 82 patients (61 female, 21 male) with a mean age of (63.0 {+-} 11.8 SD) years on 197 vertebrae. This was followed by an interobserver variability analysis on 71 vertebrae. The longitudinal PLBMD study was carried out on 45 vertebrae from 10 patients (5 female, 5 male) with a mean age of (64.4 {+-} 11.5 SD) years. They were re-scanned with standardized scan and contrast-injection protocols within a mean and median of (33 {+-} 41 SD) and 8 days, respectively. All CT scans were acquired on an Mx8000 Quad (Philips) at Florence-Nightingale Hospital, Kaiserswerth, Germany, in a spiral acquisition mode. Results: A negligible BMD bias of -0.9 mg/cm{sup 3} for the PLBMD option was observed with respect to phantom-based QCT BMD. Applying CT number matching of muscle and fat ROIs, the analysis of cross-sectional interobserver and of longitudinal variability yielded precision values of 3.1 mg/cm{sup 3} (CV% = 4.0) and 4.2 mg/cm{sup 3} (CV% = 5.3), respectively. Conclusion: Although the precision is inferior to phantom-based BMD systems, PLBMD is a robust clinical utility for the detection of lowered BMD in a large patient population. This can be achieved without additional radiation exposure from non-contrasted CT scans, to perform an ancillary diagnosis of osteopenia or osteoporosis.

  7. Screening of hepatocyte proteins binding to F protein of hepatitis C virus by yeast two-hybrid system

    Institute of Scientific and Technical Information of China (English)

    Yan-Ping Huang; Xue-Song Gao; Dong Ji; Shu-Mei Lin; Qing Shao; Jun Cheng; Shu-Lin Zhang; Lin Wang; Jiang Guo; Yan Liu; Yuan Yang; Li-Ying Zhang; Gui-Qin Bai


    AIM: To investigate the biological function of F protein by yeast two-hybrid system.METHODS: We constructed F protein bait plasmid by cloning the gene of F protein into pGBKT7, then recombinant plasmid DNA was transformed into yeast AH109 (a type). The transformed yeast AH109 was mated with yeast Y187 (α type) containing liver cDNA library plasmid in 2×YPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/-Trp-Leu-HisAde) containing X-α-gal for selection and screening.After extracting and sequencing plasmids from positive (blue) colonies, we underwent sequence analysis by bioinformatics.RESULTS: Thirty-six colonies were selected and sequenced.Among them, 11 colonies were zymogen granule protein,5 colonies were zinc finger protein, 4 colonies were zinc-α-2-glycoprotein, 1 colony was sialyltransferase, 1 colony was complement control protein factor Ⅰ, 1 colony was vitronectin, and 2 colonies were new genes with unknown function.CONCLUSION: The yeast two-hybrid system is an effective method for identifying hepatocyte proteins interacting with F protein of hepatitis C virus. F protein may bind to different proteins.

  8. Detection of Total Phenol in Green and Black Teas by Flow Injection System and Unmodified Screen Printed Electrode

    Directory of Open Access Journals (Sweden)

    Ivanildo Luiz de Mattos


    Full Text Available A flow injection system using an unmodified gold screen-printed electrode was employed for total phenol determination in black and green teas. In order to avoid passivation of the electrode surface due to the redox reaction, preoxidation of the sample was realized by hexacyanoferrate(III followed by addition of an EDTA solution. The complex formed in the presence of EDTA minimizes or avoids polymerization of the oxidized phenols. The previously filtered tea sample and hexacyanoferrate(III reagent were introduced simultaneously into two-carrier streams producing two reproducible zones. At confluence point, the pre-oxidation of the phenolic compounds occurs while this zone flows through the coiled reactor and receives the EDTA solution before phenol detection. The consumption of ferricyanide was monitorized at 360 mV versus Ag/AgCl and reflected the total amount of phenolic compounds present in the sample. Results were reported as gallic acid equivalents (GAEs. The proposed system is robust, versatile, environmentally-friendly (since the reactive is used only in the presence of the sample, and allows the analysis of about 35–40 samples per hour with detection limit = 1 mg/L without the necessity for surface cleaning after each measurement. Precise results are in agreement with those obtained by the Folin-Ciocalteu method.

  9. M2 priority screening system for near-term activities: Project documentation. Final report December 11, 1992--May 31, 1994

    Energy Technology Data Exchange (ETDEWEB)



    From May through August, 1993, the M-2 Group within M Division at LANL conducted with the support of the LANL Integration and Coordination Office (ICO) and Applied Decision Analysis, Inc. (ADA), whose purpose was to develop a system for setting priorities among activities. This phase of the project concentrated on prioritizing near-tenn activities (i.e., activities that must be conducted in the next six months) necessary for setting up this new group. Potential future project phases will concentrate on developing a tool for setting priorities and developing annual budgets for the group`s operations. The priority screening system designed to address the near-term problem was developed, applied in a series of meeting with the group managers, and used as an aid in the assignment of tasks to group members. The model was intended and used as a practical tool for documenting and explaining decisions about near-term priorities, and not as a substitute for M-2 management judgment and decision-making processes.

  10. Standard Practice for Laboratory Screening of Metallic Containment Materials for Use With Liquids in Solar Heating and Cooling Systems

    CERN Document Server

    American Society for Testing and Materials. Philadelphia


    1.1 This practice covers several laboratory test procedures for evaluating corrosion performance of metallic containment materials under conditions similar to those that may occur in solar heating and cooling systems. All test results relate to the performance of the metallic containment material only as a part of a metal/fluid pair. Performance in these laboratory test procedures, taken by itself, does not necessarily constitute an adequate basis for acceptance or rejection of a particular metal/fluid pair in solar heating and cooling systems, either in general or in a particular design. This practice is not intended to preclude the use of other screening tests, particularly when those tests are designed to more closely simulate field service conditions. 1.2 This practice describes apparatus and procedures for several tests, any one or more of which may be used to evaluate the deterioration of the metallic containment material in a metal/fluid pair. The procedures are designed to permit simulation, heating...

  11. SNP high-throughput screening in grapevine using the SNPlex™ genotyping system

    Directory of Open Access Journals (Sweden)

    Velasco Riccardo


    Full Text Available Abstract Background Until recently, only a small number of low- and mid-throughput methods have been used for single nucleotide polymorphism (SNP discovery and genotyping in grapevine (Vitis vinifera L.. However, following completion of the sequence of the highly heterozygous genome of Pinot Noir, it has been possible to identify millions of electronic SNPs (eSNPs thus providing a valuable source for high-throughput genotyping methods. Results Herein we report the first application of the SNPlex™ genotyping system in grapevine aiming at the anchoring of an eukaryotic genome. This approach combines robust SNP detection with automated assay readout and data analysis. 813 candidate eSNPs were developed from non-repetitive contigs of the assembled genome of Pinot Noir and tested in 90 progeny of Syrah × Pinot Noir cross. 563 new SNP-based markers were obtained and mapped. The efficiency rate of 69% was enhanced to 80% when multiple displacement amplification (MDA methods were used for preparation of genomic DNA for the SNPlex assay. Conclusion Unlike other SNP genotyping methods used to investigate thousands of SNPs in a few genotypes, or a few SNPs in around a thousand genotypes, the SNPlex genotyping system represents a good compromise to investigate several hundred SNPs in a hundred or more samples simultaneously. Therefore, the use of the SNPlex assay, coupled with whole genome amplification (WGA, is a good solution for future applications in well-equipped laboratories.

  12. Rapid, computer vision-enabled murine screening system identifies neuropharmacological potential of two new mechanisms

    Directory of Open Access Journals (Sweden)

    Steven L Roberds


    Full Text Available The lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology. In vivo behavioral assays are more predictive of activity in human disorders, but such assays are often highly resource-intensive. Here we describe the successful application of a computer vision-enabled system to identify potential neuropharmacological activity of two new mechanisms. The analytical system was trained using multiple drugs that are used clinically to treat depression, schizophrenia, anxiety, and other psychiatric or behavioral disorders. During blinded testing the PDE10 inhibitor TP-10 produced a signature of activity suggesting potential antipsychotic activity. This finding is consistent with TP-10’s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs. The CK1ε inhibitor PF-670462 produced a signature consistent with anxiolytic activity and, at the highest dose tested, behavioral effects similar to that of opiate analgesics. Neither TP-10 nor PF-670462 was included in the training set. Thus, computer vision-based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms.

  13. Carbon dioxide removal system for closed loop atmosphere revitalization, candidate sorbents screening and test results (United States)

    Mattox, E. M.; Knox, J. C.; Bardot, D. M.


    Due to the difficulty and expense it costs to resupply manned-spacecraft habitats, a goal is to create a closed loop atmosphere revitalization system, in which precious commodities such as oxygen, carbon dioxide, and water are continuously recycled. Our aim is to test other sorbents for their capacity for future spacecraft missions, such as on the Orion spacecraft, or possibly lunar or Mars mission habitats to see if they would be better than the zeolite sorbents on the 4-bed molecular sieve. Some of the materials being tested are currently used for other industry applications. Studying these sorbents for their specific spacecraft application is different from that for applications on earth because in space, there are certain power, mass, and volume limitations that are not as critical on Earth. In manned-spaceflight missions, the sorbents are exposed to a much lower volume fraction of CO2 (0.6% volume CO2) than on Earth. LiLSX was tested for its CO2 capacity in an atmosphere like that of the ISS. Breakthrough tests were run to establish the capacities of these materials at a partial pressure of CO2 that is seen on the ISS. This paper discusses experimental results from benchmark materials, such as results previously obtained from tests on Grade 522, and the forementioned candidate materials for the Carbon Dioxide Removal Assembly (CDRA) system.

  14. Quadruple screen test (United States)

    Quad screen; Multiple marker screening; AFP plus; Triple screen test; AFP maternal; MSAFP; 4-marker screen; Down syndrome - quadruple; Trisomy 21 - quadruple; Turner syndrome - quadruple; Spina bifida - ...

  15. Hypertension screening (United States)

    Foulke, J. M.


    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.

  16. Airport Screening (United States)

    ... cannot become radioactive from this procedure. However, some photographic film may need to be hand-screened because ... level. An American National Standards Institute/Health Physics Society industry standard states that the maxi- mum allowable ...

  17. Toxicology screen (United States)

    Toxicology screening is most often done using a blood or urine sample. However, it may be done soon after the person swallowed the medication, using stomach contents taken through gastric lavage (stomach pumping) or after vomiting.

  18. Screening of Toll-like receptors expression in multiple system atrophy brains

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Winge, Kristian; Agander, Tina Klitmøller


    their deregulation may play a role in neurodegeneration. Multiple system atrophy (MSA) together with Parkinson's disease belongs to a diverse group of neurodegenerative conditions termed α-synucleinopathies. MSA is a fatal late onset disease characterized by the presence of α-synuclein positive glial cytoplasmic...... inclusions in oligodendrocytes. α-Synuclein can act as a danger-associated molecular pattern and alter TLR expression thereby activating inflammatory responses in the brain. In this study, using real-time PCR, we assessed the expression of TLRs (TLR1-10) in selected areas of MSA brains (substantia nigra......, striatum, cerebral cortex, and nucleus dentatus) in comparison with normal controls. We show evidence for increased levels of mRNA-encoding hTLR-3, hTLR-4, and hTLR-5 in substantia nigra, striatum, cerebral cortex, and nucleus dentatus from MSA brains versus normal controls. The levels of expression of h...

  19. Emerging interface dipole versus screening effect in copolymer/metal nano-layered systems (United States)

    Torrisi, V.; Ruffino, F.; Liscio, A.; Grimaldi, M. G.; Marletta, G.


    Despite to the importance on the charge carrier injection and transport at organic/metal interface, there is yet an incomplete estimation of the various contribution to the overall dipole. This work shows how the mapping of the surface potential performed by Kelvin Probe Force Microscopy (KPFM) allows the direct observation of the interface dipole within an organic/metal multilayered structure. Moreover, we show how the sub-surface sensitivity of the KPFM depends on the thickness and surface coverage of the metallic layer. This paper proposes a way to control the surface potential of the exposed layer of an hybrid layered system by controlling the interface dipole at the organic/metal interface as a function of the nanometer scale thickness and the surface coverage of the metallic layer. We obtained a layered system constituted by repeated sequence of a copolymer film, poly(n-butylacrylate)-b-polyacrilic acid, and Au layer. We compared the results obtained by means of scanning probe microscopy technique with the results of the KPFM technique, that allows us to obtain high-contrast images of the underlying layer of copolymer behind a typical threshold, on the nanoscale, of the thickness of the metal layer. We considered the effect of the morphology of the gold layer on the covered area at different thicknesses by using the scanning electron microscopy technique. This finding represents a step forward towards the using of dynamic atomic force microscopy based characterization to explore the electrical properties of the sub-surface states of layered nanohybrid, that is a critical point for nanohybrid applications in sensors and energy storage devices.

  20. 基于PLC和触摸屏的冷冻油回收控制系统%Frozen Oil Recovery Control System Based on PLC and Touch Screen

    Institute of Scientific and Technical Information of China (English)



    本文结合实际开发项目,分析了基于PLC和触摸屏的冷冻油回收温度控制系统。%Combined with the actual development of a project, this paper analyzes the implementation of frozen oil recovery temperature control system based on PLC and touch screen.

  1. Detection of Symptoms of Prevalent Mental Health Disorders of Childhood with the Parent Form of the Behavioral and Emotional Screening System (United States)

    Dowdy, Erin; Kamphaus, Randy W.; Abdou, Annmary S.; Twyford, Jennifer M.


    This study examined the criterion-related validity of score inferences from the "Behavioral and Emotional Screening System Parent Form" (BESS Parent) for the detection of symptoms of prevalent mental health disorders of childhood. The BESS Parent was administered to 99 parents of first- through fifth-grade students, along with the…

  2. Reasons for accepting or declining Down syndrome screening in Dutch prospective mothers within the context of national policy and healthcare system characteristics : a qualitative study

    NARCIS (Netherlands)

    Crombag, Neeltje M T H; Boeije, Hennie; Iedema-Kuiper, Rita; Schielen, Peter C J I; Visser, Gerard H A; Bensing, Jozien M


    BACKGROUND: Uptake rates for Down syndrome screening in the Netherlands are low compared to other European countries. To investigate the low uptake, we explored women's reasons for participation and possible influences of national healthcare system characteristics. Dutch prenatal care is characteris

  3. Screening microalgae isolated from urban storm- and wastewater systems as feedstock for biofuel

    Directory of Open Access Journals (Sweden)

    Rebecca Massimi


    Full Text Available Exploiting microalgae as feedstock for biofuel production is a growing field of research and application, but there remain challenges related to industrial viability and economic sustainability. A solution to the water requirements of industrial-scale production is the use of wastewater as a growth medium. Considering the variable quality and contaminant loads of wastewater, algal feedstock would need to have broad tolerance and resilience to fluctuating wastewater conditions during growth. As a first step in targeting strains for growth in wastewater, our study isolated microalgae from wastewater habitats, including urban stormwater-ponds and a municipal wastewater-treatment system, to assess growth, fatty acids and metal tolerance under standardized conditions. Stormwater ponds in particular have widely fluctuating conditions and metal loads, so microalgae from this type of environment may have desirable traits for growth in wastewater. Forty-three algal strains were isolated in total, including several strains from natural habitats. All strains, with the exception of one cyanobacterial strain, are members of the Chlorophyta, including several taxa commonly targeted for biofuel production. Isolates were identified using taxonomic and 18S rRNA sequence methods, and the fastest growing strains with ideal fatty acid profiles for biodiesel production included Scenedesmus and Desmodesmus species (Growth rate (d−1 > 1. All isolates in a small, but diverse taxonomic group of test-strains were tolerant of copper at wastewater-relevant concentrations. Overall, more than half of the isolated strains, particularly those from stormwater ponds, show promise as candidates for biofuel feedstock.

  4. Screening microalgae isolated from urban storm- and wastewater systems as feedstock for biofuel. (United States)

    Massimi, Rebecca; Kirkwood, Andrea E


    Exploiting microalgae as feedstock for biofuel production is a growing field of research and application, but there remain challenges related to industrial viability and economic sustainability. A solution to the water requirements of industrial-scale production is the use of wastewater as a growth medium. Considering the variable quality and contaminant loads of wastewater, algal feedstock would need to have broad tolerance and resilience to fluctuating wastewater conditions during growth. As a first step in targeting strains for growth in wastewater, our study isolated microalgae from wastewater habitats, including urban stormwater-ponds and a municipal wastewater-treatment system, to assess growth, fatty acids and metal tolerance under standardized conditions. Stormwater ponds in particular have widely fluctuating conditions and metal loads, so microalgae from this type of environment may have desirable traits for growth in wastewater. Forty-three algal strains were isolated in total, including several strains from natural habitats. All strains, with the exception of one cyanobacterial strain, are members of the Chlorophyta, including several taxa commonly targeted for biofuel production. Isolates were identified using taxonomic and 18S rRNA sequence methods, and the fastest growing strains with ideal fatty acid profiles for biodiesel production included Scenedesmus and Desmodesmus species (Growth rate (d(-1)) > 1). All isolates in a small, but diverse taxonomic group of test-strains were tolerant of copper at wastewater-relevant concentrations. Overall, more than half of the isolated strains, particularly those from stormwater ponds, show promise as candidates for biofuel feedstock.

  5. 用于 CCD 立靶的双光幕触发系统研究%Dual-screen triggering system for CCD vertical target

    Institute of Scientific and Technical Information of China (English)

    董涛; 华灯鑫; 李言; 倪晋平


    On the request of the stable and reliable trigger required in charge-coupled device (CCD) vertical target measurement system in the condition of firing range ,a dual-screen trig-ging system was presented .The trigging detecting screen was composed of lens-type screen detector ,working with the high-intensity LED slow-scattering light ,and the velocity-measur-ing system consists of two identical screen detectors working together with chronometer ,and then it judged whether the projectile passing through the screen was real based on the measured velocity and whether to output the trigging signal or not .The time for projectile flying from impacting screen to detecting screen was achieved according to the velocity value V and the dis-tance between impacting screen and detecting screen ,and then the triggering signal was output while the projectile was approaching to CCD detecting screen .The proposed scheme can im-prove the stability of the system ,prevent the system from being interfered by unreal targets , and can transmit trigging signal at the precise time to follow-up CCD image-acquisition system . It has been proved by experiment that the speed measurement error of the designed dual-screen triggering system is not more than 0 .4% ,fully meeting the demand of the stable and reliable trigger requirement of the CCD vertical target .%针对靶场测试当中CCD立靶测量系统需要稳定可靠触发的需求,提出一种双光幕触发系统。采用镜头式光幕探测器配合高亮度L ED慢散射光源组成触发探测光幕,利用2个同样的光幕探测器配合测时装置组成区截测速系统,根据测得的速度值判定飞越探测光幕的目标是否为真实弹丸,并决定是否输出触发信号。根据速度值V 和触发光幕至CCD探测光幕的距离计算出弹丸飞越至探测光幕的时间,然后在弹丸飞越将近至探测光幕的时刻输出触发信号。该方案不但可以提高系统的稳定性,避免非真

  6. Development of Touch Screen Voting and Display System Based on Authorware%基于Authorware的触摸屏投票展示系统

    Institute of Scientific and Technical Information of China (English)



    触摸屏作为一种最新的电脑输入设备,是目前最简单、方便、自然的人机交互方式,越来越多的单位开始使用触摸屏。采用Authorware软件开发系统的一套触摸屏投票展示系统,具有视频展示和投票两大功能。%Touch screen as a kind of the latest computer input device,is the most simple,convenient and natural man-machine interactive way,so more and more units started off with touch screen.This paper introduces how to use Authorware software to develop a special touch screen voting demonstration system.

  7. Nationwide survey of glandular tissue doses for the establishment of a breast cancer screening system using mammography. Analysis of technical parameters affecting the glandular tissue dose

    Energy Technology Data Exchange (ETDEWEB)

    Higashida, Yoshiharu [Kyushu Univ., Fukuoka (Japan). School of Health Sciences; Hagiwara, Akira; Asahara, Masaki [and others


    The effects of technical parameters, such as screen-film combinations, antiscatter grids, processing conditions and X-ray beam qualities, on the average glandular tissue dose of radiation were analyzed under two exposure conditions: The standard radiographic condition for an RMI 156 phantom at each facility (Standard Radiographic Condition). The radiographic condition needed to obtain a radiographic density of 1.20 to 1.40 with an RMI 156 phantom (Canonical Radiographic Condition). The analysis included 208 dose measurements at 104 facilities. The results showed that the average glandular tissue dose depends strongly on the grid types and screen-film combinations used. There were also significant differences in radiographic density between the Standard Radiographic Condition and the Canonical Radiographic Condition. This analysis of the technical parameters affecting the glandular tissue dose will be useful in establishing a standardized mammographic breast cancer screening system. (author)

  8. Cell-based technologies for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mônica Santoro Haddad

    Full Text Available ABSTRACT Huntington's disease (HD is a fatal genetic disorder, which causes the progressive breakdown of neurons in the human brain. HD deteriorates human physical and mental abilities over time and has no cure. Stem cell-based technologies are promising novel treatments, and in HD, they aim to replace lost neurons and/or to prevent neural cell death. Herein we discuss the use of human fetal tissue (hFT, neural stem cells (NSCs of hFT origin or embryonic stem cells (ESCs and induced pluripotent stem cells (IPSCs, in clinical and pre-clinical studies. The in vivo use of mesenchymal stem cells (MSCs, which are derived from non-neural tissues, will also be discussed. All these studies prove the potential of stem cells for transplantation therapy in HD, demonstrating cell grafting and the ability to differentiate into mature neurons, resulting in behavioral improvements. We claim that there are still many problems to overcome before these technologies become available for HD patient treatment, such as: a safety regarding the use of NSCs and pluripotent stem cells, which are potentially teratogenic; b safety regarding the transplantation procedure itself, which represents a risk and needs to be better studied; and finally c technical and ethical issues regarding cells of fetal and embryonic origin.

  9. Stem Cell-Based Gene Therapy. (United States)

    Bagnis; Mannoni


    Many researchers and clinicians wonder if gene therapy remains a way to treat genetic or acquired life-threatening diseases. For the last few years, many experimental, pre-clinical, and clinical data have been published showing that it is possible to transfer with relatively high efficiency new genetic information (transgene) in many cells or tissues including both hematopoietic progenitor cells and differentiated cells. Based on experimental works, addition of the normal gene to cells with deletions, mutations, or alterations of the corresponding endogenous one has been shown to reverse the phenotype and to restore (in some case) the functional defect. In spite of very attractive preliminary results, however, suggesting the feasibility and safety of this process, therapeutically efficient gene transfer and expression in targeted cells or tissues must be proven. In this review, we will focus primarily on the attempts to use gene transfer in hematopoietic stem cells as a model for more general genetic manipulations of stem cells. Hematopoietic stem cells are included in a subset of bone marrow, cord blood, or peripheral blood cells identified by the expression of the CD34 antigen on their membrane.

  10. Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms. (United States)

    Clausell-Tormos, Jenifer; Lieber, Diana; Baret, Jean-Christophe; El-Harrak, Abdeslam; Miller, Oliver J; Frenz, Lucas; Blouwolff, Joshua; Humphry, Katherine J; Köster, Sarah; Duan, Honey; Holtze, Christian; Weitz, David A; Griffiths, Andrew D; Merten, Christoph A


    High-throughput, cell-based assays require small sample volumes to reduce assay costs and to allow for rapid sample manipulation. However, further miniaturization of conventional microtiter plate technology is problematic due to evaporation and capillary action. To overcome these limitations, we describe droplet-based microfluidic platforms in which cells are grown in aqueous microcompartments separated by an inert perfluorocarbon carrier oil. Synthesis of biocompatible surfactants and identification of gas-permeable storage systems allowed human cells, and even a multicellular organism (C. elegans), to survive and proliferate within the microcompartments for several days. Microcompartments containing single cells could be reinjected into a microfluidic device after incubation to measure expression of a reporter gene. This should open the way for high-throughput, cell-based screening that can use >1000-fold smaller assay volumes and has approximately 500x higher throughput than conventional microtiter plate assays.

  11. HCC screening; HCC-Screening

    Energy Technology Data Exchange (ETDEWEB)

    Albrecht, T. [Charite-Unversitaetsmedizin,Freie Universitaet und Humboldt-Universitaet zu Berlin, Klinik und Hochschulambulanz fuer Radiologie und Nuklearmedizin,Campus Benjamin Franklin, Berlin (Germany)


    Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed tumour diseases throughout the world. In the vast majority of cases those affected are high-risk patients with chronic viral hepatitis and/or liver cirrhosis, which means there is a clearly identifiable target group for HCC screening. With resection, transplantation, and interventional procedures for local ablation, following early diagnosis curative treatment options are available with which 5-year survival rates of over 60% can be reached. Such early diagnosis is a reality only in a minority of patients, however, and in the majority of cases the disease is already in an advanced stage at diagnosis. One of the objects of HCC screening is diagnosis in an early stage when curative treatment is still possible. Precisely this is achieved by screening, so that the proportion of patients treated with curative intent is decisively higher. There is not yet any clear evidence as to whether this leads to a lowering of the mortality of HCC. As lower mortality is the decisive indicator of success for a screening programme the benefit of HCC screening has so far been neither documented nor refuted. Nonetheless, in large regions of the world it is the practice for high-risk patients to undergo HCC screening in the form of twice-yearly ultrasound examination and determination of AFP. (orig.) [German] Das hepatozellulaere Karzinom (HCC) ist eine der weltweit haeufigsten Tumorerkrankungen. Es tritt in der grossen Mehrzahl der Faelle bei Hochrisikopatienten mit chronischer Virushepatitis bzw. Leberzirrhose auf, woraus sich eine klar identifizierbare Zielgruppe fuer das HCC-Screening ergibt. Mit der Resektion, der Transplantation und interventionellen lokal ablativen Verfahren stehen bei rechtzeitiger Diagnosestellung kurative Therapieoptionen zur Verfuegung, die 5-Jahres-Ueberlebensraten von >60% erreichen. Diese rechtzeitige Diagnosestellung erfolgt jedoch nur bei einer Minderzahl der Patienten, waehrend die

  12. High throughput cell-based assay for identification of glycolate oxidase inhibitors as a potential treatment for Primary Hyperoxaluria Type 1 (United States)

    Wang, Mengqiao; Xu, Miao; Long, Yan; Fargue, Sonia; Southall, Noel; Hu, Xin; McKew, John C.; Danpure, Christopher J.; Zheng, Wei


    Glycolate oxidase (GO) and alanine:glyoxylate aminotransferase (AGT) are both involved in the peroxisomal glyoxylate pathway. Deficiency in AGT function causes the accumulation of intracellular oxalate and the primary hyperoxaluria type 1 (PH1). AGT enhancers or GO inhibitors may restore the abnormal peroxisomal glyoxylate pathway in PH1 patients. With stably transformed cells which mimic the glyoxylate metabolic pathway, we developed an indirect glycolate cytotoxicity assay in a 1,536-well plate format for high throughput screening. This assay can be used to identify compounds that reduce indirect glycolate-induced cytotoxicity by either enhancing AGT activity or inhibiting GO. A pilot screen of 4,096 known compounds identified two membrane permeable GO inhibitors: dichromate salt and colistimethate. We also developed a GO enzyme assay using the hydrogen peroxide-Amplex red reporter system. The IC50 values of potassium dichromate, sodium dichromate, and colistimethate sodium were 0.096, 0.108, and 2.3 μM in the GO enzyme assay, respectively. Further enzyme kinetic study revealed that both types of compounds inhibit GO activity by the mixed linear inhibition. Our results demonstrate that the cell-based assay and GO enzyme assay developed in this study are useful for further screening of large compound libraries for drug development to treat PH1. PMID:27670739

  13. Evaluation of Complexation Ability Using a Sensor Electrode Chip Equipped with a Wireless Screening System

    Directory of Open Access Journals (Sweden)

    Takaaki Isoda


    Full Text Available We fabricated an electrode chip with a structure coated by an insulation layer that contains dispersed SiO2 adsorbent particles modified by an amino-group on a source-drain electrode. Voltage changes caused by chelate molecule adsorption onto electrode surfaces and by specific cation interactions were investigated. The detection of specific cations without the presence of chelate molecules on the free electrode was also examined. By comparing both sets of results the complexation ability of the studied chelate molecules onto the electrode was evaluated. Five pairs of source-drain electrodes (×8 arrays were fabricated on a glass substrate of 20 × 30 mm in size. The individual Au/Cr (1.0/0.1 μm thickness electrodes had widths of 50 μm and an inter-electrode interval of 100 μm. The fabricated source-drain electrodes were further coated with an insulation layer comprising a porous SiO2 particle modified amino-group to adsorb the chelate molecules. The electrode chip was equipped with a handy-type sensor signal analyzer that was mounted on an amplifier circuit using a MinishipTM or a system in a packaged LSI device. For electrode surfaces containing different adsorbed chelate molecules an increase in the sensor voltage depended on a combination of host-guest reactions and generally decreased in the following order: 5,10,15,20-tetrakis(N-methylpyridinium-4-yl-21H,23H-porphine, tetrakis(p-toluenesulfonate (TMPyP as a Cu2+ chelator and Cu2+ > 2-nitroso-5-[N-n-propyl-N-(3-sulfopropylamino]phenol (nitroso-PSAP as an Fe2+ chelator and Fe2+ > 4,7-diphenyl-1,10-phenanthrolinedisulfonic acid, disodium salt (BPDSA as an Fe2+ chelator and Fe2+ > 3-[3-(2,4-dimethylphenylcarbamoyl-2-hydroxynaphthalene-1-yl-azo]-4-hydroxybenzenesulfonic acid, sodium salt (XB-1 as a Mg2+ chelator

  14. Use of cryopreserved cell aliquots in the high-throughput screening of small interfering RNA libraries. (United States)

    Swearingen, Elissa A; Fajardo, Flordeliza; Wang, Xiangyun; Watson, J E Vivienne; Quon, Kim C; Kassner, Paul D


    Screening small interfering RNA (siRNA) libraries holds the potential to elucidate gene function as well as discover new targets for the therapeutic treatment of disease. Since the inception of siRNA as a discovery tool, there have been progressive improvements in siRNA design algorithms, the transfection reagents used to deliver them, and the assay formats used to monitor phenotypic changes. These changes have helped to improve the quality of the data emerging from siRNA screens. One variable that introduces inconsistency into high-throughput screening (HTS) of siRNA libraries is the state of the cells used in the assays. Multiple factors can contribute to differences in transfection efficiency as well as the basic cell biology, which can lead to differences in the genes identified in siRNA screens. The authors have developed a system using frozen cell aliquots to use in siRNA HTS, so that a major source of variability introduced into cell-based screens can be standardized. In addition, by transiently transfecting plasmids into cell lines and then freezing these cells down to use in siRNA transfection experiments, they have used this same technology to create new cell lines. This process of using aliquots of frozen cells is logistically advantageous in an HTS setting, as it reduces the time spent maintaining cell lines, as well as reducing possible downtime in screening due to lack of cells or poor cell health.

  15. Enhanced epidemic intelligence using a web-based screening system during the 2010 FIFA World Cup in South Africa. (United States)

    Mantero, J; Szegedi, E; Payne Hallstrom, L; Lenglet, A; Depoortere, E; Kaic, B; Blumberg, L; Linge, J P; Coulombier, D


    The 2010 FIFA World Cup took place in South Africa between 11 June and 11 July 2010. The European Centre for Disease Prevention and Control (ECDC), in collaboration with the hosting authorities, carried out enhanced epidemic intelligence activities from 7 June to 16 July 2010 for timely detection and monitoring of signals of public health events with a potential to pose a risk to participants and visitors. We adapted ECDC’s routine epidemic intelligence process to targeted event-based surveillance of official and unofficial online information sources. A set of three specifically adapted alerts in the web-based screening system MedISys were set up: potential public health events in South Africa, those occurring in the participating countries and those in the rest of the world. Results were shared with national and international public health partners through daily bulletins. According to pre-established ECDC criteria for the World Cup, 21 events of potential public health relevance were identified at local and international level. Although none of the events detected were evaluated as posing a serious risk for the World Cup, we consider that the investment in targeted event-based surveillance activities during the tournament was relevant as it facilitated real-time detection and assessment of potential threats. An additional benefit was early communication of relevant information to public health partners.

  16. The application of the Escherichia coli giant spheroplast for drug screening with automated planar patch clamp system

    Directory of Open Access Journals (Sweden)

    Kyoko Kikuchi


    Full Text Available Kv2.1, the voltage-gated ion channel, is ubiquitously expressed in variety of tissues and dysfunction of this ion channel is responsible for multiple diseases. Electrophysiological properties of ion channels are so far characterized with eukaryotic cells using the manual patch clamp which requires skilful operators and expensive equipments. In this research, we created a simple and sensitive drug screen method using bacterial giant spheroplasts and the automated patch clamp which does not require special skills. We expressed a eukaryotic voltage-gated ion channel Kv2.1 in Escherichia coli using prokaryotic codon, and prepared giant spheroplasts large enough for the patch clamp. Human Kv2.1 currents were successfully recorded from giant spheroplasts with the automated system, and Kv2.1-expressed E. coli spheroplasts could steadily reacted to the dose–response assay with TEA and 4-AP. Collectively, our results indicate for the first time that the bacterial giant spheroplast can be applied for practical pharmaceutical assay using the automated patch clamp.

  17. Barriers to screening mammography. (United States)

    Sarma, Elizabeth A


    Breast cancer (BRCA) is the second most commonly diagnosed cancer among women in the USA, and mammography is an effective means for the early detection of BRCA. Identifying the barriers to screening mammography can inform research, policy and practice aiming to increase mammography adherence. A literature review was conducted to determine common barriers to screening mammography adherence. PsycINFO and PubMed databases were searched to identify studies published between 2000 and 2012 that examined barriers associated with reduced mammography adherence. Three thematic groups of barriers, based on social ecology, were identified from the literature: healthcare system-level, social and individual-level barriers. Researchers must consider screening behaviour in context and, therefore, should simultaneously consider each level of barriers when attempting to understand screening behaviour and create interventions to increase mammography adherence.

  18. Quantitative comparison between microfluidic and microtiter plate formats for cell-based assays. (United States)

    Yin, Huabing; Pattrick, Nicola; Zhang, Xunli; Klauke, Norbert; Cordingley, Hayley C; Haswell, Steven J; Cooper, Jonathan M


    In this paper, we compare a quantitative cell-based assay measuring the intracellular Ca2+ response to the agonist uridine 5'-triphosphate in Chinese hamster ovary cells, in both microfluidic and microtiter formats. The study demonstrates that, under appropriate hydrodynamic conditions, there is an excellent agreement between traditional well-plate assays and those obtained on-chip for both suspended immobilized cells and cultured adherent cells. We also demonstrate that the on-chip assay, using adherent cells, provides the possibility of faster screening protocols with the potential for resolving subcellular information about local Ca2+ flux.

  19. Cell-based semiquantitative assay for sulfated glycosaminoglycans facilitating the identification of chondrogenesis. (United States)

    Yen, Ching-Yu; Wu, Yu-Wei; Hsiung, Chao-Nan; Yeh, Min-I; Lin, Yi-Ming; Lee, Sheng-Yang


    Glycosaminoglycans (GAGs), in particular chondroitin sulfate, are an accepted marker of chondrogenic cells. In this study, a cell-based sulfated GAG assay for identifying the chondrogenesis of mesenchymal stem cells was developed. Based on fluorescent staining using safranin O and 4',6-diamidino-2-phenylindole (DAPI), this method was highly sensitive. The results were both qualitative and quantitative. The method is suitable for identifying the chondrogenic process and also for screening compounds. The method may be helpful for discovering novel bioactive compounds for cartilage regeneration.

  20. Screening on Medium of Subsurface Filtration System%地下渗滤系统基质的筛选

    Institute of Scientific and Technical Information of China (English)

    戴强; 张卫民; 艾林芳


    [ Objective ] The study aime to screen the medium of the subsurface filtration system. [ Method ] With the river sand, steel slag, fly coal ash and and coal cinder as the research object, their adsorption properties to the phosphorus were investigated when they were taken as the matrix of the infiltration filter system. [Result] Among the 4 kinds of matrix, as for the matrix to the theoretical saturated adsorption capacity of phosphorus, the steel slag had biggest theoretical saturated adsorption quantity of phosphorus, followed by fly coal ash, coal cinder and river sand; it was kown from the desorption test that the desorption rate of the steel slag was very samll, that of the fly coal ash was slightly great, followed by the coal cinders and river sand; the largest phosphorus removal rate counted by the pseudosecond order kinetic equation were in order of steel slag > coal cinder > river sand > fly coal ash; as for the price and material-taking of the matrix, the river sand, fly coal ash, steel slag and coal cinder all belonged to the cheap materials, compared with them, the river sand could be eazy to get a lot and its phosphorus removal rate was also aobut 60% , so it could be taken as the main matrix of the subsurface filtration system. [ Conclusion ] The study provided the theoretical basis for screening the suatable matixex for the subsurface filtration system.%[目的]筛选地下渗滤系统的基质材料.[方法]以河砂、钢渣、粉煤灰、煤渣为研究对象,考察其作为地下渗滤系统基质对磷的吸附特性.[结果]这4种基质中,从基质对磷的理论饱和吸附量看,钢渣对磷的理论饱和吸附量最大,其次是粉煤灰、煤渣和河砂;从基质的解吸试验可知,钢渣的解析率非常小,粉煤灰的解析率稍大,其次是煤渣和河砂;由准二级动力学方程计算出最大除磷速率Vmax依次为:钢渣>煤渣>河砂>粉煤灰;从基质的价格和取材情况看,河砂、粉煤灰、钢渣

  1. Genome-wide screen for salmonella genes required for long-term systemic infection of the mouse.

    Directory of Open Access Journals (Sweden)


    Full Text Available A microarray-based negative selection screen was performed to identify Salmonella enterica serovar Typhimurium (serovar Typhimurium genes that contribute to long-term systemic infection in 129X1/SvJ (Nramp1(r mice. A high-complexity transposon-mutagenized library was used to infect mice intraperitoneally, and the selective disappearance of mutants was monitored after 7, 14, 21, and 28 d postinfection. One hundred and eighteen genes were identified to contribute to serovar Typhimurium infection of the spleens of mice by 28 d postinfection. The negatively selected mutants represent many known aspects of Salmonella physiology and pathogenesis, although the majority of the identified genes are of putative or unknown function. Approximately 30% of the negatively selected genes correspond to horizontally acquired regions such as those within Salmonella pathogenicity islands (SPI 1-5, prophages (Gifsy-1 and -2 and remnant, and the pSLT virulence plasmid. In addition, mutations in genes responsible for outer membrane structure and remodeling, such as LPS- and PhoP-regulated and fimbrial genes, were also selected against. Competitive index experiments demonstrated that the secreted SPI2 effectors SseK2 and SseJ as well as the SPI4 locus are attenuated relative to wild-type bacteria during systemic infection. Interestingly, several SPI1-encoded type III secretion system effectors/translocases are required by serovar Typhimurium to establish and, unexpectedly, to persist systemically, challenging the present description of Salmonella pathogenesis. Moreover, we observed a progressive selection against serovar Typhimurium mutants based upon the duration of the infection, suggesting that different classes of genes may be required at distinct stages of infection. Overall, these data indicate that Salmonella long-term systemic infection in the mouse requires a diverse repertoire of virulence factors. This diversity of genes presumably reflects the fact that

  2. Screening of hepatocyte proteins binding to complete S protein of hepatitis B virus by yeast-two hybrid system

    Institute of Scientific and Technical Information of China (English)

    Gui-Qin Bai; Jun Cheng; Shu-Lin Zhang; Yan-Ping Huang; Lin Wang; Yan Liu; Shu-Mei Lin


    AIM: To investigate the biological function of complete S protein and to look for proteins interacting with complete S protein in hepatocytes.METHODS: We constructed bait plasmid expressing complete S protein of HBV by cloning the gene of complete S protein into pGBKT7, then the recombinant plasmid DNA was transformed into yeast AH109 (a type). The transformed yeast AH109 was mated with yeast Y187 (α type) containing liver cDNA library plasmid in 2xYPDA medium. Diploid yeast was plated on synthetic dropout nutrient medium (SD/Trp-Leu-His-Ade) containing X-α-gal for selection and screening. After extracting and sequencing of plasmids from positive (blue) colonies, we underwent sequence analysis by bioinformatics.RESULTS: Nineteen colonies were selected and sequenced.Among them, five colonies were Homo sapiens solute carrier family 25, member 23 (SLC25A23), one was Homo sapiens calreticulin, one was human serum albumin (ALB)gene, one was Homo sapiens metallothionein 2A, two were Homo sapiens betaine-homocysteine methyltransferase,three were Homo sapiensNa+ and H+ coupled amino acid transport system N, one was Homo sapiens CD81 antigen (target of anti-proliferative antibody 1) (CD81), three were Homo sapiens diazepam binding inhibitor, two colonies were new genes with unknown function.CONCLUSION: The yeast-two hybrid system is an effective method for identifying hepatocyte proteins interacting with complete S protein of HBV. The complete S protein may bind to different proteins i.e., its multiple functions in vivo.

  3. Performance characteristics of two automated solid-phase red cell adherence systems for pretransfusion antibody screening: a cautionary tale. (United States)

    Quillen, K; Caron, J; Murphy, K


    Out institution has implemented two instruments, the Galileo and the Echo, that use different solid-phase red cell adherence assays for antibody screening in pretransfusion compatibility testing.During the initial implementation of these two instruments, we noticed very different problems: falsely positive results on the Galileo, and falsely negative results and lack of reproducibility on the Echo. Comparison of falsely positive antibody screen results from approximately equivalent numbers of samples run on the Galileo and samples tested by standard manual tube technique using low-ionic-strength saline enhancement showed a false-positive rate of 1.4 percent on the Galileo (defined as a positive screen with a negative panel). Testing using the Echo identified four cases of falsely negative antibody screens, (defined as a negative screen on a patient sample subsequently shown to be positive by the same method). In addition, we note a lack of reproducibility on the Echo, which emphasizes the importance of replicate testing during validation of automated antibody screening platforms.

  4. Fluorogenic Cell-Based Biosensors for Monitoring Microbes (United States)

    Curtis, Theresa; Salazar, Noe; Tabb, Joel; Chase, Chris


    Fluorogenic cell-based sensor systems for detecting microbes (especially pathogenic ones) and some toxins and allergens are undergoing development. These systems harness the natural signaltransduction and amplification cascades that occur in mast cells upon activation with antigens. These systems include (1) fluidic biochips for automated containment of samples, reagents, and wastes and (2) sensitive, compact fluorometers for monitoring the fluorescent responses of mast cells engineered to contain fluorescent dyes. It should be possible to observe responses within minutes of adding immune complexes. The systems have been shown to work when utilizing either immunoglobulin E (IgE) antibodies or traditionally generated rat antibodies - a promising result in that it indicates that the systems could be developed to detect many target microbes. Chimeric IgE antibodies and rat immunoglobulin G (IgG) antibodies could be genetically engineered for recognizing biological and chemical warfare agents and airborne and food-borne allergens. Genetic engineering efforts thus far have yielded (1) CD14 chimeric antibodies that recognize both Grampositive and Gram-negative bacteria and bind to the surfaces of mast cells, eliciting a degranulation response and (2) rat IgG2a antibodies that act similarly in response to low levels of canine parvovirus.

  5. Application of Touch Screen in the Pneumatic Line Training System%触摸屏在气动生产线实训系统中的应用

    Institute of Scientific and Technical Information of China (English)



    This paper in introduces the structure and function of pneumatic line teaching and training system,and mainly researches on the reform of the system based On MT4300 touch screen configuration,The touch screen is configured by EV5000 configuration software,which finally completes the monitoring and controlling of the feeding Station in the system.%本文在介绍了模块化生产线教学实训系统的结构和功能基础上,着重研究了运用MT4300触摸屏组态对该系统进行升级改造。通过EV5000组态软件实现触摸屏组态,完成对该系统上料站的监视与控制。

  6. The validation of a three-stage screening methodology for detecting active convulsive epilepsy in population-based studies in health and demographic surveillance systems

    Directory of Open Access Journals (Sweden)

    Ngugi Anthony K


    Full Text Available Abstract Background There are few studies on the epidemiology of epilepsy in large populations in Low and Middle Income Countries (LMIC. Most studies in these regions use two-stage population-based screening surveys, which are time-consuming and costly to implement in large populations required to generate accurate estimates. We examined the sensitivity and specificity of a three-stage cross-sectional screening methodology in detecting active convulsive epilepsy (ACE, which can be embedded within on-going census of demographic surveillance systems. We validated a three-stage cross-sectional screening methodology on a randomly selected sample of participants of a three-stage prevalence survey of epilepsy. Diagnosis of ACE by an experienced clinician was used as ‘gold standard’. We further compared the expenditure of this method with the standard two-stage methodology. Results We screened 4442 subjects in the validation and identified 35 cases of ACE. Of these, 18 were identified as false negatives, most of whom (15/18 were missed in the first stage and a few (3/18 in the second stage of the three-stage screening. Overall, this methodology had a sensitivity of 48.6% and a specificity of 100%. It was 37% cheaper than a two-stage survey. Conclusion This was the first study to evaluate the performance of a multi-stage screening methodology used to detect epilepsy in demographic surveillance sites. This method had poor sensitivity attributed mainly to stigma-related non-response in the first stage. This method needs to take into consideration the poor sensitivity and the savings in expenditure and time as well as validation in target populations. Our findings suggest the need for continued efforts to develop and improve case-ascertainment methods in population-based epidemiological studies of epilepsy in LMIC.

  7. Application of an improved operational strategy for a high temperature-proton exchange membrane fuel cell-based micro-combined heat and power system for Danish single-family households

    DEFF Research Database (Denmark)

    Arsalis, Alexandros; Nielsen, Mads Pagh; Kær, Søren Knudsen


    characteristics. Based on these findings, an improved operational strategy is formulated and applied in an attempt to minimize the shortcomings of conventional strategies. System parameters, such as electrical and thermal efficiencies, heat dumping, and import/export of electricity, are analyzed. The applied load......A proposed residential energy system based on the PBI (Polybenzimidazole) fuel cell technology is analyzed in terms of operational performance. Conventional operational strategies, such as heat-led and electricity-led, are applied to the simulated system to investigate their performance...... profile is based on average data for a single-family household in Denmark and includes consumption data for electricity and heat demands. The study analyzes the potential of the proposed system on market penetration in the area of residential heat-and-power generation and whether this deployment can...

  8. 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)


    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. Flow-through synthesis on Teflon-patterned paper to produce peptide arrays for cell-based assays. (United States)

    Deiss, Frédérique; Matochko, Wadim L; Govindasamy, Natasha; Lin, Edith Y; Derda, Ratmir


    A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform for parallel organic synthesis and cell-based assays. Solvent-repelling barriers made of Teflon-impregnated paper confine organic solvents to specific zones of the patterned array and allow for 96 parallel flow-through syntheses on paper. The confinement and flow-through mixing significantly improves the peptide yield and simplifies the automation of this synthesis. The synthesis of 100 peptides ranging from 7 to 14 amino acids in length gave over 60% purity for the majority of the peptides (>95% yield per coupling/deprotection cycle). The resulting peptide arrays were used in cell-based screening to identify 14 potent bioactive peptides that support the adhesion or proliferation of breast cancer cells in a 3D environment. In the future, this technology could be used for the screening of more complex phenotypic responses, such as cell migration or differentiation.

  10. Endothelium-specific gene and stem cell-based therapy for erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Travis D. Strong; Milena A. Gebska; Arthur L. Burnett; Hunter C. Champion; Trinity J. Bivalacqua


    Erectile dysfunction (ED) commonly results from endothelial dysfunction of the systemic vasculature. Although phosphodiesterase type 5 (PDE-5) inhibitors are effective at treating most cases of ED, they must be taken routinely and are ineffectual for a meaningful number of men. In recent years gene and stem cell-based therapies targeted at the penile endothelium have been gaining momentum in preclinical studies. These early studies reveal that gene and stem cell-based therapies may be both enduring and efficacious, and may eventually lead to a cure for ED. The following review will highlight our current understanding of endothelial-specific gene and stem cell-based therapies performed to date in a number of experimental animal models.

  11. Some potential material supply constraints in solar systems for heating and cooling of buildings and process heat. (A preliminary screening to identify critical materials)

    Energy Technology Data Exchange (ETDEWEB)

    Watts, R.L.; Gurwell, W.E.; Nelson, T.A.; Smith, S.A.


    Nine Solar Heating and Cooling of Buildings (SHACOB) designs and three Agricultural and Industrial Process Heat (AIPH) designs have been studied to identify potential future material constraints to their large scale installation and use. The nine SHACOB and three AIPH systems were screened and found to be free of serious future material constraints. The screening was carried out for each individual system design assuming 500 million m/sup 2/ of collector area installed by the year 2000. Also, two mixed design scenarios, containing equal portions of each system design, were screened. To keep these scenarios in perspective, note that a billion m/sup 2/ containing a mixture of the nine SHACOB designs will yield an annual solar contribution of about 1.3 Quads or will displace about 4.2 Quads of fossil fuel used to generate electricity. For AIPH a billion square meters of the mixed designs will yield about 2.8 Quads/year. Three materials were identified that could possibly restrain the deployment of solar systems in the specific scenarios investigated. They are iron and steel, soda lime glass and polyvinyl fluoride. All three of these materials are bulk materials. No raw material supply constraints were found.

  12. LED cross screen cluster control system with wireless transmission%无线传输LED十字屏集群控制系统

    Institute of Scientific and Technical Information of China (English)

    谢琦明; 李强; 富金龙; 付亮


    Aiming at the problem that the traditional LED screen is inflexible and not timely information publishing, unable to display animation, wiring complexity, high cost and so on, this paper puts forward a cross screen cluster management solution using wireless transmission technology. The control system on PC can edit textual and 3D information, and send them out to the LED cross screen cluster in real-time by the wireless communication module, and can monitor the fault of LED cross screen. Cross screen cluster can use master/slave mode to exchange information, so the control system can sense the external environment by temperature and brightness sensors and automatically adjusts the brightness of the display. Practical application shows that it has better adaptability and application value.%针对传统LED屏信息发布不灵活、不及时、无法显示动画、布线复杂、成本高等问题,提出采用无线传输的十字屏集群管理解决方案。PC端的监控系统能编辑文本信息和3D动画,通过无线通讯模块实时发布或定时发送到十字屏集群,并能够对故障进行监控;十字屏集群能够采用主/从模式进行信息交互,十字屏控制系统能够通过温度、亮度传感器感知外部环境并自动调整显示屏的亮度。通过实际应用证明了其具有较好的适应性和应用价值。

  13. 触摸屏和PLC在物料分拣系统中的应用%Application of Touch Screen and PLC in Material Sorting System

    Institute of Scientific and Technical Information of China (English)

    吴迎春; 徐连强; 张家骅


    介绍了物料自动分拣系统的组成及功能,根据其控制要求设计了PLC控制程序,用三菱触摸屏GT1055设计了人机交互界面;PLC程序可读性强、调试方便,触摸屏界面友好直观,系统运行稳定,并提高了物料分拣控制系统的灵活性.%This paper introduces the composition and function of automatic material sorting system and designs PLC program according to its control requirement, which is easy to be read and debugged. It also designs the human - machine interface with Mitsubishi GT1055 touch screen, This touch screen interface is friendly and intuitive. The material sorting control system operates stably and its flexibility is improved.

  14. FastTrack to supercritical fluid chromatographic purification: Implementation of a walk-up analytical supercritical fluid chromatography/mass spectrometry screening system in the medicinal chemistry laboratory. (United States)

    Aurigemma, Christine; Farrell, William


    Medicinal chemists often depend on analytical instrumentation for reaction monitoring and product confirmation at all stages of pharmaceutical discovery and development. To obtain pure compounds for biological assays, the removal of side products and final compounds through purification is often necessary. Prior to purification, chemists often utilize open-access analytical LC/MS instruments because mass confirmation is fast and reliable, and the chromatographic separation of most sample constituents is sufficient. Supercritical fluid chromatography (SFC) is often used as an orthogonal technique to HPLC or when isolation of the free base of a compound is desired. In laboratories where SFC is the predominant technique for analysis and purification of compounds, a reasonable approach for quickly determining suitable purification conditions is to screen the sample against different columns. This can be a bottleneck to the purification process. To commission SFC for open-access use, a walk-up analytical SFC/MS screening system was implemented in the medicinal chemistry laboratory. Each sample is automatically screened through six column/method conditions, and on-demand data processing occurs for the chromatographers after each screening method is complete. This paper highlights the "FastTrack" approach to expediting samples through purification.


    Mahalatchimy, Aurélie


    Cell-based regenerative therapies are presented as being able to cure the diseases of the twenty-first century, especially those coming from the degeneration of the aging human body. But their specific nature based on biological materials raises particular challenging issues on how regulation should frame biomedical innovation for society's benefit regarding public health. The European Union (EU) supports the development of cell-based regenerative therapies that are medicinal products with a specific regulation providing their wide access to the European market for European patients. However, once these medicinal products have obtained a European marketing authorisation, they are still far away from being fully accessible to European patients in all EU Member States. Whereas there is much written on the EU regulatory system for new biotechnologies, there is no systematic legal study comparing the insurance provisions in two EU countries. Focussing on the situation in the UK and France that are based on two different healthcare systems, this paper is based on a comparative methodological approach. It raises the question of regulatory reimbursement mechanisms that determine access to innovative treatments and their consequences for social protection systems in the general context of public health. After having compared the French and English regulations of cell-based regenerative therapy regarding pricing and reimbursement, this papers analyses how England and France are addressing two main challenges of cell-based regenerative therapy, to take into account their long-term benefit through their potential curative nature and their high upfront cost, towards their adoption within the English and French healthcare systems. It concludes that England and France have different general legal frameworks that are not specific to the reimbursement of cell-based regenerative therapy, although their two current and respective trends would bring more convergence between the two


    Energy Technology Data Exchange (ETDEWEB)

    JIANG, YI [Los Alamos National Laboratory


    Cancer remains to be one of the leading causes of death due to diseases. We use a systems approach that combines mathematical modeling, numerical simulation, in vivo and in vitro experiments, to develop a predictive model that medical researchers can use to study and treat cancerous tumors. The multiscale, cell-based model includes intracellular regulations, cellular level dynamics and intercellular interactions, and extracellular level chemical dynamics. The intracellular level protein regulations and signaling pathways are described by Boolean networks. The cellular level growth and division dynamics, cellular adhesion and interaction with the extracellular matrix is described by a lattice Monte Carlo model (the Cellular Potts Model). The extracellular dynamics of the signaling molecules and metabolites are described by a system of reaction-diffusion equations. All three levels of the model are integrated through a hybrid parallel scheme into a high-performance simulation tool. The simulation results reproduce experimental data in both avasular tumors and tumor angiogenesis. By combining the model with experimental data to construct biologically accurate simulations of tumors and their vascular systems, this model will enable medical researchers to gain a deeper understanding of the cellular and molecular interactions associated with cancer progression and treatment.

  17. Synthesis and high content cell-based profiling of simplified analogues of the microtubule stabilizer (+)-discodermolide. (United States)

    Minguez, Jose M; Giuliano, Kenneth A; Balachandran, Raghavan; Madiraju, Charitha; Curran, Dennis P; Day, Billy W


    (+)-Discodermolide, a C24:4, trihydroxylated, octamethyl, carbamate-bearing fatty acid lactone originally isolated from a Caribbean sponge, has proven to be the most potent of the microtubule-stabilizing agents. Recent studies suggest that it or its analogues may have advantages over other classes of microtubule-stabilizing agents. (+)-Discodermolide's complex molecular architecture has made structure-activity relationship analysis in this class of compounds a formidable task. The goal of this study was to prepare simplified analogues of (+)-discodermolide and to analyze their biological activities to expand structure-activity relationships. A small library of analogues was prepared wherein the (+)-discodermolide methyl groups at C-14 and C-16 and the C-7 hydroxyl were removed, and the lactone was replaced by simple esters. The library components were analyzed for microtubule-stabilizing actions in vitro, antiproliferative activity against a small panel of human carcinoma cells, and cell signaling, microtubule architecture and mitotic spindle alterations by a multiparameter fluorescence cell-based screening technique. The results show that even drastic structural simplification can lead to analogues with actions related to microtubule targeting and signal transduction, but that these subtle effects were illuminated only through the high information content cell-based screen.

  18. The adaptive computer-aided diagnosis system based on tumor sizes for the classification of breast tumors detected at screening ultrasound. (United States)

    Moon, Woo Kyung; Chen, I-Ling; Chang, Jung Min; Shin, Sung Ui; Lo, Chung-Ming; Chang, Ruey-Feng


    Screening ultrasound (US) is increasingly used as a supplement to mammography in women with dense breasts, and more than 80% of cancers detected by US alone are 1cm or smaller. An adaptive computer-aided diagnosis (CAD) system based on tumor size was proposed to classify breast tumors detected at screening US images using quantitative morphological and textural features. In the present study, a database containing 156 tumors (78 benign and 78 malignant) was separated into two subsets of different tumor sizes (<1cm and ⩾1cm) to explore the improvement in the performance of the CAD system. After adaptation, the accuracies, sensitivities, specificities and Az values of the CAD for the entire database increased from 73.1% (114/156), 73.1% (57/78), 73.1% (57/78), and 0.790 to 81.4% (127/156), 83.3% (65/78), 79.5% (62/78), and 0.852, respectively. In the data subset of tumors larger than 1cm, the performance improved from 66.2% (51/77), 68.3% (28/41), 63.9% (23/36), and 0.703 to 81.8% (63/77), 85.4% (35/41), 77.8% (28/36), and 0.855, respectively. The proposed CAD system can be helpful to classify breast tumors detected at screening US.

  19. Developmental Validation of the ParaDNA® Screening System - A presumptive test for the detection of DNA on forensic evidence items. (United States)

    Dawnay, Nick; Stafford-Allen, Beccy; Moore, Dave; Blackman, Stephen; Rendell, Paul; Hanson, Erin K; Ballantyne, Jack; Kallifatidis, Beatrice; Mendel, Julian; Mills, DeEtta K; Nagy, Randy; Wells, Simon


    Current assessment of whether a forensic evidence item should be submitted for STR profiling is largely based on the personal experience of the Crime Scene Investigator (CSI) and the submissions policy of the law enforcement authority involved. While there are chemical tests that can infer the presence of DNA through the detection of biological stains, the process remains mostly subjective and leads to many samples being submitted that give no profile or not being submitted although DNA is present. The ParaDNA(®) Screening System was developed to address this issue. It consists of a sampling device, pre-loaded reaction plates and detection instrument. The test uses direct PCR with fluorescent HyBeacon™ detection of PCR amplicons to identify the presence and relative amount of DNA on an evidence item and also provides a gender identification result in approximately 75 minutes. This simple-to-use design allows objective data to be acquired by both DNA analyst and non-specialist personnel, to enable a more informed submission decision to be made. The developmental validation study described here tested the sensitivity, reproducibility, accuracy, inhibitor tolerance, and performance of the ParaDNA Screening System on a range of mock evidence items. The data collected demonstrates that the ParaDNA Screening System identifies the presence of DNA on a variety of evidence items including blood, saliva and touch DNA items.

  20. Chest radiographic image quality: comparison of asymmetric screen-film, digital storage phosphor, and digital selenium drum systems--preliminary study. (United States)

    Beute, G H; Flynn, M J; Eyler, W R; Samei, E; Spizarny, D L; Zylak, C J


    Conventional screen-film radiography does not display all regions of the thorax satisfactorily. Three chest radiographic techniques display both the lung and the mediastinum with good contrast. These techniques are asymmetric screen-film (ASF), digital storage phosphor (DSP), and digital selenium drum (DSD) imaging. ASF systems use two asymmetric screen-film combinations to produce a wide-latitude image of the thorax with good contrast in the lungs. In DSP systems, image data are acquired digitally with a wide dynamic range by using the optical output of a photostimulable phosphor plate; in DSD systems, the wide-range digital image data are acquired by using the electronic charge generated on a drum coated with a thin layer of amorphous selenium. The appearance of a DSP or DSD radiograph is then determined by user-selected image processing operations: tone scaling, spatial frequency processing, and dynamic range compensation. Digital chest radiographs processed with strong regional equalization provide both excellent contrast in the lungs and effective display of the mediastinum and chest wall. At visual comparison, the high lung contrast and good mediastinal, retrocardiac, and subdiaphragmatic detail provided by the DSD method distinguish it from the other two methods.

  1. Identification of compounds that modulate retinol signaling using a cell-based qHTS assay. (United States)

    Chen, Yanling; Sakamuru, Srilatha; Huang, Ruili; Reese, David H; Xia, Menghang


    In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling.

  2. Resonances below the {\\rm{Ps}}(n=2) excitation threshold of the {{\\rm{e}}}^{+}-{\\rm{He}}(1{\\rm{s}}2{\\rm{s}}{}^{3}{{\\rm{S}}}^{{\\rm{e}}}) system interacting with screened potentials (United States)

    Ghoshal, Arijit; Ho, Yew Kam


    We have investigated the resonances in the {{{e}}}+-{{He}}{(}3{{{S}}}{{e}}) system interacting with screened potentials by using the stabilization method. Two types of screened potential have been considered: static screened Coulomb potential and exponential cosine-screened Coulomb potential. A model potential has been used to describe the interaction between the outer electron and the {{{He}}}+ ionic core. We have found two resonances below the {{Ps}}(n=2)-{{{He}}}+ threshold. For the unscreened case, our results are in nice agreement with some of the most accurate results available in the literature.

  3. A cell-based high-throughput screening assay for radiation susceptibility using automated cell counting

    NARCIS (Netherlands)

    Hodzic, J.; Dingjan, I.; Maas, M.J.M.; Meulen-Muileman, I.H. van der; Menezes, R.X. de; Heukelom, S.; Verheij, M.; Gerritsen, W.R.; Geldof, A.A.; Triest, B. van; Beusechem, V.W. van


    BACKGROUND: Radiotherapy is one of the mainstays in the treatment for cancer, but its success can be limited due to inherent or acquired resistance. Mechanisms underlying radioresistance in various cancers are poorly understood and available radiosensitizers have shown only modest clinical benefit.

  4. A Cell-Based Pharmacokinetics Assay for Evaluating Tubulin-Binding Drugs (United States)

    Wang, Yuwei; Liu, Jihua; Zhang, Jun; Wang, Liping; Chan, Jonathon; Wang, Hai; Jin, Yi; Yu, Lei; Grainger, David W.; Ying, Wenbin


    Increasing evidence reveals that traditional pharmacokinetics parameters based on plasma drug concentrations are insufficient to reliably demonstrate accurate pharmacological effects of drugs in target organs or cells in vivo. This underscores the increasing need to improve the types and qualities of cellular pharmacokinetic information for drug preclinical screening and clinical efficacy assessments. Here we report a whole cell-based method to assess drugs that disturb microtubule dynamics to better understand different formulation-mediated intracellular drug release profiles. As proof of concept for this approach, we compared the well-known taxane class of anti-microtubule drugs based on paclitaxel (PTX), including clinically familiar albumin nanoparticle-based Abraxane™, and a polymer nanoparticle-based degradable paclitaxel carrier, poly(L-glutamic acid)-paclitaxel conjugate (PGA-PTX, also known as CT-2103) versus control PTX. This in vitro cell-based evaluation of PTX efficacy includes determining the cellular kinetics of tubulin polymerization, relative populations of cells under G2 mitotic arrest, cell proliferation and total cell viability. For these taxane tubulin-binding compounds, the kinetics of cell microtubule stabilization directly correlate with G2 arrest and cell proliferation, reflecting the kinetics and amounts of intracellular PTX release. Each individual cell-based dose-response experiment correlates with published, key therapeutic parameters and taken together, provide a comprehensive understanding of drug intracellular pharmacokinetics at both cellular and molecular levels. This whole cell-based evaluating method is convenient, quantitative and cost-effective for evaluating new formulations designed to optimize cellular pharmacokinetics for drugs perturbing tubulin polymerization as well as assisting in explaining drug mechanisms of action at cellular levels. PMID:24688312

  5. A cell-based pharmacokinetics assay for evaluating tubulin-binding drugs. (United States)

    Wang, Yuwei; Liu, Jihua; Zhang, Jun; Wang, Liping; Chan, Jonathon; Wang, Hai; Jin, Yi; Yu, Lei; Grainger, David W; Ying, Wenbin


    Increasing evidence reveals that traditional pharmacokinetics parameters based on plasma drug concentrations are insufficient to reliably demonstrate accurate pharmacological effects of drugs in target organs or cells in vivo. This underscores the increasing need to improve the types and qualities of cellular pharmacokinetic information for drug preclinical screening and clinical efficacy assessments. Here we report a whole cell-based method to assess drugs that disturb microtubule dynamics to better understand different formulation-mediated intracellular drug release profiles. As proof of concept for this approach, we compared the well-known taxane class of anti-microtubule drugs based on paclitaxel (PTX), including clinically familiar albumin nanoparticle-based Abraxane™, and a polymer nanoparticle-based degradable paclitaxel carrier, poly(L-glutamic acid)-paclitaxel conjugate (PGA-PTX, also known as CT-2103) versus control PTX. This in vitro cell-based evaluation of PTX efficacy includes determining the cellular kinetics of tubulin polymerization, relative populations of cells under G2 mitotic arrest, cell proliferation and total cell viability. For these taxane tubulin-binding compounds, the kinetics of cell microtubule stabilization directly correlate with G2 arrest and cell proliferation, reflecting the kinetics and amounts of intracellular PTX release. Each individual cell-based dose-response experiment correlates with published, key therapeutic parameters and taken together, provide a comprehensive understanding of drug intracellular pharmacokinetics at both cellular and molecular levels. This whole cell-based evaluating method is convenient, quantitative and cost-effective for evaluating new formulations designed to optimize cellular pharmacokinetics for drugs perturbing tubulin polymerization as well as assisting in explaining drug mechanisms of action at cellular levels.

  6. Discovery of secondary metabolites in an extractive liquid-surface immobilization system and its application to high-throughput interfacial screening of antibiotic-producing fungi. (United States)

    Oda, Shinobu; Kameda, Arisa; Okanan, Masanori; Sakakibara, Yusuke; Ohashi, Shinichi


    An extractive liquid-surface immobilization (Ext-LSI) system, which consists of a hydrophobic organic solvent (an upper phase), a fungal cell-ballooned microsphere layer (a middle phase) and a liquid medium (a lower phase), is a unique interfacial cultivation system for fungi. The fungal cells growing at the interface between the organic and aqueous phases efficiently produce hydrophobic metabolites, which are continuously extracted into the organic phase, and/or hydrophilic metabolites that migrate into the aqueous phase without carbon catabolite repression and product and/or feed-back inhibitions. Application of the system to fermentation of Penicillium multicolor IAM 7153 and Trichoderma atroviride AG2755-5NM398 afforded remarkably different profiles of secondary metabolites in the organic phase compared with those in an aqueous phase in traditional submerged cultivation (SmC). Various hydrophobic metabolites exhibiting unique UV-visible spectra were accumulated into the organic phase. The system was applied to a novel interfacial screening system of antibiotic-producing fungi. Compared with the SmC, the interfacial cultivation system exhibited some interesting and important advantages, such as the higher accumulation of hydrophobic secondary metabolites, the lack of requirement for shaking and troublesome solvent extraction, and the small scale of the vessels (medium, 5 ml; dimethylsilicone oil, 1 ml), as well as the significantly different metabolite profiles. The interfacial screening system yielded a high incidence of antimicrobial activity, with 21.9% of the fungi tested exhibiting antifungal activity against Pichia anomala NBRC 10213. This novel interfacial high-throughput screening approach has the potential to discover new biologically active secondary metabolites even from strains previously found to be unproductive.

  7. Using multiplexed regulation of luciferase activity and GFP translocation to screen for FOXO modulators

    Directory of Open Access Journals (Sweden)

    Carnero Amancio


    Full Text Available Abstract Background Independent luciferase reporter assays and fluorescent translocation assays have been successfully used in drug discovery for several molecular targets. We developed U2transLUC, an assay system in which luciferase and fluorescent read-outs can be multiplexed to provide a powerful cell-based high content screening method. Results The U2transLUC system is based on a stable cell line expressing a GFP-tagged FOXO transcription factor and a luciferase reporter gene under the control of human FOXO-responsive enhancers. The U2transLUC assay measures nuclear-cytoplasmic FOXO shuttling and FOXO-driven transcription, providing a means to analyze these two key features of FOXO regulation in the same experiment. We challenged the U2transLUC system with chemical probes with known biological activities and we were able to identify compounds with translocation and/or transactivation capacity. Conclusion Combining different biological read-outs in a single cell line offers significant advantages over conventional cell-based assays. The U2transLUC assay facilitates the maintenance and monitoring of homogeneous FOXO transcription factor expression and allows the reporter gene activity measured to be normalized with respect to cell viability. U2transLUC is suitable for high throughput screening and can identify small molecules that interfere with FOXO signaling at different levels.

  8. Effects of TiO2 and TiC Nanofillers on the Performance of Dye Sensitized Solar Cells Based on the Polymer Gel Electrolyte of a Cobalt Redox System. (United States)

    Venkatesan, Shanmuganathan; Liu, I-Ping; Chen, Li-Tung; Hou, Yi-Chen; Li, Chiao-Wei; Lee, Yuh-Lang


    Polymer gel electrolytes (PGEs) of cobalt redox system are prepared for dye sensitized solar cell (DSSC) applications. Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) is used as a gelator of an acetonitrile (ACN) liquid electrolyte containing tris(2,2'-bipyridine)cobalt(II/III) redox couple. Titanium dioxide (TiO2) and titanium carbide (TiC) nanoparticles are utilized as nanofillers (NFs) of this PGE, and the effects of the two NFs on the conductivity of the PGEs, charge-transfer resistances at the electrode/PGE interface, and the performance of the gel-state DSSCs are studied and compared. The results show that the presence of TiC NFs significantly increases the conductivity of the PGE and decreases the charge-transfer resistance at the Pt counter-electrode (CE)/PGE interface. Therefore, the gel-state DSSC utilizing TiC NFs can achieve a conversion efficiency (6.29%) comparable to its liquid counterpart (6.30%), and, furthermore, the cell efficiency can retain 94% of its initial value after a 1000 h stability test at 50 °C. On the contrary, introduction of TiO2 NFs in the PGE causes a decrease of cell performances. It shows that the presence of TiO2 NFs increases the charge-transfer resistance at the Pt CE/PGE interface, induces the charge recombination at the photoanode/PGE interface, and, furthermore, causes a dye desorption in a long-term-stability test. These results are different from those reported for the iodide redox system and are ascribed to a specific attractive interaction between TiO2 and cobalt redox ions.

  9. REPROVIS-DB: a benchmark system for ligand-based virtual screening derived from reproducible prospective applications. (United States)

    Ripphausen, Peter; Wassermann, Anne Mai; Bajorath, Jürgen


    Benchmark calculations are essential for the evaluation of virtual screening (VS) methods. Typically, classes of known active compounds taken from the medicinal chemistry literature are divided into reference molecules (search templates) and potential hits that are added to background databases assumed to consist of compounds not sharing this activity. Then VS calculations are carried out, and the recall of known active compounds is determined. However, conventional benchmarking is affected by a number of problems that reduce its value for method evaluation. In addition to often insufficient statistical validation and the lack of generally accepted evaluation standards, the artificial nature of typical benchmark settings is often criticized. Retrospective benchmark calculations generally overestimate the potential of VS methods and do not scale with their performance in prospective applications. In order to provide additional opportunities for benchmarking that more closely resemble practical VS conditions, we have designed a publicly available compound database (DB) of reproducible virtual screens (REPROVIS-DB) that organizes information from successful ligand-based VS applications including reference compounds, screening databases, compound selection criteria, and experimentally confirmed hits. Using the currently available 25 hand-selected compound data sets, one can attempt to reproduce successful virtual screens with other than the originally applied methods and assess their potential for practical applications.

  10. Expression profiling of colon cancer cell lines and colon biopsies: Towards a screening system for potential cancer-preventive compounds

    NARCIS (Netherlands)

    Erk, van M.J.; Krul, C.A.M.; Caldenhoven, E.; Stierum, R.H.; Peters, W.H.; Woutersen, R.A.; Ommen, van B.


    Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived fr

  11. Expression profiling of colon cancer cell lines and colon biopsies: towards a screening system for potential cancer-preventive compounds.

    NARCIS (Netherlands)

    Erk, M.J. van; Krul, C.A.; Caldenhoven, E.; Stierum, R.H.; Peters, W.H.M.; Woutersen, R.A.; Ommen, B.


    Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived fr

  12. Three distinct surgical clothing systems in a turbulent mixing operating room equipped with mobile ultraclean laminar airflow screen

    DEFF Research Database (Denmark)

    Sadrizadeh, Sasan; Holmberg, Sture; Nielsen, Peter Vilhelm


    Two types of mobile screens producing ultraclean local laminar airflow were investigated as an addition to turbulent mixing operating room ventilation. The exploration was carried out numerically using computational fluid dynamics. Surface and volumetric particle counts were simulated on the oper......Two types of mobile screens producing ultraclean local laminar airflow were investigated as an addition to turbulent mixing operating room ventilation. The exploration was carried out numerically using computational fluid dynamics. Surface and volumetric particle counts were simulated...... on the operating and instrument tables with and without the additional mobile airflow screen. Three different source strengths (the mean bacteria-carrying particle value emitted from one person per second) due to staff clothing variety were considered. Model validation was performed through result comparisons...... with experimental data from the literature. Results confirmed that the mobile screen units reduced the airborne bacteria to an acceptable level for infection-prone surgeries. No significant particle concentration differences existed in the periphery of the operating room. Lower source strength resulting from...

  13. Principles of successful cancer screening. (United States)

    Smith, R A


    Screening for cancer is the application of various tests to apparently healthy individuals in order to identify who among them has occult disease, which may be either invasive disease or a precursor lesion. For any given cancer site, the potential of screening to reduce morbidity and mortality is based on well-defined criteria for the evaluation of screening effectiveness and on acceptable performance to be realized in the average community setting. Screening programs are most successful when they are organized into a system that leads to high rates of participation, high quality, and constant surveillance and evaluation. If the elements that contribute to a successful screening program are not well organized and integrated, then the fullest potential of screening will not be realized.

  14. Application of linear discriminant analysis in performance evaluation of extractable nuclear antigen immunoassay systems in the screening and diagnosis of systemic autoimmune rheumatic diseases. (United States)

    Pi, David; de Badyn, Monika Hudoba; Nimmo, Mike; White, Rick; Pal, Jason; Wong, Patrick; Phoon, Carmen; O'Connor, Deidre; Pi, Steven; Shojania, Kam


    This study applied a linear discriminant analysis model to evaluate the performance of 2 types of commercially available extractable nuclear antigen (ENA) immunoassays for the screening and diagnosis of systemic autoimmune rheumatic diseases (SARDs) in a large tertiary hospital reference laboratory: (1) an enzyme-linked immunosorbent assay (ELISA) and (2) a multiplex bead-based immunoassay (MPBI). The results of the study showed both ENA immunoassays had comparable sensitivity for the detection of SARDs compared with the antinuclear antigen immunofluorescence (ANA-IF) method (ANA-IF: 85.6%, ENA-ELISA: 91.5%, ENA-MPBI: 83.1%, pairwise comparisons with ANA-IF: P > .05). However, both ENA immunoassays offered improved specificity compared with the ANA-IF (ANA-IF: 24.2%; ENA-ELISA: 39.8%; ENA-MPBI: 53.1%; pairwise comparison with ANA-IF: P diseases. Diagnostic performance of the ENA/dsDNA components by the MPBI and ELISA methods did not differ significantly (area under the curve [AUC], 81.0% vs 83.0%, respectively, P > .05), but the key ENA/dsDNA variables contributing to the discriminating power of the assays for the diagnosis of specific SARDs were reagent/method dependent.

  15. The yeast two hybrid system in a screen for proteins interacting with axolotl (Ambystoma mexicanum) Msx1 during early limb regeneration. (United States)

    Abuqarn, Mehtap; Allmeling, Christina; Amshoff, Inga; Menger, Bjoern; Nasser, Inas; Vogt, Peter M; Reimers, Kerstin


    Urodele amphibians are exceptional in their ability to regenerate complex body structures such as limbs. Limb regeneration depends on a process called dedifferentiation. Under an inductive wound epidermis terminally differentiated cells transform to pluripotent progenitor cells that coordinately proliferate and eventually redifferentiate to form the new appendage. Recent studies have developed molecular models integrating a set of genes that might have important functions in the control of regenerative cellular plasticity. Among them is Msx1, which induced dedifferentiation in mammalian myotubes in vitro. Herein, we screened for interaction partners of axolotl Msx1 using a yeast two hybrid system. A two hybrid cDNA library of 5-day-old wound epidermis and underlying tissue containing more than 2×10⁶ cDNAs was constructed and used in the screen. 34 resulting cDNA clones were isolated and sequenced. We then compared sequences of the isolated clones to annotated EST contigs of the Salamander EST database (BLASTn) to identify presumptive orthologs. We subsequently searched all no-hit clone sequences against non redundant NCBI sequence databases using BLASTx. It is the first time, that the yeast two hybrid system was adapted to the axolotl animal model and successfully used in a screen for proteins interacting with Msx1 in the context of amphibian limb regeneration.

  16. Evidence-based development and first usability testing of a social serious game based multi-modal system for early screening for atypical socio-cognitive development. (United States)

    Gyori, Miklos; Borsos, Zsófia; Stefanik, Krisztina


    At current, screening for, and diagnosis of, autism spectrum disorders (ASD) are based on purely behavioral data; established screening tools rely on human observation and ratings of relevant behaviors. The research and development project in the focus of this paper is aimed at designing, creating and evaluating a social serious game based multi-modal, interactive software system for screening for high functioning cases of ASD at kindergarten age. The aims of this paper are (1) to summarize the evidence-based design process and (2) to present results from the first usability test of the system. Game topic, candidate responses, and candidate game contents were identified via an iterative literature review. On this basis, the 1st partial prototype of the fully playable game has been created, with complete data recording functionality but without the decision making component. A first usability test was carried out on this prototype (n=13). Overall results were unambiguously promising. Although sporadic difficulties in, and slightly negative attitudes towards, using the game occasionally arose, these were confined to non-target-group children only. The next steps of development include (1) completing the game design; (2) carrying out first large-n field test; (3) creating the first prototype of the decision making component.

  17. Vision Alignment System of Solar Cell Screen Printing Machine%太阳能硅片丝印机视觉定位系统

    Institute of Scientific and Technical Information of China (English)

    魏海滨; 朱跃红; 郎鹏; 郑海红; 张素枝


    Solar Cell Screen Printing Machine is the key equipment in solar cell production industry. How to improve the precision, quality and efficiency of screen printing is very important, the alignment is one of the key technologies. Introduce the typical application of precision alighnment based on computer vision in the solar cell screen printing, and illustrate the basic components, design principle and hardware selection of vision precision alignment system, give out the motional relationship between CCD optical system and UVWworktable and the alionment orocess.%太阳能硅片丝印机是太阳能电池生产行业中的关键设备,如何提高丝印精度、印刷质量和印刷效率成为研究重点,而对位技术则是其中的关键技术之一。介绍了基于机器视觉的精密对位技术在太阳能硅片丝印机中的典型应用,阐述了视觉精密定位系统的基本组成、设计原理及硬件选型,给出了CCD光学系统与UVW工作平台坐标系之间的各运动关系和对位过程。

  18. 基于MotoTron平台的燃料电池共轨喷射系统的研发%Research and Development of the Common-rail Injector System for Fuel Cell Based on MotoTron Platform

    Institute of Scientific and Technical Information of China (English)

    何雍; 李亚超; 吴兵; 王丙龙; 王鸿鹄


    针对目前常用的燃料电池氢气供应方式存在氢气利用率低、耗能大和使用范围小等缺点,本文中提出了基于MotoTron平台的氢共轨喷射系统快速原型开发技术.通过对控制参数的整定,达到共轨喷射系统氢气输出稳态误差合理、出口流量动态可调的目的.结果表明,该方法能使氢气在燃料电池阳极分布更为均匀,提高了氢气利用率,延长了燃料电池寿命,为后续的整车开发奠定了基础.%In view of the low utilization rate of hydrogen, high energy consumption, narrow use scope and other defects of the way of hydrogen supply commonly used in fuel cell at present, a rapid prototyping development technique for common rail hydrogen injection system is proposed based on MotoTron platform. By tuning the control parameters, reasonable steady-state error of hydrogen output and dynamically adjustable exit flow rate are realized. The results show that the technique proposed can enable evener distribution of hydrogen at fuel cell anode, raise the utilization rate of hydrogen and extend the lifespan of fuel cell, laying a foundation for subsequent vehicle development.

  19. A rapid screening method to monitor expression of various recombinant proteins from prokaryotic and eukaryotic expression systems using MALDI-TOF mass spectrometry

    DEFF Research Database (Denmark)

    Jebanathirajah, J.A.; Andersen, S.; Blagoev, B.;


    Rapid methods using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to monitor recombinant protein expression from various prokaryotic and eukaryotic cell culture systems were devised. Intracellular as well as secreted proteins from both induced and constitutive...... expression systems were measured and monitored from whole cells and growth media, thus providing an alternative to time-consuming traditional methods for screening and monitoring of protein expression. The methods described here involve minimal processing of samples and are therefore relevant to high...

  20. Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science. (United States)

    Lenas, Petros; Moos, Malcolm; Luyten, Frank P


    The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has

  1. Breast cancer screening (United States)

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

  2. Protocol for population testing of an Internet-based Personalised Decision Support system for colorectal cancer screening

    Directory of Open Access Journals (Sweden)

    Wilson Carlene J


    Full Text Available Abstract Background Australia has a comparatively high incidence of colorectal (bowel cancer; however, population screening uptake using faecal occult blood test (FOBT remains low. This study will determine the impact on screening participation of a novel, Internet-based Personalised Decision Support (PDS package. The PDS is designed to measure attitudes and cognitive concerns and provide people with individually tailored information, in real time, that will assist them with making a decision to screen. The hypothesis is that exposure to (tailored PDS will result in greater participation in screening than participation following exposure to non-tailored PDS or resulting from the current non-tailored, paper-based approach. Methods/design A randomised parallel trial comprising three arms will be conducted. Men and women aged 50-74 years (N = 3240 will be recruited. They must have access to the Internet; have not had an FOBT within the previous 12 months, or sigmoidoscopy or colonoscopy within the previous 5 years; have had no clinical diagnosis of bowel cancer. Groups 1 and 2 (PDS arms will access a website and complete a baseline survey measuring decision-to-screen stage, attitudes and cognitive concerns and will receive immediate feedback; Group 1 will receive information 'tailored' to their responses in the baseline survey and group 2 will received 'non-tailored' bowel cancer information. Respondents in both groups will subsequently receive an FOBT kit. Group 3 (usual practice arm will complete a paper-based version of the baseline survey and respondents will subsequently receive 'non-tailored' paper-based bowel cancer information with accompanying FOBT kit. Following despatch of FOBTs, all respondents will be requested to complete an endpoint survey. Main outcome measures are (1 completion of FOBT and (2 change in decision-to-screen stage. Secondary outcomes include satisfaction with decision and change in attitudinal scores from baseline to

  3. Design of non-contact touch screen system%非接触式触摸屏系统的设计

    Institute of Scientific and Technical Information of China (English)

    向斌宾; 蒋向东; 王继岷; 李建国


    针对目前触摸屏必须接触式控制的缺陷,提出了一种基于图像处理技术的新型触摸屏系统.该系统以微软VX-6000USB2.0摄像头为图像传感器,由PC机采集图像序列,识别和跟踪定位激光光斑,并对用户的指点控制信息做出相应反应.阐述了该系统结构及定位原理,使用基于OpenCV(open source computer vision library)的图像处理算法辅助开发其软件系统.提出一种基于边界修复的图像二次校正法,通过对训练样本的测量发现,系统拥有很好的指点精度.实验结果表明,所设计触摸屏系统能够初步实现非接触式指点的要求,为大屏幕挂壁式非接触式触摸屏系统的研究提供了有效的思路.%When the current touch screen must be contacted control,it proposes a new touch screen system based on the image processing technology.The system introduces Microsoft VX-6000 USB2.0 camera as its image sensor, gathers image sequences, identifies and positions the laser spot,and responds with users' pointing describes the architecture of the system, a software for positioning,and uses image processing algorithm based on OpenCV(open source computer vision library) to help developing its software proposes an image secondary correction method based on edge-restoration.By training samples, it finds that the system has excellent accuracy.The experimental results indicate that the system can realize the non-contact requirement and provide an effective thought for the study of non-contact large screen wall touch screen system.

  4. A computer touch screen system and training procedure for use with primate infants: Results from pigtail monkeys (Macaca nemestrina). (United States)

    Mandell, Dorothy J; Sackett, Gene P


    Computerized cognitive and perceptual testing has resulted in many advances towards understanding adult brain-behavior relations across a variety of abilities and species. However, there has been little migration of this technology to the assessment of very young primate subjects. We describe a training procedure and software that was developed to teach infant monkeys to interact with a touch screen computer. Eighteen infant pigtail macaques began training at 90-postnatal days and five began at 180-postnatal days. All animals were trained to reliably touch a stimulus presented on a computer screen and no significant differences were found between the two age groups. The results demonstrate the feasibility of using computers to assess cognitive and perceptual abilities early in development.

  5. Implementation of a DOD ELAP Conforming Quality System at a FUSRAP Site Field Temporary Radiological Screening Laboratory - 13500

    Energy Technology Data Exchange (ETDEWEB)

    Winters, M.S.; McElheny, G. [Cabrera Services Inc. 473 Silver Lane, East Hartford, CT (United States); Houston, L.M.; Masset, M.R.; Spector, H.L. [United States Army Corps of Engineers -1776 Niagara Street, Buffalo, NY (United States)


    A case study is presented on specific program elements that supported the transition of a temporary field radiological screening lab to an accredited operation capable of meeting client quality objectives for definitive results data. The temporary field lab is located at the Formerly Utilized Sites Remedial Action Program Linde Site in Tonawanda, NY. The site is undergoing remediation under the direction of the United States Army Corps of Engineers - Buffalo District, with Cabrera Services Inc. as the remediation contractor and operator of the on-site lab. Analysis methods employed in the on-site lab include gross counting of alpha and beta particle activity on swipes and air filters and gamma spectroscopy of soils and other solid samples. A discussion of key program elements and lessons learned may help other organizations considering pursuit of accreditation for on-site screening laboratories. (authors)

  6. Microfluidic Cell Deformability Assay for Rapid and Efficient Kinase Screening with the CRISPR-Cas9 System. (United States)

    Han, Xin; Liu, Zongbin; Zhao, Li; Wang, Feng; Yu, Yang; Yang, Jianhua; Chen, Rui; Qin, Lidong


    Herein we report a CRISPR-Cas9-mediated loss-of-function kinase screen for cancer cell deformability and invasive potential in a high-throughput microfluidic chip. In this microfluidic cell separation platform, flexible cells with high deformability and metastatic propensity flowed out, while stiff cells remained trapped. Through deep sequencing, we found that loss of certain kinases resulted in cells becoming more deformable and invasive. High-ranking candidates identified included well-reported tumor suppressor kinases, such as chk2, IKK-α, p38 MAPKs, and DAPK2. A high-ranking candidate STK4 was chosen for functional validation and identified to play an important role in the regulation of cell deformability and tumor suppression. Collectively, we have demonstrated that CRISPR-based on-chip mechanical screening is a potentially powerful strategy to facilitate systematic genetic analyses.

  7. Amperometric screen-printed algal biosensor with flow injection analysis system for detection of environmental toxic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shitanda, Isao [Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 (Japan)], E-mail:; Takamatsu, Satoshi; Watanabe, Kunihiro; Itagaki, Masayuki [Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 (Japan)


    A screen-printed algal biosensor was fabricated for evaluation of toxicity of chemicals. An algal ink was prepared by mixing unicellular microalga Chlorella vulgaris cells, carbon nanotubes and sodium alginate solution. The algal ink was immobilized directly on a screen-printed carbon electrode surface using screen-printing technique. Photosynthetically generated oxygen of the immobilized algae was monitored amperometically. Responses of the algal biosensor to four toxic compounds, 6-chloro-N-ethyl-N-isopropyl-1,3,5-triazine-2,4-diamine (atrazine) and 3-(3,4-dichlorophenyl)-1,1-diethylurea (DCMU) were evaluated as inhibition ratios of the reduction current. The concentrations that gave 50% inhibition of the oxygen reduction current (IC{sup '}{sub 50}) for atrazine and DCMU were 12 and 1 {mu}mol dm{sup -3}, respectively. In comparison with the conventional algal biosensors, in which the algal cells were entrapped in an alginate gel and immobilized on the surface of a transparent indium tin oxide electrode, the present sensor is much smaller and less expensive, with the shorter assay time.

  8. Split-screen display system and standardized methods for ultrasound image acquisition and multi-frame data processing (United States)

    Selzer, Robert H. (Inventor); Hodis, Howard N. (Inventor)


    A standardized acquisition methodology assists operators to accurately replicate high resolution B-mode ultrasound images obtained over several spaced-apart examinations utilizing a split-screen display in which the arterial ultrasound image from an earlier examination is displayed on one side of the screen while a real-time "live" ultrasound image from a current examination is displayed next to the earlier image on the opposite side of the screen. By viewing both images, whether simultaneously or alternately, while manually adjusting the ultrasound transducer, an operator is able to bring into view the real-time image that best matches a selected image from the earlier ultrasound examination. Utilizing this methodology, dynamic material properties of arterial structures, such as IMT and diameter, are measured in a standard region over successive image frames. Each frame of the sequence has its echo edge boundaries automatically determined by using the immediately prior frame's true echo edge coordinates as initial boundary conditions. Computerized echo edge recognition and tracking over multiple successive image frames enhances measurement of arterial diameter and IMT and allows for improved vascular dimension measurements, including vascular stiffness and IMT determinations.

  9. A novel multi-functional cell-based microphysiometer

    Institute of Scientific and Technical Information of China (English)

    XU Ying; XU Gaixia; LIU Qingjun; CAI Hua; LI Yan; LI Rong; WANG Ping


    This paper presents a novel multi-functional microphysiometer for simultaneous measurements of several extracellular ion concentrations and action potential measurement in living cells based on MLAPS (multi-light addressable potentiometric sensor). In the microphysiometer, sorts of sensitive membranes are illuminated in parallel with n light sources at working frequencies, and the response amplitudes of each frequency component can be measured on-line by parallel processing algorithm. In the experiments, the relations of the extracellular environmental H+, Na +, K +, Ca2 + under the effects of western medicines (dilantin, phenobarbital sodium) and Chinese drugs (scutellaria, medlar, hemlock parsley) were analyzed, and the effects of several drugs were evaluated. Moreover, the action potential signals of different cell types (cardiac myocytes and neurons) could be measured and analyzed by LAPS. By detecting these parameters, the system can monitor the real-time process of the cell metabolism and action potential, observe the functional responses of different kinds of membrane-bound receptors, and evaluate the activities of drugs.

  10. Spherical Individual Cell-Based Models


    Krinner, Axel


    Over the last decade a huge amount of experimental data on biological systems has been generated by modern high-throughput methods. Aided by bioinformatics, the '-omics' (genomics, transcriptomics, proteomics, metabolomics and interactomics) have listed, quantif ed and analyzed molecular components and interactions on all levels of cellular regulation. However, a comprehensive framework, that does not only list, but links all those components, is still largely missing. The biology-based but h...

  11. Identification of RSK and TTK as Modulators of Blood Vessel Morphogenesis Using an Embryonic Stem Cell-Based Vascular Differentiation Assay

    Directory of Open Access Journals (Sweden)

    Lamis Hammoud


    Full Text Available Blood vessels are formed through vasculogenesis, followed by remodeling of the endothelial network through angiogenesis. Many events that occur during embryonic vascular development are recapitulated during adult neoangiogenesis, which is critical to tumor growth and metastasis. Current antiangiogenic tumor therapies, based largely on targeting the vascular endothelial growth factor pathway, show limited clinical benefits, thus necessitating the discovery of alternative targets. Here we report the development of a robust embryonic stem cell-based vascular differentiation assay amenable to small-molecule screens to identify novel modulators of angiogenesis. In this context, RSK and TTK were identified as angiogenic modulators. Inhibition of these pathways inhibited angiogenesis in embryoid bodies and human umbilical vein endothelial cells. Furthermore, inhibition of RSK and TTK reduced tumor growth, vascular density, and improved survival in an in vivo Lewis lung carcinoma mouse model. Our study suggests that RSK and TTK are potential targets for antiangiogenic therapy, and provides an assay system for further pathway screens.

  12. Development of cell-based bioassay with Sf9 cells expressing TcSKR1 and TcSKR2 and differential activation by sulfated and non-sulfated SK peptides. (United States)

    Yu, Na; Swevers, Luc; Nachman, Ronald J; Smagghe, Guy


    Insect sulfakinin receptors (SKRs) are G-protein-coupled receptors (GPCRs) that interact with sulfakinins (SKs) to modulate diverse biological processes. One of the indispensable roles of SKs is in the regulation of food intake in insects. In this project we report on the development of a cell-based receptor assay system with insect Sf9 cells, expressing TcSKR1 and TcSKR2 from the red flour beetle Tribolium castaneum, a model and important pest insect in agriculture. In this system, a stable presence of the two TcSKRs was supported by Western blotting. The expressed TcSKRs were coupled to Gαs-protein upon activation and stimulated cAMP accumulation in Sf9 cells. Exposure of the transfected cell lines to sulfated SK (sSK) activated TcSKR1 at 1 nM; the EC50 of sSK to obtain 50% of receptor activation was similar for both receptors. In contrast, μM concentrations of non-sulfated SK were necessary to activate both TcSKRs. In conclusion, this cell-based TcSKR assay system is useful to screen SK-related peptides and mimetics and to better document ligand-receptor structure-activity relationships. Given the importance of SK signaling system in insects, the present study may provide new insights on the development of new methods to control pest insects.

  13. 基于PLC和触摸屏的电梯群控系统设计%Design of elevator group control system based on PLC and touch screen

    Institute of Scientific and Technical Information of China (English)

    张梅; 何福贵; 张力展


    In allusion to two four-story group control elevators,the implementation procedure of elevator group control based on PLC and touch screen is presented in this paper. The control for single elevator is described,mainly including elevator leveling processing,touch screen control and display. On the basis of single elevator control,the structure for the elevator group control system with PLC,touch screen,frequency converter is offered;the communication setting between PLCs,elevator level-ing processing and scheduling algorithm of group control elevator.%针对具体的二座四层群控电梯,描述了基于PLC和触摸屏的电梯群控的实现过程。针对单梯控制,主要叙述了电梯平层的处理,触摸屏控制和显示的结构和工程设计。在此基础上,给出了基于触摸屏、PLC、变频器的电梯群控的系统结构,叙述了群控电梯PLC组之间的通信设定、群控电梯平层的处理、电梯群控调度算法,并进行了不断优化。

  14. A transfer-less, multi-well liquid culture feeding system for screening small molecules that affect the longevity of Caenorhabditis elegans. (United States)

    Fitzgerald, Vanessa; Mensack, Meghan; Wolfe, Pamela; Thompson, Henry


    Agricultural sciences rely almost entirely on chemical assays to screen the thousands of crop cultivars generated in a crop improvement program for potential human health benefits. This situation exists in part because most animal models are expensive to implement, utilize large amounts of plant material, and require specialized facilities and technical training. A cost-effective, high-throughput animal model to screen crop extracts for small molecules with biological activity related to human health benefits would provide a much-needed resource. Here we introduce a new, relatively high-throughput method incorporating the microscopic Caenorhabditis elegans nematode, which is suitable for screening chemical extracts for bioactivity without the need for robotics. This system was chosen because longevity extension in C. elegans has been previously associated with human health benefits. Through the use of cell culture inserts, C. elegans can be exposed to fresh crop extracts daily throughout their lifespan without mechanical manipulation of the worm, thus minimizing stress and creating an environment suitable for experiments measuring longevity. Additionally, the duration of longevity experiments can be reduced by using type II right censoring in experimental design and survival analyses.

  15. Screening for Novel Binding Proteins Interacting with Human Papillomavirus Type 18 E6 Oncogene in the Hela cDNA Library by Yeast Two-Hybrid System

    Institute of Scientific and Technical Information of China (English)

    Shuang LI; Ping LIU; Ling XI; Xuefeng JIANG; Jianfeng ZHOU; Shixuan WANG; Li MENG; Yunping LU; Ding Ma


    To screen for novel binding proteins interacting with high-risk HPV 18 E6 oncogene, the strain AH109 was transformed with pGBKT7-HPV18 E6 plasmid, and subsequent transference was utilized to screen for interacting proteins with HPV 18 E6 in human Hela cDNA library. HPVl8 E6 mRNA was expressed in yeast and there was no self-activation and toxicity in AH109. Seven proteins that interacted with HPV18 E6, including transmembrane protein 87B, phosphonoformate im- muno-associated protein 5, vimentin, KM-HN-1 protein, dedicator of cytokinesis 7, vaccinia related kinase 2 and a hypothetical protein, were identified. It was suggested that yeast two-hybrid system is an efficient for screening interacting proteins. The high-risk HPV 18 E6 oncogene may interact with the proteins, which may be associated with signal transduction and transeriptional control, epithelial cell invasion and migration, as well as humoral and cellular immune etc. This investigation provides functional clues for further exploration of potential oncogenesis targets for cancer biotherapy.

  16. Risks of Cervical Cancer Screening (United States)

    ... are at increased risk for HPV infections. Other risk factors for cervical cancer include: Giving birth to many children. Smoking cigarettes. Using oral contraceptives ("the Pill"). Having a weakened immune system . Cervical Cancer Screening ...

  17. Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Baixin Ye


    Full Text Available A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR T-cell therapy and engineered T-cell receptor (TCR T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells. In clinic trials, CAR-T-cell- and TCR-T-cell-based adoptive immunotherapy have produced encouraging clinical outcomes, thereby demonstrating their therapeutic potential in mitigating tumor development. The purpose of the present review is to (1 provide a detailed overview of the multiple mechanisms for immune evasion related with T-cell-based therapies; (2 provide a current summary of the applications of CAR-T-cell- as well as neoantigen-specific TCR-T-cell-based adoptive immunotherapy and routes taken to overcome immune evasion; and (3 evaluate alternative approaches targeting immune evasion via optimization of CAR-T and TCR-T-cell immunotherapies.

  18. A high-throughput screening system targeting the nuclear export pathway via the third nuclear export signal of influenza A virus nucleoprotein. (United States)

    Kakisaka, Michinori; Mano, Takafumi; Aida, Yoko


    Two classes of antiviral drugs, M2 channel inhibitors and neuraminidase (NA) inhibitors, are currently approved for the treatment of influenza; however, the development of resistance against these agents limits their efficacy. Therefore, the identification of new targets and the development of new antiviral drugs against influenza are urgently needed. The third nuclear export signal (NES3) of nucleoprotein (NP) is the most important for viral replication among seven NESs encoded by four viral proteins, NP, M1, NS1, and NS2. NP-NES3 is critical for the nuclear export of NP, and targeting NP-NES3 is therefore a promising strategy that may lead to the development of antiviral drugs. However, a high-throughput screening (HTS) system to identify inhibitors of NP nuclear export has not been established. Here, we developed a novel HTS system to evaluate the inhibitory effects of compounds on the nuclear export pathway mediated by NP-NES3 using a MDCK cell line stably expressing NP-NES3 fused to a green fluorescent protein from aequorea coerulescens (AcGFP-NP-NES3) and a cell imaging analyzer. This HTS system was used to screen a 9600-compound library, leading to the identification of several hit compounds with inhibitory activity against the nuclear export of AcGFP-NP-NES3. The present HTS system provides a useful strategy for the identification of inhibitors targeting the nuclear export of NP via its NES3 sequence.

  19. A Dual-reporter system for real-time monitoring and high-throughput CRISPR/Cas9 library screening of the hepatitis C virus. (United States)

    Ren, Qingpeng; Li, Chan; Yuan, Pengfei; Cai, Changzu; Zhang, Linqi; Luo, Guangxiang George; Wei, Wensheng


    The hepatitis C virus (HCV) is one of the leading causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinomas and infects approximately 170 million people worldwide. Although several reporter systems have been developed, many shortcomings limit their use in the assessment of HCV infections. Here, we report a real-time live-cell reporter, termed the NIrD (NS3-4A Inducible rtTA-mediated Dual-reporter) system, which provides an on-off switch specifically in response to an HCV infection. Using the NIrD system and a focused CRISPR/Cas9 library, we identified CLDN1, OCLN and CD81 as essential genes for both the cell-free entry and the cell-to-cell transmission of HCV. The combination of this ultra-sensitive reporter system and the CRISPR knockout screening provides a powerful and high-throughput strategy for the identification of critical host components for HCV infections.

  20. Development of a Cell-Based Functional Assay for the Detection of Clostridium botulinum Neurotoxin Types A and E

    Directory of Open Access Journals (Sweden)

    Uma Basavanna


    Full Text Available The standard procedure for definitive detection of BoNT-producing Clostridia is a culture method combined with neurotoxin detection using a standard mouse bioassay (MBA. The mouse bioassay is highly sensitive and specific, but it is expensive and time-consuming, and there are ethical concerns due to use of laboratory animals. Cell-based assays provide an alternative to the MBA in screening for BoNT-producing Clostridia. Here, we describe a cell-based assay utilizing a fluorescence reporter construct expressed in a neuronal cell model to study toxin activity in situ. Our data indicates that the assay can detect as little as 100 pM BoNT/A activity within living cells, and the assay is currently being evaluated for the analysis of BoNT in food matrices. Among available in vitro assays, we believe that cell-based assays are widely applicable in high-throughput screenings and have the potential to at least reduce and refine animal assays if not replace it.

  1. A one-day, dispense-only IP-One HTRF assay for high-throughput screening of Galphaq protein-coupled receptors: towards cells as reagents. (United States)

    Bergsdorf, Christian; Kropp-Goerkis, Carmen; Kaehler, Irene; Ketscher, Lars; Boemer, Ulf; Parczyk, Karsten; Bader, Benjamin


    Abstract: Compared to biochemical high-throughput screening (HTS) assays, cell-based functional assays are generally thought to be more time consuming and complex because of additional efforts for running continuous cell cultures as well as the numerous assay steps when transferring media and compounds. A common strategy to compensate the anticipated reduction in overall throughput is to implement highly automated cell culture and screening systems. However, such systems require substantial investments in sophisticated hardware and highly specialized personnel. In trying to set up alternatives to increasing throughput in functional cell-based screening, we combined several approaches. By using (1) cryopreserved cell aliquots instead of continuous cell culture, (2) cells in suspension instead of adherent cells, and (3) "ready-to-screen" assay plates with nanoliter aliquots of test compounds, an assay procedure was developed that very much resembles a standard biochemical, enzymatic assay comprising only a few dispense steps. Chinese hamster ovary cells stably overexpressing a Galphaq-coupled receptor were used as a model system to measure receptor activation by detection of intracellular D-myo-inositol 1-phosphate with the help of homogeneous time-resolved fluorescence (HTRF, CISbio International, Bagnols-sur-Cèze, France). Initially established in 384-well adherent cell format, the assay was successfully transferred to 1,536-well format. The assay quality was sufficient to run HTS campaigns in both formats with good Z'-factors and excellent reproducibility of antagonists. Subsequently, the assay procedure was optimized for usage of suspension cells. The influences of cell culture media, plate type, cell number, and incubation time were assessed. Finally, the suspension cell assay was applied to pharmacological characterization of a small molecule antagonist by Schild plot analysis. Our data demonstrate not only the application of the IP-One HTRF assay (CISbio

  2. The exceptional stem cell system of Macrostomum lignano: Screening for gene expression and studying cell proliferation by hydroxyurea treatment and irradiation

    Directory of Open Access Journals (Sweden)

    Eichberger Paul


    Full Text Available Abstract Background Flatworms are characterized by an outstanding stem cell system. These stem cells (neoblasts can give rise to all cell types including germ cells and power the exceptional regenerative capacity of many flatworm species. Macrostomum lignano is an emerging model system to study stem cell biology of flatworms. It is complementary to the well-studied planarians because of its small size, transparency, simple culture maintenance, the basal taxonomic position and its less derived embryogenesis that is more closely related to spiralians. The development of cell-, tissue- and organ specific markers is necessary to further characterize the differentiation potential of flatworm stem cells. Large scale in situ hybridization is a suitable tool to identify possible markers. Distinguished genes identified in a large scale screen in combination with manipulation of neoblasts by hydroxyurea or irradiation will advance our understanding of differentiation and regulation of the flatworm stem cell system. Results We have set up a protocol for high throughput large scale whole mount in situ hybridization for the flatworm Macrostomum lignano. In the pilot screen, a number of cell-, tissue- or organ specific expression patterns were identified. We have selected two stem cell- and germ cell related genes – macvasa and macpiwi – and studied effects of hydroxyurea (HU treatment or irradiation on gene expression. In addition, we have followed cell proliferation using a mitosis marker and bromodeoxyuridine labeling of S-phase cells after various periods of HU exposure or different irradiation levels. HU mediated depletion of cell proliferation and HU induced reduction of gene expression was used to generate a cDNA library by suppressive subtractive hybridization. 147 differentially expressed genes were sequenced and assigned to different categories. Conclusion We show that Macrostomum lignano is a suitable organism to perform high throughput large

  3. An improved sensitive assay for the detection of PSP toxins with neuroblastoma cell-based impedance biosensor. (United States)

    Zou, Ling; Wu, Chunsheng; Wang, Qin; Zhou, Jie; Su, Kaiqi; Li, Hongbo; Hu, Ning; Wang, Ping


    Paralytic shellfish poisoning (PSP) toxins are well-known sodium channel-blocking marine toxins, which block the conduction of nerve impulses and lead to a series of neurological disorders symptoms. However, PSP toxins can inhibit the cytotoxicity effect of compounds (e.g., ouabain and veratridine). Under the treatment of ouabain and veratridine, neuroblastoma cell will swell and die gradually, since veratridine causes the persistent inflow of Na(+) and ouabain inhibits the activity of Na(+)/K(+)-ATPases. Therefore, PSP toxins with antagonism effect can raise the chance of cell survival by blocking inflow of Na(+). Based on the antagonism effect of PSP toxins, we designed an improved cell-based assay to detect PSP toxins using a neuroblastoma cell-based impedance biosensor. The results demonstrated that this biosensor showed high sensitivity and good specificity for saxitoxins detection. The detection limit of this biosensor was as low as 0.03 ng/ml, which was lower than previous reported cell-based assays and mouse bioassays. With the improvement of biosensor performance, the neuroblastoma cell-based impedance biosensor has great potential to be a universal PSP screening method.

  4. A Touch-screen Experimental Information System Based on JSP%基于JS P技术的触摸屏实验信息系统

    Institute of Scientific and Technical Information of China (English)

    李帅鹏; 林晓珑; 高春歌; 姜永恒


    This paper presented a touch-screen experimental information system based on JSP.The construction of this system mainly considers that according to the combination of JSP,JDK and JDBC, we establish an experimental information database,and the client user can use a touch-screen to query, add and delete the contents of the experimental information database by executing standard SQL com-mands on a web page.Compare to the past,the system seems more convenient and quicker.%阐述了一种基于JSP技术的触摸屏实验信息系统。该系统的构建重点考虑了通过JSP、JDK与JDBC技术相结合,建立实验信息数据库,在网页上执行SQL命令,使用触摸屏实现查询、添加和删除服务器上实验信息数据库的内容。

  5. Evaluation of a 3D system based on a high-quality flat screen and polarized glasses for use by surgical assistants during robotic surgery

    Directory of Open Access Journals (Sweden)

    Kazushi Tanaka


    Full Text Available Introduction: One of the main benefits of robotic surgery is the surgeon′s three-dimensional (3D vision system. The purpose of this study is to evaluate the efficacy of 3D vision using a flat screen and polarized glasses for surgical skills during robotic surgeries. Materials and Methods: In an experimental model, six surgeons performed three surgical tasks with laparoscopic devices using a standard 2D and a flat-screen 3D model with polarized glasses. Performance times were compared between two-dimensional (2D and 3D vision for each task. The surgeons also graded the efficiency of the 3D system, on a subjective scale of 0-100. Results: Performance times for task 1 (seven holes and 2 (elastic bands were significantly reduced by 84% and 56% using 3D compared with a 2D system and experienced surgeons performed all three tasks faster in 3D than 2D. The surgeons reported the polarized glasses were comfortable to wear and direct vision was seldom affected. Conclusions: The use of 3D visualization seems to improve the efficiency of surgical skills during robotic surgery and reduce performance time for characteristic surgical procedure tasks.

  6. Screening and assessment of performance and molecule quality attributes of industrial cell lines across different fed-batch systems. (United States)

    Rouiller, Yolande; Bielser, Jean-Marc; Brühlmann, David; Jordan, Martin; Broly, Hervé; Stettler, Matthieu


    The major challenge in the selection process of recombinant cell lines for the production of biologics is the choice, early in development, of a clonal cell line presenting a high productivity and optimal cell growth. Most importantly, the selected candidate needs to generate a product quality profile which is adequate with respect to safety and efficacy and which is preserved across cell culture scales. We developed a high-throughput screening and selection strategy of recombinant cell lines, based on their productivity in shaking 96-deepwell plates operated in fed-batch mode, which enables the identification of cell lines maintaining their high productivity at larger scales. Twelve recombinant cell lines expressing the same antibody with different productivities were selected out of 470 clonal cell lines in 96-deepwell plate fed-batch culture. They were tested under the same conditions in 50 mL vented shake tubes, microscale and lab-scale bioreactors in order to confirm the maintenance of their performance at larger scales. The use of a feeding protocol and culture conditions which are essentially the same across the different scales was essential to maintain productivity and product quality profiles across scales. Compared to currently used approaches, this strategy has the advantage of speeding up the selection process and increases the number of screened clones for getting high-producing recombinant cell lines at manufacturing scale with the desired performance and quality.

  7. A high-throughput fluorescence-based assay system for appetite-regulating gene and drug screening.

    Directory of Open Access Journals (Sweden)

    Yasuhito Shimada

    Full Text Available The increasing number of people suffering from metabolic syndrome and obesity is becoming a serious problem not only in developed countries, but also in developing countries. However, there are few agents currently approved for the treatment of obesity. Those that are available are mainly appetite suppressants and gastrointestinal fat blockers. We have developed a simple and rapid method for the measurement of the feeding volume of Danio rerio (zebrafish. This assay can be used to screen appetite suppressants and enhancers. In this study, zebrafish were fed viable paramecia that were fluorescently-labeled, and feeding volume was measured using a 96-well microplate reader. Gene expression analysis of brain-derived neurotrophic factor (bdnf, knockdown of appetite-regulating genes (neuropeptide Y, preproinsulin, melanocortin 4 receptor, agouti related protein, and cannabinoid receptor 1, and the administration of clinical appetite suppressants (fluoxetine, sibutramine, mazindol, phentermine, and rimonabant revealed the similarity among mechanisms regulating appetite in zebrafish and mammals. In combination with behavioral analysis, we were able to evaluate adverse effects on locomotor activities from gene knockdown and chemical treatments. In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers.

  8. Standard Cell-Based Implementation of a Digital Optoelectronic Neural-Network Hardware (United States)

    Maier, Klaus D.; Beckstein, Clemens; Blickhan, Reinhard; Erhard, Werner


    A standard cell-based implementation of a digital optoelectronic neural-network architecture is presented. The overall structure of the multilayer perceptron network that was used, the optoelectronic interconnection system between the layers, and all components required in each layer are defined. The design process from VHDL-based modeling from synthesis and partly automatic placing and routing to the final editing of one layer of the circuit of the multilayer perceptrons are described. A suitable approach for the standard cell-based design of optoelectronic systems is presented, and shortcomings of the design tool that was used are pointed out. The layout for the microelectronic circuit of one layer in a multilayer perceptron neural network with a performance potential 1 magnitude higher than neural networks that are purely electronic based has been successfully designed.

  9. A multi-agent cell-based model for wound contraction. (United States)

    Boon, W M; Koppenol, D C; Vermolen, F J


    A mathematical model for wound contraction is presented. The model is based on a cell-based formalism where fibroblasts, myofibroblasts and the immune reaction are taken into account. The model is used to simulate contraction of a wound using point forces on the cell boundary and it also determines the orientation of collagen after restoration of the damage. The paper presents the mathematical model in terms of the equations and assumptions, as well as some implications of the modelling. The present model predicts that the amount of final contraction is larger if the migration velocity of the leukocytes is larger and hence it is important that the immune system functions well to prevent contractures. Further, the present model is the first cell-based model that combines the immune system to final contractions.

  10. Cell-based delivery of brain-derived neurotrophic factor in experimental allergic encephalomyelitis. (United States)

    Makar, Tapas K; Nimmagadda, Vamshi K C; Trisler, David; Bever, Christopher T


    Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine with neuroprotective properties that has been identified as a potential therapeutic agent for diseases of the central nervous system (CNS). The use of BDNF has been limited by a short serum half-life and poor penetration of the blood-brain barrier. To address this limitation we have explored cell-based approaches to delivery. We have used experimental allergic encephalomyelitis (EAE), an inflammatory disease of the CNS, as a model system. We engineered hematopoietic stem cells to produce BDNF to determine the feasibility and effectiveness of cell-based delivery of BDNF into the CNS in EAE. We review those studies here.

  11. Potentiometric strip cell based on carbon nanotubes as transducer layer: toward low-cost decentralized measurements. (United States)

    Rius-Ruiz, F Xavier; Crespo, Gastón A; Bejarano-Nosas, Diego; Blondeau, Pascal; Riu, Jordi; Rius, F Xavier


    In this study, we developed a potentiometric planar strip cell based on single-walled carbon nanotubes that aims to exploit the attributes of solid-contact ion-selective electrodes for decentralized measurements. That is, the ion-selective and reference electrodes have been simultaneously miniaturized onto a plastic planar substrate by screen-printing and drop-casting techniques, obtaining disposable strip cells with satisfactory performance characteristics (i.e., the sensitivity is 57.4 ± 1.3 mV/dec, the response time is ≤30 s within the linear range from log a(K+) = -5 to -2, and the limit of detection is -6.5), no need of maintenance during long dry storage, quick signal stabilization, and light insensitivity in short-term measurements. We also show how the new potentiometric strip cell makes it possible to perform decentralized and rapid determinations of ions in real samples, such as saliva or beverages.

  12. Stem Cell-Based Therapies in Chagasic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Campos de Carvalho


    Full Text Available Chagas disease is caused by Trypanosoma cruzi and can lead to a dilated cardiomyopathy decades after the prime infection by the parasite. As with other dilated cardiomyopathies, conventional pharmacologic therapies are not always effective and as heart failure progresses patients need heart transplantation. Therefore alternative therapies are highly desirable and cell-based therapies have been investigated in preclinical and clinical studies. In this paper we review the main findings of such studies and discuss future directions for stem cell-based therapies in chronic chagasic cardiomyopathy.

  13. A novel multiplex cell viability assay for high-throughput RNAi screening.

    Directory of Open Access Journals (Sweden)

    Daniel F Gilbert

    Full Text Available Cell-based high-throughput RNAi screening has become a powerful research tool in addressing a variety of biological questions. In RNAi screening, one of the most commonly applied assay system is measuring the fitness of cells that is usually quantified using fluorescence, luminescence and absorption-based readouts. These methods, typically implemented and scaled to large-scale screening format, however often only yield limited information on the cell fitness phenotype due to evaluation of a single and indirect physiological indicator. To address this problem, we have established a cell fitness multiplexing assay which combines a biochemical approach and two fluorescence-based assaying methods. We applied this assay in a large-scale RNAi screening experiment with siRNA pools targeting the human kinome in different modified HEK293 cell lines. Subsequent analysis of ranked fitness phenotypes assessed by the different assaying methods revealed average phenotype intersections of 50.7±2.3%-58.7±14.4% when two indicators were combined and 40-48% when a third indicator was taken into account. From these observations we conclude that combination of multiple fitness measures may decrease false-positive rates and increases confidence for hit selection. Our robust experimental and analytical method improves the classical approach in terms of time, data comprehensiveness and cost.

  14. A novel multiplex cell viability assay for high-throughput RNAi screening. (United States)

    Gilbert, Daniel F; Erdmann, Gerrit; Zhang, Xian; Fritzsche, Anja; Demir, Kubilay; Jaedicke, Andreas; Muehlenberg, Katja; Wanker, Erich E; Boutros, Michael


    Cell-based high-throughput RNAi screening has become a powerful research tool in addressing a variety of biological questions. In RNAi screening, one of the most commonly applied assay system is measuring the fitness of cells that is usually quantified using fluorescence, luminescence and absorption-based readouts. These methods, typically implemented and scaled to large-scale screening format, however often only yield limited information on the cell fitness phenotype due to evaluation of a single and indirect physiological indicator. To address this problem, we have established a cell fitness multiplexing assay which combines a biochemical approach and two fluorescence-based assaying methods. We applied this assay in a large-scale RNAi screening experiment with siRNA pools targeting the human kinome in different modified HEK293 cell lines. Subsequent analysis of ranked fitness phenotypes assessed by the different assaying methods revealed average phenotype intersections of 50.7±2.3%-58.7±14.4% when two indicators were combined and 40-48% when a third indicator was taken into account. From these observations we conclude that combination of multiple fitness measures may decrease false-positive rates and increases confidence for hit selection. Our robust experimental and analytical method improves the classical approach in terms of time, data comprehensiveness and cost.

  15. Essential attributes identified in the design of a Laboratory Information Management System for a high throughput siRNA screening laboratory. (United States)

    Grandjean, Geoffrey; Graham, Ryan; Bartholomeusz, Geoffrey


    In recent years high throughput screening operations have become a critical application in functional and translational research. Although a seemingly unmanageable amount of data is generated by these high-throughput, large-scale techniques, through careful planning, an effective Laboratory Information Management System (LIMS) can be developed and implemented in order to streamline all phases of a workflow. Just as important as data mining and analysis procedures at the end of complex processes is the tracking of individual steps of applications that generate such data. Ultimately, the use of a customized LIMS will enable users to extract meaningful results from large datasets while trusting the robustness of their assays. To illustrate the design of a custom LIMS, this practical example is provided to highlight the important aspects of the design of a LIMS to effectively modulate all aspects of an siRNA screening service. This system incorporates inventory management, control of workflow, data handling and interaction with investigators, statisticians and administrators. All these modules are regulated in a synchronous manner within the LIMS.

  16. The promise of fuel cell-based automobiles

    Indian Academy of Sciences (India)

    A K Shukla; C L Jackson; K Scott


    Fuel cell-based automobiles have gained attention in the last few years due to growing public concern about urban air pollution and consequent environmental problems. From an analysis of the power and energy requirements of a modern car, it is estimated that a base sustainable power of $ca$. 50 kW supplemented with short bursts up to 80 kW will suffice in most driving requirements. The energy demand depends greatly on driving characteristics but under normal usage is expected to be 200 Wh/km. The advantages and disadvantages of candidate fuel-cell systems and various fuels are considered together with the issue of whether the fuel should be converted directly in the fuel cell or should be reformed to hydrogen onboard the vehicle. For fuel cell vehicles to compete successfully with conventional internal-combustion engine vehicles, it appears that direct conversion fuel cells using probably hydrogen, but possibly methanol, are the only realistic contenders for road transportation applications. Among the available fuel cell technologies, polymer–electrolyte fuel cells directly fueled with hydrogen appear to be the best option for powering fuel cell vehicles as there is every prospect that these will exceed the performance of the internal-combustion engine vehicles but for their first cost. A target cost of $ 50/kW would be mandatory to make polymer–electrolyte fuel cells competitive with the internal combustion engines and can only be achieved with design changes that would substantially reduce the quantity of materials used. At present, prominent car manufacturers are deploying important research and development efforts to develop fuel cell vehicles and are projecting to start production by 2005.

  17. Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening

    Directory of Open Access Journals (Sweden)

    Nancy S. Green MD


    Full Text Available Sickle cell disease (SCD is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa.

  18. Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening. (United States)

    Green, Nancy S; Mathur, Sanyukta; Kiguli, Sarah; Makani, Julie; Fashakin, Victoria; LaRussa, Philip; Lyimo, Magdalena; Abrams, Elaine J; Mulumba, Lukia; Mupere, Ezekiel


    Sickle cell disease (SCD) is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa.

  19. Erkitinib, a novel EGFR tyrosine kinase inhibitor screened using a ProteoChip system from a phytochemical library

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eung-Yoon; Choi, Young-Jin [Biochip Research Center, Hoseo University, Asan 336-795 (Korea, Republic of); Innopharmascreen, Inc., Asan 336-795 (Korea, Republic of); Park, Chan-Won [Biochip Research Center, Hoseo University, Asan 336-795 (Korea, Republic of); Dept. of Biological Science, Hoseo University, Asan 336-795 (Korea, Republic of); Kang, In-Cheol, E-mail: [Biochip Research Center, Hoseo University, Asan 336-795 (Korea, Republic of); Dept. of Biological Science, Hoseo University, Asan 336-795 (Korea, Republic of); Innopharmascreen, Inc., Asan 336-795 (Korea, Republic of)


    Receptor tyrosine kinases (PTKs) play key roles in the pathogenesis of numerous human diseases, including cancer. Therefore PTK inhibitors are currently under intensive investigation as potential drug candidates. Herein, we report on a ProteoChip-based screening of an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor, Erkitinibs, from phytochemical libraries. PLC-{gamma}-1 was used as a substrate immobilized on a ProteoChip and incubated with an EGFR kinase to phosphorylate tyrosine residues of the substrate, followed by a fluorescence detection of the substrate recognized by a phospho-specific monoclonal antibody. Erkitinibs inhibited HeLa cell proliferation in a dose-dependent manner. In conclusion, these data suggest that Erkitinibs can be a specific inhibitor of an EGFR kinase and can be further developed as a potent anti-tumor agent.

  20. Human cell-based micro electrode array platform for studying neurotoxicity

    Directory of Open Access Journals (Sweden)

    Laura eYlä-Outinen


    Full Text Available At present, most of the neurotoxicological analyses are based on in vitro and in vivo models utilizing animal cells or animal models. In addition, the used in vitro models are mostly based on molecular biological end-point analyses. Thus, for neurotoxicological screening, human cell-based analysis platforms in which the functional neuronal networks responses for various neurotoxicants can be also detected real-time are highly needed. Microelectrode array (MEA is a method which enables the measurement of functional activity of neuronal cell networks in vitro for long periods of time. Here, we utilize MEA to study the neurotoxicity of methyl mercury chloride (MeHgCl, concentrations 0.5-500 nM to human embryonic stem cell (hESC-derived neuronal cell networks exhibiting spontaneous electrical activity. The neuronal cell cultures were matured on MEAs into networks expressing spontaneous spike train-like activity before exposing the cells to MeHgCl for 72 hours. MEA measurements were performed acutely and 24, 48, and 72 hours after the onset of the exposure. Finally, exposed cells were analyzed with traditional molecular biological methods for cell proliferation, cell survival, and gene and protein expression. Our results show that 500 nM MeHgCl decreases the electrical signaling and alters the pharmacologic response of hESC-derived neuronal networks in delayed manner whereas effects can not be detected with qRT-PCR, immunostainings, or proliferation measurements. Thus, we conclude that human cell-based MEA-platform is a sensitive online method for neurotoxicological screening.

  1. Mapping quantum yield for (Fe-Zn-Sn-Ti)Ox photoabsorbers using a high throughput photoelectrochemical screening system. (United States)

    Xiang, Chengxiang; Haber, Joel; Marcin, Martin; Mitrovic, Slobodan; Jin, Jian; Gregoire, John M


    Combinatorial synthesis and screening of light absorbers are critical to material discoveries for photovoltaic and photoelectrochemical applications. One of the most effective ways to evaluate the energy-conversion properties of a semiconducting light absorber is to form an asymmetric junction and investigate the photogeneration, transport and recombination processes at the semiconductor interface. This standard photoelectrochemical measurement is readily made on a semiconductor sample with a back-side metallic contact (working electrode) and front-side solution contact. In a typical combinatorial material library, each sample shares a common back contact, requiring novel instrumentation to provide spatially resolved and thus sample-resolved measurements. We developed a multiplexing counter electrode with a thin layer assembly, in which a rectifying semiconductor/liquid junction was formed and the short-circuit photocurrent was measured under chopped illumination for each sample in a material library. The multiplexing counter electrode assembly demonstrated a photocurrent sensitivity of sub-10 μA cm(-2) with an external quantum yield sensitivity of 0.5% for each semiconductor sample under a monochromatic ultraviolet illumination source. The combination of cell architecture and multiplexing allows high-throughput modes of operation, including both fast-serial and parallel measurements. To demonstrate the performance of the instrument, the external quantum yields of 1819 different compositions from a pseudoquaternary metal oxide library, (Fe-Zn-Sn-Ti)Ox, at 385 nm were collected in scanning serial mode with a throughput of as fast as 1 s per sample. Preliminary screening results identified a promising ternary composition region centered at Fe0.894Sn0.103Ti0.0034Ox, with an external quantum yield of 6.7% at 385 nm.

  2. Breast cancer screening: ''reassuring'' the worried well?

    DEFF Research Database (Denmark)

    Brodersen, John; Siersma, Volkert; Ryle, Mette


    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...

  3. 360度可环视全屏体三维显示系统%360° Viewable Volumetric 3D Display System with Full Screen

    Institute of Scientific and Technical Information of China (English)

    刘影; 潘文平; 张赵行; 刘永; 陈兴华


    研究了一种全屏体三维显示系统.以数字微镜器件(DMD)作为空间光调制器(SLM),将三维模型的螺旋切片序列投射到高速旋转的螺旋屏上,由于视觉暂留效应,切片序列便被人眼感知为360度可环视的三维立体图像.重点分析了基于全屏的成像空间的性能,研究了基于增强型体心立方(EBCC)采样算法的体素化策略.实验结果表明,增强型BCC采样算法较基于笛卡尔栅格的采样算法减少了30%的体素量,同时避免了体素模型出现空洞; 基于全屏的体三维空间超过原来半屏体三维显示系统的4倍,生成的图像亮度均匀;在400mm×300mm×250mm的长方体形成像空间内显示的立体图像,可从360°范围内任意视点裸眼观看.%Abstract: A volumetric display system with full helical screen is presented. When a series of helical slices of a 3D model is projected onto a rotating helical screen through a Digital Micro-mirror Device (DMD) as a fast Space Light Modulator (SLM), due to the persistence of vision, human observers are able to perceive a 360° viewable 3D image by fusing together the successive helical slices into a 3D image. We analyze the performance of the 3D imaging space created by a rotating helical screen, and emphasize the volexlization approach based on Enhanced Body-center Cubic (EBCC) sampling algorithm. Experimental results demonstrate that, compared with the voxelization approach based on Cartesian lattice, voxel hole avoidance and a voxel reduction of more than 30% are both achieved through utilizing EBCC sampling algorithm, and the prototype is capable of generating images with consistent brightness in a imaging space three times bigger than our former system with half screen. In the cuboid imaging space with length 400 mm, width 300 mm and height of 250 mm, 3D images can be viewed from any viewpoint without any special eyewear.

  4. Lung Cancer Screening (United States)

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

  5. Skin Cancer Screening (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 ...

  6. Mental Health Screening Center (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 This screening form was developed from ...

  7. Testicular Cancer Screening (United States)

    ... Health Professional Testicular Cancer Treatment Testicular Cancer Screening Testicular Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Testicular Cancer Key Points Testicular cancer is a disease in ...

  8. Design of the fancy fountain control system based on the touch screen%基于触摸屏的花式喷泉控制系统设计

    Institute of Scientific and Technical Information of China (English)



    This article introduces the fancy fountain control system based on the touch screen, inclu-ding its main circuit design, control circuit design, PLC programming, touch screen configuration etc.%介绍了基于触摸屏的花式喷泉控制系统的主电路设计,控制电路设计,PLC程序设计,触摸屏组态等内容。

  9. Touch Screen and PLC in Cement Tank Monitoring System of Drilling Ship%触摸屏和PLC在钻井船输灰监测系统中的应用

    Institute of Scientific and Technical Information of China (English)

    孔祥伟; 于祥春; 孔凡旭; 杜刚; 宫俭纯


    The touch screen and PLC application in the cement tank monitoring system of drilling ship was introduced , including its working principle, PLC hardware configuration, network configuration and main touch screen interfaces.%将PLC和触摸屏应用于钻井船输灰监测系统,对灰罐工作原理、PLC硬件配置、网络组态和触摸屏主要界面进行了介绍.

  10. Establishment of an in vitro Peyer's patch cell culture system correlative to in vivo study using intestine and screening of lactic acid bacteria enhancing intestinal immunity. (United States)

    Jin, Hekui; Higashikawa, Fumiko; Noda, Masafumi; Zhao, Xingrong; Matoba, Yasuyuki; Kumagai, Takanori; Sugiyama, Masanori


    Some lactic acid bacteria (LAB) are known as representative of probiotics. To screen LAB effective to enhance intestinal immunity, in the present study, we developed an accurate and convenient in vitro evaluation system using Peyer's patch cells (PP-cells) isolated from the mice intestine. We observed that the amount of immunoglobulin A (IgA) produced by PP-cells co-cultured with LAB was well correlative to that in PP-cells, intestine and feces isolated from live mice after oral administration of LAB [correlation coefficient (r)=0.888, 0.883, and 0.920, respectively]. In addition, using this in vitro system, we suggest that the IgA level of PP-cells co-culturing with plant-derived LAB might be more enhanced than with animal-derived LAB.

  11. 酵母双杂交筛选PMEPA1互作蛋白%Screening for PMEPA1 Interacting Protein Using Yeast Two-hybrid System

    Institute of Scientific and Technical Information of China (English)

    罗深恒; 许丽红; 楚雯; 马岳; 刁爱坡


    采用酵母双杂交技术筛选与前列腺跨膜蛋白PMEPA1相互作用的蛋白质,构建了pGBKT7-PMEPA1诱饵质粒,获得与PMEPA1互作蛋白,GST pull-down实验确定2种蛋白间的相互作用.构建了诱饵载体转化酵母菌Y2HGold,对酵母宿主无毒性、无自激活活性.得到阳性克隆Dynactin6,GST pull-down实验证实PMEPA1与Dynactin6蛋白间相互作用.推测蛋白Dynactin6可能参与调控PMEPA1在细胞的运输.%To screen the candidate protein interacting with prostate transmembrane protein, androgen induced 1 (PMEPA1). The bait plasmid pGBKT7 - PMEPA1 was constructed and transformed into yeast strain Y2H Gold, and then validated by auto - activation and toxicity assays. A universal human library was used for screening with the bait plasmid pGBKT7 - PMEPA1, and positive clones were selected after screening and co - transformation identification. The interaction between two proteins was further analyzed by GST pull - down. The bait plasmid pG-BKT7 - PMEPA1 was successfully constructed. No auto - activation and toxicity were detected. A target protein of Dynactin6 was fished out and GST pull - down assay confirmed the interaction between PMEPA1 and Dynactin6. Dynactin6 was identified as a PMEPA1 interacting protein using yeast two - hybrid system, suggesting that Dynac-tin6 might be involved in regulating intracellular protein transport of PMEPA1. These results will lay a foundation to further study the biological function of PMEPA1.

  12. An integrated microfluidic system for screening of phage-displayed peptides specific to colon cancer cells and colon cancer stem cells. (United States)

    Che, Yu-Jui; Wu, Huei-Wen; Hung, Lien-Yu; Liu, Ching-Ann; Chang, Hwan-You; Wang, Kuan; Lee, Gwo-Bin


    Affinity reagents recognizing biomarkers specifically are essential components of clinical diagnostics and target therapeutics. However, conventional methods for screening of these reagents often have drawbacks such as large reagent consumption, the labor-intensive or time-consuming procedures, and the involvement of bulky or expensive equipment. Alternatively, microfluidic platforms could potentially automate the screening process within a shorter period of time and reduce reagent and sample consumption dramatically. It has been demonstrated recently that a subpopulation of tumor cells known as cancer stem cells possess high drug resistance and proliferation potential and are regarded as the main cause of metastasis. Therefore, a peptide that recognizes cancer stem cells and differentiates them from other cancer cells will be extremely useful in early diagnosis and target therapy. This study utilized M13 phage display technology to identify peptides that bind, respectively, to colon cancer cells and colon cancer stem cells using an integrated microfluidic system. In addition to positive selection, a negative selection process was integrated on the chip to achieve the selection of peptides of high affinity and specificity. We successfully screened three peptides specific to colon cancer cells and colon cancer stem cells, namely, HOLC-1, HOLC-2, and COLC-1, respectively, and their specificity was measured by the capture rate between target, control, and other cell lines. The capture rates are 43.40 ± 7.23%, 45.16 ± 7.12%, and 49.79 ± 5.34% for colon cancer cells and colon cancer stem cells, respectively, showing a higher specificity on target cells than on control and other cell lines. The developed technique may be promising for early diagnosis of cancer cells and target therapeutics.

  13. Global Distribution of Businesses Marketing Stem Cell-Based Interventions. (United States)

    Berger, Israel; Ahmad, Amina; Bansal, Akhil; Kapoor, Tanvir; Sipp, Douglas; Rasko, John E J


    A structured search reveals that online marketing of stem-cell-based interventions is skewed toward developed economies including the United States, Ireland, Australia, and Germany. Websites made broad, imprecise therapeutic claims and frequently failed to detail procedures. Widespread marketing poses challenges to regulators, bioethicists, and those seeking realistic hope from therapies.

  14. Meganuclease-driven targeted integration in CHO-K1 cells for the fast generation of HTS-compatible cell-based assays. (United States)

    Cabaniols, Jean-Pierre; Ouvry, Christine; Lamamy, Véronique; Fery, Isabelle; Craplet, Marie-Laure; Moulharat, Natacha; Guenin, Sophie-Pénélope; Bedut, Stéphane; Nosjean, Olivier; Ferry, Gilles; Devavry, Séverine; Jacqmarcq, Cécile; Lebuhotel, Céline; Mathis, Luc; Delenda, Christophe; Boutin, Jean A; Duchâteau, Philippe; Cogé, Francis; Pâques, Frédéric


    The development of cell-based assays for high-throughput screening (HTS) approaches often requires the generation of stable transformant cell lines. However, these cell lines are essentially created by random integration of a gene of interest (GOI) with no control over the level and stability of gene expression. The authors developed a targeted integration system in Chinese hamster ovary (CHO) cells, called the cellular genome positioning system (cGPS), based on the stimulation of homologous gene targeting by meganucleases. Five different GOIs were knocked in at the same locus in cGPS CHO-K1 cells. Further characterization revealed that the cGPS CHO-K1 system is more rapid (2-week protocol), efficient (all selected clones expressed the GOI), reproducible (GOI expression level variation of 12%), and stable over time (no change in GOI expression after 23 weeks of culture) than classical random integration. Moreover, in all cGPS CHO-K1 targeted clones, the recombinant protein was biologically active and its properties similar to the endogenous protein. This fast and robust method opens the door for creating large collections of cell lines of better quality and expressing therapeutically relevant GOIs at physiological levels, thereby enhancing the potential scope of HTS.

  15. Development of a miniature dielectric barrier discharge–optical emission spectrometric system for bromide and bromate screening in environmental water samples

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yong-Liang [Department of Chemistry, College of Sciences, Northeastern University, Box 332, Shenyang 110819 (China); Research Center for Analytical Sciences, College of Sciences, Northeastern University, Box 332, Shenyang 110819 (China); Cai, Yi [Research Center for Analytical Sciences, College of Sciences, Northeastern University, Box 332, Shenyang 110819 (China); Chen, Ming-Li, E-mail: [Research Center for Analytical Sciences, College of Sciences, Northeastern University, Box 332, Shenyang 110819 (China); Wang, Jian-Hua, E-mail: [Research Center for Analytical Sciences, College of Sciences, Northeastern University, Box 332, Shenyang 110819 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071 (China)


    Graphical abstract: -- Highlights: •Dielectric barrier discharge (DBD) is for the first time used as a radiation source for the excitation of bromine and its emission. •A DBD–optical emission spectrometric (OES) system was developed for the detection of bromide and bromate. •The DBD–OES system has been demonstrated by screening trace bromide and bromate in a series of environmental water samples. -- Abstract: Dielectric barrier discharge (DBD) at atmospheric pressure provides an efficient radiation source for the excitation of bromine and it is used for the first time for optical emission spectrometric (OES) detection of bromide and bromate. A portable DBD–OES system is developed for screening potential pollution from bromide and bromate in environmental waters. Bromide is on-line oxidized to bromine for in-situ generation of volatile bromine. Meanwhile, a helium stream carries bromine into the DBD micro-plasma for its excitation at a discharging voltage of 3.7 kV and optical emission spectrometric detection with a QE65000 charge-coupled device (CCD) spectrometer in the near-infrared spectral region. Similarly, the quantification of bromate is performed by its pre-reduction into bromide and then oxidized to bromine. The spectral characteristics and configuration of the DBD micro-plasma excitation source in addition to the oxidation vapor generation of bromine have been thoroughly investigated. With a sampling volume of 1 mL, a linear range of 0.05–10.0 mg L{sup −1} is obtained with a detection limit of 0.014 mg L{sup −1} by measuring the emission at 827 nm. A precision of 2.3% is achieved at 3 mg L{sup −1} bromide. The system is validated by bromine detection in certified reference material of laver (GBW10023) at mg L{sup −1} level, giving rise to satisfactory agreement. In addition, it is further demonstrated by screening trace bromide and bromate as well as spiking recoveries in a series of environmental water samples.

  16. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

    Directory of Open Access Journals (Sweden)

    Chan Koon H


    Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

  17. Screen-Capturing System with Two-Layer Display for PowerPoint Presentation to Enhance Classroom Education (United States)

    Lai, Yen-Shou; Tsai, Hung-Hsu; Yu, Pao-Ta


    This paper proposes a new presentation system integrating a Microsoft PowerPoint presentation in a two-layer method, called the TL system, to promote learning in a physical classroom. With the TL system, teachers can readily control hints or annotations as a way of making them visible or invisible to students so as to reduce information load. In…

  18. Multidimensional GPCR profiling and screening using impedance-based label-free and real-time assay. (United States)

    Ke, Ning; Nguyen, Khanh; Irelan, Jeffery; Abassi, Yama A


    GPCRs constitute one of the most sought-after targets in drug discovery because they are associated with conditions ranging from cardiovascular diseases, autoimmune diseases, inflammation, cancer, and diseases of the nervous system. Moreover, they are one of the most amenable targets for drug discovery because they can be modulated by small molecules, peptides, proteins, and antibodies. Therefore it may not come as a surprise that close to 40 % of the drugs that are currently on the market are targeting GPCRs. It has become evident that GPCR signaling is highly complex and may involve multiple or a subset of pathways depending on the interaction of a GPCR with an agonist or antagonist. It is imperative that any functional screening for GPCR activity integrates this complexity. In this assay protocol, we describe how the xCELLigence RTCA HT impedance-based platform which can be used for functional cell-based GPCR assays can be utilized for GPCR screening.

  19. Screening of hepatocyte proteins binding with the middle surface protein of the hepatitis B virus by the yeast two-hybrid system.