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Sample records for cell-based screen reverses

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Cell-based screens and phenomics with fission yeast.

    Science.gov (United States)

    Rallis, Charalampos; Bähler, Jürg

    2016-01-01

    Next-generation sequencing approaches have considerably advanced our understanding of genome function and regulation. However, the knowledge of gene function and complex cellular processes remains a challenge and bottleneck in biological research. Phenomics is a rapidly emerging area, which seeks to rigorously characterize all phenotypes associated with genes or gene variants. Such high-throughput phenotyping under different conditions can be a potent approach toward gene function. The fission yeast Schizosaccharomyces pombe (S. pombe) is a proven eukaryotic model organism that is increasingly used for genomewide screens and phenomic assays. In this review, we highlight current large-scale, cell-based approaches used with S. pombe, including computational colony-growth measurements, genetic interaction screens, parallel profiling using barcodes, microscopy-based cell profiling, metabolomic methods and transposon mutagenesis. These diverse methods are starting to offer rich insights into the relationship between genotypes and phenotypes. PMID:26523839

  3. Methane Screening in JET Reverse Field Experiments

    International Nuclear Information System (INIS)

    JET plasmas with reverse magnetic field feature a different SOL flow than those with normal field. The observed carbon fueling efficiency from injecting methane gas was similar in reverse and normal field. EDGE2D modeling used an externally applied force to create the SOL flows, without specifying the origin of the force. The resulting flow agreed reasonably with the experimental values between the separatrix and 4 cm mid-plane depth in the SOL. The effect of the flow on the calculated carbon screening was 5 to 15% higher carbon fueling efficiency for the low flow velocity with reverse field

  4. Cell-based phenotypic screening of mast cell degranulation unveils kinetic perturbations of agents targeting phosphorylation

    Science.gov (United States)

    Qin, Shenlu; Wang, Xumeng; Wu, Huanwen; Xiao, Peng; Cheng, Hongqiang; Zhang, Xue; Ke, Yuehai

    2016-01-01

    Mast cells play an essential role in initiating allergic diseases. The activation of mast cells are controlled by a complicated signal network of reversible phosphorylation, and finding the key regulators involved in this network has been the focus of the pharmaceutical industry. In this work, we used a method named Time-dependent cell responding profile (TCRP) to track the process of mast cell degranulation under various perturbations caused by agents targeting phosphorylation. To test the feasibility of this high-throughput cell-based phenotypic screening method, a variety of biological techniques were used. We further screened 145 inhibitors and clustered them based on the similarities of their TCRPs. Stat3 phosphorylation has been widely reported as a key step in mast cell degranulation. Interestingly, our TCRP results showed that a Stat3 inhibitor JSI124 did not inhibit degranulation like other Stat3 inhibitors, such as Stattic, clearly inhibited degranulation. Regular endpoint assays demonstrated that the distinctive TCRP of JSI124 potentially correlated with the ability to induce apoptosis. Consequently, different agents possibly have disparate functions, which can be conveniently detected by TCRP. From this perspective, our TCRP screening method is reliable and sensitive when it comes to discovering and selecting novel compounds for new drug developments. PMID:27502076

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...... will continue to be valuable discovery tools, the most exciting developments in the field involve cell-based assays for GPCR function. Some cell-based discovery strategies, such as the use of beta-arrestin as a surrogate marker for GPCR function, have already been reduced to practice, and have been used...... as valuable discovery tools for several years. The application of high content cell-based screening to GPCR discovery has opened up additional possibilities, such as direct tracking of GPCRs, G proteins and other signaling pathway components using intracellular translocation assays. These assays provide...

  6. Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

    International Nuclear Information System (INIS)

    Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

  7. A cell-based screening system for anti-influenza A virus agents

    Science.gov (United States)

    Wong, Wan Ying; Loh, Sheng Wei; Ng, Wei Lun; Tan, Ming Cheang; Yeo, Kok Siong; Looi, Chung Yeng; Maah, Mohd Jamil; Ea, Chee-Kwee

    2015-01-01

    Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication. PMID:25728279

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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.

  9. Cell-based land use screening procedure for regional siting analysis

    International Nuclear Information System (INIS)

    An energy facility site-screening methodology which permits the land resource planner to identify candidate siting areas was developed. Through the use of spatial analysis procedures and computer graphics, a selection of candidate areas is obtained. Specific sites then may be selected from among candidate areas for environmental impact analysis. The computerized methodology utilizes a cell-based geographic information system for specifying the suitability of candidate areas for an energy facility. The criteria to be considered may be specified by the user and weighted in terms of importance. Three primary computer programs have been developed. These programs produce thematic maps, proximity calculations, and suitability calculations. Programs are written so as to be transferrable to regional planning or regulatory agencies to assist in rational and comprehensive power plant site identification and analysis

  10. 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

    2004-01-01

    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.

  11. Cell-Based Assay Design for High-Content Screening of Drug Candidates.

    Science.gov (United States)

    Nierode, Gregory; Kwon, Paul S; Dordick, Jonathan S; Kwon, Seok-Joon

    2016-02-01

    To reduce attrition in drug development, it is crucial to consider the development and implementation of translational phenotypic assays as well as decipher diverse molecular mechanisms of action for new molecular entities. High-throughput fluorescence and confocal microscopes with advanced analysis software have simplified the simultaneous identification and quantification of various cellular processes through what is now referred to as highcontent screening (HCS). HCS permits automated identification of modifiers of accessible and biologically relevant targets and can thus be used to detect gene interactions or identify toxic pathways of drug candidates to improve drug discovery and development processes. In this review, we summarize several HCS-compatible, biochemical, and molecular biology-driven assays, including immunohistochemistry, RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions to assess a variety of cellular processes, including proliferation, morphological changes, protein expression, localization, post-translational modifications, and protein-protein interactions. These cell-based assay methods can be applied to not only 2D cell culture but also 3D cell culture systems in a high-throughput manner. PMID:26428732

  12. A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening.

    Science.gov (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

    2015-12-01

    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.

  13. Development of an Online Cell-Based Bioactivity Screening Method by Coupling Liquid Chromatography to Flow Cytometry with Parallel Mass Spectrometry.

    Science.gov (United States)

    Otvos, Reka A; van Nierop, Pim; Niessen, Wilfried M A; Kini, R Manjunatha; Somsen, Govert W; Smit, August B; Kool, Jeroen

    2016-05-01

    This study describes a new platform for the fast and efficient functional screening for bioactive compounds in complex natural mixtures using a cell-based assay. The platform combines reversed-phase liquid chromatography (LC) with online flow cytometry (FC) and mass spectrometry (MS). As a model (an example or proof-of-concept study) we have used a functional calcium-flux assay in human neuroblastoma SH-SY5Y cells stably overexpressing the α-7 nicotinic acetylcholine receptor (α7-nAChR), a potential therapeutic target for central nervous system (CNS) related diseases. We have designed the coupled LC-FC system employing the neuroblastoma cells followed by analytical and pharmacological evaluation of the hyphenated setup in agonist and mixed antagonist-agonist assay modes. Using standard receptor ligands we have validated pharmacological responses and standardized good assay quality parameters. The applicability of the screening system was evaluated by analysis of various types of natural samples, such as a tobacco plant extract (in agonist assay mode) and snake venoms (in mixed antagonist-agonist assay mode). The bioactivity responses were correlated directly to the respective accurate masses of the compounds. Using simultaneous functional agonist and antagonist responses nicotine and known neurotoxins were detected from tobacco extract and snake venoms, respectively. Thus, the developed analytical screening technique represents a new tool for rapid measurement of functional cell-based responses and parallel separation and identification of compounds in complex mixtures targeting the α7-nAChR. It is anticipated that other fast-response cell-based assays (e.g., other ion flux assays) can be incorporated in this analytical setup. PMID:27046509

  14. A mammalian cell-based reverse two-hybrid system for functional analysis of 3C viral protease of human enterovirus 71.

    Science.gov (United States)

    Lee, Jin-Ching; Shih, Shin-Ru; Chang, Ten-Yuan; Tseng, Huan-Yi; Shih, Ya-Feng; Yen, Kuei-Jung; Chen, Wei-Chun; Shie, Jiun-Jie; Fang, Jim-Min; Liang, Po-Huang; Chao, Yu-Sheng; Hsu, John T-A

    2008-04-01

    Although several cell-based reporter assays have been developed for screening of viral protease inhibitors, most of these assays have a significant limitation in that numerous false positives can be generated for the compounds that are interfering with reporter gene detection due to the cellular viability. To improve, we developed a mammalian cell-based assay based on the reverse two-hybrid system to monitor the proteolytic activity of human enterovirus 71 (EV71) 3C protease and to validate the cytotoxicity of compounds at the same time. In this system, the GAL4 DNA binding domain (M3) and transactivation domain (VP16) were fused, in-frame, with 3C or 3C(mut). The 3C(mut) was an inactivated protease with mutations at the predicted catalytic triad. The reporter plasmid contains a secreted alkaline phosphatase (SEAP) gene under the control of GAL4 activating sequences. We demonstrated that M3-3C-VP16 failed to turn on the expression of SEAP due to the separation of M3 and the VP16 domains by self-cleavage of 3C. In contrast, SEAP expression was induced by the M3-3C(mut)-VP16 fusion protein or the M3-3C-VP16 in cells treated with AG7088, a potent inhibitor of human rhinoviruses (HRVs) 3C protease. Potentially, this protease detection system should greatly facilitate anti-EV71 drug discovery through a high-throughput screening. PMID:18190777

  15. Cell-Based High-Throughput Screening Identifies Rifapentine as an Inhibitor of Amyloid and Biofilm Formation in Escherichia coli.

    Science.gov (United States)

    Maher, Marie C; Lim, Ji Youn; Gunawan, Cheston; Cegelski, Lynette

    2015-10-01

    Escherichia coli assemble functional amyloid fibers termed curli that contribute to bacterial adhesion, biofilm formation, and host pathogenesis. We developed a cell-based high-throughput screen to identify inhibitors of curli-mediated adhesion in the laboratory strain MC4100 and curli-associated biofilm formation in the uropathogenic E. coli clinical isolate UTI89. Inhibitors of biofilm formation can operate through many mechanisms, and such inhibitors could hold therapeutic value in preventing and treating urinary tract infections. The curli-specific screen allows the identification of compounds that inhibit either curli expression, curli biogenesis, or adhesion by normally produced curli. In screening the NIH Clinical Collection of 446 compounds, we identified rifapentine as a potent inhibitor in both of these screens. Rifapentine is an antibiotic used to treat tuberculosis that targets RNA polymerase, but prevents curli-dependent adhesion and biofilm formation in E. coli at concentrations below those that affect viability. Rifapentine inhibits curli production and prevents biofilm formation on plastic, on agar, and at the air-liquid interface by inhibiting curli gene transcription. Comparisons with a cephalosporin antibiotic further revealed that curli production is not affected by standard antibiotic treatment and cell killing pressure. Thus, we reveal a new role independent of killing activity for rifapentine as an inhibitor of curli and curli-mediated biofilm formation. PMID:27623312

  16. A cell-based high-throughput screening assay for radiation susceptibility using automated cell counting

    International Nuclear Information System (INIS)

    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. There is thus a need to identify new targets and drugs for more effective sensitization of cancer cells to irradiation. Compound and RNA interference high-throughput screening technologies allow comprehensive enterprises to identify new agents and targets for radiosensitization. However, the gold standard assay to investigate radiosensitivity of cancer cells in vitro, the colony formation assay (CFA), is unsuitable for high-throughput screening. We developed a new high-throughput screening method for determining radiation susceptibility. Fast and uniform irradiation of batches up to 30 microplates was achieved using a Perspex container and a clinically employed linear accelerator. The readout was done by automated counting of fluorescently stained nuclei using the Acumen eX3 laser scanning cytometer. Assay performance was compared to that of the CFA and the CellTiter-Blue homogeneous uniform-well cell viability assay. The assay was validated in a whole-genome siRNA library screening setting using PC-3 prostate cancer cells. On 4 different cancer cell lines, the automated cell counting assay produced radiation dose response curves that followed a linear-quadratic equation and that exhibited a better correlation to the results of the CFA than did the cell viability assay. Moreover, the cell counting assay could be used to detect radiosensitization by silencing DNA-PKcs or by adding caffeine. In a high-throughput screening setting, using 4 Gy irradiated and control PC-3 cells, the effects of DNA-PKcs siRNA and non-targeting control siRNA could be clearly discriminated. We developed a simple assay for radiation susceptibility that can be used for high-throughput screening. This will aid

  17. Microengineering Methods for Cell Based Microarrays and High-Throughput Drug Screening Applications

    OpenAIRE

    Xu, Feng; Wu, Jinhui; Wang, Shuqi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

    2011-01-01

    Screening for effective therapeutic agents from millions of drug candidates is costly, time-consuming and often face ethical concerns due to extensive use of animals. To improve cost-effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems have facilitated automated and controlled component loading, significantly reducing the consumpti...

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

    Science.gov (United States)

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

    2015-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Du Peige

    2008-10-01

    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.

  20. 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

    2010-12-01

    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.

  1. Characterization of Sera with Discordant Results from Reverse Sequence Screening for Syphilis

    OpenAIRE

    Kyunghoon Lee; Hyewon Park; Eun Youn Roh; Sue Shin; Kyoung Un Park; Myoung Hee Park; Eun Young Song

    2013-01-01

    Reverse sequence screening for syphilis (RSSS) (screening with treponemal tests, followed by confirmation with nontreponemal tests) has been increasingly adopted. CDC recommends confirmation of discordant results (reactive EIA/CIA and nonreactive nontreponemal test) with Treponema pallidum particle agglutination assay (TP-PA). We characterized sera with discordant results from RSSS with Architect Syphilis TP CIA. Among 15,713 screening tests using Architect Syphilis TP at Seoul National Unive...

  2. Development of a quantitative, cell-based, high-content screening assay for epidermal growth factor receptor modulators

    Institute of Scientific and Technical Information of China (English)

    Jue WANG; Xin XIE

    2007-01-01

    Aim: To develop a robust, cell-based, high-content screening (HCS) assay based on receptor internalization for the identification of novel modulators of the epidermal growth factor receptor (EGFR). Methods: Agonist-induced receptor internalization is part of the signaling cascade of EGFR. Fluorescent-tagged epidermal growth factor (EGF) was used to visualize the internalized receptorligand complex. The fluorescent intracellular spots were detected and measured with an ArrayScan HCS reader. Compounds that can competitively bind to EGFR or interfere with EGFR internalization process would result in a reduced number and intensity of intracellular fluorescent spots. This assay was validated,optimized, and applied to a large-scale screening of a library containing 48 000 synthetic compounds. Results: The competition between fluorescent EGF and unlabeled EGF reveals the IC50 of unlabeled EGF is approximately 0.2 nmol/L,which is comparable with other published reports. Thirteen compounds with a relatively high degree of interference with EGFR internalization were identified.One of the compounds was proven to be agonist of the EGFR since it induced phosphorylation of the receptor and extracellular signal-regulated protein kinase (ERK). Conclusion: This automated, objective, and easy-to-use assay provided abundant information, quantitative results, and demonstrated the potential use of HCS methods in searching membrane receptor modulators.

  3. Cell-based assays and animal models for GPCR drug screening.

    Science.gov (United States)

    Takakura, Hideo; Hattori, Mitsuru; Tanaka, Miho; Ozawa, Takeaki

    2015-01-01

    The family of G protein-coupled receptors (GPCRs) remains a central focus of basic pharmacology and drug discovery efforts. Convenient methods to assess the efficacy of potentially therapeutic reagents for GPCRs are strongly required for high-throughput screening (HTS) assay. We recently developed a rapid, sensitive, and quantitative method for detecting potential chemicals that act on GPCRs using split luciferase complementation. In principle, this is based on the detection of interactions of GPCR with β-arrestin, which translocates to the activated GPCRs. This method can facilitate the construction of HTS systems in a multi-well plate format. Particularly, the method is compatible with single-cell imaging and animal models and even deeper tissues such as organs, because of its high sensitivity, suggesting that promising candidates from HTS assay can be moved easily to the next phase for additional analysis. This system can contribute to the effective evaluation of potentially therapeutic reagents and expedite the development of new drugs for GPCRs. PMID:25563190

  4. A cell-based model of α-synucleinopathy for screening compounds with therapeutic potential of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Da-long ZHAO; Li-bo ZOU; Lan-fang ZHOU; Ping ZHU; Hai-bo ZHU

    2007-01-01

    Aim: To develop a cell-based model by stable transfection of SH-SY5Y with mu-tant A53T human α-synuclein, recapitulating neurotoxicity of α-synuclein overexpression. Methods: The overexpression of mutant α-synuclein was ana-lyzed by Western blotting, immunocytochemistry, and RT-PCR. Cell viability was processed when treated with different concentrations of 1-methyl-4-phenyl-pyridinium (MPP+) and exogenous dopamine (DA) for 24, 48, and 72 h by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Early apoptosis and late apoptosis/necrosis were analyzed by flow cytometry using Annexin V and propidium iodide double staining, respectively. DNA was isolated and applied to agarose gel for electrophoresis; the typical DNA "ladder" repre-sented severe apoptosis. We also used this model to screen 99 compounds with therapeutic potential by MTT assay. Results: One of the stably-transfected clones overexpressed exogenous genes on both the protein level and the transcriptive level. Significant differences in cytotoxicity were found between the pcDNA3.1(+) group and the pcDNA3.1(+)-hmα-synuclein group in the presence of the same concentration of MPP+ and DA within the same incubation time. The level of either early apoptosis or late apoptosis/necrosis was remarkably increased in transfected cells compared with the control after treatment with 100 μmol/L MPP+ for 24 h. In addition, the presence of the typical DNA "ladder" was ob-served in the pcDNA3.1 (+)-hmα-synuclein group when treated with 200 μmol/L MPF+ for 48 h. After the screening experiment, 12 of the 99 compounds were found to decrease DA-induced cytotoxicity on cell viability. Conclusion: We estab-lished a cell-based model which is useful for studying the function of α-synuclein and screening compounds with therapeutic potential. In addition, it was identi-fied that cells overexpressing A53T mutant α-synuclein were significantly vulner-able against MPP+ or dopamine exposures.

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

    Directory of Open Access Journals (Sweden)

    Frick A

    2015-02-01

    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

  6. Direct Comparison of the Traditional and Reverse Syphilis Screening Algorithms in a Population with a Low Prevalence of Syphilis

    OpenAIRE

    Binnicker, Matthew J.; Jespersen, Deborah J.; Rollins, Leonard O.

    2012-01-01

    We describe the first direct comparison of the reverse and traditional syphilis screening algorithms in a population with a low prevalence of syphilis. Among 1,000 patients tested, the results for 6 patients were falsely reactive by reverse screening, compared to none by traditional testing. However, reverse screening identified 2 patients with possible latent syphilis that were not detected by rapid plasma reagin (RPR).

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

    DEFF Research Database (Denmark)

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

    multiplexing readouts, but this has a natural limitation. High-content screening via image acquisition and analysis allows multiplexing of few parameters, but is connected to substantial time consumption and complex logistics. We report on integration of Reverse Phase Protein Arrays (RPPA)-based readouts...

  8. 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

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

    Science.gov (United States)

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

    2016-08-15

    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. PMID:27235172

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

    Science.gov (United States)

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

    2016-08-15

    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.

  11. 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

    2007-10-24

    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.

  12. Reverse MAPPIT: screening for protein-protein interaction modifiers in mammalian cells.

    Science.gov (United States)

    Eyckerman, Sven; Lemmens, Irma; Catteeuw, Dominiek; Verhee, Annick; Vandekerckhove, Joel; Lievens, Sam; Tavernier, Jan

    2005-06-01

    Interactions between proteins are at the heart of the cellular machinery. It is therefore not surprising that altered interaction profiles caused by aberrant protein expression patterns or by the presence of mutations can trigger cellular dysfunction, eventually leading to disease. Moreover, many viral and bacterial pathogens rely on protein-protein interactions to exert their damaging effects. Interfering with such interactions is an obvious pharmaceutical goal, but detailed insights into the protein binding properties as well as efficient screening platforms are needed. In this report, we describe a cytokine receptor-based assay with a positive readout to screen for disrupters of designated protein-protein interactions in intact mammalian cells and evaluate this concept using polypeptides as well as small organic molecules. These reverse mammalian protein-protein interaction trap (MAPPIT) screens were developed to monitor interactions between the erythropoietin receptor (EpoR) and suppressors of cytokine signaling (SOCS) proteins, between FKBP12 and ALK4, and between MDM2 and p53. PMID:15908921

  13. Characterization of Sera with Discordant Results from Reverse Sequence Screening for Syphilis

    Directory of Open Access Journals (Sweden)

    Kyunghoon Lee

    2013-01-01

    Full Text Available Reverse sequence screening for syphilis (RSSS (screening with treponemal tests, followed by confirmation with nontreponemal tests has been increasingly adopted. CDC recommends confirmation of discordant results (reactive EIA/CIA and nonreactive nontreponemal test with Treponema pallidum particle agglutination assay (TP-PA. We characterized sera with discordant results from RSSS with Architect Syphilis TP CIA. Among 15,713 screening tests using Architect Syphilis TP at Seoul National University Gangnam Center between October 2010 and May 2011, 260 (1.7% showed reactive results. Rapid plasma reagin (RPR and TP-PA were performed on 153 available sera among them. On sera with discordant results between Architect Syphilis TP and TP-PA, INNO-LIA Syphilis Score and FTA-ABS were performed. Among 153 sera, RPR was nonreactive in 126 (82.4%. Among them, TP-PA was positive in 103 (81.7%, indeterminate (± in 7 (5.6%, and negative in 16 (12.7%. Out of 16 CIA(+/RPR(−/TP-PA(− sera, INNO-LIA Syphilis Score and/or FTA-ABS were negative on 14 sera. Out of 7 CIA(+/RPR(−/TP-PA(± sera, INNO-LIA Syphilis Score and FTA-ABS were positive/reactive in 6 sera. RSSS with confirmation by TP-PA on sera with discordant results between Architect Syphilis TP and RPR effectively delineated those discordant results and could be successfully adopted for routine checkup for syphilis.

  14. Syntheses and Cell-Based Phenotypic Screen of Novel 7-Amino pyrido[2,3-d]pyrimidine-6-carbonitrile Derivatives as Potential Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Yan-Ni Lin

    2012-02-01

    Full Text Available A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC50 value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC50 value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Yamashita, Atsuya; Fujimoto, Yuusuke; Tamaki, Mayumi; Setiawan, Andi; Tanaka, Tomohisa; Okuyama-Dobashi, Kaori; Kasai, Hirotake; Watashi, Koichi; Wakita, Takaji; Toyama, Masaaki; Baba, Masanori; de Voogd, Nicole J; Maekawa, Shinya; Enomoto, Nobuyuki; Tanaka, Junichi; Moriishi, Kohji

    2015-11-01

    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. PMID:26561821

  17. Identification of mechanistically distinct inhibitors of HIV-1 reverse transcriptase through fragment screening.

    Science.gov (United States)

    La, Jennifer; Latham, Catherine F; Tinetti, Ricky N; Johnson, Adam; Tyssen, David; Huber, Kelly D; Sluis-Cremer, Nicolas; Simpson, Jamie S; Headey, Stephen J; Chalmers, David K; Tachedjian, Gilda

    2015-06-01

    Fragment-based screening methods can be used to discover novel active site or allosteric inhibitors for therapeutic intervention. Using saturation transfer difference (STD) NMR and in vitro activity assays, we have identified fragment-sized inhibitors of HIV-1 reverse transcriptase (RT) with distinct chemical scaffolds and mechanisms compared to nonnucleoside RT inhibitors (NNRTIs) and nucleoside/nucleotide RT inhibitors (NRTIs). Three compounds were found to inhibit RNA- and DNA-dependent DNA polymerase activity of HIV-1 RT in the micromolar range while retaining potency against RT variants carrying one of three major NNRTI resistance mutations: K103N, Y181C, or G190A. These compounds also inhibit Moloney murine leukemia virus RT but not the Klenow fragment of Escherichia coli DNA polymerase I. Steady-state kinetic analyses demonstrate that one of these fragments is a competitive inhibitor of HIV-1 RT with respect to deoxyribonucleoside triphosphate (dNTP) substrate, whereas a second compound is a competitive inhibitor of RT polymerase activity with respect to the DNA template/primer (T/P), and consequently also inhibits RNase H activity. The dNTP competing RT inhibitor retains activity against the NRTI-resistant mutants K65R and M184V, demonstrating a drug resistance profile distinct from the nucleotide competing RT inhibitors indolopyridone-1 (INDOPY-1) and 4-dimethylamino-6-vinylpyrimidine-1 (DAVP-1). In antiviral assays, the T/P competing compound inhibits HIV-1 replication at a step consistent with an RT inhibitor. Screening of additional structurally related compounds to the three fragments led to the discovery of molecules with improved potency against HIV-1 RT. These fragment inhibitors represent previously unidentified scaffolds for development of novel drugs for HIV-1 prevention or treatment. PMID:26038551

  18. 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

    2015-11-01

    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.

  19. 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

    2015-03-01

    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

  20. Reverse Fluorescence Enhancement and Colorimetric Bimodal Signal Readout Immunochromatography Test Strip for Ultrasensitive Large-Scale Screening and Postoperative Monitoring.

    Science.gov (United States)

    Yao, Yingyi; Guo, Weisheng; Zhang, Jian; Wu, Yudong; Fu, Weihua; Liu, Tingting; Wu, Xiaoli; Wang, Hanjie; Gong, Xiaoqun; Liang, Xing-Jie; Chang, Jin

    2016-09-01

    Ultrasensitive and quantitative fast screening of cancer biomarkers by immunochromatography test strip (ICTS) is still challenging in clinic. The gold nanoparticles (NPs) based ICTS with colorimetric readout enables a quick spectrum screening but suffers from nonquantitative performance; although ICTS with fluorescence readout (FICTS) allows quantitative detection, its sensitivity still deserves more efforts and attentions. In this work, by taking advantages of colorimetric ICTS and FICTS, we described a reverse fluorescence enhancement ICTS (rFICTS) with bimodal signal readout for ultrasensitive and quantitative fast screening of carcinoembryonic antigen (CEA). In the presence of target, gold NPs aggregation in T line induced colorimetric readout, allowing on-the-spot spectrum screening in 10 min by naked eye. Meanwhile, the reverse fluorescence enhancement signal enabled more accurately quantitative detection with better sensitivity (5.89 pg/mL for CEA), which is more than 2 orders of magnitude lower than that of the conventional FICTS. The accuracy and stability of the rFICTS were investigated with more than 100 clinical serum samples for large-scale screening. Furthermore, this rFICTS also realized postoperative monitoring by detecting CEA in a patient with colon cancer and comparing with CT imaging diagnosis. These results indicated this rFICTS is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings. PMID:27547984

  1. Ion pair-reversed phase HPLC approach facilitates subcloning of PCR products and screening of recombinant colonies.

    Science.gov (United States)

    Shaw-Bruha, C M; Lamb, K A

    2000-04-01

    The isolation of a single DNA molecule for cloning is technically difficult, and the subsequent screening of colonies for recombinant DNA clones is time consuming. Ion pair-reversed phase HPLC (IP-RP-HPLC) analysis of nucleic acids improves the resolution and isolation of PCR products to be cloned. We demonstrate that PCR products analyzed and collected using the IP-RP-HPLC approach (WAVE DNA Fragment Analysis System) can be cloned directly into a plasmid vector. In addition, we demonstrate that when IP-RP-HPLC analysis is extended to the colony screening process, the time required for these procedures is reduced.

  2. Low resource screening method of pre-cancerous lesions and its reversal by Triphala in teen-age Indian population

    OpenAIRE

    Deshpande, Anshula; Tandon, Shobha; Deshpande, Neeraj

    2014-01-01

    Background: Cancer screening is the main weapon for early detection at a pre-invasive or premalignant stage. It has been reported that over 12 million people use some form of tobacco, which is one of the high risk factors and has hence become an alarming world-wide problem. Aim: To evaluate the effective diagnostic screening of disease in its early stage by inexpensive method and also to evaluate the effect of indigenous mouthrinse on reversal of pre-cancerous lesions. Materials and Methods: ...

  3. Identification of novel anti-hepatitis C virus agents by a quantitative high throughput screen in a cell-based infection assay.

    Science.gov (United States)

    Hu, Zongyi; Hu, Xin; He, Shanshan; Yim, Hyung Joon; Xiao, Jingbo; Swaroop, Manju; Tanega, Cordelle; Zhang, Ya-qin; Yi, Guanghui; Kao, C Cheng; Marugan, Juan; Ferrer, Marc; Zheng, Wei; Southall, Noel; Liang, T Jake

    2015-12-01

    Hepatitis C virus (HCV) poses a major health threat to the world. The recent development of direct-acting antivirals (DAAs) against HCV has markedly improved the response rate of HCV and reduced the side effects in comparison to the interferon-based therapy. Despite this therapeutic advance, there is still a need to develop new inhibitors that target different stages of the HCV life cycle because of various limitations of the current regimens. In this study, we performed a quantitative high throughput screening of the Molecular Libraries Small Molecule Repository (MLSMR) of ∼350,000 chemicals for novel HCV inhibitors using our previously developed cell-based HCV infection assay. Following confirmation and structural clustering analysis, we narrowed down to 158 compounds from the initial ∼3000 molecules that showed inhibitory activity for further structural and functional analyses. We were able to assign the majority of these compounds to specific stage(s) in the HCV life cycle. Three of them are direct inhibitors of NS3/4A protease. Most of the compounds appear to act on novel targets in HCV life cycle. Four compounds with novel structure and excellent drug-like properties, three targeting HCV entry and one targeting HCV assembly/secretion, were advanced for further development as lead hits. These compounds represent diverse chemotypes that are potential lead compounds for further optimization and may offer promising candidates for the development of novel therapeutics against HCV infection. In addition, they represent novel molecular probes to explore the complex interactions between HCV and the cells. PMID:26515788

  4. 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

    2014-02-01

    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

  5. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Directory of Open Access Journals (Sweden)

    Tia DiTommaso

    2014-10-01

    Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  6. A modified reverse one-hybrid screen identifies transcriptional activation in Phyochrome-Interacting Factor 3

    Science.gov (United States)

    Transcriptional activation domains (TAD) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput...

  7. Effective siRNA targets screening for human telomerase reverse transcriptase

    Institute of Scientific and Technical Information of China (English)

    Yun Xia; Ru-Xian Lin; Su-Jun Zheng; Ying Yang; Xiao-Chen Bo; Dao-Yin Zhu; Sheng-Qi Wang

    2005-01-01

    AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000TM. At 48-72 h after siRNAs transfection, MTT assay,RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.RESULTS: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2cells.CONCLUSION: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method,synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.

  8. Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase

    Science.gov (United States)

    2016-01-01

    We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs. PMID:27713931

  9. Syphilis detection: evaluation of serological screening and pilot reverse confirmatory assay algorithm in blood donors.

    Science.gov (United States)

    Sommese, Linda; Paolillo, Rossella; Sabia, Chiara; Costa, Dario; De Pascale, Maria Rosaria; Iannone, Carmela; Esposito, Antonella; Schiano, Concetta; Napoli, Claudio

    2016-07-01

    Serological assays are still considered the most useful tests in the diagnosis of syphilis. Since no single serological assay is able to provide a satisfactory result, in our laboratory we have evaluated the usefulness of a commercially-available immunoblot to diagnose syphilis infection among blood donors. From October 2012 to June 2013, 4572 blood donors were screened for syphilis with an automated chemiluminescent microparticle immunoassay (CMIA). To confirm the presence of treponemal antibodies, CMIA-reactive sera were tested by standard Treponema pallidum haemagglutination assay (TPHA). In addition, an alternative confirmatory test - the immunoblot INNO-LIA assay was introduced in our laboratory. Since two additional positives among CMIA-reactive-TPHA-negative samples were found, we concluded that the INNO-LIA immunoblot allowed a better detection of syphilis compared to TPHA. A confirmatory strategy based on the use of two treponemal assays could meet the screening requirements for blood donors as well as in our centre. PMID:26068964

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

    OpenAIRE

    Atsuya Yamashita; Yuusuke Fujimoto; Mayumi Tamaki; Andi Setiawan; Tomohisa Tanaka; Kaori Okuyama-Dobashi; Hirotake Kasai; Koichi Watashi; Takaji Wakita; Masaaki Toyama; Masanori Baba; de Voogd, Nicole J.; Shinya Maekawa; Nobuyuki Enomoto; Junichi Tanaka

    2015-01-01

    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 extr...

  11. Data on synthesis of methylene bisphosphonates and screening of their inhibitory activity towards HIV reverse transcriptase.

    Science.gov (United States)

    Yanvarev, D V; Korovina, A N; Usanov, N N; Khomich, O A; Vepsäläinen, J; Puljula, E; Kukhanova, M K; Kochetkov, S N

    2016-09-01

    Inorganic pyrophosphate (PPi) mimetics designed on a basis of methylenediphosphonic acid backbone are promising inhibitors of two key HIV replication enzymes, IN [1] and RT [2]. Herein, we present chemical synthesis of eleven methylenebisphosphonates (BPs) with their NMR and HRMS analysis synthesized via five different ways. Also, we present data on inhibition of HIV RT catalyzed phosphorolysis and polymerization by synthesized BPs using two methods based on denaturing urea PAGE. Tests were also performed for thymidine analogue mutations reverse transcriptase (TAM RT), which was expressed and purified for that. Structure-activity relationships and inhibitory activity data of synthesized BPs are presented in "Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity" [2]. PMID:27547792

  12. Automated screening of reversed-phase stationary phases for small-molecule separations using liquid chromatography with mass spectrometry.

    Science.gov (United States)

    Appulage, Dananjaya K; Wang, Evelyn H; Carroll, Frances; Schug, Kevin A

    2016-05-01

    There are various reversed-phase stationary phases that offer significant differences in selectivity and retention. To investigate different reversed-phase stationary phases (aqueous stable C18 , biphenyl, pentafluorophenyl propyl, and polar-embedded alkyl) in an automated fashion, commercial software and associated hardware for mobile phase and column selection were used in conjunction with liquid chromatography and a triple quadrupole mass spectrometer detector. A model analyte mixture was prepared using a combination of standards from varying classes of analytes (including drugs, drugs of abuse, amino acids, nicotine, and nicotine-like compounds). Chromatographic results revealed diverse variations in selectivity and peak shape. Differences in the elution order of analytes on the polar-embedded alkyl phase for several analytes showed distinct selectivity differences compared to the aqueous C18 phase. The electron-rich pentafluorophenyl propyl phase showed unique selectivity toward protonated amines. The biphenyl phase provided further changes in selectivity relative to C18 with a methanolic phase, but it behaved very similarly to a C18 when an acetonitrile-based mobile phase was evaluated. This study shows the value of rapid column screening as an alternative to excessive mobile phase variation to obtain suitable chromatographic settings for analyte separation. PMID:26959840

  13. A Modified Reverse One-Hybrid Screen Identifies Transcriptional Activation Domains in PHYTOCHROME-INTERACTING FACTOR 3.

    Science.gov (United States)

    Dalton, Jutta C; Bätz, Ulrike; Liu, Jason; Curie, Gemma L; Quail, Peter H

    2016-01-01

    Transcriptional activation domains (TADs) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput manner. A plant transcriptional activator, PIF3 (phytochrome interacting factor 3), was fused to the yeast GAL4-DNA-binding Domain (BD), driving expression of the URA3 (Orotidine 5'-phosphate decarboxylase) reporter, and used for negative selection on 5-fluroorotic acid (5FOA). Randomly mutagenized variants of PIF3 were then selected for a loss or reduction in transcriptional activation activity by survival on FOA. In the process, we developed a strategy to eliminate false positives from negative selection that can be used for both reverse-1- and 2-hybrid screens. With this method we were able to identify two distinct regions in PIF3 with transcriptional activation activity, both of which are functionally conserved in PIF1, PIF4, and PIF5. Both are collectively necessary for full PIF3 transcriptional activity, but neither is sufficient to induce transcription autonomously. We also found that the TAD appear to overlap physically with other PIF3 functions, such as phyB binding activity and consequent phosphorylation. Our protocol should provide a valuable tool for identifying, analyzing and characterizing novel TADs in eukaryotic transcription factors, and thus potentially contribute to the unraveling of the mechanism underlying transcriptional activation. PMID:27379152

  14. A Modified Reverse One-Hybrid Screen Identifies Transcriptional Activation Domains in PHYTOCHROME-INTERACTING FACTOR 3.

    Science.gov (United States)

    Dalton, Jutta C; Bätz, Ulrike; Liu, Jason; Curie, Gemma L; Quail, Peter H

    2016-01-01

    Transcriptional activation domains (TADs) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput manner. A plant transcriptional activator, PIF3 (phytochrome interacting factor 3), was fused to the yeast GAL4-DNA-binding Domain (BD), driving expression of the URA3 (Orotidine 5'-phosphate decarboxylase) reporter, and used for negative selection on 5-fluroorotic acid (5FOA). Randomly mutagenized variants of PIF3 were then selected for a loss or reduction in transcriptional activation activity by survival on FOA. In the process, we developed a strategy to eliminate false positives from negative selection that can be used for both reverse-1- and 2-hybrid screens. With this method we were able to identify two distinct regions in PIF3 with transcriptional activation activity, both of which are functionally conserved in PIF1, PIF4, and PIF5. Both are collectively necessary for full PIF3 transcriptional activity, but neither is sufficient to induce transcription autonomously. We also found that the TAD appear to overlap physically with other PIF3 functions, such as phyB binding activity and consequent phosphorylation. Our protocol should provide a valuable tool for identifying, analyzing and characterizing novel TADs in eukaryotic transcription factors, and thus potentially contribute to the unraveling of the mechanism underlying transcriptional activation.

  15. A Modified Reverse One-Hybrid Screen Identifies Transcriptional Activation Domains in PHYTOCHROME-INTERACTING FACTOR 3

    Science.gov (United States)

    Dalton, Jutta C.; Bätz, Ulrike; Liu, Jason; Curie, Gemma L.; Quail, Peter H.

    2016-01-01

    Transcriptional activation domains (TADs) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput manner. A plant transcriptional activator, PIF3 (phytochrome interacting factor 3), was fused to the yeast GAL4-DNA-binding Domain (BD), driving expression of the URA3 (Orotidine 5′-phosphate decarboxylase) reporter, and used for negative selection on 5-fluroorotic acid (5FOA). Randomly mutagenized variants of PIF3 were then selected for a loss or reduction in transcriptional activation activity by survival on FOA. In the process, we developed a strategy to eliminate false positives from negative selection that can be used for both reverse-1- and 2-hybrid screens. With this method we were able to identify two distinct regions in PIF3 with transcriptional activation activity, both of which are functionally conserved in PIF1, PIF4, and PIF5. Both are collectively necessary for full PIF3 transcriptional activity, but neither is sufficient to induce transcription autonomously. We also found that the TAD appear to overlap physically with other PIF3 functions, such as phyB binding activity and consequent phosphorylation. Our protocol should provide a valuable tool for identifying, analyzing and characterizing novel TADs in eukaryotic transcription factors, and thus potentially contribute to the unraveling of the mechanism underlying transcriptional activation. PMID:27379152

  16. Novel cell-based in vitro screen to identify small-molecule inhibitors against intracellular replication of Cryptococcus neoformans in macrophages.

    Science.gov (United States)

    Samantaray, Sweta; Correia, Joao N; Garelnabi, Mariam; Voelz, Kerstin; May, Robin C; Hall, Rebecca A

    2016-07-01

    The fungal pathogen Cryptococcus neoformans poses a major threat to immunocompromised patients and is a leading killer of human immunodeficiency virus (HIV)-infected patients worldwide. Cryptococci are known to manipulate host macrophages and can either remain latent or proliferate intracellularly within the host phagocyte, a favourable niche that also renders them relatively insensitive to antifungal agents. Here we report an attempt to address this limitation by using a fluorescence-based drug screening method to identify potential inhibitors of intracellular proliferation of C. neoformans. The Prestwick Chemical Library(®) of FDA-approved small molecules was screened for compounds that limit the intracellular replication of a fluorescently-tagged C. neoformans reference strain (H99-GFP) in macrophages. Preliminary screening revealed 19 of 1200 compounds that could significantly reduce intracellular growth of the pathogen. Secondary screening and host cell cytotoxicity assays highlighted fendiline hydrochloride as a potential drug candidate for the development of future anticryptococcal therapies. Live cell imaging demonstrated that this Ca(2+) channel blocker strongly enhanced phagosome maturation in macrophages leading to improved fungal killing and reduced intracellular replication. Whilst the relatively high dose of fendiline hydrochloride required renders it unfit for clinical deployment against cryptococcosis, this study highlights a novel approach for identifying new lead compounds and unravels a pharmacologically promising scaffold towards the development of novel antifungal therapies for this neglected disease. PMID:27289450

  17. An agonist sensitive, quick and simple cell-based signaling assay for determination of ligands mimicking prostaglandin E2 or E1 activity through subtype EP1 receptor: Suitable for high throughput screening

    Directory of Open Access Journals (Sweden)

    Ruan Ke-He

    2011-02-01

    Full Text Available Abstract Background Conventionally the active ingredients in herbal extracts are separated into individual components, by fractionation, desalting, and followed by high-performance liquid chromatography (HPLC. In this study we have tried to directly screen water-soluble fractions of herbs with potential active ingredients before purification or extraction. We propose that the herbal extracts mimicking prostaglandin E1 (PGE1 and E2 (PGE2 can be identified in the water-soluble non-purified fraction. PGE1 is a potent anti-inflammatory molecule used for treating peripheral vascular diseases while PGE2 is an inflammatory molecule. Methods We used cell-based assays (CytoFluor multi-well plate reader and fluorescence microscopy in which a calcium signal was generated by the recombinant EP1 receptor stably expressed in HEK293 cells (human embryonic kidney. PGE1 and PGE2 were tested for their ability to generate a calcium signal. Ninety-six water soluble fractions of Treasures of the east (single Chinese herb dietary supplements were screened. Results After screening, the top ten stimulators were identified. The identified herbs were then desalted and the calcium fluorescent signal reconfirmed using fluorescence microscopy. Among these top ten agonists identified, seven stimulated the calcium signaling (1-40 μM concentration using fluorescence microscopy. Conclusions Fluorescence microscopy and multi-well plate readers can be used as a target specific method for screening water soluble fractions with active ingredients at a very early stage, before purification. Our future work consists of purifying and separating the active ingredients and repeating fluorescence microscopy. Under ordinary circumstances we would have to purify the compounds first and then test all the extracts from 96 herbs. Conventionally, for screening natural product libraries, the procedure followed is the automated separation of all constituents into individual components using

  18. Multiplex reverse transcription-polymerase chain reaction combined with on-chip electrophoresis as a rapid screening tool for candidate gene sets

    DEFF Research Database (Denmark)

    Wittig, Rainer; Salowsky, Rüdiger; Blaich, Stephanie;

    2005-01-01

    Combining multiplex reverse transcription-polymerase chain reaction (mRT-PCR) with microfluidic amplicon analysis, we developed an assay for the rapid and reliable semiquantitative expression screening of 11 candidate genes for drug resistance in human malignant melanoma. The functionality of thi...

  19. A Cell-Based Internalization and Degradation Assay with an Activatable Fluorescence-Quencher Probe as a Tool for Functional Antibody Screening.

    Science.gov (United States)

    Li, Yan; Liu, Peter Corbett; Shen, Yang; Snavely, Marshall D; Hiraga, Kaori

    2015-08-01

    For the development of therapeutically potent anti-cancer antibody drugs, it is often important to identify antibodies that internalize into cells efficiently, rather than just binding to antigens on the cell surface. Such antibodies can mediate receptor endocytosis, resulting in receptor downregulation on the cell surface and potentially inhibiting receptor function and tumor growth. Also, efficient antibody internalization is a prerequisite for the delivery of cytotoxic drugs into target cells and is critical for the development of antibody-drug conjugates. Here we describe a novel activatable fluorescence-quencher pair to quantify the extent of antibody internalization and degradation in the target cells. In this assay, candidate antibodies were labeled with a fluorescent dye and a quencher. Fluorescence is inhibited outside and on the surface of cells, but activated upon endocytosis and degradation of the antibody. This assay enabled the development of a process for rapid characterization of candidate antibodies potentially in a high-throughput format. By employing an activatable secondary antibody, primary antibodies in purified form or in culture supernatants can be screened for internalization and degradation. Because purification of candidate antibodies is not required, this method represents a direct functional screen to identify antibodies that internalize efficiently early in the discovery process. PMID:26024945

  20. Multiplex Reverse Transcription-Polymerase Chain Reaction for Simultaneous Screening of 29 Chromosomal Translocation in Hematologic Malignancies

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Multiplex reverse transcription-polymerase chain reaction (M-RT-PCR) has been proved to possess great clinical potential for simultaneous screening of 29 chromosomal translocations in acute leukemia. To evaluate the clinical value of M-RT-PCR in hematologic malignancies, bone marrow samples from 90 patients with various hematologic malignancies, including 25 acute myeloge nous leukemia (AML), 22 acute lymphoblastic leukemia (ALL), 27 chronic myelogenous leukemia (CML), 4 myeloproliferative diseases (MPD), 3 chronic lymphoblastic leukemia (CLL), 3 and 1 malignant histocytosis (MH) were subjected to both M-RT-PCR and chromosome karyotypic analysis. Some of cases were subjected to follow-up examination of M-RT-PCR during the period of ukemia. In our hand, 12 of 29chromosomal translocation transcripts including TEL/PDGFR, DEK/CAN, MLL/AF6, AML1/ETO,F9, BCR/ABL, MLL/MLL, PML/RARα, TLS/ERG, E2A/HLF, EVIl and HOXI1 were detected in 57 cases (63.3 %) of the 90 samples, which were in consistence with the results of karyore, M-RT-PCR had also shown good clinical relevance when used as an approach to detect minimal residual leukemia. We concluded that M-RT-PCR could be used as an effiy in the initial diagnosis of hematologic malignancies but also in subsequent monitor of minimal residual leukemia.

  1. Evaluation of reverse sequence screening for syphilis%梅毒反向筛查方法应用评价

    Institute of Scientific and Technical Information of China (English)

    郭大文; 方秀菊; 李坤; 杨柳; 张英辉; 单娜; 孟冬娅

    2013-01-01

    Objective To assess the value of reverse sequence screening algorithm to syphilis test in population with high and low syphilis prevalence,as well as the value of treponemal pallidum particle agglutination (TPPA) to confirmatory trepomemal test.Methods Of total 50 585 patients,49 040 patients received operation,endoscopic examination or blood transfusion (low-prevalence syphilis group) and 1 645 patients suffered from suspected sexually transmitted diseases (high-prevalence syphilis group).Sera were initially screened by treponemal enzyme immunoassays (EIA),followed by nontreponemal rapid plasma reagin (RPR) test for positive specimens,and sera with discordant results (i.e.EIA-positive,RPR-negative) were tested with confirmatory TPPA.Results Among the total of 50 685 specimens screened with EIA,1 610 (3.2%) had positive results.Among the 1 610 EIA-positive sera specimens,1 009 (62.7%) were RPR-negative,of which 138 (13.7%) were TPPA-negative.The percentage of EIA-positive was significantly lower in lowprevalence syphilis group (1.5%) than that in high-prevalence syphilis group (51.6%) (P<0.01).The percentage of discordant results (EIA+RPR-) was significantly higher in low-prevalence syphilis group (73.4 %) than that in highprevalence syphilis group (53.1%) (P< 0.01).The percentage of false-positive results (EIA + RPR-TPPA-) was significantly higher in low-prevalence syphilis group (20.4%) than that in high-prevalence syphilis group (5.3 %) (P<0.01).Conclusion Reverse sequence screening algorithm results in a high percentage of false positive especially in lowprevalence syphilis population.All EIA-positive sera should undergo nontreponemal test (e.g.RPR),and discordant sera should be tested reflexively with the second treponemal test (e.g.TPPA).%目的 评价反向筛查方法在梅毒高流行人群和梅毒低流行人群中应用价值,及梅毒螺旋体明胶颗粒凝集试验(treponemal pallidum particle agglutination,TPPA)作为确

  2. Screening suitable reference genes for normalization in reverse transcription quantitative real-time PCR analysis in melon.

    Directory of Open Access Journals (Sweden)

    Qiusheng Kong

    Full Text Available Melon (Cucumis melo. L is not only an economically important cucurbitaceous crop but also an attractive model for studying many biological characteristics. Screening appropriate reference genes is essential to reverse transcription quantitative real-time PCR (RT-qPCR, which is key to many studies involving gene expression analysis. In this study, 14 candidate reference genes were selected, and the variations in their expression in roots and leaves of plants subjected to biotic stress, abiotic stress, and plant growth regulator treatment were assessed by RT-qPCR. The stability of the expression of the selected genes was determined and ranked using geNorm and NormFinder. geNorm identified the two most stable genes for each set of conditions: CmADP and CmUBIep across all samples, CmUBIep and CmRPL in roots, CmRAN and CmACT in leaves, CmADP and CmRPL under abiotic stress conditions, CmTUA and CmACT under biotic stress conditions, and CmRAN and CmACT under plant growth regulator treatments. NormFinder determined CmRPL to be the best reference gene in roots and under biotic stress conditions and CmADP under the other experimental conditions. CmUBC2 and CmPP2A were not found to be suitable under many experimental conditions. The catalase family genes CmCAT1, CmCAT2, and CmCAT3 were identified in melon genome and used as target genes to validate the reliability of identified reference genes. The catalase family genes showed the most upregulation 3 days after inoculation with Fusarium wilt in roots, after which they were downregulated. Their levels of expression were significantly overestimated when the unsuitable reference gene was used for normalization. These results not only provide guidelines for the selection of reference genes for gene expression analyses in melons but may also provide valuable information for studying the functions of catalase family genes in stress responses.

  3. Cell-based Assays to Identify Inhibitors of Viral Disease

    Science.gov (United States)

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

    2009-01-01

    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

  4. INTERLABORATORY APPLICABILITY OF A RETENTION INDEX LIBRARY OF DRUGS FOR SCREENING BY REVERSED-PHASE HPLC IN SYSTEMATIC TOXICOLOGICAL ANALYSIS

    NARCIS (Netherlands)

    BOGUSZ, M; ERKENS, M; FRANKE, JP; WIJSBEEK, J; DEZEEUW, RA

    1993-01-01

    The retention indices (RI) of 47 selected acidic, neutral and basic drugs were determined on 7 reversed-phase (octyl- and octadecylsilica) columns in two laboratories in the 1-nitroalkane scale, using either 1-nitroalkane homologues or selected drugs, whose RI values were previously determined on th

  5. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Cele FN

    2016-04-01

    Full Text Available Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621 showed a significant potential with regard to free binding energy. Reported results obtained from

  6. A Cell-Based Screening Model for Human PPARα Agonist Ligands Discovery and Its Applicability%基于人PPARα为靶标的药物筛选细胞模型的建立与应用评价

    Institute of Scientific and Technical Information of China (English)

    马晶晶; 张潜; 方宁; 万卫红; 刘祖林; 章涛

    2011-01-01

    目的 构建一种新的、具有生物活性检测能力的人过氧化物酶体增殖物激活受体α(hPPARo)配体药物筛选细胞模型.方法 采用Lipofectamine 2000将含人PPARα基因质粒phPPARα-IRES2-EGFP、含人PPRE报告质粒ptk-PPRE×3-1uc及内部对照质粒pRL-CMV共转染293T细胞,并对phPPARα-IRES2-EGFP转染效率进行流式细胞仪(FCM)分析;通过双荧光素酶报告基因法(DLR)检测不同浓度、不同时间阳性药物WY14643干预共转染细胞体系的荧光素酶表达活性;实验还换用RXRα激动剂全反式维甲酸(ATRA)干预,以评价该细胞模型反应的特异性;并用贝特类降脂药苯扎贝特、环丙贝特、氯贝丁酯对建立的药物筛选细胞模型进行应用能力评价.结果 FCM检测共转染293T细胞phPPARα-IRES2-EGFP质粒转染效率为68%;DLR检测WY14643干预该hPPARα药物筛选模型获得了理想的量—效、时—效关系结果,且该模型不能通过RXRα配体激动剂ATRA激活.苯扎贝特、环丙贝特、氯贝丁酯干预模型均呈现良好的量—效反应性,且反应强度存在差异(P<0.05).结论 成功构建了基于hPPARα为靶标的药物筛选细胞模型,为筛选具有生物活性的hPPARα配体激动剂新药提供了一种可靠的新平台.%OBJECTIVE To establish a novel cell-based model for the screening of human PPARa agonist ligands. METHODS Recombinant plasmid phPPARa-IRES2-EGFP, firefly luciferase-containing report plasmid ptk-PPRE x3-luc and renilla luciferase-containing inner control plasmid pRL-CMV were co-transfected into 293T cells using lipofectamine 2000. The transfection efficiency of phPPARot-IRES2-EGFP was measured by flow cytometry (FCM). Dual-luciferase reporter assay (DLR) was used to detect the lucifer-ase activity of co-transfected 293T cells under concentration gradient at different time points of positive drug WY14643 intervention. Furthermore, WY14643 was replaced by all-trans-retinoic acid (ATRA) , a RXRa

  7. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents.

    Science.gov (United States)

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud Es

    2016-01-01

    A novel virtual screening approach is implemented herein, which is a further improvement of our previously published "target-bound pharmacophore modeling approach". The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD) simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621) showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  8. Screening of new non-nucleoside reverse transcriptase inhibitors of HIV-1 based on traditional Chinese medicines database

    Institute of Scientific and Technical Information of China (English)

    Tao Liu; Ai Xiu Li; You Pan Miao; Ke Zhu Wu; Yi Ma

    2009-01-01

    HIV-1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV-1 RT have been identified, nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database (TCMD) using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 (a compound derived from TCMD) has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy.

  9. Mammalian Cell-Based Sensor System

    Science.gov (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.

  10. Use of reverse transcriptase polymerase chain reaction (RT-PCR) in molecular screening of Newcastle disease virus in poultry and free-living bird populations.

    Science.gov (United States)

    Carrasco, Adriano de Oliveira Torres; Rodrigues, Juliana Nogueira Martins; Seki, Meire Christina; de Moraes, Fabricio Edgar; Silva, Jaqueline Raymondi; Durigon, Edison Luis; Pinto, Aramis Augusto

    2013-02-01

    The aim of this study was to evaluate a simple molecular method of reverse transcriptase polymerase chain reaction (RT-PCR) to differentiate Newcastle disease virus strains according to their pathogenicity, in order to use it in molecular screening of Newcastle disease virus in poultry and free-living bird populations. Specific primers were developed to differentiate LaSota--LS--(vaccine strain) and Sao Joao do Meriti--SJM--strain (highly pathogenic strain). Chickens and pigeons were experimentally vaccinated/infected for an in vivo study to determine virus shedding in feces. Validation of sensitivity and specificity of the primers (SJM and LS) by experimental models used in the present study and results obtained in the molecular analysis of the primers by BLAST made it possible to generalize results. The development of primers that differentiate the level of pathogenicity of NDV stains is very important, mainly in countries where real-time RT-PCR is still not used as a routine test. These primers were able to determine the presence of the agent and to differentiate it according to its pathogenicity.

  11. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.

    Science.gov (United States)

    Li, Wanbo; Sartelet, Arnaud; Tamma, Nico; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2016-02-01

    In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed. PMID:26582259

  12. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.

    Science.gov (United States)

    Li, Wanbo; Sartelet, Arnaud; Tamma, Nico; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2016-02-01

    In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed.

  13. Cell-based bioassays in microfluidic systems

    Science.gov (United States)

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

    2004-12-01

    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.

  14. Cell-Based Therapy for Silicosis.

    Science.gov (United States)

    Lopes-Pacheco, Miquéias; Bandeira, Elga; Morales, Marcelo M

    2016-01-01

    Silicosis is the most common pneumoconiosis globally, with higher prevalence and incidence in developing countries. To date, there is no effective treatment to halt or reverse the disease progression caused by silica-induced lung injury. Significant advances have to be made in order to reduce morbidity and mortality related to silicosis. In this review, we have highlighted the main mechanisms of action that cause lung damage by silica particles and summarized the data concerning the therapeutic promise of cell-based therapy for silicosis. PMID:27066079

  15. Cell-Based Therapy for Silicosis

    Directory of Open Access Journals (Sweden)

    Miquéias Lopes-Pacheco

    2016-01-01

    Full Text Available Silicosis is the most common pneumoconiosis globally, with higher prevalence and incidence in developing countries. To date, there is no effective treatment to halt or reverse the disease progression caused by silica-induced lung injury. Significant advances have to be made in order to reduce morbidity and mortality related to silicosis. In this review, we have highlighted the main mechanisms of action that cause lung damage by silica particles and summarized the data concerning the therapeutic promise of cell-based therapy for silicosis.

  16. The in-capillary DPPH-capillary electrophoresis-the diode array detector combined with reversed-electrode polarity stacking mode for screening and quantifying major antioxidants in Cuscuta chinensis Lam.

    Science.gov (United States)

    Liu, Jiao; Tian, Ji; Li, Jin; Azietaku, John Teye; Zhang, Bo-Li; Gao, Xiu-Mei; Chang, Yan-Xu

    2016-07-01

    An in-capillary 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-CE-the DAD (in-capillary DPPH-CE-DAD) combined with reversed-electrode polarity stacking mode has been developed to screen and quantify the active antioxidant components of Cuscuta chinensis Lam. The operation parameters were optimized with regard to the pH and concentration of buffer solution, SDS, β-CDs, organic modifier, as well as separation voltage and temperature. Six antioxidants including chlorogenic acid, p-coumaric acid, rutin, hyperin, isoquercitrin, and astragalin were screened and the total antioxidant activity of the complex matrix was successfully evaluated based on the decreased peak area of DPPH by the established DPPH-CE-DAD method. Sensitivity was enhanced under reversed-electrode polarity stacking mode and 10- to 31-fold of magnitude improvement in detection sensitivity for each analyte was attained. The results demonstrated that the newly established in-capillary DPPH-CE-DAD method combined with reversed-electrode polarity stacking mode could integrate sample concentration, the oxidizing reaction, separation, and detection into one capillary to fully automate the system. It was considered a suitable technique for the separation, screening, and determination of trace antioxidants in natural products. PMID:26955793

  17. 基于马氏距离的太阳能电池可靠性筛选方法研究%Reliability screening method for solar cells based on Mahalanobis distance

    Institute of Scientific and Technical Information of China (English)

    周求湛; 张彦创; 陈永志; 刘萍萍; 吴丹娥

    2012-01-01

    通过测量太阳能电池的内部低频噪声,可以快速、无损地实现太阳能电池的可靠性筛选分类。提出基于马氏距离的筛选方法分析噪声数据,进而得到全频段的噪声筛选判据。实验结果表明,本文方法和基于个别频率点的噪声分类方法相比,马氏距离筛选方法更加全面地反映了太阳能电池的整体低频噪声水平,不仅可以剔除1/f噪声大的太阳能电池,还可以剔除G-R(genera-tion-recombination)噪声和爆裂噪声大的太阳能电池,因此能将一批太阳能电池进行更为准确、精细的可靠性分类。%The reliability screening and sorting of the solar cells can be quickly and nondestructively realized by measuring their internal low frequency noise.In this paper the screening method based on Mahalanobis distance is proposed to analyze the noise data,so the screening criterion for the whole frequency band can be achieved.Experimental results show that this method is more efficient compared with the usual screening method based on the value of a special frequency point.The screening method based on Mahalanobis distance comprehensively reflects the low frequency noise of the solar cell;it can distinguish not only the solar cells with big 1/f noise,but also the solar cells with G-R noise and burst noise.So this method can sort solar cells more accurately and precisely according to their reliability.

  18. 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.

    Science.gov (United States)

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

    2016-02-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    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.

  20. PCR Reverse Hybridization Membrane Applications in Screening of CT,UU,NG Three Kinds of STD%PCR反向膜杂交法在CT、UU、NG三种性病筛查中的应用价值

    Institute of Scientific and Technical Information of China (English)

    王涛; 王鹏; 董丽

    2014-01-01

    Objective:To investigate the value of PCR reverse hybridization membrane application in screening of CT,UU,NG three kinds of STD. Method:1486 suspected patients with genitourinary tract infections were detected by PCR reverse hybridization membrane and fluorescence quantitative PCR(FQ-PCR),and test results were compared with culture results. Result:FQ-PCR detection of CT,UU,NG was higher than culture(P<0.01). PCR reverse hybridization membrane,culture and FQ-PCR positive rate difference was not statistically significant. PCR reverse hybridization membrane,FQ-PCR detection sensitivity difference was not statistically significant,but the film PCR reverse hybridization assay specificity was higher than FQ-PCR(P<0.01). Conclusion:PCR reverse hybridization in screening of CT,UU,NG,is accurate,rapid,and specific is higher than FQ-PCR,worthy of promotion apply.%目的:探讨PCR反向膜杂交法在CT、UU、NG三种性病筛查中的应用价值。方法:对1486例疑为泌尿生殖道感染患者分别采用PCR反向膜杂交法及荧光定量PCR(FQ-PCR)检测,并将检测结果与培养结果比较。结果:FQ-PCR检测CT、UU、NG阳性率高于培养法,比较差异有统计学意义(P<0.01);PCR反向膜杂交法与培养法及FQ-PCR检测阳性率比较差异均无统计学意义;PCR反向膜杂交法、FQ-PCR检测敏感性比较差异无统计学意义,但PCR反向膜杂交法检测特异性高于FQ-PCR,比较差异有统计学意义(P<0.01)。结论:PCR反向膜杂交法筛查CT、UU、NG准确,快速,且筛查特异性高于FQ-PCR,值得临床推广适用。

  1. In vitro screening of reversible and time-dependent inhibition on CYP3A by TM208 and TM209 in rat liver microsomes

    Directory of Open Access Journals (Sweden)

    Miaoran Ning

    2012-04-01

    Full Text Available TM208 and TM209, dithiocarbamate derivatives with potential anti-cancer effects, were evaluated in reversible and time-dependent cytochrome P450 (CYP 3A inhibition assays in rat liver microsomes using testosterone as probe substrate. Both compounds were found to be weak reversible inhibitors and moderate mechanism-based inhibitors of rat CYP3A. For reversible inhibition on rat CYP3A, the Ki values of competitive inhibition model were 12.10±1.75 and 13.94±1.31 μM, respectively. For time-dependent inhibition, the inactivation constants (Kl were 31.93±12.64 and 32.91±15.58 μM, respectively, and the maximum inactivation rates (kinact were 0.03497±0.0069 and 0.07259±0.0172 min−1 respectively. These findings would provide useful in vitro information for future in vivo DDI studies on TM208 or TM209.

  2. Fast Gradient Elution Reversed-Phase HPLC with Diode-Array Detection as a High Throughput Screening Method for Drugs of Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Peter W. Carr; K.M. Fuller; D.R. Stoll; L.D. Steinkraus; M.S. Pasha; Glenn G. Hardin

    2005-12-30

    A new approach has been developed by modifying a conventional gradient elution liquid chromatograph for the high throughput screening of biological samples to detect the presence of regulated intoxicants. The goal of this work was to improve the speed of a gradient elution screening method over current approaches by optimizing the operational parameters of both the column and the instrument without compromising the reproducibility of the retention times, which are the basis for the identification. Most importantly, the novel instrument configuration substantially reduces the time needed to re-equilibrate the column between gradient runs, thereby reducing the total time for each analysis. The total analysis time for each gradient elution run is only 2.8 minutes, including 0.3 minutes for column reequilibration between analyses. Retention times standard calibration solutes are reproducible to better than 0.002 minutes in consecutive runs. A corrected retention index was adopted to account for day-to-day and column-to-column variations in retention time. The discriminating power and mean list length were calculated for a library of 47 intoxicants and compared with previous work from other laboratories to evaluate fast gradient elution HPLC as a screening tool.

  3. A Cell-based β2-adrenergic Receptor Agonist Functional Screening Assay for Chinese Traditional Medicines%基于细胞的β2肾上腺素能受体激动剂功能性筛选体系在中草药中的应用

    Institute of Scientific and Technical Information of China (English)

    杨洋; 王超; 潘鹏炜; 白钢

    2009-01-01

    为了建立基于细胞的β2肾上腺素能受体激动剂筛选体系,将大鼠β2受体基因克隆人pcDNA3.1载体.转染具有cAMP应答元件调控的绿色荧光蛋白报告基因的中国仓鼠卵巢细胞(CHO),从得到的阳性单克隆细胞中筛选得到一个稳定表达β2受体,并且在受到激动剂刺激后发出剂量依赖绿色荧光强度的细胞株.将此筛选体系用于从中药中筛选具有β2受体激动剂活性的化合物.从几种芸香科药材中得到了辛弗林(synephine),从细辛和附子中得到了去甲乌药碱(higenamine),首次从受体水平证明了它们的β2激动剂活性.此筛选体系适合从大量天然化合物中快速筛选具有β2激动剂活性的成分.%To construct a cell-based agonists screening system for β2-adrenergic receptor (β2-AR) from chi- nese traditional medicines, β2-AR gene was amplified by PCR from rat genomic DNA. The PCR products were cloned into pcDNA3.1 and transfected into chinese hamster ovary (CHO) cell, which contained a cyclic AMP response element-linked enhanced green fluorescent protein reporter gene. One stable cell line was generated from the single-cell-derived colonies. It expressed β2-AR and provided green fluorescence when stimulated by ligands. Expression of β2-AR was monitored by RT-PCR and western blotting anti-β2-AR. The function of re- porter gene system was studied by flow cytometry. This cell-based screening system was applied to the extracts of chinese traditional medicines (TCMs). Synephine which was obtained from Rutaceae generic plant, and hige- namine which was obtained from Herba Asari or Radix Aconiti Lateralis Preparata were verified to have β2-AR agonist activity at receptor level. This assay could be applied in the pharmaceutical industry for screening thou- sands or indeed millions of natural compounds of TCMs for β2-AR agonists very rapidly.

  4. Reverse transcription-polymerase chain reaction construction of plasmid-based, full-length cDNA libraries from Leishmania infantum for in vitro expression screening

    Directory of Open Access Journals (Sweden)

    Bernard Couvreur

    2003-06-01

    Full Text Available We describe a streamlined reverse transcription-polymerase chain reaction methodology for constructing full-length cDNA libraries of trypanosomatids on the basis of conserved sequences located at the 5' and 3'ends of trans-spliced mRNAs. The amplified cDNA corresponded to full-length messengers and was amenable to in vitro expression. Fractionated libraries could be rapidly constructed in a plasmid vector by the TA cloning method (Invitrogen. We believe this is useful when there are concerns over the use of restriction enzymes and phage technology as well as in cases where expression of proteins in their native conformation is desired.

  5. Evidence of a tick RNAi pathway by comparative genomics and reverse genetics screen of targets with known loss-of-function phenotypes in Drosophila

    Directory of Open Access Journals (Sweden)

    Kurscheid Sebastian

    2009-03-01

    Full Text Available Abstract Background The Arthropods are a diverse group of organisms including Chelicerata (ticks, mites, spiders, Crustacea (crabs, shrimps, and Insecta (flies, mosquitoes, beetles, silkworm. The cattle tick, Rhipicephalus (Boophilus microplus, is an economically significant ectoparasite of cattle affecting cattle industries world wide. With the availability of sequence reads from the first Chelicerate genome project (the Ixodes scapularis tick and extensive R. microplus ESTs, we investigated evidence for putative RNAi proteins and studied RNA interference in tick cell cultures and adult female ticks targeting Drosophila homologues with known cell viability phenotype. Results We screened 13,643 R. microplus ESTs and I. scapularis genome reads to identify RNAi related proteins in ticks. Our analysis identified 31 RNAi proteins including a putative tick Dicer, RISC associated (Ago-2 and FMRp, RNA dependent RNA polymerase (EGO-1 and 23 homologues implicated in dsRNA uptake and processing. We selected 10 R. microplus ESTs with >80% similarity to D. melanogaster proteins associated with cell viability for RNAi functional screens in both BME26 R. microplus embryonic cells and female ticks in vivo. Only genes associated with proteasomes had an effect on cell viability in vitro. In vivo RNAi showed that 9 genes had significant effects either causing lethality or impairing egg laying. Conclusion We have identified key RNAi-related proteins in ticks and along with our loss-of-function studies support a functional RNAi pathway in R. microplus. Our preliminary studies indicate that tick RNAi pathways may differ from that of other Arthropods such as insects.

  6. Simultaneous screening for lipophilic and hydrophilic toxins in marine harmful algae using a serially coupled reversed-phase and hydrophilic interaction liquid chromatography separation system with high-resolution mass spectrometry.

    Science.gov (United States)

    Chen, Junhui; Gao, Liyuan; Li, Zhaoyong; Wang, Shuai; Li, Jingxi; Cao, Wei; Sun, Chengjun; Zheng, Li; Wang, Xiaoru

    2016-03-31

    The presence of toxins in harmful algal blooms (HABs) poses considerable concerns because of their potential adverse effects on ecological environments and human health. When marine HABs occur, efficient screening and identification of toxins in different kinds of HAB algae remains a challenge. In this study, the applicability of serial coupling of reversed-phase liquid chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) combined with high resolution mass spectrometry (HR-MS) for the simultaneous screening and identification of various kinds of known lipophilic and hydrophilic toxins in HAB algae was investigated for the first time. Ultrasound-assisted extraction (UAE) was explored to extract both lipophilic and hydrophilic toxins in algae simultaneously. As in most cases, toxin standards were not available; therefore, an identification procedure based on accurate mass data and chromatographic behavior was proposed. According to this procedure, eight known lipophilic toxins and 11 hydrophilic toxins were successfully detected in a single injection, and the proposed method was validated. Satisfactory sensitivity, repeatability (RSD <14.87%) and recovery (89.4-105.8%) of the method were achieved. A major advantage of the proposed method is that it can almost detect members of all eight groups of marine algal toxins in a single run. Using this method, several known toxins in different marine toxigenic algae including Alexandrium tamarense, Alexandrium minutum and Prorocentrum lima were successfully observed and identified. This work demonstrates that RPLC/HILIC-HR-MS combined with an accurate mass list of known marine algal toxins may be used as a powerful tool for screening of different classes of known toxins in marine harmful algae. PMID:26965334

  7. Vasectomy Reversal

    Medline Plus

    Full Text Available ... to make referrals, make appointments or request more information. Just click on the buttons on your screen ... to learn more. Just click on the “Request Information” button on your Webcast screen and open the ...

  8. Vasectomy Reversal

    Medline Plus

    Full Text Available ... screen and open the door to informed medical care. "OR Live," the vision of improving health. Hello, ... screen and open the door to informed medical care. "OR Live," the vision of improving health. 10

  9. Neuroblastoma Screening

    Science.gov (United States)

    ... Health Professional Neuroblastoma Treatment Neuroblastoma Screening Research Neuroblastoma Screening (PDQ®)–Patient Version What is screening? Go to Health Professional Version Screening is looking ...

  10. Novel Alleles of gon-2, a C. elegans Ortholog of Mammalian TRPM6 and TRPM7, Obtained by Genetic Reversion Screens.

    Directory of Open Access Journals (Sweden)

    Eric J Lambie

    Full Text Available TRP (Transient Receptor Potential cation channels of the TRPM subfamily have been found to be critically important for the regulation of Mg2+ homeostasis in both protostomes (e.g., the nematode, C. elegans, and the insect, D. melanogaster and deuterostomes (e.g., humans. Although significant progress has been made toward understanding how the activities of these channels are regulated, there are still major gaps in our understanding of the potential regulatory roles of extensive, evolutionarily conserved, regions of these proteins. The C. elegans genes, gon-2, gtl-1 and gtl-2, encode paralogous TRP cation channel proteins that are similar in sequence and function to human TRPM6 and TRPM7. We isolated fourteen revertants of the missense mutant, gon-2(q338, and these mutations affect nine different residues within GON-2. Since eight of the nine affected residues are situated within regions that have high similarity to human TRPM1,3,6 and 7, these mutations identify sections of these channels that are potentially critical for channel regulation. We also isolated a single mutant allele of gon-2 during a screen for revertants of the Mg2+-hypersensitive phenotype of gtl-2(- mutants. This allele of gon-2 converts a serine to phenylalanine within the highly conserved TRP domain, and is antimorphic against both gon-2(+ and gtl-1(+. Interestingly, others have reported that mutation of the corresponding residue in TRPM7 to glutamate results in deregulated channel activity.

  11. Reverse Engineering

    International Nuclear Information System (INIS)

    This book gives descriptions of reverse engineering with principle and structure of it, including what reverse engineering is, prospect and concerned laws, basic knowledge for reverse engineering like manual and back to user mode, using tool such as IDA installation, dependency walker and dump bin, network monitoring and universal extractor. It indicates analysis of malignant code, giving explanations of file virus, spy ware, an infection way of malignant code, anti debugging like Find window.

  12. Identification of a novel sulfonamide non-nucleoside reverse transcriptase inhibitor by a phenotypic HIV-1 full replication assay.

    Directory of Open Access Journals (Sweden)

    Tae-Hee Kim

    Full Text Available Classical target-based, high-throughput screening has been useful for the identification of inhibitors for known molecular mechanisms involved in the HIV life cycle. In this study, the development of a cell-based assay that uses a phenotypic drug discovery approach based on automated high-content screening is described. Using this screening approach, the antiviral activity of 26,500 small molecules from a relevant chemical scaffold library was evaluated. Among the selected hits, one sulfonamide compound showed strong anti-HIV activity against wild-type and clinically relevant multidrug resistant HIV strains. The biochemical inhibition, point resistance mutations and the activity of structural analogs allowed us to understand the mode of action and propose a binding model for this compound with HIV-1 reverse transcriptase.

  13. Docking mode of delvardine and its analogues into the p66 domain of HIV-1 reverse transcriptase: screening using molecular mechanics-generalized born/surface area and absorption, distribution, metabolism and excretion properties

    Indian Academy of Sciences (India)

    Dipankar Sengupta; Deeptak Verma; Pradeep K Naik

    2007-12-01

    Delvardine and its structural derivatives are important non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs). In this work, 15 delvardine analogues were studied. A free energy-of-binding (FEB) expression was developed in the form of an optimized linear combination of van der Waal (vdW), electrostatic, solvation and solvent-accessible surface area (SASA) energy terms. The solvation energy terms estimated by generalized born/surface area (GB/SA) play an important role in predicting the binding affinity of delvardine analogues. Out of 15 derivatives, substitution of CH3 with H at the Y and R positions, as well as substitution of SO2CH3 with only CH2 at the Z position in S2, S8 and S12 analogues, were found to be the most potent (glide score = –7.60, –8.06 and –7.44; pIC50 = 7.28, 7.37 and 7.64) in comparison with the template delvardine (which is used currently as the drug candidate). All the three analogues also passed the absorption, distribution, metabolism and excretion (ADME) screening and Lipinski’s rule of 5, and have the potential to be used for second-generation drug development. The work demonstrates that dock molecular mechanics-generalized born/surface area (MM–GB/SA–ADME) is a promising approach to predict the binding activity of ligands to the receptor and further screen for a successful candidate drug in a computer-aided rational drug design.

  14. Cell-Based Biosensors Principles and Applications

    CERN Document Server

    Wang, Ping

    2009-01-01

    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

  15. Cell-Based Genotoxicity Testing

    Science.gov (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

  16. Vasectomy Reversal

    Medline Plus

    Full Text Available ... screen and open the door to informed medical care. "OR Live," the vision of improving health. Hello, my name is Harris Nagler. I'm ... screen and open the door to informed medical care. "OR Live," the vision of improving health. 10

  17. Stem cell-based therapy in neural repair.

    Science.gov (United States)

    Hsu, Yi-Chao; Chen, Su-Liang; Wang, Dan-Yen; Chiu, Ing-Ming

    2013-01-01

    Cell-based therapy could aid in alleviating symptoms or even reversing the progression of neurodegenerative diseases and nerve injuries. Fibroblast growth factor 1 (FGF1) has been shown to maintain the survival of neurons and induce neurite outgrowth. Accumulating evidence suggests that combination of FGF1 and cell-based therapy is promising for future therapeutic application. Neural stem cells (NSCs), with the characteristics of self-renewal and multipotency, can be isolated from embryonic stem cells, embryonic ectoderm, and developing or adult brain tissues. For NSC clinical application, several critical problems remain to be resolved: (1) the source of NSCs should be personalized; (2) the isolation methods and protocols of human NSCs should be standardized; (3) the clinical efficacy of NSC transplants must be evaluated in more adequate animal models; and (4) the mechanism of intrinsic brain repair needs to be better characterized. In addition, the ideal imaging technique for tracking NSCs would be safe and yield high temporal and spatial resolution, good sensitivity and specificity. Here, we discuss recent progress and future development of cell-based therapy, such as NSCs, induced pluripotent stem cells, and induced neurons, in neurodegenerative diseases and peripheral nerve injuries. PMID:23806879

  18. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  19. Vasectomy Reversal

    Medline Plus

    Full Text Available ... improving health. Hello, my name is Harris Nagler. I'm the Chairman of the Sol and Margaret ... Israel Medical Center in New York City. Today I'm going to perform a vasectomy reversal using ...

  20. Vasectomy Reversal

    Medline Plus

    Full Text Available ... Today we are going to go to the operating room and show you microsurgical vasectomy reversal. We ... vas and that will be examined under the operating- under the microscope to see if there’s sperm ...

  1. Vasectomy Reversal

    Medline Plus

    Full Text Available ... is a realistic option for many patients. Today we are going to go to the operating room and show you microsurgical vasectomy reversal. We start the procedure by localizing the site of ...

  2. Vasectomy Reversal

    Medline Plus

    Full Text Available Vasectomy Reversal Beth Israel Medical Center, New York, NY February 19, 2009 Welcome to this "OR Live" Webcast presentation premiering from Beth Israel Medical Center in New York City. ...

  3. Auxiliary pattern for cell-based OPC

    Science.gov (United States)

    Kahng, Andrew B.; Park, Chul-Hong

    2006-10-01

    The runtime of model-based optical proximity correction (OPC) tools has grown unacceptably with each successive technology generation, and has emerged as one of the major bottlenecks for turnaround time (TAT) of IC data preparation and manufacturing. The cell-based OPC approach improves runtime by performing OPC once per cell definition as opposed to once per cell instantiation in the layout. However, cell-based OPC does not comprehend inter-cell optical interactions that affect feature printability in a layout context. In this work, we propose auxiliary pattern-enabled cell-based OPC which can minimize the CD differences between cell-based OPC and model-based OPC. To enable effective insertion of auxiliary pattern (AP) in the design, we also propose a post-placement optimization of a standard cell block with respect to detailed placement. By dynamic programming-based placement perturbation, we achieve 100% AP applicability in designs with placement utilizations of cell-based OPC with AP can match gate edge placement error (EPE) count of model-based OPC within 4%. This is an improvement of 90%, on average, over cell-based OPC without APs. The AP-based OPC approach can reduce OPC runtimes versus model-based OPC by up to 40X in our benchmark designs. We can also achieve reduction of GDSII file size and ORC runtimes due to hierarchy maintenance of cell-based OPC.

  4. Vasectomy Reversal

    Medline Plus

    Full Text Available ... retrieving greenish urine, demonstrating patency of the entire system. This can be also achieved just by instilling ... to learn more. Just click on the “Request Information” button on your Webcast screen and open the ...

  5. Vision Screening

    Science.gov (United States)

    ... offer vision screening programs for children. At what age should a child have his or her vision screened? Vision screening ... a child fails a vision screening at any age, the child should be referred for a comprehensive eye examination. ...

  6. Biotoxin Detection Using Cell-Based Sensors

    OpenAIRE

    Pratik Banerjee; Spyridon Kintzios; Balabhaskar Prabhakarpandian

    2013-01-01

    Cell-based biosensors (CBBs) utilize the principles of cell-based assays (CBAs) by employing living cells for detection of different analytes from environment, food, clinical, or other sources. For toxin detection, CBBs are emerging as unique alternatives to other analytical methods. The main advantage of using CBBs for probing biotoxins and toxic agents is that CBBs respond to the toxic exposures in the manner related to actual physiologic responses of the vulnerable subjects. The results ob...

  7. Reversible dementias

    OpenAIRE

    Tripathi, Manjari; Vibha, Deepti

    2009-01-01

    In recent years, more attention has been given to the early diagnostic evaluation of patients with dementia which is essential to identify patients with cognitive symptoms who may have treatable conditions. Guidelines suggest that all patients presenting with dementia or cognitive symptoms should be evaluated with a range of laboratory tests, and with structural brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI). While many of the disorders reported as ‘reversible...

  8. Health Screening

    Science.gov (United States)

    Screenings are tests that look for diseases before you have symptoms. Screening tests can find diseases early, when they're easier to treat. You can get some screenings in your doctor's office. Others need special equipment, ...

  9. A stem cell-based approach to cartilage repair.

    Science.gov (United States)

    Johnson, Kristen; Zhu, Shoutian; Tremblay, Matthew S; Payette, Joshua N; Wang, Jianing; Bouchez, Laure C; Meeusen, Shelly; Althage, Alana; Cho, Charles Y; Wu, Xu; Schultz, Peter G

    2012-05-11

    Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ), and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis. PMID:22491093

  10. Cell-Based Therapies for Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Stella Bernardi

    2012-01-01

    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.

  11. Congenital hypothyroidism: Screening dilemma

    Directory of Open Access Journals (Sweden)

    Meena P Desai

    2012-01-01

    Full Text Available Primary sporadic congenital hypothyroidism (CH is the most common cause of hypothyroidism infancy early childhood in iodine sufficient region. Screening for neonatal CH began in 1970s. The rationale and reason for neonatal screening for CH (NSCH are well established. It is mandatory in most developed countries along with the screen for metabolic disorder. The possibility of measuring TSH and thyroid hormones in cord blood paved the way for newborn screening (NS for CH. Worldwide it is estimated that 25% of the live born population of 130 million babies undergo NSCH. Klein et al., by 1972 had shown improved CNS prognosis in CH treated by age 3 months. NSCH has largely eradicated the severe irreversible neurodevelopmental damage and reversed the chances of growth failure in infancy and early childhood.

  12. Marburg Virus Reverse Genetics Systems

    Directory of Open Access Journals (Sweden)

    Kristina Maria Schmidt

    2016-06-01

    Full Text Available The highly pathogenic Marburg virus (MARV is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  13. Mesenchymal Stromal Cells as Cell-Based Therapeutics for Wound Healing

    OpenAIRE

    Samir Malhotra; Hu, Michael S.; Marshall, Clement D.; Tripp Leavitt; Alexander T. M. Cheung; Gonzalez, Jennifer G.; Harleen Kaur; Peter Lorenz, H.; Longaker, Michael T.

    2016-01-01

    Chronic wounds are a source of substantial morbidity for patients and are a major financial burden for the healthcare system. There are no current therapies that reliably improve nonhealing wounds or reverse pathological scarring. Mesenchymal stromal cells (MSCs) are a promising source of novel cell-based therapies due to the ease of their harvest and their integral role in the native wound repair process. Recent work has addressed the problems of loss of plasticity and off-target delivery th...

  14. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  15. Stem cell-based bone repair

    OpenAIRE

    Fei, Yurong; Xu, Ren-He; Hurley, Marja M.

    2012-01-01

    To accelerate bone repair, one strategy is to deliver the cells that make bone. The current review focuses on stem cell-based bone repair. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can self-renew unlimitedly and differentiate into the bone forming cells – osteoblasts. Scientists have been actively investigating culture conditions to stably and efficiently induce differentiation of these stem cells into osteoblasts. However, ESCs have the issues of ethnics, immune ...

  16. Use of viral promoters in mammalian cell-based bioassays: How reliable?

    OpenAIRE

    Gill-Sharma Manjit; Choudhuri Jyoti; Betrabet Shrikant S

    2004-01-01

    Abstract Cell-based bioassays have been suggested for screening of hormones and drug bioactivities. They are a plausible alternative to animal based methods. The technique used is called receptor/reporter system. Receptor/reporter system was initially developed as a research technique to understand gene function. Often reporter constructs containing viral promoters were used because they could be expressed with very 'high' magnitude in a variety of cell types in the laboratory. On the other h...

  17. Iterative Cellular Screening System for Nanoparticle Safety Testing

    OpenAIRE

    Franziska Sambale; Frank Stahl; Ferdinand Rüdinger; Dror Seliktar; Cornelia Kasper; Detlef Bahnemann; Thomas Scheper

    2015-01-01

    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 ...

  18. Polymer microarrays for cell based applications

    OpenAIRE

    Hansen, Anne Klara Brigitte

    2012-01-01

    The development and identification of new biomaterials that can replace specific tissues and organs is desirable. In the presented PhD thesis polymer microarrays were applied for the screening of polyacrylates and polyurethanes and evaluation for material discovery for applications in the life sciences. In the first part of the thesis, the largest polymer microarray ever made with more than 7000 features was fabricated and subsequently used for the screening of polyacrylates...

  19. MRSA Screening

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? MRSA Screening Share this page: Was this page helpful? Formal name: Methicillin resistant Staphylococcus aureus Screening Related tests: Wound Culture At a Glance Test ...

  20. Cancer screening

    OpenAIRE

    Krishna Prasad

    1987-01-01

    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.

  1. Sensitive-cell-based fish chromatophore biosensor

    Science.gov (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.

    2004-07-01

    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.

  2. Cell-based strategies for vascular regeneration.

    Science.gov (United States)

    Zou, Tongqiang; Fan, Jiabing; Fartash, Armita; Liu, Haifeng; Fan, Yubo

    2016-05-01

    Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1297-1314, 2016. PMID:26864677

  3. Biotoxin Detection Using Cell-Based Sensors

    Directory of Open Access Journals (Sweden)

    Pratik Banerjee

    2013-11-01

    Full Text Available Cell-based biosensors (CBBs utilize the principles of cell-based assays (CBAs by employing living cells for detection of different analytes from environment, food, clinical, or other sources. For toxin detection, CBBs are emerging as unique alternatives to other analytical methods. The main advantage of using CBBs for probing biotoxins and toxic agents is that CBBs respond to the toxic exposures in the manner related to actual physiologic responses of the vulnerable subjects. The results obtained from CBBs are based on the toxin-cell interactions, and therefore, reveal functional information (such as mode of action, toxic potency, bioavailability, target tissue or organ, etc. about the toxin. CBBs incorporate both prokaryotic (bacteria and eukaryotic (yeast, invertebrate and vertebrate cells. To create CBB devices, living cells are directly integrated onto the biosensor platform. The sensors report the cellular responses upon exposures to toxins and the resulting cellular signals are transduced by secondary transducers generating optical or electrical signals outputs followed by appropriate read-outs. Examples of the layout and operation of cellular biosensors for detection of selected biotoxins are summarized.

  4. Biotoxin detection using cell-based sensors.

    Science.gov (United States)

    Banerjee, Pratik; Kintzios, Spyridon; Prabhakarpandian, Balabhaskar

    2013-12-01

    Cell-based biosensors (CBBs) utilize the principles of cell-based assays (CBAs) by employing living cells for detection of different analytes from environment, food, clinical, or other sources. For toxin detection, CBBs are emerging as unique alternatives to other analytical methods. The main advantage of using CBBs for probing biotoxins and toxic agents is that CBBs respond to the toxic exposures in the manner related to actual physiologic responses of the vulnerable subjects. The results obtained from CBBs are based on the toxin-cell interactions, and therefore, reveal functional information (such as mode of action, toxic potency, bioavailability, target tissue or organ, etc.) about the toxin. CBBs incorporate both prokaryotic (bacteria) and eukaryotic (yeast, invertebrate and vertebrate) cells. To create CBB devices, living cells are directly integrated onto the biosensor platform. The sensors report the cellular responses upon exposures to toxins and the resulting cellular signals are transduced by secondary transducers generating optical or electrical signals outputs followed by appropriate read-outs. Examples of the layout and operation of cellular biosensors for detection of selected biotoxins are summarized. PMID:24335754

  5. Use of viral promoters in mammalian cell-based bioassays: How reliable?

    Directory of Open Access Journals (Sweden)

    Gill-Sharma Manjit

    2004-01-01

    Full Text Available Abstract Cell-based bioassays have been suggested for screening of hormones and drug bioactivities. They are a plausible alternative to animal based methods. The technique used is called receptor/reporter system. Receptor/reporter system was initially developed as a research technique to understand gene function. Often reporter constructs containing viral promoters were used because they could be expressed with very 'high' magnitude in a variety of cell types in the laboratory. On the other hand mammalian genes are expressed in a cell/tissue specific manner, which makes them (i.e. cells/tissues specialized for specific function in vivo. Therefore, if the receptor/reporter system is to be used as a cell-based screen for testing of hormones and drugs for human therapy then the choice of cell line as well as the promoter in the reporter module is of prime importance so as to get a realistic measure of the bioactivities of 'test' compounds. We evaluated two conventionally used viral promoters and a natural mammalian promoter, regulated by steroid hormone progesterone, in a cell-based receptor/reporter system. The promoters were spliced into vectors expressing enzyme CAT (chloramphenicol acetyl transferase, which served as a reporter of their magnitudes and consistencies in controlling gene expressions. They were introduced into breast cell lines T47D and MCF-7, which served as a cell-based source of progesterone receptors. The yardstick of their reliability was highest magnitude as well as consistency in CAT expression on induction by sequential doses of progesterone. All the promoters responded to induction by progesterone doses ranging from 10-12 to 10-6 molar by expressing CAT enzyme, albeit with varying magnitudes and consistencies. The natural mammalian promoter showed the most coherence in magnitude as well as dose dependent expression profile in both the cell lines. Our study casts doubts on use of viral promoters in a cell-based bioassay for

  6. A novel sensitive cell-based Love Wave biosensor for marine toxin detection.

    Science.gov (United States)

    Zhang, Xi; Fang, Jiaru; Zou, Ling; Zou, Yingchang; Lang, Lang; Gao, Fan; Hu, Ning; Wang, Ping

    2016-03-15

    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.

  7. Screening CO

    NARCIS (Netherlands)

    Ramírez, A.; Hagedoorn, S.; Kramers, L.; Wildenborg, T.; Hendriks, C.

    2010-01-01

    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

  8. Ethics of dental health screening.

    Science.gov (United States)

    Janakiram, Chandrashekar; Taha, Farheen

    2016-01-01

    Screening is the detection of disease at a point in its natural history when it is not yet symptomatic. In the natural history of dental caries, for example, the incipient lesions are at a reversible stage, which is a pre-symptomatic or an unrecognised symptomatic disease. Ideally, this is the stage during which screening should identify the risk of dental caries; however, presently, the so-called dental screening employed identifies the clinical cavitation of the tooth, which is very obvious to the individual. The individual already knows that he/she has dental caries and needs treatment, which the screening personnel (dental doctor) explains again during the screening procedure. Is it ethical to call such an event screening? The mushrooming of dental teaching hospitals has promoted regular screening of dental diseases among the communities and schoolchildren through their community dentistry-related activities. More often, it is a dental "check-up" that is carried out on the pretext of screening for dental diseases. Though the basic intention of this activity is to promote awareness of dental diseases and promote good health, there is also a hidden agenda to it. An artificial demand for dental care is created that is easily capitalised on by the dental teaching institutions to enhance its clinical activity. Dental screening is doing more harm than good as patients are made aware of the diseases for which they may not be able to afford treatment. This narrative review gives an account of the scientific evidence on screening for oral diseases, the current practices in screening and the ethical dilemmas of dental screening programmes. PMID:27474698

  9. Reversible arithmetic logic unit

    OpenAIRE

    zhou, Rigui; Shi, Yang; Zhang, Manqun

    2011-01-01

    Quantum computer requires quantum arithmetic. The sophisticated design of a reversible arithmetic logic unit (reversible ALU) for quantum arithmetic has been investigated in this letter. We provide explicit construction of reversible ALU effecting basic arithmetic operations. By provided the corresponding control unit, the proposed reversible ALU can combine the classical arithmetic and logic operation in a reversible integrated system. This letter provides actual evidence to prove the possib...

  10. Screening for Panic Disorder

    Science.gov (United States)

    ... Conference & Education Membership Journal & Multimedia Resources Awards Consumers Screening for Panic Disorder Main navigation FAQs Screen Yourself Screening for Depression Screening for Generalized Anxiety Disorder (GAD) ...

  11. Micromachined nanocalorimetric sensor for ultra-low-volume cell-based assays.

    Science.gov (United States)

    Johannessen, Erik A; Weaver, John M R; Bourova, Lenka; Svoboda, Petr; Cobbold, Peter H; Cooper, Jonathan M

    2002-05-01

    Current strategies for cell-based screening generally focus on the development of highly specific assays, which require an understanding of the nature of the signaling molecules and cellular pathways involved. In contrast, changes in temperature of cells provides a measure of altered cellular metabolism that is not stimulus specific and hence could have widespread applications in cell-based screening of receptor agonists and antagonists, as well as in the assessment of toxicity of new lead compounds. Consequently, we have developed a micromachined nanocalorimetric biological sensor using a small number of isolated living cells integrated within a subnanoliter format, which is capable of detecting 13 nW of generated power from the cells, upon exposure to a chemical or pharmaceutical stimulus. The sensor comprises a 10-junction gold and nickel thermopile, integrated on a silicon chip which was back-etched to span a 800-nm-thick membrane of silicon nitride. The thin-film membrane, which supported the sensing junctions of the thermoelectric transducer, gave the system a temperature resolution of 0.125 mK, a low heat capacity of 1.2 nJ mK(-1), and a rapid (unfiltered) response time of 12 ms. The application of the system in ultra-low-volume cell-based assays could provide a rapid endogenous screen. It offers important additional advantages over existing methods in that it is generic in nature, it does not require the use of recombinant cell lines or of detailed assay development, and finally, it can enable the use of primary cell lines or tissue biopsies. PMID:12033326

  12. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse log

  13. Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases

    NARCIS (Netherlands)

    Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.

    2014-01-01

    Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be

  14. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

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

  15. Airport Screening

    Science.gov (United States)

    ... ionizing radiation for security screening individuals [online]. Health Physics Society Position Statement. 2009. Available at http: / / hps. org/ documents/ securityscreening_ ps017- 1. pdf. Accessed 7 January 2011. Interagency Steering Committee on ...

  16. Quantitative comparison between microfluidic and microtiter plate formats for cell-based assays.

    Science.gov (United States)

    Yin, Huabing; Pattrick, Nicola; Zhang, Xunli; Klauke, Norbert; Cordingley, Hayley C; Haswell, Steven J; Cooper, Jonathan M

    2008-01-01

    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.

  17. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  18. Design, discovery, modelling, synthesis, and biological evaluation of novel and small, low toxicity s-triazine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors.

    Science.gov (United States)

    Viira, Birgit; Selyutina, Anastasia; García-Sosa, Alfonso T; Karonen, Maarit; Sinkkonen, Jari; Merits, Andres; Maran, Uko

    2016-06-01

    A set of top-ranked compounds from a multi-objective in silico screen was experimentally tested for toxicity and the ability to inhibit the activity of HIV-1 reverse transcriptase (RT) in cell-free assay and in cell-based assay using HIV-1 based virus-like particles. Detailed analysis of a commercial sample that indicated specific inhibition of HIV-1 reverse transcription revealed that a minor component that was structurally similar to that of the main compound was responsible for the strongest inhibition. As a result, novel s-triazine derivatives were proposed, modelled, discovered, and synthesised, and their antiviral activity and cellular toxicity were tested. Compounds 18a and 18b were found to be efficient HIV-1 RT inhibitors, with an IC50 of 5.6±1.1μM and 0.16±0.05μM in a cell-based assay using infectious HIV-1, respectively. Compound 18b also had no detectable toxicity for different human cell lines. Their binding mode and interactions with the RT suggest that there was strong and adaptable binding in a tight (NNRTI) hydrophobic pocket. In summary, this iterative study produced structural clues and led to a group of non-toxic, novel compounds to inhibit HIV-RT with up to nanomolar potency. PMID:27108399

  19. Reversibility of hyperhidrosis post axillary depilatory laser.

    Science.gov (United States)

    Helou, Josiane; Habre, Maya; Soutou, Boutros; Maatouk, Ismael; Ibrahim, Tony; Tomb, Roland

    2014-03-01

    Hyperhidrosis and bromhidrosis were lately reported as novel side effects of laser-assisted removal of axillary hair. The goal of our study was to evaluate the reversibility of these two side effects. An observational, single-center cohort study included over a 30-month screening period 30 patients with newly reported hyperhidrosis and/or bromhidrosis related to axillary depilatory laser. After 26 weeks of follow-up, each patient was assessed for spontaneous reversibility. A 12-week duration treatment with topical aluminum chloride was evaluated in patients with persisting hyperhidrosis. Hyperhidrosis was assessed using the Hyperhidrosis Disease Severity Scale (HDSS). Spontaneous reversibility was observed in 20% of patients. In total, 23 out of 30 patients recovered normal axillary transpiration either spontaneously or after treatment. Mean HDSS score was significantly lower in the treated group. It appears that axillary hyperhidrosis and bromhidrosis, secondary to laser depilation, reverse either spontaneously or after using topical antiperspirant. PMID:23887660

  20. 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)

    2008-01-15

    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

  1. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... you can use for reverse shoulder replacement. The standard delto-pectoral approach, or the superior approach, which ... that are different between a reverse and a standard total is, first of all, we don't ...

  2. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  3. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of product

  4. 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

    2005-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2012-04-01

    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.

  6. Screening for Specific Phobias

    Science.gov (United States)

    ... Screening for Posttraumatic Stress Disorder (PTSD) Screening for Social Anxiety Disorder Screening for Specific Phobias Screening for an Anxiety Disorder: Children Screening for an Anxiety Disorder: Family Member Self- ...

  7. Carotid Artery Screening

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Carotid Artery Screening What is carotid artery screening? Who should consider ... about carotid artery screening? What is carotid artery screening? Screening examinations are tests performed to find disease ...

  8. Preconception Carrier Screening

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG Preconception Carrier Screening Home For Patients Search FAQs Preconception Carrier Screening ... Screening FAQ179, August 2012 PDF Format Preconception Carrier Screening Pregnancy What is preconception carrier screening? What is ...

  9. Microsystems for cell-based electrophysiology

    Science.gov (United States)

    Yobas, Levent

    2013-08-01

    Among the electrophysiology techniques, the voltage clamp and its subsequent scaling to smaller mammalian cells, the so-called patch clamp, led to fundamental discoveries in the last century, revealing the ionic mechanisms and the role of single-ion channels in the generation and propagation of action potentials through excitable membranes (e.g. nerves and muscles). Since then, these techniques have gained a reputation as the gold standard of studying cellular ion channels owing to their high accuracy and rich information content via direct measurements under a controlled membrane potential. However, their delicate and skill-laden procedure has put a serious constrain on the throughput and their immediate utilization in the discovery of new cures targeting ion channels until researchers discovered ‘lab-on-a-chip’ as a viable platform for the automation of these techniques into a reliable high-throughput screening functional assay on ion channels. This review examines the innovative ‘lab-on-a-chip’ microtechnologies demonstrated towards this target over a period of slightly more than a decade. The technologies are categorically reviewed according to their considerations for design, fabrication, as well as microfluidic integration from a performance perspective with reference to their ability to secure G Ω seals (gigaseals) on cells, the norm broadly accepted among electrophysiologists for quality recordings that reflect ion-channel activity with high fidelity.

  10. Microsystems for cell-based electrophysiology

    International Nuclear Information System (INIS)

    Among the electrophysiology techniques, the voltage clamp and its subsequent scaling to smaller mammalian cells, the so-called patch clamp, led to fundamental discoveries in the last century, revealing the ionic mechanisms and the role of single-ion channels in the generation and propagation of action potentials through excitable membranes (e.g. nerves and muscles). Since then, these techniques have gained a reputation as the gold standard of studying cellular ion channels owing to their high accuracy and rich information content via direct measurements under a controlled membrane potential. However, their delicate and skill-laden procedure has put a serious constrain on the throughput and their immediate utilization in the discovery of new cures targeting ion channels until researchers discovered ‘lab-on-a-chip’ as a viable platform for the automation of these techniques into a reliable high-throughput screening functional assay on ion channels. This review examines the innovative ‘lab-on-a-chip’ microtechnologies demonstrated towards this target over a period of slightly more than a decade. The technologies are categorically reviewed according to their considerations for design, fabrication, as well as microfluidic integration from a performance perspective with reference to their ability to secure G Ω seals (gigaseals) on cells, the norm broadly accepted among electrophysiologists for quality recordings that reflect ion-channel activity with high fidelity. (topical review)

  11. Luminescent screens

    International Nuclear Information System (INIS)

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

  12. Synthesis and high content cell-based profiling of simplified analogues of the microtubule stabilizer (+)-discodermolide.

    Science.gov (United States)

    Minguez, Jose M; Giuliano, Kenneth A; Balachandran, Raghavan; Madiraju, Charitha; Curran, Dennis P; Day, Billy W

    2002-12-01

    (+)-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.

  13. 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.

  14. A new method for screening splice variants using gene-specific primer for reverse transcription followed by nested PCR approaches%利用GSP逆转录结合巢式PCR技术鉴定剪接变体的新方法及其在小鼠TrkC基因变体发现中的应用

    Institute of Scientific and Technical Information of China (English)

    张艳春; 严瑞芬; 吴永红; 张成岗

    2011-01-01

    Objective To develop a new method for screening splice variants using gene-specific reverse primer ( GSP ) to specifically reverse transcribe ( RT ) the target genes followed by nested PCR( nPCR ) approaches. Methods The reverse primer for transcription and nPCR primers of the known splicing variant No. I and variant No. 2 of the mouse TrlcC gene were used to obtain the GSP-transcribed cDNA products, followed by two or three rounds of nPCR. The PCR products were separated and extracted by 1. 5% agarase gel electrophoresis and subcloned into the pMD19-T vector for direct sequencing and similarity analysis with the known cDNA sequence of the TrkC gene in the RefSeq database. Results Not only was the known variant ( splicing variant No. I ) of the TrlcC gene obtained, but the new splicing variant was found. The 1669 bp from 520 to 2188 of the sequence of splicing variant No. 1 of the TrkC gene was spliced in the newly identified variant No. 3 , indicating a splicing pattern of cassette exon. Conclusion This method of screening gene splice variants using RT-GSPs and nPCR is a simple and valuable approach to screening novel splice variants, which is important for the function studies of eukaryotic genes and for understanding the mechanism of aberrant splicing-related diseases.%目的 利用基因特异性引物(gene specific primer,GSP)逆转录结合巢式PCR(nPCR)技术,建立鉴定剪接变体的新方法.方法 以小鼠TrkC基因为例,参考其已知变体1和变体2的序列分别设计GSP和nPCR引物,以逆转录产物为模板进行nPCR反应,扩增产物采用1.5%琼脂糖凝胶分离并回收具有递减趋势的DNA片段,利用T/A克隆技术亚克隆到载体pMD19-T进行直接测序,并与小鼠RefSeq数据库进行比对.结果 利用GSP逆转录结合nPCR技术不仅可鉴定出TrkC基因的已知剪接变体,而且还能够筛选到TrkC基因的新剪接变体并命名为变体3,与变体1相比属于盒式外显子剪接模式,缺失了变体1的520

  15. Current screens

    OpenAIRE

    Cubitt, Sean

    2011-01-01

    The architecture of screen design, including LCD, LED and DLP projection, is analysed in terms of the political economy and their aesthetics and phenomenological impacts, in association with the use of codecs as constraining as well as enabling tools in the control and management of visual data transmission.

  16. Hearing Screening

    Science.gov (United States)

    Johnson-Curiskis, Nanette

    2012-01-01

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

  17. Identification of compounds that modulate retinol signaling using a cell-based qHTS assay.

    Science.gov (United States)

    Chen, Yanling; Sakamuru, Srilatha; Huang, Ruili; Reese, David H; Xia, Menghang

    2016-04-01

    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. PMID:26820057

  18. A cell-based pharmacokinetics assay for evaluating tubulin-binding drugs.

    Science.gov (United States)

    Wang, Yuwei; Liu, Jihua; Zhang, Jun; Wang, Liping; Chan, Jonathon; Wang, Hai; Jin, Yi; Yu, Lei; Grainger, David W; Ying, Wenbin

    2014-01-01

    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.

  19. Development of a high-throughput cell-based reporter assay for screening JAK3 inhibitors

    OpenAIRE

    Yin, Chang-Hong; Bach, Erika A.; Baeg, Gyeong-Hun

    2011-01-01

    JAK3 has become an ideal target for the therapeutic treatment of immune-related diseases, as well as for the prevention of organ allograft rejection. A number of JAK3 inhibitors have been identified by in vitro biochemical enzymatic assays, but the majority display significant off-target effects on JAK2. Therefore, there is an urgent need to develop new experimental approaches to identify compounds that specifically inhibit JAK3. Here, we showed that in 32D/IL-2Rβ cells, STAT5 becomes phospho...

  20. 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

    2015-01-01

    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.

  1. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  2. Design of Reversible Counter

    OpenAIRE

    Md. Selim Al Mamun; B. K. Karmaker

    2014-01-01

    This article presents a research work on the design and synthesis of sequential circuits and flip-flops that are available in digital arena; and describes a new synthesis design of reversible counter that is optimized in terms of quantum cost, delay and garbage outputs compared to the existing designs. We proposed a new model of reversible T flip-flop in designing reversible counter.

  3. Posterior Reversible Encephalopathy Syndrome

    OpenAIRE

    J Gordon Millichap

    2013-01-01

    Investigators at Children's Hospital of Montefiore, Albert Einstein College of Medicine, NY, determined the incidence of posterior reversible encephalopathy syndrome (PRES) in a pediatric critical care unit.

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

    Directory of Open Access Journals (Sweden)

    Yoon Hyerim

    2012-09-01

    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.

  5. Reverse Genetic Approaches in Zebrafish

    Institute of Scientific and Technical Information of China (English)

    Peng Huang; Zuoyan Zhu; Shuo Lin; Bo Zhang

    2012-01-01

    Zebrafish (Danio rerio) is a well-established vertebrate animal model.A comprehensive collection of reverse genetics tools has been developed for studying gene function in this useful organism.Morpholino is the most widely used reagent to knock down target gene expression post-transcriptionally.For a long time,targeted genome modification has been heavily relied on large-scale traditional forward genetic screens,such as ENU (N-ethyl-N-nitrosourea) mutagenesis derived TILLING (Targeting Induced Local Lesions IN Genomes)strategy and pseudo-typed retrovirus mediated insertional mutagenesis.Recently,engineered endonucleases,including ZFNs (zinc finger nucleases) and TALENs (transcription activator-like effector nucleases),provide new and efficient strategies to directly generate sitespecific indel mutations by inducing double strand breaks in target genes.Here we summarize the major reverse genetic approaches for loss-of-function studies used and emerging in zebrafish,including strategies based on genome-wide mutagenesis and methods for sitespecific gene targeting.Future directions and expectations will also be discussed.

  6. Quantum reverse hypercontractivity

    Energy Technology Data Exchange (ETDEWEB)

    Cubitt, Toby [Department of Computer Science, University College London, London, United Kingdom and Centre for Quantum Information and Foundations, DAMTP, University of Cambridge, Cambridge (United Kingdom); Kastoryano, Michael [NBIA, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Montanaro, Ashley [School of Mathematics, University of Bristol, Bristol (United Kingdom); Temme, Kristan [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  7. Quadruple screen test

    Science.gov (United States)

    ... screen; Multiple marker screening; AFP plus; Triple screen test; AFP maternal; MSAFP; 4-marker screen ... This test is most often done between the 15th and 22nd weeks of the pregnancy. It is most accurate ...

  8. Quadruple screen test

    Science.gov (United States)

    ... screen; Multiple marker screening; AFP plus; Triple screen test; AFP maternal; MSAFP; 4-marker screen; Down syndrome - ... This test is most often done between the 15th and 22nd weeks of the pregnancy. It is most accurate ...

  9. Autism Screening and Diagnosis

    Science.gov (United States)

    ... Websites About Us Information For... Media Policy Makers Screening and Diagnosis Language: English Español (Spanish) Recommend on ... two steps: Developmental Screening Comprehensive Diagnostic Evaluation Developmental Screening Developmental screening is a short test to tell ...

  10. Reverse Pharmacognosy and Reverse Pharmacology; Two Closely Related Approaches for Drug Discovery Development.

    Science.gov (United States)

    Saeidnia, Soodabeh; Gohari, Ahmad R; Manayi, Azadeh

    2016-01-01

    Pharmacognosy is a science, which study natural products as a source of new drug leads and effective drug development. Rational and economic search for novel lead structures could maximize the speed of drug discovery by using powerful high technology methods. Reverse pharmacognosy, a complementary to pharmacognosy, couples the high throughput screening (HTS), virtual screening and databases along with the knowledge of traditional medicines. These strategies lead to identification of numerous in vitro active and selective hits enhancing the speed of drug discovery from natural sources. Besides, reverse pharmacology is a target base drug discovery approach; in the first step, a hypothesis is made that the alteration of specific protein activity will produce beneficial curative effects. Both, reverse pharmacognosy and reverse pharmacology take advantages of high technology methods to accomplish their particular purposes. Moreover, reverse pharmacognosy effectively utilize traditional medicines and natural products as promising sources to provide new drug leads as well as promote the rational use of them by using valuable information like protein structure databases and chemical libraries which prepare pharmacological profile of traditional medicine, plant extract or natural compounds. PMID:27396403

  11. 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

    2013-01-01

    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.

  12. Intensity-dependent equivalent circuit parameters of organic solar cells based on pentacene and C60

    Science.gov (United States)

    Yoo, Seunghyup; Domercq, Benoit; Kippelen, Bernard

    2005-05-01

    We present studies of the current-voltage characteristics of organic solar cells based on heterojunctions of pentacene and C60 as a function of illumination intensity. The photovoltaic response at a given illumination level is parameterized and modeled using the equivalent circuit model developed for inorganic pn-junction solar cells. Reduction in shunt resistance and increase in diode reverse saturation current density are observed upon increase of the light intensity. We demonstrate that this effect can be modeled by a refined equivalent circuit model that contains an additional shunt resistance and an additional diode the properties of which are functions of the light intensity. The effects of these additional components on the overall photovoltaic performance are discussed.

  13. An Algebra of Reversible Computation

    OpenAIRE

    Wang, Yong

    2014-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules, basic reversible processes algebra (BRPA), algebra of reversible communicating processes (ARCP), recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  14. On the construction of reversible automata for reversible languages

    OpenAIRE

    Lombardy, Sylvain

    2002-01-01

    International audience Reversible languages occur in many different domains. Although the decision for the membership of reversible languages was solved in 1992 by Pin, an effective construction of a reversible automaton for a reversible language was still unknown. We give in this paper a method to compute a reversible automaton from the minimal automaton of a reversible language. With this intention, we use the universal automaton of the language that can be obtained from the minimal auto...

  15. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow o...... justification for low-level machine code for reversible microprocessors as well as high-level block-structured reversible languages. We give examples for both such languages and illustrate them with a lossless encoder for permutations given by Dijkstra....

  16. The art and design of genetic screens: maize

    Science.gov (United States)

    Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

  17. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... stability and soft tissue envelope. In the early days of reverse arthroplasty, it used to be said ... often we'll drain these patients for a day to try to prevent hematoma formation, especially in ...

  18. Purchasing As Reverse Marketing

    OpenAIRE

    Blenkhorn, D L; Banting, P M

    1989-01-01

    This paper describes a new concept called reverse marketing, which is changing the conventional buyer-seller relationship and has important implications for the traditional role of the industrial marketer.

  19. Reversible Data Hiding Techniques

    Directory of Open Access Journals (Sweden)

    Dhananjay Yadav

    2012-03-01

    Full Text Available Reversible data hiding is a technique that is used to hide data inside an image. The data is hidden in such a way that the exact or original data is not visible. The hidden data can be retrieved as and when required. There are several methods that are used in reversible data hiding techniques like Watermarking, Lossless embedding and encryption. In this paper we present a review of reversible watermarking techniques and show different methods that are used to get reversible data hiding technique with higher embedding capacity and invisible objects. Watermark need not be hidden. Watermarking can be applied to 1. Images, 2. Text, 3. Audio/video, 4. Software.

  20. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... dislocations, although it's also reported to have a higher rate of getting the components in not perfect ... about infection and other things. There is a higher rate of infection with reverse replacement, probably because ...

  1. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... here in New York to bring you a video of a recent case of reverse shoulder arthroplasty ... helped design the system that's shown in this video, so I receive royalties and therefore have a ...

  2. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... a friction bite that if you try to work it around the corner, you can get an ... stability and soft tissue envelope. In the early days of reverse arthroplasty, it used to be said ...

  3. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... with an intact cuff, we would consider a traditional shoulder replacement. There are two basic approaches you ... less limited with the superior reverse versus the traditional. And I assume the question means the approach: ...

  4. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... the reverse allow patients to play tennis or sports where the arm swings backward. Our experience has ... who simply wants to be stronger or play sports better. But in terms of the patients that ...

  5. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... case of reverse shoulder arthroplasty for cuff deficient arthritis. You should be aware that I helped design ... in the last decade for cuff deficient shoulder arthritis in the United States. The indications are a ...

  6. Vasectomy reversal in humans

    OpenAIRE

    Bernie, Aaron M.; Osterberg, E Charles; Stahl, Peter J.; Ramasamy, Ranjith; Goldstein, Marc

    2012-01-01

    Vasectomy is the most common urological procedure in the United States with 18% of men having a vasectomy before age 45. A significant proportion of vasectomized men ultimately request vasectomy reversal, usually due to divorce and/or remarriage. Vasectomy reversal is a commonly practiced but technically demanding microsurgical procedure that restores patency of the male excurrent ductal system in 80–99.5% of cases and enables unassisted pregnancy in 40–80% of couples. The discrepancy between...

  7. PROCESSING REVERSE LOGISTICS INVENTORIES

    OpenAIRE

    Bajor, Ivona; Novačko, Luka; Ogrizović, Dario

    2014-01-01

    Developed logistics systems have organized reverse logistics flows and are continuously analyzing product returns, tending to detect patterns in oscillations of returning products in certain time periods. Inventory management in reverse logistics systems depends on different criteria, regarding goods categories, formed contracts between subjects of supply chains, uncertainty in manufacturer’s quantities of DOA (dead on arrival) products, etc. The developing logistics systems, such as the Croa...

  8. Reverse vending machine update

    Energy Technology Data Exchange (ETDEWEB)

    Rypins, S.; Papke, C.

    1986-02-01

    The document discusses reverse vending machines. Placed outdoors in supermarket parking lots or indoors in the lobby of the grocery market, these hightech machines exchange aluminum cans (or other containers in more specialized machines) for cash, coupons or redeemable receipts. The placement of reverse venders (RV) in or near supermarkets has made recycling more visible and more convenient, although the machines have yet to fully reach industry goals.

  9. Human cell-based micro electrode array platform for studying neurotoxicity

    Directory of Open Access Journals (Sweden)

    Laura eYlä-Outinen

    2010-09-01

    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.

  10. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available ... to get some of your questions through the Web link that you shown on the screen. Dr. ... a little tug -- we call it the tug test -- on the nerve and convince myself know where ...

  11. Global Distribution of Businesses Marketing Stem Cell-Based Interventions.

    Science.gov (United States)

    Berger, Israel; Ahmad, Amina; Bansal, Akhil; Kapoor, Tanvir; Sipp, Douglas; Rasko, John E J

    2016-08-01

    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. PMID:27494673

  12. Lung Cancer Screening

    Science.gov (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 ...

  13. Skin Cancer Screening

    Science.gov (United States)

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

  14. What Is Carrier Screening?

    Science.gov (United States)

    ... you want to learn. Search form Search Carrier screening You are here Home Testing & Services Testing for ... help you make the decision. What Is Carrier Screening? Carrier screening checks if a person is a " ...

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

    Directory of Open Access Journals (Sweden)

    Miki Yamamoto-Hino

    2013-11-01

    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.

  16. Reversed extension flow

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.

    2008-01-01

    Afilament stretching rheometer (FSR) was used for measuring the start-up of uni-axial elongational flow followed by reversed bi-axial flow, both with a constant elongational rate. A narrow molecular mass distribution linear polystyrene with a molecular weight of 145 kg / mole wis subjected...... to the start-up of elongation for three Hencky strain units and subsequently the reversed flow. The integral molecular stress function formulation within the 'interchain pressure' concept agrees with the experiments. In the experiments the Hencky strain at which the str~ss becomes zero (the recovery strain......) in the reversed flow has been identified. The recovery strain is found to increase with elongational rate, and has a maximum value of approximately 1.45. The Doi Edwards model using any stretch evolution equation is not able to predict the correct level of the recovery strain....

  17. Radiation controlling reversible window

    Energy Technology Data Exchange (ETDEWEB)

    Gell, H.A. Jr.

    1980-01-01

    A coated glass glazing system is presented including a transparent glass substrate having one surface coated with a radiation absorptive film which is overcoated with a radiation reflective film by a technique which renders the radiation reflective film radiation absorptive at the surface contracting the radiating absorptive film. The coated glass system is used as glazing for storm windows which are adapted to be reversible so that the radiation reflective surface may be exposed to the outside of the dwelling during the warm seasons to prevent excessive solar radiation from entering a dwelling and reversed during cold seasons to absorb solar radiation and utilize it to aid in keeping the dwelling interior warm.

  18. Characterization of hereditarily reversible posets

    OpenAIRE

    Kukieła, Michał

    2013-01-01

    A poset P is called reversible if every order preserving bijective self map of P is an order automorphism. P is called hereditarily reversible if every subposet of P is reversible. We give a complete characterization of hereditarily reversible posets in terms of forbidden subsets. A similar result is stated also for preordered sets. As a corollary we extend the list of known examples of hereditarily reversible topological spaces.

  19. Prenatal screening and genetics

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  20. Stem Cell-Based Therapies for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Lei Hao

    2014-01-01

    Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

  1. Reverse Coherent Information

    OpenAIRE

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2008-01-01

    In this letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well known coherent information. This lead to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  2. Reverse Coherent Information

    Science.gov (United States)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-05-01

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  3. Reversible focal splenial lesions

    Energy Technology Data Exchange (ETDEWEB)

    Gallucci, Massimo; Limbucci, Nicola [University of L' Aquila, Department of Radiology, S. Salvatore Hospital, L' Aquila (Italy); Paonessa, Amalia [Loreto Nuovo Hospital, Department of Neuroradiology, Napoli (Italy); Caranci, Ferdinando [Federico II University, Department of Neurological Sciences, Napoli (Italy)

    2007-07-15

    Reversible focal lesions in the splenium of the corpus callosum (SCC) have recently been reported.They are circumscribed and located in the median aspect of the SCC. On MRI, they are hyperintense on T2-W and iso-hypointense on T1-W sequences, with no contrast enhancement. On DWI, SCC lesions are hyperintense with low ADC values, reflecting restricted diffusion due to cytotoxic edema. The common element is the disappearance of imaging abnormalities with time, including normalization of DWI. Clinical improvement is often reported. The most established and frequent causes of reversible focal lesions of the SCC are viral encephalitis, antiepileptic drug toxicity/withdrawal and hypoglycemic encephalopathy. Many other causes have been reported, including traumatic axonal injury. The similar clinical and imaging features suggest a common mechanism induced by different pathological events leading to the same results. Edema and diffusion restriction in focal reversible lesions of the SCC have been attributed to excitotoxic mechanisms that can result from different mechanisms; no unifying relationship has been found to explain all the pathologies associated with SCC lesions. In our opinion, the similar imaging, clinical and prognostic aspects of these lesions depend on a high vulnerability of the SCC to excitotoxic edema and are less dependent on the underlying pathology. In this review, the relevant literature concerning reversible focal lesions in the SCC is analyzed and hypotheses about their pathogenesis are proposed. (orig.)

  4. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  5. On reverse hypercontractivity

    CERN Document Server

    Mossel, Elchanan; Sen, Arnab

    2011-01-01

    We study the notion of reverse hypercontractivity. We show that reverse hypercontractive inequalities are implied by standard hypercontractive inequalities as well as by the modified log-Sobolev inequality. Our proof is based on a new comparison lemma for Dirichlet forms and an extension of the Strook-Varapolos inequality. A consequence of our analysis is that {\\em all} simple operators $L=Id-\\E$ as well as their tensors satisfy uniform reverse hypercontractive inequalities. That is, for all $qreverse hypercontractive inequalities established here imply new mixing and isoperimetric results for short random walks in product spaces, for certain card-shufflings, for Glauber dynamics in high-temperat...

  6. Reversing insect pollinator decline

    OpenAIRE

    Potts, Simon; Wentworth, Jonathan

    2013-01-01

    Pollination by insects enables the reproduction of flowering plants and is critical to UK agriculture.1 Insect pollinators have declined globally, with implications for food security and wild habitats. This POSTnote summarises the causes for the recent trends, gaps in knowledge and possible strategies for reversing pollinator decline.

  7. Reverse Shoulder Arthroplasty

    Medline Plus

    Full Text Available Reverse Shoulder Arthroplasty Zimmer, Inc. New York City, New York March 17, 2010 Welcome to this OR Live presentation, brought to you by Zimmer. Hi. I'm ... my partner, Brad Parsons. We're here in New York to bring you a video of a ...

  8. Cell-Based Strategies for Meniscus Tissue Engineering

    OpenAIRE

    Wei Niu; Weimin Guo; Shufeng Han; Yun Zhu; Shuyun Liu; Quanyi Guo

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a ...

  9. Stem Cell-Based Therapeutics to Improve Wound Healing

    OpenAIRE

    Hu, Michael S.; Tripp Leavitt; Samir Malhotra; Dominik Duscher; Pollhammer, Michael S.; Walmsley, Graham G.; Zeshaan N. Maan; Alexander T. M. Cheung; Manfred Schmidt; Georg M. Huemer; Longaker, Michael T.; Peter Lorenz, H.

    2015-01-01

    Issues surrounding wound healing have garnered deep scientific interest as well as booming financial markets invested in novel wound therapies. Much progress has been made in the field, but it is unsurprising to find that recent successes reveal new challenges to be addressed. With regard to wound healing, large tissue deficits, recalcitrant wounds, and pathological scar formation remain but a few of our most pressing challenges. Stem cell-based therapies have been heralded as a promising mea...

  10. Safety issues in cell-based intervention trials

    OpenAIRE

    Dawson, Liza; Bateman-House, Alison S; Mueller Agnew, Dawn; Bok, Hilary; Brock, Dan W.; Chakravarti, Aravinda; Greene, Mark; King, Patricia A.; O'Brien, Stephen J.; Sachs, David H.; Schill, Kathryn E; Siegel, Andrew; Solter, Davor; Suter, Sonia M; Verfaillie, Catherine

    2003-01-01

    We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects ...

  11. Research of detecting embB mutation to screen MDR-TB by reverse line blot assay%反向线性点杂交方法检测embB基因突变在筛查结核分枝杆菌耐多药株的研究

    Institute of Scientific and Technical Information of China (English)

    张楠; 胡继红; 高振祥; 张然

    2011-01-01

    目的:利用反向线性点杂交(Reverse Line Blot assay,RLB)技术建立检测embB基因突变筛查结核分枝杆菌耐多药株(指至少对异烟肼和利福平两种以上药物产生耐药的结核分枝杆菌.multi-drug resistant tuberculosis,MDR-TB)的方法.方法:采用比例法药敏试验检测301株结核分枝杆菌临床分离株的耐药表型.分别用测序及反向线性点杂交方法检测embB基因突变位点,并用比例法药敏试验作为表型检测对照方法,测序作为基因型检测对照方法,对RLB方法筛查耐多药株进行评价.结果:经表型药敏检测耐多药株占57.9%,非耐多药株占25.2%,全敏感株占16.9%.经测序检测94株发生embB Met306突变,其中89.4%(84/94)的突变发生在耐多药株,10.6%为非耐多药株.Met306突变率在乙胺丁醇(Ethambutol,EMB)耐药组46.9%与乙胺丁醇敏感组47.8%间差异无统计学意义(x2=0.01,P>0.05),而突变率在耐多药组为48.3%与非耐多药组13.2%间差异有统计学意义(x2=48.53,P<0.01).用反向线性点杂交检测embB基因突变位点与测序法相比敏感度为96.8%,特异度为99.0%,二者一致率达98.3%.用反向线性点杂交检测耐多药株与表型检测方法相比敏感度为48.3%,特异度为88.2%.二者一致率为60.4%.结论:反向线性点杂交方法检测embB基因突变可在常规检测中替代测序法快速筛查结核分枝杆菌耐多药株.%Objective:To establish a new rapid method to screen the MDR - TB by detecting the embB mutation based on RLB.Methods: Totally of 301 isolates collected in China were tested by drug sensitive test (DST) to detect the phenotype resistance.Sequencing and RLB technique were applied to detect embB mutation genotype resistance.Meanwhile, we evaluated the results of detecting embB mutation to screen MDR- TB based on RLB by phenotype method and genotype method.Results: By genotype detecting 57.9% was MDR - TB, 25.2% was nonMDR - TB, 16.9% was whole - susceptibility

  12. A novel molecule integrating therapeutic and diagnostic activities reveals multiple aspects of stem cell-based therapy.

    Science.gov (United States)

    Hingtgen, Shawn D; Kasmieh, Randa; van de Water, Jeroen; Weissleder, Ralph; Shah, Khalid

    2010-04-01

    Stem cells are promising therapeutic delivery vehicles; however pre-clinical and clinical applications of stem cell-based therapy would benefit significantly from the ability to simultaneously determine therapeutic efficacy and pharmacokinetics of therapies delivered by engineered stem cells. In this study, we engineered and screened numerous fusion variants that contained therapeutic (TRAIL) and diagnostic (luciferase) domains designed to allow simultaneous investigation of multiple events in stem cell-based therapy in vivo. When various stem cell lines were engineered with the optimized molecule, SRL(O)L(2)TR, diagnostic imaging showed marked differences in the levels and duration of secretion between stem cell lines, while the therapeutic activity of the molecule showed the different secretion levels translated to significant variability in tumor cell killing. In vivo, simultaneous diagnostic and therapeutic monitoring revealed that stem cell-based delivery significantly improved pharmacokinetics and anti-tumor effectiveness of the therapy compared to intravenous or intratumoral delivery. As treatment for highly malignant brain tumor xenografts, tracking SRL(O)L(2)TR showed stable stem cell-mediated delivery significantly regressed peripheral and intracranial tumors. Together, the integrated diagnostic and therapeutic properties of SRL(O)L(2)TR answer critical questions necessary for successful utilization of stem cells as novel therapeutic vehicles. PMID:20127797

  13. Suppressor Screens in Arabidopsis.

    Science.gov (United States)

    Li, Xin; Zhang, Yuelin

    2016-01-01

    Genetic screens have proven to be a useful tool in the dissection of biological processes in plants. Specifically, suppressor screens have been widely used to study signal transduction pathways. Here we provide a detailed protocol for ethyl methanesulfonate (EMS) mutagenesis used in our suppressor screens in Arabidopsis and discuss the basic principles behind suppressor screen design and downstream analyses. PMID:26577776

  14. Prenatal screening and genetics

    NARCIS (Netherlands)

    Alderson, P.; Aro, A.R.; Dragonas, T.; Ettorre, E.; Hemminki, E.; Jalinoja, P.; Santalahti, P.; Tijmstra, T.

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we exami

  15. Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus.

    Science.gov (United States)

    Barcala Tabarrozzi, A E; Castro, C N; Dewey, R A; Sogayar, M C; Labriola, L; Perone, M J

    2013-02-01

    Type 1 diabetes mellitus (T1DM) results from death of insulin-secreting β cells mediated by self-immune cells, and the consequent inability of the body to maintain insulin levels for appropriate glucose homeostasis. Probably initiated by environmental factors, this disease takes place in genetically predisposed individuals. Given the autoimmune nature of T1DM, therapeutics targeting immune cells involved in disease progress have been explored over the last decade. Several high-cost trials have been attempted to prevent and/or reverse T1DM. Although a definitive solution to cure T1DM is not yet available, a large amount of information about its nature and development has contributed greatly to both the improvement of patient's health care and design of new treatments. In this study, we discuss the role of different types of immune cells involved in T1DM pathogenesis and their therapeutic potential as targets and/or modified tools to treat patients. Recently, encouraging results and new approaches to sustain remnant β cell mass and to increase β cell proliferation by different cell-based means have emerged. Results coming from ongoing clinical trials employing cell therapy designed to arrest T1DM will probably proliferate in the next few years. Strategies under consideration include infusion of several types of stem cells, dendritic cells and regulatory T cells, either manipulated genetically ex vivo or non-manipulated. Their use in combination approaches is another therapeutic alternative. Cell-based interventions, without undesirable side effects, directed to block the uncontrollable autoimmune response may become a clinical reality in the next few years for the treatment of patients with T1DM.

  16. Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory.

    Science.gov (United States)

    Fiegel, Henning C; Kaufmann, Peter M; Bruns, Helge; Kluth, Dietrich; Horch, Raymund E; Vacanti, Joseph P; Kneser, Ulrich

    2008-01-01

    Today, liver transplantation is still the only curative treatment for liver failure due to end-stages liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, e.g. liver tissue engineering, are under investigation with the aim, that in future an artificial liver tissue could be created and be used for the replacement of the liver function in patients. Using cells instead of organs in this setting should permit (i) expansion of cells in an in vitro phase, (ii) genetic or immunological manipulation of cells for transplantation, (iii) tissue typing and cryopreservation in a cell bank, and (iv) the ex vivo genetic modification of patient's own cells prior re-implantation. Function and differentiation of liver cells are influenced by the three-dimensional organ architecture. The use of polymeric matrices permits the three dimensional formation of a neo-tissue and specific stimulation by adequate modification of the matrix-surface which might be essential for appropriate differentiation of transplanted cells. Additionally, culturing hepatocytes on three dimensional matrices permits culture in a flow bioreactor system with increased function and survival of the cultured cells. Based on bioreactor technology, bioartificial liver devices (BAL) are developed for extracorporeal liver support. Although BALs improved clinical and metabolic conditions, increased patient survival rates have not been proven yet. For intra-corporeal liver replacement, a concept which combines Tissue Engineering using three-dimensional, highly porous matrices with cell transplantation could be useful. In such a concept, whole liver mass transplantation, long term engraftment and function as well as correction of a metabolic defect in animal models could be achieved with a principally reversible procedure. Future studies have to

  17. Screening for Malnutrition in Older People.

    Science.gov (United States)

    Guyonnet, Sophie; Rolland, Yves

    2015-08-01

    Malnutrition risk increases with age and level of care. Despite significant medical advances, malnutrition remains a significant and highly prevalent public health problem of developed countries. Earlier identification and appropriate nutrition support may help to reverse or halt the malnutrition trajectory and the negative outcomes associated with poor nutritional status. A nutrition screening process is recommended to help detect people with protein-energy malnutrition (PEM) or at malnutrition risk. Evidence supports that oral nutritional supplements and dietary counseling can increase dietary intake and improve quality of life in elderly with PEM or at malnutrition risk. This article examines nutritional screening and assessment tools designated for older adults. PMID:26195101

  18. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  19. Reversible Multi-Head Finite Automata Characterize Reversible Logarithmic Space

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock

    2012-01-01

    Deterministic and non-deterministic multi-head finite automata are known to characterize the deterministic and non- deterministic logarithmic space complexity classes, respectively. Recently, Morita introduced reversible multi-head finite automata (RMFAs), and posed the question of whether RMFAs...... characterize reversible logarithmic space as well. Here, we resolve the question affirmatively, by exhibiting a clean RMFA simulation of logarithmic space reversible Turing machines. Indirectly, this also proves that reversible and deterministic multi-head finite automata recognize the same languages....

  20. Novel patient cell-based HTS assay for identification of small molecules for a lysosomal storage disease.

    Directory of Open Access Journals (Sweden)

    Haifeng Geng

    Full Text Available Small molecules have been identified as potential therapeutic agents for lysosomal storage diseases (LSDs, inherited metabolic disorders caused by defects in proteins that result in lysosome dysfunctional. Some small molecules function assisting the folding of mutant misfolded lysosomal enzymes that are otherwise degraded in ER-associated degradation. The ultimate result is the enhancement of the residual enzymatic activity of the deficient enzyme. Most of the high throughput screening (HTS assays developed to identify these molecules are single-target biochemical assays. Here we describe a cell-based assay using patient cell lines to identify small molecules that enhance the residual arylsulfatase A (ASA activity found in patients with metachromatic leukodystrophy (MLD, a progressive neurodegenerative LSD. In order to generate sufficient cell lines for a large scale HTS, primary cultured fibroblasts from MLD patients were transformed using SV40 large T antigen. These SV40 transformed (SV40t cells showed to conserve biochemical characteristics of the primary cells. Using a specific colorimetric substrate para-nitrocatechol sulfate (pNCS, detectable ASA residual activity were observed in primary and SV40t fibroblasts from a MLD patient (ASA-I179S cultured in multi-well plates. A robust fluorescence ASA assay was developed in high-density 1,536-well plates using the traditional colorimetric pNCS substrate, whose product (pNC acts as "plate fluorescence quencher" in white solid-bottom plates. The quantitative cell-based HTS assay for ASA generated strong statistical parameters when tested against a diverse small molecule collection. This cell-based assay approach can be used for several other LSDs and genetic disorders, especially those that rely on colorimetric substrates which traditionally present low sensitivity for assay-miniaturization. In addition, the quantitative cell-based HTS assay here developed using patient cells creates an

  1. Reversible watermarking for images

    Science.gov (United States)

    van Leest, Arno J.; van der Veen, Michiel; Bruekers, Fons

    2004-06-01

    Reversible watermarking is a technique for embedding data in a digital host signal in such a manner that the original host signal can be restored in a bit-exact manner in the restoration process. In this paper, we present a general framework for reversible watermarking in multi-media signals. A mapping function, which is in general neither injective nor surjective, is used to map the input signal to a perceptually equivalent output signal. The resulting unused sample values of the output signal are used to encode additional (watermark) information and restoration data. At the 2003 SPIE conference, examples of this technique applied to digital audio were presented. In this paper we concentrate on color and gray-scale images. A particular challenge in this context is not only the optimization of rate-distortion, but also the measure of perceptual quality (i.e. the distortion). In literature distortion is often expressed in terms of PSNR, making comparison among different techniques relatively straightforward. We show that our general framework for reversible watermarking applies to digital images and that results can be presented in terms of PSNR rate-distortions. However, the framework allows for more subtle signal manipulations that are not easily expressed in terms of PSNR distortion. These changes involve manipulations of contrast and/or saturation.

  2. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

    Directory of Open Access Journals (Sweden)

    Robert Kraft

    2013-01-01

    The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the ‘filagree’ phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity. The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the ‘beads-on-a-string’ defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery.

  3. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    Science.gov (United States)

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

    2016-05-01

    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. PMID:27158196

  4. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    Science.gov (United States)

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

    2016-05-01

    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.

  5. Designing Parity Preserving Reversible Circuits

    OpenAIRE

    Paul, Goutam; Chattopadhyay, Anupam; Chandak, Chander

    2013-01-01

    Making a reversible circuit fault-tolerant is much more difficult than classical circuit and there have been only a few works in the area of parity-preserving reversible logic design. Moreover, all of these designs are ad hoc, based on some pre-defined parity preserving reversible gates as building blocks. In this paper, we for the first time propose a novel and systematic approach towards parity preserving reversible circuits design. We provide some related theoretical results and give two a...

  6. Reverse Engineering of RFID devices

    OpenAIRE

    Bokslag, Wouter

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID technology and possible countermeasures that could limit the potential of such reverse engineering attempts.

  7. Stem cell-based therapies for HIV/AIDS.

    Science.gov (United States)

    Pernet, Olivier; Yadav, Swati Seth; An, Dong Sung

    2016-08-01

    One of the current focuses in HIV/AIDS research is to develop a novel therapeutic strategy that can provide a life-long remission of HIV/AIDS without daily drug treatment and, ultimately, a cure for HIV/AIDS. Hematopoietic stem cell-based anti-HIV gene therapy aims to reconstitute the patient immune system by transplantation of genetically engineered hematopoietic stem cells with anti-HIV genes. Hematopoietic stem cells can self-renew, proliferate and differentiate into mature immune cells. In theory, anti-HIV gene-modified hematopoietic stem cells can continuously provide HIV-resistant immune cells throughout the life of a patient. Therefore, hematopoietic stem cell-based anti-HIV gene therapy has a great potential to provide a life-long remission of HIV/AIDS by a single treatment. Here, we provide a comprehensive review of the recent progress of developing anti-HIV genes, genetic modification of hematopoietic stem progenitor cells, engraftment and reconstitution of anti-HIV gene-modified immune cells, HIV inhibition in in vitro and in vivo animal models, and in human clinical trials. PMID:27151309

  8. Cell-Based Strategies for Meniscus Tissue Engineering

    Science.gov (United States)

    Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

  9. Stem Cell-Based Cell Therapy for Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Meiling Jin

    2014-01-01

    Full Text Available Glomerulonephritis (GN, characterized by immune-mediated inflammatory changes in the glomerular, is a common cause of end stage renal disease. Therapeutic options for glomerulonephritis applicable to all cases mainly include symptomatic treatment and strategies to delay progression. In the attempt to yield innovative interventions fostering the limited capability of regeneration of renal tissue after injury and the uncontrolled pathological process by current treatments, stem cell-based therapy has emerged as novel therapy for its ability to inhibit inflammation and promote regeneration. Many basic and clinical studies have been performed that support the ability of various stem cell populations to ameliorate glomerular injury and improve renal function. However, there is a long way before putting stem cell-based therapy into clinical practice. In the present article, we aim to review works performed with respect to the use of stem cell of different origins in GN, and to discuss the potential mechanism of therapeutic effect and the challenges for clinical application of stem cells.

  10. Cell-based microfluidic platform for mimicking human olfactory system.

    Science.gov (United States)

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

    2015-12-15

    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.

  11. Cell-Based Strategies for Meniscus Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Wei Niu

    2016-01-01

    Full Text Available Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering.

  12. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  13. Screening for hypertension.

    OpenAIRE

    Tomson, P R V

    1983-01-01

    In an open access screening campaign for hypertension lasting six weeks 6259 individuals were screened with a Vita-Stat blood pressure computer and an estimated 4.2% to 5.4% of new cases were detected.

  14. Screening Tests and Vaccines

    Science.gov (United States)

    ... Contact Us Text size | Print | Screening Tests and Vaccines This information in Spanish ( en español ) Getting important screening tests and vaccines can save your life. Check this section of ...

  15. Colon cancer screening

    Science.gov (United States)

    ... screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test ... called the fecal immunochemical test (FIT) and stool DNA test (sDNA). Sigmoidoscopy : This test uses a small flexible ...

  16. Breast cancer screenings

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000837.htm Breast cancer screenings To use the sharing features on this page, please enable JavaScript. Breast cancer screenings can help find breast cancer early, before ...

  17. Prostate cancer screenings

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000846.htm Prostate cancer screenings To use the sharing features on this ... Intern Med . 2011;155(11):762-71. National Cancer Institute. Prostate Cancer Screening -- for health professionals. Revised April 2, ...

  18. Video Screen Capture Basics

    Science.gov (United States)

    Dunbar, Laura

    2014-01-01

    This article is an introduction to video screen capture. Basic information of two software programs, QuickTime for Mac and BlueBerry Flashback Express for PC, are also discussed. Practical applications for video screen capture are given.

  19. Cervical Cancer Screening

    Science.gov (United States)

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

  20. Human Papillomavirus (HPV) Screening

    Science.gov (United States)

    ... Diseases HPV-Associated Cancers Gynecologic Cancers Redirect CDC - Screening Recommend on Facebook Tweet Share Compartir You are being redirected to the HPV Cancer Screening page. Please update your bookmarks to the link ...

  1. Prostate Cancer Screening

    Science.gov (United States)

    ... man's bladder that produces fluid for semen. Cancer screening is looking for cancer before you have any ... be easier to treat. There is no standard screening test for prostate cancer. Researchers are studying different ...

  2. Fundamentals of reversible flowchart languages

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2016-01-01

    . Although reversible flowcharts are superficially similar to classical flowcharts, there are crucial differences: atomic steps are limited to locally invertible operations, and join points require an explicit orthogonalizing conditional expression. Despite these constraints, we show that reversible......Abstract This paper presents the fundamentals of reversible flowcharts. They are intended to naturally represent the structure and control flow of reversible (imperative) programming languages in a simple computation model, in the same way classical flowcharts do for conventional languages......, structured reversible flowcharts are as expressive as unstructured ones, as shown by a reversible version of the classic Structured Program Theorem. We illustrate how reversible flowcharts can be concretized with two example programming languages, complete with syntax and semantics: a low-level unstructured...

  3. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  4. Potential of neural stem cell-based therapies for Alzheimer's disease.

    Science.gov (United States)

    Li, Xue-Yuan; Bao, Xin-Jie; Wang, Ren-Zhi

    2015-09-01

    Alzheimer's disease (AD), known to be a leading cause of dementia that causes heavy social and financial burdens worldwide, is characterized by progressive loss of neurons and synaptic connectivity after depositions of amyloid-β (Aβ) protein. Current therapies for AD patients can only alleviate symptoms but cannot deter the neural degeneration, thus providing no long-term recovery. Neural stem cells (NSCs), capable of self-renewal and of differentiation into functional neurons and glia, have been shown to repair damaged networks and reverse memory and learning deficits in animal studies, providing new hope for curing AD patients by cell transplantation. Under AD pathology, the microenvironment also undergoes great alterations that affect the propagation of NSCs and subsequent therapeutic efficiency, calling for measures to improve the hostile environment for cell transplantation. This article reviews the therapeutic potential of both endogenous and exogenous NSCs in the treatment of AD and the challenges to application of stem cells in AD treatment, particularly those from the microenvironmental alterations, in the hope of providing more information for future research in exploiting stem cell-based therapies for AD. © 2015 Wiley Periodicals, Inc.

  5. Development of a New High-throughput Screening Model for Human High Density Lipoprotein Receptor (CLA-1) Agonists

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To develop a new high-throughput screening model for human high-density lipoprotein (HDL) receptor (CD36 and LIMPII analogous-1, CLA-1) agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA (cDNA) of CLA-1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR). Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV) into donor vector pFastBac1 and recombinant pFastBac1-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacmid DNA. Recombinant bacmid-CLA-1 was transfected into Spodoptera frugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA-1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.

  6. Exploiting PubChem for Virtual Screening

    Science.gov (United States)

    Xie, Xiang-Qun

    2011-01-01

    Importance of the field PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. Areas covered in this review This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. What the reader will gain These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. Take home message Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design. PMID:21691435

  7. Reversible posterior leukoencephalopathy syndrome

    International Nuclear Information System (INIS)

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  8. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  9. Reversed field pinches

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, H.A.B. (Euratom/UKAEA Fusion Association, Abingdon (UK). Culham Lab.)

    1983-03-15

    The present status of RFP research is reviewed with emphasis on recent experimental developments. The basic properties of the RFP are summarised in section 2 including equilibrium and relaxed states, self-reversal and stability. The remainder of the paper deals with experimental results. There are five intermediate sized machines operating with the minor radii of the metal bellows liner in the range 9-26 cm, peak currents of a few hundred kA reached in between 0.1 and 4 ms with pulse lengths of up to more than 10 ms. The field configuration is set up using self-reversal usually assisted by slow Bsub(PHI) control. The temperatures are typically a few hundred eV (maximum approx.=600 eV on TPE-IR(M) in Japan) and the density is typically 10/sup 13/-10/sup 14/ cm/sup -3/ with maximum ..beta..sub(THETA)> or approx.10%. It is found that some plasma properties depend on the value of I/N (I is the current and N the line density) with a clear high-density limit due to radiation. The electron temperature increases with current; much of the data fits a dependence T..cap alpha..Isup(n) where 0.5reversed field pinch research will be highlighted with an indication of future trends in this work.

  10. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test. PMID:21954677

  11. Partial Reversible Gates(PRG) for Reversible BCD Arithmetic

    OpenAIRE

    Thapliyal, Himanshu; Arabnia, Hamid R; Bajpai, Rajnish; Sharma, Kamal K

    2007-01-01

    IEEE 754r is the ongoing revision to the IEEE 754 floating point standard and a major enhancement to the standard is the addition of decimal format. Furthermore, in the recent years reversible logic has emerged as a promising computing paradigm having its applications in low power CMOS, quantum computing, nanotechnology, and optical computing. The major goal in reversible logic is to minimize the number of reversible gates and garbage outputs. Thus, this paper proposes the novel concept of pa...

  12. Improved Computational Model of Grid Cells Based on Column Structure

    Institute of Scientific and Technical Information of China (English)

    Yang Zhou; Dewei Wu; Weilong Li; Jia Du

    2016-01-01

    To simulate the firing pattern of biological grid cells, this paper presents an improved computational model of grid cells based on column structure. In this model, the displacement along different directions is processed by modulus operation, and the obtained remainder is associated with firing rate of grid cell. Compared with the original model, the improved parts include that: the base of modulus operation is changed, and the firing rate in firing field is encoded by Gaussian⁃like function. Simulation validates that the firing pattern generated by the improved computational model is more consistent with biological characteristic than original model. Besides, the firing pattern is badly influenced by the cumulative positioning error, but the computational model can also generate the regularly hexagonal firing pattern when the real⁃time positioning results are modified.

  13. Glial progenitor cell-based treatment of the childhood leukodystrophies

    DEFF Research Database (Denmark)

    Osorio, M Joana; Goldman, Steven A

    2016-01-01

    stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group...... genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease....... and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent...

  14. Cell-Based Microarrays for In Vitro Toxicology

    Science.gov (United States)

    Wegener, Joachim

    2015-07-01

    DNA/RNA and protein microarrays have proven their outstanding bioanalytical performance throughout the past decades, given the unprecedented level of parallelization by which molecular recognition assays can be performed and analyzed. Cell microarrays (CMAs) make use of similar construction principles. They are applied to profile a given cell population with respect to the expression of specific molecular markers and also to measure functional cell responses to drugs and chemicals. This review focuses on the use of cell-based microarrays for assessing the cytotoxicity of drugs, toxins, or chemicals in general. It also summarizes CMA construction principles with respect to the cell types that are used for such microarrays, the readout parameters to assess toxicity, and the various formats that have been established and applied. The review ends with a critical comparison of CMAs and well-established microtiter plate (MTP) approaches.

  15. Screen Practice in Curating

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2014-01-01

    in curating has emerged from a critical discourse in response to a particular "screen topos", which has relied on a Foucauldian, apparatus-theoretical mechanism of the screen as a broadcasting medium of mass entertainment. This topos, I argue, has transferred the dispositif of the screen apparatus...... to the dispositif of screen practice in curating, resulting in a medium-based curatorial discourse. With reference to the nomadic exhibition project Nordic Outbreak that I co-curated with Nina Colosi in 2013 and 2014, I suggest that the topos of the defined visual display area, frequently still known as "the screen...

  16. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  17. Multiple stimulus reversible hydrogels

    Science.gov (United States)

    Gutowska, Anna; Krzyminski, Karol J.

    2006-04-25

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  18. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  19. Reverse osmosis application studies

    International Nuclear Information System (INIS)

    To assess the feasibility of applying reverse osmosis (RO) and ultrafiltration (UF) for effective treatment of process and waste streams from operations at Ontario Hydro's thermal and nuclear stations, an extensive literature survey has been carried out. It is concluded that RO is not at present economic for pretreatment of Great Lakes water prior to ion exchange demineralization for boiler makeup. Using both conventional and novel commercial membrane modules, RO pilot studies are recommended for treatment of boiler cleaning wastes, fly ash leachates, and flue gas desulphurization scrubber discharges for removal of heavy metals. Volume reduction and decontamination of nuclear station low-level active liquid waste streams by RO/UF also appear promising. Research programmes are proposed

  20. Reverse photoacoustic standoff spectroscopy

    Science.gov (United States)

    Van Neste, Charles W.; Senesac, Lawrence R.; Thundat, Thomas G.

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  1. A Reversible Processor Architecture and its Reversible Logic Design

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    We describe the design of a purely reversible computing architecture, Bob, and its instruction set, BobISA. The special features of the design include a simple, yet expressive, locally-invertible instruction set, and fully reversible control logic and address calculation. We have designed...... an architecture with an ISA that is expressive enough to serve as the target for a compiler from a high-level structured reversible programming language. All-in-all, this paper demonstrates that the design of a complete reversible computing architecture is possible and can serve as the core of a programmable...

  2. An Algebra of Reversible Quantum Computing

    OpenAIRE

    Wang, Yong

    2015-01-01

    Based on the axiomatization of reversible computing RACP, we generalize it to quantum reversible computing which is called qRACP. By use of the framework of quantum configuration, we show that structural reversibility and quantum state reversibility must be satisfied simultaneously in quantum reversible computation. RACP and qRACP has the same axiomatization modulo the so-called quantum forward-reverse bisimularity, that is, classical reversible computing and quantum reversible computing are ...

  3. Defining the Polar Field Reversal

    Science.gov (United States)

    Upton, Lisa; Hathaway, David H.

    2013-01-01

    The polar fields on the Sun are directly related to solar cycle variability. Recently there has been interest in studying an important characteristic of the polar fields: the timing of the polar field reversals. However this characteristic has been poorly defined, mostly due to the limitations of early observations. In the past, the reversals have been calculated by averaging the flux above some latitude (i.e. 55deg or 75deg). Alternatively, the reversal could be defined by the time in which the previous polarity is completely canceled and replaced by the new polarity at 90de, precisely at the pole. We will use a surface flux transport model to illustrate the differences in the timing of the polar field reversal based on each of these definitions and propose standardization in the definition of the polar field reversal. The ability to predict the timing of the polar field reversal using a surface flux transport model will also be discussed.

  4. Company policy toward reverse logistics

    OpenAIRE

    Klapalová Alena; Králová Maria

    2012-01-01

    The paper deals with the results of questionnaire survey examining the character of companies’ policies towards management of reverse flows logistics, namely innovativeness of policy related to the reasons of involvement to manage reverse flows and to the planning system of reverse logistics. Answers from the informants and respondents from 150 Czech companies were analysed with the employment of statistical methods (frequencies, contingency tables and Man – Whitney test) to explore the poten...

  5. Geomagnetic Reversals during the Phanerozoic.

    Science.gov (United States)

    McElhinny, M W

    1971-04-01

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency. PMID:17735224

  6. Magnetic reversals and mass extinctions

    Science.gov (United States)

    Raup, D. M.

    1985-01-01

    The results of a study of reversals of the earth's magnetic field over the past 165 Myr are presented. A stationary periodicity of 30 Myr emerges which predicts pulses of increased reversal activity centered at 10, 40, 70, . . . Myr before the present. The correlation between the reversal intensity and biological extinctions is examined, and a nontrivial discrepancy is found between the magnetic and extinction periodicity.

  7. Magnetic Reversal on Vicinal Surfaces

    OpenAIRE

    Hyman, R. A.; Zangwill, A.; Stiles, M. D.

    1998-01-01

    We present a theoretical study of in-plane magnetization reversal for vicinal ultrathin films using a one-dimensional micromagnetic model with nearest-neighbor exchange, four-fold anisotropy at all sites, and two-fold anisotropy at step edges. A detailed "phase diagram" is presented that catalogs the possible shapes of hysteresis loops and reversal mechanisms as a function of step anisotropy strength and vicinal terrace length. The steps generically nucleate magnetization reversal and pin the...

  8. Initiation of HIV Reverse Transcription

    Directory of Open Access Journals (Sweden)

    Roland Marquet

    2010-01-01

    Full Text Available Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

  9. Reversal of underground mine ventilation

    Energy Technology Data Exchange (ETDEWEB)

    Ray, S.K.; Sahay, N.; Singh, R.P.; Singh, A.K.; Bhowmick, B.C. [Central Mining Research Institute, Dhanbad (India)

    2002-09-01

    Reversal of main ventilation is one of the important means to isolate a fire during emergency. In America, it has been reported that by fan reversal lives have been saved in underground coal mines. Indian coal mines have so far not come forward to adopt this method. Not much research work has so far been carried out in India. This paper deals with international review of the work carried out in other countries. Laws relating to the reversal of ventilation in different countries of the world is discussed. The effect of reversal on goaf gases and adjustment of ventilation flow is also outlined. 17 refs., 1 fig., 2 tabs.

  10. Importance of the stem cell microenvironment forophthalmological cell-based therapy

    Institute of Scientific and Technical Information of China (English)

    Peng-Xia Wan; Bo-Wen Wang; Zhi-Chong Wang

    2015-01-01

    suggest that to explore how to reconstructthe stem cell microenvironment and strengthen itscombination with the transplanted cells are key steps tosuccessful cell therapy. In this review, we will describethe interactions of the stem cell microenvironmentwith the stem cells, discuss the importance of the stemcell microenvironment for cell-based therapy in oculardiseases, and introduce the progress of stem cell-based therapy for ocular diseases.

  11. Reversibility and Retrievability in Finland

    International Nuclear Information System (INIS)

    The spent nuclear fuel disposal project in Finland proceeds in stepwise manner. The site selection process continued with several stages from 1984 to 2000, including a country-wide site screening of potential sites and finally the investigations of four final candidate sites. Licensing of a nuclear facility includes three steps: - The Decision in Principle, which can be made if a '..construction project is in line with the overall good of society'. The decision is made by the government, requiring endorsement from the Parliament. Host municipality consent and a positive preliminary safety evaluation by the nuclear regulatory body, STUK, is required. - Construction license - granted by government, a positive safety evaluation by STUK is a prerequisite. - Operating license - granted by government, a positive safety evaluation by STUK is a prerequisite. The decision in principle for the Olkiluoto disposal facility was ratified by the Parliament in 2001. An application for a construction license is expected to be submitted in 2010 and for operation license in 2018, with the goal for start of operation in 2020. The closure of the facility is expected early in the next century. The stepwise decision process and the long time frame allow consideration of new developments and information. When the Decision in Principle for the Olkiluoto repository was made, retrievability-related requirements did exist in the regulation. The applicable government decision and regulatory guide in force at the time stipulated the following: - Disposal shall be planned so that no monitoring of the disposal site is required for ensuring long-term safety and so that retrievability of the waste canisters is maintained to provide for such development of technology that makes it a preferred option. - In the post-closure phase, retrieval of the waste canisters from the repository shall be feasible during the period in which the engineered barriers are required to provide practically complete

  12. Lung Cancer Screening Update.

    Science.gov (United States)

    Ruchalski, Kathleen L; Brown, Kathleen

    2016-07-01

    Since the release of the US Preventive Services Task Force and Centers for Medicare and Medicaid Services recommendations for lung cancer screening, low-dose chest computed tomography screening has moved from the research arena to clinical practice. Lung cancer screening programs must reach beyond image acquisition and interpretation and engage in a multidisciplinary effort of clinical shared decision-making, standardization of imaging and nodule management, smoking cessation, and patient follow-up. Standardization of radiologic reports and nodule management will systematize patient care, provide quality assurance, further reduce harm, and contain health care costs. Although the National Lung Screening Trial results and eligibility criteria of a heavy smoking history are the foundation for the standard guidelines for low-dose chest computed tomography screening in the United States, currently only 27% of patients diagnosed with lung cancer would meet US lung cancer screening recommendations. Current and future efforts must be directed to better delineate those patients who would most benefit from screening and to ensure that the benefits of screening reach all socioeconomic strata and racial and ethnic minorities. Further optimization of lung cancer screening program design and patient eligibility will assure that lung cancer screening benefits will outweigh the potential risks to our patients. PMID:27306387

  13. Screening in liver disease

    Institute of Scientific and Technical Information of China (English)

    Paolo Del Poggio; Marzio Mazzoleni

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines,although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors,such as transfusion before 1992 and drug addiction,is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation.

  14. Screening in liver disease.

    Science.gov (United States)

    Del Poggio, Paolo; Mazzoleni, Marzio

    2006-09-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  15. Design of Reversible Sequential Circuit Using Reversible Logic Synthesis

    Directory of Open Access Journals (Sweden)

    Md. Mosharof Hossin

    2012-01-01

    Full Text Available Reversible logic is one of the most vital issue at present time and it has different areas for its application, those are low power CMOS, quantum computing, nanotechnology, cryptography, optical computing, DNA computing, digital signal processing (DSP, quantum dot cellular automata, communication, computer graphics. It is not possible to realize quantum computing without implementation of reversible logic. The main purposes of designing reversible logic are to decrease quantum cost, depth of the circuits and the number of garbage outputs. In this paper, we have proposed a new reversible gate. And we have designedRS flip flop and D flip flop by using our proposed gate and Peres gate. The proposed designs are better than the existing proposed ones in terms of number of reversible gates and garbage outputs. So, this realization is more efficient and less costly than other realizations.

  16. Design of Reversible Sequential Circuit Using Reversible Logic Synthesis

    Directory of Open Access Journals (Sweden)

    Md. Belayet Ali

    2011-12-01

    Full Text Available Reversible logic is one of the most vital issue at present time and it has different areas for its application,those are low power CMOS, quantum computing, nanotechnology, cryptography, optical computing, DNA computing, digital signal processing (DSP, quantum dot cellular auto meta, communication, computer graphics. It is not possible to realize quantum computing without implementation of reversible logic. The main purposes of designing reversible logic are to decrease quantum cost, depth of the circuits and the number of garbage outputs. In this paper, we have proposed a new reversible gate. And we have designed RS flip flop and D flip flop by using our proposed gate and Peres gate. The proposed designs are better than the existing proposed ones in terms of number of reversible gates and garbage outputs. So, this realization is more efficient and less costly than other realizations.

  17. Development of a Cell-Based Fluorescence Resonance Energy Transfer Reporter for Bacillus anthracis Lethal Factor Protease

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, R H; Steenblock, E R; Camarero, J A

    2007-03-22

    We report the construction of a cell-based fluorescent reporter for anthrax lethal factor (LF) protease activity using the principle of fluorescence resonance energy transfer (FRET). This was accomplished by engineering an Escherichia coli cell line to express a genetically encoded FRET reporter and LF protease. Both proteins were encoded in two different expression plasmids under the control of different tightly controlled inducible promoters. The FRET-based reporter was designed to contain a LF recognition sequence flanked by the FRET pair formed by CyPet and YPet fluorescent proteins. The length of the linker between both fluorescent proteins was optimized using a flexible peptide linker containing several Gly-Gly-Ser repeats. Our results indicate that this FRET-based LF reporter was readily expressed in E. coli cells showing high levels of FRET in vivo in the absence of LF. The FRET signal, however, decreased 5 times after inducing LF expression in the same cell. These results suggest that this cell-based LF FRET reporter may be used to screen genetically encoded libraries in vivo against LF.

  18. Field reversal experiments (FRX)

    International Nuclear Information System (INIS)

    The equilibrium, confinement, and stability properties of the reversed-field configuration (RFC) are being studied in two theta-pinch facilities. The RFC is an elongated toroidal plasma confined in a purely poloidal field geometry. The open field lines of the linear theta pinch support the closed-field RFC much like the vertical field centers the toroidal plasma in a tokamak. Depending on stability and confinement properties, the RFC might be used to greatly reduce the axial losses in linear fusion devices such as mirrors, theta pinches, and liners. The FRX systems produce RFC's with a major radius R = 2-6 cm, minor radius a approximately 2 cm, and a total length l approximately 35 cm. The observed temperatures are T/sub e/ approximately 100 eV and T/sub i/ = 150-350 eV with a peak density n approximately 2 x 1015 cm-3. After the plasma reaches equilibrium, the RFC remains stable for up to 30 μs followed by the rapid growth of the rotational m = 2 instability, which terminates the confinement. During the stable equilibrium, the particle and energy confinement times are more than 10 times longer than in an open-field system. The behavior of the m = 2 mode qualitatively agrees with the theoretically predicted instability for rotational velocities exceeding some critical value

  19. Driving forward in reverse

    International Nuclear Information System (INIS)

    We describe the use of TILLING in Lotus japonicus and the development of deletion (De)-TILLING in Medicago truncatula. The evolution of RevGenUK has been driven by the development of reverse genetics technologies in these two model legumes and Brassica rapa, which functions as a translational species for brassica crops. TILLING and De-TILLING, are underpinned by populations of plants mutagenised with either EMS (that causes point mutations) or fast neutrons (that cause deletions) respectively. They permit the isolation of either allelic series of mutants or knockouts. Mutation detection will be developed from a number of independent gel-based systems to be carried out on a single platform - capillary electrophoresis. We are currently TILLING in both model legumes, but these developments will be applied to all three species. The resource will develop an open source database-driven system to support laboratory information management, analysis and the cataloguing of mutants in a genome context across all the species. (author)

  20. Driving Forward in Reverse

    International Nuclear Information System (INIS)

    We describe the use of TILLING in Lotus japonicus and the development of deletion (De)-TILLING in Medicago truncatula. The evolution of RevGen UK has been driven by the development of reverse genetics technologies in these two model legumes and Brassica rapa, which functions as a translational species for brassica crops. TILLING and De-TILLING are underpinned by populations of plants mutagenized with either EMS (that causes point mutations) or fast neutrons (that cause deletions), respectively. They permit the isolation of either allelic series of mutants or knockouts. Mutation detection will be developed from a number of independent gel-based systems to be carried out on a single platform - capillary electrophoresis. We are currently TILLING in both model legumes, but these developments will be applied to all three species. The resource will develop an open source database-driven system to support laboratory information management, analysis and the cataloguing of mutants in a genome context across all the species. (author)

  1. Time Reversal Violation

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, H; /SLAC

    2009-01-27

    This talk briefly reviews three types of time-asymmetry in physics, which I classify as universal, macroscopic and microscopic. Most of the talk is focused on the latter, namely the violation of T-reversal invariance in particle physics theories. In sum tests of microscopic T-invariance, or observations of its violation, are limited by the fact that, while we can measure many processes, only in very few cases can we construct a matched pair of process and inverse process and observe it with sufficient sensitivity to make a test. In both the cases discussed here we can achieve an observable T violation making use of flavor tagging, and in the second case also using the quantum properties of an antisymmetric coherent state of two B mesons to construct a CP-tag. Both these tagging properties depend only on very general properties of the flavor and/or CP quantum numbers and so provide model independent tests for T-invariance violations. The microscopic laws of physics are very close to T-symmetric. There are small effects that give CP- and T-violating processes in three-generation-probing weak decays. Where a T-violating observable can be constructed we see the relationships between T-violation and CP-violation expected in a CPT conserving theory. These microscopic effects are unrelated to the 'arrow of time' that is defined by increasing entropy, or in the time direction defined by the expansion of our Universe.

  2. Macroscopic model of self-propelled bacteria swarming with regular reversals

    CERN Document Server

    Gejji, Richard; Alber, Mark

    2011-01-01

    Periodic reversals of the direction of motion in systems of self-propelled rod shaped bacteria enable them to effectively resolve traffic jams formed during swarming and maximize their swarming rate. In this paper, a connection is found between a microscopic one dimensional cell-based stochastic model of reversing non-overlapping bacteria and a macroscopic non-linear diffusion equation describing dynamics of the cellular density. Boltzmann-Matano analysis is used to determine the nonlinear diffusion equation corresponding to the specific reversal frequency. Macroscopically (ensemble-vise) averaged stochastic dynamics is shown to be in a very good agreement with the numerical solutions of the nonlinear diffusion equation. Critical density $p_0$ is obtained such that nonlinear diffusion is dominated by the collisions between cells for the densities $p>p_0$. An analytical approximation of the pairwise collision time and semi-analytical fit for the total jam time per reversal period are also obtained. It is shown...

  3. Demonstrating trend reversal of groundwater quality in relation to time of recharge determined by 3H/3He

    NARCIS (Netherlands)

    Visser, A.; Broers, H.P.; Grift, B. van der; Bierkens, M.F.P.

    2007-01-01

    Recent EU legislation is directed to reverse the upward trends in the concentrations of agricultural pollutants in groundwater. However, uncertainty of the groundwater travel time towards the screens of the groundwater quality monitoring networks complicates the demonstration of trend reversal. We i

  4. 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

    2003-01-01

    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.

  5. Polarity-adjustable reversed phase ultrathin-layer chromatography.

    Science.gov (United States)

    Hall, J Z; Taschuk, M T; Brett, M J

    2012-11-30

    Reversed phase thin layer chromatography (TLC) or high performance thin layer chromatography (HPTLC) plates modified with C18, C8 or C2 to provide the silica-gel stationary phase with different polarities are available on the market, however, reversed phase plates with tunable polarity have not been reported. Given the limited variety of reversed phase plates, mobile phase composition optimization is necessary to obtain better separation of analytes with similar characteristics, which is often a time consuming step. We present polarity-adjustable reversed phase ultrathin-layer chromatography (UTLC) plates, which simplifies the mobile phase screening process and greatly expands the selection of reversed phase plates. The plates were fabricated on glass substrates with SiO(2) nanopillars deposited using the glancing angle deposition (GLAD) technique. SiO(2) nanopillars were functionalized with octadecyltrichlorosilane to generate a super hydrophobic stationary phase. Unlike commercial silica-gel based stationary phases, the isolated nanopillar architecture presented here exposes a high surface area to post-fabrication surface treatments. In our work, an O(2) plasma treatment at different powers, pressures and exposure times was used to shorten the silane carbon chain and introduce COOH groups to the surface, producing plates with finely tunable polarities. Separation of a model dye mixture of Sudan blue and Sudan IV confirmed the tuning of surface polarities by measurement of retention behavior changes. The dye elution order reversed as a result of the change in surface polarity. When the same plasma treatment process was tested on commercial reversed phase plates, separation behavior did not change because the disordered and tortuous silica gel restricts the accessible surface area. Plasma treatment of GLAD structures with highly accessible surfaces improved control over interfacial properties, producing better reverse phase separations. PMID:23116804

  6. Diabetes Screening Among Immigrants

    OpenAIRE

    Creatore, Maria I.; Gillian L Booth; Manuel, Douglas G.; Moineddin, Rahim; Glazier, Richard H.

    2012-01-01

    OBJECTIVE To examine diabetes screening, predictors of screening, and the burden of undiagnosed diabetes in the immigrant population and whether these estimates differ by ethnicity. RESEARCH DESIGN AND METHODS A population-based retrospective cohort linking administrative health data to immigration files was used to follow the entire diabetes-free population aged 40 years and up in Ontario, Canada (N = 3,484,222) for 3 years (2004–2007) to determine whether individuals were screened for diabe...

  7. The Kondo Screening Cloud

    OpenAIRE

    Affleck, Ian

    2001-01-01

    Renormalization group theory of the Kondo effect predicts that an impurity spin is screened by a conduction electron spread over a large distance of order >.1 to 1 micron. This review has the following sections: 1. The Kondo effect and the screening cloud, 2. Non-observation of the Kondo cloud in conventional experiments, 3. Kondo effect in transmission through a quantum dot, 4. Observing the screening cloud in persistent current experiments, 5. Side-coupled quantum dot, 6. Conclusions

  8. In-bead screening

    DEFF Research Database (Denmark)

    2013-01-01

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

  9. Enzyme recovery using reversed micelles.

    NARCIS (Netherlands)

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.Reversed micelles are aggregates of surfactant molecules containing an

  10. Towards a Reversible Functional Language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    We identify concepts of reversibility for a functional language by means of a set of semantic rules with specific properties. These properties include injectivity along with local backward determinism, an important operational property for an efficient reversible language. We define a concise rev...

  11. Iterative Cellular Screening System for Nanoparticle Safety Testing

    Directory of Open Access Journals (Sweden)

    Franziska Sambale

    2015-01-01

    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.

  12. Breast cancer screening

    OpenAIRE

    Skrabanek, P

    1988-01-01

    Consensus is still lacking on guidelines for breast-cancer screening with mammography: who should be screened, how frequently at what age, to what benefits and at what risks. American, Dutch, Swedish and Italian studies spanning the 1960s to the 1980s reveal a benefit from screening (reduced mortality from breast cancer) that occurs unambiguously only in women 50 years of age and over. Physicians who choose to screen mammographically their over-49-year-old female patients must do so with the ...

  13. ScreenOS Cookbook

    CERN Document Server

    Brunner, Stefan; Delcourt, David

    2008-01-01

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

  14. Screening for colorectal cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. Mammography screening in Denmark

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  16. [Safety monitoring of cell-based medicinal products (CBMPs)].

    Science.gov (United States)

    Funk, Markus B; Frech, Marion; Spranger, Robert; Keller-Stanislawski, Brigitte

    2015-11-01

    Cell-based medicinal products (CBMPs), a category of advanced-therapy medicinal products (ATMPs), are authorised for the European market by the European Commission by means of the centralized marketing authorisation. By conforming to the German Medicinal Products Act (Sec. 4b AMG), national authorisation can be granted by the Paul-Ehrlich-Institut in Germany exclusively for ATMPs not based on a routine manufacturing procedure. In both procedures, quality, efficacy, and safety are evaluated and the risk-benefit balance is assessed. For the centralised procedure, mainly controlled clinical trial data must be submitted, whereas the requirements for national procedures could be modified corresponding to the stage of development of the ATMP. After marketing authorization, the marketing authorization/license holder is obligated to report all serious adverse reactions to the competent authority and to provide periodic safety update reports. If necessary, post-authorization safety studies could be imposed. On the basis of these regulatory measures, the safety of advanced therapies can be monitored and improved.

  17. Neural stem cell-based treatment for neurodegenerative diseases.

    Science.gov (United States)

    Kim, Seung U; Lee, Hong J; Kim, Yun B

    2013-10-01

    Human neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generation of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenerative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury.

  18. A MULTISCALE, CELL-BASED FRAMEWORK FOR MODELING CANCER DEVELOPMENT

    Energy Technology Data Exchange (ETDEWEB)

    JIANG, YI [Los Alamos National Laboratory

    2007-01-16

    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.

  19. Stem cell-based therapies for acute radiation syndrome

    International Nuclear Information System (INIS)

    Exposure to high doses of ionizing radiation in the event of accidental or intentional incident such as nuclear/radiological terrorism can lead to debilitating injuries to multiple organs resulting in death within days depending on the amount of radiation dose and the quality of radiation. Unfortunately, there is not a single FDA-licensed drug approved against acute radiation injury. The RadStem Center for Medical Countermeasures against Radiation (RadStem CMGR) program at Einstein is developing stem cell-based therapies to treat acute radiation syndrome (ARS). We have demonstrated that intravenous transplantation of bone marrow-derived and adipose-derived stromal cells, consisting of a mixture of mesenchymal, endothelial and myeloid progenitors can mitigate mice exposed to whole body irradiation of 12 Gy or whole abdominal irradiation of up to 20 Gy. We identified a variety of growth and differentiation factors that individually is unable to improve survival of animals exposed to lethal irradiation, but when administered sequentially mitigates radiation injury and improves survival. We termed this phenomenon as synthetic survival and describe a new paradigm whereby the 'synthetic survival' of irradiated tissues can be promoted by systemic administration of growth factors to amplify residual stem cell clonogens post-radiation exposure, followed by a differentiation factor that favors tissue stem cell differentiation. Synthetic survival can be applied to mitigate lethal radiation injury in multiple organs following radiation-induced hematopoeitic, gastrointestinal and pulmonary syndromes. (author)

  20. [Safety monitoring of cell-based medicinal products (CBMPs)].

    Science.gov (United States)

    Funk, Markus B; Frech, Marion; Spranger, Robert; Keller-Stanislawski, Brigitte

    2015-11-01

    Cell-based medicinal products (CBMPs), a category of advanced-therapy medicinal products (ATMPs), are authorised for the European market by the European Commission by means of the centralized marketing authorisation. By conforming to the German Medicinal Products Act (Sec. 4b AMG), national authorisation can be granted by the Paul-Ehrlich-Institut in Germany exclusively for ATMPs not based on a routine manufacturing procedure. In both procedures, quality, efficacy, and safety are evaluated and the risk-benefit balance is assessed. For the centralised procedure, mainly controlled clinical trial data must be submitted, whereas the requirements for national procedures could be modified corresponding to the stage of development of the ATMP. After marketing authorization, the marketing authorization/license holder is obligated to report all serious adverse reactions to the competent authority and to provide periodic safety update reports. If necessary, post-authorization safety studies could be imposed. On the basis of these regulatory measures, the safety of advanced therapies can be monitored and improved. PMID:26391098

  1. Microbial fuel cell based on electroactive sulfate-reducing biofilm

    International Nuclear Information System (INIS)

    Highlights: ► Regulation and management of electricity generation by variation of residence time. ► Design of microbial fuel cell based on electroactive biofilm on zeolite. ► Engineering solution for removing of the obtained elemental sulfur. - abstract: A two chambered laboratory scale microbial fuel cell (MFC) has been developed, based on natural sulfate-reducing bacterium consortium in electroactive biofilm on zeolite. The MFC utilizes potassium ferricyanide in the cathode chamber as an electron acceptor that derives electrons from the obtained in anode chamber H2S. The molecular oxygen is finally used as a terminal electron acceptor at cathode compartment. The generated power density was 0.68 W m−2 with current density of 3.2 A m−2 at 150 Ω electrode resistivity. The hydrogen sulfide itself is produced by microbial dissimilative sulfate reduction process by utilizing various organic substrates. Finally, elemental sulfur was identified as the predominant final oxidation product in the anode chamber. It was removed from MFC through medium circulation and gathering in an external tank. This report reveals dependence relationship between the progress of general electrochemical parameters and bacterial sulfate-reduction rate. The presented MFC design can be used for simultaneous sulfate purification of mining drainage wastewater and generation of renewable electricity

  2. Preclinical safety testing for cell-based products using animals.

    Science.gov (United States)

    McBlane, James W

    2015-09-01

    The objectives of preclinical testing include to show why there might be therapeutic benefit in patients and to provide information on the product's toxicity. For cell-based products, given even once, there may be long term exposure and this could imply, unlike for conventional drugs, that all preclinical studies may be needed prior to first human use. The duration of exposure to cells should be studied in animals to guide toxicity assessments. Distribution of cells after administration by a route resembling that intended in humans should be studied to understand potential risks. Risk of tumour formation with the product may also need to be characterised. To the extent that this information can be generated by in vitro testing, studies in animals may not be needed and limitations on the capability of preclinical data to predict human toxicity are recognised: species-specificity make some cell products act only in humans and a human cell-product might be expected to be rejected by immunocompetent animals. Does this suggest testing in immunosuppressed animals or of development of an animal-cell product supposedly similar to the human cell product? No single answer seems to fit every situation.

  3. Regulations and guidelines governing stem cell based products: Clinical considerations

    Directory of Open Access Journals (Sweden)

    Bobby George

    2011-01-01

    Full Text Available The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US and European Union (EU regulations are in place, in India, we do not have a well-defined regulatory framework for "stem cell based products (SCBP". There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects.

  4. 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

    2006-01-01

    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.

  5. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng;

    2015-01-01

    secondary market introduction, this study expands the espoused definition of reverse innovation beyond its market-introduction focus with reversals in the flow of innovation in the ideation and product development phases. Recognizing that each phase can take place in different geographical locations......Reverse innovation commonly refers to an innovation initially launched in a developing country and later introduced to an advanced country. Adopting a linear innovation model with the four sequential phases of concept ideation, product development, primary target market introduction, and subsequent......, the paper then introduces a typology of global innovation with 16 different types of innovation flows between advanced and emerging countries, 10 of which are reverse innovation flows. The latter are further differentiated into weak and strong reverse innovation, depending on the number of innovation phases...

  6. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

    Science.gov (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

    2015-01-01

    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. PMID:26132533

  7. Reversed polarity patches at the CMB and geomagnetic field reversal

    Institute of Scientific and Technical Information of China (English)

    XU; Wenyao(徐文耀); WEI; Zigang(魏自刚)

    2002-01-01

    The International Geomagnetic Reference Field models (IGRF) for 1900-2000 are used to calculate the geomagnetic field distribution in the Earth' interior from the ground surface to the core-mantle boundary (CMB) under the assumption of insulated mantle. Four reversed polarity patches, as one of the most important features of the CMB field, are revealed. Two patches with +Z polarity (downward) at the southern African and the southern American regions stand out against the background of -Z polarity (upward) in the southern hemisphere, and two patches of -Z polarity at the North Polar and the northern Pacific regions stand out against the +Z background in the northern hemisphere. During the 1900-2000 period the southern African (SAF) patch has quickly drifted westward at a speed of 0.2-0.3°/a; meanwhile its area has expanded 5 times, and the magnetic flux crossing the area has intensified 30 times. On the other hand, other three patches show little if any change during this 100-year period. Extending upward, each of the reversed polarity patches at the CMB forms a chimney-shaped "reversed polarity column" in the mantle with the bottom at the CMB. The height of the SAF column has grown rapidly from 200km in 1900 to 900km in 2000. If the column grows steadily at the same rate in the future, its top will reach to the ground surface in 600-700 years. And then a reversed polarity patch will be observed at the Earth's surface, which will be an indicator of the beginning of a magnetic field reversal. On the basis of this study, one can describe the process of a geomagnetic polarity reversal, the polarity reversal may be observed firstly in one or several local regions; then the areas of these regions expand, and at the same time, other new reversed polarity regions may appear. Thus several poles may exist during a polarity reversal.

  8. Reversible computing and cellular automata - A survey

    OpenAIRE

    Morita, Kenichi

    2008-01-01

    Reversible computing is a paradigm where computing models are defined so that they reflect physical reversibility, one of the fundamental microscopic physical property of Nature. In this survey/tutorial paper, we discuss how computation can be carried out in a reversible system, how a universal reversible computer can be constructed by reversible logic elements, and how such logic elements are related to reversible physical phenomena. We shall see that, in reversible systems, computation can ...

  9. Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

    Institute of Scientific and Technical Information of China (English)

    Quan Jiang

    2016-01-01

    Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance im-aging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

  10. Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

    Directory of Open Access Journals (Sweden)

    Quan Jiang

    2016-01-01

    Full Text Available Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

  11. Aneuploidy Screening in Pregnancy.

    Science.gov (United States)

    Dashe, Jodi S

    2016-07-01

    Prenatal aneuploidy screening has changed dramatically in recent years with increases in the types of chromosomal abnormalities reliably identified and in the proportion of aneuploid fetuses detected. Initially, screening was available only for trisomies 21 and 18 and was offered only to low-risk pregnancies. Improved detection with the quadruple- and first-trimester multiple marker screens led to the option of aneuploidy screening for women 35 years of age and older. Cell-free DNA tests now screen for common autosomal trisomies and sex chromosome aneuploidies. Cell-free DNA screening is particularly effective in older women because of higher positive predictive values and lower false-positive rates. Integrated first- and second-trimester multiple marker tests provide specific risks for trisomies 21, 18, and possibly 13, and may detect an even wider range of aneuploidies. Given current precision in risk assessment, based on maternal age and preferences for screening or diagnostic tests, counseling has become more complex. This review addresses the benefits and limitations of available aneuploidy screening methods along with counseling considerations when offering them. PMID:27275786

  12. Colorectal Cancer Screening

    Science.gov (United States)

    ... laxatives to clear the colon, shows polyps clearly. DNA stool test This test checks DNA in stool cells for genetic changes that may be a sign of colorectal cancer. Screening clinical trials are taking place in many parts of the ... Screening tests have risks. False-negative test results can occur. ...

  13. Mammography screening in denmark

    DEFF Research Database (Denmark)

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

    2011-01-01

    Mammography screening is offered healthy women, and a high standard on professional and organizational level is mandatory not only in the screening programme but even in the diagnostic work-up and treatment. The main goal is to achieve a substantial reduction in disease specific mortality...

  14. Mammography screening in Denmark

    DEFF Research Database (Denmark)

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

    2011-01-01

    Mammography screening is offered healthy women, and a high standard on professional and organizational level is mandatory not only in the screening programme but even in the diagnostic work-up and treatment. The main goal is to achieve a substantial reduction in disease specific mortality...

  15. Scoliosis Screening in Schools.

    Science.gov (United States)

    New York State Education Dept., Albany. Div. of Pupil Personnel Services.

    The booklet outlines New York state school policy and procedures for screening students for scoliosis, lateral curvature of the spine. It is explained that screening is designed to discover spinal deformities early enough to prevent surgery. Planning aspects, including organizing a planning team for the school district, are discussed. Among…

  16. EIA screening in Denmark

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  17. Touch screens go optical

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  18. Modeling and control of fuel cell based distributed generation systems

    Science.gov (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

  19. Practical assay issues with the PERT/PBRT assay: a highly sensitive reverse transcriptase assay.

    Science.gov (United States)

    Chang, A; Dusing, S

    2006-01-01

    Product safety testing for retroviruses can be achieved by a panel of screening assays, including electron microscopy, viral gene specific PCRs, virus propagation, and detection of reverse transciptase activity. The application of PCR-based reverse transcriptase assays (PERT) that are approximately a million-fold more sensitive than conventional nucleotide incorporation assays in the testing of biologicals is described. Use of PERT assays can be applied to three areas: (i) screening for adventitious retrovirus contamination; (ii) detecting and quantifying endogenous viral particle load and (iii) monitoring levels of infectious retrovirus generation in cell lines that contain endogenous retroviruses.

  20. The promise of fuel cell-based automobiles

    Indian Academy of Sciences (India)

    A K Shukla; C L Jackson; K Scott

    2003-02-01

    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.

  1. High content cell-based assay for the inflammatory pathway

    Science.gov (United States)

    Mukherjee, Abhishek; Song, Joon Myong

    2015-07-01

    Cellular inflammation is a non-specific immune response to tissue injury that takes place via cytokine network orchestration to maintain normal tissue homeostasis. However chronic inflammation that lasts for a longer period, plays the key role in human diseases like neurodegenerative disorders and cancer development. Understanding the cellular and molecular mechanisms underlying the inflammatory pathways may be effective in targeting and modulating their outcome. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that effectively combines the pro-inflammatory features with the pro-apoptotic potential. Increased levels of TNF-α observed during acute and chronic inflammatory conditions are believed to induce adverse phenotypes like glucose intolerance and abnormal lipid profile. Natural products e. g., amygdalin, cinnamic acid, jasmonic acid and aspirin have proven efficacy in minimizing the TNF-α induced inflammation in vitro and in vivo. Cell lysis-free quantum dot (QDot) imaging is an emerging technique to identify the cellular mediators of a signaling cascade with a single assay in one run. In comparison to organic fluorophores, the inorganic QDots are bright, resistant to photobleaching and possess tunable optical properties that make them suitable for long term and multicolor imaging of various components in a cellular crosstalk. Hence we tested some components of the mitogen activated protein kinase (MAPK) pathway during TNF-α induced inflammation and the effects of aspirin in HepG2 cells by QDot multicolor imaging technique. Results demonstrated that aspirin showed significant protective effects against TNF-α induced cellular inflammation. The developed cell based assay paves the platform for the analysis of cellular components in a smooth and reliable way.

  2. 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.

  3. Screening for abdominalt aortaaneurisme

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  4. Development of reversible strain gage

    International Nuclear Information System (INIS)

    A high-temperature strain gage which can be peeled after taking required apparent strain measurements in a furnace and can be attached reverse-side-up at the point of interest on a test structure was developed. Using the ''reversible'' strain gage with selected room-temperature curing type polyester adhesive, one can expect to measure thermal strain accurately, especially for on large structures, at the first test in temperature up to 250 deg C. The repeatability of apparent strains for about 100 reversible gages was within 50 microstrains of difference at 250 deg C (within 30 microstrains of difference for 80 % of the test gages). (author)

  5. [Development of a functional cell-based HTS assay for the identification mGluR4 modulators].

    Science.gov (United States)

    Zhang, Yaling; Bai, Yanqiu

    2009-03-01

    To identify metabotropic glutamate receptor 4 (mGluR4) modulators by Ca2+ influx assay, we developed the functional cell-based high throughput-screening (HTS) assay. The human mGluR4 cDNA was transfected into HEK-293 stably expressing promiscuous G-protein (Ga alpha15) cells. Recombinant stable mGluR4 cell line was selected under Zeocin and validated by Ca2+ influx assay. The assay was optimized on loading time of Fluo Calcium Indicator, Dimethyl sulfoxide (DMSO) tolerance and sodium hydroxide (NaOH) tolerance using agonist (L-Glutamic acid (L-Glu)) of mGluR4. The rank order of the agonist potency for the stable human mGluR4 cell line was L-(+)-2-Amino-4-phosphonobutyric acid (L-AP4) > L-Serine-O-phosphate (L-SOP) > L-Glu, and of the antagonist potency was (RS)-alpha-Methylserine-O-phosphate (MSOP) > (RS)-alpha-Methyl-4-phosphonophenylglycine (MPPG). Z' factor value of the cell line in 96- and 384-well plate format was 0.80 and 0.65. Our data indicate a successful development of functional human mGluR4 recombinant stable cell line that was suitable for high throughput screening to identify mGluR4 agonist/antagonist. PMID:19621591

  6. Rapid assessment of antibody-induced ricin neutralization by employing a novel functional cell-based assay.

    Science.gov (United States)

    Gal, Yoav; Alcalay, Ron; Sabo, Tamar; Noy-Porat, Tal; Epstein, Eyal; Kronman, Chanoch; Mazor, Ohad

    2015-09-01

    Ricin is one of the most potent and lethal toxins known against which there is no available antidote. Currently, the most promising countermeasures against the toxin are based on neutralizing antibodies elicited by active vaccination or administered passively. A cell-based assay is widely applied for the primary screening and evaluation of anti-ricin antibodies, yet such assays are usually time-consuming (18-72 h). Here, we report of a novel assay to monitor ricin activity, based on HeLa cells that stably express the rapidly-degraded ubiquitin-luciferase (Ub-FL, half-life of 2 min). Ricin-induced arrest of protein synthesis could be quantified within 3 to 6h post intoxication (IC90 of 300 and 100 ng/ml, respectively). Furthermore, by stabilizing the intracellular levels of Ub-FL in the last hour of the assay, a 3-fold increase in the assay sensitivity was attained. We applied this assay to monitor the efficacy of a ricin holotoxin-based vaccine by measuring the formation of neutralizing antibodies throughout the immunization course. The potency of anti-ricin monoclonal antibodies (directed to either subunit of the toxin) could also be easily and accurately measured in this assay format. Owing to its simplicity, this assay may be implemented for high-throughput screening of ricin-neutralizing antibodies and for identification of small-molecule inhibitors of the toxin, as well as other ribosome-inactivating toxins. PMID:26003675

  7. What Do Reversible Programs Compute?

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    Reversible computing is the study of computation models that exhibit both forward and backward determinism. Understanding the fundamental properties of such models is not only relevant for reversible programming, but has also been found important in other fields, e.g., bidirectional model...... be the starting point of a computational theory of reversible computing. We provide a novel semantics-based approach to such a theory, using reversible Turing machines (RTMs) as the underlying computation model. We show that the RTMs can compute exactly all injective, computable functions. We find that the RTMs...... are not strictly classically universal, but that they support another notion of universality; we call this RTM-universality. Thus, even though the RTMs are sub-universal in the classical sense, they are powerful enough as to include a self-interpreter. Lifting this to other computation models, we propose r...

  8. Reverse Engineering Quantum Field Theory

    CERN Document Server

    Oeckl, Robert

    2012-01-01

    An approach to the foundations of quantum theory is advertised that proceeds by "reverse engineering" quantum field theory. As a concrete instance of this approach, the general boundary formulation of quantum theory is outlined.

  9. Reverse engineering quantum field theory

    Science.gov (United States)

    Oeckl, Robert

    2012-12-01

    An approach to the foundations of quantum theory is advertised that proceeds by "reverse engineering" quantum field theory. As a concrete instance of this approach, the general boundary formulation of quantum theory is outlined.

  10. An Overview of Reverse Logistics

    Institute of Scientific and Technical Information of China (English)

    WANG Jia-xiang; HE Xin

    2005-01-01

    Until recently, investment in logistics has focused mainly on the flows from companies to markets. Growing concerns for the environment and conserving resources have created new logistical approaches to more effectively manage the distribution function, and make better use of the resources available to an organization. One such approach is reverse logistics, which uses various methods to give scope for a back-load of finished products, components, waste, reusable packing, etc. from consumer to manufacturer. Back-loads allow manufacturers to reduce costs by using the distribution vehicle's return journey to create income or added value. This basic concept is now being developed to create novel solutions to the problems of reducing pollution, costs and vehicle movements, whilst maintaining high customer service levels. In this paper, the idea of reverse logistics is presented; motivations for it are analyzed, several successful practices are demonstrated and some important truths regarding successful reverse logistics are identified, trend of reverse logistics is provided.

  11. Designing the Reverse Supply Chain

    DEFF Research Database (Denmark)

    Gobbi, Chiara

    2011-01-01

    for the reverse supply chain. Design/methodology/approach – In order to identify the relevance of the Fisher model, the model needs to be recast in terms of PRV, which, in this context, is considered the independent variable in the reverse logistics arena. Products defined as innovative in Fisher's taxonomy......Purpose – The purpose of this paper is to explore the impact of the product residual value (PRV) and the loss of value over time of returned products in the reverse supply chain configuration. It also examines whether or not the distinction of Fisher's functional and innovative products holds...... correspond to disposed products with high residual value, whereas functional products correspond to disposed products with low residual value. Furthermore, the PRV and the speed at which returned products lose their value are considered in order to determine the configuration of the reverse supply chain...

  12. CEO Turnover in Reverse Splits

    OpenAIRE

    Li-Hsun Wang; Chu-Hsiung Lin; Hsien-Ming Chen

    2010-01-01

    This study examines the application of CEO turnover on reverse stock splits firms. Using Taiwanese samples, we find that non-CEO turnover firms receive negative long-term abnormal returns, and their financial performances continue to decline following reverse splits. These findings are consistent with prior studies. Contrarily, neither significantly negative long-term abnormal returns nor changes on financial performance were found for CEO turnover firms. This study concludes that applying CE...

  13. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients.......A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients....

  14. Deciphering records of geomagnetic reversals

    Science.gov (United States)

    Valet, Jean-Pierre; Fournier, Alexandre

    2016-06-01

    Polarity reversals of the geomagnetic field are a major feature of the Earth's dynamo. Questions remain regarding the dynamical processes that give rise to reversals and the properties of the geomagnetic field during a polarity transition. A large number of paleomagnetic reversal records have been acquired during the past 50 years in order to better constrain the structure and geometry of the transitional field. In addition, over the past two decades, numerical dynamo simulations have also provided insights into the reversal mechanism. Yet despite the large paleomagnetic database, controversial interpretations of records of the transitional field persist; they result from two characteristics inherent to all reversals, both of which are detrimental to an ambiguous analysis. On the one hand, the reversal process is rapid and requires adequate temporal resolution. On the other hand, weak field intensities during a reversal can affect the fidelity of magnetic recording in sedimentary records. This paper is aimed at reviewing critically the main reversal features derived from paleomagnetic records and at analyzing some of these features in light of numerical simulations. We discuss in detail the fidelity of the signal extracted from paleomagnetic records and pay special attention to their resolution with respect to the timing and mechanisms involved in the magnetization process. Records from marine sediments dominate the database. They give rise to transitional field models that often lead to overinterpret the data. Consequently, we attempt to separate robust results (and their subsequent interpretations) from those that do not stand on a strong observational footing. Finally, we discuss new avenues that should favor progress to better characterize and understand transitional field behavior.

  15. Vasectomy reversal: a clinical update

    OpenAIRE

    Patel, Abhishek P; Smith, Ryan P.

    2016-01-01

    textabstractVasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and...

  16. Reversals of the solar dipole

    OpenAIRE

    Moss, David; Kitchatinov, Leonid L.; Sokoloff, Dmitri

    2012-01-01

    During a solar magnetic field reversal the magnetic dipole moment does not vanish, but migrates between poles, in contradiction to the predictions of mean-field dynamo theory. We try to explain this as a consequence of magnetic fluctuations. We exploit the statistics of fluctuations to estimate observable signatures. Simple statistical estimates, taken with results from mean-field dynamo theory, suggest that a non-zero dipole moment may persist through a global field reversal. Fluctuations in...

  17. Proceedings of the Interdisciplinary colloquium on reversibility

    International Nuclear Information System (INIS)

    This document contains the contributions to a colloquium, presented either in full text or as Power Point presentations. After an opening speech on decision reversibility of waste retrieval, the contributions respectively addressed: The charge taking ability, Proving and demonstrating reversibility, The issue of reversibility in an evolutional system in the case of CO2 geological disposal, Interactions between reversibility and disposal safety, Reversible disposal of radioactive wastes, Reversibility and retrievability within debates on decision-making about nuclear wastes in Finland and United Kingdom, The political qualities of technologies (irreversibility and reversibility in nuclear waste management), The contribution of economic analysis to the reversibility of nuclear waste disposal, The economic cost of reversibility, The appropriation of the notion of reversibility by the Andra, Arguments about the notion of reversibility, The notion of reversibility as a political symbol or actual concern, The project of document space 'ExploRe' (opened pluri-disciplinary exploration of reversibility), The participatory documentarisation at the service of reversibility. Posters addressed the following topics: Andra and reversibility, Reversibility, operational safety and long term safety in geological disposal, Andra's R and D in relationship the monitoring and survey of reversible disposal installations, Numerical simulation for the prediction and the analysis of disposal operation and aid-to-decision for its management, Demand of reversibility with respect to disposal progressive development, Taking reversibility into account for the complementarity between warehousing and storage

  18. Sources of Error in Mammalian Genetic Screens.

    Science.gov (United States)

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z; Elledge, Stephen J

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  19. Lung Cancer Screening.

    Science.gov (United States)

    Wu, Geena X; Raz, Dan J

    2016-01-01

    Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Since lung cancer outcomes are dependent on stage at diagnosis with early disease resulting in longer survival, the goal of screening is to capture lung cancer in its early stages when it can be treated and cured. Multiple studies have evaluated the use of chest X-ray (CXR) with or without sputum cytologic examination for lung cancer screening, but none has demonstrated a mortality benefit. In contrast, the multicenter National Lung Screening Trial (NLST) from the United States found a 20 % reduction in lung cancer mortality following three consecutive screenings with low-dose computed tomography (LDCT) in high-risk current and former smokers. Data from European trials are not yet available. In addition to a mortality benefit, lung cancer screening with LDCT also offers a unique opportunity to promote smoking cessation and abstinence and may lead to the diagnoses of treatable chronic diseases, thus decreasing the overall disease burden. The risks of lung cancer screening include overdiagnosis, radiation exposure, and false-positive results leading to unnecessary testing and possible patient anxiety and distress. However, the reduction in lung cancer mortality is a benefit that outweighs the risks and major health organizations currently recommend lung cancer screening using age, smoking history, and quit time criteria derived from the NLST. Although more research is needed to clearly define and understand the application and utility of lung cancer screening in the general population, current data support that lung cancer screening is effective and should be offered to eligible beneficiaries. PMID:27535387

  20. Screening and diagnosis for HIV

    Science.gov (United States)

    HIV testing; HIV screening; HIV screening test; HIV confirmatory test ... Task Force. Final Update Summary: Human Immunodeficiency Virus (HIV) Infection: Screening. July 2015. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/ ...

  1. Lung cancer screening: radiological aspects

    NARCIS (Netherlands)

    de Hoop, B.J.

    2010-01-01

    Lung Cancer Screening: Radiological Aspects Multiple lung cancer screening studies are currently being conducted to study whether lung cancer screening with Computed Tomography (CT) can decrease lung cancer mortality. This thesis addresses radiological methods that can increase efficacy and efficien

  2. Cervical cancer - screening and prevention

    Science.gov (United States)

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

  3. Risks of Skin Cancer Screening

    Science.gov (United States)

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

  4. Design of High speed Low Power Reversible Vedic multiplier and Reversible Divider

    OpenAIRE

    Srikanth G Department of Electronics & Communication Engineerig, Indur Institute of Engineering & Technology, Siddipet, Medak, JNTUH University, Telangana, India.; Nasam Sai Kumar

    2014-01-01

    This paper bring out a 32X32 bit reversible Vedic multiplier using "Urdhva Tiryakabhayam" sutra meaning vertical and crosswise, is designed using reversible logic gates, which is the first of its kind. Also in this paper we propose a new reversible unsigned division circuit. This circuit is designed using reversible components like reversible parallel adder, reversible left-shift register, reversible multiplexer, reversible n-bit register with parallel load line. The reversibl...

  5. Colorectal cancer screening

    Institute of Scientific and Technical Information of China (English)

    Ramona M McLoughlin; Colm A O'Morain

    2006-01-01

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

  6. Screening for Pancreatic Cancer.

    Science.gov (United States)

    Wada, Keita; Takaori, Kyoichi; Traverso, L William

    2015-10-01

    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.

  7. Chemical Screening in Zebrafish.

    Science.gov (United States)

    Brady, Colleen A; Rennekamp, Andrew J; Peterson, Randall T

    2016-01-01

    Phenotypic small molecule screens in zebrafish have gained popularity as an unbiased approach to probe biological processes. In this chapter we outline basic methods for performing chemical screens with larval zebrafish including breeding large numbers of embryos, plating larval fish into multi-well dishes, and adding small molecules to these wells. We also highlight important considerations when designing and interpreting the results of a phenotypic screen and possible follow-up approaches, including popular methods used to identify the mechanism of action of a chemical compound. PMID:27464797

  8. Screening for asbestbetingede sygdomme?

    DEFF Research Database (Denmark)

    Brauer, Charlotte; Baandrup, Ulrik; Jacobsen, Peter;

    2009-01-01

    Screening programs for early detection of asbestos-related cancer have been considered. Conventional X-ray, computed tomography of the thorax, and the biomarkers osteopontin and mesothelin have been critically reviewed in the literature, together with survival data from screening programs in...... asbestos-exposed populations. Data do not currently support implementation of screening programs for asbestos-exposed persons in Denmark. Since mesothelioma is most often an occupational disease, these patients should be admitted to an occupational clinic for aetiological evaluation. Udgivelsesdato: 2009...

  9. Design of Reversible Random Access Memory

    OpenAIRE

    Mamun, Md. Selim Al; Hossain, Syed Monowar

    2013-01-01

    Reversible logic has become immensely popular research area and its applications have spread in various technologies for their low power consumption. In this paper we proposed an efficient design of random access memory using reversible logic. In the way of designing the reversible random access memory we proposed a reversible decoder and a write enable reversible master slave D flip-flop. All the reversible designs are superior in terms of quantum cost, delay and garbage outputs compared to ...

  10. Content adaptive screen image scaling

    OpenAIRE

    Zhai, Yao; Wang, Qifei; Lu, Yan; Li, Shipeng

    2015-01-01

    This paper proposes an efficient content adaptive screen image scaling scheme for the real-time screen applications like remote desktop and screen sharing. In the proposed screen scaling scheme, a screen content classification step is first introduced to classify the screen image into text and pictorial regions. Afterward, we propose an adaptive shift linear interpolation algorithm to predict the new pixel values with the shift offset adapted to the content type of each pixel. The shift offse...

  11. Screening for Generalized Anxiety Disorder (GAD)

    Science.gov (United States)

    ... Conference & Education Membership Journal & Multimedia Resources Awards Consumers Screening for Generalized Anxiety Disorder (GAD) Main navigation FAQs Screen Yourself Screening for Depression Screening for Generalized Anxiety Disorder (GAD) ...

  12. Organic electrochemical transistors for cell-based impedance sensing

    Science.gov (United States)

    Rivnay, Jonathan; Ramuz, Marc; Leleux, Pierre; Hama, Adel; Huerta, Miriam; Owens, Roisin M.

    2015-01-01

    Electrical impedance sensing of biological systems, especially cultured epithelial cell layers, is now a common technique to monitor cell motion, morphology, and cell layer/tissue integrity for high throughput toxicology screening. Existing methods to measure electrical impedance most often rely on a two electrode configuration, where low frequency signals are challenging to obtain for small devices and for tissues with high resistance, due to low current. Organic electrochemical transistors (OECTs) are conducting polymer-based devices, which have been shown to efficiently transduce and amplify low-level ionic fluxes in biological systems into electronic output signals. In this work, we combine OECT-based drain current measurements with simultaneous measurement of more traditional impedance sensing using the gate current to produce complex impedance traces, which show low error at both low and high frequencies. We apply this technique in vitro to a model epithelial tissue layer and show that the data can be fit to an equivalent circuit model yielding trans-epithelial resistance and cell layer capacitance values in agreement with literature. Importantly, the combined measurement allows for low biases across the cell layer, while still maintaining good broadband signal.

  13. Organic electrochemical transistors for cell-based impedance sensing

    Energy Technology Data Exchange (ETDEWEB)

    Rivnay, Jonathan, E-mail: rivnay@emse.fr, E-mail: owens@emse.fr; Ramuz, Marc; Hama, Adel; Huerta, Miriam; Owens, Roisin M., E-mail: rivnay@emse.fr, E-mail: owens@emse.fr [Department of Bioelectronics, Ecole des Mines de St. Etienne, 13541 Gardanne (France); Leleux, Pierre [Department of Bioelectronics, Ecole des Mines de St. Etienne, 13541 Gardanne (France); Microvitae Technologies, Pole d' Activite Y. Morandat, 13120 Gardanne (France)

    2015-01-26

    Electrical impedance sensing of biological systems, especially cultured epithelial cell layers, is now a common technique to monitor cell motion, morphology, and cell layer/tissue integrity for high throughput toxicology screening. Existing methods to measure electrical impedance most often rely on a two electrode configuration, where low frequency signals are challenging to obtain for small devices and for tissues with high resistance, due to low current. Organic electrochemical transistors (OECTs) are conducting polymer-based devices, which have been shown to efficiently transduce and amplify low-level ionic fluxes in biological systems into electronic output signals. In this work, we combine OECT-based drain current measurements with simultaneous measurement of more traditional impedance sensing using the gate current to produce complex impedance traces, which show low error at both low and high frequencies. We apply this technique in vitro to a model epithelial tissue layer and show that the data can be fit to an equivalent circuit model yielding trans-epithelial resistance and cell layer capacitance values in agreement with literature. Importantly, the combined measurement allows for low biases across the cell layer, while still maintaining good broadband signal.

  14. Screening for Prostate Cancer

    Science.gov (United States)

    ... absolute reduction in mortal- ity. Preliminary results from PIVOT (Prostate Cancer In- tervention Versus Observation Trial), in ... early PSA screening era, prelim- inary findings from PIVOT show that, after 12 years, in- tention to ...

  15. Screening for Glaucoma

    Science.gov (United States)

    ... t know which people with early signs of disease will develop serious vision problems or blindness. There are two major ... for advice about glaucoma screening. Glaucoma is a serious disease that affects the health and quality of life ...

  16. Rapid Lead Screening Test

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Lab Tests Rapid Lead Screening Test Share Tweet Linkedin Pin it More ... reducing the need for a follow-up visit. Lead Risk Links Centers for Disease Control and Prevention ( ...

  17. Urine drug screen

    Science.gov (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 ...

  18. Health Screenings at School

    Science.gov (United States)

    ... blackboard may not know that she is seeing differently from anyone else. Nevertheless, even mild deficiencies of sight can significantly affect a child's ability to learn. In some states these screening tests are mandated ...

  19. Screening efficiency and screen length of a linear vibrating screen using DEM 3D simulation

    Institute of Scientific and Technical Information of China (English)

    Wang Guifeng; Tong Xin

    2011-01-01

    The effect of screen length on the screening efficiency of particles is studied under various single parameter conditions including frequency,amplitude,vibration angle,and screen inclination.The Discrete Element Method (DEM) has been used to simulate the screening process.A functional relationship between screening efficiency and screen length is established.It is shown that screening efficiency and screen length have a complicated exponential relationship.Relationships between them are profoundly discussed and conclusions are easily drawn:low values of the parameters do not benefit screening; screening efficiency generally increases with screen length; screening efficiency reaches a plateau when these parameters are in range frequently encountered in practical applications.

  20. Reversals in nature and the nature of reversals

    CERN Document Server

    Stefani, F; Günther, U; Sorriso-Valvo, L; Xu, M; G\\"unther, Uwe; Gerbeth, Gunter; Sorriso-Valvo, Luca; Stefani, Frank; Xu, Mingtian

    2007-01-01

    The asymmetric shape of reversals of the Earth's magnetic field indicates a possible connection with relaxation oscillations as they were early discussed by van der Pol. A simple mean-field dynamo model with a spherically symmetric $\\alpha$ coefficient is analysed with view on this similarity, and a comparison of the time series and the phase space trajectories with those of paleomagnetic measurements is carried out. For highly supercritical dynamos a very good agreement with the data is achieved. Deviations of numerical reversal sequences from Poisson statistics are analysed and compared with paleomagnetic data. The role of the inner core is discussed in a spectral theoretical context and arguments and numerical evidence is compiled that the growth of the inner core might be important for the long term changes of the reversal rate and the occurrence of superchrons.

  1. Lung cancer screening: Update

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  2. NERVE: New Enhanced Reverse Vaccinology Environment

    Directory of Open Access Journals (Sweden)

    Filippini Francesco

    2006-07-01

    Full Text Available Abstract Background Since a milestone work on Neisseria meningitidis B, Reverse Vaccinology has strongly enhanced the identification of vaccine candidates by replacing several experimental tasks using in silico prediction steps. These steps have allowed scientists to face the selection of antigens from the predicted proteome of pathogens, for which cell culture is difficult or impossible, saving time and money. However, this good example of bioinformatics-driven immunology can be further developed by improving in silico steps and implementing biologist-friendly tools. Results We introduce NERVE (New Enhanced Reverse Vaccinology Environment, an user-friendly software environment for the in silico identification of the best vaccine candidates from whole proteomes of bacterial pathogens. The software integrates multiple robust and well-known algorithms for protein analysis and comparison. Vaccine candidates are ranked and presented in a html table showing relevant information and links to corresponding primary data. Information concerning all proteins of the analyzed proteome is not deleted along selection steps but rather flows into an SQL database for further mining and analyses. Conclusion After learning from recent years' works in this field and analysing a large dataset, NERVE has been implemented and tuned as the first available tool able to rank a restricted pool (~8–9% of the whole proteome of vaccine candidates and to show high recall (~75–80% of known protective antigens. These vaccine candidates are required to be "safe" (taking into account autoimmunity risk and "easy" for further experimental, high-throughput screening (avoiding possibly not soluble antigens. NERVE is expected to help save time and money in vaccine design and is available as an additional file with this manuscript; updated versions will be available at http://www.bio.unipd.it/molbinfo.

  3. Vasectomy reversal: a clinical update

    Directory of Open Access Journals (Sweden)

    Abhishek P Patel

    2016-01-01

    Full Text Available Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.

  4. Cylindrical air flow reversal barrier

    Energy Technology Data Exchange (ETDEWEB)

    Woznica, C.; Rodziewicz, M.

    1988-06-01

    Describes an innovative design introduced in the ZMP mine in Zory for quick reversal of ventilation air flow. Geologic mining conditions at the 705 m deep horizon, where the barrier was built, are described. According to the design used until now, a reversal system consisted of safety barriers, ventilation air locks, a ventilation bridge and stopping needed in case of a fire when air flow direction must be reversed. Nine air locks and an expensive concrete ventilation bridge were needed and the air locks had to be operated at 8 points of the region to effect reversal. The new design consists of a 2-storey cylindrical barrier which also fulfills the function of a ventilation bridge. It can be manually or remotely operated by a mechanical or pneumatic system. Tests showed that the new barrier permits immediate air flow reversal while retaining 60% of the original air, which is important in the case of fire and methane hazards. It permits improved seam panelling and splitting of pillars and brings an economy of about 40 million zlotys in construction cost. Design and operation of the barrier is illustrated and ventilation air circulation is explained. 7 figs.

  5. REVERSE LOGISTICS RETAIL LEVEL RETURN

    Directory of Open Access Journals (Sweden)

    Ivona Bajor

    2014-06-01

    Full Text Available Conducting scientific research regarding reverse logistics systems includes certain difficulties. Developed logistics systems are aimed at analysing reverse logistics issues and tend to continuously detect differences and oscillations in the flow of returned products and their characteristics. Developing logistics systems, as Croatian, find reverse logistics issues, regarding product returns, significantly complex and very often these issues are not observed as issues of priority. As distributive flow, reverse logistics systems fundaments should be also based on detailed analysis. Analysis in this flow presents amounts, reasons, process flows and quality of returned items. Because of complex product evaluation on individual level, reverse logistics procedures should be implemented as a methodology individually developed for every supply chain subject. This paper presents a research of retail level returns on the Croatian market, where the analysis implicated that the majority of products in return for this level is directed from final consumers and presents noncurrent inventories of distribution chain. The paper will present conducted research regarding characteristics of returns and routing these products from the retail level.

  6. Low Cost Reversible Signed Comparator

    Directory of Open Access Journals (Sweden)

    Farah Sharmin

    2013-10-01

    Full Text Available Nowadays exponential advancement in reversible comp utation has lead to better fabrication and integration process. It has become very popular ove r the last few years since reversible logic circuit s dramatically reduce energy loss. It consumes less p ower by recovering bit loss from its unique input-o utput mapping. This paper presents two new gates called RC-I and RC-II to design an n-bit signed binary comparator where simulation results show that the p roposed circuit works correctly and gives significa ntly better performance than the existing counterparts. An algorithm has been presented in this paper for constructing an optimized reversible n-bit signed c omparator circuit. Moreover some lower bounds have been proposed on the quantum cost, the numbers of g ates used and the number of garbage outputs generated for designing a low cost reversible sign ed comparator. The comparative study shows that the proposed design exhibits superior performance consi dering all the efficiency parameters of reversible logic design which includes number of gates used, quantum cost, garbage output and constant inputs. This proposed design has certainly outperformed all the other existing approaches.

  7. 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.

  8. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction.

    Directory of Open Access Journals (Sweden)

    Naoki Okumura

    Full Text Available The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs in combination with a Rho kinase (ROCK inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use.

  9. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction.

    Science.gov (United States)

    Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373

  10. Fault Testing for Reversible Circuits

    CERN Document Server

    Patel, K N; Markov, I L; Patel, Ketan N.; Hayes, John P.; Markov, Igor L.

    2004-01-01

    Applications of reversible circuits can be found in the fields of low-power computation, cryptography, communications, digital signal processing, and the emerging field of quantum computation. Furthermore, prototype circuits for low-power applications are already being fabricated in CMOS. Regardless of the eventual technology adopted, testing is sure to be an important component in any robust implementation. We consider the test set generation problem. Reversibility affects the testing problem in fundamental ways, making it significantly simpler than for the irreversible case. For example, we show that any test set that detects all single stuck-at faults in a reversible circuit also detects all multiple stuck-at faults. We present efficient test set constructions for the standard stuck-at fault model as well as the usually intractable cell-fault model. We also give a practical test set generation algorithm, based on an integer linear programming formulation, that yields test sets approximately half the size o...

  11. Ice ages and geomagnetic reversals

    Science.gov (United States)

    Wu, Patrick

    1992-01-01

    There have been speculations on the relationship between climatic cooling and polarity reversals of the earth's magnetic field during the Pleistocene. Two of the common criticisms on this relationship have been the reality of these short duration geomagnetic events and the accuracy of their dates. Champion et al. (1988) have reviewed recent progress in this area. They identified a total of 10 short-duration polarity events in the last 1 Ma and 6 of these events have been found in volcanic rocks, which also have K-Ar dates. Supposing that the speculated relationship between climatic cooling and geomagnetic reversals actually exist, two mechanisms that assume climatic cooling causes short period magnetic reversals will be investigated. These two methods are core-mantle boundary topography and transfer of the rotational energy to the core.

  12. Reverse Knowledge Transfer in MNEs

    DEFF Research Database (Denmark)

    Mudambi, Ram; Piscitello, Lucia; Rabbiosi, Larissa

    2014-01-01

    It is now well recognized that multinational enterprises (MNEs) are differentiated networks wherein subsidiaries vary in terms of their ability to create new knowledge and competencies for their parent groups. In much of this theory, it is taken for granted that subsidiary innovativeness has...... a positive correlation with the extent of reverse knowledge transfers to the parent MNE. Relying on the headquarters-subsidiary view of the MNE, we argue that, beyond a point, increasing subsidiary innovativeness will be associated with lower reverse knowledge transfers. Further, we argue...... that this relationship is sensitive to the subsidiary entry mode. Using data from a sample of 293 Italian subsidiaries, we find strong support for our hypotheses. In particular, our results confirm that the effect of subsidiary innovativeness on reverse knowledge transfers displays an inverted-U shape...

  13. Learning course adjustments during arm movements with reversed sensitivity derivatives

    Directory of Open Access Journals (Sweden)

    Tweed Douglas B

    2010-11-01

    Full Text Available Abstract Background To learn, a motor system needs to know its sensitivity derivatives, which quantify how its neural commands affect motor error. But are these derivatives themselves learned, or are they known solely innately? Here we test a recent theory that the brain's estimates of sensitivity derivatives are revisable based on sensory feedback. In its simplest form, the theory says that each control system has a single, adjustable estimate of its sensitivity derivatives which affects all aspects of its task, e.g. if you learn to reach to mirror-reversed targets then your revised estimate should reverse not only your initial aiming but also your online course adjustments when the target jumps in mid-movement. Methods Human subjects bent a joystick to move a cursor to a target on a computer screen, but the cursor's motion was reversed relative to the joystick's. The target jumped once during each movement. Subjects had up to 4000 trials to practice aiming and responding to target jumps. Results All subjects learned to reverse both initial aiming and course adjustments. Conclusions Our study confirms that sensitivity derivatives can be relearned. It is consistent with the idea of a single, all-purpose estimate of those derivatives; and it suggests that the estimate is a function of context, as one would expect given that the true sensitivity derivatives may vary with the state of the controlled system, the target, and the motor commands.

  14. Simulation studies of nucleation of ferroelectric polarization reversal.

    Energy Technology Data Exchange (ETDEWEB)

    Brennecka, Geoffrey L.; Winchester, Benjamin Michael

    2014-08-01

    Electric field-induced reversal of spontaneous polarization is the defining characteristic of a ferroelectric material, but the process(es) and mechanism(s) associated with the initial nucleation of reverse-polarity domains are poorly understood. This report describes studies carried out using phase field modeling of LiTaO3, a relatively simple prototype ferroelectric material, in order to explore the effects of either mechanical deformation or optically-induced free charges on nucleation and resulting domain configuration during field-induced polarization reversal. Conditions were selected to approximate as closely as feasible those of accompanying experimental work in order to provide not only support for the experimental work but also ensure that additional experimental validation of the simulations could be carried out in the future. Phase field simulations strongly support surface mechanical damage/deformation as effective for dramatically reducing the overall coercive field (Ec) via local field enhancements. Further, optically-nucleated polarization reversal appears to occur via stabilization of latent nuclei via the charge screening effects of free charges.

  15. Reversible arithmetic logic unit for quantum arithmetic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert; Axelsen, Holger Bock

    2010-01-01

    This communication presents the complete design of a reversible arithmetic logic unit (ALU) that can be part of a programmable reversible computing device such as a quantum computer. The presented ALU is garbage free and uses reversible updates to combine the standard reversible arithmetic...

  16. Fragment screening: an introduction.

    Science.gov (United States)

    Leach, Andrew R; Hann, Michael M; Burrows, Jeremy N; Griffen, Ed J

    2006-09-01

    There are clearly many different philosophies associated with adapting fragment screening into mainstream Drug Discovery Lead Generation strategies. Scientists at Astex, for instance, focus entirely on strategies involving use of X-ray crystallography and NMR. However, AstraZeneca uses a number of different fragment screening strategies. One approach is to screen a 2000 compound fragment set (with close to "lead-like" complexity) at 100 microM in parallel with every HTS such that the data are obtained on the entire screening collection at 10 microM plus the extra samples at 100 microM; this provides valuable compound potency data in a concentration range that is usually unexplored. The fragments are then screen-specific "privileged structures" that can be searched for in the rest of the HTS output and other databases as well as having synthesis follow-up. A typical workflow for a fragment screen within AstraZeneca is shown below (Figure 24) and highlights the desirability (particularly when screening >100 microM) for NMR and X-ray information to validate weak hits and give information on how to optimise them. In this chapter, we have provided an introduction to the theoretical and practical issues associated with the use of fragment methods and lead-likeness. Fragment-based approaches are still in an early stage of development and are just one of many interrelated techniques that are now used to identify novel lead compounds for drug development. Fragment based screening has some advantages, but like every other drug hunting strategy will not be universally applicable. There are in particular some practical challenges associated with fragment screening that relate to the generally lower level of potency that such compounds initially possess. Considerable synthetic effort has to be applied for post-fragment screening to build the sort of potency that would be expected to be found from a traditional HTS. However, if there are no low-hanging fruit in a screening

  17. Development of fluorescence-based high-throughput screening assays: choice of appropriate instrumentation

    Science.gov (United States)

    Burns, David J.; Alder, Elisabeth; Fan, Yi-Hong; McKeegan, Evelyn; Warrior, Usha; Beutel, Bruce

    1998-04-01

    Fluorescence-based assays have become increasingly popular in high throughput screening for a variety of reasons (e.g. sensitivity). However, new screening technologies are pushing the limits of conventional fluorescence plate readers. For example, instruments that have optical sensitivities beyond most of the commercially available plate readers are required to reproducibly measure the fluorescence generated by the green fluorescent protein (GFP)--a novel reporter gene. Also, miniaturization of screening formats (with densities higher than the conventional 96-well plate) requires high resolution instrumentation to measure fluorescence. Several assays based on optical fluorescence measurements have been developed and screened in our Biological Screening group. These assays include various fluorescence-based protease assays (standard end-point and kinetic modes) and a functional cell-based screen using the green fluorescent protein as a reporter gene. The choice of instrumentation was the critical factor in the performance and success of each of these arrays. Data will be presented for the cell- based reporter assay including the type of instrumentation (fluorescence plate readers; fluorescence imaging systems) used for detection of GFP fluorescence.

  18. Loan Sales and Screening Incentives

    OpenAIRE

    Bester, Helmut; Gehrig, Thomas; Stenbacka, Rune

    2012-01-01

    We analyze the effect of loan sales on the intensity of costly screening. Loan sales strengthen screening incentives when screening primarily improves the bank’s ability to identify profitable loans and when banks retain most of those profitable loans. However, loan sales dampen screening incentives when the benefit of screening primarily helps to weed out unprofitable projects. Moreover, alternative institutions of information production and the institutional market framework affect the rela...

  19. Comparison of PC12 and Cerebellar Granule Cell Cultures for Evaluating Neurite Outgrowth Using High Content Screening

    Science.gov (United States)

    Development of high-throughput assays for chemical screening and hazard identification is a pressing priority worldwide. One approach uses in vitro, cell-based assays which recapitulate biological events observed in vivo. Neurite outgrowth is one such critical cellular process un...

  20. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    Science.gov (United States)

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  1. Vasectomy reversal : a clinical update

    NARCIS (Netherlands)

    A.P. Patel (Abhishek); R.P. Smith (Ryan)

    2016-01-01

    textabstractVasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage,

  2. Reverse ventilation--perfusion mismatch

    International Nuclear Information System (INIS)

    Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients

  3. Nano-mechanical magnetization reversal

    OpenAIRE

    Kovalev, Alexey A.; Bauer, Gerrit E. W.; Brataas, Arne

    2004-01-01

    The dynamics of the ferromagnetic order parameter in thin magnetic films is strongly affected by the magnetomechanical coupling at certain resonance frequencies. By solving the equation of motion of the coupled mechanical and magnetic degrees of freedom we show that the magnetic-field induced magnetization switching can be strongly accelerated by the lattice and illustrate the possibility of magnetization reversal by mechanical actuation.

  4. Implication of Cord Blood for Cell-Based Therapy in Refractory Childhood Diseases

    OpenAIRE

    Lee, Young-Ho

    2010-01-01

    Since cord blood (CB) contains hematopoietic stem cells as well as a mixture of multipotent stem cells, CB has the ability to give rise to hematopoietic, epithelial, endothelial and neural tissues. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. This review focuses clinical and pre-clinical application of CB cell-based therapy for inherited metabolic diseases as well as tissu...

  5. Dance on screen

    OpenAIRE

    Roichman, Limor

    2001-01-01

    This thesis explores dance on screen from the artist's point of view following the making of the video GAIA - Mysterious Rhythms (20 min,Digital Betacam). The video and the thesis together form the PhD submission. The interaction of practice and theory, through a process of creative work, analysis and reflection resulted in the structuring of a model with which I claim the autonomy of dance on screen as a hybrid art form, a form which like other creative forms, such as painting, sculpture ...

  6. Lunar Dust Mitigation Screens

    Science.gov (United States)

    Knutson, Shawn; Holloway, Nancy

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

  7. Screening for Intimate Partner Violence.

    Science.gov (United States)

    Paterno, Mary T; Draughon, Jessica E

    2016-05-01

    Intimate partner violence (IPV) is a serious concern for women that is associated with significant adverse health effects. Routine screening for IPV is recommended, but there are many barriers to screening that have been identified by providers, including discomfort, lack of training, and not knowing how to respond to a positive screen. This article reviews IPV screening and appropriate techniques for responding to a positive screen. IPV screening best practices include using a systematic protocol, developing a screening script, using a validated screening tool, and considerations for privacy and mandatory reporting. Responding to a positive screen should include acknowledging the experience, asking if the woman desires help, offering support and referrals, encouraging safety planning, and completing additional assessments to determine level of danger and to identify any comorbidities. Using these techniques along with therapeutic communication may increase IPV identification and create an environment in which women feel empowered to get help. PMID:26990666

  8. Brassica greens herbicide screening

    Science.gov (United States)

    The objective of this study was to screen herbicides for potential use in brassica greens. Plots were in a RBD with 4 replications. The study was direct seeded on May 19, 2009 with a seeding rate of 272,000 seeds/acre (‘Savanna’ mustard). Treatments included trifluralin PPI + DCPA pre-emergence ap...

  9. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

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

  10. Allergic sensitization: screening methods

    DEFF Research Database (Denmark)

    Ladics, Gregory S.; Fry, Jeremy; Goodman, Richard;

    2014-01-01

    Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus...

  11. Screening and merger activity

    NARCIS (Netherlands)

    A. Banal-Estañol; P. Heidhues; R. Nitsche; J. Seldeslachts

    2010-01-01

    In our paper, the target of a proposed merger, by setting a reserve price, is able to screen prospective acquirers according to their (expected) ability to generate merger-specific synergies. Both empirical evidence and many merger models suggest that the difference between high and low-synergy merg

  12. Early Dementia Screening

    Directory of Open Access Journals (Sweden)

    Peter K. Panegyres

    2016-01-01

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

  13. Screening Pesticides for Neuropathogenicity

    OpenAIRE

    Doherty, John D.

    2006-01-01

    Pesticides are routinely screened in studies that follow specific guidelines for possible neuropathogenicity in laboratory animals. These tests will detect chemicals that are by themselves strong inducers of neuropathogenesis if the tested strain is susceptible relative to the time of administration and methodology of assessment. Organophosphate induced delayed neuropathy (OPIDN) is the only known human neurodegenerative disease associated with pesticides and the existing...

  14. Hazard screening application guide

    International Nuclear Information System (INIS)

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

  15. Reversible Watermarking Using Statistical Information

    Directory of Open Access Journals (Sweden)

    Kurugollu Fatih

    2010-01-01

    Full Text Available In most reversible watermarking methods, a compressed location map is exploited in order to ensure reversibility. Besides, in some methods, a header containing critical information is appended to the payload for the extraction and recovery process. Such schemes have a highly fragile nature; that is, changing a single bit in watermarked data may prohibit recovery of the original host as well as the embedded watermark. In this paper, we propose a new scheme in which utilizing a compressed location map is completely removed. In addition, the amount of auxiliary data is decreased by employing the adjacent pixels information. Therefore, in addition to quality improvement, independent authentication of different regions of a watermarked image is possible.

  16. Nitrooxyethylation Reverses the Healing-Suppressant Effect of Ibuprofen

    Directory of Open Access Journals (Sweden)

    Mandeep Kaushal

    2006-01-01

    Full Text Available Nonsteroidal antiinflammatory drugs like ibuprofen impede tissue repair by virtue of retarding inflammation. The present study was undertaken to explore if linking of nitrooxyethyl ester to ibuprofen reverses its healing-depressant propensity. Nitrooxyethyl ester of ibuprofen (NOE-Ibu was synthesized in our laboratory through a well-established synthetic pathway. NOE-Ibu was screened for its influence on collagenation, wound contraction and epithelialization phases of healing, and scar size of healed wound in three wound models, namely, incision, dead space, and excision wounds. Besides, its influence on the oxidative stress (levels of GSH and TBARS was also determined in 10-day-old granulation tissue. NOE-Ibu was further screened for its antiinflammatory activity in rat paw edema model. NOE-Ibu promoted collagenation (increase in breaking strength, granulation weight, and collagen content, wound contraction and epithelialization phases of healing. NOE-Ibu also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to ibuprofen. Results vindicate that the esterification of ibuprofen with nitrooxyethyl group reverses the healing-suppressant effect of ibuprofen. The compound also showed equipotent antiinflammatory activity as ibuprofen.

  17. Reversible Simulations of Elastic Collisions

    OpenAIRE

    Perumalla, Kalyan S.; Protopopescu, Vladimir A.

    2013-01-01

    Consider a system of N identical hard spherical particles moving in a d-dimensional box and undergoing elastic, possibly multi-particle, collisions. We develop a new algorithm that recovers the pre-collision state from the post-collision state of the system, across a series of consecutive collisions, with essentially no memory overhead. The challenge in achieving reversibility for an n-particle collision (where, n

  18. Reverse ventilation--perfusion mismatch

    Energy Technology Data Exchange (ETDEWEB)

    Palmaz, J.C.; Barnett, C.A.; Reich, S.B.; Krumpe, P.E.; Farrer, P.A.

    1984-01-01

    Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients.

  19. Theory of field reversed configurations

    International Nuclear Information System (INIS)

    This final report surveys the results of work conducted on the theory of field reversed configurations. This project has spanned ten years, beginning in early 1980. During this period, Spectra Technology was one of the leading contributors to the advances in understanding FRC. The report is organized into technical topic areas, FRC formation, equilibrium, stability, and transport. Included as an appendix are papers published in archival journals that were generated in the course of this report. 33 refs

  20. Construction of Cell-based Neurotransmitter Fluorescent Engineered Reporters (CNiFERs) for Optical Detection of Neurotransmitters In Vivo.

    Science.gov (United States)

    Lacin, Emre; Muller, Arnaud; Fernando, Marian; Kleinfeld, David; Slesinger, Paul A

    2016-01-01

    Cell-based neurotransmitter fluorescent engineered reporters (CNiFERs) provide a new tool for neuroscientists to optically detect the release of neurotransmitters in the brain in vivo. A specific CNiFER is created from a human embryonic kidney cell that stably expresses a specific G protein-coupled receptor, which couples to Gq/11 G proteins, and a FRET-based Ca(2+)-detector, TN-XXL. Activation of the receptor leads to an increase in the FRET signal. CNiFERs have nM sensitivity and a temporal response of seconds because a CNiFER clone utilizes the native receptor for a particular neurotransmitter, e.g., D2R for dopamine. CNiFERs are directly implanted into the brain, enabling them to sense neurotransmitter release with a spatial resolution of less than one hundred µm, making them ideal to measure volume transmission in vivo. CNiFERs can also be used to screen other drugs for potential cross-reactivity in vivo. We recently expanded the family of CNiFERs to include GPCRs that couple to Gi/o G proteins. CNiFERs are available for detecting acetylcholine (ACh), dopamine (DA) and norepinephrine (NE). Given that any GPCR can be used to create a novel CNiFER and that there are approximately 800 GPCRs in the human genome, we describe here the general procedure to design, realize, and test any type of CNiFER. PMID:27214050

  1. Reversible Seeding in Storage Rings

    Energy Technology Data Exchange (ETDEWEB)

    Ratner, Daniel; Chao, Alex; /SLAC

    2011-12-14

    We propose to generate steady-state microbunching in a storage ring with a reversible seeding scheme. High gain harmonic generation (HGHG) and echo-enabled harmonic generation (EEHG) are two promising methods for microbunching linac electron beams. Because both schemes increase the energy spread of the seeded beam, they cannot drive a coherent radiator turn-by-turn in a storage ring. However, reversing the seeding process following the radiator minimizes the impact on the electron beam and may allow coherent radiation at or near the storage ring repetition rate. In this paper we describe the general idea and outline a proof-of-principle experiment. Electron storage rings can drive high average power light sources, and free-electron lasers (FELs) are now producing coherent light sources of unprecedented peak brightness While there is active research towards high repetition rate FELs (for example, using energy recovery linacs), at present there are still no convenient accelerator-based sources of high repetition rate, coherent radiation. As an alternative avenue, we recently proposed to establish steady-state microbunching (SSMB) in a storage ring. By maintaining steady-state coherent microbunching at one point in the storage ring, the beam generates coherent radiation at or close to the repetition rate of the storage ring. In this paper, we propose a method of generating a microbunched beam in a storage ring by using reversible versions of linac seeding schemes.

  2. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2014-01-01

    Full Text Available As the power of consumers is growing, the product return for customer service and customer retention has become a common practice in the competitive market, which propels the recent practice of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle. Reverse logistics is the flow and management of products, packaging, components and information from the point of consumption to the point of origin. It is a collection of practices similar to those of supply chain management, but in the opposite direction, from downstream to upstream. It involves activities such as reuse, repair, remanufacture, refurbish, reclaim and recycle. For the conventional forward logistics systems, the flow starts upstream as raw materials, later as manufactured parts and components to be assembled and continues downstream to reach customers as final products to be disposed once they reach their economic or useful lives. In reverse logistics, the disposed products are pushed upstream to be repaired, remanufactured, refurbished, and disassembled into components to be reused or as raw material to be recycled for later use.

  3. Three distinct reversing modes in the geodynamo

    Science.gov (United States)

    Gallet, Y.; Pavlov, V. E.

    2016-03-01

    The data that describe the long-term reversing behavior of the geodynamo show strong and sudden changes in magnetic reversal frequency. This concerns both the onset and the end of superchrons and most probably the occurrence of episodes characterized by extreme geomagnetic reversal frequency (>10-15 rev./Myr). To account for the complexity observed in geomagnetic reversal frequency evolution, we propose a simple scenario in which the geodynamo operates in three distinct reversing modes: i—a "normal" reversing mode generating geomagnetic polarity reversals according to a stationary random process, with on average a reversal rate of ˜3 rev./Myr; ii—a non-reversing "superchron" mode characterizing long time intervals without reversal; iii—a hyper-active reversing mode characterized by an extreme geomagnetic reversal frequency. The transitions between the different reversing modes would be sudden, i.e., on the Myr time scale. Following previous studies, we suggest that in the past, the occurrence of these transitions has been modulated by thermal conditions at the core-mantle boundary governed by mantle dynamics. It might also be possible that they were more frequent during the Precambrian, before the nucleation of the inner core, because of a stronger influence on geodynamo activity of the thermal conditions at the core-mantle boundary.

  4. Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells

    OpenAIRE

    Abraham, Ioana; Jain, Sandeep; Wu, Chung-pu; Khanfar, Mohammad A.; Kuang, Yehong; Dai, Chun-ling; Shi, Zhi; Chen, Xiang; FU, LIWU; Suresh V Ambudkar; Sayed, Khalid El; Chen, Zhe-Sheng

    2010-01-01

    Previously, we reported sipholenol A, a sipholane triterpenoid from the Red Sea sponge Callyspongia siphonella, as a potent reversal of multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp). Through extensive screening of several related sipholane triterpenoids that have been isolated from the same sponge, we identified sipholenone E, sipholenol L and siphonellinol D as potent reversals of MDR in cancer cells. These compounds enhanced the cytotoxicity of several ...

  5. High throughput cell-based assay for identification of glycolate oxidase inhibitors as a potential treatment for Primary Hyperoxaluria Type 1

    Science.gov (United States)

    Wang, Mengqiao; Xu, Miao; Long, Yan; Fargue, Sonia; Southall, Noel; Hu, Xin; McKew, John C.; Danpure, Christopher J.; Zheng, Wei

    2016-01-01

    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

  6. Screening Newborns' Hearing Now Standard

    Science.gov (United States)

    ... Hearing, Language, Voice, Balance Screening Newborns' Hearing Now Standard Past Issues / Fall 2013 Table of Contents Click ... the World from Spinning / Screening Newborns' Hearing Now Standard Fall 2013 Issue: Volume 8 Number 3 Page ...

  7. National Lung Screening Trial (NLST)

    Science.gov (United States)

    The National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.

  8. Screening for Chronic Kidney Disease

    Science.gov (United States)

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

  9. Purpose of Newborn Hearing Screening

    Science.gov (United States)

    ... Size Email Print Share Purpose of Newborn Hearing Screening Page Content Article Body Before you bring your ... from the hospital. Why do newborns need hearing screening? Babies learn from the time they are born. ...

  10. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Summer 2016 Table of Contents Dr. Asad Umar, ... know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  11. Second Trimester Maternal Serum Screening

    Science.gov (United States)

    ... Global Sites Search Help? Second Trimester Maternal Serum Screening Share this page: Was this page helpful? Also ... should know? How is it used? Maternal serum screening is used in the second trimester of pregnancy ...

  12. Screening Tests for Birth Defects

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Screening Tests for Birth Defects Home For Patients Search ... for Birth Defects FAQ165, April 2014 PDF Format Screening Tests for Birth Defects Pregnancy What is a ...

  13. Development of a High-Throughput Functional Screen Using Nanowell-Assisted Cell Patterning.

    Science.gov (United States)

    Ozkumur, Ayca Yalcin; Goods, Brittany A; Love, J Christopher

    2015-09-01

    Living-cell-based screens can facilitate lead discovery of functional therapeutics of interest. A versatile and scalable method is reported that uses dense arrays of nanowells for imparting defined patterns on monolayers of cells. It is shown that this approach can coordinate a multi-component biological assay by designing and implementing a high-throughput, functional nanoliter-scale neutralization assay to identify neutralizing antibodies against HIV. PMID:26121321

  14. 14 CFR 33.97 - Thrust reversers.

    Science.gov (United States)

    2010-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Block Tests; Turbine Aircraft Engines § 33.97 Thrust reversers. (a) If the engine incorporates a reverser, the endurance calibration, operation, and vibration tests prescribed...

  15. Design of a High Performance Reversible Multiplier

    Directory of Open Access Journals (Sweden)

    Md.Belayet Ali

    2011-11-01

    Full Text Available Reversible logic circuits are increasingly used in power minimization having applications such as low power CMOS design, optical information processing, DNA computing, bioinformatics, quantum computing and nanotechnology. The problem of minimizing the number of garbage outputs is an important issue in reversible logic design. In this paper we propose a new 44 universal reversible logic gate. The proposed reversible gate can be used to synthesize any given Boolean functions. The proposed reversible gate also can be used as a full adder circuit. In this paper we have used Peres gate and the proposed Modified HNG (MHNG gate to construct the reversible fault tolerant multiplier circuit. We show that the proposed 44 reversible multiplier circuit has lower hardware complexity and it is much better and optimized in terms of number of reversible gates and number of garbage outputs with compared to the existing counterparts.

  16. Ancient Magnetic Reversals: Clues to the Geodynamo.

    Science.gov (United States)

    Hoffman, Kenneth A.

    1988-01-01

    Discusses the question posed by some that the earth's magnetic field may reverse. States that rocks magnetized by ancient fields may offer clues to the underlying reversal mechanism in the earth's core. (TW)

  17. Drug Screening in Neonates.

    Science.gov (United States)

    Bell, Susan Givens

    2016-01-01

    Gestational substance exposure continues to be a significant problem. Neonates may be exposed to various substances including illicit drugs, prescription drugs, and other legal substances that are best not used during pregnancy because of their potential deleterious effects as possible teratogens or their potential to create dependence and thus withdrawal in the neonate. Screening the newborn for gestational substance exposure is important for both acute care and early intervention to promote the best possible long-term outcomes. This column provides insight into what is known about the extent of substance use by pregnant women, an overview of neonatal biologic matrices for drug testing, and a discussion of the legal implications of neonatal substance screening. PMID:27636697

  18. Exploring Urban Screens

    Directory of Open Access Journals (Sweden)

    Zlatan Krajina

    2009-12-01

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

  19. Identification of New Influenza B Virus Variants by Multiplex Reverse Transcription-PCR and the Heteroduplex Mobility Assay

    OpenAIRE

    Zou, Shimian; Stansfield, Carol; Bridge, Jodi

    1998-01-01

    A quick genetic approach for the screening of influenza virus variants was developed in this laboratory (S. Zou, J. Clin. Microbiol. 35:2623–2627, 1997). It uses multiplex reverse transcription and multiplex PCR to amplify and differentiate the variable region of the hemagglutinin genes of different types and subtypes of influenza viruses. Variants within the same type or subtype are then identified by the heteroduplex mobility shift assay of the amplicons. The method was used to screen influ...

  20. Periodicity and Immortality in Reversible Computing

    OpenAIRE

    Kari, Jarkko; Ollinger, Nicolas

    2008-01-01

    Additional material available on the web at http://www.lif.univ-mrs.fr/~nollinge/rec/gnirut/ We investigate the decidability of the periodicity and the immortality problems in three models of reversible computation: reversible counter machines, reversible Turing machines and reversible one-dimensional cellular automata. Immortality and periodicity are properties that describe the behavior of the model starting from arbitrary initial configurations: immortality is the property of having at ...

  1. Fast magnetization reversal of nanoclusters in resonator

    OpenAIRE

    Yukalov, V. I.; Yukalova, E. P.

    2012-01-01

    An effective method for ultrafast magnetization reversal of nanoclusters is suggested. The method is based on coupling a nanocluster to a resonant electric circuit. This coupling causes the appearance of a magnetic feedback field acting on the cluster, which drastically shortens the magnetization reversal time. The influence of the resonator properties, nanocluster parameters, and external fields on the magnetization dynamics and reversal time is analyzed. The magnetization reversal time can ...

  2. Design of High speed Low Power Reversible Vedic multiplier and Reversible Divider

    Directory of Open Access Journals (Sweden)

    Srikanth G Department of Electronics & Communication Engineerig, Indur Institute of Engineering & Technology, Siddipet, Medak, JNTUH University, Telangana, India.

    2014-09-01

    Full Text Available This paper bring out a 32X32 bit reversible Vedic multiplier using "Urdhva Tiryakabhayam" sutra meaning vertical and crosswise, is designed using reversible logic gates, which is the first of its kind. Also in this paper we propose a new reversible unsigned division circuit. This circuit is designed using reversible components like reversible parallel adder, reversible left-shift register, reversible multiplexer, reversible n-bit register with parallel load line. The reversible vedic multiplier and reversible divider modules have been written in Verilog HDL and then synthesized and simulated using Xilinx ISE 9.2i. This reversible vedic multiplier results shows less delay and less power consumption by comparing with array multiplier.

  3. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...... trials underway in Europe and in the USA. Our purpose is to update the readers on recent progress in medical knowledge in this field....

  4. Blood Screening for Influenza

    OpenAIRE

    Hourfar, Michael Kai; Themann, Anna; Eickmann, Markus; Puthavathana, Pilaipan; Laue, Thomas; Seifried, Erhard; Schmidt, Michael

    2007-01-01

    Influenza viruses, including highly pathogenic avian influenza virus (H5N1), could threaten blood safety. We analyzed 10,272 blood donor samples with a minipool nucleic acid amplication technique. Analytical sensitivity of the method was 804 geq/mL and 444 geq/mL for generic influenza primers and influenza (H5N1) subtype–specific primers. This study demonstrates that such screening for influenza viruses is feasible.

  5. Screening for helicobacter pylori

    OpenAIRE

    de Sousa, Jaime Correia; Thomas, Roger

    2006-01-01

    The aim of this review is to assess whether a screening programme for Helicobacter pylori will be both successful and cost-effective. Method: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the NHS Database of Abstracts of Reviews of Effectiveness; MEDLINE; EMBASE; SilverPlatter, Biological Abstracts and Science Citation Index-Expanded. We used the search terms Helicobacter pylori and (diagnos$ or identif$ or find$) and (syst...

  6. Screening Devices at School

    DEFF Research Database (Denmark)

    Ratner, Helene

    2011-01-01

    it as a “screening device”. It is a “device” in the sense that it distributes agency, and it “screens” in the word’s multiple meanings: “projecting” as in creating a viewer position;“sifting” and “systematizing” as in discriminating “knowledge” from mere “opinionings”; and “protecting” teachers from noise. Using...

  7. Screened Anode N2 Laser

    OpenAIRE

    Sabry, M. Montaser Foad

    1985-01-01

    An experimental study of the effect of screening the discharge channel on the output energy is presented. It has been found that a screened anode nitrogen laser generates higher output energy than that of a screened cathode, and also higher than that when both cathode and anode are unshielded at higher pressures.

  8. What Screening Tests Are There?

    Science.gov (United States)

    ... Research Related Links Stay Informed Cancer Home What Screening Tests Are There? Language: English Español (Spanish) Recommend ... packs a day for 15 years. Risks of Screening Lung cancer screening has at least three risks— ...

  9. Comparison of Automated Treponemal and Nontreponemal Test Algorithms as First-Line Syphilis Screening Assays

    OpenAIRE

    Huh, Hee Jin; Chung, Jae-Woo; Park, Seong Yeon; Chae, Seok Lae

    2015-01-01

    Background Automated Mediace Treponema pallidum latex agglutination (TPLA) and Mediace rapid plasma reagin (RPR) assays are used by many laboratories for syphilis diagnosis. This study compared the results of the traditional syphilis screening algorithm and a reverse algorithm using automated Mediace RPR or Mediace TPLA as first-line screening assays in subjects undergoing a health checkup. Methods Samples from 24,681 persons were included in this study. We routinely performed Mediace RPR and...

  10. Weak bond screening system

    Science.gov (United States)

    Chuang, S. Y.; Chang, F. H.; Bell, J. R.

    Consideration is given to the development of a weak bond screening system which is based on the utilization of a high power ultrasonic (HPU) technique. The instrumentation of the prototype bond strength screening system is described, and the adhesively bonded specimens used in the system developmental effort are detailed. Test results obtained from these specimens are presented in terms of bond strength and level of high power ultrasound irradiation. The following observations were made: (1) for Al/Al specimens, 2.6 sec of HPU irradiation will screen weak bond conditions due to improper preparation of bonding surfaces; (2) for composite/composite specimens, 2.0 sec of HPU irradiation will disrupt weak bonds due to under-cured conditions; (3) for Al honeycomb core with composite skin structure, 3.5 sec of HPU irradiation will disrupt weak bonds due to bad adhesive or oils contamination of bonding surfaces; and (4) for Nomex honeycomb with Al skin structure, 1.3 sec of HPU irradiation will disrupt weak bonds due to bad adhesive.

  11. Garbage collection for reversible functional languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2015-01-01

    Reversible languages are programming languages where all programs can run both forwards and backwards. Reversible functional languages have been proposed that use symmetric pattern matching and data construction. To be reversible, these languages require linearity: Every variable must be used exa...

  12. THEORETICAL FRAMES FOR DESIGNING REVERSE LOGISTICS PROCESSES

    OpenAIRE

    Grabara, Janusz K.; Sebastian Kot

    2009-01-01

    Logistics processes of return flow became more and more important in present business practice. Because of better customer satisfaction, environmental and financial aspects many enterprises deal with reverse logistics performance. The paper is a literature review focused on the design principles of reverse logistics processes Keywords: reverse logistics, designing.

  13. Kinetic Line Voronoi Operations and Their Reversibility

    DEFF Research Database (Denmark)

    Mioc, Darka; Anton, François; Gold, Christopher;

    2010-01-01

    , as the basic algorithms for addition, deletion and moving of spatial objects. Having developed reversible map operations on the lowest level, we were able to maintain reversibility of the map updates at higher levels as well. The reversibility in GIS can be used for efficient implementation of rollback...

  14. A Functional Language for Describing Reversible Logic

    DEFF Research Database (Denmark)

    Carøe, Michael Kirkedal

    2012-01-01

    . Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...

  15. Cleaning Our World through Reverse Graffiti

    Science.gov (United States)

    Randazzo, Gabe; LaJevic, Lisa

    2013-01-01

    Over the last decade artists have begun to experiment with "reverse pollution" techniques, such as reverse graffiti, which focuses on cleaning environmental surfaces. Having recently been introduced to the works of Moose, the artist known for inventing the reverse graffiti technique, the authors decided to design a curriculum to increase…

  16. REVERSE ENGINEERING AND ITS REALISTIC APPLICATIONS

    OpenAIRE

    Nikita Bakshi; Shruti Gujral

    2014-01-01

    Reverse-engineering is used for many purposes like as a learning tool, as a way to make compatible products that are cheaper than what is currently on the market. This paper discusses what is software, its type, reverse engineering, applications of reverse engineering and their tools.

  17. 14 CFR 25.933 - Reversing systems.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Reversing systems. 25.933 Section 25.933... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.933 Reversing systems. (a) For turbojet reversing systems— (1) Each system intended for ground operation only must be designed so that during...

  18. 14 CFR 23.933 - Reversing systems.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Reversing systems. 23.933 Section 23.933... systems. (a) For turbojet and turbofan reversing systems. (1) Each system intended for ground operation... flight and landing under any possible position of the thrust reverser. (2) Each system intended for...

  19. 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

    2008-01-01

    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.

  20. Remote Whispering Applying Time Reversal

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Brian Eric [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-16

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wires and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.

  1. Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound

    International Nuclear Information System (INIS)

    Allergic contact dermatitis is the result of an adaptive immune response of the skin to direct exposure to an allergen. Since many chemicals are also allergens, European regulations require strict screening of all ingredients in consumer products. Until recently, identifying a potential allergen has completely relied on animal testing (e.g.: Local Lymph Node Assay). In addition to the ethical problems, both the 7th Amendment to the Cosmetics Directive and REACH have stimulated the development of alternative tests for the assessment of potential sensitizers. This review is aimed at summarising the progress on cell based assays, in particular dendritic cell based assays, being developed as animal alternatives. Primary cells (CD34+ derived dendritic cells, monocyte derived dendritic cells) as well as dendritic cell-like cell lines (THP-1, U-937, MUTZ-3, KG-1, HL-60, and K562) are extensively described along with biomarkers such as cell surface markers, cytokines, chemokines and kinases. From this review, it can be concluded that no single cell based assay nor single marker is yet able to distinguish all sensitizers from non-sensitizers in a test panel of chemicals, nor is it possible to rank the sensitizing potential of the test chemicals. This suggests that sensitivity and specificity may be increased by a tiered assay approach. Only a limited number of genomic and proteomic studies have been completed until now. Such studies have the potential to identify novel biomarkers for inclusion in future assay development. Although progress is promising, this review suggests that it may be difficult to meet the up and coming European regulatory deadlines.

  2. Reverse geometric engineering of singularities

    International Nuclear Information System (INIS)

    One can geometrically engineer supersymmetric field theories theories by placing D-branes at or near singularities. The opposite process is described, where one can reconstruct the singularities from quiver theories. The description is in terms of a noncommutative quiver algebra which is constructed from the quiver diagram and the superpotential. The center of this noncommutative algebra is a commutative algebra, which is the ring of holomorphic functions on a variety V. If certain algebraic conditions are met, then the reverse geometric engineering produces V as the geometry that D-branes probe. It is also argued that the identification of V is invariant under Seiberg dualities. (author)

  3. How to play Reverse Hex

    DEFF Research Database (Denmark)

    Toft, Bjarne; Hayward, Ryan B.; Henderson, Philip

    2012-01-01

    We present new results on how to play Reverse Hex, also known as Rex, or Misère Hex, on n × n boards. We give new proofs – and strengthened versions – of Lagarias and Sleator’s theorem (for n × n boards, each player can prolong the game until the board is full, so the first/second player can always......, we find second-player winning replies. Finally, in response to comments by Martin Gardner, for each n ≤ 5, we give a simple winning strategy for the n × n board....

  4. Doping effects for organic photovoltaic cells based on small-molecular-weight semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Taima, Tetsuya; Yamanari, Toshihiro; Saito, Kazuhiro [Research Center for Photovoltaics, National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1 Umezono, Tsukuba 305-8568 (Japan); Sakai, Jun [Advanced Technologies Development Laboratory, Matsushita Electric Works, Ltd., 1048 Kadoma, Osaka 571-8686 (Japan)

    2009-06-15

    We have studied highly efficient organic photovoltaic (OPV) cells based on small-molecular-weight semiconductors: zinc phthalocyanine (ZnPc) and C60. To improve the efficiency furthermore, open-circuit voltage (V{sub oc}) has to be increased. We reported that 5,6,11,12-tetraphenylnaphthacene (rubrene) produces the highest V{sub oc} of 0.91 V by p-n heterojunction OPV cells with C60. In this paper, we report rubrene doping effects for OPV cells based on ZnPc to obtain higher V{sub oc}. (author)

  5. Challenges of stem cell-based pulp and dentin regeneration: a clinical perspective

    OpenAIRE

    Huang, George T.-J.; Al-Habib, Mey; Gauthier, Philippe

    2013-01-01

    There are two types of approaches to regenerate tissues: cell-based and cell-free. The former approach is to introduce exogenous cells into the host to regenerate tissues, and the latter is to use materials other than cells in an attempt to regenerate tissues. There has been a significant advancement in stem cell-based pulp and dentin regeneration research in the past few years. Studies in small and large animals have demonstrated that pulp/dentin-like tissues can be regenerated partially or ...

  6. The history and advances of reversible terminators used in new generations of sequencing technology.

    Science.gov (United States)

    Chen, Fei; Dong, Mengxing; Ge, Meng; Zhu, Lingxiang; Ren, Lufeng; Liu, Guocheng; Mu, Rong

    2013-02-01

    DNA sequencing using reversible terminators, as one sequencing by synthesis strategy, has garnered a great deal of interest due to its popular application in the second-generation high-throughput DNA sequencing technology. In this review, we provided its history of development, classification, and working mechanism of this technology. We also outlined the screening strategies for DNA polymerases to accommodate the reversible terminators as substrates during polymerization; particularly, we introduced the "REAP" method developed by us. At the end of this review, we discussed current limitations of this approach and provided potential solutions to extend its application.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  8. Overdiagnosis in screening mammography in Denmark

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Olsen, Anne Helene; Blichert-Toft, Mogens;

    2013-01-01

    To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography.......To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography....

  9. Screening for Obsessive-Compulsive Disorder (OCD)

    Science.gov (United States)

    ... Conference & Education Membership Journal & Multimedia Resources Awards Consumers Screening for Obsessive-Compulsive Disorder (OCD) Main navigation FAQs Screen Yourself Screening for Depression Screening for Generalized Anxiety Disorder (GAD) ...

  10. Online Testable Decoder using Reversible Logic

    Directory of Open Access Journals (Sweden)

    Hemalatha. K. N. Manjula B. B. Girija. S

    2012-02-01

    Full Text Available The project proposes to design and test 2 to 4 reversible Decoder circuit with arbitrary number of gates to an online testable reversible one and is independent of the type of reversible gate used. The constructed circuit can detect any single bit errors and to convert a decoder circuit that is designed by reversible gates to an online testable reversible decoder circuit. Conventional digital circuits dissipate a significant amount of energy because bits of information are erased during the logic operations. Thus if logic gates are designed such that the information bits are not destroyed, the power consumption can be reduced. The information bits are not lost in case of a reversible computation. Reversible logic can be used to implement any Boolean logic function.

  11. A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity.

    Science.gov (United States)

    Astashkina, Anna; Mann, Brenda; Grainger, David W

    2012-04-01

    Drug candidate and toxicity screening processes currently rely on results from early-stage in vitro cell-based assays expected to faithfully represent essential aspects of in vivo pharmacology and toxicology. Several in vitro designs are optimized for high throughput to benefit screening efficiencies, allowing the entire libraries of potential pharmacologically relevant or possible toxin molecules to be screened for different types of cell signals relevant to tissue damage or to therapeutic goals. Creative approaches to multiplexed cell-based assay designs that select specific cell types, signaling pathways and reporters are routine. However, substantial percentages of new chemical and biological entities (NCEs/NBEs) that fail late-stage human drug testing, or receive regulatory "black box" warnings, or that are removed from the market for safety reasons after regulatory approvals all provide strong evidence that in vitro cell-based assays and subsequent preclinical in vivo studies do not yet provide sufficient pharmacological and toxicity data or reliable predictive capacity for understanding drug candidate performance in vivo. Without a reliable translational assay tool kit for pharmacology and toxicology, the drug development process is costly and inefficient in taking initial in vitro cell-based screens to in vivo testing and subsequent clinical approvals. Commonly employed methods of in vitro testing, including dissociated, organotypic, organ/explant, and 3-D cultures, are reviewed here with specific focus on retaining cell and molecular interactions and physiological parameters that determine cell phenotypes and their corresponding responses to bioactive agents. Distinct advantages and performance challenges for these models pertinent to cell-based assay and their predictive capabilities required for accurate correlations to in vivo mechanisms of drug toxicity are compared. PMID:22252140

  12. Internal surface reverse phase HPLC

    International Nuclear Information System (INIS)

    Two recent goals in the field o nuclear medicine have been the development of 99m-Technetium radiopharmaceuticals for diagnostic perfusion imaging of the heart and brain. The neutral seven coordinate technetium compounds known as the BATOs (boronic acid adducts of technetium dioximes) with the general formula TcCl(dioxime)3BR (BR = Boronic Acid Adduct) have shown their utility as both myocardial and cerebral perfusion agents. Variability in serum binding and metabolism between animal models and humans is of major concern when determining the potential clinical utility of 99m-Tc radiopharmaceuticals from animal data. This paper introduces an in vitro method that has been developed which permits interspecies comparisons of serum binding and metabolism of the TcCl(dioxime)3BR radiopharmaceuticals. The method involves the HPLC analysis of TcCl(dioxime)3BR samples incubated in sera using a two column system. Sera samples are injected directly onto an Internal Surface Reverse Phase ISRP precolumn, which separates free from protein bound material. Non-protein bound material is passed through an analytical reverse phase column of separation of metabolites. With this method of analysis, significant species variation in both the rate of serum binding and metabolism of different TcCl(dioxime)3BR complexes can be demonstrated. The method allows for the prescreening of potential 99m-Tc radiopharmaceuticals prior to extensive animal testing

  13. To screen or not to screen: What factors influence complex screening decisions?

    Science.gov (United States)

    Petrova, Dafina; Garcia-Retamero, Rocio; Catena, Andrés; van der Pligt, Joop

    2016-06-01

    Contrary to people's intuitions, many screenings can have both benefits (e.g., lives saved) and harms (e.g., unnecessary treatments). Statistical information is often provided to ensure informed decision making. However, few theoretical models have addressed the role of comprehension of such information in screening decisions. In an experiment, we studied how cognitive skills, emotions, and a priori beliefs about screening affect comprehension of the evidence of benefits and harms from screening and intentions to get screened. Young adults (N = 347) received information about a disease for which a screening test was available and numerical information about the benefits and harms from screening. Results showed that comprehension and perceptions of benefits are central to decisions; however, lay perceptions of harms along the screening cascade require further study. Numeracy, science literacy, and emotions can promote informed decision making by facilitating comprehension of the evidence. At the same time emotions and beliefs resulting from persuasive campaigns can have strong effects on screening intentions beyond the available evidence. To apply to screening procedures where informed decision making is recommended, theoretical models of screening decisions need to include comprehension of benefits and harms, and account for how cognitive skills, emotions, and beliefs influence comprehension and decisions. (PsycINFO Database Record PMID:27295468

  14. Excitons and Two-dimensional Screening: Critical Screening Lengths

    OpenAIRE

    Tanguy, Christian

    2001-01-01

    A beautiful and intriguing relationship has recently been proposed to express the critical screening lengths associated with the apparition of new bound states for the two-dimensional statically screened Coulomb potential. Semiclassical quantum theory show that this relationship is unfortunately not strictly exact. These results are confirmed by a variational calculation, which provides upper bounds for the critical screening lengths in the case $l \\geq 1$.

  15. Investigation of Organic Solar Cells Based on Donor——A ccepter Heterojunction%Investigation of Organic Solar Cells Based onDonor——A ccepter Heterojunction

    Institute of Scientific and Technical Information of China (English)

    Gao Yinhao

    2008-01-01

    The single-l ayer structure and heterojunction structure organic solar cells based on copper phthalocyanine (CuPc),3,4,9,10-Perylenetetracarboxylic dianhydride (PTCDA) and fullerene C60 were fabricated to study their photovoltaic (PV) properties. The PV performance of heterojunction structure solar cells was improved compared with the single layer structure cell.This is due to the introduction of donor-acceptor heterojunction that both expands the absorption range and offers efficient excit on dissociation site.In heterojunction structure solar cells,the PV performance of device with C60 as acceptor has highly improved because C60 has longer diffusion length o f excitons.

  16. Engineering spinal fusion: evaluating ceramic materials for cell based tissue engineered approaches

    NARCIS (Netherlands)

    Wilson, C.E.

    2011-01-01

    The principal aim of this thesis was to advance the development of tissue engineered posterolateral spinal fusion by investigating the potential of calcium phosphate ceramic materials to support cell based tissue engineered bone formation. This was accomplished by developing several novel model syst

  17. Ambient roll-to-roll fabrication of flexible solar cells based on small molecules

    DEFF Research Database (Denmark)

    Lin, Yuze; Dam, Henrik Friis; Andersen, Thomas Rieks;

    2013-01-01

    All solution-processed roll-to-roll flexible solar cells based on a starshaped small molecule donor and PCBMacceptor were fabricated by slot-die coating, as the first successful example reported for small molecule roll-to-roll flexible solar cells....

  18. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  19. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release

    DEFF Research Database (Denmark)

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen;

    2015-01-01

    models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we...

  20. Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

    NARCIS (Netherlands)

    Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, J.C.H.; Khademhosseini, A.

    2016-01-01

    Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives, s

  1. The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence

    DEFF Research Database (Denmark)

    Gräs, Søren; Lose, Gunnar

    2011-01-01

    Stress urinary incontinence is a common disorder affecting the quality of life for millions of women worldwide. Effective surgical procedures involving synthetic permanent meshes exist, but significant short- and long-term complications occur. Cell-based therapy using autologous stem cells...

  2. Catalyst Degradation in High Temperature Proton Exchange Membrane Fuel Cells Based on Acid Doped Polybenzimidazole Membranes

    DEFF Research Database (Denmark)

    Cleemann, Lars Nilausen; Buazar, F.; Li, Qingfeng;

    2013-01-01

    Degradation of carbon supported platinum catalysts is a major failure mode for the long term durability of high temperature proton exchange membrane fuel cells based on phosphoric acid doped polybenzimidazole membranes. With Vulcan carbon black as a reference, thermally treated carbon black...

  3. Single-cell-based sensors and synchrotron FTIR spectroscopy: a hybrid system towards bacterial detection.

    Science.gov (United States)

    Veiseh, Mandana; Veiseh, Omid; Martin, Michael C; Bertozzi, Carolyn; Zhang, Miqin

    2007-09-30

    Microarrays of single macrophage cell-based sensors were developed and demonstrated for potential real-time bacterium detection by synchrotron FTIR microscopy. The cells were patterned on gold electrodes of silicon oxide substrates by a surface engineering technique, in which the gold electrodes were immobilized with fibronectin to mediate cell adhesion and the silicon oxide background was passivated with polyethylene glycol (PEG) to resist protein adsorption and cell adhesion. Cell morphology and IR spectra of single, double, and triple cells on gold electrodes exposed to lipopolysaccharide (LPS) of different concentrations were compared to reveal the detection capability of this cell-based sensing platform. The single-cell-based system was found to generate the most significant and consistent IR spectrum shifts upon exposure to LPS, thus providing the highest detection sensitivity. Changes in cell morphology and IR shifts upon cell exposure to LPS were found to be dependent on the LPS concentration and exposure time, which established a method for the identification of LPS concentration and infected cell population. Possibility of using this single-cell system with conventional IR spectroscopy as well as its limitation was investigated by comparing IR spectra of single-cell arrays with gold electrode surface areas of 25, 100, and 400 microm2 using both synchrotron and conventional FTIR spectromicroscopes. This cell-based platform may potentially provide real-time, label-free, and rapid bacterial detection, and allow for high-throughput statistical analyses, and portability. PMID:17560777

  4. Molecular screening in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  5. Substation noise screening tool

    Energy Technology Data Exchange (ETDEWEB)

    Maybee, Nigel; Everton, Pascal [HFP Acoustical Consultants Corp. (Canada)], email: nigel.maybee@hfpacoustical.com; Chow, Vincent [Altalink Management Ltd. (Canada)], email: Vincent.Chow@AltaLink.ca

    2011-07-01

    Alberta noise regulations require energy-related facilities to conduct predictions on sound levels, especially for large and medium noise sources. This is usually done with well-known modelling software, but that can be disadvantageous when assessing the noise impact of smaller noise sources, such as transformer substations. This paper focuses on the development of a spreadsheet substation noise screening tool to assess the noise impact of a small transformer substation with precision and ease-of-use. Three aspects must be considered: transformer sound levels, which can be provided by the manufacturer or extracted from accepted sound level references; sound power calculations, which depend on the substation size and operating regime; and sound propagation calculations, which take into account the distance of the receptor from the substation and sound absorption by the air and ground. Comparison of results obtained with this tool with results generated by standard sound modelling software shows the utility, accuracy and ease-of-use of this screening method for assessing the noise impact of transformer substations.

  6. Celiac disease during pregnancy: to screen or not to screen?

    Science.gov (United States)

    Pope, Rachel; Sheiner, Eyal

    2009-01-01

    Permanent intolerance to gluten, known as celiac disease, affects both fertility and pregnancy outcomes when left untreated. Recent research on celiac disease and reproduction urge increased screening for celiac disease. While this may be beneficial for couples facing idiopathic infertility or those from particular risk groups, screening involves its own risks and expenses, and has not been consistently proven effective for the general population while pregnant. The present editorial discusses the potential advantages and disadvantages of screening during pregnancy and examines when screening may be helpful. PMID:18818937

  7. REIMBURSEMENT OF CELL-BASED REGENERATIVE THERAPY IN THE UK AND FRANCE.

    Science.gov (United States)

    Mahalatchimy, Aurélie

    2016-01-01

    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

  8. REIMBURSEMENT OF CELL-BASED REGENERATIVE THERAPY IN THE UK AND FRANCE.

    Science.gov (United States)

    Mahalatchimy, Aurélie

    2016-01-01

    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

  9. Reverse genetics with animal viruses

    International Nuclear Information System (INIS)

    Full text: Reverse genetics of negative-strand RNA viruses (NSV), which allows generation of recombinant viruses entirely from cloned cDNA, has progressed rapidly in the past decade. NSV are a large and diverse group of enveloped viruses of both medical and veterinary importance. They differ widely in morphology, genome structure and host interactions. The first NSV that was completely amenable to genetic manipulation is the neurotropathogenic rabies virus of the rhabdovirus family. In subsequent years, vesicular stomatitis virus and a number of viruses belonging to the family Paramyxoviridae, including viruses causing important animal diseases such as rinderpest virus, canine distemper virus, bovine respiratory syncytial virus, bovine parainfluenza virus and Newcastle disease virus (NDV), succumbed to genetic engineering. The ability to genetically manipulate NSV opens a wide range of possibilities to study the virus biology and develop improved vaccines. Identification and analysis of attenuating mutations using the recombinant system could lead to generation of safe vaccine strains. Introduction of one of the previously studied mutation into an infectious rabies virus (RV) clone by replacing the arginine at position 333 of RV glycoprotein (G-protein) by an aspartic acid resulted in a dramatic attenuation. Combination of this mutation with a deletion that eliminates the interaction between RV P-protein and the cytoplasmic dynein light chain (LC8), which is presumably involved in retrograde transport of RV, further attenuates the rabies virus by 30-fold after intramuscular inoculation. Since extreme attenuation may adversely affect immunogenicity, reverse genetics was used to introduce an additional Gprotein to the step-wise attenuated RV to increase its effectiveness. The resultant recombinant virus may be helpful in developing a highly safe and effective live RV vaccine for oral immunizations of animals. Reverse genetics of NSV has also helped in providing

  10. Reversibly assembled cellular composite materials.

    Science.gov (United States)

    Cheung, Kenneth C; Gershenfeld, Neil

    2013-09-13

    We introduce composite materials made by reversibly assembling a three-dimensional lattice of mass-produced carbon fiber-reinforced polymer composite parts with integrated mechanical interlocking connections. The resulting cellular composite materials can respond as an elastic solid with an extremely large measured modulus for an ultralight material (12.3 megapascals at a density of 7.2 milligrams per cubic centimeter). These materials offer a hierarchical decomposition in modeling, with bulk properties that can be predicted from component measurements and deformation modes that can be determined by the placement of part types. Because site locations are locally constrained, structures can be produced in a relative assembly process that merges desirable features of fiber composites, cellular materials, and additive manufacturing.

  11. Investigations of reversible thermochromic mixtures

    Science.gov (United States)

    MacLaren, Douglas C.

    Three-component organic thermochromic systems have potential applications in reversible, rewritable thermal printing. In principle, such mixtures could maintain a coloured or non-coloured state at ambient temperature depending on their thermal treatment. These systems generally consist of a functional dye (1--3 mol%), a weakly acidic colour developer (5--25 mol%), and a high-melting organic solvent (75--90 mol%). Colour development occurs at the fusion temperature of the mixture, which triggers the interaction of the dye and developer. Slow cooling of the melt results in an equilibrium state with low colour density, whereas rapid cooling of the melt results in a metastable state with high colour density. The metastable state can be decoloured by heating to an intermediate decolourisation temperature at which the coloured state becomes unstable. Barriers to the widespread use of reversible, rewritable thermochromic materials include problems with colour contrast, colour stability, and decolourisation rates. Development is hindered by a lack of detailed knowledge of the interactions between components in these systems. In this study the developer-dye and developer-solvent interactions were examined for an archetypal dye/developer/solvent thermochromic system. Vibrational spectroscopy, NMR, and thermal analysis were used to examine compounds formed in developer/dye and developer/solvent binary mixtures. Rewritable thermochromic properties such as metastable colour density, equilibrium colour density, and decolourisation rates were examined and discussed in terms of the thermodynamics of the developer/dye and developer/solvent interactions. Observed thermochromic properties are shown to be strongly correlated to a competition between the dye and the solvent for interaction with the developer. Increasing the attractive interaction between the solvent and developer results in enhanced rewritable thermochromic properties.

  12. Process of forming compounds using reverse micelle or reverse microemulsion systems

    Science.gov (United States)

    Linehan, John C.; Fulton, John L.; Bean, Roger M.

    1998-01-01

    The present invention is directed to a process for producing a nanometer-sized metal compound. The process comprises forming a reverse micelle or reverse microemulsion system comprising a polar fluid in a non-polar or low-polarity fluid. A first reactant comprising a multi-component, water-soluble metal compound is introduced into the polar fluid in a non-polar or low-polarity fluid. This first reactant can be introduced into the reverse micelle or reverse microemulsion system during formation thereof or subsequent to the formation of the reverse micelle or microemulsion system. The water-soluble metal compound is then reacted in the reverse micelle or reverse microemulsion system to form the nanometer-sized metal compound. The nanometer-sized metal compound is then precipitated from the reverse micelle or reverse microemulsion system.

  13. Antenatal haemoglobinopathy screening in Australia.

    Science.gov (United States)

    Tan, Yi Ling; Kidson-Gerber, Giselle

    2016-04-01

    Haemoglobinopathy screening should be performed in women with microcytic indices, women from high risk ethnic populations and those with unexplained anaemia. Early testing of women and their partners expedites appropriate management prior to and during pregnancy. Haemoglobinopathy screening is a multistep process beginning with a full blood count, ferritin assay, screening tests for haemoglobinopathies (ie, haemoglobin electrophoresis, high performance liquid chromatography, capillary electrophoresis) and assessment of clinical risk. Iron deficiency may obscure the diagnosis of β-thalassaemia trait. If possible, haemoglobinopathy testing should be performed when the woman is iron-replete. Genetic testing can be offered on the basis of the combined risk of the couple; but turnaround times are lengthy at present, hence the emphasis on early pregnancy or pre-conception screening. Screening processes vary between states and local health districts; a uniform approach to screening and genetic testing with a national registry to record results would improve management of this growing problem. PMID:27031395

  14. Push for the Second Screen

    DEFF Research Database (Denmark)

    Sørensen, Jannick Kirk; Sørensen, Lene Tolstrup

    Users’ perception of the relation between the TV screen and a secondary screen (e.g. smartphone or tablet) is examined empirically in a pilot project through a low-fi prototype and interviews. Early observations indicate that the user value/acceptance of push-messages delivered to the second screen...... during the TV viewing depends on a number of interwoven factors such as TV-genre, rhythm and number of messages, semantic correlation and user’s general media habits....

  15. Carbon nanotube composites for glucose biosensor incorporated with reverse iontophoresis function for noninvasive glucose monitoring

    OpenAIRE

    Sun, Tai-ping; Shieh, Hsiu-Li; Ching, Congo Tak-Shing; Yao, Yan-Dong; Huang, Su-Hua; Liu, Chia-Ming; Liu, Wei-Hao; Chen, Chung-Yuan

    2010-01-01

    This study aims to develop an amperometric glucose biosensor, based on carbon nanotubes material for reverse iontophoresis, fabricated by immobilizing a mixture of glucose oxidase (GOD) and multiwalled carbon nanotubes (MWCNT) epoxy-composite, on a planar screen-printed carbon electrode. MWCNT was employed to ensure proper incorporation into the epoxy mixture and faster electron transfer between the GOD and the transducer. Results showed this biosensor possesses a low detection potential (+50...

  16. Securing Biometric Images using Reversible Watermarking

    CERN Document Server

    Thampi, Sabu M

    2011-01-01

    Biometric security is a fast growing area. Protecting biometric data is very important since it can be misused by attackers. In order to increase security of biometric data there are different methods in which watermarking is widely accepted. A more acceptable, new important development in this area is reversible watermarking in which the original image can be completely restored and the watermark can be retrieved. But reversible watermarking in biometrics is an understudied area. Reversible watermarking maintains high quality of biometric data. This paper proposes Rotational Replacement of LSB as a reversible watermarking scheme for biometric images. PSNR is the regular method used for quality measurement of biometric data. In this paper we also show that SSIM Index is a better alternate for effective quality assessment for reversible watermarked biometric data by comparing with the well known reversible watermarking scheme using Difference Expansion.

  17. Optimized Reversible Binary-Coded Decimal Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert

    2008-01-01

    Abstract Babu and Chowdhury [H.M.H. Babu, A.R. Chowdhury, Design of a compact reversible binary coded decimal adder circuit, Journal of Systems Architecture 52 (5) (2006) 272-282] recently proposed, in this journal, a reversible adder for binary-coded decimals. This paper corrects and optimizes...... in reversible logic design by drastically reducing the number of garbage bits. Specialized designs benefit from support by reversible logic synthesis. All circuit components required for optimizing the original design could also be synthesized successfully by an implementation of an existing synthesis algorithm....... Keywords: Reversible logic circuit; Full-adder; Half-adder; Parallel adder; Binary-coded decimal; Application of reversible logic synthesis...

  18. Principles of a reversible programming language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    features of the language include explicit post-condition assertions, direct access to an inverse semantics and the possibility of clean (i.e., garbage-free) computation of injective functions. We suggest the clean simulation of reversible Turing machines as a criterion for computing strength of reversible......The principles of reversible programming languages are explicated and illustrated with reference to the design of a high-level imperative language, Janus. The fundamental properties for such languages include backward as well as forward determinism and reversible updates of data. The unique design...... languages, and demonstrate this for Janus. We show the practicality of the language by implementation of a reversible fast Fourier transform. Our results indicate that the reversible programming paradigm has fundamental properties that are relevant to many different areas of computer science....

  19. Periodicity of the earth's magnetic reversals

    Science.gov (United States)

    Stothers, R. B.

    1986-01-01

    Results are presented from an attempt to perform a relatively comprehensive analysis of the evidence for a periodicity, with harmonics, of the observed regular reversals of the earth's magnetic field. The database considered covers 296 reversals over the past 165 Myr. Histograms with bins 1 Myr apart reveal only 30 Myr reversal patterns. The reversal dates are fitted to a linear periodic function and a spectrum is computed for the residuals at the adopted dates. The possible presence of multiple periodicities is evaluated and over various time intervals. The analysis shows that a recently observed 15 Myr periodicity is probably a harmonic of the 29.5-30.5 Myr period. The calculations do not confirm an inherent magnetic reversal property of the earth. The reversals may arise from tectonic events or from impacts from extraterrestrial objects.

  20. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal

    Directory of Open Access Journals (Sweden)

    Mateusz Stoszko

    2016-01-01

    Full Text Available Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4+ T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal.

  1. Online Reverse Auctions for Procurement of Services

    OpenAIRE

    Radkevitch, Uladzimir

    2008-01-01

    textabstractOnline reverse auctions, in which a buyer seeks to select a supplier and suppliers compete for contracts by bidding online, revolutionized corporate procurement early this century. Shortly after they had been pioneered by General Electric, many companies rushed to adopt reverse auctions but the adoption soon slowed down due to the negative effects of auction-induced competition. Today, as firms continue to experiment with the reverse auctions, it is important to understand how the...

  2. Reverse polarization in conjugated heterocycle polythiophene

    Institute of Scientific and Technical Information of China (English)

    王鹿霞; 刘德胜; 张大成; 解士杰; 韩圣浩; 梅良模

    2005-01-01

    Reverse polarization in polythiophene under an applied electric field has been studied in the framework of the tightbinding model. It is found that the applied electronic field has a great influence on the excited states of polythiophene.The effect of the heteroatoms on the polarization has been calculated and analysed carefully. It is indicated that a reverse polarization of biexcitons in polythiophene will be observed more easily. The heteroatoms increase this reversed polarization strength apparently.

  3. Thwarting reverse engineering of machine code

    OpenAIRE

    Pajntar, Sašo

    2011-01-01

    Reverse engineering is a process in which we try to discover the details of software, while we do not have access to its source code. In the diploma thesis we present reverse engineering process on Microsoft Windows operating system. First, we describe PE format and structure of x86 assembler. Then we describe tools, which are used in process of reverse engineering. The focus is on debuggers, dissasemblers and system monitors. We describe functionality of such tools to detect and thwart rever...

  4. Neural correlates of response reversal: considering acquisition.

    Science.gov (United States)

    Budhani, S; Marsh, A A; Pine, D S; Blair, R J R

    2007-02-15

    Previous work on response reversal has typically used a single pair of stimuli that serially reverse. This conflation of acquisition and reversal processes has prevented an examination of the functional role of neural systems implicated in response reversal during acquisition despite the relevance of such data in evaluating accounts of response reversal. In the current study, participants encountered 16 independent reversing stimulus pairs in the context of a probabilistic response reversal paradigm. Functional regions of interest identified as involved in response reversal through a contrast used in the previous literature (punished errors made in the reversal phase versus rewarded correct responses), were interrogated across conditions. Consistent with suggestions that middle frontal cortex codes reward, this region showed significantly greater responses to rewarded rather than punished trials irrespective of accuracy or learning phase (acquisition or reversal). Consistent with the suggestion that this coding of the expectation of reinforcement is acquired via input from the amygdala, we observed significant positive connectivity between activity within the amygdala and a region of rostral anterior cingulate cortex highly proximal to this region of middle frontal/mesial prefrontal cortex. In contrast, inferior frontal cortex, anterior cingulate cortex and caudate showed greater responses to punished errors than to the rewarded correct responses. These three regions also showed significant activation to rewarded errors during acquisition, in contrast to positions suggesting that inferior frontal cortex represents punishment or suppresses previously rewarded responses. Moreover, a connectivity analysis with an anterior cingulate cortex seed revealed highly significant positive connectivity among them. The implications of these data for recent accounts of response reversal and of response reversal impairments in specific neuropsychiatric populations are discussed.

  5. Reversible Lithium Neurotoxicity: Review of the Literature

    OpenAIRE

    Netto, Ivan; Phutane, Vivek H

    2012-01-01

    Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical pre...

  6. Magnetic Reversal in Nanoscopic Ferromagnetic Rings

    OpenAIRE

    Martens, Kirsten; Stein, D. L.; Kent, A. D.

    2004-01-01

    We present a theory of magnetization reversal due to thermal fluctuations in thin submicron-scale rings composed of soft magnetic materials. The magnetization in such geometries is more stable against reversal than that in thin needles and other geometries, where sharp ends or edges can initiate nucleation of a reversed state. The 2D ring geometry also allows us to evaluate the effects of nonlocal magnetostatic forces. We find a `phase transition', which should be experimentally observable, b...

  7. Novel Reversible TSG Gate and Its Application for Designing Components of Primitive Reversible/Quantum ALU

    OpenAIRE

    Thapliyal, Himanshu; Srinivas, M. B

    2006-01-01

    In recent years, reversible logic has emerged as a promising computing paradigm having application in low power CMOS, quantum computing, nanotechnology, and optical computing. The classical set of gates such as AND, OR, and EXOR are not reversible. This paper utilizes a new 4 * 4 reversible gate called TSG gate to build the components of a primitive reversible/quantum ALU. The most significant aspect of the TSG gate is that it can work singly as a reversible full adder, that is reversible ful...

  8. Electromagnetic pollution. Screens accused

    Energy Technology Data Exchange (ETDEWEB)

    Vincent, J.

    1996-04-01

    A recent experiment carried out by M. Bastide (Montpellier University, France) has shown an important increase of mortality, immunosuppression and morphological changes for chicks embryos when submitted to the very low frequency electromagnetic field of a personal computer screen during incubation. Similar effects on pregnant women working in front of cathode ray tubes have never been demonstrated. The paper gives an overview of the epidemiological studies carried out so far to determine the possible noxious effects of electromagnetic fields on public health. In particular, EdF (Electricite de France) has started three different inquiries involving 400000 workmens from electric power industry in order to determine some possible correlation between the exposure to electromagnetic fields and the occurrence of leukemias, brain tumors and melanomas. William Dab, from EdF Medical Studies Service indicates that only a very small relation with the occurrence of brain tumors and acute myeloid leukemias have been shown so far. (J.S.). 4 refs., 2 photos.

  9. Congenital Cataract Screening.

    Science.gov (United States)

    Rajavi, Zhale; Sabbaghi, Hamideh

    2016-01-01

    Congenital cataract is a leading cause of visual deprivation which can damage the developing visual system of a child; therefore early diagnosis, management and long-term follow-up are essential. It is recommended that all neonates be screened by red reflex examination at birth and suspected cases be referred to ophthalmic centers. Early surgery (1 year) is highly recommended. After surgery, amblyopia treatment and periodic follow-up examinations should be started as soon as possible to achieve a satisfactory visual outcome. Practitioners should consider the possibility of posterior capsular opacity, elevated intraocular pressure and amblyopia during follow-up, especially in eyes with microphthalmia and/or associated congenital anomalies. All strabismic children should undergo slit lamp examination prior to strabismus surgery to rule out congenital lens opacities. From a social point of view, equal and fair medical care should be provided to all children regardless of gender. PMID:27621790

  10. Comments on Gaugino Screening

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Timothy; Hook, Anson; Wecht, Brian

    2012-02-15

    Gauge mediated models of supersymmetry breaking often exhibit 'gaugino screening,' where to leading order in F, gaugino masses are unaffected by higher dimensional Kahler potential interactions between the supersymmetry breaking spurion and the messengers. We provide a derivation of this phenomenon which utilizes the gaugino counterterm originally proposed in the context of anomaly mediation by Dine and Seiberg. We argue that this counterterm is present when there are non-zero messenger F-terms, and can cancel the leading order Feynman diagram contribution to the gaugino mass. We provide a nontrivial check of the regulator independence of our results by performing the computation using both dimensional reduction and Pauli-Villars. This analysis reconciles an apparent contradiction between diagrammatics and analytic continuation into superspace.

  11. Congenital cataract screening

    Directory of Open Access Journals (Sweden)

    Zhale Rajavi

    2016-01-01

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

  12. Congenital Cataract Screening

    Science.gov (United States)

    Rajavi, Zhale; Sabbaghi, Hamideh

    2016-01-01

    Congenital cataract is a leading cause of visual deprivation which can damage the developing visual system of a child; therefore early diagnosis, management and long-term follow-up are essential. It is recommended that all neonates be screened by red reflex examination at birth and suspected cases be referred to ophthalmic centers. Early surgery (1 year) is highly recommended. After surgery, amblyopia treatment and periodic follow-up examinations should be started as soon as possible to achieve a satisfactory visual outcome. Practitioners should consider the possibility of posterior capsular opacity, elevated intraocular pressure and amblyopia during follow-up, especially in eyes with microphthalmia and/or associated congenital anomalies. All strabismic children should undergo slit lamp examination prior to strabismus surgery to rule out congenital lens opacities. From a social point of view, equal and fair medical care should be provided to all children regardless of gender. PMID:27621790

  13. The Diagnostic Accuracy of Dementia-Screening Instruments With an Administration Time of 10 to 45 Minutes for Use in Secondary Care : A Systematic Review

    NARCIS (Netherlands)

    Appels, Bregje A.; Scherder, Erik

    2010-01-01

    Early screening for dementia is crucial for identifying reversible causes as well as managing, counseling, and other therapeutic interventions. Many reviews have compared the suitability of very brief screening instruments for use in primary care, but reviews on more extensive instruments in seconda

  14. Delay Reduction in Optimized Reversible Multiplier Circuit

    Directory of Open Access Journals (Sweden)

    Mohammad Assarian

    2012-01-01

    Full Text Available In this study a novel reversible multiplier is presented. Reversible logic can play a significant role in computer domain. This logic can be applied in quantum computing, optical computing processing, DNA computing, and nanotechnology. One condition for reversibility of a computable model is that the number of input equate with the output. Reversible multiplier circuits are the circuits used frequently in computer system. For this reason, optimization in one reversible multiplier circuit can reduce its volume of hardware on one hand and increases the speed in a reversible system on the other hand. One of the important parameters that optimize a reversible circuit is reduction of delays in performance of the circuit. This paper investigates the performance characteristics of the gates, the circuits and methods of optimizing the performance of reversible multiplier circuits. Results showed that reduction of the reversible circuit layers has lead to improved performance due to the reduction of the propagation delay between input and output period. All the designs are in the nanometric scales.

  15. Selection of protective antigens in Lawsonia intracellularis by reverse vaccinology

    DEFF Research Database (Denmark)

    Vadekær, Dorte Fink; Lundegaard, Claus; Riber, Ulla;

    in Denmark. Experimental challenge studies previously performed at DTU-Vet show that a primary infection results in complete protection against reinfection due to induction of immunological memory. We aim to develop a subunit vaccine that mimics the induction of the immune response and hence causes...... protection against L. intracellularis. To this end, a reverse vaccinology approach was applied: the entire L. intracellularis genome encoding 1340 proteins was screened in silico using bioinformatics tools to identify potential protein antigens. Advanced software algorithms predicted 150 secreted and outer...... membrane proteins, and these were analyzed and given a score for presence of B and T cell epitopes. Using another in silico technology platform, which identifies novel B cell antigens eliciting a highly protective immune response, we obtained a second list of potential vaccine candidates. Six proteins were...

  16. Identification of small-molecule agonists of human relaxin family receptor 1 (RXFP1) by using a homogenous cell-based cAMP assay.

    Science.gov (United States)

    Chen, Catherine Z; Southall, Noel; Xiao, Jingbo; Marugan, Juan J; Ferrer, Marc; Hu, Xin; Jones, Raisa E; Feng, Shu; Agoulnik, Irina U; Zheng, Wei; Agoulnik, Alexander I

    2013-07-01

    The relaxin hormone is involved in a variety of biological functions, including female reproduction and parturition, as well as regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein-coupled receptor (GPCR) relaxin family receptor 1 (RXFP1) is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. Although agonists of the receptor could have a wide range of pharmacologic utility, until now there have been no reported small-molecule agonists for relaxin receptors. Here, we report the development of a quantitative high-throughput platform for an RXFP1 agonist screen based on homogenous cell-based HTRF cyclic AMP (cAMP) assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365 677 compounds. Neither compound showed activity in a counterscreen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small-molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists. PMID:23212924

  17. A novel cell-based assay for inhibitory anti-muscarinic type 3 receptor antibodies in primary Sjögren's syndrome.

    Science.gov (United States)

    Bastian, Isabell; Gordon, Tom P; Jackson, Michael W

    2015-12-01

    Inhibitory autoantibodies acting at the muscarinic acetylcholine receptor type 3 (M3R) are postulated to mediate autonomic dysfunction, including decreased salivary and lacrimal gland output and extra-glandular manifestations, in patients with primary Sjögren's syndrome. However, the contention that anti-M3R antibodies are pathogenic in patients remains untested, due to a lack of assays both sophisticated enough to detect inhibitory anti-M3R antibodies yet suitable for screening large patient cohorts. In the current study, we have established a cell-based bioassay of M3R activity, based on dual transfection of the M3R and a luciferase reporter gene. The bioassay is capable of capturing real-time agonist-mediated signalling of the M3R, which is inhibited specifically by patient IgG that have previously been demonstrated to have anti-M3R activity. The assay can be run in multi-well culture plates, and analysed using simple luminescence readers. As such, the new bioassay incorporating M3R-mediated luciferase transduction is the first assay adaptable to common diagnostic platforms that is capable of determining the presence in patient serum of functionally active anti-M3R autoantibodies. The new bioassay should prove useful for large cohort screening studies aiming to correlate the presence in patients of inhibitory anti-M3R antibodies with symptoms of both glandular and extra-glandular autonomic dysfunction. PMID:26584897

  18. Mesenchymal Stem Cells as a Biological Drug for Heart Disease: Where Are We With Cardiac Cell-Based Therapy?

    Science.gov (United States)

    Sanina, Cristina; Hare, Joshua M

    2015-07-17

    Cell-based treatment represents a new generation in the evolution of biological therapeutics. A prototypic cell-based therapy, the mesenchymal stem cell, has successfully entered phase III pivotal trials for heart failure, signifying adequate enabling safety and efficacy data from phase I and II trials. Successful phase III trials can lead to approval of a new biological therapy for regenerative medicine.

  19. Reverse genetics in ecological research.

    Directory of Open Access Journals (Sweden)

    Jens Schwachtje

    Full Text Available By precisely manipulating the expression of individual genetic elements thought to be important for ecological performance, reverse genetics has the potential to revolutionize plant ecology. However, untested concerns about possible side-effects of the transformation technique, caused by Agrobacterium infection and tissue culture, on plant performance have stymied research by requiring onerous sample sizes. We compare 5 independently transformed Nicotiana attenuata lines harboring empty vector control (EVC T-DNA lacking silencing information with isogenic wild types (WT, and measured a battery of ecologically relevant traits, known to be important in plant-herbivore interactions: phytohormones, secondary metabolites, growth and fitness parameters under stringent competitive conditions, and transcriptional regulation with microarrays. As a positive control, we included a line silenced in trypsin proteinase inhibitor gene (TPI expression, a potent anti-herbivore defense known to exact fitness costs in its expression, in the analysis. The experiment was conducted twice, with 10 and 20 biological replicates per genotype. For all parameters, we detected no difference between any EVC and WT lines, but could readily detect a fitness benefit of silencing TPI production. A statistical power analyses revealed that the minimum sample sizes required for detecting significant fitness differences between EVC and WT was 2-3 orders of magnitude larger than the 10 replicates required to detect a fitness effect of TPI silencing. We conclude that possible side-effects of transformation are far too low to obfuscate the study of ecologically relevant phenotypes.

  20. REVERSE LOGISTICS OF ELECTRONICS WASTE

    Directory of Open Access Journals (Sweden)

    ADRIANO NICOLAU SELPIS

    2012-07-01

    Full Text Available The growing demand for electronics equipment, its fast obsolescence, lack of oversight and legislation of its final destination, has contributed them to be discarted in common junk. Electronic equipments and their parts such as computers, TVs, cell phones, refrigerators, batteries, among others, contains highly toxic heavy metals such as mercury, cadmium, arsenic, copper, lead, and others, that if they are burned, pollute the air, besides being potential risk to the health of the garbage collectors, and also, when being in contact with the ground, they can pollute the water table, plants, animals, and consequently affect the human health. Based on research conducted by the analytical-descriptive method, we tried to link the the main threats to the environment and health that the incorrect disposal of waste electronics may represent, as well as identify and present some actions to minimize this impact. It was concluded that the main factors that contribute to the indiscriminate disposal of waste electronics are the lack of legislation to responsibility the manufacturers, strict supervision, tax incentives for the practice of reverse logistics, technology for sophisticated components recycling and environmental education.