A Data Analysis Pipeline Accounting for Artifacts in Tox21 Quantitative High-Throughput Screening Assays.

PubMed

Hsieh, Jui-Hua; Sedykh, Alexander; Huang, Ruili; Xia, Menghang; Tice, Raymond R

2015-08-01

A main goal of the U.S. Tox21 program is to profile a 10K-compound library for activity against a panel of stress-related and nuclear receptor signaling pathway assays using a quantitative high-throughput screening (qHTS) approach. However, assay artifacts, including nonreproducible signals and assay interference (e.g., autofluorescence), complicate compound activity interpretation. To address these issues, we have developed a data analysis pipeline that includes an updated signal noise-filtering/curation protocol and an assay interference flagging system. To better characterize various types of signals, we adopted a weighted version of the area under the curve (wAUC) to quantify the amount of activity across the tested concentration range in combination with the assay-dependent point-of-departure (POD) concentration. Based on the 32 Tox21 qHTS assays analyzed, we demonstrate that signal profiling using wAUC affords the best reproducibility (Pearson's r = 0.91) in comparison with the POD (0.82) only or the AC(50) (i.e., half-maximal activity concentration, 0.81). Among the activity artifacts characterized, cytotoxicity is the major confounding factor; on average, about 8% of Tox21 compounds are affected, whereas autofluorescence affects less than 0.5%. To facilitate data evaluation, we implemented two graphical user interface applications, allowing users to rapidly evaluate the in vitro activity of Tox21 compounds. © 2015 Society for Laboratory Automation and Screening.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

HTS-Net: An integrated regulome-interactome approach for establishing network regulation models in high-throughput screenings

PubMed Central

Rioualen, Claire; Da Costa, Quentin; Chetrit, Bernard; Charafe-Jauffret, Emmanuelle; Ginestier, Christophe

2017-01-01

High-throughput RNAi screenings (HTS) allow quantifying the impact of the deletion of each gene in any particular function, from virus-host interactions to cell differentiation. However, there has been less development for functional analysis tools dedicated to RNAi analyses. HTS-Net, a network-based analysis program, was developed to identify gene regulatory modules impacted in high-throughput screenings, by integrating transcription factors-target genes interaction data (regulome) and protein-protein interaction networks (interactome) on top of screening z-scores. HTS-Net produces exhaustive HTML reports for results navigation and exploration. HTS-Net is a new pipeline for RNA interference screening analyses that proves better performance than simple gene rankings by z-scores, by re-prioritizing genes and replacing them in their biological context, as shown by the three studies that we reanalyzed. Formatted input data for the three studied datasets, source code and web site for testing the system are available from the companion web site at http://htsnet.marseille.inserm.fr/. We also compared our program with existing algorithms (CARD and hotnet2). PMID:28949986

Identification of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

NASA Astrophysics Data System (ADS)

Kong, Cin; Rahman, Noorsaadah Abd; Nathan, Sheila

2014-09-01

The alarming increase of antibiotic-resistant Staphylococcus aureus and a delay in antibiotics development point to the need for novel therapeutic approaches to combat infection. To discover novel anti-infective agents, we screened a number of synthetic compounds comprising mainly of chalcone derivatives to explore their potential in promoting the survival of the nematode Caenorhabditis elegans upon infection by S. aureus. Screening of seven chalcone derivatives using both agar- and liquid-based assays revealed three positive hits that significantly prolonged the survival of S. aureus-infected nematodes. All the hits did not interfere with bacterial growth in vitro, proposing that the three compounds identified most probably act through mechanisms distinct from conventional antibiotics that target bacterial replication.

Confinement effects on electron and phonon degrees of freedom in nanofilm superconductors: A Green function approach

NASA Astrophysics Data System (ADS)

Saniz, R.; Partoens, B.; Peeters, F. M.

2013-02-01

The Green function approach to the Bardeen-Cooper-Schrieffer theory of superconductivity is used to study nanofilms. We go beyond previous models and include effects of confinement on the strength of the electron-phonon coupling as well as on the electronic spectrum and on the phonon modes. Within our approach, we find that in ultrathin films, confinement effects on the electronic screening become very important. Indeed, contrary to what has been advanced in recent years, the sudden increases of the density of states when new bands start to be occupied as the film thickness increases, tend to suppress the critical temperature rather than to enhance it. On the other hand, the increase of the number of phonon modes with increasing number of monolayers in the film leads to an increase in the critical temperature. As a consequence, the superconducting critical parameters in such nanofilms are determined by these two competing effects. Furthermore, in sufficiently thin films, the condensate consists of well-defined subcondensates associated with the occupied bands, each with a distinct coherence length. The subcondensates can interfere constructively or destructively giving rise to an interference pattern in the Cooper pair probability density.

PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS

PubMed Central

2015-01-01

Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chemical basis for these adverse behaviors often goes unexplored in pursuit of lead compounds. Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds. Herein, we characterize the chemical basis for assay interference and promiscuous enzymatic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chemical probes or preclinical candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chemical matter. PMID:25634295

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

PubMed

Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

Image-based RNA interference screening reveals an individual dependence of acute lymphoblastic leukemia on stromal cysteine support

PubMed Central

Marovca, Blerim; Vonderheit, Andreas; Grotzer, Michael A.; Eckert, Cornelia; Cario, Gunnar; Wollscheid, Bernd; Horvath, Peter

2014-01-01

Interactions with the bone marrow microenvironment are essential for leukemia survival and disease progression. We developed an imaging-based RNAi platform to identify protective cues from bone marrow derived mesenchymal stromal cells (MSC) that promote survival of primary acute lymphoblastic leukemia (ALL) cells. Using a candidate gene approach, we detected distinct responses of individual ALL cases to RNA interference with stromal targets. The strongest effects were observed when interfering with solute carrier family 3 member 2 (SLC3A2) expression, which forms the cystine transporter xc− when associated with SLC7A11. Import of cystine and metabolism to cysteine by stromal cells provides the limiting substrate to generate and maintain glutathione in ALL. This metabolic interaction reduces oxidative stress in ALL cells that depend on stromal xc−. Indeed, cysteine depletion using cysteine dioxygenase resulted in leukemia cell death. Thus, functional evaluation of intercellular interactions between leukemia cells and their microenvironment identifies a selective dependency of ALL cells on stromal metabolism for a relevant subgroup of cases, providing new opportunities to develop more personalized approaches to leukemia treatment. PMID:25415224

Dana-Farber Cancer Institute: Genome-wide shRNA Screens with DEMETER Inferred Gene Effects | Office of Cancer Genomics

Cancer.gov

In this study RNA interference (RNAi) screens were performed on 285 cell lines and combined with 216 lines previously screened, which were then analyzed together with DEMETER to discover genetic dependencies across the entire pool of cell lines. Read the abstract

Identification of Small-Molecule Frequent Hitters of Glutathione S-Transferase-Glutathione Interaction.

PubMed

Brenke, Jara K; Salmina, Elena S; Ringelstetter, Larissa; Dornauer, Scarlett; Kuzikov, Maria; Rothenaigner, Ina; Schorpp, Kenji; Giehler, Fabian; Gopalakrishnan, Jay; Kieser, Arnd; Gul, Sheraz; Tetko, Igor V; Hadian, Kamyar

2016-07-01

In high-throughput screening (HTS) campaigns, the binding of glutathione S-transferase (GST) to glutathione (GSH) is used for detection of GST-tagged proteins in protein-protein interactions or enzyme assays. However, many false-positives, so-called frequent hitters (FH), arise that either prevent GST/GSH interaction or interfere with assay signal generation or detection. To identify GST-FH compounds, we analyzed the data of five independent AlphaScreen-based screening campaigns to classify compounds that inhibit the GST/GSH interaction. We identified 53 compounds affecting GST/GSH binding but not influencing His-tag/Ni(2+)-NTA interaction and general AlphaScreen signals. The structures of these 53 experimentally identified GST-FHs were analyzed in chemoinformatic studies to categorize substructural features that promote interference with GST/GSH binding. Here, we confirmed several existing chemoinformatic filters and more importantly extended them as well as added novel filters that specify compounds with anti-GST/GSH activity. Selected compounds were also tested using different antibody-based GST detection technologies and exhibited no interference clearly demonstrating specificity toward their GST/GSH interaction. Thus, these newly described GST-FH will further contribute to the identification of FH compounds containing promiscuous substructures. The developed filters were uploaded to the OCHEM website (http://ochem.eu) and are publicly accessible for analysis of future HTS results. © 2016 Society for Laboratory Automation and Screening.

Phase singularities, correlation singularities, and conditions for complete destructive interference.

PubMed

Rosenbury, Christopher; Gu, Yalong; Gbur, Greg

2012-04-01

A previously derived condition for the complete destructive interference of partially coherent light emerging from a trio of pinholes in an opaque screen is generalized to the case when the coherence properties of the field are asymmetric. It is shown by example that the interference condition is necessary, but not sufficient, and that the existence of complete destructive interference also depends on the intensity of light emerging from the pinholes and the system geometry; more general conditions for such interference are derived. The phase of the wave field exhibits both phase singularities and correlation singularities, and a number of nonintuitive situations in which complete destructive interference occurs are described and explained.

Precursor ion scan driven fast untargeted screening and semi-determination of caffeoylquinic acid derivatives in Cynara scolymus L.

PubMed

Shen, Qing; Lu, Yanbin; Dai, Zhiyuan; Cheung, Hon-Yeung

2015-01-01

A precursor ion scan (PIS) technique based strategy was developed for rapid screening and semi-determination of caffeoylquinic acid derivatives (CADs) in artichoke (Cynara scolymus L.) using ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. 1,5-Dicaffeoylquinic acid and 5-caffeoylquinic acid were used for studying the fragmentation behaviour of two classes of CADs, setting m/z 191 as a diagnostic moiety. When it was applied to artichoke sample, ten CADs were detected and elucidated in a single PIS run. Furthermore, method validation was implemented including: specificity (no interference), linearity (≥0.9993), limit of detection (LOD<0.12 ng mL(-1)) and limit of quantification (LOQ<0.25 ng mL(-1)), precision (RSD≤3.6), recovery (91.4-95.9%) and stability (at least 12 h). This approach was proven to be a powerful, selective and sensitive tool for rapid screening and semi-determination of untargeted components in natural products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dissecting mitochondrial apoptosis pathways by gain-of-function cell culture screens.

PubMed

Grimm, Stefan

2013-05-01

While more primitive organism such as Caenorhabditis elegans and Drosophila melanogaster feature a limited, and by now probably mostly known, array of basic cell death factors, the mammalian cell is replete with additional regulators of the cell's demise. This abundance of apoptosis mediators has made it imperative to set up a systematic inventory of mammalian cell death genes. Genetic screens in this biological system have recently uncovered the rich diversity of cell death signalling and have in particular highlighted mitochondria as an organelle loaded with apoptosis regulators. Many of the screens that have addressed this utilised the novel technique of RNA interference but some also looked at gain-of-functions with transfected cDNAs. Here we give an overview of the rationale for the latter approach, present the genes discovered by this strategy and in particular describe the involvement of mitochondria and their signalling pathways defined by those genes. Copyright © 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Knockdown of genes in the Toll pathway reveals new lethal RNA interference targets for insect pest control.

PubMed

Bingsohn, L; Knorr, E; Billion, A; Narva, K E; Vilcinskas, A

2017-02-01

RNA interference (RNAi) is a promising alternative strategy for ecologically friendly pest management. However, the identification of RNAi candidate genes is challenging owing to the absence of laboratory strains and the seasonality of most pest species. Tribolium castaneum is a well-established model, with a strong and robust RNAi response, which can be used as a high-throughput screening platform to identify potential RNAi target genes. Recently, the cactus gene was identified as a sensitive RNAi target for pest control. To explore whether the spectrum of promising RNAi targets can be expanded beyond those found by random large-scale screening, to encompass others identified using targeted knowledge-based approaches, we constructed a Cactus interaction network. We tested nine genes in this network and found that the delivery of double-stranded RNA corresponding to fusilli and cactin showed lethal effects. The silencing of cactin resulted in 100% lethality at every developmental stage from the larva to the adult. The knockdown of pelle, Dorsal-related immunity factor and short gastrulation reduced or even prevented egg hatching in the next generation. The combination of such targets with lethal and parental RNAi effects can now be tested against different pest species in field studies. © 2016 The Royal Entomological Society.

Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking.

PubMed

Shohdy, Nadim; Efe, Jem A; Emr, Scott D; Shuman, Howard A

2005-03-29

Legionella pneumophila invades and replicates intracellularly in human and protozoan hosts. The bacteria use the Icm/Dot type IVB secretion system to translocate effectors that inhibit phagosome maturation and modulate host vesicle trafficking pathways. To understand how L. pneumophila modulates organelle trafficking in host cells, we carried out pathogen effector protein screening in yeast, identifying L. pneumophila genes that produced membrane trafficking [vacuole protein sorting (VPS)] defects in yeast. We identified four L. pneumophila DNA fragments that perturb sorting of vacuolar proteins. Three encode ORFs of unknown function that are translocated via the Icm/Dot transporter from Legionella into macrophages. VPS inhibitor protein (Vip) A is a coiled-coil protein, VipD is a patatin domain-containing protein, and VipF contains an acetyltransferase domain. Processing studies in yeast indicate that VipA, VipD, and VipF inhibit lysosomal protein trafficking by different mechanisms; overexpressing VipA has an effect on carboxypeptidase Y trafficking, whereas VipD interferes with multivesicular body formation at the late endosome and endoplasmic reticulum-to-Golgi body transport. Such differences highlight the multiple strategies L. pneumophila effectors use to subvert host trafficking processes. Using yeast as an effector gene discovery tool allows for a powerful, genetic approach to both the identification of virulence factors and the study of their function.

Functional Genomic Screening Approaches in Mechanistic Toxicology and Potential Future Applications of CRISPR-Cas9

PubMed Central

Shen, Hua; McHale, Cliona M.; Smith, Martyn T; Zhang, Luoping

2015-01-01

Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Chemical toxicants act by many different mechanisms, however, and the genes involved in adverse outcome pathways (AOPs) and AOP networks are not yet characterized. Functional genomic approaches can reveal both toxicity pathways and susceptibility genes, through knockdown or knockout of all non-essential genes in a cell of interest, and identification of genes associated with a toxicity phenotype following toxicant exposure. Screening approaches in yeast and human near-haploid leukemic KBM7 cells, have identified roles for genes and pathways involved in response to many toxicants but are limited by partial homology among yeast and human genes and limited relevance to normal diploid cells. RNA interference (RNAi) suppresses mRNA expression level but is limited by off-target effects (OTEs) and incomplete knockdown. The recently developed gene editing approach called clustered regularly interspaced short palindrome repeats-associated nuclease (CRISPR)-Cas9, can precisely knock-out most regions of the genome at the DNA level with fewer OTEs than RNAi, in multiple human cell types, thus overcoming the limitations of the other approaches. It has been used to identify genes involved in the response to chemical and microbial toxicants in several human cell types and could readily be extended to the systematic screening of large numbers of environmental chemicals. CRISPR-Cas9 can also repress and activate gene expression, including that of non-coding RNA, with near-saturation, thus offering the potential to more fully characterize AOPs and AOP networks. Finally, CRISPR-Cas9 can generate complex animal models in which to conduct preclinical toxicity testing at the level of individual genotypes or haplotypes. Therefore, CRISPR-Cas9 is a powerful and flexible functional genomic screening approach that can be harnessed to provide unprecedented mechanistic insight in the field of modern toxicology. PMID:26041264

Transcription elongation factors represent in vivo cancer dependencies in glioblastoma

PubMed Central

Miller, Tyler E.; Liau, Brian B.; Wallace, Lisa C.; Morton, Andrew R.; Xie, Qi; Dixit, Deobrat; Factor, Daniel C.; Kim, Leo J. Y.; Morrow, James J.; Wu, Qiulian; Mack, Stephen C.; Hubert, Christopher G.; Gillespie, Shawn M.; Flavahan, William A.; Hoffmann, Thomas; Thummalapalli, Rohit; Hemann, Michael T.; Paddison, Patrick J.; Horbinski, Craig M.; Zuber, Johannes; Scacheri, Peter C.; Bernstein, Bradley E.; Tesar, Paul J.; Rich, Jeremy N.

2017-01-01

Glioblastoma is a universally lethal cancer with a median survival of approximately 15 months1. Despite substantial efforts to define druggable targets, there are no therapeutic options that meaningfully extend glioblastoma patient lifespan. While previous work has largely focused on in vitro cellular models, here we demonstrate a more physiologically relevant approach to target discovery in glioblastoma. We adapted pooled RNA interference (RNAi) screening technology2–4 for use in orthotopic patient-derived xenograft (PDX) models, creating a high-throughput negative selection screening platform in a functional in vivo tumour microenvironment. Using this approach, we performed parallel in vivo and in vitro screens and discovered that the chromatin and transcriptional regulators necessary for cell survival in vivo are non-overlapping with those required in vitro. We identified transcription pause-release and elongation factors as one set of in vivo-specific cancer dependencies and determined that these factors are necessary for enhancer-mediated transcriptional adaptations that enable cells to survive the tumour microenvironment. Our lead hit, JMJD6, mediates the upregulation of in vivo stress and stimulus response pathways through enhancer-mediated transcriptional pause-release, promoting cell survival specifically in vivo. Targeting JMJD6 or other identified elongation factors extends survival in orthotopic xenograft mouse models, supporting targeting the transcription elongation machinery as a therapeutic strategy for glioblastoma. More broadly, this study demonstrates the power of in vivo phenotypic screening to identify new classes of ‘cancer dependencies’ not identified by previous in vitro approaches, which could supply untapped opportunities for therapeutic intervention. PMID:28678782

CRISPR–Cas9 Genetic Analysis of Virus–Host Interactions

PubMed Central

Gebre, Makda; Nomburg, Jason L.; Gewurz, Benjamin E.

2018-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) has greatly expanded the ability to genetically probe virus–host interactions. CRISPR systems enable focused or systematic, genomewide studies of nearly all aspects of a virus lifecycle. Combined with its relative ease of use and high reproducibility, CRISPR is becoming an essential tool in studies of the host factors important for viral pathogenesis. Here, we review the use of CRISPR–Cas9 for the loss-of-function analysis of host dependency factors. We focus on the use of CRISPR-pooled screens for the systematic identification of host dependency factors, particularly in Epstein–Barr virus-transformed B cells. We also discuss the use of CRISPR interference (CRISPRi) and gain-of-function CRISPR activation (CRISPRa) approaches to probe virus–host interactions. Finally, we comment on the future directions enabled by combinatorial CRISPR screens. PMID:29385696

In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

PubMed Central

Miller, Peter G.; Al-Shahrour, Fatima; Hartwell, Kimberly A.; Chu, Lisa P.; Järås, Marcus; Puram, Rishi V.; Puissant, Alexandre; Callahan, Kevin P.; Ashton, John; McConkey, Marie E.; Poveromo, Luke P.; Cowley, Glenn S.; Kharas, Michael G.; Labelle, Myriam; Shterental, Sebastian; Fujisaki, Joji; Silberstein, Lev; Alexe, Gabriela; Al-Hajj, Muhammad A.; Shelton, Christopher A.; Armstrong, Scott A.; Root, David E.; Scadden, David T.; Hynes, Richard O.; Mukherjee, Siddhartha; Stegmaier, Kimberly; Jordan, Craig T.; Ebert, Benjamin L.

2013-01-01

SUMMARY We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. PMID:23770013

CRISPR-Cas9 Genetic Analysis of Virus-Host Interactions.

PubMed

Gebre, Makda; Nomburg, Jason L; Gewurz, Benjamin E

2018-01-30

Clustered regularly interspaced short palindromic repeats (CRISPR) has greatly expanded the ability to genetically probe virus-host interactions. CRISPR systems enable focused or systematic, genomewide studies of nearly all aspects of a virus lifecycle. Combined with its relative ease of use and high reproducibility, CRISPR is becoming an essential tool in studies of the host factors important for viral pathogenesis. Here, we review the use of CRISPR-Cas9 for the loss-of-function analysis of host dependency factors. We focus on the use of CRISPR-pooled screens for the systematic identification of host dependency factors, particularly in Epstein-Barr virus-transformed B cells. We also discuss the use of CRISPR interference (CRISPRi) and gain-of-function CRISPR activation (CRISPRa) approaches to probe virus-host interactions. Finally, we comment on the future directions enabled by combinatorial CRISPR screens.

The Moire Effect in Physics Teaching.

ERIC Educational Resources Information Center

Bernero, Bruce

1989-01-01

The Moire pattern is the shimmering pattern which looks like an odd interference pattern in window screens or folds of nylon shower curtain. Illustrates some of the ways the effect may be used, including demonstration of wave interference, detection of small displacement, persistence of vision, contour measurement, beats, and optical clearness.…

Construction of siRNA/miRNA expression vectors based on a one-step PCR process

PubMed Central

Xu, Jun; Zeng, Jie Qiong; Wan, Gang; Hu, Gui Bin; Yan, Hong; Ma, Li Xin

2009-01-01

Background RNA interference (RNAi) has become a powerful means for silencing target gene expression in mammalian cells and is envisioned to be useful in therapeutic approaches to human disease. In recent years, high-throughput, genome-wide screening of siRNA/miRNA libraries has emerged as a desirable approach. Current methods for constructing siRNA/miRNA expression vectors require the synthesis of long oligonucleotides, which is costly and suffers from mutation problems. Results Here we report an ingenious method to solve traditional problems associated with construction of siRNA/miRNA expression vectors. We synthesized shorter primers (< 50 nucleotides) to generate a linear expression structure by PCR. The PCR products were directly transformed into chemically competent E. coli and converted to functional vectors in vivo via homologous recombination. The positive clones could be easily screened under UV light. Using this method we successfully constructed over 500 functional siRNA/miRNA expression vectors. Sequencing of the vectors confirmed a high accuracy rate. Conclusion This novel, convenient, low-cost and highly efficient approach may be useful for high-throughput assays of RNAi libraries. PMID:19490634

Fluorescence-based high-throughput screening of dicer cleavage activity.

PubMed

Podolska, Katerina; Sedlak, David; Bartunek, Petr; Svoboda, Petr

2014-03-01

Production of small RNAs by ribonuclease III Dicer is a key step in microRNA and RNA interference pathways, which employ Dicer-produced small RNAs as sequence-specific silencing guides. Further studies and manipulations of microRNA and RNA interference pathways would benefit from identification of small-molecule modulators. Here, we report a study of a fluorescence-based in vitro Dicer cleavage assay, which was adapted for high-throughput screening. The kinetic assay can be performed under single-turnover conditions (35 nM substrate and 70 nM Dicer) in a small volume (5 µL), which makes it suitable for high-throughput screening in a 1536-well format. As a proof of principle, a small library of bioactive compounds was analyzed, demonstrating potential of the assay.

Stroop interference and food intake.

PubMed

Overduin, J; Jansen, A; Louwerse, E

1995-11-01

The Stroop task is aimed at assessing attentional bias. Words are displayed one by one on a computer screen and subjects are instructed to name the color in which every word is printed. The attentional bias is supposed to be reflected in the extent to which the word meanings interfere with the speed of color naming: The longer the color naming latency, the larger the attentional bias. Experiments using this task have demonstrated attentional bias for eating and body shape-related words in bulimic, anorexic, and restrained subjects. Explanations of these results have generally been formulated in terms of restricted food intake or emotional concerns about food and body shape-related themes. In contrast, in the present article it was proposed that Stroop interference might reflect a tendency either to withdraw or approach food or body shape-related stimuli. Fifty-one subjects (25 unrestrained, 26 restrained) were administered a Stroop task containing neutral, food, and body shape-related words. There were two conditions to which subjects were randomly allocated: the "appetizer" and "no-appetizer" condition. The appetizer was a bit of pudding to be ingested by the subject just before the Stroop task. Following the Stroop task an ice cream taste test was presented in which the subjects were allowed to eat as much as they liked. The amount of ice cream eaten was registered secretly. The results show that in unrestrained subjects Stroop interference for food words was found only in the appetizer condition. Restrained subjects, however, showed a permanent interference for food words. A significant correlation of .58 between Stroop food-word interference and ice cream intake was found only in unrestrained subjects. In restrained eaters the correlation was near 0. No effect of condition or restraint was found on Stroop body shape-word interference. The findings indicate that (1) ingestion of an appetizer seems to have evoked an attentional bias for food words in nonrestraints that correlated with food intake; (2) restrained eaters showed continuous attentional bias. This appears to support the urge-to-act explanation of Stroop interference. The lack of correlation between restraints' attentional bias and ad lib food intake could have been caused by inhibition of approach which is one of the characteristics of restrained eating: The present procedure seems not to have triggered disinhibited eating in these subjects. Among other things it is concluded that Stroop interference, as a measure of "craving" triggered by food cue, might be a useful aid in assessing the risk of relapse in treated binge eating patients.

Adaptive measurement selection for progressive damage estimation

NASA Astrophysics Data System (ADS)

Zhou, Wenfan; Kovvali, Narayan; Papandreou-Suppappola, Antonia; Chattopadhyay, Aditi; Peralta, Pedro

2011-04-01

Noise and interference in sensor measurements degrade the quality of data and have a negative impact on the performance of structural damage diagnosis systems. In this paper, a novel adaptive measurement screening approach is presented to automatically select the most informative measurements and use them intelligently for structural damage estimation. The method is implemented efficiently in a sequential Monte Carlo (SMC) setting using particle filtering. The noise suppression and improved damage estimation capability of the proposed method is demonstrated by an application to the problem of estimating progressive fatigue damage in an aluminum compact-tension (CT) sample using noisy PZT sensor measurements.

Fluorescence Reporter-Based Genome-Wide RNA Interference Screening to Identify Alternative Splicing Regulators.

PubMed

Misra, Ashish; Green, Michael R

2017-01-01

Alternative splicing is a regulated process that leads to inclusion or exclusion of particular exons in a pre-mRNA transcript, resulting in multiple protein isoforms being encoded by a single gene. With more than 90 % of human genes known to undergo alternative splicing, it represents a major source for biological diversity inside cells. Although in vitro splicing assays have revealed insights into the mechanisms regulating individual alternative splicing events, our global understanding of alternative splicing regulation is still evolving. In recent years, genome-wide RNA interference (RNAi) screening has transformed biological research by enabling genome-scale loss-of-function screens in cultured cells and model organisms. In addition to resulting in the identification of new cellular pathways and potential drug targets, these screens have also uncovered many previously unknown mechanisms regulating alternative splicing. Here, we describe a method for the identification of alternative splicing regulators using genome-wide RNAi screening, as well as assays for further validation of the identified candidates. With modifications, this method can also be adapted to study the splicing regulation of pre-mRNAs that contain two or more splice isoforms.

High-throughput screens in mammalian cells using the CRISPR-Cas9 system.

PubMed

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

2015-06-01

As a powerful genome-editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR)-clustered regularly interspaced short palindromic repeats-associated protein 9 (Cas9) system has been quickly developed into a large-scale function-based screening strategy in mammalian cells. This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. Compared with RNA interference screening, the CRISPR-Cas9 system demonstrates much higher levels of effectiveness and reliability with respect to both loss-of-function and gain-of-function screening. Unlike the RNA interference strategy, a CRISPR-Cas9 library can target both protein-coding sequences and regulatory elements, including promoters, enhancers and elements transcribing microRNAs and long noncoding RNAs. This powerful genetic tool will undoubtedly accelerate the mechanistic discovery of various biological processes. In this mini review, we summarize the general procedure of CRISPR-Cas9 library mediated functional screening, system optimization strategies and applications of this new genetic toolkit. © 2015 FEBS.

A Cellular High-Throughput Screening Approach for Therapeutic trans-Cleaving Ribozymes and RNAi against Arbitrary mRNA Disease Targets

PubMed Central

Yau, Edwin H.; Butler, Mark C.; Sullivan, Jack M.

2016-01-01

Major bottlenecks in development of therapeutic post transcriptional gene silencing (PTGS) agents (e.g. ribozymes, RNA interference, antisense) include the challenge of mapping rare accessible regions of the mRNA target that are open for annealing and cleavage, testing and optimization of agents in human cells to identify lead agents, testing for cellular toxicity, and preclinical evaluation in appropriate animal models of disease. Methods for rapid and reliable cellular testing of PTGS agents are needed to identify potent lead candidates for optimization. Our goal was to develop a means of rapid assessment of many RNA agents to identify a lead candidate for a given mRNA associated with a disease state. We developed a rapid human cell-based screening platform to test efficacy of hammerhead ribozyme (hhRz) or RNA interference (RNAi) constructs, using a model retinal degeneration target, human rod opsin (RHO) mRNA. The focus is on RNA Drug Discovery for diverse retinal degeneration targets. To validate the approach, candidate hhRzs were tested against NUH↓ cleavage sites (N=G,C,A,U; H=C,A,U) within the target mRNA of secreted alkaline phosphatase (SEAP), a model gene expression reporter, based upon in silico predictions of mRNA accessibility. HhRzs were embedded in a larger stable adenoviral VAI RNA scaffold for high cellular expression, cytoplasmic trafficking, and stability. Most hhRz expression plasmids exerted statistically significant knockdown of extracellular SEAP enzyme activity when readily assayed by a fluorescence enzyme assay intended for high throughput screening (HTS). Kinetics of PTGS knockdown of cellular targets is measureable in live cells with the SEAP reporter. The validated SEAP HTS platform was transposed to identify lead PTGS agents against a model hereditary retinal degeneration target, RHO mRNA. Two approaches were used to physically fuse the model retinal gene target mRNA to the SEAP reporter mRNA. The most expedient way to evaluate a large set of potential VAI-hhRz expression plasmids against diverse NUH↓ cleavage sites uses cultured human HEK293S cells stably expressing a dicistronic Target-IRES-SEAP target fusion mRNA. Broad utility of this rational RNA drug discovery approach is feasible for any ophthalmological disease-relevant mRNA targets and any disease mRNA targets in general. The approach will permit rank ordering of PTGS agents based on potency to identify a lead therapeutic compound for further optimization. PMID:27233447

Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens

PubMed Central

Meliopoulos, Victoria A.; Andersen, Lauren E.; Birrer, Katherine F.; Simpson, Kaylene J.; Lowenthal, John W.; Bean, Andrew G. D.; Stambas, John; Stewart, Cameron R.; Tompkins, S. Mark; van Beusechem, Victor W.; Fraser, Iain; Mhlanga, Musa; Barichievy, Samantha; Smith, Queta; Leake, Devin; Karpilow, Jon; Buck, Amy; Jona, Ghil; Tripp, Ralph A.

2012-01-01

Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.—Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. PMID:22247330

Single-target RNA interference for the blockade of multiple interacting proinflammatory and profibrotic pathways in cardiac fibroblasts.

PubMed

Tank, Juliane; Lindner, Diana; Wang, Xiaomin; Stroux, Andrea; Gilke, Leona; Gast, Martina; Zietsch, Christin; Skurk, Carsten; Scheibenbogen, Carmen; Klingel, Karin; Lassner, Dirk; Kühl, Uwe; Schultheiss, Heinz-Peter; Westermann, Dirk; Poller, Wolfgang

2014-01-01

Therapeutic targets of broad relevance are likely located in pathogenic pathways common to disorders of various etiologies. Screening for targets of this type revealed CCN genes to be consistently upregulated in multiple cardiomyopathies. We developed RNA interference (RNAi) to silence CCN2 and found this single-target approach to block multiple proinflammatory and profibrotic pathways in activated primary cardiac fibroblasts (PCFBs). The RNAi-strategy was developed in murine PCFBs and then investigated in "individual" human PCFBs grown from human endomyocardial biopsies (EMBs). Screening of short hairpin RNA (shRNA) sequences for high silencing efficacy and specificity yielded RNAi adenovectors silencing CCN2 in murine or human PCFBs, respectively. Comparison of RNAi with CCN2-modulating microRNA (miR) vectors expressing miR-30c or miR-133b showed higher efficacy of RNAi. In murine PCFBs, CCN2 silencing resulted in strongly reduced expression of stretch-induced chemokines (Ccl2, Ccl7, Ccl8), matrix metalloproteinases (MMP2, MMP9), extracellular matrix (Col3a1), and a cell-to-cell contact protein (Cx43), suggesting multiple signal pathways to be linked to CCN2. Immune cell chemotaxis towards CCN2-depleted PCFBs was significantly reduced. We demonstrate here that this RNAi strategy is technically applicable to "individual" human PCFBs, too, but that these display individually strikingly different responses to CCN2 depletion. Either genomically encoded factors or stable epigenetic modification may explain different responses between individual PCFBs. The new RNAi approach addresses a key regulator protein induced in cardiomyopathies. Investigation of this and other molecular therapies in individual human PCBFs may help to dissect differential pathogenic processes between otherwise similar disease entities and individuals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Plackett-Burman and Box-Behnken designs as chemometric tools for micro-determination of L-Ornithine

NASA Astrophysics Data System (ADS)

Elazazy, Marwa S.; El-Hamshary, Marwa; Sakr, Marwa; Al-Easa, Hala S.

2018-03-01

Plackett-Burman (PB) and Box-Behnken (BB) screening and response surface factorial designs were used to evaluate spectrophotometric and spectrofluorimetric approaches for the determination of L-Ornithine (ORN) as per se and in dietary supplements. Both approaches were based on the derivatization of the primary amino group of ORN via Hantzsch condensation reaction producing yellow coloured adducts (dihydrolutidine derivative). The reaction product was determined spectrophotometrically (method A) at λmax = 327 nm and spectrofluorimetrically (method B) at 480 nm (λem) after excitation at 325 nm (λex). A multivariate scheme was tailored to investigate the process numerical variables; reaction temperature, heating time, reagent volume, and pH implementing PB as a screening design followed by BB as an optimization strategy. Categorical factors including diluting solvent and sequence of addition were kept invariable. Responses of the reaction systems were the maximum absorbance (Y1) and maximum fluorescence intensity (Y2), correspondingly. Quality tools as well as ANOVA testing, before and after response transformation were used to decide upon the substantial variables. Following the optimization of reaction variables using desirability plots, calibration graphs were found to be rectilinear in the range of 6-14 μg/mL and 0.4-1.2 μg/mL for methods A and B, respectively. Both methods proved to be sensitive with detection limits (DL) of 337 and 85 ng/mL, and quantitation limits (QL) of 1086 and 283 ng/mL, for methods A and B, respectively. An interference study was performed using potential foreign species. No significant interference effect was observed on any of the proposed procedures. System performance was addressed following ICH guidelines and considering parameters such as linearity, detection and quantification limits, accuracy and precision, robustness and specificity.

Identifying Breast Tumor Suppressors Using in Vitro and in Vivo RNAi Screens

DTIC Science & Technology

2011-10-01

vivo RNA interference screen, breast cancer , tumor suppressor, leukemia inhibitory factor receptor (LIFR) 16. SECURITY CLASSIFICATION OF: 17...The identification of these genes will improve the understanding of the causes of breast cancer , which may lead to therapeutic advancements for... breast cancer prevention and treatment. BODY Objective 1: Identification of breast tumor suppressors using in vitro and in vivo RNAi screens

A Data Analysis Pipeline Accounting for Artifacts in Tox21 Quantitative High-Throughput Screening Assays

PubMed Central

Hsieh, Jui-Hua; Sedykh, Alexander; Huang, Ruili; Xia, Menghang; Tice, Raymond R.

2015-01-01

A main goal of the U.S. Tox21 program is to profile a 10K-compound library for activity against a panel of stress-related and nuclear receptor signaling pathway assays using a quantitative high-throughput screening (qHTS) approach. However, assay artifacts, including nonreproducible signals and assay interference (e.g., autofluorescence), complicate compound activity interpretation. To address these issues, we have developed a data analysis pipeline that includes an updated signal noise–filtering/curation protocol and an assay interference flagging system. To better characterize various types of signals, we adopted a weighted version of the area under the curve (wAUC) to quantify the amount of activity across the tested concentration range in combination with the assay-dependent point-of-departure (POD) concentration. Based on the 32 Tox21 qHTS assays analyzed, we demonstrate that signal profiling using wAUC affords the best reproducibility (Pearson's r = 0.91) in comparison with the POD (0.82) only or the AC50 (i.e., half-maximal activity concentration, 0.81). Among the activity artifacts characterized, cytotoxicity is the major confounding factor; on average, about 8% of Tox21 compounds are affected, whereas autofluorescence affects less than 0.5%. To facilitate data evaluation, we implemented two graphical user interface applications, allowing users to rapidly evaluate the in vitro activity of Tox21 compounds. PMID:25904095

A Perspective on the Future of High-Throughput RNAi Screening: Will CRISPR Cut Out the Competition or Can RNAi Help Guide the Way?

PubMed

Taylor, Jessica; Woodcock, Simon

2015-09-01

For more than a decade, RNA interference (RNAi) has brought about an entirely new approach to functional genomics screening. Enabling high-throughput loss-of-function (LOF) screens against the human genome, identifying new drug targets, and significantly advancing experimental biology, RNAi is a fast, flexible technology that is compatible with existing high-throughput systems and processes; however, the recent advent of clustered regularly interspaced palindromic repeats (CRISPR)-Cas, a powerful new precise genome-editing (PGE) technology, has opened up vast possibilities for functional genomics. CRISPR-Cas is novel in its simplicity: one piece of easily engineered guide RNA (gRNA) is used to target a gene sequence, and Cas9 expression is required in the cells. The targeted double-strand break introduced by the gRNA-Cas9 complex is highly effective at removing gene expression compared to RNAi. Together with the reduced cost and complexity of CRISPR-Cas, there is the realistic opportunity to use PGE to screen for phenotypic effects in a total gene knockout background. This review summarizes the exciting development of CRISPR-Cas as a high-throughput screening tool, comparing its future potential to that of well-established RNAi screening techniques, and highlighting future challenges and opportunities within these disciplines. We conclude that the two technologies actually complement rather than compete with each other, enabling greater understanding of the genome in relation to drug discovery. © 2015 Society for Laboratory Automation and Screening.

An integrated high resolution mass spectrometric data acquisition method for rapid screening of saponins in Panax notoginseng (Sanqi).

PubMed

Lai, Chang-Jiang-Sheng; Tan, Ting; Zeng, Su-Ling; Qi, Lian-Wen; Liu, Xin-Guang; Dong, Xin; Li, Ping; Liu, E-Hu

2015-05-10

The aim of this study was to develop a convenient method without pretreatments for nontarget discovery of interested compounds. The segment and exposure strategy, coupled with two mass spectrometer data acquisition methods was firstly proposed for screening the saponins in extract of Panax notoginseng (Sanqi) via high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS). By gradually removing certain major or moderate interference compounds, the developed segment and exposure strategy could significantly improve the detection efficiency for trace compounds. Moreover, the newly developed five-point screening approach based on a modified mass defect filter strategy and the visual isotopic ion technique was verified to be efficient and reliable in picking out the interested precursor ions. In total, 234 ginsenosides including 67 potential new ones were characterized or tentatively identified from the extract of Sanqi. Particularly, some unusual compounds containing the branched glycosyl group or new substituted acyl groups were firstly reported. The proposed integrated strategy held a strong promise for analyses of the complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficient elimination of nonstoichiometric enzyme inhibitors from HTS hit lists.

PubMed

Habig, Michael; Blechschmidt, Anke; Dressler, Sigmar; Hess, Barbara; Patel, Viral; Billich, Andreas; Ostermeier, Christian; Beer, David; Klumpp, Martin

2009-07-01

High-throughput screening often identifies not only specific, stoichiometrically binding inhibitors but also undesired compounds that unspecifically interfere with the targeted activity by nonstoichiometrically binding, unfolding, and/or inactivating proteins. In this study, the effect of such unwanted inhibitors on several different enzyme targets was assessed based on screening results for over a million compounds. In particular, the shift in potency on variation of enzyme concentration was used as a means to identify nonstoichiometric inhibitors among the screening hits. These potency shifts depended on both compound structure and target enzyme. The approach was confirmed by statistical analysis of thousands of dose-response curves, which showed that the potency of competitive and therefore clearly stoichiometric inhibitors was not affected by increasing enzyme concentration. Light-scattering measurements of thermal protein unfolding further verified that compounds that stabilize protein structure by stoichiometric binding show the same potency irrespective of enzyme concentration. In summary, measuring inhibitor IC(50) values at different enzyme concentrations is a simple, cost-effective, and reliable method to identify and eliminate compounds that inhibit a specific target enzyme via nonstoichiometric mechanisms.

Novel biotechnology approaches in colorectal cancer diagnosis and therapy.

PubMed

Kavousipour, Soudabeh; Khademi, Fathemeh; Zamani, Mozhdeh; Vakili, Bahareh; Mokarram, Pooneh

2017-06-01

With ever-increasing molecular information about colorectal cancer (CRC), there is an expectation to detect more sensitive and specific molecular markers for new advanced diagnostic methods that can surpass the limitations of current screening tests. Moreover, enhanced molecular pathology knowledge about cancer has led to the development of targeted therapies, designed to interfere with specific aberrant biological pathways in cancer. Furthermore, biotechnology has opened a new window in CRC diagnosis and treatment by introducing different application of antibodies, antibody fragments, non-Ig scaffold proteins, and aptamers in targeted therapy and drug delivery. This review summarizes the molecular diagnostic and therapeutic approaches in CRC with a focus on genetic and epigenetic alterations, protein and metabolite markers as well as targeted therapy and drug delivery by Ig-scaffold proteins, non-Ig scaffold proteins, nanobodies, and aptamers.

RNAi Screening with Self-Delivering, Synthetic siRNAs for Identification of Genes That Regulate Primary Human T Cell Migration.

PubMed

Freeley, Michael; Derrick, Emily; Dempsey, Eugene; Hoff, Antje; Davies, Anthony; Leake, Devin; Vermeulen, Annaleen; Kelleher, Dermot; Long, Aideen

2015-09-01

Screening of RNA interference (RNAi) libraries in primary T cells is labor-intensive and technically challenging because these cells are hard to transfect. Chemically modified, self-delivering small interfering RNAs (siRNAs) offer a solution to this problem, because they enter hard-to-transfect cell types without needing a delivery reagent and are available in library format for RNAi screening. In this study, we have screened a library of chemically modified, self-delivering siRNAs targeting the expression of 72 distinct genes in conjunction with an image-based high-content-analysis platform as a proof-of-principle strategy to identify genes involved in lymphocyte function-associated antigen-1 (LFA-1)-mediated migration in primary human T cells. Our library-screening strategy identified the small GTPase RhoA as being crucial for T cell polarization and migration in response to LFA-1 stimulation and other migratory ligands. We also demonstrate that multiple downstream assays can be performed within an individual RNAi screen and have used the remainder of the cells for additional assays, including cell viability and adhesion to ICAM-1 (the physiological ligand for LFA-1) in the absence or presence of the chemokine SDF-1α. This study therefore demonstrates the ease and benefits of conducting siRNA library screens in primary human T cells using self-delivering, chemically modified siRNAs, and it emphasizes the feasibility and potential of this approach for elucidating the signaling pathways that regulate T cell function. © 2015 Society for Laboratory Automation and Screening.

Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches

PubMed Central

Ekland, Eric H.; Schneider, Jessica; Fidock, David A.

2011-01-01

Malarial parasites have evolved resistance to all previously used therapies, and recent evidence suggests emerging resistance to the first-line artemisinins. To identify antimalarials with novel mechanisms of action, we have developed a high-throughput screen targeting the apicoplast organelle of Plasmodium falciparum. Antibiotics known to interfere with this organelle, such as azithromycin, exhibit an unusual phenotype whereby the progeny of drug-treated parasites die. Our screen exploits this phenomenon by assaying for “delayed death” compounds that exhibit a higher potency after two cycles of intraerythrocytic development compared to one. We report a primary assay employing parasites with an integrated copy of a firefly luciferase reporter gene and a secondary flow cytometry-based assay using a nucleic acid stain paired with a mitochondrial vital dye. Screening of the U.S. National Institutes of Health Clinical Collection identified known and novel antimalarials including kitasamycin. This inexpensive macrolide, used for agricultural applications, exhibited an in vitro IC50 in the 50 nM range, comparable to the 30 nM activity of our control drug, azithromycin. Imaging and pharmacologic studies confirmed kitasamycin action against the apicoplast, and in vivo activity was observed in a murine malaria model. These assays provide the foundation for high-throughput campaigns to identify novel chemotypes for combination therapies to treat multidrug-resistant malaria.—Ekland, E. H., Schneider, J., Fidock, D. A. Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches. PMID:21746861

The C. elegans Excretory Canal as a Model for Intracellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis in a Single Cell: labeling by GFP-fusions, RNAi Interaction Screen and Imaging.

PubMed

Zhang, Nan; Membreno, Edward; Raj, Susan; Zhang, Hongjie; Khan, Liakot A; Gobel, Verena

2017-10-03

The four C. elegans excretory canals are narrow tubes extended through the length of the animal from a single cell, with almost equally far extended intracellular endotubes that build and stabilize the lumen with a membrane and submembraneous cytoskeleton of apical character. The excretory cell expands its length approximately 2,000 times to generate these canals, making this model unique for the in vivo assessment of de novo polarized membrane biogenesis, intracellular lumen morphogenesis and unicellular tubulogenesis. The protocol presented here shows how to combine standard labeling, gain- and loss-of-function genetic or RNA interference (RNAi)-, and microscopic approaches to use this model to visually dissect and functionally analyze these processes on a molecular level. As an example of a labeling approach, the protocol outlines the generation of transgenic animals with fluorescent fusion proteins for live analysis of tubulogenesis. As an example of a genetic approach, it highlights key points of a visual RNAi-based interaction screen designed to modify a gain-of-function cystic canal phenotype. The specific methods described are how to: label and visualize the canals by expressing fluorescent proteins; construct a targeted RNAi library and strategize RNAi screening for the molecular analysis of canal morphogenesis; visually assess modifications of canal phenotypes; score them by dissecting fluorescence microscopy; characterize subcellular canal components at higher resolution by confocal microscopy; and quantify visual parameters. The approach is useful for the investigator who is interested in taking advantage of the C. elegans excretory canal for identifying and characterizing genes involved in the phylogenetically conserved processes of intracellular lumen and unicellular tube morphogenesis.

Research into the usage of integrated jamming of IR weakening and smoke-screen resisting the IR imaging guided missiles

NASA Astrophysics Data System (ADS)

Wang, Long-tao; Jiang, Ning; Lv, Ming-shan

2015-10-01

With the emergence of the anti-ship missle with the capability of infrared imaging guidance, the traditional single jamming measures, because of the jamming mechanism and technical flaws or unsuitable use, greatly reduced the survival probability of the war-ship in the future naval battle. Intergrated jamming of IR weakening + smoke-screen Can not only make jamming to the search and tracking of IR imaging guidance system , but also has feasibility in conjunction, besides , which also make the best jamming effect. The research conclusion has important realistic meaning for raising the antimissile ability of surface ships. With the development of guidance technology, infrared guidance system has expanded by ir point-source homing guidance to infrared imaging guidance, Infrared imaging guidance has made breakthrough progress, Infrared imaging guidance system can use two-dimensional infrared image information of the target, achieve the precise tracking. Which has Higher guidance precision, better concealment, stronger anti-interference ability and could Target the key parts. The traditional single infrared smoke screen jamming or infrared decoy flare interference cannot be imposed effective interference. So, Research how to effectively fight against infrared imaging guided weapons threat measures and means, improving the surface ship antimissile ability is an urgent need to solve.

Trace lead analysis based on carbon-screen-printed-electrodes modified via 4-carboxy-phenyl diazonium salt electroreduction.

PubMed

Bouden, Sarra; Chaussé, Annie; Dorbes, Stephane; El Tall, Omar; Bellakhal, Nizar; Dachraoui, Mohamed; Vautrin-Ul, Christine

2013-03-15

This paper describes the use of 4-carboxyphenyl-grafted screen-printed carbon electrodes (4-CP-SPEs) for trace lead analysis. These novel and simple use of electrodes were easily prepared by the electrochemical reduction of the corresponding diazonium salt. Pb detection was then performed by a three-steps method in order to avoid oxygen interference: (i) immersion of the grafted screen-printed electrode (SPE) in the sample and adsorption of Pb(II), (ii) reduction of adsorbed Pb(II) by chronoamperometry (CA), and (iii) oxidation of Pb by Anodic Square Wave Voltammetry (SWV). The reoxidation response was exploited for lead detection and quantification. In order to optimize the analytical responses, the influence of the adsorption medium pH and the adsorption time were investigated. Moreover, an interference study was carried out with Cu(II), Hg(II), Al(III), Mn(II), Zn(II), Cd(II) and no major interference can be expected to quantify Pb(II). The described method provided a limit of detection and a limit of quantification of 1.2 × 10(-9)M and 4.1 × 10(-9)M, respectively. These performances indicate that the 4-CP-SPE could be considered as an efficient tool for environmental analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Language and the Cultural Life of a Child. (Lenguaje y Cultura de La Vida de un Nino).

ERIC Educational Resources Information Center

Buckenmeyer, Robert

These guidelines offer information necessary to define, organize, and implement a screening program for preschool children that identifies suspected physical, behavioral, and educational problems that may interfere with children's ability to achieve success in school. An Early Screening Program (ESP) utilizes testing devices to aid problem…

In Vitro Toxicity Screening Technique for Volatile Substances ...

EPA Pesticide Factsheets

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the challenge is that many of these chemicals are volatile and not amenable to HTS robotic liquid handling applications. We assembled an in vitro cell culture apparatus capable of screening volatile chemicals for toxicity with potential for miniaturization for high throughput. BEAS-2B lung cells were grown in an enclosed culture apparatus under air-liquid interface (ALI) conditions, and exposed to an array of xenobiotics in 5% CO2. Use of ALI conditions allows direct contact of cells with a gas xenobiotic, as well as release of endogenous gaseous molecules without interference by medium on the apical surface. To identify potential xenobiotic-induced perturbations in cell homeostasis, we monitored for alterations of endogenously-produced gaseous molecules in air directly above the cells, termed “headspace”. Alterations in specific endogenously-produced gaseous molecules (e.g., signaling molecules nitric oxide (NO) and carbon monoxide (CO) in headspace is indicative of xenobiotic-induced perturbations of specific cellular processes. Additionally, endogenously produced volatile organic compounds (VOCs) may be monitored in a nonspecific, discovery manner to determine whether cell processes are

Minimizing the effects of oxygen interference on l-lactate sensors by a single amino acid mutation in Aerococcus viridansl-lactate oxidase.

PubMed

Hiraka, Kentaro; Kojima, Katsuhiro; Lin, Chi-En; Tsugawa, Wakako; Asano, Ryutaro; La Belle, Jeffrey T; Sode, Koji

2018-04-30

l-lactate biosensors employing l-lactate oxidase (LOx) have been developed mainly to measure l-lactate concentration for clinical diagnostics, sports medicine, and the food industry. Some l-lactate biosensors employ artificial electron mediators, but these can negatively impact the detection of l-lactate by competing with the primary electron acceptor: molecular oxygen. In this paper, a strategic approach to engineering an AvLOx that minimizes the effects of oxygen interference on sensor strips was reported. First, we predicted an oxygen access pathway in Aerococcus viridans LOx (AvLOx) based on its crystal structure. This was subsequently blocked by a bulky amino acid substitution. The resulting Ala96Leu mutant showed a drastic reduction in oxidase activity using molecular oxygen as the electron acceptor and a small increase in dehydrogenase activity employing an artificial electron acceptor. Secondly, the Ala96Leu mutant was immobilized on a screen-printed carbon electrode using glutaraldehyde cross-linking method. Amperometric analysis was performed with potassium ferricyanide as an electron mediator under argon or atmospheric conditions. Under argon condition, the response current increased linearly from 0.05 to 0.5mM l-lactate for both wild-type and Ala96Leu. However, under atmospheric conditions, the response of wild-type AvLOx electrode was suppressed by 9-12% due to oxygen interference. The Ala96Leu mutant maintained 56-69% of the response current at the same l-lactate level and minimized the relative bias error to -19% from -49% of wild-type. This study provided significant insight into the enzymatic reaction mechanism of AvLOx and presented a novel approach to minimize oxygen interference in sensor applications, which will enable accurate detection of l-lactate concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Incorporating interaction networks into the determination of functionally related hit genes in genomic experiments with Markov random fields

PubMed Central

Robinson, Sean; Nevalainen, Jaakko; Pinna, Guillaume; Campalans, Anna; Radicella, J. Pablo; Guyon, Laurent

2017-01-01

Abstract Motivation: Incorporating gene interaction data into the identification of ‘hit’ genes in genomic experiments is a well-established approach leveraging the ‘guilt by association’ assumption to obtain a network based hit list of functionally related genes. We aim to develop a method to allow for multivariate gene scores and multiple hit labels in order to extend the analysis of genomic screening data within such an approach. Results: We propose a Markov random field-based method to achieve our aim and show that the particular advantages of our method compared with those currently used lead to new insights in previously analysed data as well as for our own motivating data. Our method additionally achieves the best performance in an independent simulation experiment. The real data applications we consider comprise of a survival analysis and differential expression experiment and a cell-based RNA interference functional screen. Availability and implementation: We provide all of the data and code related to the results in the paper. Contact: sean.j.robinson@utu.fi or laurent.guyon@cea.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28881978

Applications of Biophysics in High-Throughput Screening Hit Validation.

PubMed

Genick, Christine Clougherty; Barlier, Danielle; Monna, Dominique; Brunner, Reto; Bé, Céline; Scheufler, Clemens; Ottl, Johannes

2014-06-01

For approximately a decade, biophysical methods have been used to validate positive hits selected from high-throughput screening (HTS) campaigns with the goal to verify binding interactions using label-free assays. By applying label-free readouts, screen artifacts created by compound interference and fluorescence are discovered, enabling further characterization of the hits for their target specificity and selectivity. The use of several biophysical methods to extract this type of high-content information is required to prevent the promotion of false positives to the next level of hit validation and to select the best candidates for further chemical optimization. The typical technologies applied in this arena include dynamic light scattering, turbidometry, resonance waveguide, surface plasmon resonance, differential scanning fluorimetry, mass spectrometry, and others. Each technology can provide different types of information to enable the characterization of the binding interaction. Thus, these technologies can be incorporated in a hit-validation strategy not only according to the profile of chemical matter that is desired by the medicinal chemists, but also in a manner that is in agreement with the target protein's amenability to the screening format. Here, we present the results of screening strategies using biophysics with the objective to evaluate the approaches, discuss the advantages and challenges, and summarize the benefits in reference to lead discovery. In summary, the biophysics screens presented here demonstrated various hit rates from a list of ~2000 preselected, IC50-validated hits from HTS (an IC50 is the inhibitor concentration at which 50% inhibition of activity is observed). There are several lessons learned from these biophysical screens, which will be discussed in this article. © 2014 Society for Laboratory Automation and Screening.

An Evaluation of the Eclox Chemiluminescence Test, Hach Pesticide/Nerve Agent Test Strips, and Agri-Screen Test Tickets

DTIC Science & Technology

2010-06-30

Interference Testing Our testing shows that it is unlikely that the Eclox Chemiluminescence Test will respond to the common disinfectant chloramine ...common disinfectants (chlorine and chloramine ), cyanobacterial byproducts (geosmin and MIB) or water quality parameters (humic/fulvic acids or water...toxicity sensor testing Table 2-2: Interferences Test Chemicals Concentration (mg/L) Chlorine 10 Chloramines 10 Geosmin 0.0001 Methyl-isoborneol

Highly Sensitive Aluminium(III) Ion Sensor Based on a Self-assembled Monolayer on a Gold Nanoparticles Modified Screen-printed Carbon Electrode.

PubMed

See, Wong Pooi; Heng, Lee Yook; Nathan, Sheila

2015-01-01

A new approach for the development of a highly sensitive aluminium(III) ion sensor via the preconcentration of aluminium(III) ion with a self-assembled monolayer on a gold nanoparticles modified screen-printed carbon electrode and current mediation by potassium ferricyanide redox behavior during aluminium(III) ion binding has been attempted. A monolayer of mercaptosuccinic acid served as an effective complexation ligand for the preconcentration of trace aluminium; this led to an enhancement of aluminium(III) ion capture and thus improved the sensitivity of the sensor with a detection limit of down to the ppb level. Under the optimum experimental conditions, the sensor exhibited a wide linear dynamic range from 0.041 to 12.4 μM. The lower detection limit of the developed sensor was 0.037 μM (8.90 ppb) using a 10 min preconcentration time. The sensor showed excellent selectivity towards aluminium(III) ion over other interference ions.

Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians.

PubMed

Newmark, Phillip A; Reddien, Peter W; Cebrià, Francesc; Sánchez Alvarado, Alejandro

2003-09-30

Freshwater planarian flatworms are capable of regenerating complete organisms from tiny fragments of their bodies; the basis for this regenerative prowess is an experimentally accessible stem cell population that is present in the adult planarian. The study of these organisms, classic experimental models for investigating metazoan regeneration, has been revitalized by the application of modern molecular biological approaches. The identification of thousands of unique planarian ESTs, coupled with large-scale whole-mount in situ hybridization screens, and the ability to inhibit planarian gene expression through double-stranded RNA-mediated genetic interference, provide a wealth of tools for studying the molecular mechanisms that regulate tissue regeneration and stem cell biology in these organisms. Here we show that, as in Caenorhabditis elegans, ingestion of bacterially expressed double-stranded RNA can inhibit gene expression in planarians. This inhibition persists throughout the process of regeneration, allowing phenotypes with disrupted regenerative patterning to be identified. These results pave the way for large-scale screens for genes involved in regenerative processes.

Total cross sections for electron scattering by 1-propanol at impact energies in the range 40-500 eV

NASA Astrophysics Data System (ADS)

da Silva, D. G. M.; Gomes, M.; Ghosh, S.; Silva, I. F. L.; Pires, W. A. D.; Jones, D. B.; Blanco, F.; Garcia, G.; Buckman, S. J.; Brunger, M. J.; Lopes, M. C. A.

2017-11-01

Absolute total cross section (TCS) measurements for electron scattering from 1-propanol molecules are reported for impact energies from 40 to 500 eV. These measurements were obtained using a new apparatus developed at Juiz de Fora Federal University—Brazil, which is based on the measurement of the attenuation of a collimated electron beam through a gas cell containing the molecules to be studied at a given pressure. Besides these experimental measurements, we have also calculated TCS using the Independent-Atom Model with Screening Corrected Additivity Rule and Interference (IAM-SCAR+I) approach with the level of agreement between them being typically found to be very good.

Considerations involved with the use of semipermeable membrane devices for monitoring environmental contaminants

USGS Publications Warehouse

Petty, J.D.; Orazio, C.E.; Huckins, J.N.; Gale, R.W.; Lebo, J.A.; Meadows, J.C.; Echols, K.R.; Cranor, W.L.

2000-01-01

Semipermeable membrane devices (SPMDs) are used with increasing frequency, and throughout the world as samplers of organic contaminants. The devices can be used to detect a variety of lipophilic chemicals in water, sediment/soil, and air. SPMDs are designed to sample nonpolar, hydrophobic chemicals. The maximum concentration factor achievable for a particular chemical is proportional to its octanol–water partition coefficient. Techniques used for cleanup of SPMD extracts for targeted analytes and for general screening by full-scan mass spectrometry do not differ greatly from techniques used for extracts of other matrices. However, SPMD extracts contain potential interferences that are specific to the membrane–lipid matrix. Procedures have been developed or modified to alleviate these potential interferences. The SPMD approach has been demonstrated to be applicable to sequestering and analyzing a wide array of environmental contaminants including organochlorine pesticides, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, polychlorinated dioxins and dibenzofurans, selected organophosphate pesticides and pyrethroid insecticides, and other nonpolar organic chemicals. We present herein an overview of effective procedural steps for analyzing exposed SPMDs for trace to ultra-trace levels of contaminants sequestered from environmental matrices.

"Dip-and-read" paper-based analytical devices using distance-based detection with color screening.

PubMed

Yamada, Kentaro; Citterio, Daniel; Henry, Charles S

2018-05-15

An improved paper-based analytical device (PAD) using color screening to enhance device performance is described. Current detection methods for PADs relying on the distance-based signalling motif can be slow due to the assay time being limited by capillary flow rates that wick fluid through the detection zone. For traditional distance-based detection motifs, analysis can take up to 45 min for a channel length of 5 cm. By using a color screening method, quantification with a distance-based PAD can be achieved in minutes through a "dip-and-read" approach. A colorimetric indicator line deposited onto a paper substrate using inkjet-printing undergoes a concentration-dependent colorimetric response for a given analyte. This color intensity-based response has been converted to a distance-based signal by overlaying a color filter with a continuous color intensity gradient matching the color of the developed indicator line. As a proof-of-concept, Ni quantification in welding fume was performed as a model assay. The results of multiple independent user testing gave mean absolute percentage error and average relative standard deviations of 10.5% and 11.2% respectively, which were an improvement over analysis based on simple visual color comparison with a read guide (12.2%, 14.9%). In addition to the analytical performance comparison, an interference study and a shelf life investigation were performed to further demonstrate practical utility. The developed system demonstrates an alternative detection approach for distance-based PADs enabling fast (∼10 min), quantitative, and straightforward assays.

Design, Fabrication and Characterization of Micro Opto-Electro-Mechanical Systems.

DTIC Science & Technology

1995-12-01

interference problems (see Fig. 3-6). Improvements in the lithography of the MCNC process would allow for grating spaces of less than 2 gm and therefore...A micro-spectrometer has been fabricated using LIGA, an acronym for lithography , electroforming, and micromolding (the acronym came from the German...location for test samples and an adjustable mirror. The beams are brought back together to form an interference pattern. At an observation screen the

Chemical Approaches to Control Gene Expression

PubMed Central

Gottesfeld, Joel M.; Turner, James M.; Dervan, Peter B.

2000-01-01

A current goal in molecular medicine is the development of new strategies to interfere with gene expression in living cells in the hope that novel therapies for human disease will result from these efforts. This review focuses on small-molecule or chemical approaches to manipulate gene expression by modulating either transcription of messenger RNA-coding genes or protein translation. The molecules under study include natural products, designed ligands, and compounds identified through functional screens of combinatorial libraries. The cellular targets for these molecules include DNA, messenger RNA, and the protein components of the transcription, RNA processing, and translational machinery. Studies with model systems have shown promise in the inhibition of both cellular and viral gene transcription and mRNA utilization. Moreover, strategies for both repression and activation of gene transcription have been described. These studies offer promise for treatment of diseases of pathogenic (viral, bacterial, etc.) and cellular origin (cancer, genetic diseases, etc.). PMID:11097426

Analysis of Stem Cell Motility In Vivo Based on Immunodetection of Planarian Neoblasts and Tracing of BrdU-Labeled Cells After Partial Irradiation.

PubMed

Tasaki, Junichi; Uchiyama-Tasaki, Chihiro; Rouhana, Labib

2016-01-01

Planarian flatworms have become an important system for the study of stem cell behavior and regulation in vivo. These organisms are able to regenerate any part of their body upon damage or amputation. A crucial cellular event in the process of planarian regeneration is the migration of pluripotent stem cells (known as neoblasts) to the site of injury. Here we describe two approaches for analyzing migration of planarian stem cells to an area where these have been ablated by localized X-ray irradiation. The first approach involves immunolabeling of mitotic neoblasts, while the second is based on tracing stem cells and their progeny after BrdU incorporation. The use of planarians in studies of cell motility is suitable for the identification of factors that influence stem cell migration in vivo and is amenable to RNA interference or pharmacological screening.

Reflection Coefficients.

ERIC Educational Resources Information Center

Greenslade, Thomas B., Jr.

1994-01-01

Discusses and provides an example of reflectivity approximation to determine whether reflection will occur. Provides a method to show thin-film interference on a projection screen. Also applies the reflectivity concepts to electromagnetic wave systems. (MVL)

Interference of daratumumab with pretransfusion testing, mimicking a high-titer, low avidity like antibody.

PubMed

Lin, Mei-Hwa; Liu, Fei-Yun; Wang, Hsiu-Mien; Cho, Hsin-Ching; Lo, Shyh-Chyi

2017-01-01

Daratumumab is a monoclonal immunoglobulin against CD38 and has been approved for treating patients with refractory multiple myeloma. The presence of daratumumab in the sera can interfere with pretransfusion testing due to the weakly expression of CD38 on red cells. The reactivity could be mistaken as autoantibody (if autocontrol is positive) or alloantibody (if autocontrol is negative). We present a case that demonstrates daratumumab could mimic a high titer low avidity (HTLA) alloantibody. A 34-year-old male patient of refractory myeloma was recruited in phase three clinical trial involving daratumumab. Samples were sent to the blood bank for pretransfusion testing. Without knowledge of patient having used daratumumab, we mistook the reactivity in the patient's sera as an HTLA antibody due to the results of negative autocontrol and high titers of antibody activity. Antibody screen showed a panreactive pattern and the reactivity against screening cells was up to a titer of 1: 1240. The reactivity was weaker against cord cells than adult cells, became weaker against ZZAP-treated cells and became negative against DDT-treated cells. A discussion with attending physician finally revealed the reactivity was due to the interference caused by daratumumab. The case demonstrates good communication is essential in performing pretransfusion testing for patients receiving daratumumab and other new biological regimens that can interfere with compatibility test.

Interference of daratumumab with pretransfusion testing, mimicking a high-titer, low avidity like antibody

PubMed Central

Lin, Mei-Hwa; Liu, Fei-Yun; Wang, Hsiu-Mien; Cho, Hsin-Ching; Lo, Shyh-Chyi

2017-01-01

Daratumumab is a monoclonal immunoglobulin against CD38 and has been approved for treating patients with refractory multiple myeloma. The presence of daratumumab in the sera can interfere with pretransfusion testing due to the weakly expression of CD38 on red cells. The reactivity could be mistaken as autoantibody (if autocontrol is positive) or alloantibody (if autocontrol is negative). We present a case that demonstrates daratumumab could mimic a high titer low avidity (HTLA) alloantibody. A 34-year-old male patient of refractory myeloma was recruited in phase three clinical trial involving daratumumab. Samples were sent to the blood bank for pretransfusion testing. Without knowledge of patient having used daratumumab, we mistook the reactivity in the patient's sera as an HTLA antibody due to the results of negative autocontrol and high titers of antibody activity. Antibody screen showed a panreactive pattern and the reactivity against screening cells was up to a titer of 1: 1240. The reactivity was weaker against cord cells than adult cells, became weaker against ZZAP-treated cells and became negative against DDT-treated cells. A discussion with attending physician finally revealed the reactivity was due to the interference caused by daratumumab. The case demonstrates good communication is essential in performing pretransfusion testing for patients receiving daratumumab and other new biological regimens that can interfere with compatibility test. PMID:28970695

Understanding the Transformation, Speciation, and Hazard Potential of Copper Particles in a Model Septic Tank System using Zebrafish to Monitor the Effluent

PubMed Central

Lin, Sijie; Taylor, Alicia A.; Zhaoxia, Ji; Chang, Chong Hyun; Kinsinger, Nichola M.; Ueng, William; Walker, Sharon L.; Nel, André E.

2015-01-01

Although copper-containing nanoparticles are used in commercial products such as fungicides and bactericides, we presently do not understand the environmental impact on other organisms that may be inadvertently exposed. In this study, we used the zebrafish embryo as a screening tool to study the potential impact of two nano Cu-based materials, CuPRO and Kocide, in comparison to nano-sized and micron-sized Cu and CuO particles in their pristine form (0 – 10 ppm) as well as following their transformation in an experimental wastewater treatment system. This was accomplished by construction of a modeled domestic septic tank system from which effluents could be retrieved at different stages following particle introduction (10 ppm). The Cu speciation in the effluent was identified as non-dissolvable inorganic Cu(H2PO2)2 and non-diffusible organic Cu by X-ray diffraction, inductively coupled plasma mass spectrometry (ICP-MS), diffusive gradients in thin-films (DGT), and Visual MINTEQ software. While the nanoscale materials, including the commercial particles, were clearly more potent (showing 50% hatching interference above 0.5 ppm) than the micron-scale particulates with no effect on hatching up to 10 ppm, the Cu released from the particles in the septic tank underwent transformation into non-bioavailable species that failed to interfere with the function of the zebrafish embryo hatching enzyme. Moreover, we demonstrate that the addition of humic acid, as an organic carbon component, could lead to a dose-dependent decrease in Cu toxicity in our high content zebrafish embryo screening assay. Thus, the use of zebrafish embryo screening, in combination with the effluents obtained from a modeled exposure environment, enables a bioassay approach to follow the change in the speciation, and hazard potential of Cu particles instead of difficult-to-perform direct particle tracking. PMID:25625504

Understanding the transformation, speciation, and hazard potential of copper particles in a model septic tank system using zebrafish to monitor the effluent.

PubMed

Lin, Sijie; Taylor, Alicia A; Ji, Zhaoxia; Chang, Chong Hyun; Kinsinger, Nichola M; Ueng, William; Walker, Sharon L; Nel, André E

2015-02-24

Although copper-containing nanoparticles are used in commercial products such as fungicides and bactericides, we presently do not understand the environmental impact on other organisms that may be inadvertently exposed. In this study, we used the zebrafish embryo as a screening tool to study the potential impact of two nano Cu-based materials, CuPRO and Kocide, in comparison to nanosized and micron-sized Cu and CuO particles in their pristine form (0-10 ppm) as well as following their transformation in an experimental wastewater treatment system. This was accomplished by construction of a modeled domestic septic tank system from which effluents could be retrieved at different stages following particle introduction (10 ppm). The Cu speciation in the effluent was identified as nondissolvable inorganic Cu(H2PO2)2 and nondiffusible organic Cu by X-ray diffraction, inductively coupled plasma mass spectrometry (ICP-MS), diffusive gradients in thin-films (DGT), and Visual MINTEQ software. While the nanoscale materials, including the commercial particles, were clearly more potent (showing 50% hatching interference above 0.5 ppm) than the micron-scale particulates with no effect on hatching up to 10 ppm, the Cu released from the particles in the septic tank underwent transformation into nonbioavailable species that failed to interfere with the function of the zebrafish embryo hatching enzyme. Moreover, we demonstrate that the addition of humic acid, as an organic carbon component, could lead to a dose-dependent decrease in Cu toxicity in our high content zebrafish embryo screening assay. Thus, the use of zebrafish embryo screening, in combination with the effluents obtained from a modeled exposure environment, enables a bioassay approach to follow the change in the speciation and hazard potential of Cu particles instead of difficult-to-perform direct particle tracking.

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

PubMed

Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako

2014-02-28

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.

Quantitative CRISPR interference screens in yeast identify chemical-genetic interactions and new rules for guide RNA design.

PubMed

Smith, Justin D; Suresh, Sundari; Schlecht, Ulrich; Wu, Manhong; Wagih, Omar; Peltz, Gary; Davis, Ronald W; Steinmetz, Lars M; Parts, Leopold; St Onge, Robert P

2016-03-08

Genome-scale CRISPR interference (CRISPRi) has been used in human cell lines; however, the features of effective guide RNAs (gRNAs) in different organisms have not been well characterized. Here, we define rules that determine gRNA effectiveness for transcriptional repression in Saccharomyces cerevisiae. We create an inducible single plasmid CRISPRi system for gene repression in yeast, and use it to analyze fitness effects of gRNAs under 18 small molecule treatments. Our approach correctly identifies previously described chemical-genetic interactions, as well as a new mechanism of suppressing fluconazole toxicity by repression of the ERG25 gene. Assessment of multiple target loci across treatments using gRNA libraries allows us to determine generalizable features associated with gRNA efficacy. Guides that target regions with low nucleosome occupancy and high chromatin accessibility are clearly more effective. We also find that the best region to target gRNAs is between the transcription start site (TSS) and 200 bp upstream of the TSS. Finally, unlike nuclease-proficient Cas9 in human cells, the specificity of truncated gRNAs (18 nt of complementarity to the target) is not clearly superior to full-length gRNAs (20 nt of complementarity), as truncated gRNAs are generally less potent against both mismatched and perfectly matched targets. Our results establish a powerful functional and chemical genomics screening method and provide guidelines for designing effective gRNAs, which consider chromatin state and position relative to the target gene TSS. These findings will enable effective library design and genome-wide programmable gene repression in many genetic backgrounds.

Research and Development of Hazardous/Toxic Waste Analytical Screening Procedures. Available Field Methods for Rapid Screening of Hazardous Waste Materials at Waste Sites (Class A Poisons).

DTIC Science & Technology

1982-01-01

bromide is listed as a positive interference. Nitric oxide and nitrogen dioxide can be detected by using the Draeger nitrous fumes detector tube. A... fumes exhibit a delay from the time of exposure to the onset of symptoms. This time delay would not be conducive for a rapid field screening test. It...Dangerous when strongly heated, emits highly toxic fumes . THRESHOLD LIMIT VALUE: No information available PHYSIOLOGICAL EFFECTS: A. Intensely irritating to

The EAP Part of Personnel Function.

ERIC Educational Resources Information Center

Delaney, Thomas J., Jr.

1987-01-01

Substance abuse among workers and its interference with job performance has remained constant over the past 15 years. Employee assistance programs educate the public, screen referrals, and provide feedback on how employees are progressing. (JOW)

Article Screening System

NASA Technical Reports Server (NTRS)

Fernandez, Kenneth R. (Inventor)

2004-01-01

During the last ten years patents directed to luggage scanning apparatus began to appear in the patent art. Absent from the variety of approaches in the art is stereoscopic imaging that entails exposing two or more images of the same object, each taken from a slightly different perspective. If the perspectives are too different, that is. if there is too much separation of the X-ray exposures, the image will look flat. Yet with a slight separation, a stereo separation, interference occurs. Herein a system is provided for the production of stereo pairs. One perspective, a left or a right perspective angle, is first established. Next, the other perspective angle is computed. Using these left and right perspectives the X-ray sources can then be spaced away from each other.

A sensitive electrochemical immunosensor based on poly(2-aminobenzylamine) film modified screen-printed carbon electrode for label-free detection of human immunoglobulin G.

PubMed

Putnin, Thitirat; Jumpathong, Watthanachai; Laocharoensuk, Rawiwan; Jakmunee, Jaroon; Ounnunkad, Kontad

2018-08-01

This work focuses on fabricating poly(2-aminobenzylamine)-modified screen-printed carbon electrode as an electrochemical immunosensor for the label-free detection of human immunoglobulin G. To selectively detect immunoglobulin G, the anti-immunoglobulin G antibody with high affinity to immunoglobulin G was covalently linked with the amine group of poly(2-aminobenzylamine) film-deposited screen-printed carbon electrode. The selectivity for immunoglobulin G was subsequently assured by being challenged with redox-active interferences and adventitious adsorption did not significantly interfere the analyte signal. To obviate the use of costly secondary antibody, the [Fe(CN) 6 ] 4-/3- redox probe was instead applied to measure the number of human immunoglobulin G through the immunocomplex formation that is quantitatively related to the level of the differential pulse voltammetric current. The resulting immunosensor exhibited good sensitivity with the detection limit of 0.15 ng mL -1 , limit of quantitation of 0.50 ng mL -1 and the linear range from 1.0 to 50 ng mL -1 . Given those striking analytical performances and the affordability arising from using cheap screen-printed carbon electrode with label-free detection, the immunosensor serves as a promising model for the next-step development of a diagnostic tool.

Another look at retroactive and proactive interference: a quantitative analysis of conversion processes.

PubMed

Blank, Hartmut

2005-02-01

Traditionally, the causes of interference phenomena were sought in "real" or "hard" memory processes such as unlearning, response competition, or inhibition, which serve to reduce the accessibility of target items. I propose an alternative approach which does not deny the influence of such processes but highlights a second, equally important, source of interference-the conversion (Tulving, 1983) of accessible memory information into memory performance. Conversion is conceived as a problem-solving-like activity in which the rememberer tries to find solutions to a memory task. Conversion-based interference effects are traced to different conversion processes in the experimental and control conditions of interference designs. I present a simple theoretical model that quantitatively predicts the resulting amount of interference. In two paired-associate learning experiments using two different types of memory tests, these predictions were corroborated. Relations of the present approach to traditional accounts of interference phenomena and implications for eyewitness testimony are discussed.

Investigation of Interference Models for RFID Systems.

PubMed

Zhang, Linchao; Ferrero, Renato; Gandino, Filippo; Rebaudengo, Maurizio

2016-02-04

The reader-to-reader collision in an RFID system is a challenging problem for communications technology. In order to model the interference between RFID readers, different interference models have been proposed, mainly based on two approaches: single and additive interference. The former only considers the interference from one reader within a certain range, whereas the latter takes into account the sum of all of the simultaneous interferences in order to emulate a more realistic behavior. Although the difference between the two approaches has been theoretically analyzed in previous research, their effects on the estimated performance of the reader-to-reader anti-collision protocols have not yet been investigated. In this paper, the influence of the interference model on the anti-collision protocols is studied by simulating a representative state-of-the-art protocol. The results presented in this paper highlight that the use of additive models, although more computationally intensive, is mandatory to improve the performance of anti-collision protocols.

A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors.

PubMed

Esposito, Marta; Szadocka, Sára; Degiacomi, Giulia; Orena, Beatrice S; Mori, Giorgia; Piano, Valentina; Boldrin, Francesca; Zemanová, Júlia; Huszár, Stanislav; Barros, David; Ekins, Sean; Lelièvre, Joel; Manganelli, Riccardo; Mattevi, Andrea; Pasca, Maria Rosalia; Riccardi, Giovanna; Ballell, Lluis; Mikušová, Katarína; Chiarelli, Laurent R

2017-06-09

Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds. To this purpose the publically available GlaxoSmithKline antimycobacterial compound set was assayed, uncovering a series of 4-(pyridin-2-yl)thiazole derivatives which efficiently inhibit the Mycobacterium tuberculosis PyrG enzyme activity, one of them showing low activity against the human CTP synthetase. The three best compounds were ATP binding site competitive inhibitors, with K i values ranging from 3 to 20 μM, but did not show any activity against a small panel of different prokaryotic and eukaryotic kinases, thus demonstrating specificity for the CTP synthetases. Metabolic labeling experiments demonstrated that the compounds directly interfere not only with CTP biosynthesis, but also with other CTP dependent biochemical pathways, such as lipid biosynthesis. Moreover, using a M. tuberculosis pyrG conditional knock-down strain, it was shown that the activity of two compounds is dependent on the intracellular concentration of the CTP synthetase. All these results strongly suggest a role of PyrG as a target of these compounds, thus strengthening the value of this kind of approach for the identification of new scaffolds for drug development.

High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

PubMed Central

Li, Xiaolan; Milan Bonotto, Rafaela; No, Joo Hwan; Kim, Keum Hyun; Baek, Sungmin; Kim, Hee Young; Windisch, Marc Peter; Pamplona Mosimann, Ana Luiza; de Borba, Luana; Liuzzi, Michel; Hansen, Michael Adsetts Edberg; Nunes Duarte dos Santos, Claudia; Freitas-Junior, Lucio Holanda

2013-01-01

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. PMID:23437413

Assessing HTS Performance Using BioAssay Ontology: Screening and Analysis of a Bacterial Phospho-N-Acetylmuramoyl-Pentapeptide Translocase Campaign

PubMed Central

Moberg, Andreas; Hansson, Eva; Boyd, Helen

2014-01-01

Abstract With the public availability of biochemical assays and screening data constantly increasing, new applications for data mining and method analysis are evolving in parallel. One example is BioAssay Ontology (BAO) for systematic classification of assays based on screening setup and metadata annotations. In this article we report a high-throughput screening (HTS) against phospho-N-acetylmuramoyl-pentapeptide translocase (MraY), an attractive antibacterial drug target involved in peptidoglycan synthesis. The screen resulted in novel chemistry identification using a fluorescence resonance energy transfer assay. To address a subset of the false positive hits, a frequent hitter analysis was performed using an approach in which MraY hits were compared with hits from similar assays, previously used for HTS. The MraY assay was annotated according to BAO and three internal reference assays, using a similar assay design and detection technology, were identified. Analyzing the assays retrospectively, it was clear that both MraY and the three reference assays all showed a high false positive rate in the primary HTS assays. In the case of MraY, false positives were efficiently identified by applying a method to correct for compound interference at the hit-confirmation stage. Frequent hitter analysis based on the three reference assays with similar assay method identified additional false actives in the primary MraY assay as frequent hitters. This article demonstrates how assays annotated using BAO terms can be used to identify closely related reference assays, and that analysis based on these assays clearly can provide useful data to influence assay design, technology, and screening strategy. PMID:25415593

Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles

PubMed Central

Michailidis, George

2014-01-01

Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction problem. However, such data can be limited in size and/or are expensive to acquire. On the other hand, observational data of the organism in steady state (e.g., wild-type) are more readily available, but their informational content is inadequate for the task at hand. We develop a computational approach to appropriately utilize both data sources for estimating a regulatory network. The proposed approach is based on a three-step algorithm to estimate the underlying directed but cyclic network, that uses as input both perturbation screens and steady state gene expression data. In the first step, the algorithm determines causal orderings of the genes that are consistent with the perturbation data, by combining an exhaustive search method with a fast heuristic that in turn couples a Monte Carlo technique with a fast search algorithm. In the second step, for each obtained causal ordering, a regulatory network is estimated using a penalized likelihood based method, while in the third step a consensus network is constructed from the highest scored ones. Extensive computational experiments show that the algorithm performs well in reconstructing the underlying network and clearly outperforms competing approaches that rely only on a single data source. Further, it is established that the algorithm produces a consistent estimate of the regulatory network. PMID:24586224

Semantic and Syntactic Interference in Sentence Comprehension: A Comparison of Working Memory Models

PubMed Central

Tan, Yingying; Martin, Randi C.; Van Dyke, Julie A.

2017-01-01

This study investigated the nature of the underlying working memory system supporting sentence processing through examining individual differences in sensitivity to retrieval interference effects during sentence comprehension. Interference effects occur when readers incorrectly retrieve sentence constituents which are similar to those required during integrative processes. We examined interference arising from a partial match between distracting constituents and syntactic and semantic cues, and related these interference effects to performance on working memory, short-term memory (STM), vocabulary, and executive function tasks. For online sentence comprehension, as measured by self-paced reading, the magnitude of individuals' syntactic interference effects was predicted by general WM capacity and the relation remained significant when partialling out vocabulary, indicating that the effects were not due to verbal knowledge. For offline sentence comprehension, as measured by responses to comprehension questions, both general WM capacity and vocabulary knowledge interacted with semantic interference for comprehension accuracy, suggesting that both general WM capacity and the quality of semantic representations played a role in determining how well interference was resolved offline. For comprehension question reaction times, a measure of semantic STM capacity interacted with semantic but not syntactic interference. However, a measure of phonological capacity (digit span) and a general measure of resistance to response interference (Stroop effect) did not predict individuals' interference resolution abilities in either online or offline sentence comprehension. The results are discussed in relation to the multiple capacities account of working memory (e.g., Martin and Romani, 1994; Martin and He, 2004), and the cue-based retrieval parsing approach (e.g., Lewis et al., 2006; Van Dyke et al., 2014). While neither approach was fully supported, a possible means of reconciling the two approaches and directions for future research are proposed. PMID:28261133

Visualizing the Solute Vaporization Interference in Flame Atomic Absorption Spectroscopy

ERIC Educational Resources Information Center

Dockery, Christopher R.; Blew, Michael J.; Goode, Scott R.

2008-01-01

Every day, tens of thousands of chemists use analytical atomic spectroscopy in their work, often without knowledge of possible interferences. We present a unique approach to study these interferences by using modern response surface methods to visualize an interference in which aluminum depresses the calcium atomic absorption signal. Calcium…

STK33 kinase activity is nonessential in KRAS-dependent cancer cells.

PubMed

Babij, Carol; Zhang, Yihong; Kurzeja, Robert J; Munzli, Anke; Shehabeldin, Amro; Fernando, Manory; Quon, Kim; Kassner, Paul D; Ruefli-Brasse, Astrid A; Watson, Vivienne J; Fajardo, Flordeliza; Jackson, Angela; Zondlo, James; Sun, Yu; Ellison, Aaron R; Plewa, Cherylene A; San, Miguel Tisha; Robinson, John; McCarter, John; Schwandner, Ralf; Judd, Ted; Carnahan, Josette; Dussault, Isabelle

2011-09-01

Despite the prevalence of KRAS mutations in human cancers, there remain no targeted therapies for treatment. The serine-threonine kinase STK33 has been proposed to be required for the survival of mutant KRAS-dependent cell lines, suggesting that small molecule kinase inhibitors of STK33 may be useful to treat KRAS-dependent tumors. In this study, we investigated the role of STK33 in mutant KRAS human cancer cells using RNA interference, dominant mutant overexpression, and small molecule inhibitors. As expected, KRAS downregulation decreased the survival of KRAS-dependent cells. In contrast, STK33 downregulation or dominant mutant overexpression had no effect on KRAS signaling or survival of these cells. Similarly, a synthetic lethal siRNA screen conducted in a broad panel of KRAS wild-type or mutant cells identified KRAS but not STK33 as essential for survival. We also obtained similar negative results using small molecule inhibitors of the STK33 kinase identified by high-throughput screening. Taken together, our findings refute earlier proposals that STK33 inhibition may be a useful therapeutic approach to target human KRAS mutant tumors. ©2011 AACR.

Optical spectroscopy of excited exciton states in MoS2 monolayers in van der Waals heterostructures

NASA Astrophysics Data System (ADS)

Robert, C.; Semina, M. A.; Cadiz, F.; Manca, M.; Courtade, E.; Taniguchi, T.; Watanabe, K.; Cai, H.; Tongay, S.; Lassagne, B.; Renucci, P.; Amand, T.; Marie, X.; Glazov, M. M.; Urbaszek, B.

2018-01-01

The optical properties of MoS2 monolayers are dominated by excitons, but for spectrally broad optical transitions in monolayers exfoliated directly onto SiO2 substrates detailed information on excited exciton states is inaccessible. Encapsulation in hexagonal boron nitride (hBN) allows approaching the homogenous exciton linewidth, but interferences in the van der Waals heterostructures make direct comparison between transitions in optical spectra with different oscillator strength more challenging. Here we reveal in reflectivity and in photoluminescence excitation spectroscopy the presence of excited states of the A exciton in MoS2 monolayers encapsulated in hBN layers of calibrated thickness, allowing us to extrapolate an exciton binding energy of ≈220 meV. We theoretically reproduce the energy separations and oscillator strengths measured in reflectivity by combining the exciton resonances calculated for a screened two-dimensional Coulomb potential with transfer matrix calculations of the reflectivity for the van der Waals structure. Our analysis shows a very different evolution of the exciton oscillator strength with principal quantum number for the screened Coulomb potential as compared to the ideal two-dimensional hydrogen model.

On-chip polarimetry for high-throughput screening of nanoliter and smaller sample volumes

NASA Technical Reports Server (NTRS)

Bachmann, Brian O. (Inventor); Bornhop, Darryl J. (Inventor); Dotson, Stephen (Inventor)

2012-01-01

A polarimetry technique for measuring optical activity that is particularly suited for high throughput screening employs a chip or substrate (22) having one or more microfluidic channels (26) formed therein. A polarized laser beam (14) is directed onto optically active samples that are disposed in the channels. The incident laser beam interacts with the optically active molecules in the sample, which slightly alter the polarization of the laser beam as it passes multiple times through the sample. Interference fringe patterns (28) are generated by the interaction of the laser beam with the sample and the channel walls. A photodetector (34) is positioned to receive the interference fringe patterns and generate an output signal that is input to a computer or other analyzer (38) for analyzing the signal and determining the rotation of plane polarized light by optically active material in the channel from polarization rotation calculations.

Fizeau simultaneous phase-shifting interferometry based on extended source

NASA Astrophysics Data System (ADS)

Wang, Shanshan; Zhu, Qiudong; Hou, Yinlong; Cao, Zheng

2016-09-01

Coaxial Fizeau simultaneous phase-shifting interferometer plays an important role in many fields for its characteristics of long optical path, miniaturization, and elimination of reference surface high-frequency error. Based on the matching of coherence between extended source and interferometer, orthogonal polarization reference wave and measurement wave can be obtained by Fizeau interferometry with Michelson interferometer preposed. Through matching spatial coherence length between preposed interferometer and primary interferometer, high contrast interference fringes can be obtained and additional interference fringes can be eliminated. Thus, the problem of separation of measurement and reference surface in the common optical path Fizeau interferometer is solved. Numerical simulation and principle experiment is conducted to verify the feasibility of extended source interferometer. Simulation platform is established by using the communication technique of DDE (dynamic data exchange) to connect Zemax and Matlab. The modeling of the extended source interferometer is realized by using Zemax. Matlab codes are programmed to automatically rectify the field parameters of the optical system and conveniently calculate the visibility of interference fringes. Combined with the simulation, the experimental platform of the extended source interferometer is established. After experimental research on the influence law of scattering screen granularity to interference fringes, the granularity of scattering screen is determined. Based on the simulation platform and experimental platform, the impacts on phase measurement accuracy of the imaging system aberration and collimation system aberration of the interferometer are analyzed. Compared the visibility relation curves between experimental measurement and simulation result, the experimental result is in line with the theoretical result.

Automated microscopy for high-content RNAi screening

PubMed Central

2010-01-01

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

Post-transcriptional gene silencing in the root system of the actinorhizal tree Allocasuarina verticillata.

PubMed

Gherbi, Hassen; Nambiar-Veetil, Mathish; Zhong, Chonglu; Félix, Jessy; Autran, Daphné; Girardin, Raphaël; Vaissayre, Virginie; Auguy, Florence; Bogusz, Didier; Franche, Claudine

2008-05-01

In recent years, RNA interference has been exploited as a tool for investigating gene function in plants. We tested the potential of double-stranded RNA interference technology for silencing a transgene in the actinorhizal tree Allocasuarina verticillata. The approach was undertaken using stably transformed shoots expressing the beta-glucuronidase (GUS) gene under the control of the constitutive promoter 35S; the shoots were further transformed with the Agrobacterium rhizogenes A4RS containing hairpin RNA (hpRNA) directed toward the GUS gene, and driven by the 35S promoter. The silencing and control vectors contained the reporter gene of the green fluorescent protein (GFP), thus allowing a screening of GUS-silenced composite plantlets for autofluorescence. With this rapid procedure, histochemical data established that the reporter gene was strongly silenced in both fluorescent roots and actinorhizal nodules. Fluorometric data further established that the level of GUS silencing was usually greater than 90% in the hairy roots containing the hairpin GUS sequences. We found that the silencing process of the reporter gene did not spread to the aerial part of the composite A. verticillata plants. Real-time quantitative polymerase chain reaction showed that GUS mRNAs were substantially reduced in roots and, thereby, confirmed the knock-down of the GUS transgene in the GFP(+) hairy roots. The approach described here will provide a versatile tool for the rapid assessment of symbiotically related host genes in actinorhizal plants of the Casuarinaceae family.

Science and Art--Rotating and Vibrating Soap Films.

ERIC Educational Resources Information Center

Ramme, Goran

1993-01-01

Describes activities concerning interference phenomena derived from illuminated rotating soap films. Suggests reflecting incident light off of the soap film onto a projection screen. Discusses several possible experiments, how to make soap solutions, and vibrating soap films. (MVL)

Discovery of Prostate Cancer Tumor Suppressors and Mediators of MDV3100 Resistance Through in Vivo RNA Interference Screen

DTIC Science & Technology

2015-11-01

concept of increase of NSE and decrease of PSMA with NED. Right, the quadrants of a hypothetical FACS-plot after Enzalutamide treatment from which...antigen ( PSMA ) expression. Thus, we also decided to sort for cells that have decreased PSMA expression with prolonged Enzalutamide treatment. Using the...cells, till there was almost plateauing of the GFP signals, Figure 6. PSMA expression FACS%based+screen+strategy+ AR#independent# AR

Web usability evaluation with screen reader users: implementation of the partial concurrent thinking aloud technique.

PubMed

Federici, Stefano; Stefano, Federici; Borsci, Simone; Stamerra, Gianluca

2010-08-01

A verbal protocol technique, adopted for a web usability evaluation, requires that the users are able to perform a double task: surfing and talking. Nevertheless, when blind users surf by using a screen reader and talk about the way they interact with the computer, the evaluation is influenced by a structural interference: users are forced to think aloud and listen to the screen reader at the same time. The aim of this study is to build up a verbal protocol technique for samples of visual impaired users in order to overcome the limits of concurrent and retrospective protocols. The technique we improved, called partial concurrent thinking aloud (PCTA), integrates a modified set of concurrent verbalization and retrospective analysis. One group of 6 blind users and another group of 6 sighted users evaluated the usability of a website using PCTA. By estimating the number of necessary users by the means of an asymptotic test, it was found out that the two groups had an equivalent ability of identifying usability problems, both over 80%. The result suggests that PCTA, while respecting the properties of classic verbal protocols, also allows to overcome the structural interference and the limits of concurrent and retrospective protocols when used with screen reader users. In this way, PCTA reduces the efficiency difference of usability evaluation between blind and sighted users.

New antibody and immunoassay pretreatment strategy to screen polychlorinated biphenyls in Korean transformer oil.

PubMed

Terakado, Shingo; Ohmura, Naoya; Park, Seok-Un; Lee, Seung-Min; Glass, Thomas R

2013-01-01

Development and modifications are described that expand the application of an immunoassay from the detection of Kanechlors (Japanese technical PCBs mixtures) to the detection of Aroclors (U. S. technical PCB mixtures, used in Korea) in contaminated Korean transformer oil. The first necessary modification was the development of a new antibody with a reactivity profile favorable for Aroclors. The second modification was the addition of a second column to the solid-phase extraction method to reduce assay interference caused by the Korean oil matrix. The matrix interference is suspected to be caused by the presence of synthetic oils (or similar materials) present as contaminants. The modified assay was validated by comparison to high-resolution gas chromatography/high-resolution mass spectrometry analysis, and was shown to be tolerant of up to 10% of several common synthetic insulating oils. Finally the screening performance of the modified assay was evaluated using 500 used transformer oil samples of Korean origin, and was shown to have good performance in terms of false positive and false negative rates. This report provides evidence for the first establishment of immunoassay screening for Aroclor based PCB contamination in Korean transformer oil.

Molecular dynamics simulation of S100B protein to explore ligand blockage of the interaction with p53 protein

NASA Astrophysics Data System (ADS)

Zhou, Zhigang; Li, Yumin

2009-10-01

As a tumor suppressor, p53 plays an important role in cancer suppression. The biological function of p53 as a tumor suppressor is disabled when it binds to S100B. Developing the ligands to block the S100B-p53 interaction has been proposed as one of the most important approaches to the development of anti-cancer agents. We screened a small compound library against the binding interface of S100B and p53 to identify potential compounds to interfere with the interaction. The ligand-binding effect on the S100B-p53 interaction was explored by molecular dynamics at the atomic level. The results show that the ligand bound between S100B and p53 propels the two proteins apart by about 2 Å compared to the unligated S100B-p53 complex. The binding affinity of S100B and p53 decreases by 8.5-14.6 kcal/mol after a ligand binds to the interface from the original unligated state of the S100B-p53 complex. Ligand-binding interferes with the interaction of S100B and p53. Such interference could impact the association of S100B and p53, which would free more p53 protein from the pairing with S100B and restore the biological function of p53 as a tumor suppressor. The analysis of the binding mode and ligand structural features would facilitate our effort to identify and design ligands to block S100B-p53 interaction effectively. The results from the work suggest that developing ligands targeting the interface of S100B and p53 could be a promising approach to recover the normal function of p53 as a tumor suppressor.

Luminogenic cytochrome P450 assays.

PubMed

Cali, James J; Ma, Dongping; Sobol, Mary; Simpson, Daniel J; Frackman, Susan; Good, Troy D; Daily, William J; Liu, David

2006-08-01

Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dependent CYP inhibition by test compounds against recombinant CYP enzymes or liver microsomes. Induction or inhibition of CYP activities in cultured hepatocytes is measured in a nonlytic approach that leaves cells intact for additional analysis. Luminogenic CYP assays offer advantages of speed and safety over HPLC and radiochemical-based methods. Compared with fluorogenic methods the approach offers advantages of improved sensitivity and decreased interference between optical properties of test compound and CYP substrate. These homogenous assays are sensitive and robust tools for high-throughput CYP screening in early drug discovery.

Small-Molecule Inhibitors of the SOX18 Transcription Factor.

PubMed

Fontaine, Frank; Overman, Jeroen; Moustaqil, Mehdi; Mamidyala, Sreeman; Salim, Angela; Narasimhan, Kamesh; Prokoph, Nina; Robertson, Avril A B; Lua, Linda; Alexandrov, Kirill; Koopman, Peter; Capon, Robert J; Sierecki, Emma; Gambin, Yann; Jauch, Ralf; Cooper, Matthew A; Zuegg, Johannes; Francois, Mathias

2017-03-16

Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors. We identified two compounds, which inspired a series of synthetic SOX18 inhibitors, able to interfere with the SOX18 HMG DNA-binding domain, and to disrupt HMG-dependent protein-protein interaction with RBPJ. These compounds also perturbed SOX18 transcriptional activity in a cell-based reporter gene system. This approach may prove useful in developing a new class of anti-angiogenic compounds based on the inhibition of TF activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optically Remote Noncontact Heart Rates Sensing Technique

NASA Astrophysics Data System (ADS)

Thongkongoum, W.; Boonduang, S.; Limsuwan, P.

2017-09-01

Heart rate monitoring via optically remote noncontact technique was reported in this research. A green laser (5 mW, 532±10 nm) was projected onto the left carotid artery. The reflected laser light on the screen carried the deviation of the interference patterns. The interference patterns were recorded by the digital camera. The recorded videos of the interference patterns were frame by frame analysed by 2 standard digital image processing (DIP) techniques, block matching (BM) and optical flow (OF) techniques. The region of interest (ROI) pixels within the interference patterns were analysed for periodically changes of the interference patterns due to the heart pumping action. Both results of BM and OF techniques were compared with the reference medical heart rate monitoring device by which a contact measurement using pulse transit technique. The results obtained from BM technique was 74.67 bpm (beats per minute) and OF technique was 75.95 bpm. Those results when compared with the reference value of 75.43±1 bpm, the errors were found to be 1.01% and 0.69%, respectively.

Time-resolved double-slit interference pattern measurement with entangled photons

PubMed Central

Kolenderski, Piotr; Scarcella, Carmelo; Johnsen, Kelsey D.; Hamel, Deny R.; Holloway, Catherine; Shalm, Lynden K.; Tisa, Simone; Tosi, Alberto; Resch, Kevin J.; Jennewein, Thomas

2014-01-01

The double-slit experiment strikingly demonstrates the wave-particle duality of quantum objects. In this famous experiment, particles pass one-by-one through a pair of slits and are detected on a distant screen. A distinct wave-like pattern emerges after many discrete particle impacts as if each particle is passing through both slits and interfering with itself. Here we present a temporally- and spatially-resolved measurement of the double-slit interference pattern using single photons. We send single photons through a birefringent double-slit apparatus and use a linear array of single-photon detectors to observe the developing interference pattern. The analysis of the buildup allows us to compare quantum mechanics and the corpuscular model, which aims to explain the mystery of single-particle interference. Finally, we send one photon from an entangled pair through our double-slit setup and show the dependence of the resulting interference pattern on the twin photon's measured state. Our results provide new insight into the dynamics of the buildup process in the double-slit experiment, and can be used as a valuable resource in quantum information applications. PMID:24770360

"Proceedings of the 22nd Aschauer Soiree on Growth and Health Screening", held at Altenhof, Germany, November 15th, 2014.

PubMed

Hermanussen, Michael; Anisimova, Anna; Abmann, Christian; Van Buuren, Stef; Camara, Antonio D; Elhusseini, Mona Abbas; Hassan, Mortada; El-Shabrawi, Mortada Hassan; Godina, Elena Zinovyevna; Gomula, Aleksandra; Groth, Detlef; Koziel, Slawomir; Lieberman, Leslie Sue; Meigen, Christof; Mumm, Rebekka; Nariyama, Koichi; Nowak-Szczepanska, Natalia; Novokmet, Natalija; Satake, Takashi; Scheffler, Christiane; Soderhall, Jani; Suchomlinov, Andrej; Tutkuviene, Janina; Wit, Jan M; Witwer-Backofen, Ursula; Yestrebsky, Cherie Lynn

2015-03-01

Twenty-five scientists met at Aschauhof, Altenhof, Germany, to discuss various aspects of the complex network of modern health screening, focusing on current scientific topics including medical sciences, human biology, and mathematics; on problems in implementing these results at the practical level of physicians, nurses, technicians, and engineers; and the level of administrative and political decisions. Whereas major scientific advancements have been published in the understanding and the bio-statistical evaluation of anthropometric screening parameters such as serial measurements of height and weight for preventive medical check-ups, BMI screening and surveillance in schools, etc., the implementation of these advancements into current health screening concepts, strategies and decision-making is poor. Fear of discrimination, misperception of body image, behavioural responses and political concerns, meanwhile dominate and negatively interfere with the implementation of recent scientific results into public health screening concepts and practices.

Evaluation of urine culture screening by light-scatter photometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hale, D.C.; Thrupp, L.D.; Matsen, J.M.

1981-08-01

Urine screening for bacteriuria by light-scatter photometry (Autobac) was evaluated for accuracy and compared with a colony count by the calibrated loop method. Incubation time, inoculum size, precision, and interference of particulate matter were evaluated in an effort to standardize the screening procedure. Results showed that urines could be accurately screened for Enterobacteriaceae by inoculating a single Autobac cuvette chamber with 0.1 or 0.2 ml of urine and determining the voltage change after four hours. A change of greater than or equal to 0.2 units indicates significant bacteriuria. Decreased accuracy was noted for urines having greater than 10(5) cfu/ml ofmore » Pseudomonas species or gram-positive cocci, possibly because these organisms grow more slowly.« less

Microelectroporation device for genomic screening

DOEpatents

Perroud, Thomas D.; Renzi, Ronald F.; Negrete, Oscar; Claudnic, Mark R.

2014-09-09

We have developed an microelectroporation device that combines microarrays of oligonucleotides, microfluidic channels, and electroporation for cell transfection and high-throughput screening applications (e.g. RNA interference screens). Microarrays allow the deposition of thousands of different oligonucleotides in microscopic spots. Microfluidic channels and microwells enable efficient loading of cells into the device and prevent cross-contamination between different oligonucleotides spots. Electroporation allows optimal transfection of nucleic acids into cells (especially hard-to-transfect cells such as primary cells) by minimizing cell death while maximizing transfection efficiency. This invention has the advantage of a higher throughput and lower cost, while preventing cross-contamination compared to conventional screening technologies. Moreover, this device does not require bulky robotic liquid handling equipment and is inherently safer given that it is a closed system.

A multi-model approach to nucleic acid-based drug development.

PubMed

Gautherot, Isabelle; Sodoyer, Regís

2004-01-01

With the advent of functional genomics and the shift of interest towards sequence-based therapeutics, the past decades have witnessed intense research efforts on nucleic acid-mediated gene regulation technologies. Today, RNA interference is emerging as a groundbreaking discovery, holding promise for development of genetic modulators of unprecedented potency. Twenty-five years after the discovery of antisense RNA and ribozymes, gene control therapeutics are still facing developmental difficulties, with only one US FDA-approved antisense drug currently available in the clinic. Limited predictability of target site selection models is recognized as one major stumbling block that is shared by all of the so-called complementary technologies, slowing the progress towards a commercial product. Currently employed in vitro systems for target site selection include RNAse H-based mapping, antisense oligonucleotide microarrays, and functional screening approaches using libraries of catalysts with randomized target-binding arms to identify optimal ribozyme/DNAzyme cleavage sites. Individually, each strategy has its drawbacks from a drug development perspective. Utilization of message-modulating sequences as therapeutic agents requires that their action on a given target transcript meets criteria of potency and selectivity in the natural physiological environment. In addition to sequence-dependent characteristics, other factors will influence annealing reactions and duplex stability, as well as nucleic acid-mediated catalysis. Parallel consideration of physiological selection systems thus appears essential for screening for nucleic acid compounds proposed for therapeutic applications. Cellular message-targeting studies face issues relating to efficient nucleic acid delivery and appropriate analysis of response. For reliability and simplicity, prokaryotic systems can provide a rapid and cost-effective means of studying message targeting under pseudo-cellular conditions, but such approaches also have limitations. To streamline nucleic acid drug discovery, we propose a multi-model strategy integrating high-throughput-adapted bacterial screening, followed by reporter-based and/or natural cellular models and potentially also in vitro assays for characterization of the most promising candidate sequences, before final in vivo testing.

S-aryl-L-cysteine sulphoxides and related organosulphur compounds alter oral biofilm development and AI-2-based cell-cell communication.

PubMed

Kasper, S H; Samarian, D; Jadhav, A P; Rickard, A H; Musah, R A; Cady, N C

2014-11-01

To design and synthesize a library of structurally related, small molecules related to homologues of compounds produced by the plant Petiveria alliacea and determine their ability to interfere with AI-2 cell-cell communication and biofilm formation by oral bacteria. Many human diseases are associated with persistent bacterial biofilms. Oral biofilms (dental plaque) are problematic as they are often associated with tooth decay, periodontal disease and systemic disorders such as heart disease and diabetes. Using a microplate-based approach, a bio-inspired small molecule library was screened for anti-biofilm activity against the oral species Streptococcus mutans UA159, Streptococcus sanguis 10556 and Actinomyces oris MG1. To complement the static screen, a flow-based BioFlux microfluidic system screen was also performed under conditions representative of the human oral cavity. Several compounds were found to display biofilm inhibitory activity in all three of the oral bacteria tested. These compounds were also shown to inhibit bioluminescence by Vibrio harveyi and were thus inferred to be quorum sensing (QS) inhibitors. Due to the structural similarity of these compounds to each other, and to key molecules in AI-2 biosynthetic pathways, we propose that these molecules potentially reduce biofilm formation via antagonism of QS or QS-related pathways. This study highlights the potential for a non-antimicrobial-based strategy, focused on AI-2 cell-cell signalling, to control the development of dental plaque. Considering that many bacterial species use AI-2 cell-cell signalling, as well as the increased concern of the use of antimicrobials in healthcare products, such an anti-biofilm approach could also be used to control biofilms in environments beyond the human oral cavity. © 2014 The Society for Applied Microbiology.

Discovery of Prostate Cancer Tumor Suppressors and Mediators of MDV3100 Resistance through in Vivo RNA Interference Screen

DTIC Science & Technology

2014-05-01

NE phenotype. Figure 5: Rational of the FACS-based screen. Left, the concept of increase of NSE and decrease of PSMA with NED. Right, the...of AR dependency is associated with increase in Prostate specific membrane antigen ( PSMA ) expression. Thus, we also decided to sort for cells that...have decreased PSMA expression with prolonged Enzalutamide treatment. Using the above markers and FACS we attempted to sort out 4 populations of

Fabrication and Characterization of Three Dimensional Photonic Crystals Generated by Multibeam Interference Lithography

DTIC Science & Technology

2009-01-01

and J. A. Lewis, "Microperiodic structures - Direct writing of three-dimensional webs ," Nature, vol. 428, pp. 386-386, 2004. [9] M. Campbell, D. N...of Applied Physics Part 1-Regular Papers Brief Communications & Review Papers , vol. 44, pp. 6355-6367, 2005. [75] P. Cloetens, W. Ludwig, J... paper screen on the sample holder and marking the beam position. If the central beam is properly aligned, the spot on the screen remains at the

Establishing MALDI-TOF as Versatile Drug Discovery Readout to Dissect the PTP1B Enzymatic Reaction.

PubMed

Winter, Martin; Bretschneider, Tom; Kleiner, Carola; Ries, Robert; Hehn, Jörg P; Redemann, Norbert; Luippold, Andreas H; Bischoff, Daniel; Büttner, Frank H

2018-07-01

Label-free, mass spectrometric (MS) detection is an emerging technology in the field of drug discovery. Unbiased deciphering of enzymatic reactions is a proficient advantage over conventional label-based readouts suffering from compound interference and intricate generation of tailored signal mediators. Significant evolvements of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, as well as associated liquid handling instrumentation, triggered extensive efforts in the drug discovery community to integrate the comprehensive MS readout into the high-throughput screening (HTS) portfolio. Providing speed, sensitivity, and accuracy comparable to those of conventional, label-based readouts, combined with merits of MS-based technologies, such as label-free parallelized measurement of multiple physiological components, emphasizes the advantages of MALDI-TOF for HTS approaches. Here we describe the assay development for the identification of protein tyrosine phosphatase 1B (PTP1B) inhibitors. In the context of this precious drug target, MALDI-TOF was integrated into the HTS environment and cross-compared with the well-established AlphaScreen technology. We demonstrate robust and accurate IC 50 determination with high accordance to data generated by AlphaScreen. Additionally, a tailored MALDI-TOF assay was developed to monitor compound-dependent, irreversible modification of the active cysteine of PTP1B. Overall, the presented data proves the promising perspective for the integration of MALDI-TOF into drug discovery campaigns.

Regulation of Meiotic Recombination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregory p. Copenhaver

Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diversemore » as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system for assaying recombination using tetrad analysis in a higher eukaryotic system (6). This system enabled the measurement of the frequency and distribution of recombination events at a genome wide level in wild type Arabidopsis (7), construction of genetic linkage maps which include positions for each centromere (8), and modeling of the strength and pattern of interference (9). This proposal extends the use of tetrad analysis in Arabidopsis by using it as the basis for assessing the phenotypes of mutants in genes important for recombination and the regulation of crossover interference and performing a novel genetic screen. In addition to broadening our knowledge of a classic genetic problem - the regulation of recombination by crossover interference - this proposal also provides broader impact by: generating pedagogical tools for use in hands-on classroom experience with genetics, building interdisciplinary collegial partnerships, and creating a platform for participation by junior scientists from underrepresented groups. There are three specific aims: (1) Isolate mutants in Arabidopsis MUS81 homologs using T-DNA and TILLING (2) Characterize recombination levels and interference in mus81 mutants (3) Execute a novel genetic screen, based on tetrad analysis, for genes that regulate meiotic recombination« less

Performance comparison of optical interference cancellation system architectures.

PubMed

Lu, Maddie; Chang, Matt; Deng, Yanhua; Prucnal, Paul R

2013-04-10

The performance of three optics-based interference cancellation systems are compared and contrasted with each other, and with traditional electronic techniques for interference cancellation. The comparison is based on a set of common performance metrics that we have developed for this purpose. It is shown that thorough evaluation of our optical approaches takes into account the traditional notions of depth of cancellation and dynamic range, along with notions of link loss and uniformity of cancellation. Our evaluation shows that our use of optical components affords performance that surpasses traditional electronic approaches, and that the optimal choice for an optical interference canceller requires taking into account the performance metrics discussed in this paper.

Considerations and Some Practical Solutions to Overcome Nanoparticle Interference with LAL Assays and to Avoid Endotoxin Contamination in Nanoformulations.

PubMed

Neun, Barry W; Dobrovolskaia, Marina A

2018-01-01

Monitoring endotoxin contamination in drugs and medical devices is required to avoid pyrogenic response and septic shock in patients receiving these products. Endotoxin contamination of engineered nanomaterials and nanotechnology-based medical products represents a significant translational hurdle. Nanoparticles often interfere with an in vitro Limulus Amebocyte Lysate (LAL) assay commonly used in the pharmaceutical industry for the detection and quantification of endotoxin. Such interference challenges the preclinical development of nanotechnology-formulated drugs and medical devices containing engineered nanomaterials. Protocols for analysis of nanoparticles using LAL assays have been reported before. Here, we discuss considerations for selecting an LAL format and describe a few experimental approaches for overcoming nanoparticle interference with the LAL assays to obtain more accurate estimation of endotoxin contamination in nanotechnology-based products. The discussed approaches do not solve all types of nanoparticle interference with the LAL assays but could be used as a starting point to address the problem. This chapter also describes approaches to prevent endotoxin contamination in nanotechnology-formulated products.

Two Swedish screening instruments for exhaustion disorder: cross-sectional associations with burnout, work stress, private life stress, and personality traits.

PubMed

Persson, Roger; Österberg, Kai; Viborg, Njördur; Jönsson, Peter; Tenenbaum, Artur

2017-06-01

To examine the relationships of two screening instruments recently developed for assessment of exhaustion disorder (ED) with some other well-known inventories intended to assess ED-related concepts and self-reports of job demands, job control, job support, private life stressors, and personality factors. A cross-sectional population sample ( n = 1355) completed: the Karolinska Exhaustion Disorder Scale (KEDS), Self-reported Exhaustion Disorder Scale (s-ED), Shirom-Melamed Burnout Questionnaire (SMBQ), Utrecht Work Engagement Scale (UWES-9), Job Content Questionnaire (JCQ), Big Five Inventory (BFI), and items concerning family-to-work interference and stress in private life. Compared to participants without any indication of ED, participants classified as having ED on KEDS or s-ED had higher scores on all four SMBQ subscales, lower scores on the UWES-9 subscales vigor and dedication, higher JCQ job demands scores, lower JCQ job support scores, higher degrees of family-to-work interference and stress in private life, and higher BFI neuroticism and openness scores. In addition, participants classified as having ED on KEDS had lower scores on the UWES-9 absorption subscale, the JCQ job control scale, and lower BFI extraversion, agreeableness and conscientiousness scores, compared to the subgroup not classified as having ED. As expected, we observed an overall pattern of associations between the ED screening inventories KEDS and s-ED and measures of burnout, work engagement, job demands-control-support, stress in private life, family-to-work interference, and personality factors. The results suggest that instruments designed to assess burnout, work engagement, and ED share common ground, despite their conceptual differences.

Effect of electrocardiogram interference on cortico-cortical connectivity analysis and a possible solution.

PubMed

Govindan, R B; Kota, Srinivas; Al-Shargabi, Tareq; Massaro, An N; Chang, Taeun; du Plessis, Adre

2016-09-01

Electroencephalogram (EEG) signals are often contaminated by the electrocardiogram (ECG) interference, which affects quantitative characterization of EEG. We propose null-coherence, a frequency-based approach, to attenuate the ECG interference in EEG using simultaneously recorded ECG as a reference signal. After validating the proposed approach using numerically simulated data, we apply this approach to EEG recorded from six newborns receiving therapeutic hypothermia for neonatal encephalopathy. We compare our approach with an independent component analysis (ICA), a previously proposed approach to attenuate ECG artifacts in the EEG signal. The power spectrum and the cortico-cortical connectivity of the ECG attenuated EEG was compared against the power spectrum and the cortico-cortical connectivity of the raw EEG. The null-coherence approach attenuated the ECG contamination without leaving any residual of the ECG in the EEG. We show that the null-coherence approach performs better than ICA in attenuating the ECG contamination without enhancing cortico-cortical connectivity. Our analysis suggests that using ICA to remove ECG contamination from the EEG suffers from redistribution problems, whereas the null-coherence approach does not. We show that both the null-coherence and ICA approaches attenuate the ECG contamination. However, the EEG obtained after ICA cleaning displayed higher cortico-cortical connectivity compared with that obtained using the null-coherence approach. This suggests that null-coherence is superior to ICA in attenuating the ECG interference in EEG for cortico-cortical connectivity analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Material dependence of 2H(d,p)3H cross section at the very low energies

NASA Astrophysics Data System (ADS)

Kılıç, Ali İhsan; Czerski, Konrad; Kuştan-Kılıç, Fadime; Targosz-Sleczka, Natalia; Weissbach, Daniel; Huke, Armin; Ruprecht, Götz

2017-09-01

Calculations of the material dependence of 2H(d,p)3H cross section and neutron-to-proton branching ratio of d+d reactions have been performed including a concept of the 0+ threshold single particle resonance. The resonance has been assumed to explain the enhanced electron screening effect observed in the d+d reaction for different metallic targets. Here, we have included interference effects between the flat and resonance part of the cross section, which allowed us to enlighten observed suppression of the neutron channel in some metals such as Sr and Li. Since the position of the resonance depends on the screening energy that strongly depends on the local electron density. The resonance width, observed for the d+d reactions in the very hygroscopic metals (Sr and Li) and therefore probably contaminated by oxides, should be much larger than for other metals. Thus, the interference term of the cross section depending on the total resonance width provides the material dependences.

Direct Detection of Nucleic Acid with Minimizing Background and Improving Sensitivity Based on a Conformation-Discriminating Indicator.

PubMed

Zhu, Lixuan; Qing, Zhihe; Hou, Lina; Yang, Sheng; Zou, Zhen; Cao, Zhong; Yang, Ronghua

2017-08-25

As is well-known, the nucleic acid indicator-based strategy is one of the major approaches to monitor the nucleic acid hybridization-mediated recognition events in biochemical analysis, displaying obvious advantages including simplicity, low cost, convenience, and generality. However, conventional indicators either hold strong self-fluorescence or can be lighted by both ssDNA and dsDNA, lacking absolute selectivity for a certain conformation, always with high background interference and low sensitivity in sensing; and additional processing (e.g., nanomaterial-mediated background suppression, and enzyme-catalyzed signal amplification) is generally required to improve the detection performance. In this work, a carbazole derivative, EBCB, has been synthesized and screened as a dsDNA-specific fluorescent indicator. Compared with conventional indicators under the same conditions, EBCB displayed a much higher selective coefficient for dsDNA, with little self-fluorescence and negligible effect from ssDNA. Based on its superior capability in DNA conformation-discrimination, high sensitivity with minimizing background interference was demonstrated for direct detection of nucleic acid, and monitoring nucleic acid-based circuitry with good reversibity, resulting in low detection limit and high capability for discriminating base-mismatching. Thus, we expect that this highly specific DNA conformation-discriminating indicator will hold good potential for application in biochemical sensing and molecular logic switching.

A Reverse Stroop Task with Mouse Tracking.

PubMed

Yamamoto, Naohide; Incera, Sara; McLennan, Conor T

2016-01-01

In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed-for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants' responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants' performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse's approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks.

A Reverse Stroop Task with Mouse Tracking

PubMed Central

Yamamoto, Naohide; Incera, Sara; McLennan, Conor T.

2016-01-01

In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed—for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants’ responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants’ performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse’s approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID:27199881

Bacterial cell identification in differential interference contrast microscopy images.

PubMed

Obara, Boguslaw; Roberts, Mark A J; Armitage, Judith P; Grau, Vicente

2013-04-23

Microscopy image segmentation lays the foundation for shape analysis, motion tracking, and classification of biological objects. Despite its importance, automated segmentation remains challenging for several widely used non-fluorescence, interference-based microscopy imaging modalities. For example in differential interference contrast microscopy which plays an important role in modern bacterial cell biology. Therefore, new revolutions in the field require the development of tools, technologies and work-flows to extract and exploit information from interference-based imaging data so as to achieve new fundamental biological insights and understanding. We have developed and evaluated a high-throughput image analysis and processing approach to detect and characterize bacterial cells and chemotaxis proteins. Its performance was evaluated using differential interference contrast and fluorescence microscopy images of Rhodobacter sphaeroides. Results demonstrate that the proposed approach provides a fast and robust method for detection and analysis of spatial relationship between bacterial cells and their chemotaxis proteins.

The Contextual Interference Effect in Applied Settings

ERIC Educational Resources Information Center

Barreiros, Joao; Figueiredo, Teresa; Godinho, Mario

2007-01-01

This paper analyses the research literature that approaches the contextual interference effect in applied settings. In contrast to the laboratory settings, in which high interference conditions depress acquisition and promote learning evaluated in retention and transfer tests, in applied settings most of the studies (60%) fail to observe positive…

Feasibility of FT–Raman spectroscopy for rapid screening for DON toxin in ground wheat and barley.

PubMed

Liu, Y; Delwiche, S R; Dong, Y

2009-10-01

Rapid detection of deoxynivalenol (DON) in cereal-based food and feed has long been the goal of regulators and manufacturers. As non-destructive approaches, infrared (IR) and near-infrared (NIR) spectroscopic techniques have been used for the prediction and classification of contaminated single-kernel and ground grain without any DON extraction steps. These methods, however, are hindered by the intense and broad spectral bands attributed to naturally occurring moisture. Raman spectroscopy could be an alternative to IR and NIR due to its insensitivity to water and fewer overlapped bands. This study explored the feasibility of the Raman technique for rapid and non-destructive screening of DON-contaminated wheat and barley meal. The advantages of this technique include the use of a 1064-nm NIR excitation laser that reduces interference from fluorescence of biological compounds in wheat and barley, the use of a simple intensity-intensity algorithm at two unique frequencies, plus the technique's ease of sample preparation. The results indicate that the simple algorithm, as well as principal component analysis applied to the Raman spectra, can be used to classify low from high DON grain.

Summary of Research 1998, Department of Electrical and Computer Engineering.

DTIC Science & Technology

1999-08-01

Channel Interference," Master’s Thesis, Naval Postgraduate School, December 1998. Erdogan , V, "Time Domain Simulation of MPSK Communications System...1998, several new user interface screens have been designed. Software for reading data from analog tape has been completed and interfaced to the

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

PubMed

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

2015-09-01

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

Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.

PubMed

Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel

2016-08-01

Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of bilirubin concentration in hemolysed samples, is it really impossible? The altitude-curve cartography approach to interfered assays.

PubMed

Brunori, Paola; Masi, Piergiorgio; Faggiani, Luigi; Villani, Luciano; Tronchin, Michele; Galli, Claudio; Laube, Clarissa; Leoni, Antonella; Demi, Maila; La Gioia, Antonio

2011-04-11

Neonatal jaundice might lead to severe clinical consequences. Measurement of bilirubin in samples is interfered by hemolysis. Over a method-depending cut-off value of measured hemolysis, bilirubin value is not accepted and a new sample is required for evaluation although this is not always possible, especially with newborns and cachectic oncological patients. When usage of different methods, less prone to interferences, is not feasible an alternative recovery method for analytical significance of rejected data might help clinicians to take appropriate decisions. We studied the effects of hemolysis over total bilirubin measurement, comparing hemolysis-interfered bilirubin measurement with the non-interfered value. Interference curves were extrapolated over a wide range of bilirubin (0-30 mg/mL) and hemolysis (H Index 0-1100). Interference "altitude" curves were calculated and plotted. A bimodal acceptance table was calculated. Non-interfered bilirubin of given samples was calculated, by linear interpolation between the nearest lower and upper interference curves. Rejection of interference-sensitive data from hemolysed samples for every method should be based not upon the interferent concentration but upon a more complex algorithm based upon the concentration-dependent bimodal interaction between the interfered analyte and the measured interferent. The altitude-curve cartography approach to interfered assays may help laboratories to build up their own method-dependent algorithm and to improve the trueness of their data by choosing a cut-off value different from the one (-10% interference) proposed by manufacturers. When re-sampling or an alternative method is not available the altitude-curve cartography approach might also represent an alternative recovery method for analytical significance of rejected data. Copyright © 2011 Elsevier B.V. All rights reserved.

High Content Screening in Zebrafish Speeds up Hazard Ranking of Transition Metal Oxide Nanoparticles

PubMed Central

Lin, Sijie; Zhao, Yan; Xia, Tian; Meng, Huan; Zhaoxia, Ji; Liu, Rong; George, Saji; Xiong, Sijing; Wang, Xiang; Zhang, Haiyuan; Pokhrel, Suman; Mädler, Lutz; Damoiseaux, Robert; Lin, Shuo; Nel, Andre E.

2014-01-01

Zebrafish is an aquatic organism that can be used for high content safety screening of engineered nanomaterials (ENMs). We demonstrate, for the first time, the use of high content bright-field and fluorescence-based imaging to compare the toxicological effect of transition metal oxide (CuO, ZnO, NiO and Co3O4) nanoparticles in zebrafish embryos and larvae. High content bright-field imaging demonstrated potent and dose-dependant hatching interference in the embryos, with the exception of Co3O4 which was relatively inert. We propose that the hatching interference was due to the shedding of Cu and Ni ions, compromising the activity of the hatching enzyme, ZHE1, similar to what we previously proposed for Zn2+. This hypothesis is based on the presence of metal–sensitive histidines in the catalytic center of this enzyme. Co-introduction of a metal ion chelator, diethylene triamine pentaacetic acid (DTPA), reversed the hatching interference of Cu, Zn and Ni. While neither the embryos nor larvae demonstrated morphological abnormalities, high content fluorescence-based imaging demonstrated that CuO, ZnO and NiO could induce increased expression of the heat shock protein 70:enhanced green fluorescence protein (hsp70:eGFP) in transgenic zebrafish larvae. Induction of this response by CuO required a higher nanoparticle dose than the amount leading to hatching interference. This response was also DTPA sensitive. In conclusion, we demonstrate that high content imaging of embryo development, morphological abnormalities and HSP70 expression can be used for hazard ranking and determining the dose-response relationships leading to ENM effects on the development of the zebrafish embryo. PMID:21851096

Analysis of compounds that interfere with herpes simplex virus-host receptor interactions using surface plasmon resonance.

PubMed

Gopinath, Subash C B; Hayashi, Kyoko; Lee, Jung-Bum; Kamori, Akiko; Dong, Cai-Xia; Hayashi, Toshimitsu; Kumar, Penmetcha K R

2013-11-05

The entry of herpes simplex virus into host cells involves a complex series of events that require concerted inputs from multiple HSV glycoproteins. Among these glycoproteins, the gD protein of HSV-1 and HSV-2 plays an important role for host receptor binding and membrane fusion. In the present study, we evaluated the ability of different sulfated saccharides to interfere with gD-host receptor (HVEM) interactions using our recently reported molecular assay (Gopinath, S. C. B.; Hayashi, K.; Kumar, P. K. R. J. Virol. 2012, 86, 6732-6744). Initially, we tested the ability of heparan sulfate to interfere with the HVEM-HSV-1 gD interaction and found that heparan sulfate is able to interfere efficiently, with an apparent EC50 of 2.1 μM. In addition, we tested different synthetic sulfated polysaccharides and natural sulfated polysaccharides from an edible alga, Sargassum horneri , after fractionation into different sizes and sulfate and uronic acid contents. Six polysaccharides isolated from S. horneri were found to efficiently interfere with the HVEM-gD interaction. Three others caused moderate interference, and five caused weak interference. These results were confirmed with plaque assays, and good agreement was found with the results of the SPR assay for the identification of compounds that interfere with HVEM-HSV-1 gD binding. These studies suggest that our molecular assay based on surface plasmon resonance is not only useful for the analysis of viral-host protein interactions but is also applicable for the routine screening of compounds to identify those that interfere with the first step of viral entry, thus facilitating the rapid development of novel antiviral compounds that target HSV.

A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. | Office of Cancer Genomics

Cancer.gov

Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis.

CRT Monitors: Do They Interfere with Learning?

ERIC Educational Resources Information Center

Garland, Kate J.; Noyes, Jan M.

2004-01-01

Research suggests screen reading is slower and possibly less accurate than reading from paper. Six study and test sessions over 10 months examined correct scores and retrieval responses for learning material presented via these two media. Correct scores did not differ suggesting that close matching of material can eliminate any decrement in…

Maltreatment, Conscience Functioning and Dopamine Beta Hydroxylase in Emotionally Disturbed Boys.

ERIC Educational Resources Information Center

Galvin, Matthew R.; And Others

1997-01-01

Nineteen hospitalized, emotionally disturbed boys screened for maltreatment either before or after age 3 were compared with a normal control group for enzyme activity and conscience functions in moral valuation. Subjects who experienced early maltreatment had more developmental delays and more interferences with conscience functions than other…

DEVELOPMENT OF TWO ANDROGEN RECEPTOR ASSAYS USING ADENOVIRAL TRANSDUCTION OF MMTV-LUC REPORTER AND/OR HAR FOR ENDOCRINE SCREENING

EPA Science Inventory

Abstract
The discovery of xenobiotics which interfere with androgen activity has highlighted the need to assess chemicals for their ability to modulate dihydrotestosterone (DHT)-receptor binding. Previous test systems have used cells transfected with plasmid containing a rep...

Creating Workplaces Where People Can Think: Cognitive Ergonomics.

ERIC Educational Resources Information Center

Kearny, Lynn; Smith, Phyl

1999-01-01

Presents ideas about how the workplace affects job performance, how to diagnose workplace-related problems, and how to make modest improvements. Highlights include: workplace-imposed limits on performance; the mental and physical steps of work; screening behavior; how adaptation interferes with performance; task- and human-based workspaces;…

Interference Mitigation for Cyber-Physical Wireless Body Area Network System Using Social Networks.

PubMed

Zhang, Zhaoyang; Wang, Honggang; Wang, Chonggang; Fang, Hua

2013-06-01

Wireless body area networks (WBANs) are cyber-physical systems (CPS) that have emerged as a key technology to provide real-time health monitoring and ubiquitous healthcare services. WBANs could operate in dense environments such as in a hospital and lead to a high mutual communication interference in many application scenarios. The excessive interferences will significantly degrade the network performance including depleting the energy of WBAN nodes more quickly, and even eventually jeopardize people's lives due to unreliable (caused by the interference) healthcare data collections. Therefore, It is critical to mitigate the interference among WBANs to increase the reliability of the WBAN system while minimizing the system power consumption. Many existing approaches can deal with communication interference mitigation in general wireless networks but are not suitable for WBANs due to their ignoring the social nature of WBANs. Unlike the previous research, we for the first time propose a power game based approach to mitigate the communication interferences for WBANs based on the people's social interaction information. Our major contributions include: (1) model the inter-WBANs interference, and determine the distance distribution of the interference through both theoretical analysis and Monte Carlo simulations; (2) develop social interaction detection and prediction algorithms for people carrying WBANs; (3) develop a power control game based on the social interaction information to maximize the system's utility while minimize the energy consumption of WBANs system. The extensive simulation results show the effectiveness of the power control game for inter-WBAN interference mitigation using social interaction information. Our research opens a new research vista of WBANs using social networks.

Interference Mitigation for Cyber-Physical Wireless Body Area Network System Using Social Networks

PubMed Central

Zhang, Zhaoyang; Wang, Honggang; Wang, Chonggang; Fang, Hua

2014-01-01

Wireless body area networks (WBANs) are cyber-physical systems (CPS) that have emerged as a key technology to provide real-time health monitoring and ubiquitous healthcare services. WBANs could operate in dense environments such as in a hospital and lead to a high mutual communication interference in many application scenarios. The excessive interferences will significantly degrade the network performance including depleting the energy of WBAN nodes more quickly, and even eventually jeopardize people’s lives due to unreliable (caused by the interference) healthcare data collections. Therefore, It is critical to mitigate the interference among WBANs to increase the reliability of the WBAN system while minimizing the system power consumption. Many existing approaches can deal with communication interference mitigation in general wireless networks but are not suitable for WBANs due to their ignoring the social nature of WBANs. Unlike the previous research, we for the first time propose a power game based approach to mitigate the communication interferences for WBANs based on the people’s social interaction information. Our major contributions include: (1) model the inter-WBANs interference, and determine the distance distribution of the interference through both theoretical analysis and Monte Carlo simulations; (2) develop social interaction detection and prediction algorithms for people carrying WBANs; (3) develop a power control game based on the social interaction information to maximize the system’s utility while minimize the energy consumption of WBANs system. The extensive simulation results show the effectiveness of the power control game for inter-WBAN interference mitigation using social interaction information. Our research opens a new research vista of WBANs using social networks. PMID:25436180

NEW APPROACHES: Demonstration of a dancing interference fringe

NASA Astrophysics Data System (ADS)

Kagawa, K.; Yamanaka, H.; Yokoi, S.; Hattori, H.

1997-11-01

A unique and amusing piece of laser art is proposed for use in physics education. It is shown that a dynamic and beautiful interference fringe can be produced when a He - Ne laser beam illuminates a droplet, which is called Brandy's tear, on a glass surface. This interference fringe can be explained in terms of the interference of multiple spherical waves scattered by the droplet. This kind of demonstration experiment is very helpful for exciting students' curiosity.

How to translate a bioassay into a screening assay for natural products: general considerations and implementation of antimicrobial screens.

PubMed

Fallarero, Adyary; Hanski, Leena; Vuorela, Pia

2014-09-01

Natural product sources have been a valuable provider of molecular diversity in many drug discovery programs and several therapeutically important drugs have been isolated from these. However, the screening of such materials can be very complicated due to the fact that they contain a complex mixture of secondary metabolites, but also the purified natural compounds exert a challenge for bioactivity screening. Success in identifying new therapeutics using in vitro bioassays is largely dependent upon the proper design, validation, and implementation of the screening assay. In this review, we discuss some aspects which are of significant concern when screening natural products in a microtiter plate-based format, being partly applicable to other assay formats as well, such as validation parameters, layouts for assay protocols, and common interferences caused by natural products samples, as well as various troubleshooting strategies. Examples from the field of natural product drug discovery of antibacterial compounds are discussed, and contributions from the realm of academic screenings are highlighted. Georg Thieme Verlag KG Stuttgart · New York.

Integrated Lateral Flow Test Strip with Electrochemical Sensor for Quantification of Phosphorylated Cholinesterase: Biomarker of Exposure to Organophosphorus Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Dan; Wang, Jun; Wang, Limin

An integrated lateral flow test strip with electrochemical sensor (LFTSES) device with rapid, selective and sensitive response for quantification of exposure to organophosphorus (OP) pesticides and nerve agents has been developed. The principle of this approach is based on parallel measurements of post-exposure and baseline acetylcholinesterase (AChE) enzyme activity, where reactivation of the phosphorylated AChE is exploited to enable measurement of total amount of AChE (including inhibited and active) which is used as a baseline for calculation of AChE inhibition. Quantitative measurement of phosphorylated adduct (OP-AChE) was realized by subtracting the active AChE from the total amount of AChE. Themore » proposed LFTSES device integrates immunochromatographic test strip technology with electrochemical measurement using a disposable screen printed electrode which is located under the test zone. It shows linear response between AChE enzyme activity and enzyme concentration from 0.05 to 10 nM, with detection limit of 0.02 nM. Based on this reactivation approach, the LFTSES device has been successfully applied for in vitro red blood cells inhibition studies using chlorpyrifos oxon as a model OP agent. This approach not only eliminates the difficulty in screening of low-dose OP exposure because of individual variation of normal AChE values, but also avoids the problem in overlapping substrate specificity with cholinesterases and avoids potential interference from other electroactive species in biological samples. It is baseline free and thus provides a rapid, sensitive, selective and inexpensive tool for in-field and point-of-care assessment of exposures to OP pesticides and nerve agents.« less

A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus.

PubMed

Voisset, Cécile; Daskalogianni, Chrysoula; Contesse, Marie-Astrid; Mazars, Anne; Arbach, Hratch; Le Cann, Marie; Soubigou, Flavie; Apcher, Sébastien; Fåhraeus, Robin; Blondel, Marc

2014-04-01

Epstein-Barr virus (EBV) is tightly associated with certain human cancers, but there is as yet no specific treatment against EBV-related diseases. The EBV-encoded EBNA1 protein is essential to maintain viral episomes and for viral persistence. As such, EBNA1 is expressed in all EBV-infected cells, and is highly antigenic. All infected individuals, including individuals with cancer, have CD8(+) T cells directed towards EBNA1 epitopes, yet the immune system fails to detect and destroy cells harboring the virus. EBV immune evasion depends on the capacity of the Gly-Ala repeat (GAr) domain of EBNA1 to inhibit the translation of its own mRNA in cis, thereby limiting the production of EBNA1-derived antigenic peptides presented by the major histocompatibility complex (MHC) class I pathway. Here we establish a yeast-based assay for monitoring GAr-dependent inhibition of translation. Using this assay we identify doxorubicin (DXR) as a compound that specifically interferes with the GAr effect on translation in yeast. DXR targets the topoisomerase-II-DNA complexes and thereby causes genomic damage. We show, however, that the genotoxic effect of DXR and various analogs thereof is uncoupled from the effect on GAr-mediated translation control. This is further supported by the observation that etoposide and teniposide, representing another class of topoisomerase-II-DNA targeting drugs, have no effect on GAr-mediated translation control. DXR and active analogs stimulate, in a GAr-dependent manner, EBNA1 expression in mammalian cells and overcome GAr-dependent restriction of MHC class I antigen presentation. These results validate our approach as an effective high-throughput screening assay to identify drugs that interfere with EBV immune evasion and, thus, constitute candidates for treating EBV-related diseases, in particular EBV-associated cancers.

A method for testing the spectraltransmittance of infrared smoke interference

NASA Astrophysics Data System (ADS)

Lei, Hao; Zhang, Yazhou; Wang, Guangping; Wu, Jingli

2018-02-01

Infrared smoke is mainly used for shielding, blind, deception and recognition on the battlefield. The traditional shelter smoke is mainly placed in the friendly positions or positions between the friendly positions and enemy positions, to reduce the enemy observation post investigative capacity. The passive interference capability of the smoke depends on the infrared extinction ability of the smoke. The infrared transmittance test is an objective and accurate representation of the extinction ability of the smoke. In this paper, a method for testing the spectral transmittance of infrared smoke interference is introduced. The uncertainty of the measurement results is analyzed. The results show that this method can effectively obtain the spectral transmittance of the infrared smoke and uncertainty of the measurement is 7.16%, which can be effective for the smoke detection, smoke composition analysis, screening effect evaluation to provide test parameters support.

A Novel Polyaminocarboxylate Compound To Treat Murine Pulmonary Aspergillosis by Interfering with Zinc Metabolism.

PubMed

Laskaris, Paris; Vicentefranqueira, Rocío; Helynck, Olivier; Jouvion, Grégory; Calera, José Antonio; du Merle, Laurence; Suzenet, Franck; Buron, Frédéric; de Sousa, Rodolphe Alves; Mansuy, Daniel; Cavaillon, Jean-Marc; Latgé, Jean-Paul; Munier-Lehmann, Hélène; Ibrahim-Granet, Oumaima

2018-06-01

Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to a lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59,223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild-type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen, 116 molecules were selected whose inhibitory effects on fungal growth were further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as by toxicity assays on HeLa cells and mice. Six compounds were selected following a rescreening, of which two were pyrazolones, two were porphyrins, and two were polyaminocarboxylates. All three groups showed good in vitro activity, but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with in vivo fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections by administration of this compound either as a monotherapy or as part of a combination therapy. Copyright © 2018 American Society for Microbiology.

Neural Basis of Semantic and Syntactic Interference in Sentence Comprehension

PubMed Central

Glaser, Yi G.; Martin, Randi C.; Van Dyke, Julie A.; Hamilton, A. Cris; Tan, Yingying

2013-01-01

According to the cue-based parsing approach (Lewis, Vasishth, & Van Dyke, 2006), sentence comprehension difficulty derives from interference from material that partially matches syntactic and semantic retrieval cues. In a 2 (low vs. high semantic interference) × 2 (low vs. high syntactic interference) fMRI study, greater activation was observed in left BA 44/45 for high versus low syntactic interference conditions following sentences and in BA 45/47 for high versus low semantic interference following comprehension questions. A conjunction analysis showed BA45 associated with both types of interference, while BA47 was associated with only semantic interference. Greater activation was also observed in the left STG in the high interference conditions. Importantly, the results for the LIFG could not be attributed to greater working memory capacity demands for high interference conditions. The results favor a fractionation of LIFG wherein BA45 is associated with post-retrieval selection and BA47 with controlled retrieval of semantic information. PMID:23933471

Identification of novel target sites and an inhibitor of the dengue virus E protein.

PubMed

Yennamalli, Ragothaman; Subbarao, Naidu; Kampmann, Thorsten; McGeary, Ross P; Young, Paul R; Kobe, Bostjan

2009-06-01

Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus life cycle. In this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus E protein to identify potential novel sites that could bind small molecules, which could interfere with the conformational transitions that mediate the fusion process. We used an in silico virtual screening approach combining three different docking algorithms (DOCK, GOLD and FlexX) to identify compounds that are likely to bind to these sites. Seven structurally diverse molecules were selected to test experimentally for inhibition of dengue virus propagation. The best compound showed an IC(50) in the micromolar range against dengue virus type 2.

Identification of novel target sites and an inhibitor of the dengue virus E protein

NASA Astrophysics Data System (ADS)

Yennamalli, Ragothaman; Subbarao, Naidu; Kampmann, Thorsten; McGeary, Ross P.; Young, Paul R.; Kobe, Bostjan

2009-06-01

Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus life cycle. In this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus E protein to identify potential novel sites that could bind small molecules, which could interfere with the conformational transitions that mediate the fusion process. We used an in silico virtual screening approach combining three different docking algorithms (DOCK, GOLD and FlexX) to identify compounds that are likely to bind to these sites. Seven structurally diverse molecules were selected to test experimentally for inhibition of dengue virus propagation. The best compound showed an IC50 in the micromolar range against dengue virus type 2.

Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

PubMed

Estrada, L D; Soto, C

2007-01-01

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

The Use of AlphaScreen Technology in HTS: Current Status

PubMed Central

Eglen, Richard M; Reisine, Terry; Roby, Philippe; Rouleau, Nathalie; Illy, Chantal; Bossé, Roger; Bielefeld, Martina

2008-01-01

AlphaScreen (Amplified Luminescent Proximity Homogeneous Assay Screen) is versatile assay technology developed to measuring analytes using a homogenous protocol. This technology is an example of a bead-based proximity assay and was developed from a diagnostic assay technology known as LOCI (Luminescent Oxygen Channeling Assay). Here, singlet oxygen molecules, generated by high energy irradiation of Donor beads, travel over a constrained distance (approx. 200 nm) to Acceptor beads. This results in excitation of a cascading series of chemical reactions, ultimately causing generation of a chemiluminescent signal. In the past decade, a wide variety of applications has been reported, ranging from detection of analytes involved in cell signaling, including protein:protein, protein:peptide, protein:small molecule or peptide:peptide interactions. Numerous homogeneous HTS-optimized assays have been reported using the approach, including generation of second messengers (such as accumulation of cyclic AMP, cyclic GMP, inositol [1, 4, 5] trisphosphate or phosphorylated ERK) from liganded GPCRs or tyrosine kinase receptors, post-translational modification of proteins (such as proteolytic cleavage, phosphorylation, ubiquination and sumoylation) as well as protein-protein and protein-nucleic acid interactions. Recently, the basic AlphaScreen technology was extended in that the chemistry of the Acceptor bead was modified such that emitted light is more intense and spectrally defined, thereby markedly reducing interference from biological fluid matrices (such as trace hemolysis in serum and plasma). In this format, referred to as AlphaLISA, it provides an alternative technology to classical ELISA assays and is suitable for high throughput automated fluid dispensing and detection systems. Collectively, AlphaScreen and AlphaLISA technologies provide a facile assay platform with which one can quantitate complex cellular processes using simple no-wash microtiter plate based assays. They provide the means by which large compound libraries can be screened in a high throughput fashion at a diverse range of therapeutically important targets, often not readily undertaken using other homogeneous assay technologies. This review assesses the current status of the technology in drug discovery, in general, and high throughput screening (HTS), in particular. PMID:20161822

RNA interference in the clinic: challenges and future directions

PubMed Central

Pecot, Chad V.; Calin, George A.; Coleman, Robert L.; Lopez-Berestein, Gabriel; Sood, Anil K.

2011-01-01

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. Although exploitation of RNAi has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release. PMID:21160526

Detecting and overcoming systematic bias in high-throughput screening technologies: a comprehensive review of practical issues and methodological solutions.

PubMed

Caraus, Iurie; Alsuwailem, Abdulaziz A; Nadon, Robert; Makarenkov, Vladimir

2015-11-01

Significant efforts have been made recently to improve data throughput and data quality in screening technologies related to drug design. The modern pharmaceutical industry relies heavily on high-throughput screening (HTS) and high-content screening (HCS) technologies, which include small molecule, complementary DNA (cDNA) and RNA interference (RNAi) types of screening. Data generated by these screening technologies are subject to several environmental and procedural systematic biases, which introduce errors into the hit identification process. We first review systematic biases typical of HTS and HCS screens. We highlight that study design issues and the way in which data are generated are crucial for providing unbiased screening results. Considering various data sets, including the publicly available ChemBank data, we assess the rates of systematic bias in experimental HTS by using plate-specific and assay-specific error detection tests. We describe main data normalization and correction techniques and introduce a general data preprocessing protocol. This protocol can be recommended for academic and industrial researchers involved in the analysis of current or next-generation HTS data. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Enhancing Infant-Toddler Adjustment during Transitions to Child Care: A Screening and Intervention Tool for Practitioners

ERIC Educational Resources Information Center

Fernandez, Mari T.; Marfo, Kofi

2005-01-01

Children's successful adjustment to child care involves effectively managing their separation from parents. Persistent problems with separation interfere with other relationships and with learning opportunities. The authors of this article developed a tool that caregivers can use to identify adjustment difficulties in young children who are …

Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

PubMed Central

Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

2004-01-01

Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. PMID:15084750

A New Reassigned Spectrogram Method in Interference Detection for GNSS Receivers.

PubMed

Sun, Kewen; Jin, Tian; Yang, Dongkai

2015-09-02

Interference detection is very important for Global Navigation Satellite System (GNSS) receivers. Current work on interference detection in GNSS receivers has mainly focused on time-frequency (TF) analysis techniques, such as spectrogram and Wigner-Ville distribution (WVD), where the spectrogram approach presents the TF resolution trade-off problem, since the analysis window is used, and the WVD method suffers from the very serious cross-term problem, due to its quadratic TF distribution nature. In order to solve the cross-term problem and to preserve good TF resolution in the TF plane at the same time, in this paper, a new TF distribution by using a reassigned spectrogram has been proposed in interference detection for GNSS receivers. This proposed reassigned spectrogram method efficiently combines the elimination of the cross-term provided by the spectrogram itself according to its inherent nature and the improvement of the TF aggregation property achieved by the reassignment method. Moreover, a notch filter has been adopted in interference mitigation for GNSS receivers, where receiver operating characteristics (ROCs) are used as metrics for the characterization of interference mitigation performance. The proposed interference detection method by using a reassigned spectrogram is evaluated by experiments on GPS L1 signals in the disturbing scenarios in comparison to the state-of-the-art TF analysis approaches. The analysis results show that the proposed interference detection technique effectively overcomes the cross-term problem and also keeps good TF localization properties, which has been proven to be valid and effective to enhance the interference Sensors 2015, 15 22168 detection performance; in addition, the adoption of the notch filter in interference mitigation has shown a significant acquisition performance improvement in terms of ROC curves for GNSS receivers in jamming environments.

A New Reassigned Spectrogram Method in Interference Detection for GNSS Receivers

PubMed Central

Sun, Kewen; Jin, Tian; Yang, Dongkai

2015-01-01

Interference detection is very important for Global Navigation Satellite System (GNSS) receivers. Current work on interference detection in GNSS receivers has mainly focused on time-frequency (TF) analysis techniques, such as spectrogram and Wigner–Ville distribution (WVD), where the spectrogram approach presents the TF resolution trade-off problem, since the analysis window is used, and the WVD method suffers from the very serious cross-term problem, due to its quadratic TF distribution nature. In order to solve the cross-term problem and to preserve good TF resolution in the TF plane at the same time, in this paper, a new TF distribution by using a reassigned spectrogram has been proposed in interference detection for GNSS receivers. This proposed reassigned spectrogram method efficiently combines the elimination of the cross-term provided by the spectrogram itself according to its inherent nature and the improvement of the TF aggregation property achieved by the reassignment method. Moreover, a notch filter has been adopted in interference mitigation for GNSS receivers, where receiver operating characteristics (ROCs) are used as metrics for the characterization of interference mitigation performance. The proposed interference detection method by using a reassigned spectrogram is evaluated by experiments on GPS L1 signals in the disturbing scenarios in comparison to the state-of-the-art TF analysis approaches. The analysis results show that the proposed interference detection technique effectively overcomes the cross-term problem and also keeps good TF localization properties, which has been proven to be valid and effective to enhance the interference detection performance; in addition, the adoption of the notch filter in interference mitigation has shown a significant acquisition performance improvement in terms of ROC curves for GNSS receivers in jamming environments. PMID:26364637

Design issues of a multimode interference-based 3-dB splitter.

PubMed

Themistos, Christos; Rahman, B M Azizur

2002-11-20

We have investigated important issues such as the power loss, the loss imbalance the fabrication tolerances, and the wavelength dependence for the design of a multimode interference-based 3-dB splitter on deeply etched InP waveguides under general, restricted, and symmetric interference mechanisms. For this investigation, we used the finite-element-based beam propagation approach. Results are presented.

Silicon Carbide Mixers Demonstrated to Improve the Interference Immunity of Radio-Based Aircraft Avionics

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.

1998-01-01

Concern over the interference of stray radiofrequency (RF) emissions with key aircraft avionics is evident during takeoff and landing of every commercial flight when the flight attendant requests that all portable electronics be switched off. The operation of key radio-based avionics (such as glide-slope and localizer approach instruments) depends on the ability of front-end RF receivers to detect and amplify desired information signals while rejecting interference from undesired RF sources both inside and outside the aircraft. Incidents where key navigation and approach avionics malfunction because of RF interference clearly represent an increasing threat to flight safety as the radio spectrum becomes more crowded. In an initial feasibility experiment, the U.S. Army Research Laboratory and the NASA Lewis Research Center recently demonstrated the strategic use of silicon carbide (SiC) semiconductor components to significantly reduce the susceptibility of an RF receiver circuit to undesired RF interference. A pair of silicon carbide mixer diodes successfully reduced RF interference (intermodulation distortion) in a prototype receiver circuit by a factor of 10 (20 dB) in comparison to a pair of commercial silicon-based mixer diodes.

[Key effect genes responding to nerve injury identified by gene ontology and computer pattern recognition].

PubMed

Pan, Qian; Peng, Jin; Zhou, Xue; Yang, Hao; Zhang, Wei

2012-07-01

In order to screen out important genes from large gene data of gene microarray after nerve injury, we combine gene ontology (GO) method and computer pattern recognition technology to find key genes responding to nerve injury, and then verify one of these screened-out genes. Data mining and gene ontology analysis of gene chip data GSE26350 was carried out through MATLAB software. Cd44 was selected from screened-out key gene molecular spectrum by comparing genes' different GO terms and positions on score map of principal component. Function interferences were employed to influence the normal binding of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite extension. Gene ontology analysis showed that the first genes on score map (marked by red *) mainly distributed in molecular transducer activity, receptor activity, protein binding et al molecular function GO terms. Cd44 is one of six effector protein genes, and attracted us with its function diversity. After adding different reagents into the medium to interfere the normal binding of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite extension were observed. CSC can inhibit neurite extension through binding Cd44 on the neuron membrane. This verifies that important genes in given physiological processes can be identified by gene ontology analysis of gene chip data.

[Screening of anti-lung cancer bioactive compounds from Curcuma longa by target cell extraction and UHPLC/LTQ Orbitrap MS].

PubMed

Zhou, Jian-Liang; Wu, Ye-Qing; Tan, Chun-Mei; Zhu, Ming; Ma, Lin-Ke

2016-10-01

A target cell extraction-chemical profiling method based on human alveolar adenocarcinoma cell line (A549 cells) and UHPLC/LTQ Orbitrap MS for screening the anti-lung cancer bioactive compounds from Curcuma longa has been developed in this paper. According to the hypothesis that when cells are incubated together with the extract of Curcuma longa, the potential bioactive compounds in the extract should selectively combine with the cells, then the cell-binding compounds could be separated and analyzed by LC-MS. The bioactive compounds in C. longa are lipophilic components. They intend to be absorbed on the inner wall of cell culture flask when they were incubated with A549 cells, which will produce interference in the blank solution. In this paper, by using cells digestion and multi-step centrifugation and transfer strategy, the interference problem has been solved. Finally, using the developed method, three cell-binding compounds were screened out and were identified as bisdemethoxycurcumin, demethoxycurcumin, and curcumin. These compounds are the main bioactive compounds with anti-lung cancer bioactivity in C. longa. The improved method developed in this paper could avoid the false positive results due to the absorption of lipophilic compounds on the inner wall of cell culture flask, which will to be an effective complementary method for current target cell extraction-chemical profiling technology. Copyright© by the Chinese Pharmaceutical Association.

Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

PubMed

Koike-Yusa, Hiroko; Li, Yilong; Tan, E-Pien; Velasco-Herrera, Martin Del Castillo; Yusa, Kosuke

2014-03-01

Identification of genes influencing a phenotype of interest is frequently achieved through genetic screening by RNA interference (RNAi) or knockouts. However, RNAi may only achieve partial depletion of gene activity, and knockout-based screens are difficult in diploid mammalian cells. Here we took advantage of the efficiency and high throughput of genome editing based on type II, clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems to introduce genome-wide targeted mutations in mouse embryonic stem cells (ESCs). We designed 87,897 guide RNAs (gRNAs) targeting 19,150 mouse protein-coding genes and used a lentiviral vector to express these gRNAs in ESCs that constitutively express Cas9. Screening the resulting ESC mutant libraries for resistance to either Clostridium septicum alpha-toxin or 6-thioguanine identified 27 known and 4 previously unknown genes implicated in these phenotypes. Our results demonstrate the potential for efficient loss-of-function screening using the CRISPR-Cas9 system.

When instructions fail. The effects of stimulus control training on brain injury survivors' attending and reporting during hearing screenings.

PubMed

Schlund, M W

2000-10-01

Bedside hearing screenings are routinely conducted by speech and language pathologists for brain injury survivors during rehabilitation. Cognitive deficits resulting from brain injury, however, may interfere with obtaining estimates of auditory thresholds. Poor comprehension or attention deficits often compromise patient abilities to follow procedural instructions. This article describes the effects of jointly applying behavioral methods and psychophysical methods to improve two severely brain-injured survivors' attending and reporting on auditory test stimuli presentation. Treatment consisted of stimulus control training that involved differentially reinforcing responding in the presence and absence of an auditory test tone. Subsequent hearing screenings were conducted with novel auditory test tones and a common titration procedure. Results showed that prior stimulus control training improved attending and reporting such that hearing screenings were conducted and estimates of auditory thresholds were obtained.

A strategy for screening antioxidants in Ginkgo biloba extract by comprehensive two-dimensional ultra high performance liquid chromatography.

PubMed

Guo, Ru-Zhou; Liu, Xin-Guang; Gao, Wen; Dong, Xin; Fanali, Salvatore; Li, Ping; Yang, Hua

2015-11-27

Recently, screening of bioactive compounds by on-line ultra-high performance liquid chromatography (UHPLC) draws increasing attentions for the advantages of rapidity and intuition. Nevertheless, most on-line methods were limited to the shortcoming like low resolution and peak capacity, which could interfere the active ingredient identification. Comprehensive two-dimensional UHPLC (LC×LC) has revealed to be a powerful tool to separate complex mixtures. Herein, a strategy based on LC×LC analysis coupled with pre-column 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was proposed to screen the antioxidants from the extract of Ginkgo biloba (EGB). A total of 61 compounds were identified in EGB, and 25 of them showed appreciable radical scavenging capacity. This work may offer pharmacodynamics base for further research about EGB, also the strategy is likelihood to be applied in screening antioxidant in other herbal medicine. Copyright © 2015 Elsevier B.V. All rights reserved.

Sequence-specific inhibition of Dicer measured with a force-based microarray for RNA ligands.

PubMed

Limmer, Katja; Aschenbrenner, Daniela; Gaub, Hermann E

2013-04-01

Malfunction of protein translation causes many severe diseases, and suitable correction strategies may become the basis of effective therapies. One major regulatory element of protein translation is the nuclease Dicer that cuts double-stranded RNA independently of the sequence into pieces of 19-22 base pairs starting the RNA interference pathway and activating miRNAs. Inhibiting Dicer is not desirable owing to its multifunctional influence on the cell's gene regulation. Blocking specific RNA sequences by small-molecule binding, however, is a promising approach to affect the cell's condition in a controlled manner. A label-free assay for the screening of site-specific interference of small molecules with Dicer activity is thus needed. We used the Molecular Force Assay (MFA), recently developed in our lab, to measure the activity of Dicer. As a model system, we used an RNA sequence that forms an aptamer-binding site for paromomycin, a 615-dalton aminoglycoside. We show that Dicer activity is modulated as a function of concentration and incubation time: the addition of paromomycin leads to a decrease of Dicer activity according to the amount of ligand. The measured dissociation constant of paromomycin to its aptamer was found to agree well with literature values. The parallel format of the MFA allows a large-scale search and analysis for ligands for any RNA sequence.

Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome.

PubMed

Mansilla, Alicia; Chaves-Sanjuan, Antonio; Campillo, Nuria E; Semelidou, Ourania; Martínez-González, Loreto; Infantes, Lourdes; González-Rubio, Juana María; Gil, Carmen; Conde, Santiago; Skoulakis, Efthimios M C; Ferrús, Alberto; Martínez, Ana; Sánchez-Barrena, María José

2017-02-07

The protein complex formed by the Ca 2+ sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a coregulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses, such as fragile X syndrome (FXS), the most common heritable autism disorder. Using crystallographic data and the virtual screening of a chemical library, we identified a set of heterocyclic small molecules as potential inhibitors of the NCS-1/Ric8a interaction. The aminophenothiazine FD44 interferes with NCS-1/Ric8a binding, and it restores normal synapse number and associative learning in a Drosophila FXS model. The synaptic effects elicited by FD44 feeding are consistent with the genetic manipulation of NCS-1. The crystal structure of NCS-1 bound to FD44 and the structure-function studies performed with structurally close analogs explain the FD44 specificity and the mechanism of inhibition, in which the small molecule stabilizes a mobile C-terminal helix inside a hydrophobic crevice of NCS-1 to impede Ric8a interaction. Our study shows the drugability of the NCS-1/Ric8a interface and uncovers a suitable region in NCS-1 for development of additional drugs of potential use on FXS and related synaptic disorders.

Proving allelopathy in crop-weed interactions

USDA-ARS?s Scientific Manuscript database

Allelopathy (plant/plant chemical warfare) is difficult to prove, especially when competition for resources is the dominant component of plant/plant interference (interference = allelopathy +competition). This paper describes experimental approaches for proving allelopathy and points out common pit...

Non-ARC solution to metal reflective notching: its evaluation and selection

NASA Astrophysics Data System (ADS)

Buffat, Stephen J.

1997-07-01

Patterning photoresists on reflective topography such as aluminum is one of the more difficult problems in device manufacturing. Interference effects caused by reflected light from the substrate/photoresist interface and surface topography result in coupling of additional energy into the film. This leads to linewidth variation known as reflective notching which severely impacts process latitude and increases critical dimension variation. For many years, suppliers approached the problem by adding dyes that absorb in the actinic region to create a larger non-bleachable absorption. In recent years, strongly absorbing intermediate layers or ARC's, both organic and inorganic, have seen widespread implementation to control reflective notching. However, if a fab is not equipped to accommodate the required ARC process, the processing can be very time consuming, cumbersome and costly. This study was undertaken to determine if a non-ARC, i-line photoresist process could be developed to reduce or eliminate aluminum reflective notching and accompanying critical dimension variation. This study was designed to screen, identify, and characterize various resist chemistries. Based on the screening characterization, a final, cost effective resist chemistry without ARC was selected, fully characterized and transferred into production. The selected material is currently being used in a high volume 0.60 micrometers CMOS, 200 mm wafer manufacturing process.

Accession Medical Standards Analysis and Research Activity (AMSARA)

DTIC Science & Technology

2004-01-01

young adults with psychiatric disorders 15. SUBJECT TERMS Accession, medical, standards, attrition, waiver, discharge, hospitalization, disability...86 Research to Develop a Screening Test for Detection of Psychiatric Disorders in Young Adults ...secondary to organic or functional mental disorders that interfere with work or school after age 12 or current use of medication to improve or maintain

Kindergarten Screening and Parent Engagement to Enhance Mental Health Service Utilization

ERIC Educational Resources Information Center

Girio, Erin L.

2010-01-01

The majority of youth in need of mental health services do not receive intervention as many are not identified as having a problem or their families experience practical or attitudinal barriers that interfere with service utilization. The school environment provides a unique point of access to reach all children, yet this setting has been…

A Simple Double-Source Model for Interference of Capillaries

ERIC Educational Resources Information Center

Hou, Zhibo; Zhao, Xiaohong; Xiao, Jinghua

2012-01-01

A simple but physically intuitive double-source model is proposed to explain the interferogram of a laser-capillary system, where two effective virtual sources are used to describe the rays reflected by and transmitted through the capillary. The locations of the two virtual sources are functions of the observing positions on the target screen. An…

Effect of amphiphilic additives on the behavior of water-based acrylic pressure-sensitive adhesives during paper recycling

Treesearch

Jihui Guo; Steven J. Severtson; Larry E. Gwin; Carl J. Houtman

2008-01-01

Pressure-sensitive adhesives (PSAs) in recovered paper reduce efficiency and increase operating costs for paper recycling mills. Increased PSA fragmentation during pulping and the corresponding reduction in screening efficiency are indications that a PSA will likely interfere with paper recycling. Water-based PSAs, which dominate the label market, have complex...

Virtual-Instrument-Based Online Monitoring System for Hands-on Laboratory Experiment of Partial Discharges

ERIC Educational Resources Information Center

Karmakar, Subrata

2017-01-01

Online monitoring of high-voltage (HV) equipment is a vital tool for early detection of insulation failure. Most insulation failures are caused by partial discharges (PDs) inside the HV equipment. Because of the very high cost of establishing HV equipment facility and the limitations of electromagnetic interference-screened laboratories, only a…

Evaluation of the Japanese Version of the Developmental Coordination Disorder Questionnaire as a Screening Tool for Clumsiness of Japanese Children

ERIC Educational Resources Information Center

Nakai, Akio; Miyachi, Taishi; Okada, Ryo; Tani, Iori; Nakajima, Shunji; Onishi, Masafumi; Fujita, Chikako; Tsujii, Masatsugu

2011-01-01

Developmental Coordination Disorder (DCD) is characterized by clumsiness and coordination difficulties. DCD interferes with academic performance and participation in physical activities and psychosocial functions, such as self-esteem, cognition, or emotion, from childhood through adolescence to adulthood. DCD is a common pediatric condition and…

Reading "Sky" and Seeing a Cloud: On the Relevance of Events for Perceptual Simulation

ERIC Educational Resources Information Center

Ostarek, Markus; Vigliocco, Gabriella

2017-01-01

Previous research has shown that processing words with an up/down association (e.g., bird, foot) can influence the subsequent identification of visual targets in congruent location (at the top/bottom of the screen). However, as facilitation and interference were found under similar conditions, the nature of the underlying mechanisms remained…

Coherence and visibility for vectorial light.

PubMed

Luis, Alfredo

2010-08-01

Two-path interference of transversal vectorial waves is embedded within a larger scheme: this is four-path interference between four scalar waves. This comprises previous approaches to coherence between vectorial waves and restores the equivalence between correlation-based coherence and visibility.

[Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children].

PubMed

Guo, Li-Hua; Zhao, Wei; Zhang, Jun-Jie; Zhang, Qian; Fan, Ying-Zhong; Wang, Jia-Xiang

2016-12-01

To screen and identify serum biomarkers for childhood hepatoblastoma (HB). The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

A Real-Time Interference Monitoring Technique for GNSS Based on a Twin Support Vector Machine Method.

PubMed

Li, Wutao; Huang, Zhigang; Lang, Rongling; Qin, Honglei; Zhou, Kai; Cao, Yongbin

2016-03-04

Interferences can severely degrade the performance of Global Navigation Satellite System (GNSS) receivers. As the first step of GNSS any anti-interference measures, interference monitoring for GNSS is extremely essential and necessary. Since interference monitoring can be considered as a classification problem, a real-time interference monitoring technique based on Twin Support Vector Machine (TWSVM) is proposed in this paper. A TWSVM model is established, and TWSVM is solved by the Least Squares Twin Support Vector Machine (LSTWSVM) algorithm. The interference monitoring indicators are analyzed to extract features from the interfered GNSS signals. The experimental results show that the chosen observations can be used as the interference monitoring indicators. The interference monitoring performance of the proposed method is verified by using GPS L1 C/A code signal and being compared with that of standard SVM. The experimental results indicate that the TWSVM-based interference monitoring is much faster than the conventional SVM. Furthermore, the training time of TWSVM is on millisecond (ms) level and the monitoring time is on microsecond (μs) level, which make the proposed approach usable in practical interference monitoring applications.

A Real-Time Interference Monitoring Technique for GNSS Based on a Twin Support Vector Machine Method

PubMed Central

Li, Wutao; Huang, Zhigang; Lang, Rongling; Qin, Honglei; Zhou, Kai; Cao, Yongbin

2016-01-01

Interferences can severely degrade the performance of Global Navigation Satellite System (GNSS) receivers. As the first step of GNSS any anti-interference measures, interference monitoring for GNSS is extremely essential and necessary. Since interference monitoring can be considered as a classification problem, a real-time interference monitoring technique based on Twin Support Vector Machine (TWSVM) is proposed in this paper. A TWSVM model is established, and TWSVM is solved by the Least Squares Twin Support Vector Machine (LSTWSVM) algorithm. The interference monitoring indicators are analyzed to extract features from the interfered GNSS signals. The experimental results show that the chosen observations can be used as the interference monitoring indicators. The interference monitoring performance of the proposed method is verified by using GPS L1 C/A code signal and being compared with that of standard SVM. The experimental results indicate that the TWSVM-based interference monitoring is much faster than the conventional SVM. Furthermore, the training time of TWSVM is on millisecond (ms) level and the monitoring time is on microsecond (μs) level, which make the proposed approach usable in practical interference monitoring applications. PMID:26959020

Interference-free ultrasound imaging during HIFU therapy, using software tools

NASA Technical Reports Server (NTRS)

Vaezy, Shahram (Inventor); Held, Robert (Inventor); Sikdar, Siddhartha (Inventor); Managuli, Ravi (Inventor); Zderic, Vesna (Inventor)

2010-01-01

Disclosed herein is a method for obtaining a composite interference-free ultrasound image when non-imaging ultrasound waves would otherwise interfere with ultrasound imaging. A conventional ultrasound imaging system is used to collect frames of ultrasound image data in the presence of non-imaging ultrasound waves, such as high-intensity focused ultrasound (HIFU). The frames are directed to a processor that analyzes the frames to identify portions of the frame that are interference-free. Interference-free portions of a plurality of different ultrasound image frames are combined to generate a single composite interference-free ultrasound image that is displayed to a user. In this approach, a frequency of the non-imaging ultrasound waves is offset relative to a frequency of the ultrasound imaging waves, such that the interference introduced by the non-imaging ultrasound waves appears in a different portion of the frames.

Rendezvous Protocols and Dynamic Frequency Hopping Interference Design for Anti-Jamming Satellite Communication

DTIC Science & Technology

2013-11-25

previously considered this proactive approach to combat unintentional, persistent (non- reactive) interference . In this project, we plan on extending our...channel” (or code ) by chance, through public knowledge of the underlying protocol semantics , or by compromising one of the network devices. An alternative...AFRL-RV-PS- AFRL-RV-PS- TR-2013-0142 TR-2013-0142 RENDEZVOUS PROTOCOLS AND DYNAMIC FREQUENCY HOPPING INTERFERENCE DESIGN FOR ANTI-JAMMING

Evaluation of two glucose meters and interference corrections for screening neonatal hypoglycemia.

PubMed

Wada, Yuka; Nakamura, Tomoo; Kaneshige, Masao; Takahashi, Shigehiro; Fujinaga, Hideshi; Tsukamoto, Keiko; Ito, Yushi; Sago, Haruhiko

2015-08-01

Many neonatal intensive care and maternal units still use self-monitoring of blood glucose (SMBG) devices as a tool to aid diagnosis despite the introduction of point-of-care testing (POCT) devices, which are known to have higher accuracy. We evaluated the performance of two glucose meters, the StatStrip (Nova Biomedical), a POCT device, and the Medisafe Mini (Terumo), an SMBG device, to detect hypoglycemia in neonates. In addition, we evaluated the interference of hematocrit, acetaminophen and ascorbic acid. Whole blood samples were drawn from neonates who were at risk of hypoglycemia and analyzed with the StatStrip and Medisafe Mini. The results were further confirmed with blood gas analyzers ABL825 and BM6050. To evaluate the interference of hematocrit, acetaminophen and ascorbic acid, concentrated solutions of glucose and interfering substances were gravimetrically prepared and analyzed. Among the 222 blood samples analyzed, results from the StatStrip were more closely aligned to those of the ABL825 at all levels of glucose than the Medisafe Mini. StatStrip appears to be unaffected by hematocrit, ascorbic acid or acetaminophen. We recommend its use in neonates in hospital. Further studies are required to identify other interference effects. © 2014 Japan Pediatric Society.

Chapter 17: Bioimage Informatics for Systems Pharmacology

PubMed Central

Li, Fuhai; Yin, Zheng; Jin, Guangxu; Zhao, Hong; Wong, Stephen T. C.

2013-01-01

Recent advances in automated high-resolution fluorescence microscopy and robotic handling have made the systematic and cost effective study of diverse morphological changes within a large population of cells possible under a variety of perturbations, e.g., drugs, compounds, metal catalysts, RNA interference (RNAi). Cell population-based studies deviate from conventional microscopy studies on a few cells, and could provide stronger statistical power for drawing experimental observations and conclusions. However, it is challenging to manually extract and quantify phenotypic changes from the large amounts of complex image data generated. Thus, bioimage informatics approaches are needed to rapidly and objectively quantify and analyze the image data. This paper provides an overview of the bioimage informatics challenges and approaches in image-based studies for drug and target discovery. The concepts and capabilities of image-based screening are first illustrated by a few practical examples investigating different kinds of phenotypic changes caEditorsused by drugs, compounds, or RNAi. The bioimage analysis approaches, including object detection, segmentation, and tracking, are then described. Subsequently, the quantitative features, phenotype identification, and multidimensional profile analysis for profiling the effects of drugs and targets are summarized. Moreover, a number of publicly available software packages for bioimage informatics are listed for further reference. It is expected that this review will help readers, including those without bioimage informatics expertise, understand the capabilities, approaches, and tools of bioimage informatics and apply them to advance their own studies. PMID:23633943

The Use of ICP-MS and IC-ICP-MS in Environmental and Exposure Assesssment

EPA Science Inventory

OVERVIEW: Application of collision/reaction cell interference reduction technology for the minimization of polyatomic interferences in environmental matrices. Improved risk assessments through the use of arsenic speciation approaches that estimate the bio-accessibility asso...

A fast, robust algorithm for power line interference cancellation in neural recording

NASA Astrophysics Data System (ADS)

Keshtkaran, Mohammad Reza; Yang, Zhi

2014-04-01

Objective. Power line interference may severely corrupt neural recordings at 50/60 Hz and harmonic frequencies. The interference is usually non-stationary and can vary in frequency, amplitude and phase. To retrieve the gamma-band oscillations at the contaminated frequencies, it is desired to remove the interference without compromising the actual neural signals at the interference frequency bands. In this paper, we present a robust and computationally efficient algorithm for removing power line interference from neural recordings. Approach. The algorithm includes four steps. First, an adaptive notch filter is used to estimate the fundamental frequency of the interference. Subsequently, based on the estimated frequency, harmonics are generated by using discrete-time oscillators, and then the amplitude and phase of each harmonic are estimated by using a modified recursive least squares algorithm. Finally, the estimated interference is subtracted from the recorded data. Main results. The algorithm does not require any reference signal, and can track the frequency, phase and amplitude of each harmonic. When benchmarked with other popular approaches, our algorithm performs better in terms of noise immunity, convergence speed and output signal-to-noise ratio (SNR). While minimally affecting the signal bands of interest, the algorithm consistently yields fast convergence (<100 ms) and substantial interference rejection (output SNR >30 dB) in different conditions of interference strengths (input SNR from -30 to 30 dB), power line frequencies (45-65 Hz) and phase and amplitude drifts. In addition, the algorithm features a straightforward parameter adjustment since the parameters are independent of the input SNR, input signal power and the sampling rate. A hardware prototype was fabricated in a 65 nm CMOS process and tested. Software implementation of the algorithm has been made available for open access at https://github.com/mrezak/removePLI. Significance. The proposed algorithm features a highly robust operation, fast adaptation to interference variations, significant SNR improvement, low computational complexity and memory requirement and straightforward parameter adjustment. These features render the algorithm suitable for wearable and implantable sensor applications, where reliable and real-time cancellation of the interference is desired.

Hierarchical virtual screening approaches in small molecule drug discovery.

PubMed

Kumar, Ashutosh; Zhang, Kam Y J

2015-01-01

Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway

PubMed Central

2012-01-01

Background Genome-scale RNA-interference (RNAi) screens are becoming ever more common gene discovery tools. However, whilst every screen identifies interacting genes, less attention has been given to how factors such as library design and post-screening bioinformatics may be effecting the data generated. Results Here we present a new genome-wide RNAi screen of the Drosophila JAK/STAT signalling pathway undertaken in the Sheffield RNAi Screening Facility (SRSF). This screen was carried out using a second-generation, computationally optimised dsRNA library and analysed using current methods and bioinformatic tools. To examine advances in RNAi screening technology, we compare this screen to a biologically very similar screen undertaken in 2005 with a first-generation library. Both screens used the same cell line, reporters and experimental design, with the SRSF screen identifying 42 putative regulators of JAK/STAT signalling, 22 of which verified in a secondary screen and 16 verified with an independent probe design. Following reanalysis of the original screen data, comparisons of the two gene lists allows us to make estimates of false discovery rates in the SRSF data and to conduct an assessment of off-target effects (OTEs) associated with both libraries. We discuss the differences and similarities between the resulting data sets and examine the relative improvements in gene discovery protocols. Conclusions Our work represents one of the first direct comparisons between first- and second-generation libraries and shows that modern library designs together with methodological advances have had a significant influence on genome-scale RNAi screens. PMID:23006893

Material-specific retroactive interference effects of the Wechsler Adult Intelligence Scale-Fourth Edition on the Wechsler Memory Scale-Fourth Edition in a nonclinical sample.

PubMed

Ingram, Nicolette S; Diakoumakos, Jessica V; Sinclair, Erin R; Crowe, Simon F

2016-01-01

This study investigated proactive and retroactive interference effects between the Wechsler Memory Scale-Fourth Edition (WMS-IV) using the flexible approach, and the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). One hundred and eighty nonclinical participants were assigned to a four (visual interference, verbal interference, visual and verbal interference, vs. no interference) by two (retroactive vs. proactive) between-subjects design. The administration order of the tests was counterbalanced (i.e., administration of the WAIS-IV prior to the WMS-IV, and the WAIS-IV administered during the delay interval of the WMS-IV). The WAIS-IV produced significant retroactive interference effects on the WMS-IV; however, no proactive interference effect was observed. The retroactive interference effect was dependent on material specificity. The results indicate that material presented within the delay of the WMS-IV can have a significant effect on subsequent delayed recall. Clinicians should carefully consider the effects associated with carry-over effects of these tests when using them in combination.

A media player causes clinically significant telemetry interference with implantable loop recorders.

PubMed

Thaker, Jay P; Patel, Mehul B; Shah, Ashok J; Liepa, Valdis V; Jongnarangsin, Krit; Thakur, Ranjan K

2009-03-01

The implantable loop recorder is a useful diagnostic tool for intermittent cardiovascular symptoms because it can automatically record arrhythmias as well as a patient-triggered ECG. Media players have been shown to cause telemetry interference with pacemakers. Telemetry interference may be important in patients with implantable loop recorders because capturing a patient-triggered ECG requires a telemetry link between a hand-held activator and the implanted device. The purpose of this study was to determine if a media player causes interference with implantable loop recorders. Fourteen patients with implantable loop recorders underwent evaluation for interference with a 15 GB third generation iPod (Apple, Inc.) media player. All patients had the Reveal Plus (Medtronic, Inc.) implantable loop recorder. We tested for telemetry interference on the programmer by first establishing a telemetry link with the loop recorder and then, the media player was placed next to it, first turned off and then, on. We evaluated for telemetry interference between the activator and the implanted device by placing the activator over the device (normal use) and the media player next to it, first turned off and then, on. We made 5 attempts to capture a patient-triggered ECG by depressing the activator switch 5 times while the media player was off or on. Telemetry interference on the programmer screen, consisting of either high frequency spikes or blanking of the ECG channel was seen in all patients. Telemetry interference with the activator resulted in failure to capture an event in 7 patients. In one of these patients, a green indicator light on the activator suggested that a patient-triggered event was captured, but loop recorder interrogation did not show a captured event. In the remaining 7 patients, an event was captured and appropriately recognized by the device at least 1 out of 5 times. A media player playing in close proximity to an implanted loop recorder may interfere with capture of a patient-triggered event. Patients should be advised to keep media players away from their implanted loop recorder.

Thermooptic two-mode interference device for reconfigurable quantum optic circuits

NASA Astrophysics Data System (ADS)

Sahu, Partha Pratim

2018-06-01

Reconfigurable large-scale integrated quantum optic circuits require compact component having capability of accurate manipulation of quantum entanglement for quantum communication and information processing applications. Here, a thermooptic two-mode interference coupler has been introduced as a compact component for generation of reconfigurable complex multi-photons quantum interference. Both theoretical and experimental approaches are used for the demonstration of two-photon and four-photon quantum entanglement manipulated with thermooptic phase change in TMI region. Our results demonstrate complex multi-photon quantum interference with high fabrication tolerance and quantum fidelity in smaller dimension than previous thermooptic Mach-Zehnder implementations.

Quantum cascade laser-based screening portal for the detection of explosive precursors

NASA Astrophysics Data System (ADS)

Lindley, Ruth; Normand, Erwan; Howieson, Iain; McCulloch, Michael; Black, Paul; Lewis, Colin; Foulger, Brian

2007-10-01

In recent years, quantum cascade lasers (QCL) have been proven in robust, high-performance gas analyzers designed for continuous emission monitoring (CEM) in harsh environments. In 2006, Cascade Technologies reported progress towards adapting its patented technology for homeland security applications by publishing initial results on explosive compound detection. This paper presents the performance and results from a QCL-based people screening portal developed during the past year and aimed at the detection of precursors used in the make up of improvised explosive devices (IED). System tests have been carried out on a large number of potential interferents, together with target precursor materials, reinforcing original assumptions that compound fingerprinting can be effectively demonstrated using this technique. Results have shown that an extremely high degree of specificity can be achieved with a sub-second response time. Furthermore, it has been shown that unambiguous precursor signature recognition can be extended to compound mixtures associated with the intermediate stages in the make up of IEDs, whilst maintaining interferent immunity. The portal sensitivity was configured for parts per billion (ppb) detection level thresholds, but is currently being reconfigured for sub-ppb detection. In summary, the results obtained from the QCL based portal indicate that development of a low cost detection system, with enhanced features such as low false positive and high throughput screening of individuals or items, is possible. Development and testing was carried out with the support of the UK government.

Potential interference to GPS from UWB transmitters : phase II test results

DOT National Transportation Integrated Search

2001-03-16

In 1999, the U.S. Department of Transportation (DOT") approached Stanford University to research the compatibility of UWB and GPS and to conduct tests to help quantify any interference problems. This is the second report from Stanford to the Departme...

Refreshable Braille displays using EAP actuators

NASA Astrophysics Data System (ADS)

Bar-Cohen, Yoseph

2010-04-01

Refreshable Braille can help visually impaired persons benefit from the growing advances in computer technology. The development of such displays in a full screen form is a great challenge due to the need to pack many actuators in small area without interferences. In recent years, various displays using actuators such as piezoelectric stacks have become available in commercial form but most of them are limited to one line Braille code. Researchers in the field of electroactive polymers (EAP) investigated methods of using these materials to form full screen displays. This manuscript reviews the state of the art of producing refreshable Braille displays using EAP-based actuators.

Refreshable Braille Displays Using EAP Actuators

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph

2010-01-01

Refreshable Braille can help visually impaired persons benefit from the growing advances in computer technology. The development of such displays in a full screen form is a great challenge due to the need to pack many actuators in small area without interferences. In recent years, various displays using actuators such as piezoelectric stacks have become available in commercial form but most of them are limited to one line Braille code. Researchers in the field of electroactive polymers (EAP) investigated methods of using these materials to form full screen displays. This manuscript reviews the state of the art of producing refreshable Braille displays using EAP-based actuators..

Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death

PubMed Central

Zhu, Ping Jun; Hobson, Peyton; Southall, Noel; Qiu, Cunping; Thomas, Craig J.; Lu, Jiamo; Inglese, James; Zheng, Wei; Leppla, Stephen H.; Bugge, Thomas H.; Austin, Christopher P.; Liu, Shihui

2009-01-01

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization. PMID:19540764

Potential of phytoceuticals to affect antibiotic residue detection tests in cow milk in a randomised trial

PubMed Central

Mullen, Keena AE; Beasley, Erin; Rizzo, Julio Q; Washburn, Steven P; Baynes, Ronald E; Mason, Sharon E

2017-01-01

Mastitis is a costly disease for dairy farmers. Some dairy farmers use herbal products, or phytoceuticals, to treat mastitis. Phytoceuticals have not been approved for this use by the United States Food and Drug Administration, and have not been tested to determine how they impact antibiotic residue detection testing. The current study tested the potential for phytoceuticals to cause positive results on two milk antibiotic residue screening tests, the Delvotest P and Charm SL Beta-lactam test, or to interfere with the detection of antibiotics by these tests. The three phytoceuticals tested were labelled for intramammary, topical or intravulvar administration. Testing was performed in vitro using the products diluted in milk obtained from healthy organic dairy cows. Phytoceuticals were tested at concentrations ranging from 1.5 per cent to 100 per cent. Concentration levels were replicated at least twice on each milk antibiotic residue screening test. The Delvotest P is based on detection of bacterial inhibitors and no positive results were obtained for any product at concentrations less than 50 per cent. The Charm SL Beta-lactam test uses a receptor for the detection of beta-lactam antibiotics and no concentration of phytoceuticals caused an interference with these tests. Based on dilution of the products in bovine milk at physiologically achievable levels, phytoceutical products tested at levels expected after treatment do not cause positive test results for the Delvotest P nor do they interfere with the Charm SL Beta-lactam test in detection of various antibiotics. PMID:28890791

Comparison of a rational vs. high throughput approach for rapid salt screening and selection.

PubMed

Collman, Benjamin M; Miller, Jonathan M; Seadeek, Christopher; Stambek, Julie A; Blackburn, Anthony C

2013-01-01

In recent years, high throughput (HT) screening has become the most widely used approach for early phase salt screening and selection in a drug discovery/development setting. The purpose of this study was to compare a rational approach for salt screening and selection to those results previously generated using a HT approach. The rational approach involved a much smaller number of initial trials (one salt synthesis attempt per counterion) that were selected based on a few strategic solubility determinations of the free form combined with a theoretical analysis of the ideal solvent solubility conditions for salt formation. Salt screening results for sertraline, tamoxifen, and trazodone using the rational approach were compared to those previously generated by HT screening. The rational approach produced similar results to HT screening, including identification of the commercially chosen salt forms, but with a fraction of the crystallization attempts. Moreover, the rational approach provided enough solid from the very initial crystallization of a salt for more thorough and reliable solid-state characterization and thus rapid decision-making. The crystallization techniques used in the rational approach mimic larger-scale process crystallization, allowing smoother technical transfer of the selected salt to the process chemist.

Histological Analysis of the Arabidopsis Gynoecium and Ovules Using Chloral Hydrate Clearing and Differential Interference Contrast Light Microscopy.

PubMed

Franks, Robert G

2016-01-01

The use of chloral hydrate optical clearing paired with differential interference contrast microscopy allows the analysis of internal structures of developing plant organs without the need for paraffin embedding and sectioning. This approach is appropriate for the analysis of the developing gynoecium or seedpod of the flowering plant Arabidopsis thaliana and many other types of fixed plant material. Early stages of ovule development are observable with this approach.

Colonoscopy and Colorectal Cancer Screening in Adults with Intellectual and Developmental Disabilities: Review of a Series of Cases and Recommendations for Examination

ERIC Educational Resources Information Center

Fischer, Leonard S.; Becker, Andrew; Paraguya, Maria; Chukwu, Cecilia

2012-01-01

Adults with intellectual and developmental disabilities (IDD) frequently have comorbidities that might interfere with colonoscopy preparation and examination. In this article, the authors review their experience with colonoscopies performed from 2002 through 2010 on adults with IDD at a state institution to evaluate quality and safety of…

Water toxicity monitoring using Vibrio fischeri: a method free of interferences from colour and turbidity.

PubMed

Faria, Elsa Correia; Treves Brown, Bernard J; Snook, Richard D

2004-02-01

In this paper the kinetic method for the determination of toxicity using Vibrio fischeri is described and suggested as a potential method for the continuous screening of wastewater toxicity. The kinetic method was demonstrated to be free from interferences due to colour and turbidity normally observed when testing wastewater samples with this organism. This is of great importance for the application of the method to remote toxicity screening of wastewaters. The effect of colour, investigated using 50 ppm Zn(2+) solutions containing the food-dye tropaeolin O, and the effect of turbidity, investigated using 50 ppm Zn(2+) solutions containing white optically reflective and coloured optically absorbing polystyrene beads, is reported. It was also found that the design of the light detection system of the instrument ensures efficient collection of the light scattered by particles in the sample, which enables a greater range of turbid samples to be tested. In addition the natural light decay was found to be negligible during the duration of a 10 min test and thus one channel would be enough to carry out the tests. This would mean halving the quantity of bacterial reagent used and reducing the cost of the tests.

From The Cover: Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation

NASA Astrophysics Data System (ADS)

Nollen, Ellen A. A.; Garcia, Susana M.; van Haaften, Gijs; Kim, Soojin; Chavez, Alejandro; Morimoto, Richard I.; Plasterk, Ronald H. A.

2004-04-01

Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. protein misfolding | neurodegenerative diseases

Measurement environments and testing

NASA Astrophysics Data System (ADS)

Marvin, A. C.

1991-06-01

The various methods used to assess both the emission (interference generation) performance of electronic equipment and the immunity of electronic equipment to external electromagnetic interference are described. The measurement methods attempt to simulate realistic operating conditions for the equipment being tested, yet at the same time they must be repeatable and practical to operate. This has led to the development of a variety of test methods, each of which has its limitations. Concentration is on the most common measurement methods such as open-field test sites, screened enclosures and transverse electromagnetic (TEM) cells. The physical justification for the methods, their limitations, and measurement precision are described. Ways of relating similar measurements made by different methods are discussed, and some thoughts on future measurement improvements are presented.

Test strips based on iron(iii)-impregnated alginate/polyacrylonitrile nanofibers for naked eye screening of tetracycline.

PubMed

Li, Yan; Mohammed, Abedalwafa; Li, De; Wang, Lu

2018-05-03

Tetracycline (TC) is an inexpensive broad-spectrum antibiotic used to treat infectious diseases and to promote growth in animals. However, driven by economic interest, abuse of TC poses a serious threat to human beings, and it remains a significant challenge to create easy-to-use TC colorimetric test strips for public use. Herein, we present a strategy to prepare free-standing, nanofibrous structured test strips with tortuous porous structure and large surface area by combining polyacrylonitrile nanofibrous membranes (PAN NMs), alginate, and Fe3+. In this approach, alginate was first functionalized on the PAN NMs and then, Fe3+ was assembled into the alginate to construct a TC-sensing surface. The resultant test strips exhibited the following integrated properties: fast sensing process (10 min), low naked eye detection limit (5 μg kg-1), excellent anti-interference ability, and satisfactory reusability. Furthermore, the TC concentration-dependent color change (yellow to maroon) was quantitatively visualized by an iPhone read-out hue parameter. All the findings indicate that this intriguing approach may pave the way for versatile designing of NMs to serve as a preventive treatment for the public.

Inhibitory Effect of 2,3,5,6-Tetrafluoro-4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide Derivatives on HIV Reverse Transcriptase Associated RNase H Activities

PubMed Central

Pala, Nicolino; Esposito, Francesca; Rogolino, Dominga; Carcelli, Mauro; Sanna, Vanna; Palomba, Michele; Naesens, Lieve; Corona, Angela; Grandi, Nicole; Tramontano, Enzo; Sechi, Mario

2016-01-01

The HIV-1 ribonuclease H (RNase H) function of the reverse transcriptase (RT) enzyme catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate, and represents a suitable target for drug development. A particularly attractive approach is constituted by the interference with the RNase H metal-dependent catalytic activity, which resides in the active site located at the C-terminus p66 subunit of RT. Herein, we report results of an in-house screening campaign that allowed us to identify 4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamides, prepared by the “click chemistry” approach, as novel potential HIV-1 RNase H inhibitors. Three compounds (9d, 10c, and 10d) demonstrated a selective inhibitory activity against the HIV-1 RNase H enzyme at micromolar concentrations. Drug-likeness, predicted by the calculation of a panel of physicochemical and ADME properties, putative binding modes for the active compounds, assessed by computational molecular docking, as well as a mechanistic hypothesis for this novel chemotype are reported. PMID:27556447

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

PubMed

Wu, Junjun; Zhang, Xia; Zhu, Yingjie; Tan, Qinyu; He, Jiacheng; Dong, Mingsheng

2017-05-03

Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.

40 CFR 80.47 - Performance-based Analytical Test Method Approach.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chemistry and statistics, or at least a bachelor's degree in chemical engineering, from an accredited... be compensated for any known chemical interferences using good laboratory practices. (3) The test... section, individual test results shall be compensated for any known chemical interferences using good...

RNA Interference Therapies for an HIV-1 Functional Cure.

PubMed

Scarborough, Robert J; Gatignol, Anne

2017-12-27

HIV-1 drug therapies can prevent disease progression but cannot eliminate HIV-1 viruses from an infected individual. While there is hope that elimination of HIV-1 can be achieved, several approaches to reach a functional cure (control of HIV-1 replication in the absence of drug therapy) are also under investigation. One of these approaches is the transplant of HIV-1 resistant cells expressing anti-HIV-1 RNAs, proteins or peptides. Small RNAs that use RNA interference pathways to target HIV-1 replication have emerged as competitive candidates for cell transplant therapy and have been included in all gene combinations that have so far entered clinical trials. Here, we review RNA interference pathways in mammalian cells and the design of therapeutic small RNAs that use these pathways to target pathogenic RNA sequences. Studies that have been performed to identify anti-HIV-1 RNA interference therapeutics are also reviewed and perspectives on their use in combination gene therapy to functionally cure HIV-1 infection are provided.

Acoustic Droplet Ejection Technology and Its Application in High-Throughput RNA Interference Screening.

PubMed

Nebane, N Miranda; Coric, Tatjana; McKellip, Sara; Woods, LaKeisha; Sosa, Melinda; Rasmussen, Lynn; Bjornsti, Mary-Ann; White, E Lucile

2016-02-01

The development of acoustic droplet ejection (ADE) technology has resulted in many positive changes associated with the operations in a high-throughput screening (HTS) laboratory. Originally, this liquid transfer technology was used to simply transfer DMSO solutions of primarily compounds. With the introduction of Labcyte's Echo 555, which has aqueous dispense capability, the application of this technology has been expanded beyond its original use. This includes the transfer of many biological reagents solubilized in aqueous buffers, including siRNAs. The Echo 555 is ideal for siRNA dispensing because it is accurate at low volumes and a step-down dilution is not necessary. The potential for liquid carryover and cross-contamination is eliminated, as no tips are needed. Herein, we describe the siRNA screening platform at Southern Research's HTS Center using the ADE technology. With this technology, an siRNA library can be dispensed weeks or even months in advance of the assay itself. The protocol has been optimized to achieve assay parameters comparable to small-molecule screening parameters, and exceeding the norm reported for genomewide siRNA screens. © 2015 Society for Laboratory Automation and Screening.

A Whole Cell Pathway Screen Reveals Seven Novel Chemosensitizers to Combat Chloroquine Resistant Malaria

PubMed Central

Ch'ng, Jun-Hong; Mok, Sachel; Bozdech, Zbynek; Lear, Martin James; Boudhar, Aicha; Russell, Bruce; Nosten, Francois; Tan, Kevin Shyong-Wei

2013-01-01

Due to the widespread prevalence of resistant parasites, chloroquine (CQ) was removed from front-line antimalarial chemotherapy in the 1990s despite its initial promise of disease eradication. Since then, resistance-conferring mutations have been identified in transporters such as the PfCRT, that allow for the efflux of CQ from its primary site of action, the parasite digestive vacuole. Chemosensitizing/chemoreversing compounds interfere with the function of these transporters thereby sensitizing parasites to CQ once again. However, compounds identified thus far have disappointing in vivo efficacy and screening for alternative candidates is required to revive this strategy. In this study, we propose a simple and direct means to rapidly screen for such compounds using a fluorescent-tagged CQ molecule. When this screen was applied to a small library, seven novel chemosensitizers (octoclothepin, methiothepin, metergoline, loperamide, chlorprothixene, L-703,606 and mibefradil) were quickly elucidated, including two which showed greater potency than the classical chemosensitizers verapamil and desipramine. PMID:23615863

Screening utility of the social anxiety screening scale in Spanish speaking adolescents.

PubMed

Piqueras, José Antonio; Olivares, José; Hidalgo, María Dolores

2012-07-01

The aim of this study was to analyse the screening utility of the Social Anxiety Screening Scale (SASS/EDAS) in a sample of 227 adolescents with social anxiety disorder and 156 Without it (14-17 years). Results showed that the EDAS subscales (Avoidance, Distress and Interference) scores were reliable in terms of internal consistency (alpha > .80). All the subscales discriminated between adolescents with and without the disorder. They also showed a positive and significant correlation with other empirically validated measures of social anxiety. The three subscales indicated relevant sensitivity (69.16-84.14%), specificity (63.46-66.03%) and areas under the curve (.74-.81%). Binary logistic regression analyses indicated the adequate predictive utility of EDAS subscales, with the Distress subscale as the best diagnostic predictor. The data provide empirical evidence of the usefulness of EDAS as a screener for adolescent social anxiety disorder in terms of reliability, convergent and discriminant validity, diagnostic accuracy and clinical usefulness.

Evaluation of the dispersion effect in through movement bicycles at signalized intersection via cellular automata simulation

NASA Astrophysics Data System (ADS)

Jiang, Hang; Ma, Yongjian; Jiang, Lin; Chen, Guozhou; Wang, Dongwei

2018-05-01

At signalized intersection areas, bicycle traffic presents a dispersion feature which may influence the movements of vehicles during peak period. The primary objective of this study is to simulate the dispersion effect in through-movement bicycle traffic at intersection areas and evaluate its influence on through-movement traffic. A cellular automata (CA) model is developed and validated to simulate the operations of through-movement bicycle traffic departing from two types of intersection approaches. Simulation results show that bicycles benefit from the dispersion effect when they depart from the approach with an exclusive right-turn vehicle lane. But when bicycles travel from the approach with a shared right-turn and through vehicle lane, the dispersion effect will result in friction interference and block interference on through-movement vehicles. Bicycle interferences reduce the vehicle speed and increase the delay of through-movement vehicles. The policy implications in regard to the dispersion effect from two types of approaches are discussed to improve the performance of through-movement traffic operations at signalized intersections.

Lions, tigers, and bears, oh sh!t: Semantics versus tabooness in speech production.

PubMed

White, Katherine K; Abrams, Lise; Koehler, Sarah M; Collins, Richard J

2017-04-01

While both semantic and highly emotional (i.e., taboo) words can interfere with speech production, different theoretical mechanisms have been proposed to explain why interference occurs. Two experiments investigated these theoretical approaches by comparing the magnitude of these two types of interference and the stages at which they occur during picture naming. Participants named target pictures superimposed with semantic, taboo, or unrelated distractor words that were presented at three different stimulus-onset asynchronies (SOA): -150 ms, 0 ms, or +150 ms. In addition, the duration of distractor presentation was manipulated across experiments, with distractors appearing for the duration of the picture (Experiment 1) or for 350 ms (Experiment 2). Taboo distractors interfered more than semantic distractors, i.e., slowed target naming times, at all SOAs. While distractor duration had no effect on type of interference at -150 or 0 SOAs, briefly presented distractors eliminated semantic interference but not taboo interference at +150 SOA. Discussion focuses on how existing speech production theories can explain interference from emotional distractors and the unique role that attention may play in taboo interference.

shRNA target prediction informed by comprehensive enquiry (SPICE): a supporting system for high-throughput screening of shRNA library.

PubMed

Kamatuka, Kenta; Hattori, Masahiro; Sugiyama, Tomoyasu

2016-12-01

RNA interference (RNAi) screening is extensively used in the field of reverse genetics. RNAi libraries constructed using random oligonucleotides have made this technology affordable. However, the new methodology requires exploration of the RNAi target gene information after screening because the RNAi library includes non-natural sequences that are not found in genes. Here, we developed a web-based tool to support RNAi screening. The system performs short hairpin RNA (shRNA) target prediction that is informed by comprehensive enquiry (SPICE). SPICE automates several tasks that are laborious but indispensable to evaluate the shRNAs obtained by RNAi screening. SPICE has four main functions: (i) sequence identification of shRNA in the input sequence (the sequence might be obtained by sequencing clones in the RNAi library), (ii) searching the target genes in the database, (iii) demonstrating biological information obtained from the database, and (iv) preparation of search result files that can be utilized in a local personal computer (PC). Using this system, we demonstrated that genes targeted by random oligonucleotide-derived shRNAs were not different from those targeted by organism-specific shRNA. The system facilitates RNAi screening, which requires sequence analysis after screening. The SPICE web application is available at http://www.spice.sugysun.org/.

Best Practices for Intrathecal Baclofen Therapy: Patient Selection.

PubMed

Saulino, Michael; Ivanhoe, Cindy B; McGuire, John R; Ridley, Barbara; Shilt, Jeffrey S; Boster, Aaron L

2016-08-01

When spasticity interferes with comfort, function, activities of daily living, mobility, positioning, or caregiver assistance, patients should be considered for intrathecal baclofen (ITB) therapy. An expert panel consulted on best practices. ITB can be considered for problematic spasticity involving muscles/muscle groups during all phases of diseases, including progressive neurologic diseases. ITB alone or with other treatments should not be exclusively reserved for individuals who have failed other approaches. ITB combined with rehabilitation can be effective in certain ambulatory patients. ITB is also highly effective in managing spasticity in children, who may suffer limb deformity, joint dislocation, and poor motor function from spasticity and muscle tightness on the growing musculoskeletal system. Spasticity management often allows individuals to achieve higher function. When cognition is impaired, ITB controls spasticity without the cognitive side effects of some oral medications. Goal setting addresses expectations and treatment in the framework of pathology, impairment, and disability. ITB is contraindicated in patients with hypersensitivity to baclofen, which is rare, or active infection. Some patients with an adverse reaction to oral baclofen may be mistakenly classified as having an allergic reaction and may benefit from ITB. Relative contraindications include unrealistic goals, unmanageable mental health issues, psychosocial factors affecting compliance, and financial burden. Vascular shunting for hydrocephalus is not a contraindication, but concurrent use may affect cerebrospinal fluid flow. Seizures or prior abdominal or pelvic surgery should be discussed before proceeding to an ITB screening test. ITB should be considered when spasticity interferes with comfort or function. © 2016 International Neuromodulation Society.

Minimum Interference Planar Geometric Topology in Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Nguyen, Trac N.; Huynh, Dung T.

The approach of using topology control to reduce interference in wireless sensor networks has attracted attention of several researchers. There are at least two definitions of interference in the literature. In a wireless sensor network the interference at a node may be caused by an edge that is transmitting data [15], or it occurs because the node itself is within the transmission range of another [3], [1], [6]. In this paper we show that the problem of assigning power to nodes in the plane to yield a planar geometric graph whose nodes have bounded interference is NP-complete under both interference definitions. Our results provide a rigorous proof for a theorem in [15] whose proof is unconvincing. They also address one of the open issues raised in [6] where Halldórsson and Tokuyama were concerned with the receiver model of node interference, and derived an O(sqrt {Δ}) upper bound for the maximum node interference of a wireless ad hoc network in the plane (Δ is the maximum interference of the so-called uniform radius network). The question as to whether this problem is NP-complete in the 2-dimensional case was left open.

Acoustic multipath arrivals in the horizontal plane due to approaching nonlinear internal waves.

PubMed

Badiey, Mohsen; Katsnelson, Boris G; Lin, Ying-Tsong; Lynch, James F

2011-04-01

Simultaneous measurements of acoustic wave transmissions and a nonlinear internal wave packet approaching an along-shelf acoustic path during the Shallow Water 2006 experiment are reported. The incoming internal wave packet acts as a moving frontal layer reflecting (or refracting) sound in the horizontal plane. Received acoustic signals are filtered into acoustic normal mode arrivals. It is shown that a horizontal multipath interference is produced. This has previously been called a horizontal Lloyd's mirror. The interference between the direct path and the refracted path depends on the mode number and frequency of the acoustic signal. A mechanism for the multipath interference is shown. Preliminary modeling results of this dynamic interaction using vertical modes and horizontal parabolic equation models are in good agreement with the observed data.

Hierarchical screening for multiple mental disorders.

PubMed

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

2013-10-01

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

Control and Interference in Task Switching--A Review

ERIC Educational Resources Information Center

Kiesel, Andrea; Steinhauser, Marco; Wendt, Mike; Falkenstein, Michael; Jost, Kerstin; Philipp, Andrea M.; Koch, Iring

2010-01-01

The task-switching paradigm offers enormous possibilities to study cognitive control as well as task interference. The current review provides an overview of recent research on both topics. First, we review different experimental approaches to task switching, such as comparing mixed-task blocks with single-task blocks, predictable task-switching…

Engineering Effects of Advanced Composite Materials on Avionics.

DTIC Science & Technology

1981-07-01

facilities. 77 zz~J 319 Electromagnetic-Interference Control EDWARD F. VANCE, SENIOR MEMBER, IEEE Abstract-Tbe use of shield topology concepts to design ...34 and "inside" are interchanged in Fig. 8 and A typical interference- control design for controlling both "Zone 1" and "Zone 2" are interchanged in Fig...P1 ’"EMP engineering and design principles." Bell Telephone Lab A systematic approach to interference control has as its NJ. 1975. foundation

Conditions for quantum interference in cognitive sciences.

PubMed

Yukalov, Vyacheslav I; Sornette, Didier

2014-01-01

We present a general classification of the conditions under which cognitive science, concerned, e.g. with decision making, requires the use of quantum theoretical notions. The analysis is done in the frame of the mathematical approach based on the theory of quantum measurements. We stress that quantum effects in cognition can arise only when decisions are made under uncertainty. Conditions for the appearance of quantum interference in cognitive sciences and the conditions when interference cannot arise are formulated. Copyright © 2013 Cognitive Science Society, Inc.

I saw where you have been--The topography of human demonstration affects dogs' search patterns and perseverative errors.

PubMed

Péter, András; Topál, József; Miklósi, Ádám; Pongrácz, Péter

2016-04-01

Performance in object search tasks is not only influenced by the subjects' object permanence ability. For example, ostensive cues of the human manipulating the target markedly affect dogs' choices. However, the interference between the target's location and the spatial cues of the human hiding the object is still unknown. In a five-location visible displacement task, the experimental groups differed in the hiding route of the experimenter. In the 'direct' condition he moved straight towards the actual location, hid the object and returned to the dog. In the 'indirect' conditions, he additionally walked behind each screen before returning. The two 'indirect' conditions differed from each other in that the human either visited the previously baited locations before (proactive interference) or after (retroactive interference) hiding the object. In the 'indirect' groups, dogs' performance was significantly lower than in the 'direct' group, demonstrating that for dogs, in an ostensive context, spatial cues of the hider are as important as the observed location of the target. Based on their incorrect choices, dogs were most attracted to the previously baited locations that the human visited after hiding the object in the actual trial. This underlines the importance of retroactive interference in multiple choice tasks. Copyright © 2016 Elsevier B.V. All rights reserved.

Memory for found targets interferes with subsequent performance in multiple-target visual search.

PubMed

Cain, Matthew S; Mitroff, Stephen R

2013-10-01

Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The emotional counting Stroop: a task for assessing emotional interference during brain imaging.

PubMed

Whalen, Paul J; Bush, George; Shin, Lisa M; Rauch, Scott L

2006-01-01

The emotional counting Stroop (ecStroop) is an emotional variant of the counting Stroop. Both of these tasks require a motor response instead of a spoken response for the purpose of minimizing head movement during functional MRI (fMRI). During this task, subjects report, by button press, the number of words (1-4) that appear on a screen, regardless of word meaning. Neutral word-control trials contain common words (e.g., 'cabinet' written three times), while interference trials contain emotional words (e.g., 'murder' written three times). The degree to which this task represents a true 'Stroop' interference task, in the sense that emotional words will increase motor-response times compared with neutral words, depends upon the subjects of the study and the words that are presented. Much research on the emotional Stroop task demonstrates that interference effects are observed in psychopathological groups in response to words that are specific to their disorder, and in normal subjects when the words are related to current concerns endorsed by them. The ecStroop task described here will produce reaction time-interference effects that are comparable to the traditional color-naming emotional Stroop. This protocol can be completed in approximately 20 min per subject. The protocol described here employs neutral words and emotional words that include general-negative words, as well as words specific to combat-related trauma. However, this protocol is amenable to any emotional word lists.

Pro-static Agents in Jet Fuels

DTIC Science & Technology

1976-08-16

1000 10,000 CHARGE DENSITY (juC/ms) Fig. 5- Effect otpolar compounds on charging tendency of silica-gel-treated n-heptane Naphthenic acid is neither a...Eastmant Naphthenic acids Practical Eastman t 30 NRL REPORT 8021 Compound Purity Supplier Pararosandine hydrochloride Not available Eastmant...silica gel to remove moisture and polar contaminants that might interfere with the compound or additive being screened. This treatment Manuscript

Allelopathy in crop/weed interactions--an update.

PubMed

Belz, Regina G

2007-04-01

Since varietal differences in allelopathy of crops against weeds were discovered in the 1970s, much research has documented the potential that allelopathic crops offer for integrated weed management with substantially reduced herbicide rates. Research groups worldwide have identified several crop species possessing potent allelopathic interference mediated by root exudation of allelochemicals. Rice, wheat, barley and sorghum have attracted most attention. Past research focused on germplasm screening for elite allelopathic cultivars and the identification of the allelochemicals involved. Based on this, traditional breeding efforts were initiated in rice and wheat to breed agronomically acceptable, weed-suppressive cultivars with improved allelopathic interference. Promising suppressive crosses are under investigation. Molecular approaches have elucidated the genetics of allelopathy by QTL mapping which associated the trait in rice and wheat with several chromosomes and suggested the involvement of several allelochemicals. Potentially important compounds that are constitutively secreted from roots have been identified in all crop species under investigation. Biosynthesis and exudation of these metabolites follow a distinct temporal pattern and can be induced by biotic and abiotic factors. The current state of knowledge suggests that allelopathy involves fluctuating mixtures of allelochemicals and their metabolites as regulated by genotype and developmental stage of the producing plant, environment, cultivation and signalling effects, as well as the chemical or microbial turnover of compounds in the rhizosphere. Functional genomics is being applied to identify genes involved in biosynthesis of several identified allelochemicals, providing the potential to improve allelopathy by molecular breeding. The dynamics of crop allelopathy, inducible processes and plant signalling is gaining growing attention; however, future research should also consider allelochemical release mechanisms, persistence, selectivity and modes of action, as well as consequences of improved crop allelopathy on plant physiology, the environment and management strategies. Creation of weed-suppressive cultivars with improved allelopathic interference is still a challenge, but traditional breeding or biotechnology should pave the way.

Deconstructing host-pathogen interactions in Drosophila

PubMed Central

Bier, Ethan; Guichard, Annabel

2012-01-01

Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. PMID:21979942

Use of Whole-Cell Bioassays for Screening Quorum Signaling, Quorum Interference, and Biofilm Dispersion.

PubMed

Thornhill, Starla G; McLean, Robert J C

2018-01-01

In most bacteria, a global level of regulation, termed quorum sensing (QS), exists involving intercellular communication via the production and response to cell density-dependent signal molecules. QS has been associated with a number of important features in bacteria including virulence regulation and biofilm formation. Consequently, there is considerable interest in understanding, detecting, and inhibiting QS. N-acylated homoserine lactones (AHLs) are used as extracellular QS signals by a variety of Gram-negative bacteria. Chromobacterium violaceum, commonly found in soil and water, produces the characteristic purple pigment violacein, regulated by AHL-mediated QS. Based on this readily observed pigmentation phenotype, C. violaceum strains can be used to detect various aspects of AHL-mediated QS activity. In another commonly used bioassay organism, Agrobacterium tumefaciens, QS can be detected by the use of a reporter gene such as lacZ. Here, we describe several commonly used approaches incorporating C. violaceum and A. tumefaciens that can be used to detect AHL and QS inhibitors. Due to the inherent low susceptibility of biofilm bacteria to antimicrobial agents, biofilm dispersion, whereby bacteria reenter the planktonic community, is another increasingly important area of research. At least one signal, distinct from traditional QS, has been identified and there are a variety of other environmental factors that also trigger dispersion. We describe a microtiter-based experimental strategy whereby potential biofilm dispersion compounds can be screened.

Multicolor fluorescent biosensor for multiplexed detection of DNA.

PubMed

Hu, Rong; Liu, Tao; Zhang, Xiao-Bing; Huan, Shuang-Yan; Wu, Cuichen; Fu, Ting; Tan, Weihong

2014-05-20

Development of efficient methods for highly sensitive and rapid screening of specific oligonucleotide sequences is essential to the early diagnosis of serious diseases. In this work, an aggregated cationic perylene diimide (PDI) derivative was found to efficiently quench the fluorescence emission of a variety of anionic oligonucleotide-labeled fluorophores that emit at wavelengths from the visible to NIR region. This broad-spectrum quencher was then adopted to develop a multicolor biosensor via a label-free approach for multiplexed fluorescent detection of DNA. The aggregated perylene derivative exhibits a very high quenching efficiency on all ssDNA-labeled dyes associated with biosensor detection, having efficiency values of 98.3 ± 0.9%, 97 ± 1.1%, and 98.2 ± 0.6% for FAM, TAMRA, and Cy5, respectively. An exonuclease-assisted autocatalytic target recycling amplification was also integrated into the sensing system. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity toward target DNA, resulting in a detection limit of 20 pM, which is about 50-fold lower than that of traditional unamplified homogeneous fluorescent assay methods. The quencher did not interfere with the catalytic activity of nuclease, and the biosensor could be manipulated in either preaddition or postaddition manner with similar sensitivity. Moreover, the proposed sensing system allows for simultaneous and multicolor analysis of several oligonucleotides in homogeneous solution, demonstrating its potential application in the rapid screening of multiple biotargets.

Piezoresistive cantilever array sensor for consolidated bioprocess monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Seonghwan Sam; Rahman, Touhidur; Senesac, Larry R

2009-01-01

Cellulolytic microbes occur in diverse natural niches and are being screened for industrial modification and utility. A microbe for Consolidated bioprocessing (CBP) development can rapidly degrade pure cellulose and then ferment the resulting sugars into fuels. To identify and screen for novel microbes for CBP, we have developed a piezoresistive cantilever array sensor which is capable of simultaneous monitoring of glucose and ethanol concentration changes in a phosphate buffer solution. 4-mercaptophenylboronic acid (4-MPBA) and polyethyleneglycol (PEG)-thiol are employed to functionalize each piezoresistive cantilever for glucose and ethanol sensing, respectively. Successful concentration measurements of glucose and ethanol with minimal interferences aremore » obtained with our cantilever array sensor.« less

A statistical approach to EMI - Theory and experiment

NASA Astrophysics Data System (ADS)

Weiner, Donald; Capraro, Gerard

A probabilistic approach to electromagnetic interference (EMI) is presented. The approach is illustrated by analyzing an experimental circuit in which EMI occurs. Both random and weakly nonlinear effects are accounted for in the analysis.

Disposable screen-printed sensors for determination of duloxetine hydrochloride

PubMed Central

2012-01-01

A screen-printed disposable electrode system for the determination of duloxetine hydrochloride (DL) was developed using screen-printing technology. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi-electrode potentiometric strip containing both working and reference electrodes was used as duloxetine hydrochloride sensor. The proposed sensors worked satisfactorily in the concentration range from 1.0 × 10-6-1.0 × 10-2 mol L-1 with detection limit reaching 5.0 × 10-7 mol L-1 and adequate shelf life of 6 months. The method is accurate, precise and economical. The proposed method has been applied successfully for the analysis of the drug in pure and in its dosage forms. In this method, there is no interference from any common pharmaceutical additives and diluents. Results of the analysis were validated statistically by recovery studies. PMID:22264225

Children, adolescents, obesity, and the media.

PubMed

Strasburger, Victor C

2011-07-01

Obesity has become a worldwide public health problem. Considerable research has shown that the media contribute to the development of child and adolescent obesity, although the exact mechanism remains unclear. Screen time may displace more active pursuits, advertising of junk food and fast food increases children's requests for those particular foods and products, snacking increases while watching TV or movies, and late-night screen time may interfere with getting adequate amounts of sleep, which is a known risk factor for obesity. Sufficient evidence exists to warrant a ban on junk-food or fast-food advertising in children's TV programming. Pediatricians need to ask 2 questions about media use at every well-child or well-adolescent visit: (1) How much screen time is being spent per day? and (2) Is there a TV set or Internet connection in the child's bedroom? Copyright © 2011 by the American Academy of Pediatrics.

High-Content Functional Screening of AEG-1 and AKR1C2 for the Promotion of Metastasis in Liver Cancer.

PubMed

Li, Cong; Wu, Xia; Zhang, Wei; Li, Jia; Liu, Huawei; Hao, Ming; Wang, Junsong; Zhang, Honghai; Yang, Gengxia; Hao, Meijun; Sheng, Shoupeng; Sun, Yu; Long, Jiang; Li, Juan; Zhuang, Fengfeng; Hu, Caixia; Li, Li; Zheng, Jiasheng

2016-01-01

Liver cancer is one of the most lethal cancer types in humans, but our understanding of the molecular mechanisms underlying this process remains insufficient. Here, we conducted high-content screening of the potential genes involved in liver cancer metastasis, which we selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, based on the SAMcell method and RNA interference technology. We identified two powerful genes in the liver cancer metastasis process, AEG-1 and AKR1C2, both of which proved to be positive regulators in promoting metastasis in liver cancer. Further clinical results verified their roles in liver cancer. In summary, these findings could provide new insight into the liver cancer mechanism and potentially therapeutic novel targets for liver cancer therapies in the future. © 2015 Society for Laboratory Automation and Screening.

Genome-wide bisulfite sensitivity profiling of yeast suggests bisulfite inhibits transcription.

PubMed

Segovia, Romulo; Mathew, Veena; Tam, Annie S; Stirling, Peter C

2017-09-01

Bisulfite, in the form of sodium bisulfite or metabisulfite, is used commercially as a food preservative. Bisulfite is used in the laboratory as a single-stranded DNA mutagen in epigenomic analyses of DNA methylation. Recently it has also been used on whole yeast cells to induce mutations in exposed single-stranded regions in vivo. To understand the effects of bisulfite on live cells we conducted a genome-wide screen for bisulfite sensitive mutants in yeast. Screening the deletion mutant array, and collections of essential gene mutants we define a genetic network of bisulfite sensitive mutants. Validation of screen hits revealed hyper-sensitivity of transcription and RNA processing mutants, rather than DNA repair pathways and follow-up analyses support a role in perturbation of RNA transactions. We propose a model in which bisulfite-modified nucleotides may interfere with transcription or RNA metabolism when used in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Vibration perception threshold in relation to postural control and fall risk assessment in elderly.

PubMed

de Mettelinge, Tine Roman; Calders, Patrick; Palmans, Tanneke; Vanden Bossche, Luc; Van Den Noortgate, Nele; Cambier, Dirk

2013-09-01

This study investigates (i) the potential discriminative role of a clinical measure of peripheral neuropathy (PN) in assessing postural performance and fall risk and (ii) whether the integration of a simple screening vibration perception threshold (VPT) for PN in any physical (fall risk) assessment among elderly should be recommended, even if they do not suffer from DM. One hundred and ninety-five elderly were entered in a four-group model: DM with PN (D+; n = 75), DM without PN (D-; n = 28), non-diabetic elderly with idiopathic PN (C+; n = 31) and non-diabetic elderly without PN (C-; n = 61). Posturographic sway parameters were captured during different static balance conditions (AMTI AccuGait, Watertown, MA). VPT, fall data, Mini-Mental State Examination and Clock Drawing Test were registered. Two-factor repeated-measures ANOVA was used to compare between groups and across balance conditions. The groups with PN demonstrated a strikingly comparable, though bigger sway, and a higher prospective fall incidence than their peers without PN. The indication of PN, irrespective of its cause, interferes with postural control and fall incidence. The integration of a simple screening for PN (like bio-thesiometry) in any fall risk assessment among elderly is highly recommended. Implications for Rehabilitation The indication of peripheral neuropathy (PN), irrespective of its cause, interferes with postural control and fall incidence. Therefore, the integration of a simple screening for PN (like bio-thesiometry) in any fall risk assessment among elderly is highly recommended. It might be useful to integrate somatosensory stimulation in rehabilitation programs designed for fall prevention.

Septonex-tetraphenylborate screen-printed ion selective electrode for the potentiometric determination of Septonex in pharmaceutical preparations.

PubMed

Mohamed, Gehad G; El-Shahat, M F; Al-Sabagh, A M; Migahed, M A; Ali, Tamer Awad

2011-04-07

A screen-printed electrode (SPE) was fabricated for the determination of 1-(ethoxycarbonyl)pentadecyltrimethylammonium bromide (Septonex) based on the use of Septonex-tetraphenylborate as the electroactive substance, and o-nitrophenyloctylether (o-NPOE) as the plasticizing agent. The electrode passes a near-Nernstian cationic slope of 59.33 ± 0.85 mV from activity between pH values of 2 to 9 with a lower detection limit of 9×10(-7) M and response time of about 5 s and exhibits an adequate shelf-life of 6 months. The method was applied for the determination of Septonex in pharmaceutical preparations. A percentage recovery of 99.88% was obtained with RSD=1.24%. The electrode was successfully applied in the determination of Septonex in laboratory-prepared samples by direct potentiometric, calibration curve and standard addition methods. Potentiometric titration of Septonex with sodium tetraphenylborate and phosphotungstic acid as a titrant was monitored with the modified screen-printed electrode as an end-point indicator electrode. Selectivity coefficients for Septonex relative to a number of potential interfering substances were determined. The sensor was highly selective for Septonex over a large number of compounds. Selectivity coefficient data for some common ions show negligible interference; however, cetyltrimethylammonium bromide and iodide ions interfere significantly. The analytical usefulness of the proposed electrode was evaluated by its application in the determination of Septonex in laboratory-prepared pharmaceutical samples with satisfactory results. The results obtained with the fabricated sensor are comparable with those obtained by the British Pharmacopeia method. © The Royal Society of Chemistry 2011

Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification.

PubMed

Tarkang, Protus Arrey; Appiah-Opong, Regina; Ofori, Michael F; Ayong, Lawrence S; Nyarko, Alexander K

2016-01-01

There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.

Colorectal Cancer Deaths Attributable to Nonuse of Screening in the United States

PubMed Central

Meester, Reinier G.S.; Doubeni, Chyke A.; Lansdorp-Vogelaar, Iris; Goede, S.L.; Levin, Theodore R.; Quinn, Virginia P.; van Ballegooijen, Marjolein; Corley, Douglas A.; Zauber, Ann G.

2015-01-01

Purpose Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the U.S., but is underutilized. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. Methods The established MISCAN-colon microsimulation model was used to estimate the population attributable fraction (PAF) in people aged ≥50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake; PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin's formula to gauge how this simpler approach differs from the model-based approach. Results There were an estimated 51,500 CRC deaths in 2010, about 63% (N∼32,200) of which were attributable to non-screening. The PAF decreases slightly to 58% in 2020. Levin's approach yielded a considerably more conservative PAF of 46% (N∼23,600) for 2010. Conclusions The majority of current U.S. CRC deaths are attributable to non-screening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches. PMID:25721748

RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

PubMed Central

Zuber, Johannes; Shi, Junwei; Wang, Eric; Rappaport, Amy R.; Herrmann, Harald; Sison, Edward A.; Magoon, Daniel; Qi, Jun; Blatt, Katharina; Wunderlich, Mark; Taylor, Meredith J.; Johns, Christopher; Chicas, Agustin; Mulloy, James C.; Kogan, Scott C.; Brown, Patrick; Valent, Peter; Bradner, James E.; Lowe, Scott W.; Vakoc, Christopher R.

2012-01-01

Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs1. Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states2. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention. PMID:21814200

Development and Validation of a Computational Model for Androgen Receptor Activity

PubMed Central

2016-01-01

Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference. The in vitro HTS assays probed perturbations of the AR pathway at multiple points (receptor binding, coregulator recruitment, gene transcription, and protein production) and multiple cell types. Confirmatory in vitro antagonist assay data and cytotoxicity information were used as additional flags for potential nonspecific activity. Validating such alternative testing strategies requires high-quality reference data. We compiled 158 putative androgen-active and -inactive chemicals from a combination of international test method validation efforts and semiautomated systematic literature reviews. Detailed in vitro assay information and results were compiled into a single database using a standardized ontology. Reference chemical concentrations that activated or inhibited AR pathway activity were identified to establish a range of potencies with reproducible reference chemical results. Comparison with existing Tier 1 AR binding data from the U.S. EPA Endocrine Disruptor Screening Program revealed that the model identified binders at relevant test concentrations (<100 μM) and was more sensitive to antagonist activity. The AR pathway model based on the ToxCast/Tox21 assays had balanced accuracies of 95.2% for agonist (n = 29) and 97.5% for antagonist (n = 28) reference chemicals. Out of 1855 chemicals screened in the AR pathway model, 220 chemicals demonstrated AR agonist or antagonist activity and an additional 174 chemicals were predicted to have potential weak AR pathway activity. PMID:27933809

A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans

PubMed Central

Polley, Stanley R. G.; Fay, David S.

2012-01-01

The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified in genetic screens for mutations that display synthetic phenotypes in conjunction with loss of lin-35. To explore the intestinal role of LIN-35, we conducted a genome-wide RNA-interference-feeding screen for suppressors of lin-35; slr-2 early larval arrest. Of the 26 suppressors identified, 17 fall into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators. Further characterization indicates that different categories of suppressors act through distinct molecular mechanisms. We also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes. We identified 19 genes, most of which are evolutionarily conserved, that can suppress multiple unrelated lin-35-synthetic phenotypes. Our study reveals a network of genes broadly antagonistic to LIN-35 as well as genes specific to the role of LIN-35 in intestinal and vulval development. Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities are most directly relevant to the core functions of the shared gene. PMID:22542970

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

PubMed Central

van der Sanden, Sabine M. G.; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C.; Brooks, Paula; O'Donnell, Jason; Jones, Les P.; Brown, Cedric; Tompkins, S. Mark; Karpilow, Jon; Tripp, Ralph A.

2015-01-01

ABSTRACT Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. IMPORTANCE Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work describes a platform-enabling technology applicable to most vaccine-preventable diseases. PMID:26581994

Large-scale cross-species chemogenomic platform proposes a new drug discovery strategy of veterinary drug from herbal medicines.

PubMed

Huang, Chao; Yang, Yang; Chen, Xuetong; Wang, Chao; Li, Yan; Zheng, Chunli; Wang, Yonghua

2017-01-01

Veterinary Herbal Medicine (VHM) is a comprehensive, current, and informative discipline on the utilization of herbs in veterinary practice. Driven by chemistry but progressively directed by pharmacology and the clinical sciences, drug research has contributed more to address the needs for innovative veterinary medicine for curing animal diseases. However, research into veterinary medicine of vegetal origin in the pharmaceutical industry has reduced, owing to questions such as the short of compatibility of traditional natural-product extract libraries with high-throughput screening. Here, we present a cross-species chemogenomic screening platform to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future veterinary medicines, thereby increasing the number of treatment options. First, based on critically examined pharmacology and text mining, we build a cross-species drug-likeness evaluation approach to screen the lead compounds in veterinary medicines. Second, a specific cross-species target prediction model is developed to infer drug-target connections, with the purpose of understanding how drugs work on the specific targets. Third, we focus on exploring the multiple targets interference effects of veterinary medicines by heterogeneous network convergence and modularization analysis. Finally, we manually integrate a disease pathway to test whether the cross-species chemogenomic platform could uncover the active mechanism of veterinary medicine, which is exemplified by a specific network module. We believe the proposed cross-species chemogenomic platform allows for the systematization of current and traditional knowledge of veterinary medicine and, importantly, for the application of this emerging body of knowledge to the development of new drugs for animal diseases.

Large-scale cross-species chemogenomic platform proposes a new drug discovery strategy of veterinary drug from herbal medicines

PubMed Central

Huang, Chao; Yang, Yang; Chen, Xuetong; Wang, Chao; Li, Yan; Zheng, Chunli

2017-01-01

Veterinary Herbal Medicine (VHM) is a comprehensive, current, and informative discipline on the utilization of herbs in veterinary practice. Driven by chemistry but progressively directed by pharmacology and the clinical sciences, drug research has contributed more to address the needs for innovative veterinary medicine for curing animal diseases. However, research into veterinary medicine of vegetal origin in the pharmaceutical industry has reduced, owing to questions such as the short of compatibility of traditional natural-product extract libraries with high-throughput screening. Here, we present a cross-species chemogenomic screening platform to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future veterinary medicines, thereby increasing the number of treatment options. First, based on critically examined pharmacology and text mining, we build a cross-species drug-likeness evaluation approach to screen the lead compounds in veterinary medicines. Second, a specific cross-species target prediction model is developed to infer drug-target connections, with the purpose of understanding how drugs work on the specific targets. Third, we focus on exploring the multiple targets interference effects of veterinary medicines by heterogeneous network convergence and modularization analysis. Finally, we manually integrate a disease pathway to test whether the cross-species chemogenomic platform could uncover the active mechanism of veterinary medicine, which is exemplified by a specific network module. We believe the proposed cross-species chemogenomic platform allows for the systematization of current and traditional knowledge of veterinary medicine and, importantly, for the application of this emerging body of knowledge to the development of new drugs for animal diseases. PMID:28915268

RNA targeting with CRISPR-Cas13.

PubMed

Abudayyeh, Omar O; Gootenberg, Jonathan S; Essletzbichler, Patrick; Han, Shuo; Joung, Julia; Belanto, Joseph J; Verdine, Vanessa; Cox, David B T; Kellner, Max J; Regev, Aviv; Lander, Eric S; Voytas, Daniel F; Ting, Alice Y; Zhang, Feng

2017-10-12

RNA has important and diverse roles in biology, but molecular tools to manipulate and measure it are limited. For example, RNA interference can efficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relies on the introduction of exogenous tags. Here we demonstrate that the class 2 type VI RNA-guided RNA-targeting CRISPR-Cas effector Cas13a (previously known as C2c2) can be engineered for mammalian cell RNA knockdown and binding. After initial screening of 15 orthologues, we identified Cas13a from Leptotrichia wadei (LwaCas13a) as the most effective in an interference assay in Escherichia coli. LwaCas13a can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts with comparable levels of knockdown as RNA interference and improved specificity. Catalytically inactive LwaCas13a maintains targeted RNA binding activity, which we leveraged for programmable tracking of transcripts in live cells. Our results establish CRISPR-Cas13a as a flexible platform for studying RNA in mammalian cells and therapeutic development.

General interference law for nonstationary, separable optical fields.

PubMed

Manea, Vladimir

2009-09-01

An approach to the theory of partial coherence for nonstationary optical fields is presented. Starting with a spectral representation, a favorable decomposition of the optical signals is discussed that supports a natural extension of the mathematical formalism. The coherence functions are redefined, but still as temporal correlation functions, allowing the obtaining of a more general form of the interference law for partially coherent optical signals. The general theory is applied in some relevant particular cases of nonstationary interference, namely, with quasi-monochromatic beams of different frequencies and with phase-modulated quasi-monochromatic beams of similar frequency spectra. All the results of the general treatment are reducible to the ones given in the literature for the case of stationary interference.

Circumventing substrate interference in the Raman spectroscopic identification of blood stains.

PubMed

McLaughlin, Gregory; Sikirzhytski, Vitali; Lednev, Igor K

2013-09-10

Raman spectroscopy has demonstrated remarkable capabilities in identifying blood in controlled laboratory conditions. However, substrate interference presents a significant challenge toward characterizing body fluid traces with Raman spectroscopy at a crime scene. Here, several possible solutions are explored, including the selection of laser excitation, isolating the signal of blood using spectral subtraction and using a favorable substrate for collection which minimizes interference. Simulated blood stain evidence was prepared and analyzed using a Raman microscope with variable laser capabilities. It is shown that the best approach for detecting blood depends on the nature of the substrate and the type of interference encountered. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Validation of a Novel Bioassay for Low-level Perchlorate Determination

DTIC Science & Technology

2014-04-01

was not attractive, since these reduce PMS2 , and it was thought they would interfere with the stoichiometry of NADH and perchlorate in the bioassay...these reduce PMS2 directly, and would interfere with the stoichiometry of NADH and perchlorate in the bioassay. Thus the only approach that could be

Validation of a Novel Bioassay for Low-level Perchlorate Determination

DTIC Science & Technology

2013-05-01

since these reduce PMS2 , and it was thought they would interfere with the stoichiometry of NADH and perchlorate in the bioassay. With regard to the...reduce PMS2 directly, and would interfere with the stoichiometry of NADH and perchlorate in the bioassay. Thus the only approach that could be

Alternative Significant Contribution Approaches Evaluated

EPA Pesticide Factsheets

This Technical Support Document (TSD) discusses alternative approaches that EPA evaluated for defining emissions that constitute each upwind state’s significant contribution to nonattainment and interference with maintenance downwind.

Wind tunnel wall interference investigations in NAE/NRC High Reynolds Number 2D Facility and NASA Langley 0.3m Transonic Cryogenic Tunnel

NASA Technical Reports Server (NTRS)

Chan, Y. Y.; Nishimura, Y.; Mineck, R. E.

1989-01-01

Results are reported from a NAE/NRC and NASA cooperative program on two-dimensional wind-tunnel wall-interference research, aimed at developing the technology for correcting or eliminating wall interference effects in two-dimensional transonic wind-tunnel investigations. Both NASA Langley and NAE facilities are described, along with a NASA-designed and fabricated airfoil model. It is shown that data from the NAE facility, corrected for wall interference, agree with those obtained from the NASA tunnel, which has adaptive walls; the comparison of surface pressure data shows that the flowfield conditions in which the model is investigated appear to be nearly identical under most conditions. It is concluded that both approaches, posttest correction and an adaptive wall, adequately eliminate the tunnel-wall interference effects.

Pain in methadone patients: Time to address undertreatment and suicide risk (ANRS-Methaville trial)

PubMed Central

Nordmann, Sandra; Vilotitch, Antoine; Lions, Caroline; Michel, Laurent; Mora, Marion; Spire, Bruno; Maradan, Gwenaelle; Bendiane, Marc-Karim; Morel, Alain; Roux, Perrine; Carrieri, Patrizia

2017-01-01

Background Pain in opioid-dependent patients is common but data measuring the course of pain (and its correlates) using validated scales in patients initiating methadone treatment are sparse. We aimed to assess pain and its interference in daily life, associated correlates, and undertreatment before and during methadone treatment. Methods This is a secondary analysis using longitudinal data of a randomized trial comparing two methadone initiation models. We assessed the effect of methadone initiation and other correlates on pain intensity and interference (using the Brief Pain Inventory) at months 0, 6 and 12 using a mixed multinomial logistic regression model. Results The study group comprised 168 patients who had data for either pain intensity or interference for at least one visit. Moderate to severe pain was reported in 12.9% of patients at M0, 5.4% at M6 and 7.3% at M12. Substantial interference with daily functioning was reported in 36.0% at M0, 14.5% at M6 and 17.1% at M12. Of the 98 visits where patients reported moderate to severe pain or substantial interference, 55.1% reported no treatment for pain relief, non-opioid analgesics were reported by 34.7%, opioid analgesics by 3.1% and both opioid and non-opioid analgesics by 7.1%. Methadone was associated with decreased pain intensity at 6 months (OR = 0.29, p = 0.04) and 12 months (OR = 0.30, p = 0.05) of follow-up and tended to be associated with substantial pain interference. Suicide risk was associated with both pain intensity and pain interference. Conclusions Methadone in opioid-dependent patients can reduce pain. However, undertreatment of pain in methadone patients remains a major clinical concern. Patients with pain are at higher risk of suicide. Adequate screening and management of pain in this population is a priority and needs to be integrated into routine comprehensive care. PMID:28520735

Accuracy of self-reports of fecal occult blood tests and test results among individuals in the carpentry trade.

PubMed

Lipkus, Isaac M; Samsa, Gregory P; Dement, John; Skinner, Celette Sugg; Green, La Sonya G; Pompeii, Lisa; Ransohoff, David F

2003-11-01

Inaccuracy in self-reports of colorectal cancer (CRC) screening procedures (e.g., over- or underreporting) may interfere with individuals adhering to appropriate screening intervals, and can blur the true effects of physician recommendations to screen and the effects of interventions designed to promote screening. We assessed accuracy of self-report of having a fecal occult blood test (FOBT) within a 1-year window based on receipt of FOBT kits among individuals aged 50 and older in the carpentry trade (N = 658) who were off-schedule for having had a FOBT. Indices of evaluating accuracy of self-reports (concordance, specificity, false-positive and false-negative rates) were calculated relative to receipt of a mailed FOBT. Among those who mailed a completed FOBT, we assessed accuracy of reporting the test result. Participants underestimated having performed a FOBT (false-negative rate of 44%). Accuracy was unrelated to perceptions of getting or worrying about CRC or family history. Self-reports of having a negative FOBT result more consistently matched the laboratory result (specificity 98%) than having a positive test result (sensitivity 63%). Contrary to other findings, participants under- rather than over reported FOBT screening. Results suggest greater efforts are needed to enhance accurate recall of FOBT screening.

Above-real-time training (ARTT) improves transfer to a simulated flight control task.

PubMed

Donderi, D C; Niall, Keith K; Fish, Karyn; Goldstein, Benjamin

2012-06-01

The aim of this study was to measure the effects of above-real-time-training (ARTT) speed and screen resolution on a simulated flight control task. ARTT has been shown to improve transfer to the criterion task in some military simulation experiments. We tested training speed and screen resolution in a project, sponsored by Defence Research and Development Canada, to develop components for prototype air mission simulators. For this study, 54 participants used a single-screen PC-based flight simulation program to learn to chase and catch an F-18A fighter jet with another F-18A while controlling the chase aircraft with a throttle and side-stick controller. Screen resolution was varied between participants, and training speed was varied factorially across two sessions within participants. Pretest and posttest trials were at high resolution and criterion (900 knots) speed. Posttest performance was best with high screen resolution training and when one ARTT training session was followed by a session of criterion speed training. ARTT followed by criterion training improves performance on a visual-motor coordination task. We think that ARTT influences known facilitators of transfer, including similarity to the criterion task and contextual interference. Use high-screen resolution, start with ARTT, and finish with criterion speed training when preparing a mission simulation.

GenomeRNAi: a database for cell-based RNAi phenotypes.

PubMed

Horn, Thomas; Arziman, Zeynep; Berger, Juerg; Boutros, Michael

2007-01-01

RNA interference (RNAi) has emerged as a powerful tool to generate loss-of-function phenotypes in a variety of organisms. Combined with the sequence information of almost completely annotated genomes, RNAi technologies have opened new avenues to conduct systematic genetic screens for every annotated gene in the genome. As increasing large datasets of RNAi-induced phenotypes become available, an important challenge remains the systematic integration and annotation of functional information. Genome-wide RNAi screens have been performed both in Caenorhabditis elegans and Drosophila for a variety of phenotypes and several RNAi libraries have become available to assess phenotypes for almost every gene in the genome. These screens were performed using different types of assays from visible phenotypes to focused transcriptional readouts and provide a rich data source for functional annotation across different species. The GenomeRNAi database provides access to published RNAi phenotypes obtained from cell-based screens and maps them to their genomic locus, including possible non-specific regions. The database also gives access to sequence information of RNAi probes used in various screens. It can be searched by phenotype, by gene, by RNAi probe or by sequence and is accessible at http://rnai.dkfz.de.

GenomeRNAi: a database for cell-based RNAi phenotypes

PubMed Central

Horn, Thomas; Arziman, Zeynep; Berger, Juerg; Boutros, Michael

2007-01-01

RNA interference (RNAi) has emerged as a powerful tool to generate loss-of-function phenotypes in a variety of organisms. Combined with the sequence information of almost completely annotated genomes, RNAi technologies have opened new avenues to conduct systematic genetic screens for every annotated gene in the genome. As increasing large datasets of RNAi-induced phenotypes become available, an important challenge remains the systematic integration and annotation of functional information. Genome-wide RNAi screens have been performed both in Caenorhabditis elegans and Drosophila for a variety of phenotypes and several RNAi libraries have become available to assess phenotypes for almost every gene in the genome. These screens were performed using different types of assays from visible phenotypes to focused transcriptional readouts and provide a rich data source for functional annotation across different species. The GenomeRNAi database provides access to published RNAi phenotypes obtained from cell-based screens and maps them to their genomic locus, including possible non-specific regions. The database also gives access to sequence information of RNAi probes used in various screens. It can be searched by phenotype, by gene, by RNAi probe or by sequence and is accessible at PMID:17135194

Memory Interference as a Determinant of Language Comprehension

PubMed Central

Van Dyke, Julie A.; Johns, Clinton L.

2012-01-01

The parameters of the human memory system constrain the operation of language comprehension processes. In the memory literature, both decay and interference have been proposed as causes of forgetting; however, while there is a long history of research establishing the nature of interference effects in memory, the effects of decay are much more poorly supported. Nevertheless, research investigating the limitations of the human sentence processing mechanism typically focus on decay-based explanations, emphasizing the role of capacity, while the role of interference has received comparatively little attention. This paper reviews both accounts of difficulty in language comprehension by drawing direct connections to research in the memory domain. Capacity-based accounts are found to be untenable, diverging substantially from what is known about the operation of the human memory system. In contrast, recent research investigating comprehension difficulty using a retrieval-interference paradigm is shown to be wholly consistent with both behavioral and neuropsychological memory phenomena. The implications of adopting a retrieval-interference approach to investigating individual variation in language comprehension are discussed. PMID:22773927

An Improved Time-Frequency Analysis Method in Interference Detection for GNSS Receivers

PubMed Central

Sun, Kewen; Jin, Tian; Yang, Dongkai

2015-01-01

In this paper, an improved joint time-frequency (TF) analysis method based on a reassigned smoothed pseudo Wigner–Ville distribution (RSPWVD) has been proposed in interference detection for Global Navigation Satellite System (GNSS) receivers. In the RSPWVD, the two-dimensional low-pass filtering smoothing function is introduced to eliminate the cross-terms present in the quadratic TF distribution, and at the same time, the reassignment method is adopted to improve the TF concentration properties of the auto-terms of the signal components. This proposed interference detection method is evaluated by experiments on GPS L1 signals in the disturbing scenarios compared to the state-of-the-art interference detection approaches. The analysis results show that the proposed interference detection technique effectively overcomes the cross-terms problem and also preserves good TF localization properties, which has been proven to be effective and valid to enhance the interference detection performance of the GNSS receivers, particularly in the jamming environments. PMID:25905704

Matter-wave diffraction approaching limits predicted by Feynman path integrals for multipath interference

NASA Astrophysics Data System (ADS)

Barnea, A. Ronny; Cheshnovsky, Ori; Even, Uzi

2018-02-01

Interference experiments have been paramount in our understanding of quantum mechanics and are frequently the basis of testing the superposition principle in the framework of quantum theory. In recent years, several studies have challenged the nature of wave-function interference from the perspective of Born's rule—namely, the manifestation of so-called high-order interference terms in a superposition generated by diffraction of the wave functions. Here we present an experimental test of multipath interference in the diffraction of metastable helium atoms, with large-number counting statistics, comparable to photon-based experiments. We use a variation of the original triple-slit experiment and accurate single-event counting techniques to provide a new experimental bound of 2.9 ×10-5 on the statistical deviation from the commonly approximated null third-order interference term in Born's rule for matter waves. Our value is on the order of the maximal contribution predicted for multipath trajectories by Feynman path integrals.

Factors affecting reproducibility between genome-scale siRNA-based screens

PubMed Central

Barrows, Nicholas J.; Le Sommer, Caroline; Garcia-Blanco, Mariano A.; Pearson, James L.

2011-01-01

RNA interference-based screening is a powerful new genomic technology which addresses gene function en masse. To evaluate factors influencing hit list composition and reproducibility, we performed two identically designed small interfering RNA (siRNA)-based, whole genome screens for host factors supporting yellow fever virus infection. These screens represent two separate experiments completed five months apart and allow the direct assessment of the reproducibility of a given siRNA technology when performed in the same environment. Candidate hit lists generated by sum rank, median absolute deviation, z-score, and strictly standardized mean difference were compared within and between whole genome screens. Application of these analysis methodologies within a single screening dataset using a fixed threshold equivalent to a p-value ≤ 0.001 resulted in hit lists ranging from 82 to 1,140 members and highlighted the tremendous impact analysis methodology has on hit list composition. Intra- and inter-screen reproducibility was significantly influenced by the analysis methodology and ranged from 32% to 99%. This study also highlighted the power of testing at least two independent siRNAs for each gene product in primary screens. To facilitate validation we conclude by suggesting methods to reduce false discovery at the primary screening stage. In this study we present the first comprehensive comparison of multiple analysis strategies, and demonstrate the impact of the analysis methodology on the composition of the “hit list”. Therefore, we propose that the entire dataset derived from functional genome-scale screens, especially if publicly funded, should be made available as is done with data derived from gene expression and genome-wide association studies. PMID:20625183

Understanding the Harms and Benefits of Cancer Screening: A Model of Factors That Shape Informed Decision Making.

PubMed

Petrova, Dafina; Garcia-Retamero, Rocio; Cokely, Edward T

2015-10-01

Decisions about cancer screenings often involve the consideration of complex and counterintuitive evidence. We investigated psychological factors that promote the comprehension of benefits and harms associated with common cancer screenings and their influence on shared decision making. In experiment 1, 256 men received information about PSA-based prostate cancer screening. In experiment 2, 355 women received information about mammography-based breast cancer screening. In both studies, information about potential screening outcomes was provided in 1 of 3 formats: text, a fact box, or a visual aid (e.g., mortality with and without screening and rate of overdiagnosis). We modeled the interplay of comprehension, perceived risks and benefits, intention to participate in screening, and desire for shared decision making. Generally, visual aids were the most effective format, increasing comprehension by up to 18%. Improved comprehension was associated with 1) superior decision making (e.g., fewer intentions to participate in screening when it offered no benefit) and 2) more desire to share in decision making. However, comprehension of the evidence had a limited effect on experienced emotions, risk perceptions, and decision making among those participants who felt that the consequences of cancer were extremely severe. Even when information is counterintuitive and requires the integration of complex harms and benefits, user-friendly risk communications can facilitate comprehension, improve high-stakes decisions, and promote shared decision making. However, previous beliefs about the effectiveness of screening or strong fears about specific cancers may interfere with comprehension and informed decision making. © The Author(s) 2015.

Biosensor-based small molecule fragment screening with biolayer interferometry

NASA Astrophysics Data System (ADS)

Wartchow, Charles A.; Podlaski, Frank; Li, Shirley; Rowan, Karen; Zhang, Xiaolei; Mark, David; Huang, Kuo-Sen

2011-07-01

Biosensor-based fragment screening is a valuable tool in the drug discovery process. This method is advantageous over many biochemical methods because primary hits can be distinguished from non-specific or non-ideal interactions by examining binding profiles and responses, resulting in reduced false-positive rates. Biolayer interferometry (BLI), a technique that measures changes in an interference pattern generated from visible light reflected from an optical layer and a biolayer containing proteins of interest, is a relatively new method for monitoring small molecule interactions. The BLI format is based on a disposable sensor that is immersed in 96-well or 384-well plates. BLI has been validated for small molecule detection and fragment screening with model systems and well-characterized targets where affinity constants and binding profiles are generally similar to those obtained with surface plasmon resonsance (SPR). Screens with challenging targets involved in protein-protein interactions including BCL-2, JNK1, and eIF4E were performed with a fragment library of 6,500 compounds, and hit rates were compared for these targets. For eIF4E, a protein containing a PPI site and a nucleotide binding site, results from a BLI fragment screen were compared to results obtained in biochemical HTS screens. Overlapping hits were observed for the PPI site, and hits unique to the BLI screen were identified. Hit assessments with SPR and BLI are described.

RNA Interference Based Approach to Down Regulate Osmoregulators of Whitefly (Bemisia tabaci): Potential Technology for the Control of Whitefly

USDA-ARS?s Scientific Manuscript database

Over the past decade RNA interference (RNAi) technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs) could offer potential for insect pest management. Insects feeding exclusively on plant sap depend on osmotic pressure...

Involvement of the Parietal Cortex in Perceptual Learning (Eureka Effect): An Interference Approach Using rTMS

ERIC Educational Resources Information Center

Giovannelli, Fabio; Silingardi, Davide; Borgheresi, Alessandra; Feurra, Matteo; Amati, Gianluca; Pizzorusso, Tommaso; Viggiano, Maria Pia; Zaccara, Gaetano; Berardi, Nicoletta; Cincotta, Massimo

2010-01-01

The neural mechanisms underlying perceptual learning are still under investigation. Eureka effect is a form of rapid, long-lasting perceptual learning by which a degraded image, which appears meaningless when first seen, becomes recognizable after a single exposure to its undegraded version. We used online interference by focal 10-Hz repetitive…

The Myth of Spatial Reuse with Directional Antennas in Indoor Wireless Networks

NASA Astrophysics Data System (ADS)

Lakshmanan, Sriram; Sundaresan, Karthikeyan; Rangarajan, Sampath; Sivakumar, Raghupathy

Interference among co-channel users is a fundamental problem in wireless networks, which prevents nearby links from operating concurrently. Directional antennas allow the radiation patterns of wireless transmitters to be shaped to form directed beams. Conventionally, such beams are assumed to improve the spatial reuse (i.e. concurrency) in indoor wireless networks. In this paper, we use experiments in an indoor office setting of Wifi Access points equipped with directional antennas, to study their potential for interference mitigation and spatial reuse. In contrast to conventional wisdom, we observe that the interference mitigation benefits of directional antennas are minimal. On analyzing our experimental traces we observe that directional links do not reduce interference to nearby links due to the lack of signal confinement due to indoor multipath fading. We then use the insights derived from our study to develop an alternative approach that provides better interference reduction in indoor networks compared to directional links.

RNA Interference (RNAi) Induced Gene Silencing: A Promising Approach of Hi-Tech Plant Breeding.

PubMed

Younis, Adnan; Siddique, Muhammad Irfan; Kim, Chang-Kil; Lim, Ki-Byung

2014-01-01

RNA interference (RNAi) is a promising gene regulatory approach in functional genomics that has significant impact on crop improvement which permits down-regulation in gene expression with greater precise manner without affecting the expression of other genes. RNAi mechanism is expedited by small molecules of interfering RNA to suppress a gene of interest effectively. RNAi has also been exploited in plants for resistance against pathogens, insect/pest, nematodes, and virus that cause significant economic losses. Keeping beside the significance in the genome integrity maintenance as well as growth and development, RNAi induced gene syntheses are vital in plant stress management. Modifying the genes by the interference of small RNAs is one of the ways through which plants react to the environmental stresses. Hence, investigating the role of small RNAs in regulating gene expression assists the researchers to explore the potentiality of small RNAs in abiotic and biotic stress management. This novel approach opens new avenues for crop improvement by developing disease resistant, abiotic or biotic stress tolerant, and high yielding elite varieties.

RNA Interference (RNAi) Induced Gene Silencing: A Promising Approach of Hi-Tech Plant Breeding

PubMed Central

Younis, Adnan; Siddique, Muhammad Irfan; Kim, Chang-Kil; Lim, Ki-Byung

2014-01-01

RNA interference (RNAi) is a promising gene regulatory approach in functional genomics that has significant impact on crop improvement which permits down-regulation in gene expression with greater precise manner without affecting the expression of other genes. RNAi mechanism is expedited by small molecules of interfering RNA to suppress a gene of interest effectively. RNAi has also been exploited in plants for resistance against pathogens, insect/pest, nematodes, and virus that cause significant economic losses. Keeping beside the significance in the genome integrity maintenance as well as growth and development, RNAi induced gene syntheses are vital in plant stress management. Modifying the genes by the interference of small RNAs is one of the ways through which plants react to the environmental stresses. Hence, investigating the role of small RNAs in regulating gene expression assists the researchers to explore the potentiality of small RNAs in abiotic and biotic stress management. This novel approach opens new avenues for crop improvement by developing disease resistant, abiotic or biotic stress tolerant, and high yielding elite varieties. PMID:25332689

Proactive interference effects on sentence production

PubMed Central

FERREIRA, VICTOR S.; FIRATO, CARLA E.

2007-01-01

Proactive interference refers to recall difficulties caused by prior similar memory-related processing. Information-processing approaches to sentence production predict that retrievability affects sentence form: Speakers may word sentences so that material that is difficult to retrieve is spoken later. In this experiment, speakers produced sentence structures that could include an optional that, thereby delaying the mention of a subsequent noun phrase. This subsequent noun phrase was either (1) conceptually similar to three previous noun phrases in the same sentence, leading to greater proactive interference, or (2) conceptually dissimilar, leading to less proactive interference. Speakers produced more thats (and were more disfluencies) before conceptually similar noun phrases, suggesting that retrieval difficulties during sentence production affect the syntactic structures of sentences that speakers produce. PMID:12613685

Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies

PubMed Central

Gagnon, J.; Lévesque, E.; Borduas, F.; Chiquette, J.; Diorio, C.; Duchesne, N.; Dumais, M.; Eloy, L.; Foulkes, W.; Gervais, N.; Lalonde, L.; L’Espérance, B.; Meterissian, S.; Provencher, L.; Richard, J.; Savard, C.; Trop, I.; Wong, N.; Knoppers, B.M.; Simard, J.

2016-01-01

In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification—unlike those for population screening programs, which are currently well regulated—are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies. PMID:28050152

Quantum interference in heterogeneous superconducting-photonic circuits on a silicon chip.

PubMed

Schuck, C; Guo, X; Fan, L; Ma, X; Poot, M; Tang, H X

2016-01-21

Quantum information processing holds great promise for communicating and computing data efficiently. However, scaling current photonic implementation approaches to larger system size remains an outstanding challenge for realizing disruptive quantum technology. Two main ingredients of quantum information processors are quantum interference and single-photon detectors. Here we develop a hybrid superconducting-photonic circuit system to show how these elements can be combined in a scalable fashion on a silicon chip. We demonstrate the suitability of this approach for integrated quantum optics by interfering and detecting photon pairs directly on the chip with waveguide-coupled single-photon detectors. Using a directional coupler implemented with silicon nitride nanophotonic waveguides, we observe 97% interference visibility when measuring photon statistics with two monolithically integrated superconducting single-photon detectors. The photonic circuit and detector fabrication processes are compatible with standard semiconductor thin-film technology, making it possible to implement more complex and larger scale quantum photonic circuits on silicon chips.

Just-in-Time Compound Pooling Increases Primary Screening Capacity without Compromising Screening Quality.

PubMed

Elkin, L L; Harden, D G; Saldanha, S; Ferguson, H; Cheney, D L; Pieniazek, S N; Maloney, D P; Zewinski, J; O'Connell, J; Banks, M

2015-06-01

Compound pooling, or multiplexing more than one compound per well during primary high-throughput screening (HTS), is a controversial approach with a long history of limited success. Many issues with this approach likely arise from long-term storage of library plates containing complex mixtures of compounds at high concentrations. Due to the historical difficulties with using multiplexed library plates, primary HTS often uses a one-compound-one-well approach. However, as compound collections grow, innovative strategies are required to increase the capacity of primary screening campaigns. Toward this goal, we have developed a novel compound pooling method that increases screening capacity without compromising data quality. This method circumvents issues related to the long-term storage of complex compound mixtures by using acoustic dispensing to enable "just-in-time" compound pooling directly in the assay well immediately prior to assay. Using this method, we can pool two compounds per well, effectively doubling the capacity of a primary screen. Here, we present data from pilot studies using just-in-time pooling, as well as data from a large >2-million-compound screen using this approach. These data suggest that, for many targets, this method can be used to vastly increase screening capacity without significant reduction in the ability to detect screening hits. © 2015 Society for Laboratory Automation and Screening.

Advances in CRISPR-Cas9 genome engineering: lessons learned from RNA interference

PubMed Central

Barrangou, Rodolphe; Birmingham, Amanda; Wiemann, Stefan; Beijersbergen, Roderick L.; Hornung, Veit; Smith, Anja van Brabant

2015-01-01

The discovery that the machinery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 bacterial immune system can be re-purposed to easily create deletions, insertions and replacements in the mammalian genome has revolutionized the field of genome engineering and re-invigorated the field of gene therapy. Many parallels have been drawn between the newly discovered CRISPR-Cas9 system and the RNA interference (RNAi) pathway in terms of their utility for understanding and interrogating gene function in mammalian cells. Given this similarity, the CRISPR-Cas9 field stands to benefit immensely from lessons learned during the development of RNAi technology. We examine how the history of RNAi can inform today's challenges in CRISPR-Cas9 genome engineering such as efficiency, specificity, high-throughput screening and delivery for in vivo and therapeutic applications. PMID:25800748

Application of ToxCast High-Throughput Screening and ...

EPA Pesticide Factsheets

Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenesis Distruptors Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenssis Distruptors

Pesticide Cumulative Risk Assessment: Framework for Screening Analysis

EPA Pesticide Factsheets

This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach: begin with evaluation of available toxicological information and, if necessary, follow up with a risk-based screening approach.

Discovery of novel bacterial RNA polymerase inhibitors: pharmacophore-based virtual screening and hit optimization.

PubMed

Hinsberger, Stefan; Hüsecken, Kristina; Groh, Matthias; Negri, Matthias; Haupenthal, Jörg; Hartmann, Rolf W

2013-11-14

The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between σ(70) and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies compared to clinically used rifampicin.

Identification of Inhibitors in Lignocellulosic Slurries and Determination of Their Effect on Hydrocarbon-Producing Microorganisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shihui; Franden, Mary A; Yang, Qing

The aim of this work was to identify inhibitors in pretreated lignocellulosic slurries, evaluate high-throughput screening strategies, and investigate the impact of inhibitors on potential hydrocarbon-producing microorganisms. Compounds present in slurries that could inhibit microbial growth were identified through a detailed analysis of saccharified slurries by applying a combination of approaches of high-performance liquid chromatography, GC-MS, LC-DAD-MS, and ICP-MS. Several high-throughput assays were then evaluated to generate toxicity profiles. Our results demonstrated that Bioscreen C was useful for analyzing bacterial toxicity but not for yeast. AlamarBlue reduction assay can be a useful high-throughput assay for both bacterial and yeast strainsmore » as long as medium components do not interfere with fluorescence measurements. In addition, this work identified two major inhibitors (furfural and ammonium acetate) for three potential hydrocarbon-producing bacterial species that include Escherichia coli, Cupriavidus necator, and Rhodococcus opacus PD630, which are also the primary inhibitors for ethanologens. Here, this study was strived to establish a pipeline to quantify inhibitory compounds in biomass slurries and high-throughput approaches to investigate the effect of inhibitors on microbial biocatalysts, which can be applied for various biomass slurries or hydrolyzates generated through different pretreatment and enzymatic hydrolysis processes or different microbial candidates.« less

Identification of Inhibitors in Lignocellulosic Slurries and Determination of Their Effect on Hydrocarbon-Producing Microorganisms

DOE PAGES

Yang, Shihui; Franden, Mary A; Yang, Qing; ...

2018-04-04

The aim of this work was to identify inhibitors in pretreated lignocellulosic slurries, evaluate high-throughput screening strategies, and investigate the impact of inhibitors on potential hydrocarbon-producing microorganisms. Compounds present in slurries that could inhibit microbial growth were identified through a detailed analysis of saccharified slurries by applying a combination of approaches of high-performance liquid chromatography, GC-MS, LC-DAD-MS, and ICP-MS. Several high-throughput assays were then evaluated to generate toxicity profiles. Our results demonstrated that Bioscreen C was useful for analyzing bacterial toxicity but not for yeast. AlamarBlue reduction assay can be a useful high-throughput assay for both bacterial and yeast strainsmore » as long as medium components do not interfere with fluorescence measurements. In addition, this work identified two major inhibitors (furfural and ammonium acetate) for three potential hydrocarbon-producing bacterial species that include Escherichia coli, Cupriavidus necator, and Rhodococcus opacus PD630, which are also the primary inhibitors for ethanologens. Here, this study was strived to establish a pipeline to quantify inhibitory compounds in biomass slurries and high-throughput approaches to investigate the effect of inhibitors on microbial biocatalysts, which can be applied for various biomass slurries or hydrolyzates generated through different pretreatment and enzymatic hydrolysis processes or different microbial candidates.« less

Application of micro-TLC to the total antioxidant potential (TAP) measurement.

PubMed

Głód, Bronisław K; Wantusiak, Paweł M; Piszcz, Paweł; Lewczuk, Elwira; Zarzycki, Paweł K

2015-04-15

DPPH is commonly applied for estimation of antioxidant capacity of single and complex biological samples, and changes colour from purple to yellow during reduction to DPPH-H. Importantly, for some samples, for example coloured foods, such reaction cannot be used because of interference from pigments. Therefore, the number of reported quantitative protocols involving off- or on-line sample reaction with DPPH are based on chromatographic separation of target components. In typical planar chromatographic assay, developed plates are sprayed with DPPH solution for antioxidant screening. Such approach enables simple visualisation of separated spots exhibiting antioxidant activities, but unfortunately, such procedure may also give the misleading signal for coloured spots. In the present communication we examined a new approach for measuring antioxidant capacity using quantitative analysis of DPPH and DPPH-H molecules after reaction with the sample, and then separated from the interfering compounds by micro-thin-layer chromatography. Particularly, the antioxidant capacities of coloured food samples (such as herbs and meads) were determined and the results compared with those obtained using the classical photometric assay. The main advantages of the new micro-TLC assay are (i) low cost, (ii) multiple measurements, (iii) short analysis time, (iv) simplification of sample preparation and (v) effective separation of DPPH signal from interfering compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Localizing semantic interference from distractor sounds in picture naming: A dual-task study.

PubMed

Mädebach, Andreas; Kieseler, Marie-Luise; Jescheniak, Jörg D

2017-10-13

In this study we explored the locus of semantic interference in a novel picture-sound interference task in which participants name pictures while ignoring environmental distractor sounds. In a previous study using this task (Mädebach, Wöhner, Kieseler, & Jescheniak, in Journal of Experimental Psychology: Human Perception and Performance, 43, 1629-1646, 2017), we showed that semantically related distractor sounds (e.g., BARKING dog ) interfere with a picture-naming response (e.g., "horse") more strongly than unrelated distractor sounds do (e.g., DRUMMING drum ). In the experiment reported here, we employed the psychological refractory period (PRP) approach to explore the locus of this effect. We combined a geometric form classification task (square vs. circle; Task 1) with the picture-sound interference task (Task 2). The stimulus onset asynchrony (SOA) between the tasks was systematically varied (0 vs. 500 ms). There were three central findings. First, the semantic interference effect from distractor sounds was replicated. Second, picture naming (in Task 2) was slower with the short than with the long task SOA. Third, both effects were additive-that is, the semantic interference effects were of similar magnitude at both task SOAs. This suggests that the interference arises during response selection or later stages, not during early perceptual processing. This finding corroborates the theory that semantic interference from distractor sounds reflects a competitive selection mechanism in word production.

Trajectory description of the quantum–classical transition for wave packet interference

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, Chia-Chun, E-mail: ccchou@mx.nthu.edu.tw

2016-08-15

The quantum–classical transition for wave packet interference is investigated using a hydrodynamic description. A nonlinear quantum–classical transition equation is obtained by introducing a degree of quantumness ranging from zero to one into the classical time-dependent Schrödinger equation. This equation provides a continuous description for the transition process of physical systems from purely quantum to purely classical regimes. In this study, the transition trajectory formalism is developed to provide a hydrodynamic description for the quantum–classical transition. The flow momentum of transition trajectories is defined by the gradient of the action function in the transition wave function and these trajectories follow themore » main features of the evolving probability density. Then, the transition trajectory formalism is employed to analyze the quantum–classical transition of wave packet interference. For the collision-like wave packet interference where the propagation velocity is faster than the spreading speed of the wave packet, the interference process remains collision-like for all the degree of quantumness. However, the interference features demonstrated by transition trajectories gradually disappear when the degree of quantumness approaches zero. For the diffraction-like wave packet interference, the interference process changes continuously from a diffraction-like to collision-like case when the degree of quantumness gradually decreases. This study provides an insightful trajectory interpretation for the quantum–classical transition of wave packet interference.« less

Serum sample containing endogenous antibodies interfering with multiple hormone immunoassays. Laboratory strategies to detect interference.

PubMed

García-González, Elena; Aramendía, Maite; Álvarez-Ballano, Diego; Trincado, Pablo; Rello, Luis

2016-04-01

Endogenous antibodies (EA) may interfere with immunoassays, causing erroneous results for hormone analyses. As (in most cases) this interference arises from the assay format and most immunoassays, even from different manufacturers, are constructed in a similar way, it is possible for a single type of EA to interfere with different immunoassays. Here we describe the case of a patient whose serum sample contains EA that interfere several hormones tests. We also discuss the strategies deployed to detect interference. Over a period of four years, a 30-year-old man was subjected to a plethora of laboratory and imaging diagnostic procedures as a consequence of elevated hormone results, mainly of pituitary origin, which did not correlate with the overall clinical picture. Once analytical interference was suspected, the best laboratory approaches to investigate it were sample reanalysis on an alternative platform and sample incubation with antibody blocking tubes. Construction of an in-house 'nonsense' sandwich assay was also a valuable strategy to confirm interference. In contrast, serial sample dilutions were of no value in our case, while polyethylene glycol (PEG) precipitation gave inconclusive results, probably due to the use of inappropriate PEG concentrations for several of the tests assayed. Clinicians and laboratorians must be aware of the drawbacks of immunometric assays, and alert to the possibility of EA interference when results do not fit the clinical pattern.

The Utility of the Pattern of the Strengths and Weaknesses Approach

ERIC Educational Resources Information Center

Fiorello, Catherine A.; Flanagan, Dawn P.; Hale, James B.

2014-01-01

Unlike ability-achievement discrepancy and response-to-intervention approaches, the processing strengths and weaknesses (PSW) approach is the only empirically based approach that attempts to identify the pattern of deficit in the basic psychological processes that interferes with academic achievement for children with specific learning…

Nationally Consistent Environmental Justice Screening Approaches

EPA Pesticide Factsheets

This report discusses screening approaches through the lens of the Agency's Environmental Justice Strategic Enforcement Tool (EJSEAT), in particular, and how such approaches might better identify areas of concern.

Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.

PubMed

Thomas, Duncan C

2017-07-01

Screening behavior depends on previous screening history and family members' behaviors, which can act as both confounders and intermediate variables on a causal pathway from screening to disease risk. Conventional analyses that adjust for these variables can lead to incorrect inferences about the causal effect of screening if high-risk individuals are more likely to be screened. Analyzing the data in a manner that treats screening as randomized conditional on covariates allows causal parameters to be estimated; inverse probability weighting based on propensity of exposure scores is one such method considered here. I simulated family data under plausible models for the underlying disease process and for screening behavior to assess the performance of alternative methods of analysis and whether a targeted screening approach based on individuals' risk factors would lead to a greater reduction in cancer incidence in the population than a uniform screening policy. Simulation results indicate that there can be a substantial underestimation of the effect of screening on subsequent cancer risk when using conventional analysis approaches, which is avoided by using inverse probability weighting. A large case-control study of colonoscopy and colorectal cancer from Germany shows a strong protective effect of screening, but inverse probability weighting makes this effect even stronger. Targeted screening approaches based on either fixed risk factors or family history yield somewhat greater reductions in cancer incidence with fewer screens needed to prevent one cancer than population-wide approaches, but the differences may not be large enough to justify the additional effort required. See video abstract at, http://links.lww.com/EDE/B207.

Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Nannan; Chen, Siqi; Ma, Yan

Highlights: Black-Right-Pointing-Pointer The protein POT1 plays an important role in telomere protection. Black-Right-Pointing-Pointer Functional POT1 was overexpressed in Escherichia coli for the first time, and purified. Black-Right-Pointing-Pointer Compound Sysu-00692 was found to be the first POT1-binding ligand. Black-Right-Pointing-Pointer Sysu-00692 could interfere with the binding activity of POT1 in vivo. Black-Right-Pointing-Pointer Sysu-00692 had inhibition on telomerase and cell proliferation. -- Abstract: The protein POT1 plays an important role in telomere protection, which is related with telomere elongation and cell immortality. The protein has been recognized as a promising drug target for cancer treatment. In the present study, we cloned, overexpressed inmore » Escherichia coli for the first time, and purified recombinant human POT1. The protein was proved to be active through filter binding assay, FRET and CD experiments. In the initial screening for protein binding ligands using SPR, compound Sysu-00692 was found to bind well with the POT1, which was confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692 could interfere with the binding between human POT1 and the telomeric DNA through chromatin immunoprecipitation. Besides, the compound showed mild inhibition on telomerase and cell proliferation. As we know, compound Sysu-00692 is the first reported POT1-binding ligand, which could serve as a lead compound for further improvement. This work offered a potentially new approach for drug design for the treatment of cancers.« less

The interrelations between spiritual well-being, pain interference and depressive symptoms in patients with multiple sclerosis.

PubMed

Nsamenang, Sheri A; Hirsch, Jameson K; Topciu, Raluca; Goodman, Andrew D; Duberstein, Paul R

2016-04-01

Depressive symptoms are common in individuals with multiple sclerosis (MS), and are frequently exacerbated by pain; however, spiritual well-being may allow persons with MS to more effectively cope with pain-related deficits in physical and role functioning. We explored the associations between spiritual well-being, pain interference and depressive symptoms, assessing each as a potential mediator, in eighty-one patients being treated for MS, who completed self-report measures: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale, Pain Effects Scale, and Center for Epidemiologic Studies Depression Scale Revised. At the bivariate level, spiritual well-being and its subscale of meaning and peace were negatively associated with depression and pain interference. In mediation models, depression was not related to pain interference via spiritual well-being, or to spiritual well-being via pain interference. Pain interference was related to depression via spiritual well-being and meaning/peace, and to spiritual well-being and meaning/peace via depressive symptoms. Finally, spiritual well-being and meaning/peace were related to depression via pain interference, and to pain interference via depressive symptoms. For patients with MS, a multi-faceted approach to treatment that includes pain reduction and promotion of spiritual well-being may be beneficial, although amelioration of depression remains a critical task.

Comparison of different shielding methods in acquisition of physiological signals.

PubMed

Yanbing Jiang; Ning Ji; Hui Wang; Xueyu Liu; Yanjuan Geng; Peng Li; Shixiong Chen; Guanglin Li

2017-07-01

Power line interference in the surrounding environment could usually introduce many difficulties when collecting and analyzing physiological signals. Since power line interference is usually several orders of amplitude larger than the physiological electrical signals, methods of suppressing power line interference should be considered during the signal acquisition. Many studies used a hardware or software band-stop filter to suppress power line interference but it could easily cause attenuations and distortions to the signal of interest. In this study, two kinds of methods that used different signals to drive the shields of the electrodes were proposed to reduce the impacts of power line interference. Three channels of two physiological signals (ECG and EMG) were simultaneously collected when the electrodes were not shielded (No-Shield), shielded by ground signals (GND-Shield) and shielded by buffered signals of the corresponding electrodes (Active-Shield), respectively, on a custom hardware platform based on TI ADS1299. The results showed that power line interference would be significantly suppressed when using shielding approaches, and the Active-Shield method could achieve the best performance with a power line interference reduction up to 36dB. The study suggested that the Active-Shield method at the analog front-end was a great candidate to reduce power line interference in routine acquisitions of physiological signals.

Interference tables: a useful model for interference analysis in asynchronous multicarrier transmission

NASA Astrophysics Data System (ADS)

Medjahdi, Yahia; Terré, Michel; Ruyet, Didier Le; Roviras, Daniel

2014-12-01

In this paper, we investigate the impact of timing asynchronism on the performance of multicarrier techniques in a spectrum coexistence context. Two multicarrier schemes are considered: cyclic prefix-based orthogonal frequency division multiplexing (CP-OFDM) with a rectangular pulse shape and filter bank-based multicarrier (FBMC) with physical layer for dynamic spectrum access and cognitive radio (PHYDYAS) and isotropic orthogonal transform algorithm (IOTA) waveforms. First, we present the general concept of the so-called power spectral density (PSD)-based interference tables which are commonly used for multicarrier interference characterization in spectrum sharing context. After highlighting the limits of this approach, we propose a new family of interference tables called `instantaneous interference tables'. The proposed tables give the interference power caused by a given interfering subcarrier on a victim one, not only as a function of the spectral distance separating both subcarriers but also with respect to the timing misalignment between the subcarrier holders. In contrast to the PSD-based interference tables, the accuracy of the proposed tables has been validated through different simulation results. Furthermore, due to the better frequency localization of both PHYDYAS and IOTA waveforms, FBMC technique is demonstrated to be more robust to timing asynchronism compared to OFDM one. Such a result makes FBMC a potential candidate for the physical layer of future cognitive radio systems.

High impact technologies for natural products screening.

PubMed

Koehn, Frank E

2008-01-01

Natural products have historically been a rich source of lead molecules in drug discovery. However, natural products have been de-emphasized as high throughput screening resources in the recent past, in part because of difficulties in obtaining high quality natural products screening libraries, or in applying modern screening assays to these libraries. In addition, natural products programs based on screening of extract libraries, bioassay-guided isolation, structure elucidation and subsequent production scale-up are challenged to meet the rapid cycle times that are characteristic of the modern HTS approach. Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic techniques can greatly facilitate the first components of the process - namely the efficient creation of high-quality natural products libraries, bimolecular target or cell-based screening, and early hit characterization. The success of any high throughput screening campaign is dependent on the quality of the chemical library. The construction and maintenance of a high quality natural products library, whether based on microbial, plant, marine or other sources is a costly endeavor. The library itself may be composed of samples that are themselves mixtures - such as crude extracts, semi-pure mixtures or single purified natural products. Each of these library designs carries with it distinctive advantages and disadvantages. Crude extract libraries have lower resource requirements for sample preparation, but high requirements for identification of the bioactive constituents. Pre-fractionated libraries can be an effective strategy to alleviate interferences encountered with crude libraries, and may shorten the time needed to identify the active principle. Purified natural product libraries require substantial resources for preparation, but offer the advantage that the hit detection process is reduced to that of synthetic single component libraries. Whether the natural products library consists of crude or partially fractionated mixtures, the library contents should be profiled to identify the known components present - a process known as dereplication. The use of mass spectrometry and HPLC-mass spectrometry together with spectral databases is a powerful tool in the chemometric profiling of bio-sources for natural product production. High throughput, high sensitivity flow NMR is an emerging tool in this area as well. Whether by cell based or biomolecular target based assays, screening of natural product extract libraries continues to furnish novel lead molecules for further drug development, despite challenges in the analysis and prioritization of natural products hits. Spectroscopic techniques are now being used to directly screen natural product and synthetic libraries. Mass spectrometry in the form of methods such as ESI-ICRFTMS, and FACS-MS as well as NMR methods such as SAR by NMR and STD-NMR have been utilized to effectively screen molecular libraries. Overall, emerging advances in mass spectrometry, NMR and other technologies are making it possible to overcome the challenges encountered in screening natural products libraries in today's drug discovery environment. As we apply these technologies and develop them even further, we can look forward to increased impact of natural products in the HTS based drug discovery.

Range safety signal propagation through the SRM exhaust plume of the space shuttle

NASA Technical Reports Server (NTRS)

Boynton, F. P.; Davies, A. R.; Rajasekhar, P. S.; Thompson, J. A.

1977-01-01

Theoretical predictions of plume interference for the space shuttle range safety system by solid rocket booster exhaust plumes are reported. The signal propagation was calculated using a split operator technique based upon the Fresnel-Kirchoff integral, using fast Fourier transforms to evaluate the convolution and treating the plume as a series of absorbing and phase-changing screens. Talanov's lens transformation was applied to reduce aliasing problems caused by ray divergence.

First-trimester screening for chromosomal abnormalities: advantages of an instant results approach.

PubMed

Norton, Mary E

2010-09-01

Protocols that include first trimester screening for fetal chromosome abnormalities have become standard of care throughout the United States. Earlier screening allows for first trimester diagnostic testing in cases found to be at increased risk. However, first trimester screening requires coordination of the nuchal translucency ultrasound screening (NT) and biochemical screening, during early, specific, narrow, but slightly different gestational age ranges. Instant results can often be provided at the time of the NT ultrasound if preceded by the programs that perform the biochemical analyses; this optimizes the benefits of the first trimester approach while improving efficiency and communication with the patient. This article discusses the benefits and logistics of such an approach. Copyright 2010 Elsevier Inc. All rights reserved.

Knowledge-driven lead discovery.

PubMed

Pirard, Bernard

2005-11-01

Virtual screening encompasses several computational approaches which have proven valuable for identifying novel leads. These approaches rely on available information. Herein, we review recent successful applications of virtual screening. The extension of virtual screening methodologies to target families is also briefly discussed.

SAPT units turn-on in an interference-dominant environment. [Stand Alone Pressure Transducer

NASA Technical Reports Server (NTRS)

Peng, W.-C.; Yang, C.-C.; Lichtenberg, C.

1990-01-01

A stand alone pressure transducer (SAPT) is a credit-card-sized smart pressure sensor inserted between the tile and the aluminum skin of a space shuttle. Reliably initiating the SAPT units via RF signals in a prelaunch environment is a challenging problem. Multiple-source interference may exist if more than one GSE (ground support equipment) antenna is turned on at the same time to meet the simultaneity requirement of 10 ms. A polygon model for orbiter, external tank, solid rocket booster, and tail service masts is used to simulate the prelaunch environment. Geometric optics is then applied to identify the coverage areas and the areas which are vulnerable to multipath and/or multiple-source interference. Simulation results show that the underside areas of an orbiter have incidence angles exceeding 80 deg. For multipath interference, both sides of the cargo bay areas are found to be vulnerable to a worst-case multipath loss exceeding 20 dB. Multiple-source interference areas are also identified. Mitigation methods for the coverage and interference problem are described. It is shown that multiple-source interference can be eliminated (or controlled) using the time-division-multiplexing method or the time-stamp approach.

Ethical Perspectives on RNA Interference Therapeutics

PubMed Central

Ebbesen, Mette; Jensen, Thomas G.; Andersen, Svend; Pedersen, Finn Skou

2008-01-01

RNA interference is a mechanism for controlling normal gene expression which has recently begun to be employed as a potential therapeutic agent for a wide range of disorders, including cancer, infectious diseases and metabolic disorders. Clinical trials with RNA interference have begun. However, challenges such as off-target effects, toxicity and safe delivery methods have to be overcome before RNA interference can be considered as a conventional drug. So, if RNA interference is to be used therapeutically, we should perform a risk-benefit analysis. It is ethically relevant to perform a risk-benefit analysis since ethical obligations about not inflicting harm and promoting good are generally accepted. But the ethical issues in RNA interference therapeutics not only include a risk-benefit analysis, but also considerations about respecting the autonomy of the patient and considerations about justice with regard to the inclusion criteria for participation in clinical trials and health care allocation. RNA interference is considered a new and promising therapeutic approach, but the ethical issues of this method have not been greatly discussed, so this article analyses these issues using the bioethical theory of principles of the American bioethicists, Tom L. Beauchamp and James F. Childress. PMID:18612370

A Genome-Wide RNA Interference Screen Identifies a Role for Wnt/β-Catenin Signaling during Rift Valley Fever Virus Infection.

PubMed

Harmon, Brooke; Bird, Sara W; Schudel, Benjamin R; Hatch, Anson V; Rasley, Amy; Negrete, Oscar A

2016-08-15

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. These studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses. Copyright © 2016 Harmon et al.

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

DOE PAGES

Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.; ...

2016-05-25

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

Quantifying Overdiagnosis in Cancer Screening: A Systematic Review to Evaluate the Methodology.

PubMed

Ripping, Theodora M; Ten Haaf, Kevin; Verbeek, André L M; van Ravesteyn, Nicolien T; Broeders, Mireille J M

2017-10-01

Overdiagnosis is the main harm of cancer screening programs but is difficult to quantify. This review aims to evaluate existing approaches to estimate the magnitude of overdiagnosis in cancer screening in order to gain insight into the strengths and limitations of these approaches and to provide researchers with guidance to obtain reliable estimates of overdiagnosis in cancer screening. A systematic review was done of primary research studies in PubMed that were published before January 1, 2016, and quantified overdiagnosis in breast cancer screening. The studies meeting inclusion criteria were then categorized by their methods to adjust for lead time and to obtain an unscreened reference population. For each approach, we provide an overview of the data required, assumptions made, limitations, and strengths. A total of 442 studies were identified in the initial search. Forty studies met the inclusion criteria for the qualitative review. We grouped the approaches to adjust for lead time in two main categories: the lead time approach and the excess incidence approach. The lead time approach was further subdivided into the mean lead time approach, lead time distribution approach, and natural history modeling. The excess incidence approach was subdivided into the cumulative incidence approach and early vs late-stage cancer approach. The approaches used to obtain an unscreened reference population were grouped into the following categories: control group of a randomized controlled trial, nonattenders, control region, extrapolation of a prescreening trend, uninvited groups, adjustment for the effect of screening, and natural history modeling. Each approach to adjust for lead time and obtain an unscreened reference population has its own strengths and limitations, which should be taken into consideration when estimating overdiagnosis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Interference Aware Routing Using Spatial Reuse in Wireless Sensor Networks

DTIC Science & Technology

2013-12-01

practice there is no optimal STDMA algorithm due to the computational complexity of the STDMA implementation; therefore, the common approach is to...Applications, Springer Berlin Heidelberg, pp. 653–657, 2001. [26] B. Korte and J. Vygen, “Shortest Paths,” Combinatorial Optimization Theory and...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited INTERFERENCE

Sonoelastographic imaging of interference patterns for estimation of the shear velocity of homogeneous biomaterials

NASA Astrophysics Data System (ADS)

Wu, Zhe; Taylor, Lawrence S.; Rubens, Deborah J.; Parker, Kevin J.

2004-03-01

The shear wave velocity is one of a few important parameters that characterize the mechanical properties of bio-materials. In this paper, two noninvasive methods are proposed to measure the shear velocity by inspecting the shear wave interference patterns. In one method, two shear wave sources are placed on the opposite two sides of a sample, driven by the identical sinusoidal signals. The shear waves from the two sources interact to create interference patterns, which are visualized by the vibration sonoelastography technique. The spacing between the pattern bands equals half of the shear wavelength. The shear velocity can be obtained by taking the product of the wavelength and the frequency. An alternative method is to drive the two vibration sources at slightly different frequencies. In this case, the interference patterns no longer remain stationary. It is proved that the apparent velocity of the moving patterns is proportional to the shear velocity in the medium. Since the apparent velocity of the patterns can be measured by analysing the video sequence, the shear velocity can be obtained thereafter. These approaches are validated by a conventional shear wave time-of-flight approach, and they are accurate within 4% on various homogeneous tissue-mimicking phantoms.

Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

DTIC Science & Technology

2016-03-01

Award Number: W81XWH-12-1-0323 TITLE: Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach PRINCIPAL...SUBTITLE Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...increasing its sensitivity and specificity through nanotechnology . Hypothesis: Detection of DNA methylation from individuals with cancer can be used to

A Primer for DoD Reliability, Maintainability and Safety Standards

DTIC Science & Technology

1988-03-02

the project engineer and the concurrence of their respective managers. The primary consideration in such cases is the thoroughness of the ...basic approaches to the application of environmental stress screening. In one approach, the government explicitly specifies the screens and screening...TO USE DOD-HDBK-344 (USAF) There are two basic approaches to the application of environmental stress

Impact of in-band interference on a wake-up radio system in wireless sensor networks

NASA Astrophysics Data System (ADS)

Lebreton, J. M.; Murad, N. M.; Lorion, R.

2017-05-01

The energy efficiency of Wireless Sensor Networks (WSNs) is considerably improved with Wake-up Radio (WuR) systems. However, their resilience to interference is often neglected in the literature. This might be an issue due to the proliferation of wireless devices and the growing field of internet of things. In this paper, we evaluate the impact of in-band interference from wireless devices on a WuR system. The approach proves that WuR systems are still performing well when coexisting with external wireless networks, even if the energy-efficiency is slightly reduced.

DS/LPI autocorrelation detection in noise plus random-tone interference. [Direct Sequence Low-Probabilty of Intercept

NASA Technical Reports Server (NTRS)

Hinedi, S.; Polydoros, A.

1988-01-01

The authors present and analyze a frequency-noncoherent two-lag autocorrelation statistic for the wideband detection of random BPSK signals in noise-plus-random-multitone interference. It is shown that this detector is quite robust to the presence or absence of interference and its specific parameter values, contrary to the case of an energy detector. The rule assumes knowledge of the data rate and the active scenario under H0. It is concluded that the real-time autocorrelation domain and its samples (lags) are a viable approach for detecting random signals in dense environments.

Metabolomics Approach for Toxicity Screening of Volatile Substances

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However, the ch...

Kernel-Based Sensor Fusion With Application to Audio-Visual Voice Activity Detection

NASA Astrophysics Data System (ADS)

Dov, David; Talmon, Ronen; Cohen, Israel

2016-12-01

In this paper, we address the problem of multiple view data fusion in the presence of noise and interferences. Recent studies have approached this problem using kernel methods, by relying particularly on a product of kernels constructed separately for each view. From a graph theory point of view, we analyze this fusion approach in a discrete setting. More specifically, based on a statistical model for the connectivity between data points, we propose an algorithm for the selection of the kernel bandwidth, a parameter, which, as we show, has important implications on the robustness of this fusion approach to interferences. Then, we consider the fusion of audio-visual speech signals measured by a single microphone and by a video camera pointed to the face of the speaker. Specifically, we address the task of voice activity detection, i.e., the detection of speech and non-speech segments, in the presence of structured interferences such as keyboard taps and office noise. We propose an algorithm for voice activity detection based on the audio-visual signal. Simulation results show that the proposed algorithm outperforms competing fusion and voice activity detection approaches. In addition, we demonstrate that a proper selection of the kernel bandwidth indeed leads to improved performance.

Computer-Guided Approach to Access the Anti-influenza Activity of Licorice Constituents

PubMed Central

2013-01-01

Neuraminidase (NA), a key enzyme in viral replication, is the first-line drug target to combat influenza. On the basis of a shape-focused virtual screening, the roots of Glycyrrhiza glabra (licorice) were identified as plant species with an accumulation of constituents that show 3D similarities to known influenza NA inhibitors (NAIs). Phytochemical investigation revealed 12 constituents identified as (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(8-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)-2-propen-1-one (1), 3,4-dihydro-8,8-dimethyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-3-ol (2), biochanin B (3), glabrol (4), glabrone (5), hispaglabridin B (6), licoflavone B (7), licorice glycoside B (8), licorice glycoside E (9), liquiritigenin (10), liquiritin (11), and prunin (12). Eleven of these constituents showed significant influenza virus NA inhibition in a chemiluminescence (CL)-based assay. Additional tests, including (i) a cell-based cytopathic effect inhibition assay (general antiviral activity), (ii) the evaluation of cytotoxicity, (iii) the inhibition of the NA of Clostridium perfringens (CL- and fluorescence (FL)-based assay), and (iv) the determination of self-fluorescence and quenching, provided further perspective on their anti-influenza virus potential, revealing possible assay interference problems and false-positive results. Compounds 1, 3, 5, and 6 showed antiviral activity, most likely caused by the inhibition of NA. Of these, compounds 1, 3, and 6 were highly ranked in shape-focused virtual screening. PMID:24313801

[Screening efficient siRNAs in vitro as the candidate genes for chicken anti-avian influenza virus H5N1 breeding].

PubMed

Zhang, P; Wang, J G; Wan, J G; Liu, W Q

2010-01-01

The frequent disease outbreaks caused by avian influenza virus not only affect the poultry industry but also pose a threat to human safety. To address the problem, RNA interference (RNAi) has recently been widely used as a potential antiviral approach. Transgenesis in combination with RNAi to specifically inhibit avian enza virus gene expression has been proposed to make chickens resistant to the infection. For the transgenic breeding, screening in vitro efficient siRNAs as the candidate genes is one of the most important tasks. Here, we combined an online search tool and a series of bioinformatics programs with a set of rules for designing siRNAs targeted towards different mRNA regions of H5N1 avian influenza virus. Five rational siRNAs were chosen by this method, five U6 promoter-driven shRNA expression plasmids containing the siRNA genes were constructed and used for producing stably transfected MDCK cells. The data obtained by virus titration, IFA, PI-stained flow cytometry, real-time quantitative RT-PCR, and DAS-ELISA analyses showed that all five stably transfected cell lines we re resistant to virusreplication when exposed to 100 CCID50 of avian influenza virus H5N1. Finally, most effective plasmids (pSi-604i and pSi-1597i) as the candidates for making the transgenic chickens were chosen. These findings provide baseline information on use of RNAi technique for breeding transgenic chickens resistant to avian influenza virus.

Evaluation of PCR Systems for Field Screening of Bacillus anthracis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozanich, Richard M.; Colburn, Heather A.; Victry, Kristin D.

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

Theoretical study of the effect of ground proximity on the induced efficiency of helicopter rotors

NASA Technical Reports Server (NTRS)

Heyson, H. H.

1977-01-01

A study of rotors in forward flight within ground effect showed that the ground-induced interference is an upwash and a decrease in forward velocity. The interference velocities are large, oppose the normal flow through the rotor, and have large effects on the induced efficiency. Hovering with small ground clearances may result in significant blade stall. As speed is increased from hover in ground effect, power initially increases rather than decreases. At very low heights above the ground, the power requirements become nonlinear with speed as a result of the streamwise interference. The streamwise interference becomes greater as the wake approaches the ground and eventually distorts the wake to form the ground vortex which contributes to certain observed directional stability problems.

A New Approach to Interference Excision in Radio Astronomy: Real-Time Adaptive Cancellation

NASA Astrophysics Data System (ADS)

Barnbaum, Cecilia; Bradley, Richard F.

1998-11-01

Every year, an increasing amount of radio-frequency (RF) spectrum in the VHF, UHF, and microwave bands is being utilized to support new commercial and military ventures, and all have the potential to interfere with radio astronomy observations. Such services already cause problems for radio astronomy even in very remote observing sites, and the potential for this form of light pollution to grow is alarming. Preventive measures to eliminate interference through FCC legislation and ITU agreements can be effective; however, many times this approach is inadequate and interference excision at the receiver is necessary. Conventional techniques such as RF filters, RF shielding, and postprocessing of data have been only somewhat successful, but none has been sufficient. Adaptive interference cancellation is a real-time approach to interference excision that has not been used before in radio astronomy. We describe here, for the first time, adaptive interference cancellation in the context of radio astronomy instrumentation, and we present initial results for our prototype receiver. In the 1960s, analog adaptive interference cancelers were developed that obtain a high degree of cancellation in problems of radio communications and radar. However, analog systems lack the dynamic range, noised performance, and versatility required by radio astronomy. The concept of digital adaptive interference cancellation was introduced in the mid-1960s as a way to reduce unwanted noise in low-frequency (audio) systems. Examples of such systems include the canceling of maternal ECG in fetal electrocardiography and the reduction of engine noise in the passenger compartments of automobiles. These audio-frequency applications require bandwidths of only a few tens of kilohertz. Only recently has high-speed digital filter technology made high dynamic range adaptive canceling possible in a bandwidth as large as a few megahertz, finally opening the door to application in radio astronomy. We have built a prototype adaptive canceler that consists of two receivers: the primary channel (input from the main beam of the telescope) and a separate reference channel. The primary channel receives the desired astronomical signal corrupted by RFI (radio-frequency interference) coming in the sidelobes of the main beam. A separate reference antenna is designed to receive only the RFI. The reference channel input is processed using a digital adaptive filter and then subtracted from the primary channel input, producing the system output. The weighting coefficients of the digital filter are adjusted by way of an algorithm that minimizes, in a least-squares sense, the power output of the system. Through an adaptive-iterative process, the canceler locks onto the RFI, and the filter adjusts itself to minimize the effect of the RFI at the system output. We have designed the adaptive canceler with an intermediate frequency (IF) of 40 MHz. This prototype system will ultimately be functional with a variety of radio astronomy receivers in the microwave band. We have also built a prototype receiver centered at 100 MHz (in the FM broadcast band) to test the adaptive canceler with actual interferers, which are well characterized. The initial laboratory tests of the adaptive canceler are encouraging, with attenuation of strong frequency-modulated (FM) interference to 72 dB (a factor of more than 10 million), which is at the performance limit of our measurements. We also consider requirements of the system and the RFI environment for effective adaptive canceling.

Breast Cancer Screening in the Precision Medicine Era: Risk-Based Screening in a Population-Based Trial.

PubMed

Shieh, Yiwey; Eklund, Martin; Madlensky, Lisa; Sawyer, Sarah D; Thompson, Carlie K; Stover Fiscalini, Allison; Ziv, Elad; Van't Veer, Laura J; Esserman, Laura J; Tice, Jeffrey A

2017-01-01

Ongoing controversy over the optimal approach to breast cancer screening has led to discordant professional society recommendations, particularly in women age 40 to 49 years. One potential solution is risk-based screening, where decisions around the starting age, stopping age, frequency, and modality of screening are based on individual risk to maximize the early detection of aggressive cancers and minimize the harms of screening through optimal resource utilization. We present a novel approach to risk-based screening that integrates clinical risk factors, breast density, a polygenic risk score representing the cumulative effects of genetic variants, and sequencing for moderate- and high-penetrance germline mutations. We demonstrate how thresholds of absolute risk estimates generated by our prediction tools can be used to stratify women into different screening strategies (biennial mammography, annual mammography, annual mammography with adjunctive magnetic resonance imaging, defer screening at this time) while informing the starting age of screening for women age 40 to 49 years. Our risk thresholds and corresponding screening strategies are based on current evidence but need to be tested in clinical trials. The Women Informed to Screen Depending On Measures of risk (WISDOM) Study, a pragmatic, preference-tolerant randomized controlled trial of annual vs personalized screening, will study our proposed approach. WISDOM will evaluate the efficacy, safety, and acceptability of risk-based screening beginning in the fall of 2016. The adaptive design of this trial allows continued refinement of our risk thresholds as the trial progresses, and we discuss areas where we anticipate emerging evidence will impact our approach. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Overcoming interference with the detection of a stable isotopically labeled microtracer in the evaluation of beclabuvir absolute bioavailability using a concomitant microtracer approach.

PubMed

Jiang, Hao; Titsch, Craig; Zeng, Jianing; Jones, Barry; Joyce, Philip; Gandhi, Yash; Turley, Wesley; Burrell, Richard; Aubry, Anne F; Arnold, Mark E

2017-09-05

The oral absolute bioavailability of beclabuvir in healthy subjects was determined using a microdose (100μg) of the stable isotopically labeled tracer via intravenous (IV) infusion started after oral dosing of beclabuvir (150mg). To simultaneously analyze the concentrations of the IV microtracer ([ 13 C 6 ]beclabuvir) and beclabuvir in plasma samples, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method was initially developed. Surprisingly beclabuvir significantly interfered with the IV microtracer detection when using the selected reaction monitoring (SRM) in the assay. An interfering component from the drug substance was observed using a high resolution mass spectrometer (HRMS). The mass-to-charge (m/z) of the interfering component was -32ppm different from the nominal value for the IV microtracer and thus could not be differentiated in the SRM assay by the unit mass resolution. To overcome this interference, we evaluated two approaches by either monitoring an alternative product ion using the SRM assay or isolating the interfering component using the parallel reaction monitoring (PRM) assay on the HRMS. This case study has demonstrated two practical approaches for overcoming interferences with the detection of stable isotopically labeled IV microtracers in the evaluation of absolute bioavailability, which provides users the flexibility in using either LC-MS/MS or HRMS to mitigate unpredicted interferences in the assay to support microtracer absolute bioavailability studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined first-trimester Down syndrome screening in HIV-infected women.

PubMed

Chougrani, Imène; Muller, Françoise; Marcelin, Louis; Tsatsaris, Vassilis; Abric, Judith; Luton, Dominique; Guibourdenche, Jean; Azria, Elie

2016-08-01

To determine if human immunodeficiency virus (HIV) infection or antiretroviral therapy interferes with maternal levels of free human β-chorionic gonadotrophin (hCGβ) and pregnancy-associated plasma protein-A (PAPP-A) and whether any such influence alters first-trimester Down syndrome (DS) screening in HIV-infected women. We performed a multicenter 1:2 matched case-control study comparing 84 HIV-infected women with singleton pregnancies with controls randomly selected among uninfected women, delivered and screened in the same center and matched for maternal age, geographical origin and fetal sex. Groups did not differ significantly in screening results, although case women showed a slightly lower median free hCGβ multiple of the median (MoM) (1.11 versus 1.24 MoM, p=0.32) and higher median PAPP-A MoM (1.45 versus 1.32 MoM, p=0.23) than control women. The false-positive rate was similar in the case and control groups (5% versus 6.5%, p=0.5). Biomarker levels did not differ when comparing treated and untreated patients with their respective controls, and with one another. First-trimester DS combined screening biomarker levels and calculated risk do not seem to be significantly altered by HIV infection or antiretroviral treatment. This screening strategy appears to be suitable for HIV-infected women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of Vibration on Retention Characteristics of Screen Acquisition Systems

NASA Technical Reports Server (NTRS)

Tegart, J. R.; Park, A. C.

1977-01-01

An analytical and experimental investigation of the effect of vibration on the retention characteristics of screen acquisition systems was performed. The functioning of surface tension devices using fine-mesh screens requires that the pressure differential acting on the screen be less than its pressure retention capability. When exceeded, screen breakdown will occur and gas-free expulsion of propellant will no longer be possible. An analytical approach to predicting the effect of vibration was developed. This approach considers the transmission of the vibration to the screens of the device and the coupling of the liquid and the screen in establishing the screen response. A method of evaluating the transient response of the gas/liquid interface within the screen was also developed.

Collaborative Commercial Space Situational Awareness

NASA Astrophysics Data System (ADS)

Kelso, T. S.; Hendrix, D.; Sibert, D.; Hall, R. A.; Therien, W.

2013-09-01

There is an increasing recognition by commercial and civil space operators of the need for space situational awareness (SSA) data to support ongoing conjunction analysis, maneuver planning, and radio frequency interference mitigation as part of daily operations. While some SSA data is available from the Joint Space Operations Center via the Space Track web site, access to raw observations and photometric data is limited due to national security considerations. These data, however, are of significant value in calibrating intra- and inter-operator orbit determination results, determining inter-system biases, and assessing operating profiles in the geostationary orbit. This paper details an ongoing collaborative effort to collect and process optical observations and photometric data using a network of low-cost telescope installations and shows how these data are being used to support ongoing operations in the Space Data Center. This presentation will demonstrate how by leveraging advance photometric processing algorithms developed for Missile Defense Agency and the Ballistic Missile Defense (BMD) mission ExoAnalytic and AGI have been able to provide actionable SSA for satellite operators from small telescopes in less than optimal viewing conditions. Space has become an increasingly cluttered environment requiring satellite operators to remain forever vigilant in order to prevent collisions to preserve their assets and prevent further cluttering the space environment. The Joint Space Operations Center (JSpOC), which tracks all objects in earth orbit, reports possible upcoming conjunctions to operators by providing Conjunction Summary Messages (CSMs). However due to large positional uncertainties in the forward predicted position of space objects at the time closest approach the volume of CSMs is excessive to the point that maneuvers in response to CSMs without additional screening is cost prohibitive. CSSI and the Space Data Association have been able to screen most CSMs by using more accurate operator ephemeris. By screening with operator ephemeris alone they have been able to demonstrate that safety limits will not be exceeded in a good number of these encounters and that extra delta-V need to not be expended in a Collision Avoidance (COLA) maneuver. However there remains a decent portion of alerts that may warrant action especially when the secondary object is an uncontrolled space object such as a dead satellite or rocket body. By dynamically tasking the ESpOC observatories to provide real-time tracking and photometric characterization of the secondary objects in response to these CSMs satellite operators benefit from an additional method of conjunction screening. The refined tracks and conjunction assessments obtained by ESpOC screening allows operators to safely reduce the number of COLAs performed in response to safe close approaches and provide optimized COLA maneuver planning in response to validated threats.

Eye tracking reveals the cost of switching between self and other perspectives in a visual perspective-taking task.

PubMed

Ferguson, Heather J; Apperly, Ian; Cane, James E

2017-08-01

Previous studies have shown that while people can rapidly and accurately compute their own and other people's visual perspectives, they experience difficulty ignoring the irrelevant perspective when the two perspectives differ. We used the "avatar" perspective-taking task to examine the mechanisms that underlie these egocentric (i.e., interference from their own perspective) and altercentric (i.e., interference from the other person's perspective) tendencies. Participants were eye-tracked as they verified the number of discs in a visual scene according to either their own or an on-screen avatar's perspective. Crucially in some trials the two perspectives were inconsistent (i.e., each saw a different number of discs), while in others they were consistent. To examine the effect of perspective switching, performance was compared for trials that were preceded with the same versus a different perspective cue. We found that altercentric interference can be reduced or eliminated when participants stick with their own perspective across consecutive trials. Our eye-tracking analyses revealed distinct fixation patterns for self and other perspective taking, suggesting that consistency effects in this paradigm are driven by implicit mentalizing of what others can see, and not automatic directional cues from the avatar.

State of the art in the validation of screening methods for the control of antibiotic residues: is there a need for further development?

PubMed

Gaudin, Valérie

2017-09-01

Screening methods are used as a first-line approach to detect the presence of antibiotic residues in food of animal origin. The validation process guarantees that the method is fit-for-purpose, suited to regulatory requirements, and provides evidence of its performance. This article is focused on intra-laboratory validation. The first step in validation is characterisation of performance, and the second step is the validation itself with regard to pre-established criteria. The validation approaches can be absolute (a single method) or relative (comparison of methods), overall (combination of several characteristics in one) or criterion-by-criterion. Various approaches to validation, in the form of regulations, guidelines or standards, are presented and discussed to draw conclusions on their potential application for different residue screening methods, and to determine whether or not they reach the same conclusions. The approach by comparison of methods is not suitable for screening methods for antibiotic residues. The overall approaches, such as probability of detection (POD) and accuracy profile, are increasingly used in other fields of application. They may be of interest for screening methods for antibiotic residues. Finally, the criterion-by-criterion approach (Decision 2002/657/EC and of European guideline for the validation of screening methods), usually applied to the screening methods for antibiotic residues, introduced a major characteristic and an improvement in the validation, i.e. the detection capability (CCβ). In conclusion, screening methods are constantly evolving, thanks to the development of new biosensors or liquid chromatography coupled to tandem-mass spectrometry (LC-MS/MS) methods. There have been clear changes in validation approaches these last 20 years. Continued progress is required and perspectives for future development of guidelines, regulations and standards for validation are presented here.

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

PubMed

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

2006-01-01

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

High-Throughput RNA Interference Screening: Tricks of the Trade

PubMed Central

Nebane, N. Miranda; Coric, Tatjana; Whig, Kanupriya; McKellip, Sara; Woods, LaKeisha; Sosa, Melinda; Sheppard, Russell; Rasmussen, Lynn; Bjornsti, Mary-Ann; White, E. Lucile

2016-01-01

The process of validating an assay for high-throughput screening (HTS) involves identifying sources of variability and developing procedures that minimize the variability at each step in the protocol. The goal is to produce a robust and reproducible assay with good metrics. In all good cell-based assays, this means coefficient of variation (CV) values of less than 10% and a signal window of fivefold or greater. HTS assays are usually evaluated using Z′ factor, which incorporates both standard deviation and signal window. A Z′ factor value of 0.5 or higher is acceptable for HTS. We used a standard HTS validation procedure in developing small interfering RNA (siRNA) screening technology at the HTS center at Southern Research. Initially, our assay performance was similar to published screens, with CV values greater than 10% and Z′ factor values of 0.51 ± 0.16 (average ± standard deviation). After optimizing the siRNA assay, we got CV values averaging 7.2% and a robust Z′ factor value of 0.78 ± 0.06 (average ± standard deviation). We present an overview of the problems encountered in developing this whole-genome siRNA screening program at Southern Research and how equipment optimization led to improved data quality. PMID:23616418

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

PubMed

Smith, Kevin; Horvath, Peter

2014-06-01

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

An HTS-compatible 3D colony formation assay to identify tumor-specific chemotherapeutics.

PubMed

Horman, Shane R; To, Jeremy; Orth, Anthony P

2013-12-01

There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laser-scanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.

Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model.

PubMed

Browne, Patience; Judson, Richard S; Casey, Warren M; Kleinstreuer, Nicole C; Thomas, Russell S

2015-07-21

The U.S. Environmental Protection Agency (EPA) is considering high-throughput and computational methods to evaluate the endocrine bioactivity of environmental chemicals. Here we describe a multistep, performance-based validation of new methods and demonstrate that these new tools are sufficiently robust to be used in the Endocrine Disruptor Screening Program (EDSP). Results from 18 estrogen receptor (ER) ToxCast high-throughput screening assays were integrated into a computational model that can discriminate bioactivity from assay-specific interference and cytotoxicity. Model scores range from 0 (no activity) to 1 (bioactivity of 17β-estradiol). ToxCast ER model performance was evaluated for reference chemicals, as well as results of EDSP Tier 1 screening assays in current practice. The ToxCast ER model accuracy was 86% to 93% when compared to reference chemicals and predicted results of EDSP Tier 1 guideline and other uterotrophic studies with 84% to 100% accuracy. The performance of high-throughput assays and ToxCast ER model predictions demonstrates that these methods correctly identify active and inactive reference chemicals, provide a measure of relative ER bioactivity, and rapidly identify chemicals with potential endocrine bioactivities for additional screening and testing. EPA is accepting ToxCast ER model data for 1812 chemicals as alternatives for EDSP Tier 1 ER binding, ER transactivation, and uterotrophic assays.

A new method to address verification bias in studies of clinical screening tests: cervical cancer screening assays as an example.

PubMed

Xue, Xiaonan; Kim, Mimi Y; Castle, Philip E; Strickler, Howard D

2014-03-01

Studies to evaluate clinical screening tests often face the problem that the "gold standard" diagnostic approach is costly and/or invasive. It is therefore common to verify only a subset of negative screening tests using the gold standard method. However, undersampling the screen negatives can lead to substantial overestimation of the sensitivity and underestimation of the specificity of the diagnostic test. Our objective was to develop a simple and accurate statistical method to address this "verification bias." We developed a weighted generalized estimating equation approach to estimate, in a single model, the accuracy (eg, sensitivity/specificity) of multiple assays and simultaneously compare results between assays while addressing verification bias. This approach can be implemented using standard statistical software. Simulations were conducted to assess the proposed method. An example is provided using a cervical cancer screening trial that compared the accuracy of human papillomavirus and Pap tests, with histologic data as the gold standard. The proposed approach performed well in estimating and comparing the accuracy of multiple assays in the presence of verification bias. The proposed approach is an easy to apply and accurate method for addressing verification bias in studies of multiple screening methods. Copyright © 2014 Elsevier Inc. All rights reserved.

Foundry Microfabrication of Deformable Mirrors for Adaptive Optics

DTIC Science & Technology

1998-04-28

radians) of deflection. The 25% amplitude modulation of the piston array is due to constructive and destructive interference of light reflecting off the...34 Lithographie Galvanoformung und Abformung" is frequently applied to these plating processes. In the LIGA process synchrotron x-ray radiation is used to... interference because the support structures were metallized. In addition, only 61 mirror elements were controlled. Two approaches to improved

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

NASA Technical Reports Server (NTRS)

Barber, Peter W.; Demerdash, Nabeel A. O.; Wang, R.; Hurysz, B.; Luo, Z.

1991-01-01

The goal is to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom.The approach consists of four steps: (1) develop analytical tools (models and computer programs); (2) conduct parameterization studies; (3) predict the global space station EMI environment; and (4) provide a basis for modification of EMI standards.

Notes on Barkas-Andersen effect

NASA Astrophysics Data System (ADS)

Sigmund, Peter; Schinner, Andreas

2014-10-01

Stimulated by recent statements in the literature on electronic stopping of heavy ions in matter, we try to clarify some central theoretical aspects of the Barkas-Andersen effect, about which there does not seem to be unanimous agreement in the community. We address the role of inner versus outer target shells, of projectile screening by bound electrons, the interference between Lindhard's description and perturbation theory, as well as the equivalence between a single-electron versus Fermi-gas description of the effect.

Mathematical Modelling of Allelopathy: IV. Assessment of Contributions of Competition and Allelopathy to Interference by Barley

PubMed Central

Liu, De Li; An, Min; Johnson, I.R.; Lovett, J.V.

2005-01-01

One of the main challenges to the research on allelopathy is technically the separation of allelopathic effect from competition, and quantitatively, the assessment of the contribution of each component to overall interference. A simple mathematical model is proposed to calculate the contribution of allelopathy and competition to interference. As an example of applying the quantitative model to interference by barley (Hordeum vulgare cv. Triumph), the approach used was an addition of allelopathic effect, by an equivalent amount, to the environment of the test plant (white mustard, Sinapis alba), rather than elimination of competition. Experiments were conducted in glasshouse to determine the magnitude of the contributions of allelopathy and competition to interference by barley. The leachates of living barley roots significantly reduced the total dry weight of white mustard. The model involved the calculation of adjusted densities to an equivalent basis for modelling the contribution of allelopathy and competition to total interference. The results showed that allelopathy contributed 40%, 37% and 43% to interference by barley at 6, 12 and 18 white mustard pot−1. The consistency in magnitude of the calculated contribution of allelopathic effect by barley across various densities of receiver plant suggested that the adjusted equivalent density is effective and that the model is able to assess the contribution of each component of interference regardless of the density of receiver plant. PMID:19330162

Implementation of parallel transmit beamforming using orthogonal frequency division multiplexing--achievable resolution and interbeam interference.

PubMed

Demi, Libertario; Viti, Jacopo; Kusters, Lieneke; Guidi, Francesco; Tortoli, Piero; Mischi, Massimo

2013-11-01

The speed of sound in the human body limits the achievable data acquisition rate of pulsed ultrasound scanners. To overcome this limitation, parallel beamforming techniques are used in ultrasound 2-D and 3-D imaging systems. Different parallel beamforming approaches have been proposed. They may be grouped into two major categories: parallel beamforming in reception and parallel beamforming in transmission. The first category is not optimal for harmonic imaging; the second category may be more easily applied to harmonic imaging. However, inter-beam interference represents an issue. To overcome these shortcomings and exploit the benefit of combining harmonic imaging and high data acquisition rate, a new approach has been recently presented which relies on orthogonal frequency division multiplexing (OFDM) to perform parallel beamforming in transmission. In this paper, parallel transmit beamforming using OFDM is implemented for the first time on an ultrasound scanner. An advanced open platform for ultrasound research is used to investigate the axial resolution and interbeam interference achievable with parallel transmit beamforming using OFDM. Both fundamental and second-harmonic imaging modalities have been considered. Results show that, for fundamental imaging, axial resolution in the order of 2 mm can be achieved in combination with interbeam interference in the order of -30 dB. For second-harmonic imaging, axial resolution in the order of 1 mm can be achieved in combination with interbeam interference in the order of -35 dB.

Inhibitor of MYC identified in a Kröhnke pyridine library

PubMed Central

Hart, Jonathan R.; Garner, Amanda L.; Yu, Jing; Ito, Yoshihiro; Sun, Minghao; Ueno, Lynn; Rhee, Jin-Kyu; Baksh, Michael M.; Stefan, Eduard; Hartl, Markus; Bister, Klaus; Vogt, Peter K.; Janda, Kim D.

2014-01-01

In a fluorescence polarization screen for the MYC–MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. The Kd of KJ-Pyr-9 for MYC in vitro is 6.5 ± 1.0 nM, as determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC–MAX complex formation in the cell, as shown in a protein fragment complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in cell culture; it has no or only weak effects on the oncogenic activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation of MYC-overexpressing human and avian cells and specifically reduces the MYC-driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells. PMID:25114221

A New Method for Suppressing Periodic Narrowband Interference Based on the Chaotic van der Pol Oscillator

NASA Astrophysics Data System (ADS)

Lu, Jia; Zhang, Xiaoxing; Xiong, Hao

The chaotic van der Pol oscillator is a powerful tool for detecting defects in electric systems by using online partial discharge (PD) monitoring. This paper focuses on realizing weak PD signal detection in the strong periodic narrowband interference by using high sensitivity to the periodic narrowband interference signals and immunity to white noise and PD signals of chaotic systems. A new approach to removing the periodic narrowband interference by using a van der Pol chaotic oscillator is described by analyzing the motion characteristic of the chaotic oscillator on the basis of the van der Pol equation. Furthermore, the Floquet index for measuring the amplitude of periodic narrowband signals is redefined. The denoising signal processed by the chaotic van der Pol oscillators is further processed by wavelet analysis. Finally, the denoising results verify that the periodic narrowband and white noise interference can be removed efficiently by combining the theory of the chaotic van der Pol oscillator and wavelet analysis.

Predicting Pharmacodynamic Drug-Drug Interactions through Signaling Propagation Interference on Protein-Protein Interaction Networks.

PubMed

Park, Kyunghyun; Kim, Docyong; Ha, Suhyun; Lee, Doheon

2015-01-01

As pharmacodynamic drug-drug interactions (PD DDIs) could lead to severe adverse effects in patients, it is important to identify potential PD DDIs in drug development. The signaling starting from drug targets is propagated through protein-protein interaction (PPI) networks. PD DDIs could occur by close interference on the same targets or within the same pathways as well as distant interference through cross-talking pathways. However, most of the previous approaches have considered only close interference by measuring distances between drug targets or comparing target neighbors. We have applied a random walk with restart algorithm to simulate signaling propagation from drug targets in order to capture the possibility of their distant interference. Cross validation with DrugBank and Kyoto Encyclopedia of Genes and Genomes DRUG shows that the proposed method outperforms the previous methods significantly. We also provide a web service with which PD DDIs for drug pairs can be analyzed at http://biosoft.kaist.ac.kr/targetrw.

Inhibition of strigolactone receptors by N-phenylanthranilic acid derivatives: Structural and functional insights.

PubMed

Hamiaux, Cyril; Drummond, Revel S M; Luo, Zhiwei; Lee, Hui Wen; Sharma, Prachi; Janssen, Bart J; Perry, Nigel B; Denny, William A; Snowden, Kimberley C

2018-04-27

The strigolactone (SL) family of plant hormones regulates a broad range of physiological processes affecting plant growth and development and also plays essential roles in controlling interactions with parasitic weeds and symbiotic fungi. Recent progress elucidating details of SL biosynthesis, signaling, and transport offers many opportunities for discovering new plant-growth regulators via chemical interference. Here, using high-throughput screening and downstream biochemical assays, we identified N -phenylanthranilic acid derivatives as potent inhibitors of the SL receptors from petunia (DAD2), rice (OsD14), and Arabidopsis (AtD14). Crystal structures of DAD2 and OsD14 in complex with inhibitors further provided detailed insights into the inhibition mechanism, and in silico modeling of 19 other plant strigolactone receptors suggested that these compounds are active across a large range of plant species. Altogether, these results provide chemical tools for investigating SL signaling and further define a framework for structure-based approaches to design and validate optimized inhibitors of SL receptors for specific plant targets. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Visual stimulus presentation using fiber optics in the MRI scanner.

PubMed

Huang, Ruey-Song; Sereno, Martin I

2008-03-30

Imaging the neural basis of visuomotor actions using fMRI is a topic of increasing interest in the field of cognitive neuroscience. One challenge is to present realistic three-dimensional (3-D) stimuli in the subject's peripersonal space inside the MRI scanner. The stimulus generating apparatus must be compatible with strong magnetic fields and must not interfere with image acquisition. Virtual 3-D stimuli can be generated with a stereo image pair projected onto screens or via binocular goggles. Here, we describe designs and implementations for automatically presenting physical 3-D stimuli (point-light targets) in peripersonal and near-face space using fiber optics in the MRI scanner. The feasibility of fiber-optic based displays was demonstrated in two experiments. The first presented a point-light array along a slanted surface near the body, and the second presented multiple point-light targets around the face. Stimuli were presented using phase-encoded paradigms in both experiments. The results suggest that fiber-optic based displays can be a complementary approach for visual stimulus presentation in the MRI scanner.

Longitudinal in vivo transcutaneous observation of Raman signals from breast cancer during chemotherapy in small animal model

NASA Astrophysics Data System (ADS)

Seong, Myeongsu; Myoung, NoSoung; Yim, Sang-Youp; Kim, Jae G.

2015-02-01

Because mammography, the gold standard of breast cancer screening and monitoring treatment efficacy, has limitations, there is a necessity to have a new method for breast cancer patients. Raman spectroscopy is considered as one of the best alternative approaches due to its ability of visualizing (bio)chemical information of a matter. In this study, we hypothesized that the change of biochemical composition occurs earlier than morphological change in breast cancer during chemotherapy, and attempted to prove it by employing fiber-optic Raman spectroscopy for longitudinal Raman measurement in small animal breast cancer model. To confirm the hypothesis, we measured Raman spectra of a tumor breast and the contralateral breast during chemotherapy for 4 fisher 344 female rats longitudinally. Principal component analysis and Raman spectral differences between breast tumor and contralateral normal breast did not show a clear difference between them which may have been caused by interference from skin. Thus, spatially-offset Raman spectroscopy will be employed in order to acquire the Raman signal directly from tumor while suppressing Raman signal from skin for the future study.

Bioassay-guided isolation of proanthocyanidins with antiangiogenic activities.

PubMed

Pesca, Maria S; Dal Piaz, Fabrizio; Sanogo, Rokia; Vassallo, Antonio; Bruzual de Abreu, Maryan; Rapisarda, Antonio; Germanò, Maria P; Certo, Giovanna; De Falco, Sandro; De Tommasi, Nunziatina; Braca, Alessandra

2013-01-25

The proangiogenic members of the vascular endothelial growth factor (VEGF) family and related receptors play a central role in the modulation of pathological angiogenesis. In order to identify plant compounds able to interfere in the VEGFs/VEGFR-1 (Flt-1) recognition by VEGF family members, the extracts of the aerial parts of Campsiandra guayanensis and Feretia apodanthera were screened by a competitive ELISA-based assay. By using this bioassay-oriented approach five proanthocyanindins, including the new natural compounds (2S)-4',5,7-trihydroxyflavan-(4β→8)-afzelechin (1) and (2S)-4',5,7-trihydroxyflavan-(4β→8)-epiafzelechin (2) and the known geranin B (3), proanthocyanidin A2 (4), and proanthocyanidin A1 (5), were isolated. The study of the antiangiogenic activities of compounds 1-5 using ELISA and SPR assays showed compound 1 as being the most active. The antiangiogenic activity of 1 was also confirmed in vivo by the chicken chorioallantoic membrane assay. Our results indicated 1 as a new antiangiogenic compound inhibiting the interaction between VEGF-A or PlGF and their receptor VEGRF-1.

Polyketide synthase (PKS) reduces fusion of Legionella pneumophila-containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection.

PubMed

Shevchuk, Olga; Pägelow, Dennis; Rasch, Janine; Döhrmann, Simon; Günther, Gabriele; Hoppe, Julia; Ünal, Can Murat; Bronietzki, Marc; Gutierrez, Maximiliano Gabriel; Steinert, Michael

2014-11-01

L. pneumophila-containing vacuoles (LCVs) exclude endocytic and lysosomal markers in human macrophages and protozoa. We screened a L. pneumophila mini-Tn10 transposon library for mutants, which fail to inhibit the fusion of LCVs with lysosomes by loading of the lysosomal compartment with colloidal iron dextran, mechanical lysis of infected host cells, and magnetic isolation of LCVs that have fused with lysosomes. In silico analysis of the mutated genes, D. discoideum plaque assays and infection assays in protozoa and U937 macrophage-like cells identified well established as well as novel putative L. pneumophila virulence factors. Promising candidates were further analyzed for their co-localization with lysosomes in host cells using fluorescence microscopy. This approach corroborated that the O-methyltransferase, PilY1, TPR-containing protein and polyketide synthase (PKS) of L. pneumophila interfere with lysosomal degradation. Competitive infections in protozoa and macrophages revealed that the identified PKS contributes to the biological fitness of pneumophila strains and may explain their prevalence in the epidemiology of Legionnaires' disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

Tailoring mode interference in plasmon-induced transparency metamaterials

NASA Astrophysics Data System (ADS)

Liu, Meng; Yang, Quanlong; Xu, Quan; Chen, Xieyu; Tian, Zhen; Gu, Jianqiang; Ouyang, Chunmei; Zhang, Xueqian; Han, Jiaguang; Zhang, Weili

2018-05-01

We proposed an approach to tailor the mode interference effect in plasmon-induced transparency (PIT) metamaterials. Through introducing an extra coupling mode using an asymmetric structure configuration at terahertz (THz) frequencies, the well-known single-transparency-window PIT can be switched to dual-transparency-window PIT. Proof-of-concept subwavelength structures were fabricated and experimentally characterized. The measured results are in good agreement with the simulations, and well support our theoretical analysis. The presented research delivers a novel approach toward developing subwavelength devices with varies functionalities, such as ultra-slow group velocities, longitudinal pulse compression and light storage in the THz regime, which can also be extended to other spectral regimes.

Digital Breast Tomosynthesis in Addition to Conventional 2DMammography Reduces Recall Rates and is CostEffective.

PubMed

Pozz, Agostino; Corte, Angelo Della; Lakis, Mustapha A El; Jeong, HeonJae

2016-01-01

Digital breast tomosynthesis (DBT) as a breast cancer screening modality, through generation of three dimensional images during standard mammographic compression, can reduce interference from breast tissue overlap, increasing conspicuity of invasive cancers while concomitantly reducing falsepositive results. We here conducted a systematic review on previous studies to synthesize the evidence of DBT efficacy, eventually 18 articles being included in the analysis. The most commonly emerging topics were advantages of DBT screening tool in terms of recall rates, cancer detection rates and costeffectiveness, preventing unnecessary burdens on women and the healthcare system. Further research is needed to evaluate the potential impact of DBT on longerterm outcomes, such as interval cancer rates and mortality, to better understand the broader clinical and economic implications of its adoption.

A Druggable TCF4 and BRD4 dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm

PubMed Central

Ceribelli, Michele; Hou, Zhiying Esther; Kelly, Priscilla N.; Huang, Da Wei; Wright, George; Ganapathi, Karthik; Evbuomwan, Moses O.; Pittaluga, Stefania; Shaffer, Arthur L.; Marcucci, Guido; Forman, Stephen J.; Xiao, Wenming; Guha, Rajarshi; Zhang, Xiaohu; Ferrer, Marc; Chaperot, Laurence; Plumas, Joel; Jaffe, Elaine S.; Thomas, Craig J.; Reizis, Boris; Staudt, Louis M.

2016-01-01

SUMMARY Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNA interference screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETi’s) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETi’s retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy. PMID:27846392

A kinase-focused compound collection: compilation and screening strategy.

PubMed

Sun, Dongyu; Chuaqui, Claudio; Deng, Zhan; Bowes, Scott; Chin, Donovan; Singh, Juswinder; Cullen, Patrick; Hankins, Gretchen; Lee, Wen-Cherng; Donnelly, Jason; Friedman, Jessica; Josiah, Serene

2006-06-01

Lead identification by high-throughput screening of large compound libraries has been supplemented with virtual screening and focused compound libraries. To complement existing approaches for lead identification at Biogen Idec, a kinase-focused compound collection was designed, developed and validated. Two strategies were adopted to populate the compound collection: a ligand shape-based virtual screening and a receptor-based approach (structural interaction fingerprint). Compounds selected with the two approaches were cherry-picked from an existing high-throughput screening compound library, ordered from suppliers and supplemented with specific medicinal compounds from internal programs. Promising hits and leads have been generated from the kinase-focused compound collection against multiple kinase targets. The principle of the collection design and screening strategy was validated and the use of the kinase-focused compound collection for lead identification has been added to existing strategies.

Disseminating perinatal depression screening as a public health initiative: a train-the-trainer approach.

PubMed

Segre, Lisa S; Brock, Rebecca L; O'Hara, Michael W; Gorman, Laura L; Engeldinger, Jane

2011-08-01

This case report describes the development and implementation of the Train-the-Trainer: Maternal Depression Screening Program (TTT), a novel approach to disseminating perinatal depression screening. We trained screeners according to a standard pyramid scheme of train-the-trainer programs: three experts trained representatives from health care agencies (the TTT trainers), who in turn trained their staff and implemented depression screening at their home agencies. The TTT trainers had little or no prior mental health experience so "enhanced" components were added to ensure thorough instruction. Although TTT was implemented primarily as a services project, we evaluated both the statewide dissemination and the screening rates achieved by TTT programs. Thirty-two social service or health agencies implemented maternal depression screening in 20 counties throughout Iowa; this reached 58.2% of the Iowa population. For the 16 agencies that provided screening data, the average screening rate (number of women screened/number eligible to be screened) for the first 3 months of screening was 73.2%, 80.5% and 79.0%. We compared screening rates of our TTT programs with those of Healthy Start, a program in which screening was established via an intensive consultation model. We found the screening rates in 62.5% of TTT agencies were comparable to those in Healthy Start. Our "enhanced" train-the-trainer method is a promising approach for broadly implementing depression-screening programs in agencies serving pregnant and postpartum women.

Congressional Oversight of Judges and Justices

DTIC Science & Technology

2005-05-31

separation of powers . Further...Committee was an unconstitutional interference with judicial independence and a violation of separation of powers .86 The doctrine of separation of powers is...between two approaches to cases raising separation - of - powers claims, using a strict approach in some cases and a less rigid balancing approach in

Quantitative DIC microscopy using an off-axis self-interference approach.

PubMed

Fu, Dan; Oh, Seungeun; Choi, Wonshik; Yamauchi, Toyohiko; Dorn, August; Yaqoob, Zahid; Dasari, Ramachandra R; Feld, Michael S

2010-07-15

Traditional Normarski differential interference contrast (DIC) microscopy is a very powerful method for imaging nonstained biological samples. However, one of its major limitations is the nonquantitative nature of the imaging. To overcome this problem, we developed a quantitative DIC microscopy method based on off-axis sample self-interference. The digital holography algorithm is applied to obtain quantitative phase gradients in orthogonal directions, which leads to a quantitative phase image through a spiral integration of the phase gradients. This method is practically simple to implement on any standard microscope without stringent requirements on polarization optics. Optical sectioning can be obtained through enlarged illumination NA.

Criteria for opiate identification using liquid chromatography linked to tandem mass spectrometry: problems in routine practice.

PubMed

Fox, Elizabeth J; Twigger, Shirley; Allen, Keith R

2009-01-01

Liquid chromatography linked to tandem mass spectrometry (LC/MS/MS) is being increasingly used for drug confirmation. At present, no official criteria exist for drug identification using this technique although the European Union (EU) criteria for compound identification have been adopted. These criteria are evaluated with respect to opiate confirmation by LC/MS/MS and problems highlighted. Urine samples screened positive for opiates by immunoassay were subjected to confirmation by LC/MS/MS using multiple reaction monitoring (MRM) and two separate buffer systems of pH 6.8 and 8.0, respectively. The EU criteria for compound identification were applied for confirmation of morphine, 6-monoacetylmorphine (6MAM), codeine and dihydrocodeine (DHC). Using the pH 6.8 buffer, confirmation could be achieved for 84%, 94%, 96% and 95%, respectively, for samples demonstrating MRM chromatographic peaks at retention times for morphine, 6MAM, codeine and DHC. Failure to meet the EU criteria was mainly attributed to low signal-to-noise (S:N) ratios or excessively high drug concentrations. Isobaric interferences and poor chromatography were also contributing factors. The identification of morphine was considerably improved with chromatography at pH 8.0 owing to resolution of interferences. Oxycodone metabolites were a potential problem for the identification of DHC. Isobaric interferences can pose a problem with drug identification using LC/MS/MS. Optimizing chromatographic conditions is important to overcome these interferences. Consideration needs to be given to investigating drug metabolites as well as parent drugs in method development.

Cross-species extrapolation of toxicity information using the ...

EPA Pesticide Factsheets

In the United States, the Endocrine Disruptor Screening Program (EDSP) was established to identify chemicals that may lead to adverse effects via perturbation of the endocrine system (i.e., estrogen, androgen, and thyroid hormone systems). In the mid-1990s the EDSP adopted a two tiered approach for screening chemicals that applied standardized in vitro and in vivo toxicity tests. The Tier 1 screening assays were designed to identify substances that have the potential of interacting with the endocrine system and Tier 2 testing was developed to identify adverse effects caused by the chemical, with documentation of dose-response relationships. While this tiered approach was effective in identifying possible endocrine disrupting chemicals, the cost and time to screen a single chemical was significant. Therefore, in 2012 the EDSP proposed a transition to make greater use of computational approaches (in silico) and high-throughput screening (HTS; in vitro) assays to more rapidly and cost-efficiently screen chemicals for endocrine activity. This transition from resource intensive, primarily in vivo, screening methods to more pathway-based approaches aligns with the simultaneously occurring transformation in toxicity testing termed “Toxicity Testing in the 21st Century” which shifts the focus to the disturbance of the biological pathway predictive of the observable toxic effects. An example of such screening tools include the US Environmental Protection Agency’s

Electricity resonance-induced fast transport of water through nanochannels.

PubMed

Kou, Jianlong; Lu, Hangjun; Wu, Fengmin; Fan, Jintu; Yao, Jun

2014-09-10

We performed molecular dynamics simulations to study water permeation through a single-walled carbon nanotube with electrical interference. It was found that the water net flux across the nanochannel is greatly affected by the external electrical interference, with the maximal net flux occurred at an electrical interference frequency of 16670 GHz being about nine times as high as the net flux at the low or high frequency range of (<1000 GHz or >80,000 GHz). The above phenomena can be attributed to the breakage of hydrogen bonds as the electrical interference frequency approaches to the inherent resonant frequency of hydrogen bonds. The new mechanism of regulating water flux across nanochannels revealed in this study provides an insight into the water transportation through biological water channels and has tremendous potential in the design of high-flux nanofluidic systems.

Multimode quantum interference of photons in multiport integrated devices

PubMed Central

Peruzzo, Alberto; Laing, Anthony; Politi, Alberto; Rudolph, Terry; O'Brien, Jeremy L.

2011-01-01

Photonics is a leading approach in realizing future quantum technologies and recently, optical waveguide circuits on silicon chips have demonstrated high levels of miniaturization and performance. Multimode interference (MMI) devices promise a straightforward implementation of compact and robust multiport circuits. Here, we show quantum interference in a 2×2 MMI coupler with visibility of V=95.6±0.9%. We further demonstrate the operation of a 4×4 port MMI device with photon pairs, which exhibits complex quantum interference behaviour. We have developed a new technique to fully characterize such multiport devices, which removes the need for phase-sensitive measurements and may find applications for a wide range of photonic devices. Our results show that MMI devices can operate in the quantum regime with high fidelity and promise substantial simplification and concatenation of photonic quantum circuits. PMID:21364563

Strategies for laser-induced fluorescence detection of nitric oxide in high-pressure flames. II. A-X(0,1) excitation

NASA Astrophysics Data System (ADS)

Bessler, Wolfgang G.; Schulz, Christof; Lee, Tonghun; Jeffries, Jay B.; Hanson, Ronald K.

2003-04-01

A-X(0,1) excitation is a promising new approach for NO laser-induced fluorescence (LIF) diagnostics at elevated pressures and temperatures. We present what to our knowledge are the first detailed spectroscopic investigations within this excitation band using wavelength-resolved LIF measurements in premixed methane/air flames at pressures between 1 and 60 bar and a range of fuel/air ratios. Interference from O2 LIF is a significant problem in lean flames for NO LIF measurements, and pressure broadening and quenching lead to increased interference with increased pressure. Three different excitation schemes are identified that maximize NO/O2 LIF signal ratios, thereby minimizing the O2 interference. The NO LIF signal strength, interference by hot molecular oxygen, and temperature dependence of the three schemes are investigated.

Comfortably engaging: which approach to alcohol screening should we use?

PubMed

Vinson, Daniel C; Galliher, James M; Reidinger, Carol; Kappus, Jennifer A

2004-01-01

We wanted to compare 2 screening instruments for problem drinking, the CAGE and a single question, assessing frequency of use, patient and clinician comfort, and patient engagement in change. The study was a crossover, cluster-randomized clinical trial with 31 clinicians in Missouri and 13 in the American Academy of Family Physicians (AAFP) National Network for Family Practice and Primary Care Research; 2,800 patients provided data. The clinician was the unit of randomization. Clinicians decided whether to screen each patient; if they chose to screen, they used the screening approach assigned for that block of patients. The clinician and patient separately completed questionnaires immediately after the office visit to assess each one's comfort with screening (and any ensuing discussion) and the patient's engagement in change. Missouri clinicians screened more patients when assigned the single question (81%) than the CAGE (69%, P = .001 in weighted analysis). There was no difference among AAFP network clinicians (96% of patients screened with the CAGE, 97% with the single question). Eighty percent to 90% of clinicians and 70% of patients reported being comfortable with screening and the ensuing discussion, with no difference between approaches in either network. About one third of patients who were identified as problem drinkers reported thinking about or planning to change their drinking behavior, with no difference in engagement between screening approaches. Clinicians and patients reported similar comfort with the CAGE questions and the single-question screening tools for problem drinking, and the 2 instruments were equal in their ability to engage the patient. In Missouri, the single question was more likely to be used.

Decision-making and cancer screening: a qualitative study of older adults with multiple chronic conditions.

PubMed

Gross, Cary P; Fried, Terri R; Tinetti, Mary E; Ross, Joseph S; Genao, Inginia; Hossain, Sabina; Wolf, Elizabeth; Lewis, Carmen L

2015-03-01

To understand how older persons with multiple chronic conditions (MCC) approach decisions about cancer screening. We conducted interviews with adults >65 years old with at least two chronic conditions who were taking ≥five medications daily. Patients were first asked how age and multimorbidity influence their cancer screening decisions. After showing them an educational prompt that explained the relationship between life expectancy and the benefits of cancer screening, respondents were then asked about screening in the context of specific health scenarios. Using grounded theory, three independent readers coded responses for salient themes. Sample size was determined by thematic saturation. Most respondents (26 of 28) initially indicated that their overall health or medical conditions do not influence their cancer screening decisions. After viewing the educational prompt, respondents described two broad approaches to cancer screening in the setting of increasing age or multi-morbidity. The first was a "benefits versus harms" approach in which participants weighed direct health benefits (e.g. reducing cancer incidence or mortality) and harms (e.g. complications or inconvenience). The second was a heuristic approach. Some heuristics favored screening, such as a persistent belief in unspecified benefits from screening, value of knowledge about cancer status, and not wanting to "give up", whereas other heuristics discouraged screening, such as fatalism or a reluctance to learn about their cancer status. When considering cancer screening, some older persons with MCC employ heuristics which circumvent the traditional quantitative comparison of risks and benefits, providing an important challenge to informed decision making. Copyright © 2014 Elsevier Inc. All rights reserved.

Inkjet printing of TiO2/AlOOH heterostructures for the formation of interference color images with high optical visibility

PubMed Central

Yakovlev, Aleksandr V.; Milichko, Valentin A.; Pidko, Evgeny A.; Vinogradov, Vladimir V.; Vinogradov, Alexandr V.

2016-01-01

This paper describes a practical approach for the fabrication of highly visible interference color images using sol-gel ink technique and a common desktop inkjet printer. We show the potential of titania-boehmite inks for the production of optical heterostructures on various surfaces, which after drying on air produce optical solid layers with low and high refractive index. The optical properties of the surface heterostructures were adjusted following the principles of antireflection coating resulting in the enhancement of the interference color optical visibility of the prints by as much as 32%. Finally, the presented technique was optimized following the insights into the mechanisms of the drop-surface interactions and the drop-on-surface coalescence to make it suitable for the production of even thickness coatings suitable for printing at a large scale. We propose that the technology described herein is a promising new green and sustainable approach for color printing. PMID:27848979

Quantum interference in heterogeneous superconducting-photonic circuits on a silicon chip

PubMed Central

Schuck, C.; Guo, X.; Fan, L.; Ma, X.; Poot, M.; Tang, H. X.

2016-01-01

Quantum information processing holds great promise for communicating and computing data efficiently. However, scaling current photonic implementation approaches to larger system size remains an outstanding challenge for realizing disruptive quantum technology. Two main ingredients of quantum information processors are quantum interference and single-photon detectors. Here we develop a hybrid superconducting-photonic circuit system to show how these elements can be combined in a scalable fashion on a silicon chip. We demonstrate the suitability of this approach for integrated quantum optics by interfering and detecting photon pairs directly on the chip with waveguide-coupled single-photon detectors. Using a directional coupler implemented with silicon nitride nanophotonic waveguides, we observe 97% interference visibility when measuring photon statistics with two monolithically integrated superconducting single-photon detectors. The photonic circuit and detector fabrication processes are compatible with standard semiconductor thin-film technology, making it possible to implement more complex and larger scale quantum photonic circuits on silicon chips. PMID:26792424

Online induction heating for determination of isotope composition of woody stem water with laser spectrometry: A methods assessment

USGS Publications Warehouse

Lazarus, Brynne E.; Germino, Matthew; Vander Veen, Jessica L.

2016-01-01

Application of stable isotopes of water to studies of plant–soil interactions often requires a substantial preparatory step of extracting water from samples without fractionating isotopes. Online heating is an emerging approach for this need, but is relatively untested and major questions of how to best deliver standards and assess interference by organics have not been evaluated. We examined these issues in our application of measuring woody stem xylem of sagebrush using a Picarro laser spectrometer with online induction heating. We determined (1) effects of cryogenic compared to induction-heating extraction, (2) effects of delivery of standards on filter media compared to on woody stem sections, and (3) spectral interference from organic compounds for these approaches (and developed a technique to do so). Our results suggest that matching sample and standard media improves accuracy, but that isotopic values differ with the extraction method in ways that are not due to spectral interference from organics.

Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

PubMed

Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

2013-12-15

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

MISSION LentiPlex pooled shRNA library screening in mammalian cells.

PubMed

Coussens, Matthew J; Corman, Courtney; Fischer, Ashley L; Sago, Jack; Swarthout, John

2011-12-21

RNA interference (RNAi) is an intrinsic cellular mechanism for the regulation of gene expression. Harnessing the innate power of this system enables us to knockdown gene expression levels in loss of gene function studies. There are two main methods for performing RNAi. The first is the use of small interfering RNAs (siRNAs) that are chemically synthesized, and the second utilizes short-hairpin RNAs (shRNAs) encoded within plasmids. The latter can be transfected into cells directly or packaged into replication incompetent lentiviral particles. The main advantages of using lentiviral shRNAs is the ease of introduction into a wide variety of cell types, their ability to stably integrate into the genome for long term gene knockdown and selection, and their efficacy in conducting high-throughput loss of function screens. To facilitate this we have created the LentiPlex pooled shRNA library. The MISSION LentiPlex Human shRNA Pooled Library is a genome-wide lentiviral pool produced using a proprietary process. The library consists of over 75,000 shRNA constructs from the TRC collection targeting 15,000+ human genes. Each library is tested for shRNA representation before product release to ensure robust library coverage. The library is provided in a ready-to-use lentiviral format at titers of at least 5 x 10(8) TU/ml via p24 assay and is pre-divided into ten subpools of approximately 8,000 shRNA constructs each. Amplification and sequencing primers are also provided for downstream target identification. Previous studies established a synergistic antitumor activity of TRAIL when combined with Paclitaxel in A549 cells, a human lung carcinoma cell line. In this study we demonstrate the application of a pooled LentiPlex shRNA library to rapidly conduct a positive selection screen for genes involved in the cytotoxicity of A549 cells when exposed to TRAIL and Paclitaxel. One barrier often encountered with high-throughput screens is the cost and difficulty in deconvolution; we also detail a cost-effective polyclonal approach utilizing traditional sequencing.

Dual signal subspace projection (DSSP): a novel algorithm for removing large interference in biomagnetic measurements

NASA Astrophysics Data System (ADS)

Sekihara, Kensuke; Kawabata, Yuya; Ushio, Shuta; Sumiya, Satoshi; Kawabata, Shigenori; Adachi, Yoshiaki; Nagarajan, Srikantan S.

2016-06-01

Objective. In functional electrophysiological imaging, signals are often contaminated by interference that can be of considerable magnitude compared to the signals of interest. This paper proposes a novel algorithm for removing such interferences that does not require separate noise measurements. Approach. The algorithm is based on a dual definition of the signal subspace in the spatial- and time-domains. Since the algorithm makes use of this duality, it is named the dual signal subspace projection (DSSP). The DSSP algorithm first projects the columns of the measured data matrix onto the inside and outside of the spatial-domain signal subspace, creating a set of two preprocessed data matrices. The intersection of the row spans of these two matrices is estimated as the time-domain interference subspace. The original data matrix is projected onto the subspace that is orthogonal to this interference subspace. Main results. The DSSP algorithm is validated by using the computer simulation, and using two sets of real biomagnetic data: spinal cord evoked field data measured from a healthy volunteer and magnetoencephalography data from a patient with a vagus nerve stimulator. Significance. The proposed DSSP algorithm is effective for removing overlapped interference in a wide variety of biomagnetic measurements.

A new criterion to evaluate water vapor interference in protein secondary structural analysis by FTIR spectroscopy.

PubMed

Zou, Ye; Ma, Gang

2014-06-04

Second derivative and Fourier self-deconvolution (FSD) are two commonly used techniques to resolve the overlapped component peaks from the often featureless amide I band in Fourier transform infrared (FTIR) curve-fitting approach for protein secondary structural analysis. Yet, the reliability of these two techniques is greatly affected by the omnipresent water vapor in the atmosphere. Several criteria are currently in use as quality controls to ensure the protein absorption spectrum is negligibly affected by water vapor interference. In this study, through a second derivative study of liquid water, we first argue that the previously established criteria cannot guarantee a reliable evaluation of water vapor interference due to a phenomenon that we refer to as sample's absorbance-dependent water vapor interference. Then, through a comparative study of protein and liquid water, we show that a protein absorption spectrum can still be significantly affected by water vapor interference even though it satisfies the established criteria. At last, we propose to use the comparison between the second derivative spectra of protein and liquid water as a new criterion to better evaluate water vapor interference for more reliable second derivative and FSD treatments on the protein amide I band.

Stroop Color-Word Interference Test: Normative data for Spanish-speaking pediatric population.

PubMed

Rivera, D; Morlett-Paredes, A; Peñalver Guia, A I; Irías Escher, M J; Soto-Añari, M; Aguayo Arelis, A; Rute-Pérez, S; Rodríguez-Lorenzana, A; Rodríguez-Agudelo, Y; Albaladejo-Blázquez, N; García de la Cadena, C; Ibáñez-Alfonso, J A; Rodriguez-Irizarry, W; García-Guerrero, C E; Delgado-Mejía, I D; Padilla-López, A; Vergara-Moragues, E; Barrios Nevado, M D; Saracostti Schwartzman, M; Arango-Lasprilla, J C

2017-01-01

To generate normative data for the Stroop Word-Color Interference test in Spanish-speaking pediatric populations. The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the Stroop Word-Color Interference test as part of a larger neuropsychological battery. The Stroop Word, Stroop Color, Stroop Word-Color, and Stroop Interference scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. The final multiple linear regression models showed main effects for age on all scores, except on Stroop Interference for Guatemala, such that scores increased linearly as a function of age. Age2 affected Stroop Word scores for all countries, Stroop Color scores for Ecuador, Mexico, Peru, and Spain; Stroop Word-Color scores for Ecuador, Mexico, and Paraguay; and Stroop Interference scores for Cuba, Guatemala, and Spain. MLPE affected Stroop Word scores for Chile, Mexico, and Puerto Rico; Stroop Color scores for Mexico, Puerto Rico, and Spain; Stroop Word-Color scores for Ecuador, Guatemala, Mexico, Puerto Rico and Spain; and Stroop-Interference scores for Ecuador, Mexico, and Spain. Sex affected Stroop Word scores for Spain, Stroop Color scores for Mexico, and Stroop Interference for Honduras. This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the Stroop Word-Color Interference test in pediatric populations.

Functional genomics platform for pooled screening and mammalian genetic interaction maps

PubMed Central

Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

2014-01-01

Systematic genetic interaction maps in microorganisms are powerful tools for identifying functional relationships between genes and defining the function of uncharacterized genes. We have recently implemented this strategy in mammalian cells as a two-stage approach. First, genes of interest are robustly identified in a pooled genome-wide screen using complex shRNA libraries. Second, phenotypes for all pairwise combinations of hit genes are measured in a double-shRNA screen and used to construct a genetic interaction map. Our protocol allows for rapid pooled screening under various conditions without a requirement for robotics, in contrast to arrayed approaches. Each stage of the protocol can be implemented in ~2 weeks, with additional time for analysis and generation of reagents. We discuss considerations for screen design, and present complete experimental procedures as well as a full computational analysis suite for identification of hits in pooled screens and generation of genetic interaction maps. While the protocols outlined here were developed for our original shRNA-based approach, they can be applied more generally, including to CRISPR-based approaches. PMID:24992097

Multiplex Immunoassay Profiling.

PubMed

Stephen, Laurie

2017-01-01

Multiplex immunoassays allow for the rapid profiling of biomarker proteins in biological fluids, using less sample and labor than single immunoassays. This chapter details the methods to develop and manufacture multiplex assays for the Luminex ® platform. Although assay development is not included here, the same methods can be used to covalently couple antibodies to the Luminex beads and to label antibodies for the screening of sandwich pairs, if needed. The assay optimization, detection of cross-reactivity, and minimizing antibody interactions and matrix interferences will be addressed.

Operation, Maintenance and Performance Evaluation of the Potomac Estuary Experimental Water Treatment Plant. Appendix. Volume 1.

DTIC Science & Technology

1983-09-01

Biochemical Screening A-i-12 Quantitative Determination of Viruses A-1-13 Virus Adsorption A-1-13 Elution A-1-13 Reconcentration A-1-13 Virus Assay A-I... VIRUSES VIRUS ADSORPTION " The virus concentration method was based on an adsorption/elution procedure described in the 14th edition of Standard...the replication process of one virus may be inhibited by another. If the inoculum contains few infective viruses , interference problems are of little

Walla Walla River Basin Fish Screen Evaluations; Nursery Bridge Fishway and Garden City/Lowden II Sites, 2005-2006 Progress Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chamness, Mickie

2006-06-01

Pacific Northwest National Laboratory (PNNL) evaluated two fish screen facilities in the Walla Walla River basin in 2005 and early 2006. The Garden City/Lowden screen site was evaluated in April and June 2005 to determine whether the fish screens met National Marine Fisheries Service criteria to provide safe passage for juvenile salmonids. Louvers behind the screens at the Nursery Bridge Fishway were modified in fall 2005 in an attempt to minimize high approach velocities. PNNL evaluated the effects of those modifications in March 2006. Results of the Garden City/Lowden evaluations indicate the site performs well at varying river levels andmore » canal flows. Approach velocities did not exceed 0.4 feet per second (fps) at any time. Sweep velocities increased toward the fish ladder in March but not in June. The air-burst mechanism appears to keep large debris off the screens, although it does not prevent algae and periphyton from growing on the screen face, especially near the bottom of the screens. At Nursery Bridge, results indicate all the approach velocities were below 0.4 fps under the moderate river levels and operational conditions encountered on March 7, 2006. Sweep did not consistently increase toward the fish ladder, but the site generally met the criteria for safe passage of juvenile salmonids. Modifications to the louvers seem to allow more control over the amount of water moving through the screens. We will measure approach velocities when river levels are higher to determine whether the louver modifications can help correct excessive approach velocities under a range of river levels and auxiliary water supply flows.« less

Implementation of a fall screening program in a high risk of fracture population.

PubMed

Ritchey, Katherine; Olney, Amanda; Shofer, Jane; Phelan, Elizabeth A; Matsumoto, Alvin M

2017-10-31

Fall prevention is an important way to prevent fractures in person with osteoporosis. We developed and implemented a fall screening program in the context of routine osteoporosis care. This program was found to be feasible and showed that a significant proportion of persons with osteoporosis are at risk of falling. Falls are the most common cause of fracture in persons with osteoporosis. However, osteoporosis care rarely includes assessment and prevention of falling. We thus sought to assess the feasibility of a fall screening and management program integrated into routine osteoporosis care. The program was developed and offered to patients with osteoporosis or osteopenia seen at an outpatient clinic between May 2015 and May 2016. Feasibility was measured by physical therapist time required to conduct screening and ease of integrating the screening program into the usual clinic workflow. Self-report responses and mobility testing were conducted to describe the fall and fracture risk profile of osteoporosis patients screened. Effects on fall-related care processes were assessed via chart abstraction of patient participation in fall prevention exercise. Of the 154 clinic patients who presented for a clinic visit, 68% met screening criteria and completed in two thirds of persons. Screening was completed in a third of the time typically allotted for traditional PT evaluations and did not interfere with clinic workflow. Forty percent of those screened reported falling in the last year, and over half had two or more falls in the past year. Over half reported a balance or lower extremity impairment, and over 40% were below norms on one or more performance tests. Most patients who selected a group exercise fall prevention program completed all sessions while only a quarter completed either supervised or independent home-based programs. Implementation of a fall risk screening program in an outpatient osteoporosis clinic appears feasible. A substantial proportion of people with osteoporosis screened positive for being at risk of falling, justifying integration of fall prevention into routine osteoporosis care.

COMPUTATIONAL TOXICOLOGY - OBJECTIVE 2: DEVELOPING APPROACHES FOR PRIORITIZING CHEMICALS FOR SUBSEQUENT SCREENING AND TESTING

EPA Science Inventory

One of the strategic objectives of the Computational Toxicology Program is to develop approaches for prioritizing chemicals for subsequent screening and testing. Approaches currently available for this process require extensive resources. Therefore, less costly and time-extensi...

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

PubMed Central

Dai, Xudong; Souza, Angus T. De; Dai, Hongyue; Lewis, David L; Lee, Chang-kyu; Spencer, Andy G; Herweijer, Hans; Hagstrom, Jim E; Linsley, Peter S; Bassett, Douglas E; Ulrich, Roger G; He, Yudong D

2007-01-01

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events. PMID:17335344

Reference ranges for serum total and monomeric prolactin for the current generation Abbott Architect assay.

PubMed

Whitehead, S J; Cornes, M P; Ford, C; Gama, R

2015-01-01

Exclusion of macroprolactinaemia, a well-recognised interference, as the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and mismanagement of patients. We have derived gender-specific serum total and post-polyethylene glycol (PEG) precipitation monomeric reference ranges for the recently re-standardised Abbott Architect prolactin assay. Prolactin was measured in serum samples obtained from males (n=49) and females (n=52) using the current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender-specific reference ranges were derived for total and monomeric (post-PEG) prolactin. Routine patients' samples (n=175) with a serum total prolactin >700 mIU/L were screened for macroprolactinaemia to assess classification compared with our previous post-PEG precipitation percentage recovery-based approach. Reference ranges for serum total prolactin were 58-419 mIU/L (male) and 63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were 32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients' samples screened for macroprolactinaemia, 149 had monomeric prolactin concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above the gender-specific reference range. Monomeric prolactin concentrations (median monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were within the reference ranges. One patient classified as macroprolactin positive and another classified as macroprolactin negative would not have been identified as such using the previous recovery-based approach. The use of post-PEG monomeric reference ranges not only identifies hyperprolactinaemia due solely to macroprolactinaemia but has the added advantage of identifying patients who have simultaneous true monomeric hyperprolactinaemia and elevated concentrations of macroprolactin. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Performance-informed EEG analysis reveals mixed evidence for EEG signatures unique to the processing of time.

PubMed

Schlichting, Nadine; de Jong, Ritske; van Rijn, Hedderik

2018-06-20

Certain EEG components (e.g., the contingent negative variation, CNV, or beta oscillations) have been linked to the perception of temporal magnitudes specifically. However, it is as of yet unclear whether these EEG components are really unique to time perception or reflect the perception of magnitudes in general. In the current study we recorded EEG while participants had to make judgments about duration (time condition) or numerosity (number condition) in a comparison task. This design allowed us to directly compare EEG signals between the processing of time and number. Stimuli consisted of a series of blue dots appearing and disappearing dynamically on a black screen. Each stimulus was characterized by its duration and the total number of dots that it consisted of. Because it is known that tasks like these elicit perceptual interference effects that we used a maximum-likelihood estimation (MLE) procedure to determine, for each participant and dimension separately, to what extent time and numerosity information were taken into account when making a judgement in an extensive post hoc analysis. This approach enabled us to capture individual differences in behavioral performance and, based on the MLE estimates, to select a subset of participants who suppressed task-irrelevant information. Even for this subset of participants, who showed no or only small interference effects and thus were thought to truly process temporal information in the time condition and numerosity information in the number condition, we found CNV patterns in the time-domain EEG signals for both tasks that was more pronounced in the time-task. We found no substantial evidence for differences between the processing of temporal and numerical information in the time-frequency domain.

Critical comparison of mass analyzers for forensic hair analysis by ambient ionization mass spectrometry.

PubMed

Duvivier, Wilco F; van Beek, Teris A; Nielen, Michel W F

2016-11-15

Recently, several direct and/or ambient mass spectrometry (MS) approaches have been suggested for drugs of abuse imaging in hair. The use of mass spectrometers with insufficient selectivity could result in false-positive measurements due to isobaric interferences. Different mass analyzers have been evaluated regarding their selectivity and sensitivity for the detection of Δ9-tetrahydrocannabinol (THC) from intact hair samples using direct analysis in real time (DART) ionization. Four different mass analyzers, namely (1) an orbitrap, (2) a quadrupole orbitrap, (3) a triple quadrupole, and (4) a quadrupole time-of-flight (QTOF), were evaluated. Selectivity and sensitivity were assessed by analyzing secondary THC standard dilutions on stainless steel mesh screens and blank hair samples, and by the analysis of authentic cannabis user hair samples. Additionally, separation of isobaric ions by use of travelling wave ion mobility (TWIM) was investigated. The use of a triple quadrupole instrument resulted in the highest sensitivity; however, transitions used for multiple reaction monitoring were only found to be specific when using high mass resolution product ion measurements. A mass resolution of at least 30,000 FWHM at m/z 315 was necessary to avoid overlap of THC with isobaric ions originating from the hair matrix. Even though selectivity was enhanced by use of TWIM, the QTOF instrument in resolution mode could not indisputably differentiate THC from endogenous isobaric ions in drug user hair samples. Only the high resolution of the (quadrupole) orbitrap instruments and the QTOF instrument in high-resolution mode distinguished THC in hair samples from endogenous isobaric interferences. As expected, enhanced selectivity compromises sensitivity and THC was only detectable in hair from heavy users. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Suppression of AC railway power-line interference in ECG signals recorded by public access defibrillators

PubMed Central

Dotsinsky, Ivan

2005-01-01

Background Public access defibrillators (PADs) are now available for more efficient and rapid treatment of out-of-hospital sudden cardiac arrest. PADs are used normally by untrained people on the streets and in sports centers, airports, and other public areas. Therefore, automated detection of ventricular fibrillation, or its exclusion, is of high importance. A special case exists at railway stations, where electric power-line frequency interference is significant. Many countries, especially in Europe, use 16.7 Hz AC power, which introduces high level frequency-varying interference that may compromise fibrillation detection. Method Moving signal averaging is often used for 50/60 Hz interference suppression if its effect on the ECG spectrum has little importance (no morphological analysis is performed). This approach may be also applied to the railway situation, if the interference frequency is continuously detected so as to synchronize the analog-to-digital conversion (ADC) for introducing variable inter-sample intervals. A better solution consists of rated ADC, software frequency measuring, internal irregular re-sampling according to the interference frequency, and a moving average over a constant sample number, followed by regular back re-sampling. Results The proposed method leads to a total railway interference cancellation, together with suppression of inherent noise, while the peak amplitudes of some sharp complexes are reduced. This reduction has negligible effect on accurate fibrillation detection. Conclusion The method is developed in the MATLAB environment and represents a useful tool for real time railway interference suppression. PMID:16309558

Suppression of AC railway power-line interference in ECG signals recorded by public access defibrillators.

PubMed

Dotsinsky, Ivan

2005-11-26

Public access defibrillators (PADs) are now available for more efficient and rapid treatment of out-of-hospital sudden cardiac arrest. PADs are used normally by untrained people on the streets and in sports centers, airports, and other public areas. Therefore, automated detection of ventricular fibrillation, or its exclusion, is of high importance. A special case exists at railway stations, where electric power-line frequency interference is significant. Many countries, especially in Europe, use 16.7 Hz AC power, which introduces high level frequency-varying interference that may compromise fibrillation detection. Moving signal averaging is often used for 50/60 Hz interference suppression if its effect on the ECG spectrum has little importance (no morphological analysis is performed). This approach may be also applied to the railway situation, if the interference frequency is continuously detected so as to synchronize the analog-to-digital conversion (ADC) for introducing variable inter-sample intervals. A better solution consists of rated ADC, software frequency measuring, internal irregular re-sampling according to the interference frequency, and a moving average over a constant sample number, followed by regular back re-sampling. The proposed method leads to a total railway interference cancellation, together with suppression of inherent noise, while the peak amplitudes of some sharp complexes are reduced. This reduction has negligible effect on accurate fibrillation detection. The method is developed in the MATLAB environment and represents a useful tool for real time railway interference suppression.

HTS-DB: an online resource to publish and query data from functional genomics high-throughput siRNA screening projects.

PubMed

Saunders, Rebecca E; Instrell, Rachael; Rispoli, Rossella; Jiang, Ming; Howell, Michael

2013-01-01

High-throughput screening (HTS) uses technologies such as RNA interference to generate loss-of-function phenotypes on a genomic scale. As these technologies become more popular, many research institutes have established core facilities of expertise to deal with the challenges of large-scale HTS experiments. As the efforts of core facility screening projects come to fruition, focus has shifted towards managing the results of these experiments and making them available in a useful format that can be further mined for phenotypic discovery. The HTS-DB database provides a public view of data from screening projects undertaken by the HTS core facility at the CRUK London Research Institute. All projects and screens are described with comprehensive assay protocols, and datasets are provided with complete descriptions of analysis techniques. This format allows users to browse and search data from large-scale studies in an informative and intuitive way. It also provides a repository for additional measurements obtained from screens that were not the focus of the project, such as cell viability, and groups these data so that it can provide a gene-centric summary across several different cell lines and conditions. All datasets from our screens that can be made available can be viewed interactively and mined for further hit lists. We believe that in this format, the database provides researchers with rapid access to results of large-scale experiments that might facilitate their understanding of genes/compounds identified in their own research. DATABASE URL: http://hts.cancerresearchuk.org/db/public.

Abnormal ovarian cancer screening test result: women's informational, psychological and practical needs.

PubMed

Ryan, Patricia Y; Graves, Kristi D; Pavlik, Edward J; Andrykowski, Michael A

2007-01-01

Considerable effort has been devoted to the identification of cost-effective approaches to screening for ovarian cancer (OC). Transvaginal ultrasound (TVS) is one such screening approach. Approximately 5-7% of routine TVS screening tests yield abnormal results. Some women experience significant distress after receipt of an abnormal TVS screening test. Four focus groups provided in-depth, qualitative data regarding the informational, psychological, and practical needs of women after the receipt of an abnormal TVS result. Through question and content analytic procedures, we identified four themes: anticipation, emotional response, role of the screening technician, and impact of prior cancer experiences. Results provide initial guidance toward development of interventions to promote adaptive responses after receipt of an abnormal cancer screening test result.

A Multiplexed High-Content Screening Approach Using the Chromobody Technology to Identify Cell Cycle Modulators in Living Cells.

PubMed

Schorpp, Kenji; Rothenaigner, Ina; Maier, Julia; Traenkle, Bjoern; Rothbauer, Ulrich; Hadian, Kamyar

2016-10-01

Many screening hits show relatively poor quality regarding later efficacy and safety. Therefore, small-molecule screening efforts shift toward high-content analysis providing more detailed information. Here, we describe a novel screening approach to identify cell cycle modulators with low toxicity by combining the Cell Cycle Chromobody (CCC) technology with the CytoTox-Glo (CTG) cytotoxicity assay. The CCC technology employs intracellularly functional single-domain antibodies coupled to a fluorescent protein (chromobodies) to visualize the cell cycle-dependent redistribution of the proliferating cell nuclear antigen (PCNA) in living cells. This image-based cell cycle analysis was combined with determination of dead-cell protease activity in cell culture supernatants by the CTG assay. We adopted this multiplex approach to high-throughput format and screened 960 Food and Drug Administration (FDA)-approved drugs. By this, we identified nontoxic compounds, which modulate different cell cycle stages, and validated selected hits in diverse cell lines stably expressing CCC. Additionally, we independently validated these hits by flow cytometry as the current state-of-the-art format for cell cycle analysis. This study demonstrates that CCC imaging is a versatile high-content screening approach to identify cell cycle modulators, which can be multiplexed with cytotoxicity assays for early elimination of toxic compounds during screening. © 2016 Society for Laboratory Automation and Screening.

Comparison of procedures for correction of matrix interferences in the analysis of soils by ICP-OES with CCD detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadler, D.A.; Sun, F.; Littlejohn, D.

1995-12-31

ICP-OES is a useful technique for multi-element analysis of soils. However, as a number of elements are present in relatively high concentrations, matrix interferences can occur and examples have been widely reported. The availability of CCD detectors has increased the opportunities for rapid multi-element, multi-wave-length determination of elemental concentrations in soils and other environmental samples. As the composition of soils from industrial sites can vary considerably, especially when taken from different pit horizons, procedures are required to assess the extent of interferences and correct the effects, on a simultaneous multi-element basis. In single element analysis, plasma operating conditions can sometimesmore » be varied to minimize or even remove multiplicative interferences. In simultaneous multi-element analysis, the scope for this approach may be limited, depending on the spectrochemical characteristics of the emitting analyte species. Matrix matching, by addition of major sample components to the analyte calibrant solutions, can be used to minimize inaccuracies. However, there are also limitations to this procedure, when the sample composition varies significantly. Multiplicative interference effects can also be assessed by a {open_quotes}single standard addition{close_quotes} of each analyte to the sample solution and the information obtained may be used to correct the analyte concentrations determined directly. Each of these approaches has been evaluated to ascertain the best procedure for multi-element analysis of industrial soils by ICP-OES with CCD detection at multiple wavelengths. Standard reference materials and field samples have been analyzed to illustrate the efficacy of each procedure.« less

Micro-bead injection spectroscopy for label-free automated determination of immunoglobulin G in human serum.

PubMed

Ramos, Inês I; Magalhães, Luís M; Barreiros, Luisa; Reis, Salette; Lima, José L F C; Segundo, Marcela A

2018-01-01

Immunoglobulin G (IgG) represents the major fraction of antibodies in healthy adult human serum, and deviations from physiological levels are a generic marker of disease corresponding to different pathologies. Therefore, screening methods for IgG evaluation are a valuable aid to diagnostics. The present work proposes a rapid, automatic, and miniaturized method based on UV-vis micro-bead injection spectroscopy (μ-BIS) for the real-time determination of human serum IgG with label-free detection. Relying on attachment of IgG in rec-protein G immobilized in Sepharose 4B, a bioaffinity column is automatically assembled, where IgG is selectively retained and determined by on-column optical density measurement. A "dilution-and-shoot" approach (50 to 200 times) was implemented without further sample treatment because interferences were flushed out of the column upon sample loading, with minimization of carryover and cross-contamination by automatically discarding the sorbent (0.2 mg) after each determination. No interference from human serum albumin at 60 mg mL -1 in undiluted sample was found. The method allowed IgG determination in the range 100-300 μg mL -1 (corresponding to 5.0-60 mg mL -1 in undiluted samples), with a detection limit of 33 μg mL -1 (1.7 mg mL -1 for samples, dilution factor of 50). RSD values were < 9.4 and < 11.7%, for intra and inter-assay precision, respectively, while recovery values for human serum spiked with IgG at high pathological levels were 97.8-101.4%. Comparison to commercial ELISA kit showed no significant difference for tested samples (n = 8). Moreover, time-to-result decreased from several hours to < 5 min and analysis cost decreased 10 times, showing the potential of the proposed approach as a point-of-care method. Graphical abstract Micro-Bead Injection Spectroscopy method for real time, automated and label-free determination of total serum human Immunoglobulin G (IgG). The method was designed for Lab-on-Valve (LOV) platforms using a miniaturised protein G bioaffinity separative approach. IgG are separated from serum matrix components upon quantification with low non-specific binding in less than 5 min.

Bargaining and the MISO Interference Channel

NASA Astrophysics Data System (ADS)

Nokleby, Matthew; Swindlehurst, A. Lee

2009-12-01

We examine the MISO interference channel under cooperative bargaining theory. Bargaining approaches such as the Nash and Kalai-Smorodinsky solutions have previously been used in wireless networks to strike a balance between max-sum efficiency and max-min equity in users' rates. However, cooperative bargaining for the MISO interference channel has only been studied extensively for the two-user case. We present an algorithm that finds the optimal Kalai-Smorodinsky beamformers for an arbitrary number of users. We also consider joint scheduling and beamformer selection, using gradient ascent to find a stationary point of the Kalai-Smorodinsky objective function. When interference is strong, the flexibility allowed by scheduling compensates for the performance loss due to local optimization. Finally, we explore the benefits of power control, showing that power control provides nontrivial throughput gains when the number of transmitter/receiver pairs is greater than the number of transmit antennas.

Integrating the ECG power-line interference removal methods with rule-based system.

PubMed

Kumaravel, N; Senthil, A; Sridhar, K S; Nithiyanandam, N

1995-01-01

The power-line frequency interference in electrocardiographic signals is eliminated to enhance the signal characteristics for diagnosis. The power-line frequency normally varies +/- 1.5 Hz from its standard value of 50 Hz. In the present work, the performances of the linear FIR filter, Wave digital filter (WDF) and adaptive filter for the power-line frequency variations from 48.5 to 51.5 Hz in steps of 0.5 Hz are studied. The advantage of the LMS adaptive filter in the removal of power-line frequency interference even if the frequency of interference varies by +/- 1.5 Hz from its normal value of 50 Hz over other fixed frequency filters is very well justified. A novel method of integrating rule-based system approach with linear FIR filter and also with Wave digital filter are proposed. The performances of Rule-based FIR filter and Rule-based Wave digital filter are compared with the LMS adaptive filter.

Doppler Radar Vital Signs Detection Method Based on Higher Order Cyclostationary.

PubMed

Yu, Zhibin; Zhao, Duo; Zhang, Zhiqiang

2017-12-26

Due to the non-contact nature, using Doppler radar sensors to detect vital signs such as heart and respiration rates of a human subject is getting more and more attention. However, the related detection-method research meets lots of challenges due to electromagnetic interferences, clutter and random motion interferences. In this paper, a novel third-order cyclic cummulant (TOCC) detection method, which is insensitive to Gaussian interference and non-cyclic signals, is proposed to investigate the heart and respiration rate based on continuous wave Doppler radars. The k -th order cyclostationary properties of the radar signal with hidden periodicities and random motions are analyzed. The third-order cyclostationary detection theory of the heart and respiration rate is studied. Experimental results show that the third-order cyclostationary approach has better estimation accuracy for detecting the vital signs from the received radar signal under low SNR, strong clutter noise and random motion interferences.

American Indian Men's Perceptions of Breast Cancer Screening for American Indian Women.

PubMed

Filippi, Melissa K; Pacheco, Joseph; James, Aimee S; Brown, Travis; Ndikum-Moffor, Florence; Choi, Won S; Greiner, K Allen; Daley, Christine M

2014-01-01

Screening, especially screening mammography, is vital for decreasing breast cancer incidence and mortality. Screening rates in American Indian women are low compared to other racial/ethnic groups. In addition, American Indian women are diagnosed at more advanced stages and have lower 5-year survival rate than others. To better address the screening rates of American Indian women, focus groups (N=8) were conducted with American Indian men (N=42) to explore their perceptions of breast cancer screening for American Indian women. Our intent was to understand men's support level toward screening. Using a community-based participatory approach, focus groups were audio-taped, transcribed verbatim, and analyzed using a text analysis approach developed by our team. Topics discussed included breast cancer and screening knowledge, barriers to screening, and suggestions to improve screening rates. These findings can guide strategies to improve knowledge and awareness, communication among families and health care providers, and screening rates in American Indian communities.

A New Way of Using the Interactive Whiteboard in a High School Physics Classroom: A Case Study

NASA Astrophysics Data System (ADS)

Gregorcic, Bor; Etkina, Eugenia; Planinsic, Gorazd

2017-02-01

In recent decades, the interactive whiteboard (IWB) has become a relatively common educational tool in Western schools. The IWB is essentially a large touch screen, that enables the user to interact with digital content in ways that are not possible with an ordinary computer-projector-canvas setup. However, the unique possibilities of IWBs are rarely leveraged to enhance teaching and learning beyond the primary school level. This is particularly noticeable in high school physics. We describe how a high school physics teacher learned to use an IWB in a new way, how she planned and implemented a lesson on the topic of orbital motion of planets, and what tensions arose in the process. We used an ethnographic approach to account for the teacher's and involved students' perspectives throughout the process of teacher preparation, lesson planning, and the implementation of the lesson. To interpret the data, we used the conceptual framework of activity theory. We found that an entrenched culture of traditional white/blackboard use in physics instruction interferes with more technologically innovative and more student-centered instructional approaches that leverage the IWB's unique instructional potential. Furthermore, we found that the teacher's confidence in the mastery of the IWB plays a crucial role in the teacher's willingness to transfer agency within the lesson to the students.

In vitro screening of dual flavonoid combinations for reversing P-glycoprotein-mediated multidrug resistance: Focus on antiepileptic drugs.

PubMed

Ferreira, Ana; Santos, Adriana O; Falcão, Amílcar; Alves, Gilberto

2018-01-01

The combined use of different P-glycoprotein (P-gp) inhibitors may be a relevant approach to the synergistic and safer inhibition of the P-gp-mediated drug efflux. Herein, we aimed to explore dual combinations of the flavonoids baicalein, (-)-epigallocatechin gallate, kaempferol, quercetin and silymarin to reverse the interference of P-gp on the intracellular accumulation of antiepileptic drugs (AEDs). The intracellular accumulation of rhodamine 123 (a classic P-gp substrate) and of several commonly used AEDs (carbamazepine, phenytoin, oxcarbazepine) or their metabolites (carbamazepine-10,11-epoxide and licarbazepine) was evaluated in MDCK-MDR1 cells in the presence and absence of individual flavonoids and their combinations. A selected flavonoid combination [(-)-epigallocatechin gallate/silymarin] was also evaluated in transepithelial transport experiments using licarbazepine (active metabolite of oxcarbazepine) as a model compound. Most flavonoid combinations increased rhodamine 123 intracellular uptake in a greater extent than their additive individual effects at similar concentrations. Moreover, selected (-)-epigallocatechin gallate/silymarin and kaempferol/baicalein combinations also enhanced the intracellular accumulation of all AEDs and metabolites. Overall, the combination of (-)-epigallocatechin gallate/silymarin was the most promising one. Thus, dual flavonoid combinations may be useful to overcome the P-gp-mediated efflux of AEDs and their metabolites, making their association to AED therapy a potentially valuable approach to circumvent pharmacoresistance in epilepsy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening.

PubMed

Hübner, Joachim; Waldmann, Annika; Eisemann, Nora; Noftz, Maria; Geller, Alan C; Weinstock, Martin A; Volkmer, Beate; Greinert, Rüdiger; Breitbart, Eckhard W; Katalinic, Alexander

2017-07-07

Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany population. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to an number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

An Approach to Noise Reduction in Human Skin Admittance Measurements

DTIC Science & Technology

2001-10-25

1966, 4, 439-449. [ 4] D. H. Gordon, "Triboelectric interference in the ECG", IEEE Trans., 1975, BME -22, 252-255. [ 5] J. C. Huhta and J. G...Webster, ඄-Hz interference in electrocardiography", IEEE Trans., 1973, BME -20, 91-101. [ 6] S. Grimnes, "Electrovibration, cutaneous sensation of...this period he has published two textbooks about UNIX and Shell Programming, and concentrated at computer simulation and digital signal processing

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

NASA Technical Reports Server (NTRS)

Barber, Peter W.; Demerdash, Nabeel A. O.; Hurysz, B.; Luo, Z.; Denny, Hugh W.; Millard, David P.; Herkert, R.; Wang, R.

1992-01-01

The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards.

A Community Capacity-Enhancement Approach to Breast and Cervical Cancer Screening among Older Women of Color

ERIC Educational Resources Information Center

Bullock, Karen; McGraw, Sarah A.

2006-01-01

In the Screening Older Minority Women project, the authors applied a community capacity-enhancement approach to promoting breast and cervical cancer screening among older women of color. Members of informal support networks were recruited for this health promotion intervention to empower Latina and African American women to engage in positive…

Double-Slit Interference Pattern for a Macroscopic Quantum System

NASA Astrophysics Data System (ADS)

Naeij, Hamid Reza; Shafiee, Afshin

2016-12-01

In this study, we solve analytically the Schrödinger equation for a macroscopic quantum oscillator as a central system coupled to two environmental micro-oscillating particles. Then, the double-slit interference patterns are investigated in two limiting cases, considering the limits of uncertainty in the position probability distribution. Moreover, we analyze the interference patterns based on a recent proposal called stochastic electrodynamics with spin. Our results show that when the quantum character of the macro-system is decreased, the diffraction pattern becomes more similar to a classical one. We also show that, depending on the size of the slits, the predictions of quantum approach could be apparently different with those of the aforementioned stochastic description.

Terminate Lung Cancer (TLC) Study - A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky

PubMed Central

Cardarelli, Roberto; Reese, David; Roper, Karen L.; Cardarelli, Kathryn; Feltner, Frances J.; Studts, Jamie L.; Knight, Jennifer R.; Armstrong, Debra; Weaver, Anthony; Shaffer, Dana

2017-01-01

For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region. PMID:27866066

Assessment of the DNA damaging potential of environmental chemicals using a quantitative high-throughput screening approach to measure p53 activation.

PubMed

Witt, Kristine L; Hsieh, Jui-Hua; Smith-Roe, Stephanie L; Xia, Menghang; Huang, Ruili; Zhao, Jinghua; Auerbach, Scott S; Hur, Junguk; Tice, Raymond R

2017-08-01

Genotoxicity potential is a critical component of any comprehensive toxicological profile. Compounds that induce DNA or chromosomal damage often activate p53, a transcription factor essential to cell cycle regulation. Thus, within the US Tox21 Program, we screened a library of ∼10,000 (∼8,300 unique) environmental compounds and drugs for activation of the p53-signaling pathway using a quantitative high-throughput screening assay employing HCT-116 cells (p53 +/+ ) containing a stably integrated β-lactamase reporter gene under control of the p53 response element (p53RE). Cells were exposed (-S9) for 16 hr at 15 concentrations (generally 1.2 nM to 92 μM) three times, independently. Excluding compounds that failed analytical chemistry analysis or were suspected of inducing assay interference, 365 (4.7%) of 7,849 unique compounds were concluded to activate p53. As part of an in-depth characterization of our results, we first compared them with results from traditional in vitro genotoxicity assays (bacterial mutation, chromosomal aberration); ∼15% of known, direct-acting genotoxicants in our library activated the p53RE. Mining the Comparative Toxicogenomics Database revealed that these p53 actives were significantly associated with increased expression of p53 downstream genes involved in DNA damage responses. Furthermore, 53 chemical substructures associated with genotoxicity were enriched in certain classes of p53 actives, for example, anthracyclines (antineoplastics) and vinca alkaloids (tubulin disruptors). Interestingly, the tubulin disruptors manifested unusual nonmonotonic concentration response curves suggesting activity through a unique p53 regulatory mechanism. Through the analysis of our results, we aim to define a role for this assay as one component of a comprehensive toxicological characterization of large compound libraries. Environ. Mol. Mutagen. 58:494-507, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Targeted screening of pesticides, veterinary drugs and mycotoxins in bakery ingredients and food commodities by liquid chromatography-high-resolution single-stage Orbitrap mass spectrometry.

PubMed

De Dominicis, Emiliano; Commissati, Italo; Suman, Michele

2012-09-01

In the food industry, it is frequently necessary to check the quality of an ingredient to decide whether to use it in production and/or to have an idea of the final possible contamination of the finished product. The current need to quickly separate and identify relevant contaminants within different classes, often with legal residue limits on the order of 1-100 µg kg(-1), has led to the need for more effective analytical methods. With thousands of organic compounds present in complex food matrices, the development of new analytical solutions leaned towards simplified extraction/clean-up procedures and chromatography coupled with mass spectrometry. Efforts must also be made regarding the instrumental phase to overcome sensitivity/selectivity limits and interferences. For this purpose, high-resolution full scan analysis in mass spectrometry is an interesting alternative to the traditional tandem mass approach. A fast method for extracting and purifying bakery matrices was therefore developed and combined with the exploitation of ultra-high-pressure liquid chromatography (UHPLC) coupled to a Orbitrap Exactive™ high-resolution mass spectrometer (HRMS). Extracts of blank, naturally contaminated and fortified minicakes, prepared through a combined use of industrial and pilot plant production lines, were analyzed at different concentration levels (1-100 µg kg(-1)) of various contaminants: a limit of detection at 10 µg kg(-1) was possible for most of the analytes within all the categories analyzed, including pesticides, aflatoxins, trichothecene toxins and veterinary drugs. The application of accurate mass targeted screening described in this article demonstrates that current single-stage HRMS analytical instrumentation is well equipped to meet the challenges posed by chemical contaminants in the screening of both bakery raw materials and finished products. Copyright © 2012 John Wiley & Sons, Ltd.

Prediction of luciferase inhibitors by the high-performance MIEC-GBDT approach based on interaction energetic patterns.

PubMed

Chen, Fu; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

2017-04-12

High-throughput screening (HTS) is widely applied in many fields ranging from drug discovery to clinical diagnostics and toxicity assessment. Firefly luciferase is commonly used as a reporter to monitor the effect of chemical compounds on the activity of a specific target or pathway in HTS. However, the false positive rate of luciferase-based HTS is relatively high because many artifacts or promiscuous compounds that have direct interaction with the luciferase reporter enzyme are usually identified as active compounds (hits). Therefore, it is necessary to develop a rapid screening method to identify these compounds that can inhibit the luciferase activity directly. In this study, a virtual screening (VS) classification model called MIEC-GBDT (MIEC: Molecular Interaction Energy Components; GBDT: Gradient Boosting Decision Tree) was developed to distinguish luciferase inhibitors from non-inhibitors. The MIECs calculated by Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) free energy decomposition were used to energetically characterize the binding pattern of each small molecule at the active site of luciferase, and then the GBDT algorithm was employed to construct the classifiers based on MIECs. The predictions to the test set show that the optimized MIEC-GBDT model outperformed molecular docking and MM/GBSA rescoring. The best MIEC-GBDT model based on the MIECs with the energy terms of ΔG ele , ΔG vdW , ΔG GB , and ΔG SA achieves the prediction accuracies of 87.2% and 90.3% for the inhibitors and non-inhibitors in the test sets, respectively. Moreover, the energetic analysis of the vital residues suggests that the energetic contributions of the vital residues to the binding of inhibitors are quite different from those to the binding of non-inhibitors. These results suggest that the MIEC-GBDT model is reliable and can be used as a powerful tool to identify potential interference compounds in luciferase-based HTS experiments.

Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

PubMed

van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

2016-02-15

Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work describes a platform-enabling technology applicable to most vaccine-preventable diseases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Constraint factor graph cut-based active contour method for automated cellular image segmentation in RNAi screening.

PubMed

Chen, C; Li, H; Zhou, X; Wong, S T C

2008-05-01

Image-based, high throughput genome-wide RNA interference (RNAi) experiments are increasingly carried out to facilitate the understanding of gene functions in intricate biological processes. Automated screening of such experiments generates a large number of images with great variations in image quality, which makes manual analysis unreasonably time-consuming. Therefore, effective techniques for automatic image analysis are urgently needed, in which segmentation is one of the most important steps. This paper proposes a fully automatic method for cells segmentation in genome-wide RNAi screening images. The method consists of two steps: nuclei and cytoplasm segmentation. Nuclei are extracted and labelled to initialize cytoplasm segmentation. Since the quality of RNAi image is rather poor, a novel scale-adaptive steerable filter is designed to enhance the image in order to extract long and thin protrusions on the spiky cells. Then, constraint factor GCBAC method and morphological algorithms are combined to be an integrated method to segment tight clustered cells. Compared with the results obtained by using seeded watershed and the ground truth, that is, manual labelling results by experts in RNAi screening data, our method achieves higher accuracy. Compared with active contour methods, our method consumes much less time. The positive results indicate that the proposed method can be applied in automatic image analysis of multi-channel image screening data.

Distinct loci of lexical and semantic access deficits in aphasia: Evidence from voxel-based lesion-symptom mapping and diffusion tensor imaging.

PubMed

Harvey, Denise Y; Schnur, Tatiana T

2015-06-01

Naming pictures and matching words to pictures belonging to the same semantic category negatively affects language production and comprehension. By most accounts, semantic interference arises when accessing lexical representations in naming (e.g., Damian, Vigliocco, & Levelt, 2001) and semantic representations in comprehension (e.g., Forde & Humphreys, 1997). Further, damage to the left inferior frontal gyrus (LIFG), a region implicated in cognitive control, results in increasing semantic interference when items repeat across cycles in both language production and comprehension (Jefferies, Baker, Doran, & Lambon Ralph, 2007). This generates the prediction that the LIFG via white matter connections supports resolution of semantic interference arising from different loci (lexical vs semantic) in the temporal lobe. However, it remains unclear whether the cognitive and neural mechanisms that resolve semantic interference are the same across tasks. Thus, we examined which gray matter structures [using whole brain and region of interest (ROI) approaches] and white matter connections (using deterministic tractography) when damaged impact semantic interference and its increase across cycles when repeatedly producing and understanding words in 15 speakers with varying lexical-semantic deficits from left hemisphere stroke. We found that damage to distinct brain regions, the posterior versus anterior temporal lobe, was associated with semantic interference (collapsed across cycles) in naming and comprehension, respectively. Further, those with LIFG damage compared to those without exhibited marginally larger increases in semantic interference across cycles in naming but not comprehension. Lastly, the inferior fronto-occipital fasciculus, connecting the LIFG with posterior temporal lobe, related to semantic interference in naming, whereas the inferior longitudinal fasciculus (ILF), connecting posterior with anterior temporal regions related to semantic interference in comprehension. These neuroanatomical-behavioral findings have implications for models of the lexical-semantic language network by demonstrating that semantic interference in language production and comprehension involves different representations which differentially recruit a cognitive control mechanism for interference resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

All That Glitters: A Glimpse into the Future of Cancer Screening

Cancer.gov

Developing new screening approaches and rigorously establishing their validity is challenging. Researchers are actively searching for new screening tests that improve the benefits of screening while limiting the harms.

Coliform inhibition by bacteriocin-like substances in drinking water distribution systems.

PubMed Central

Means, E G; Olson, B H

1981-01-01

Bacterial isolates from an unchlorinated potable groundwater system and a chlorinated surface water system were screened by an agar overlay method for the ability to produce bacteriocin-like substances (BLS) inhibitory to the growth of Escherichia coli, Klebsiella sp., and Enterobacter aerogenes. The production of coliform-specific BLS by noncoliform bacteria varied with the site and date of isolation as well as the genus of the producer strain. A total of 448 bacterial isolates were screened from the chlorinated system, and 22.1% produced BLS specific for at least one of the three coliforms. In the unchlorinated system, 7.9% (n = 696) possessed this ability. Flavobacterium/Moraxella comprised 57.1% of all bacteria (from both systems) producing BLS. The possibility that BLS interfere with coliform detection in standard bacteriological water quality tests is discussed. Images PMID:7027953

Power line interference attenuation in multi-channel sEMG signals: Algorithms and analysis.

PubMed

Soedirdjo, S D H; Ullah, K; Merletti, R

2015-08-01

Electromyogram (EMG) recordings are often corrupted by power line interference (PLI) even though the skin is prepared and well-designed instruments are used. This study focuses on the analysis of some of the recent and classical existing digital signal processing approaches have been used to attenuate, if not eliminate, the power line interference from EMG signals. A comparison of the signal to interference ratio (SIR) of the output signals is presented, for four methods: classical notch filter, spectral interpolation, adaptive noise canceller with phase locked loop (ANC-PLL) and adaptive filter, applied to simulated multichannel monopolar EMG signals with different SIR. The effect of each method on the shape of the EMG signals is also analyzed. The results show that ANC-PLL method gives the best output SIR and lowest shape distortion compared to the other methods. Classical notch filtering is the simplest method but some information might be lost as it removes both the interference and the EMG signals. Thus, it is obvious that notch filter has the lowest performance and it introduces distortion into the resulting signals.

Limited Agreement of Independent RNAi Screens for Virus-Required Host Genes Owes More to False-Negative than False-Positive Factors

PubMed Central

Wang, Zhishi; Craven, Mark; Newton, Michael A.; Ahlquist, Paul

2013-01-01

Systematic, genome-wide RNA interference (RNAi) analysis is a powerful approach to identify gene functions that support or modulate selected biological processes. An emerging challenge shared with some other genome-wide approaches is that independent RNAi studies often show limited agreement in their lists of implicated genes. To better understand this, we analyzed four genome-wide RNAi studies that identified host genes involved in influenza virus replication. These studies collectively identified and validated the roles of 614 cell genes, but pair-wise overlap among the four gene lists was only 3% to 15% (average 6.7%). However, a number of functional categories were overrepresented in multiple studies. The pair-wise overlap of these enriched-category lists was high, ∼19%, implying more agreement among studies than apparent at the gene level. Probing this further, we found that the gene lists implicated by independent studies were highly connected in interacting networks by independent functional measures such as protein-protein interactions, at rates significantly higher than predicted by chance. We also developed a general, model-based approach to gauge the effects of false-positive and false-negative factors and to estimate, from a limited number of studies, the total number of genes involved in a process. For influenza virus replication, this novel statistical approach estimates the total number of cell genes involved to be ∼2,800. This and multiple other aspects of our experimental and computational results imply that, when following good quality control practices, the low overlap between studies is primarily due to false negatives rather than false-positive gene identifications. These results and methods have implications for and applications to multiple forms of genome-wide analysis. PMID:24068911

Quantitative locomotion study of freely swimming micro-organisms using laser diffraction.

PubMed

Magnes, Jenny; Susman, Kathleen; Eells, Rebecca

2012-10-25

Soil and aquatic microscopic organisms live and behave in a complex three-dimensional environment. Most studies of microscopic organism behavior, in contrast, have been conducted using microscope-based approaches, which limit the movement and behavior to a narrow, nearly two-dimensional focal field.(1) We present a novel analytical approach that provides real-time analysis of freely swimming C. elegans in a cuvette without dependence on microscope-based equipment. This approach consists of tracking the temporal periodicity of diffraction patterns generated by directing laser light through the cuvette. We measure oscillation frequencies for freely swimming nematodes. Analysis of the far-field diffraction patterns reveals clues about the waveforms of the nematodes. Diffraction is the process of light bending around an object. In this case light is diffracted by the organisms. The light waves interfere and can form a diffraction pattern. A far-field, or Fraunhofer, diffraction pattern is formed if the screen-to-object distance is much larger than the diffracting object. In this case, the diffraction pattern can be calculated (modeled) using a Fourier transform.(2) C. elegans are free-living soil-dwelling nematodes that navigate in three dimensions. They move both on a solid matrix like soil or agar in a sinusoidal locomotory pattern called crawling and in liquid in a different pattern called swimming.(3) The roles played by sensory information provided by mechanosensory, chemosensory, and thermosensory cells that govern plastic changes in locomotory patterns and switches in patterns are only beginning to be elucidated.(4) We describe an optical approach to measuring nematode locomotion in three dimensions that does not require a microscope and will enable us to begin to explore the complexities of nematode locomotion under different conditions.

Correction factors for self-selection when evaluating screening programmes.

PubMed

Spix, Claudia; Berthold, Frank; Hero, Barbara; Michaelis, Jörg; Schilling, Freimut H

2016-03-01

In screening programmes there is recognized bias introduced through participant self-selection (the healthy screenee bias). Methods used to evaluate screening programmes include Intention-to-screen, per-protocol, and the "post hoc" approach in which, after introducing screening for everyone, the only evaluation option is participants versus non-participants. All methods are prone to bias through self-selection. We present an overview of approaches to correct for this bias. We considered four methods to quantify and correct for self-selection bias. Simple calculations revealed that these corrections are actually all identical, and can be converted into each other. Based on this, correction factors for further situations and measures were derived. The application of these correction factors requires a number of assumptions. Using as an example the German Neuroblastoma Screening Study, no relevant reduction in mortality or stage 4 incidence due to screening was observed. The largest bias (in favour of screening) was observed when comparing participants with non-participants. Correcting for bias is particularly necessary when using the post hoc evaluation approach, however, in this situation not all required data are available. External data or further assumptions may be required for estimation. © The Author(s) 2015.

Evaluation of PCR Systems for Field Screening of Bacillus anthracis

PubMed Central

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

2017-01-01

There is little published data on the performance of hand-portable polymerase chain reaction (PCR) systems that can be used by first responders to determine if a suspicious powder contains a potential biothreat agent. We evaluated 5 commercially available hand-portable PCR instruments for detection of Bacillus anthracis. We used a cost-effective, statistically based test plan to evaluate systems at performance levels ranging from 0.85-0.95 lower confidence bound (LCB) of the probability of detection (POD) at confidence levels of 80% to 95%. We assessed specificity using purified genomic DNA from 13 B. anthracis strains and 18 Bacillus near neighbors, potential interference with 22 suspicious powders that are commonly encountered in the field by first responders during suspected biothreat incidents, and the potential for PCR inhibition when B. anthracis spores were spiked into these powders. Our results indicate that 3 of the 5 systems achieved 0.95 LCB of the probability of detection with 95% confidence levels at test concentrations of 2,000 genome equivalents/mL (GE/mL), which is comparable to 2,000 spores/mL. This is more than sufficient sensitivity for screening visible suspicious powders. These systems exhibited no false-positive results or PCR inhibition with common suspicious powders and reliably detected B. anthracis spores spiked into these powders, though some issues with assay controls were observed. Our testing approach enables efficient performance testing using a statistically rigorous and cost-effective test plan to generate performance data that allow users to make informed decisions regarding the purchase and use of field biodetection equipment. PMID:28192050

Automated Analysis of siRNA Screens of Virus Infected Cells Based on Immunofluorescence Microscopy

NASA Astrophysics Data System (ADS)

Matula, Petr; Kumar, Anil; Wörz, Ilka; Harder, Nathalie; Erfle, Holger; Bartenschlager, Ralf; Eils, Roland; Rohr, Karl

We present an image analysis approach as part of a high-throughput microscopy screening system based on cell arrays for the identification of genes involved in Hepatitis C and Dengue virus replication. Our approach comprises: cell nucleus segmentation, quantification of virus replication level in cells, localization of regions with transfected cells, cell classification by infection status, and quality assessment of an experiment. The approach is fully automatic and has been successfully applied to a large number of cell array images from screening experiments. The experimental results show a good agreement with the expected behavior of positive as well as negative controls and encourage the application to screens from further high-throughput experiments.

A Cognitive Framework for Understanding and Improving Interference Resolution in the Brain

PubMed Central

Mishra, Jyoti; Anguera, Joaquin A.; Ziegler, David A.; Gazzaley, Adam

2014-01-01

All of us are familiar with the negative impact of interference on achieving our task goals. We are referring to interference by information, which either impinges on our senses from an external environmental source or is internally generated by our thoughts. Informed by more than a decade of research on the cognitive and neural processing of interference, we have developed a framework for understanding how interference impacts our neural systems and especially how it is regulated and suppressed during efficient on-task performance. Importantly, externally and internally generated interferences have distinct neural signatures, and further, distinct neural processing emerges depending on whether individuals must ignore and suppress the interference, as for distractions, or engage with them in a secondary task, as during multitasking. Here, we elaborate on this cognitive framework and how it changes throughout the human lifespan, focusing mostly on research evidence from younger adults and comparing these findings to data from older adults, children, and cognitively impaired populations. With insights gleaned from our growing understanding, we then describe three novel translational efforts in our lab directed at improving distinct aspects of interference resolution using cognitive training. Critically, these training approaches were specifically developed to target improved interference resolution based on neuroplasticity principles and have shown much success in randomized controlled first version evaluations in healthy aging. Our results show not only on-task training improvements but also robust generalization of benefit to other cognitive control abilities. This research showcases how an in-depth understanding of neural mechanisms can then inform the development of effective deficit-targeted interventions, which can in turn benefit both healthy and cognitively impaired populations. PMID:24309262

Spectral and non-spectral interferences in the determination of thallium in environmental materials using electrothermal atomization and vaporization techniques—a case study

NASA Astrophysics Data System (ADS)

Vale, Maria Goreti R.; Welz, Bernhard

2002-12-01

The literature on the determination of Tl in environmental samples using electrothermal atomization (ETA) and vaporization (ETV) techniques has been reviewed with special attention devoted to potential interferences and their control. Chloride interference, which is due to the formation of the volatile monochloride in the condensed phase, is the most frequently observed problem. Due to its high dissociation energy (88 kcal/mol), TlCl is difficult to dissociate in the gas phase and is easily lost. The best means of controlling this interference in ETA is atomization under isothermal conditions according to the stabilized temperature platform furnace concept, and the use of reduced palladium as a modifier. An alternative approach appears to be the 'fast furnace' concept, wherein both the use of a modifier and the pyrolysis stage are omitted. This concept requires an efficient background correction system, and high-resolution continuum-source atomic absorption spectrometry (HR-CS AAS) appears to offer the best results. This chloride interference can also cause significant problems when ETV techniques are used. Among the spectral interferences found in the determination of thallium are those due to Pd, the most efficient modifier, and Fe, which is frequently found at high concentrations in environmental samples. Both interferences are due to nearby atomic lines, and are observed only when deuterium background correction and relatively high atomization temperatures are used. A more serious spectral interference is that due to the molecular absorption spectrum of SO 2, which has a maximum around the Tl line and exhibits a pronounced rotational fine structure. HR-CS AAS again showed the best performance in coping with this interference.

Encoding and Retrieval Interference in Sentence Comprehension: Evidence from Agreement

PubMed Central

Villata, Sandra; Tabor, Whitney; Franck, Julie

2018-01-01

Long-distance verb-argument dependencies generally require the integration of a fronted argument when the verb is encountered for sentence interpretation. Under a parsing model that handles long-distance dependencies through a cue-based retrieval mechanism, retrieval is hampered when retrieval cues also resonate with non-target elements (retrieval interference). However, similarity-based interference may also stem from interference arising during the encoding of elements in memory (encoding interference), an effect that is not directly accountable for by a cue-based retrieval mechanism. Although encoding and retrieval interference are clearly distinct at the theoretical level, it is difficult to disentangle the two on empirical grounds, since encoding interference may also manifest at the retrieval region. We report two self-paced reading experiments aimed at teasing apart the role of each component in gender and number subject-verb agreement in Italian and English object relative clauses. In Italian, the verb does not agree in gender with the subject, thus providing no cue for retrieval. In English, although present tense verbs agree in number with the subject, past tense verbs do not, allowing us to test the role of number as a retrieval cue within the same language. Results from both experiments converge, showing similarity-based interference at encoding, and some evidence for an effect at retrieval. After having pointed out the non-negligible role of encoding in sentence comprehension, and noting that Lewis and Vasishth’s (2005) ACT-R model of sentence processing, the most fully developed cue-based retrieval approach to sentence processing does not predict encoding effects, we propose an augmentation of this model that predicts these effects. We then also propose a self-organizing sentence processing model (SOSP), which has the advantage of accounting for retrieval and encoding interference with a single mechanism. PMID:29403414

Biological and Sociocultural Differences in Perceived Barriers to Physical Activity Among Fifth- to Seventh-Grade Urban Girls.

PubMed

Vermeesch, Amber L; Ling, Jiying; Voskuil, Vicki R; Bakhoya, Marion; Wesolek, Stacey M; Bourne, Kelly A; Pfeiffer, Karin A; Robbins, Lorraine B

2015-01-01

Inadequate physical activity (PA) contributes to the high prevalence of overweight and obesity among U.S. adolescent girls. Barriers preventing adolescent girls from meeting PA guidelines have not been thoroughly examined. The threefold purpose of this study was to (a) determine pubertal stage, racial/ethnic, and socioeconomic status (SES) differences in ratings of interference of barriers to PA; (b) examine relationships between perceived barriers and age, body mass index, recreational screen time, sedentary activity, and PA; and (c) identify girls' top-rated perceived barriers to PA. Girls (N = 509) from eight Midwestern U.S. schools participated. Demographic, pubertal stage, perceived barriers, and recreational screen time data were collected via surveys. Height and weight were measured. Accelerometers measured sedentary activity, moderate-to-vigorous PA (MVPA), and light plus MVPA. Girls of low SES reported greater interference of perceived barriers to PA than those who were not of low SES (1.16 vs. 0.97, p = .01). Girls in early/middle puberty had lower perceived barriers than those in late puberty (1.03 vs. 1.24, p < .001). Girls' perceived barriers were negatively related to MVPA (r = -.10, p = .03) and light plus MVPA (r = -.11, p = .02). Girls' top five perceived barriers included lack of skills, hating to sweat, difficulty finding programs, being tired, and having pain. Innovative interventions, particularly focusing on skill development, are needed to assist girls in overcoming their perceived barriers to PA.

Asymptomatic Bacteriuria and Bacterial Interference.

PubMed

Nicolle, Lindsay E

2015-10-01

Asymptomatic bacteriuria is very common. In healthy women, asymptomatic bacteriuria increases with age, from <1% in newborns to 10% to 20% of women age 80 years, but is uncommon in men until after age 50 years. Individuals with underlying genitourinary abnormalities, including indwelling devices, may also have a high frequency of asymptomatic bacteriuria, irrespective of age or gender. The prevalence is very high in residents of long-term-care facilities, from 25% to 50% of women and 15% to 40% of men. Escherichia coli is the most frequent organism isolated, but a wide variety of other organisms may occur. Bacteriuria may be transient or persist for a prolonged period. Pregnant women with asymptomatic bacteriuria identified in early pregnancy and who are untreated have a risk of pyelonephritis later in pregnancy of 20% to 30%. Bacteremia is frequent in bacteriuric subjects following mucosal trauma with bleeding, with 5% to 10% of patients developing severe sepsis or septic shock. These two groups with clear evidence of negative outcomes should be screened for bacteriuria and appropriately treated. Asymptomatic bacteriuria in other populations is benign and screening and treatment are not indicated. Antimicrobial treatment has no benefits but is associated with negative outcomes including reinfection with antimicrobial resistant organisms and a short-term increased frequency of symptomatic infection post-treatment. The observation of increased symptomatic infection post-treatment, however, has led to active investigation of bacterial interference as a strategy to prevent symptomatic episodes in selected high risk patients.

Neural Progenitor Cells as Models for High-Throughput Screens of Developmental Neurotoxicity: State of the Science

EPA Science Inventory

In vitro, high-throughput approaches have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramificat...

Analytical Protocol (GC/ECNIMS) for OSWER's Response to OIG Report (2005-P-00022) on Toxaphene Analysis

EPA Science Inventory

The research approached the large number and complexity of the analytes as four separate groups: technical toxaphene, toxaphene congeners (eight in number), chlordane, and organochlorine pesticides. This approach was advantageous because it eliminated potential interferences amon...

Screening, Brief Intervention, and Referral to Treatment (SBIRT): Toward a Public Health Approach to the Management of Substance Abuse

ERIC Educational Resources Information Center

Babor, Thomas F.; McRee, Bonnie G.; Kassebaum, Patricia A.; Grimaldi, Paul L.; Ahmed, Kazi; Bray, Jeremy

2007-01-01

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a comprehensive and integrated approach to the delivery of early intervention and treatment services through universal screening for persons with substance use disorders and those at risk. This paper describes research on the components of SBIRT conducted during the past 25 years,…

"To screen or not to screen": Comparing the health and economic benefits of early peanut introduction strategies in five countries.

PubMed

Shaker, M; Stukus, D; Chan, E S; Fleischer, D M; Spergel, J M; Greenhawt, M

2018-03-30

Early peanut introduction (EPI) in the first year of life is associated with reduced risk of developing peanut allergy in children with either severe eczema and/or egg allergy. However, EPI recommendations differ among countries with formal guidelines. Using simulation and Markov modeling over a 20-year horizon to attempt to explore optimal EPI strategies applied to the US population, we compared high-risk infant-specific IgE peanut screening (US/Canadian) with the Australiasian Society for Clinical Immunology and Allergy (Australia/New Zealand) (ASCIA) and the United Kingdom Department of Health (UKDOH)-published EPI approaches. Screening peanut skin testing of all children with early-onset eczema and/or egg allergy before in-office peanut introduction was dominated by a no screening approach, in terms of number of cases of peanut allergy prevented, quality-adjusted life years (QALY), and healthcare costs, although screening resulted in a slightly lower rate of allergic reactions to peanut per patient in high-risk children. Considering costs of peanut allergy in high-risk children, the per-patient cost of early introduction without screening over the model horizon was $6556.69 (95%CI, $6512.76-$6600.62), compared with a cost of $7576.32 (95%CI, $7531.38-$7621.26) for skin test screening prior to introduction. From a US societal perspective, screening prior to introduction cost $654 115 322 and resulted in 3208 additional peanut allergy diagnoses. Both screening and nonscreening approaches dominated deliberately delayed peanut introduction. A no-screening approach for EPI has superior health and economic benefits in terms of number of peanut allergy cases prevented, QALY, and total healthcare costs compared to screening and in-office peanut introduction. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

The role of human papillomavirus in screening for cervical cancer.

PubMed

McFadden, S E; Schumann, L

2001-03-01

To review the options for effectively screening for cervical cancer, including human papilloma virus (HPV) identification, cytologic screening, colposcopy, or a combination approach. Current pathophysiology, diagnostic criteria, treatment approaches, and patient preparation and education related to cervical cancer screening and prevention are also included. Comprehensive review of current literature, including research and review articles. Because the Papanicolau (Pap) smear is a screening tool, not a diagnostic tool, further studies must be done to identify the actual nature of discovered abnormalities. Of particular concern is the classification of atypical squamous cells of undetermined significance (ASCUS), which may simply indicate inflammation, or may be the first indicator of serious pathology. Following ASCUS Pap smears with HPV screening will allow for a clarification of the best approach to treatment. A screening algorithm supported by a review of the literature is proposed. Cervical cancer is a preventable disease caused by certain forms of HPV. Current screening protocols are based on the use of the Pap smear; and in areas where this test is routine and available, morbidity and mortality rates have dropped dramatically. Many women throughout the world and in underserved regions of the U. S. do not have adequate access to routine screening with Pap smear technology. As long as women continue to die needlessly of cervical cancer, more comprehensive and accessible screening methods must be explored. (Cutting the unnecessary worldwide and in the U. S.).

Preparation of milk samples for immunoassay and liquid chromatographic screening using matrix solid-phase dispersion.

PubMed

Barker, S A; Long, A R

1994-01-01

The use of drugs to maintain the health and maximize the output of dairy cattle has made the monitoring of milk for such agents essential. Screening tests based on immunological, microbial inhibition, and bacterial receptor assays have been developed for the detection of violative levels of therapeutic substances. However, such assays are not infallible, and false positive or negative results can occur when contaminants bind receptors or compete for the binding of the target residues. Such effects may arise from dietary sources, diseases, or other variables. Thus, a violation by such a test is not definitive until further confirmation is obtained. Our laboratory has developed extraction procedures for several drugs used in dairy production. Our method uses matrix solid-phase dispersion (MSPD) to isolate drugs away from contaminants and to eliminate many possible interferences. MSPD can also be used to enhance the specificity of such assays by fractionating various classes of drugs that may cross-react. Similarly, such methods may be used for liquid chromatographic screening and confirmation of a suspect sample.

Medium-Throughput Screen of Microbially Produced Serotonin via a G-Protein-Coupled Receptor-Based Sensor.

PubMed

Ehrenworth, Amy M; Claiborne, Tauris; Peralta-Yahya, Pamela

2017-10-17

Chemical biosensors, for which chemical detection triggers a fluorescent signal, have the potential to accelerate the screening of noncolorimetric chemicals produced by microbes, enabling the high-throughput engineering of enzymes and metabolic pathways. Here, we engineer a G-protein-coupled receptor (GPCR)-based sensor to detect serotonin produced by a producer microbe in the producer microbe's supernatant. Detecting a chemical in the producer microbe's supernatant is nontrivial because of the number of other metabolites and proteins present that could interfere with sensor performance. We validate the two-cell screening system for medium-throughput applications, opening the door to the rapid engineering of microbes for the increased production of serotonin. We focus on serotonin detection as serotonin levels limit the microbial production of hydroxystrictosidine, a modified alkaloid that could accelerate the semisynthesis of camptothecin-derived anticancer pharmaceuticals. This work shows the ease of generating GPCR-based chemical sensors and their ability to detect specific chemicals in complex aqueous solutions, such as microbial spent medium. In addition, this work sets the stage for the rapid engineering of serotonin-producing microbes.

Pharmacophore Models and Pharmacophore-Based Virtual Screening: Concepts and Applications Exemplified on Hydroxysteroid Dehydrogenases.

PubMed

Kaserer, Teresa; Beck, Katharina R; Akram, Muhammad; Odermatt, Alex; Schuster, Daniela

2015-12-19

Computational methods are well-established tools in the drug discovery process and can be employed for a variety of tasks. Common applications include lead identification and scaffold hopping, as well as lead optimization by structure-activity relationship analysis and selectivity profiling. In addition, compound-target interactions associated with potentially harmful effects can be identified and investigated. This review focuses on pharmacophore-based virtual screening campaigns specifically addressing the target class of hydroxysteroid dehydrogenases. Many members of this enzyme family are associated with specific pathological conditions, and pharmacological modulation of their activity may represent promising therapeutic strategies. On the other hand, unintended interference with their biological functions, e.g., upon inhibition by xenobiotics, can disrupt steroid hormone-mediated effects, thereby contributing to the development and progression of major diseases. Besides a general introduction to pharmacophore modeling and pharmacophore-based virtual screening, exemplary case studies from the field of short-chain dehydrogenase/reductase (SDR) research are presented. These success stories highlight the suitability of pharmacophore modeling for the various application fields and suggest its application also in futures studies.

Improving substance abuse screening and intervention in a primary care clinic.

PubMed

Neushotz, Lori A; Fitzpatrick, Joyce J

2008-04-01

Despite recent efforts to educate primary care providers in the identification and management of patients presenting with substance abuse problems, many opportunities to identify and intervene with these patients are overlooked. This project was designed to identify factors that interfere with rates of screening and brief intervention (SBI) of substance abuse problems in a primary care clinic in a major academic medical center in New York City. Six informants representing the disciplines of medicine, nursing, and social work in the primary care clinic provided information regarding SBI. Analysis was focused on substantiation of the need for enhanced diffusion of knowledge related to screening for substance abuse problems to improve rates of SBI in primary care. Recommendations for improvement included continued promotion of SBI by influential role models and opinion leaders, improvement in primary care providers' perceptions of the perceived characteristics of SBI to improve rates of adoption, implementation of interdisciplinary educational initiatives toward the goal of improving rates of SBI in the primary care clinic, and initiation of translational research at the clinic supporting SBI in primary care.

Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and Interaction-Based Assays

PubMed Central

Salas-Sarduy, Emir; Guerra, Yasel; Covaleda Cortés, Giovanni; Avilés, Francesc Xavier; Chávez Planes, María A.

2017-01-01

Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. In the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model enzymes. To this end, we first developed a screening strategy that combined enzymatic with interaction-based assays and then validated screening conditions using five reference extracts. Interferences were evaluated and minimized. The results from the massive screening of such extracts, the validation of several hits by a variety of interaction-based assays and the purification and functional characterization of PhPI, a multifunctional and reversible tight-binding inhibitor for Plasmepsin II and Falcipain 2 from the gorgonian Plexaura homomalla, are presented. PMID:28430158

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

PubMed Central

Walko, Gernot; Woodhouse, Samuel; Pisco, Angela Oliveira; Rognoni, Emanuel; Liakath-Ali, Kifayathullah; Lichtenberger, Beate M.; Mishra, Ajay; Telerman, Stephanie B.; Viswanathan, Priyalakshmi; Logtenberg, Meike; Renz, Lisa M.; Donati, Giacomo; Quist, Sven R.; Watt, Fiona M.

2017-01-01

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2. PMID:28332498

Label-free chemical imaging of live Euglena gracilis by high-speed SRS spectral microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wakisaka, Yoshifumi; Suzuki, Yuta; Tokunaga, Kyoya; Hirose, Misa; Domon, Ryota; Akaho, Rina; Kuroshima, Mai; Tsumura, Norimichi; Shimobaba, Tomoyoshi; Iwata, Osamu; Suzuki, Kengo; Nakashima, Ayaka; Goda, Keisuke; Ozeki, Yasuyuki

2016-03-01

Microbes, especially microalgae, have recently been of great interest for developing novel biofuels, drugs, and biomaterials. Imaging-based screening of live cells can provide high selectivity and is attractive for efficient bio-production from microalgae. Although conventional cellular screening techniques use cell labeling, labeling of microbes is still under development and can interfere with their cellular functions. Furthermore, since live microbes move and change their shapes rapidly, a high-speed imaging technique is required to suppress motion artifacts. Stimulated Raman scattering (SRS) microscopy allows for label-free and high-speed spectral imaging, which helps us visualize chemical components inside biological cells and tissues. Here we demonstrate high-speed SRS imaging, with temporal resolution of 0.14 seconds, of intracellular distributions of lipid, polysaccharide, and chlorophyll concentrations in rapidly moving Euglena gracilis, a unicellular phytoflagellate. Furthermore, we show that our method allows us to analyze the amount of chemical components inside each living cell. Our results indicate that SRS imaging may be applied to label-free screening of living microbes based on chemical information.

A wall interference assessment/correction interface measurement system for the NASA/ARC 12-ft PWT

NASA Technical Reports Server (NTRS)

1989-01-01

Development of complex air vehicle configurations is placing increasing demands on wind tunnel testing capabilities. A major area of concern is wall induced interference. Recent developments in wall interference technology provide a means for assessing and correcting for the wall induced interference using information contained in the distribution of flow variables measured at, or near, the wall. The restoration of the NASA-ARC 12-ft pressure wind tunnel (PWT) provides an opportunity to incorporate a measurement system with which wall interference assessment/correction (WIAC) technology can be applied. In this first phase of the development of a WIAC system for the PWT, the design criteria for the placement and the geometry of wall static pressure orifices were determined with a three step approach. First, the operational environment of the PWT was analyzed as to the requirements for the WIAC system. Second, appropriate wall interference theories were evaluated against the requirements determined from the operational environment. Third, the flow about representative models in the PWT was calculated and, specifically, the pressure signatures at the location of the test section wall were obtained. The number of discrete pressure measurements and their locations were determined by curve fitting the pressure distribution through the discrete measurements and evaluating the resulting error.

Binaural Interference: Quo Vadis?

PubMed

Jerger, James; Silman, Shlomo; Silverman, Carol; Emmer, Michele

2017-04-01

The reality of the phenomenon of binaural interference with speech recognition has been debated for two decades. Research has taken one of two avenues; group studies or case reports. In group studies, a sample of the elderly population is tested on speech recognition under three conditions; binaural, monaural right and monaural left. The aim is to determine the percent of the sample in which the expected outcome (binaural score-better-than-either-monaural score) is reversed (i.e., one of the monaural scores is better than the binaural score). This outcome has been commonly used to define binaural interference. The object of group studies is to answer the "how many" question, what is the prevalence of binaural interference in the sample. In case reports the binaural interference conclusion suggested by the speech recognition tests is not accepted until it has been corroborated by other independent diagnostic audiological measures. The aim is to attempt to determine the basis for the findings, to answer the "why" question. This article is at once tutorial, editorial and a case report. We argue that it is time to accept the reality of the phenomenon of binaural interference, to eschew group statistical approaches in search of an answer to the "how many" question, and to focus on individual case reports in search of an answer to the "why" question. American Academy of Audiology.

Walla Walla River Basin Fish Screens Evaluations, 2006 Annual Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chamness, Mickie; Abernethy, Scott; Tunnicliffe, Cherylyn

2007-01-01

Pacific Northwest National Laboratory evaluated Gardena Farms, Little Walla Walla, and Garden City/Lowden II Phase II fish screen facilities and provided underwater videography beneath a leaking rubber dam in the Walla Walla River basin in 2006. Evaluations of the fish screen facilities took place in early May 2006, when juvenile salmonids are generally outmigrating. At the Gardena Farms site, extended high river levels caused accumulations of debris and sediment in the forebay. This debris covered parts of the bottom drum seals, which could lead to early deterioration of the seals and drum screen. Approach velocities were excessive at the upstreammore » corners of most of the drums, leading to 14% of the total approach velocities exceeding 0.4 feet per second (ft/s). Consequently, the approach velocities did not meet National Marine Fisheries Service (NMFS) design criteria guidelines for juvenile fish screens. The Little Walla Walla site was found to be in good condition, with all approach, sweep, and bypass velocities within NMFS criteria. Sediment buildup was minor and did not affect the effectiveness of the screens. At Garden City/Lowden II, 94% of approach velocities met NMFS criteria of 0.4 ft/s at any time. Sweep velocities increased toward the fish ladder. The air-burst mechanism appears to keep large debris off the screens, although it does not prevent algae and periphyton from growing on the screen face, especially near the bottom of the screens. In August 2006, the Gardena Farm Irrigation District personnel requested that we look for a leak beneath the inflatable rubber dam at the Garden City/Lowden II site that was preventing water movement through the fish ladder. Using our underwater video equipment, we were able to find a gap in the sheet piling beneath the dam. Erosion of the riverbed was occurring around this gap, allowing water and cobbles to move beneath the dam. The construction engineers and irrigation district staff were able to use the video footage to resolve the problem within a couple weeks. We had hoped to also evaluate the effectiveness of modifications to louvers behind the Nursery Bridge screens when flows were higher than 350 cubic feet per second, (cfs) but were unable to do so. Based on the one measurement made in early 2006 after the modified louvers were set, it appears the modified louvers may help reduce approach velocities. The auxiliary supply water system gates also control water through the screens. Evaluating the effect of different combinations of gate and louver positions on approach velocities through the screens may help identify optimum settings for both at different river discharges.« less

A fast, robust algorithm for power line interference cancellation in neural recording.

PubMed

Keshtkaran, Mohammad Reza; Yang, Zhi

2014-04-01

Power line interference may severely corrupt neural recordings at 50/60 Hz and harmonic frequencies. The interference is usually non-stationary and can vary in frequency, amplitude and phase. To retrieve the gamma-band oscillations at the contaminated frequencies, it is desired to remove the interference without compromising the actual neural signals at the interference frequency bands. In this paper, we present a robust and computationally efficient algorithm for removing power line interference from neural recordings. The algorithm includes four steps. First, an adaptive notch filter is used to estimate the fundamental frequency of the interference. Subsequently, based on the estimated frequency, harmonics are generated by using discrete-time oscillators, and then the amplitude and phase of each harmonic are estimated by using a modified recursive least squares algorithm. Finally, the estimated interference is subtracted from the recorded data. The algorithm does not require any reference signal, and can track the frequency, phase and amplitude of each harmonic. When benchmarked with other popular approaches, our algorithm performs better in terms of noise immunity, convergence speed and output signal-to-noise ratio (SNR). While minimally affecting the signal bands of interest, the algorithm consistently yields fast convergence (<100 ms) and substantial interference rejection (output SNR >30 dB) in different conditions of interference strengths (input SNR from -30 to 30 dB), power line frequencies (45-65 Hz) and phase and amplitude drifts. In addition, the algorithm features a straightforward parameter adjustment since the parameters are independent of the input SNR, input signal power and the sampling rate. A hardware prototype was fabricated in a 65 nm CMOS process and tested. Software implementation of the algorithm has been made available for open access at https://github.com/mrezak/removePLI. The proposed algorithm features a highly robust operation, fast adaptation to interference variations, significant SNR improvement, low computational complexity and memory requirement and straightforward parameter adjustment. These features render the algorithm suitable for wearable and implantable sensor applications, where reliable and real-time cancellation of the interference is desired.

Nontarget approach for environmental monitoring by GC × GC-HRTOFMS in the Tokyo Bay basin.

PubMed

Zushi, Yasuyuki; Hashimoto, Shunji; Tanabe, Kiyoshi

2016-08-01

In this study, we developed an approach for sequential nontarget and target screening for the rapid and efficient analysis of multiple samples as an environmental monitoring using a comprehensive two-dimensional gas chromatograph coupled to a high resolution time-of-flight mass spectrometer (GC × GC-HRTOFMS). A key feature of the approach was the construction of an accurate mass spectral database learned from the sample via nontarget screening. To enhance the detection power in the nontarget screening, a global spectral deconvolution procedure based on non-negative matrix factorization was applied. The approach was applied to the monitoring of rivers in the Tokyo Bay basin. The majority of the compounds detected by the nontarget screening were alkyl chain-based compounds (55%). In the quantitative target screening based on the output from the nontarget screening, particularly high levels of organophosphorus flame retardants (median concentrations of 31, 116 and 141 ng l(-1) for TDCPP, TCIPP and TBEP, respectively) were observed among the target compounds. Flame retardants used for household furniture and building materials were detected in river basins where buildings and arterial traffic were dominated. The developed GC × GC-HRTOFMS approach was efficient and effective for environmental monitoring and provided valuable new information on various aspects of monitoring in the context of environmental management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary Evaluation of a Web-Based Psychological Screening Tool in Adolescents Undergoing Minimally Invasive Pectus Surgery: Single-Center Observational Cohort Study.

PubMed

Wildemeersch, Davina; Bernaerts, Lisa; D'Hondt, Michiel; Hans, Guy

2018-05-31

Preoperative anxiety and depression are predominant risk factors for increased postoperative pain. Thoracic wall deformities in adolescents often cause low self-esteem, which contributes to psychological concerns. Several studies have suggested a relationship between preoperative mental health support and enhanced recovery after surgery. This study investigated the validity of screening questionnaires concerning psychological trait and state characteristics via a patient-specific online platform. Patients scheduled for elective pectus surgery between June 2017 and August 2017 were invited to participate in clinical interviews and online self-report questionnaires. All patients were recruited in the Anesthesiology Department, Antwerp University Hospital, Belgium. This single-center observational cohort study was performed in accordance with the ethical standards of the International Council for Harmonisation-Good Clinical Practice guidelines and the Declaration of Helsinki after obtaining study approval by the Institutional Review Board and Ethics Committee of the Antwerp University Hospital, Belgium (study identifier: 17/08/082). An online preoperative psychological inventory was performed using the Rosenberg Self-Esteem Scale, Hospital Anxiety and Depression Scale, and State-Trait Anxiety Inventory. Postoperatively, pain intensity and interference were assessed using the Multidisciplinary Pain Inventory, Coping With Pain Questionnaire, and numeric pain rating scale assessment. Patient satisfaction of the Web-based platform was evaluated. A total of 21 adolescent patients used our Web-based psychological perioperative screening platform. Patients rated the mobile phone app, usability, and accessibility of the digital platform as good or excellent in 85% (17/20), 89% (17/19), and 95% (20/21) of the cases, respectively. A total of 89% (17/19) of the patients rated the effort of generating answers to the online questionnaires as low. The results from the completed questionnaires indicated a strong negative correlation between self-esteem and the anxiety trait (R=-0.72, P<.001) and overall anxiety characteristics (R=-0.49, P=.04). There was a positive correlation between depressive and anxiety characteristics and the anxiety trait (R=0.52, P=.03 and R=0.6, P=.02, respectively) measured by the online self-report questionnaires. Moreover, preoperative anxiety was positively correlated with postoperative pain interference (R=0.58, P=.02). Finally, there was a negative correlation between self-esteem and pain interference (R=-0.62, P=.01). Conclusions: Perioperative screening of psychological symptoms and trait characteristics with specific treatment, if necessary, could further improve postoperative pain and overall health status. Research on eHealth technology, even for psychological patient care, is rapidly increasing. ClinicalTrials.gov NCT03100669; https://clinicaltrials.gov/ct2/show/NCT03100669 (Archived by WebCite at http://www.webcitation.org/6zPvHDhU5). ©Davina Wildemeersch, Lisa Bernaerts, Michiel D’Hondt, Guy Hans. Originally published in JMIR Mental Health (http://mental.jmir.org), 31.05.2018.

Immobilized magnetic beads-based multi-target affinity selection coupled with HPLC-MS for screening active compounds from traditional Chinese medicine and natural products.

PubMed

Chen, Yaqi; Chen, Zhui; Wang, Yi

2015-01-01

Screening and identifying active compounds from traditional Chinese medicine (TCM) and other natural products plays an important role in drug discovery. Here, we describe a magnetic beads-based multi-target affinity selection-mass spectrometry approach for screening bioactive compounds from natural products. Key steps and parameters including activation of magnetic beads, enzyme/protein immobilization, characterization of functional magnetic beads, screening and identifying active compounds from a complex mixture by LC/MS, are illustrated. The proposed approach is rapid and efficient in screening and identification of bioactive compounds from complex natural products.

Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA interference.

PubMed

Xie, Ni; Mou, Lisha; Yuan, Jianhui; Liu, Wenlan; Deng, Tingting; Li, Zigang; Jing, Yi; Jin, Yi; Hu, Zhangli

2014-01-01

The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications. To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi) that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor. The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi) to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors.

78 FR 35903 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; ICR...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

...; Tier 1 Screening of Certain Chemicals Under the Endocrine Disruptor Screening Program AGENCY... Chemicals; Tier 1 Screening of Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP... effects. The EDSP consists of a two-tiered approach to screen chemicals for potential endocrine disrupting...

Screening of neuraminidase inhibitors from traditional Chinese medicines by integrating capillary electrophoresis with immobilized enzyme microreactor.

PubMed

Zhao, Haiyan; Chen, Zilin

2014-05-02

A simple and effective neuraminidase-immobilized capillary microreactor was fabricated by glutaraldehyde cross-linking technology for screening the neuraminidase inhibitors from traditional Chinese medicines. The substrate and product were separated by CE in short-end injection mode within 2 min. Dual-wavelength ultraviolet detection was employed to eliminate the interference from the screened compounds. The parameters relating to the separation efficiency and the activity of immobilized neuraminidase were systematically evaluated. The activity of the immobilized neuraminidase remained 90% after 30 days storage at 4°C. The immobilized NA microreactor could be continuously used for more than 200 runs. The Michaelis-Menten constant of neuraminidase was determined by the microreactor as 136.6 ± 10.8 μM. In addition, six in eighteen natural products were found as potent inhibitors and the inhibition potentials were ranked in the following order: bavachinin>bavachin>baicalein>baicalin>chrysin and vitexin. The half-maximal inhibitory concentrations were 59.52 ± 4.12, 65.28 ± 1.07, 44.79 ± 1.21 and 31.62 ± 2.04 for baicalein, baicalin, bavachin and bavachinin, respectively. The results demonstrated that the neuraminidase-immobilized capillary microreactor was a very effective tool for screening neuraminidase inhibitors from traditional Chinese medicines. Copyright © 2014 Elsevier B.V. All rights reserved.

[Methodology of Screening New Antibiotics: Present Status and Prospects].

PubMed

Trenin, A S

2015-01-01

Due to extensive distribution of pathogen resistance to available pharmaceuticals and serious problems in the treatment of various infections and tumor diseases, the necessity of new antibiotics is urgent. The basic methodological approaches to chemical synthesis of antibiotics and screening of new antibiotics among natural products, mainly among microbial secondary metabolites, are considered in the review. Since the natural compounds are very much diverse, screening of such substances gives a good opportunity to discover antibiotics of various chemical structure and mechanism of action. Such an approach followed by chemical or biological transformation, is capable of providing the health care with new effective pharmaceuticals. The review is mainly concentrated on screening of natural products and methodological problems, such as: isolation of microbial producers from the habitats, cultivation of microorganisms producing appropriate substances, isolation and chemical characterization of microbial metabolites, identification of the biological activity of the metabolites. The main attention is paid to the problems of microbial secondary metabolism and design of new models for screening biologically active compounds. The last achievements in the field of antibiotics and most perspective approaches to future investigations are discussed. The main methodological approach to isolation and cultivation of the producers remains actual and needs constant improvement. The increase of the screening efficiency can be achieved by more rapid chemical identification of antibiotics and design of new screening models based on the biological activity detection.

A Multi-Functional Imaging Approach to High-Content Protein Interaction Screening

PubMed Central

Matthews, Daniel R.; Fruhwirth, Gilbert O.; Weitsman, Gregory; Carlin, Leo M.; Ofo, Enyinnaya; Keppler, Melanie; Barber, Paul R.; Tullis, Iain D. C.; Vojnovic, Borivoj; Ng, Tony; Ameer-Beg, Simon M.

2012-01-01

Functional imaging can provide a level of quantification that is not possible in what might be termed traditional high-content screening. This is due to the fact that the current state-of-the-art high-content screening systems take the approach of scaling-up single cell assays, and are therefore based on essentially pictorial measures as assay indicators. Such phenotypic analyses have become extremely sophisticated, advancing screening enormously, but this approach can still be somewhat subjective. We describe the development, and validation, of a prototype high-content screening platform that combines steady-state fluorescence anisotropy imaging with fluorescence lifetime imaging (FLIM). This functional approach allows objective, quantitative screening of small molecule libraries in protein-protein interaction assays. We discuss the development of the instrumentation, the process by which information on fluorescence resonance energy transfer (FRET) can be extracted from wide-field, acceptor fluorescence anisotropy imaging and cross-checking of this modality using lifetime imaging by time-correlated single-photon counting. Imaging of cells expressing protein constructs where eGFP and mRFP1 are linked with amino-acid chains of various lengths (7, 19 and 32 amino acids) shows the two methodologies to be highly correlated. We validate our approach using a small-scale inhibitor screen of a Cdc42 FRET biosensor probe expressed in epidermoid cancer cells (A431) in a 96 microwell-plate format. We also show that acceptor fluorescence anisotropy can be used to measure variations in hetero-FRET in protein-protein interactions. We demonstrate this using a screen of inhibitors of internalization of the transmembrane receptor, CXCR4. These assays enable us to demonstrate all the capabilities of the instrument, image processing and analytical techniques that have been developed. Direct correlation between acceptor anisotropy and donor FLIM is observed for FRET assays, providing an opportunity to rapidly screen proteins, interacting on the nano-meter scale, using wide-field imaging. PMID:22506000

Evaluation of Microelectrode Array Data using Bayesian Modeling as an Approach to Screening and Prioritization for Neurotoxicity Testing*

EPA Science Inventory

The need to assess large numbers of chemicals for their potential toxicities has resulted in increased emphasis on medium- and high-throughput in vitro screening approaches. For such approaches to be useful, efficient and reliable data analysis and hit detection methods are also ...

Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity

NASA Astrophysics Data System (ADS)

Migliorelli, Carolina; Alonso, Joan F.; Romero, Sergio; Mañanas, Miguel A.; Nowak, Rafał; Russi, Antonio

2016-04-01

Objective. Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference. Approach. A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results. Main results. The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches. Significance. The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.

Frequency-domain Hong-Ou-Mandel interference with linear optics.

PubMed

Imany, Poolad; Odele, Ogaga D; Alshaykh, Mohammed S; Lu, Hsuan-Hao; Leaird, Daniel E; Weiner, Andrew M

2018-06-15

The Hong-Ou-Mandel (HOM) interference is one of the most fundamental quantum-mechanical effects that reveal a nonclassical behavior of single photons. Two identical photons that are incident on the input ports of an unbiased beam splitter always exit the beam splitter together from the same output port, an effect referred to as photon bunching. In this Letter, we utilize a single electro-optic phase modulator as a probabilistic frequency beam splitter, which we exploit to observe HOM interference between two photons that are in different spectral modes, yet are identical in other characteristics. Our approach enables linear optical quantum information processing protocols using the frequency degree of freedom in photons such as quantum computing techniques with linear optics.

Generalized energy detector for weak random signals via vibrational resonance

NASA Astrophysics Data System (ADS)

Ren, Yuhao; Pan, Yan; Duan, Fabing

2018-03-01

In this paper, the generalized energy (GE) detector is investigated for detecting weak random signals via vibrational resonance (VR). By artificially injecting the high-frequency sinusoidal interferences into an array of GE statistics formed for the detector, we show that the normalized asymptotic efficacy can be maximized when the interference intensity takes an appropriate non-zero value. It is demonstrated that the normalized asymptotic efficacy of the dead-zone-limiter detector, aided by the VR mechanism, outperforms that of the GE detector without the help of high-frequency interferences. Moreover, the maximum normalized asymptotic efficacy of dead-zone-limiter detectors can approach a quarter of the second-order Fisher information for a wide range of non-Gaussian noise types.

Detection of interference phase by digital computation of quadrature signals in homodyne laser interferometry.

PubMed

Rerucha, Simon; Buchta, Zdenek; Sarbort, Martin; Lazar, Josef; Cip, Ondrej

2012-10-19

We have proposed an approach to the interference phase extraction in the homodyne laser interferometry. The method employs a series of computational steps to reconstruct the signals for quadrature detection from an interference signal from a non-polarising interferometer sampled by a simple photodetector. The complexity trade-off is the use of laser beam with frequency modulation capability. It is analytically derived and its validity and performance is experimentally verified. The method has proven to be a feasible alternative for the traditional homodyne detection since it performs with comparable accuracy, especially where the optical setup complexity is principal issue and the modulation of laser beam is not a heavy burden (e.g., in multi-axis sensor or laser diode based systems).

Interference effect in the resonant emission of a semiconductor microcavity

NASA Astrophysics Data System (ADS)

Cassabois, G.; Bogani, F.; Triques, A. L.; Delalande, C.; Roussignol, Ph.

2001-07-01

We present a phenomenological description of the coherent emission from a semiconductor microcavity in the strong-coupling regime. We consider two main contributions which are calculated in the framework of the semiclassical approach of the linear dispersion theory: reflectivity corresponds to the response of a uniform microcavity while resonant Rayleigh scattering (RRS) arises from disorder. Our simulations are compared to experimental results obtained at normal incidence in a backscattering geometry by means of cw spectroscopy and interferometric correlation with subpicosecond resolution. In this geometry, a fair agreement is reached assuming interferences between the two aforementioned contributions. This interference effect gives evidence of the drastic modification of the RRS emission pattern of the embedded quantum well induced by the Fabry-Pérot cavity.

Design of compound libraries for fragment screening

NASA Astrophysics Data System (ADS)

Blomberg, Niklas; Cosgrove, David A.; Kenny, Peter W.; Kolmodin, Karin

2009-08-01

Approaches to the design of libraries for fragment screening are illustrated with reference to a 20 k generic fragment screening library and a 1.2 k generic NMR screening library. Tools and methods for library design that have been developed within AstraZeneca are described, including Foyfi fingerprints and the Flush program for neighborhood characterization. It will be shown how Flush and the BigPicker, which selects maximally diverse sets of compounds, are used to apply the Core and Layer method for library design. Approaches to partitioning libraries into cocktails are also described.

Recommendations for a step‐wise comparative approach to the evaluation of new screening tests for colorectal cancer

PubMed Central

Senore, Carlo; Mandel, Jack S.; Allison, James E.; Atkin, Wendy S.; Benamouzig, Robert; Bossuyt, Patrick M. M.; Silva, Mahinda De; Guittet, Lydia; Halloran, Stephen P.; Haug, Ulrike; Hoff, Geir; Itzkowitz, Steven H.; Leja, Marcis; Levin, Bernard; Meijer, Gerrit A.; O'Morain, Colm A.; Parry, Susan; Rabeneck, Linda; Rozen, Paul; Saito, Hiroshi; Schoen, Robert E.; Seaman, Helen E.; Steele, Robert J. C.; Sung, Joseph J. Y.; Winawer, Sidney J.

2016-01-01

BACKGROUND New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention‐to‐screen basis, including acceptability, is essential. Cancer‐specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac‐based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4‐phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention‐to‐screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true‐positive and false‐positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS New screening tests can be evaluated efficiently by this stepwise comparative approach. Cancer 2016;122:826–39. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. PMID:26828588

Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer.

PubMed

Young, Graeme P; Senore, Carlo; Mandel, Jack S; Allison, James E; Atkin, Wendy S; Benamouzig, Robert; Bossuyt, Patrick M M; Silva, Mahinda De; Guittet, Lydia; Halloran, Stephen P; Haug, Ulrike; Hoff, Geir; Itzkowitz, Steven H; Leja, Marcis; Levin, Bernard; Meijer, Gerrit A; O'Morain, Colm A; Parry, Susan; Rabeneck, Linda; Rozen, Paul; Saito, Hiroshi; Schoen, Robert E; Seaman, Helen E; Steele, Robert J C; Sung, Joseph J Y; Winawer, Sidney J

2016-03-15

New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion. New screening tests can be evaluated efficiently by this stepwise comparative approach. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

[Considerations when using creatinine as a measure of kidney function].

PubMed

Drion, I Iefke; Fokkert, M J Marion; Bilo, H J G Henk

2013-01-01

Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function.

A closer look: Alternative pain management practices by heart failure patients with chronic pain.

PubMed

McDonald, Deborah Dillon; Soutar, Christina; Chan, Maria Agudelo; Afriyie, Angela

2015-01-01

To describe alternative non-pharmaceutical non-nutraceutical pain self-management strategies used by people with heart failure (HF) in order to reduce chronic non-cardiac pain. Little is known about alternative pain self-treatments used by HF patients with chronic pain. A cross-sectional descriptive design was used with 25 hospitalized HF patients who had chronic pain and used at least one alternative pain treatment. Pain intensity, pain interference with function, and current pain treatments were measured with the Brief Pain Inventory. Alternative treatments included walking, stretching, use of heat and cold. Five patients used evidence-based pain treatments for their chronic pain conditions. Patients reported moderate pain intensity and pain interference with activity. Patients with HF and chronic pain use few alternative pain treatments. Screening for chronic pain and referral to Integrative Medicine and/or Palliative care for a pain management consult might reduce the added burden of pain in people with HF. Copyright © 2015 Elsevier Inc. All rights reserved.

Loss-of-function analyses of the fragile X-related and dopamine receptor genes by RNA interference in the cricket Gryllus bimaculatus.

PubMed

Hamada, Aska; Miyawaki, Katsuyuki; Honda-sumi, Eri; Tomioka, Kenji; Mito, Taro; Ohuchi, Hideyo; Noji, Sumihare

2009-08-01

In order to explore a possibility that the cricket Gryllus bimaculatus would be a useful model to unveil molecular mechanisms of human diseases, we performed loss-of-function analyses of Gryllus genes homologous to human genes that are responsible for human disorders, fragile X mental retardation 1 (fmr1) and Dopamine receptor (DopR). We cloned cDNAs of their Gryllus homologues, Gb'fmr1, Gb'DopRI, and Gb'DopRII, and analyzed their functions with use of nymphal RNA interference (RNAi). For Gb'fmr1, three major phenotypes were observed: (1) abnormal wing postures, (2) abnormal calling song, and (3) loss of the circadian locomotor rhythm, while for Gb'DopRI, defects of wing posture and morphology were found. These results indicate that the cricket has the potential to become a novel model system to explore human neuronal pathogenic mechanisms and to screen therapeutic drugs by RNAi. Copyright (c) 2009 Wiley-Liss, Inc.

A whole genome screening and RNA interference identify a juvenile hormone esterase-like gene of the diamondback moth, Plutella xylostella.

PubMed

Gu, Xiaojun; Kumar, Sunil; Kim, Eunjin; Kim, Yonggyun

2015-09-01

Juvenile hormone (JH) plays a crucial role in preventing precocious metamorphosis and stimulating reproduction. Thus, its hemolymph titer should be under a tight control. As a negative controller, juvenile hormone esterase (JHE) performs a rapid breakdown of residual JH in the hemolymph during last instar to induce a larval-to-pupal metamorphosis. A whole genome of the diamondback moth (DBM), Plutella xylostella, has been annotated and proposed 11 JHE candidates. Sequence analysis using conserved motifs commonly found in other JHEs proposed a putative JHE (Px004817). Px004817 (64.61 kDa, pI=5.28) exhibited a characteristic JHE expression pattern by showing high peak at the early last instar, at which JHE enzyme activity was also at a maximal level. RNA interference of Px004817 reduced JHE activity and interrupted pupal development with a significant increase of larval period. This study identifies Px004817 as a JHE-like gene of P. xylostella. Copyright © 2015 Elsevier Ltd. All rights reserved.

Engaging New Migrants in Infectious Disease Screening: A Qualitative Semi-Structured Interview Study of UK Migrant Community Health-Care Leads

PubMed Central

Seedat, Farah; Hargreaves, Sally; Friedland, Jonathan S.

2014-01-01

Migration to Europe - and in particular the UK - has risen dramatically in the past decades, with implications for public health services. Migrants have increased vulnerability to infectious diseases (70% of TB cases and 60% HIV cases are in migrants) and face multiple barriers to healthcare. There is currently considerable debate as to the optimum approach to infectious disease screening in this often hard-to-reach group, and an urgent need for innovative approaches. Little research has focused on the specific experience of new migrants, nor sought their views on ways forward. We undertook a qualitative semi-structured interview study of migrant community health-care leads representing dominant new migrant groups in London, UK, to explore their views around barriers to screening, acceptability of screening, and innovative approaches to screening for four key diseases (HIV, TB, hepatitis B, and hepatitis C). Participants unanimously agreed that current screening models are not perceived to be widely accessible to new migrant communities. Dominant barriers that discourage uptake of screening include disease-related stigma present in their own communities and services being perceived as non-migrant friendly. New migrants are likely to be disproportionately affected by these barriers, with implications for health status. Screening is certainly acceptable to new migrants, however, services need to be developed to become more community-based, proactive, and to work more closely with community organisations; findings that mirror the views of migrants and health-care providers in Europe and internationally. Awareness raising about the benefits of screening within new migrant communities is critical. One innovative approach proposed by participants is a community-based package of health screening combining all key diseases into one general health check-up, to lessen the associated stigma. Further research is needed to develop evidence-based community-focused screening models - drawing on models of best practice from other countries receiving high numbers of migrants. PMID:25330079

Portable Wireless LAN Device and Two-way Radio Threat Assessment for Aircraft Navigation Radios

NASA Technical Reports Server (NTRS)

Nguyen, Truong X.; Koppen, Sandra V.; Ely, Jay J.; Williams, Reuben A.; Smith, Laura J.; Salud, Maria Theresa P.

2003-01-01

Measurement processes, data and analysis are provided to address the concern for Wireless Local Area Network devices and two-way radios to cause electromagnetic interference to aircraft navigation radio systems. A radiated emission measurement process is developed and spurious radiated emissions from various devices are characterized using reverberation chambers. Spurious radiated emissions in aircraft radio frequency bands from several wireless network devices are compared with baseline emissions from standard computer laptops and personal digital assistants. In addition, spurious radiated emission data in aircraft radio frequency bands from seven pairs of two-way radios are provided, A description of the measurement process, device modes of operation and the measurement results are reported. Aircraft interference path loss measurements were conducted on four Boeing 747 and Boeing 737 aircraft for several aircraft radio systems. The measurement approach is described and the path loss results are compared with existing data from reference documents, standards, and NASA partnerships. In-band on-channel interference thresholds are compiled from an existing reference document. Using these data, a risk assessment is provided for interference from wireless network devices and two-way radios to aircraft systems, including Localizer, Glideslope, Very High Frequency Omnidirectional Range, Microwave Landing System and Global Positioning System. The report compares the interference risks associated with emissions from wireless network devices and two-way radios against standard laptops and personal digital assistants. Existing receiver interference threshold references are identified as to require more data for better interference risk assessments.

A Rapid Convergent Low Complexity Interference Alignment Algorithm for Wireless Sensor Networks.

PubMed

Jiang, Lihui; Wu, Zhilu; Ren, Guanghui; Wang, Gangyi; Zhao, Nan

2015-07-29

Interference alignment (IA) is a novel technique that can effectively eliminate the interference and approach the sum capacity of wireless sensor networks (WSNs) when the signal-to-noise ratio (SNR) is high, by casting the desired signal and interference into different signal subspaces. The traditional alternating minimization interference leakage (AMIL) algorithm for IA shows good performance in high SNR regimes, however, the complexity of the AMIL algorithm increases dramatically as the number of users and antennas increases, posing limits to its applications in the practical systems. In this paper, a novel IA algorithm, called directional quartic optimal (DQO) algorithm, is proposed to minimize the interference leakage with rapid convergence and low complexity. The properties of the AMIL algorithm are investigated, and it is discovered that the difference between the two consecutive iteration results of the AMIL algorithm will approximately point to the convergence solution when the precoding and decoding matrices obtained from the intermediate iterations are sufficiently close to their convergence values. Based on this important property, the proposed DQO algorithm employs the line search procedure so that it can converge to the destination directly. In addition, the optimal step size can be determined analytically by optimizing a quartic function. Numerical results show that the proposed DQO algorithm can suppress the interference leakage more rapidly than the traditional AMIL algorithm, and can achieve the same level of sum rate as that of AMIL algorithm with far less iterations and execution time.

Integration of Lead Discovery Tactics and the Evolution of the Lead Discovery Toolbox.

PubMed

Leveridge, Melanie; Chung, Chun-Wa; Gross, Jeffrey W; Phelps, Christopher B; Green, Darren

2018-06-01

There has been much debate around the success rates of various screening strategies to identify starting points for drug discovery. Although high-throughput target-based and phenotypic screening has been the focus of this debate, techniques such as fragment screening, virtual screening, and DNA-encoded library screening are also increasingly reported as a source of new chemical equity. Here, we provide examples in which integration of more than one screening approach has improved the campaign outcome and discuss how strengths and weaknesses of various methods can be used to build a complementary toolbox of approaches, giving researchers the greatest probability of successfully identifying leads. Among others, we highlight case studies for receptor-interacting serine/threonine-protein kinase 1 and the bromo- and extra-terminal domain family of bromodomains. In each example, the unique insight or chemistries individual approaches provided are described, emphasizing the synergy of information obtained from the various tactics employed and the particular question each tactic was employed to answer. We conclude with a short prospective discussing how screening strategies are evolving, what this screening toolbox might look like in the future, how to maximize success through integration of multiple tactics, and scenarios that drive selection of one combination of tactics over another.

Novel approaches for targeting the adenosine A2A receptor.

PubMed

Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

2015-01-01

The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

Quantitative maps of genetic interactions in yeast - comparative evaluation and integrative analysis.

PubMed

Lindén, Rolf O; Eronen, Ville-Pekka; Aittokallio, Tero

2011-03-24

High-throughput genetic screening approaches have enabled systematic means to study how interactions among gene mutations contribute to quantitative fitness phenotypes, with the aim of providing insights into the functional wiring diagrams of genetic interaction networks on a global scale. However, it is poorly known how well these quantitative interaction measurements agree across the screening approaches, which hinders their integrated use toward improving the coverage and quality of the genetic interaction maps in yeast and other organisms. Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies. We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biedermann, G. W.; McGuinness, H. J.; Rakholia, A. V.

Here, we demonstrate matter-wave interference in a warm vapor of rubidium atoms. Established approaches to light-pulse atom interferometry rely on laser cooling to concentrate a large ensemble of atoms into a velocity class resonant with the atom optical light pulse. In our experiment, we show that clear interference signals may be obtained without laser cooling. This effect relies on the Doppler selectivity of the atom interferometer resonance. Lastly, this interferometer may be configured to measure accelerations, and we demonstrate that multiple interferometers may be operated simultaneously by addressing multiple velocity classes.

The battle against noise in industry

NASA Astrophysics Data System (ADS)

Iudin, E. Ia.

The physiological effects of noise in manufacturing plants and other industrial facilities are discussed, and several common noise abatement methods are described. Consideration is given to the acoustic properties of three types of noise which are present in industrial plants: aerohydrodynamic noise; mechanical noise; and electromagnetic noise. Among the specific noise abatement techniques discussed are: sound isolation by means of noise-absorbant screens; insulation or noise-emitting media; and acoustic interference. The use of earplugs and external ear protectors for protection of individual workers in noisy work environments is also considered.

Photorefractive Tungsten Bronze Crystals for Optical Limiters and Filters.

DTIC Science & Technology

1996-01-01

vector , X is the laser light wavelength, 0 is the half- angle between the two crossing laser beams, and k0 is the Debye screening wave vector given by...between the grating and the dielectric constant E’ = 950) such that the grating’ vector is interference pattern, the intensities of the output beams from...substituting Io, I, and Id into expression 0 ple d 2o0o 25i00 (8), we can calculate the phase shift between the grating and Applied Electric Feild in V

Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

PubMed Central

Reynard, Olivier; Nguyen, Xuan-Nhi; Alazard-Dany, Nathalie; Barateau, Véronique; Cimarelli, Andrea; Volchkov, Viktor E.

2015-01-01

The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV. PMID:26633464

An Evolutionarily Conserved Innate Immunity Protein Interaction Network*

PubMed Central

De Arras, Lesly; Seng, Amara; Lackford, Brad; Keikhaee, Mohammad R.; Bowerman, Bruce; Freedman, Jonathan H.; Schwartz, David A.; Alper, Scott

2013-01-01

The innate immune response plays a critical role in fighting infection; however, innate immunity also can affect the pathogenesis of a variety of diseases, including sepsis, asthma, cancer, and atherosclerosis. To identify novel regulators of innate immunity, we performed comparative genomics RNA interference screens in the nematode Caenorhabditis elegans and mouse macrophages. These screens have uncovered many candidate regulators of the response to lipopolysaccharide (LPS), several of which interact physically in multiple species to form an innate immunity protein interaction network. This protein interaction network contains several proteins in the canonical LPS-responsive TLR4 pathway as well as many novel interacting proteins. Using RNAi and overexpression studies, we show that almost every gene in this network can modulate the innate immune response in mouse cell lines. We validate the importance of this network in innate immunity regulation in vivo using available mutants in C. elegans and mice. PMID:23209288

CellCognition: time-resolved phenotype annotation in high-throughput live cell imaging.

PubMed

Held, Michael; Schmitz, Michael H A; Fischer, Bernd; Walter, Thomas; Neumann, Beate; Olma, Michael H; Peter, Matthias; Ellenberg, Jan; Gerlich, Daniel W

2010-09-01

Fluorescence time-lapse imaging has become a powerful tool to investigate complex dynamic processes such as cell division or intracellular trafficking. Automated microscopes generate time-resolved imaging data at high throughput, yet tools for quantification of large-scale movie data are largely missing. Here we present CellCognition, a computational framework to annotate complex cellular dynamics. We developed a machine-learning method that combines state-of-the-art classification with hidden Markov modeling for annotation of the progression through morphologically distinct biological states. Incorporation of time information into the annotation scheme was essential to suppress classification noise at state transitions and confusion between different functional states with similar morphology. We demonstrate generic applicability in different assays and perturbation conditions, including a candidate-based RNA interference screen for regulators of mitotic exit in human cells. CellCognition is published as open source software, enabling live-cell imaging-based screening with assays that directly score cellular dynamics.

System for monitoring the growth of crystalline films on stationary substrates

DOEpatents

Sheldon, P.

1996-12-31

A system for monitoring the growth of crystalline films on stationary or rotating substrates includes a combination of some or all of the elements including a photodiode sensor for detecting the intensity of incoming light and converting it to a measurable current, a lens for focusing the RHEED pattern emanating from the phosphor screen onto the photodiode, an interference filter for filtering out light other than that which emanates from the phosphor screen, a current amplifier for amplifying and convening the current produced by the photodiode into a voltage, a computer for receiving the amplified photodiode current for RHEED data analysis, and a graphite impregnated triaxial cable for improving the signal to noise ratio obtained while sampling a stationary or rotating substrate. A rotating stage for supporting the substrate with diametrically positioned electron beam apertures and an optically encoded shaft can also be used to accommodate rotation of the substrate during measurement. 16 figs.

System for monitoring the growth of crystalline films on stationary substrates

DOEpatents

Sheldon, P.

1995-10-10

A system for monitoring the growth of crystalline films on stationary or rotating substrates includes a combination of some or all of the elements including a photodiode sensor for detecting the intensity of incoming light and converting it to a measurable current, a lens for focusing the RHEED pattern emanating from the phosphor screen onto the photodiode, an interference filter for filtering out light other than that which emanates from the phosphor screen, a current amplifier for amplifying and converting the current produced by the photodiode into a voltage, a computer for receiving the amplified photodiode current for RHEED data analysis, and a graphite impregnated triaxial cable for improving the signal-to-noise ratio obtained while sampling a stationary or rotating substrate. A rotating stage for supporting the substrate with diametrically positioned electron beam apertures and an optically encoded shaft can also be used to accommodate rotation of the substrate during measurement. 16 figs.

Designer babies on tap? Medical students' attitudes to pre-implantation genetic screening.

PubMed

Meisenberg, Gerhard

2009-03-01

This paper describes two studies about the determinants of attitudes to pre-implantation genetic screening in a multicultural sample of medical students from the United States. Sample sizes were 292 in study 1 and 1464 in study 2. Attitudes were of an undifferentiated nature, but respondents did make a major distinction between use for disease prevention and use for enhancement. No strong distinctions were made between embryo selection and germ line gene manipulations, and between somatic gene therapy and germ line gene manipulations. Religiosity was negatively associated with acceptance of "designer baby" technology for Christians and Muslims but not Hindus. However, the strongest and most consistent influence was an apparently moralistic stance against active and aggressive interference with natural processes in general. Trust in individuals and institutions was unrelated to acceptance of the technology, indicating that fear of abuse by irresponsible individuals and corporations is not an important determinant of opposition.

Nuisance Compounds, PAINS Filters, and Dark Chemical Matter in the GSK HTS Collection.

PubMed

Chakravorty, Subhas J; Chan, James; Greenwood, Marie Nicole; Popa-Burke, Ioana; Remlinger, Katja S; Pickett, Stephen D; Green, Darren V S; Fillmore, Martin C; Dean, Tony W; Luengo, Juan I; Macarrón, Ricardo

2018-07-01

High-throughput screening (HTS) hits include compounds with undesirable properties. Many filters have been described to identify such hits. Notably, pan-assay interference compounds (PAINS) has been adopted by the community as the standard term to refer to such filters, and very useful guidelines have been adopted by the American Chemical Society (ACS) and subsequently triggered a healthy scientific debate about the pitfalls of draconian use of filters. Using an inhibitory frequency index, we have analyzed in detail the promiscuity profile of the whole GlaxoSmithKline (GSK) HTS collection comprising more than 2 million unique compounds that have been tested in hundreds of screening assays. We provide a comprehensive analysis of many previously published filters and newly described classes of nuisance structures that may serve as a useful source of empirical information to guide the design or growth of HTS collections and hit triaging strategies.

Constrained sheath optics for high thrust density, low specific impulse ion thrusters

NASA Technical Reports Server (NTRS)

Wilbur, Paul J.; Han, Jian-Zhang

1987-01-01

The results of an experimental study showing that a contoured, fine wire mesh attached to the screen grid can be used to control the divergence characteristics of ion beamlets produced at low net-to-total accelerating voltage ratios are presented. The influence of free and constrained-sheath optics systems on beamlet divergence characteristics are found to be similar in the operating regime investigated, but it was found that constrained-sheath optics systems can be operated at higher perveance levels than free-sheath ones. The concept of a fine wire interference probe that can be used to study ion beamlet focusing behavior is introduced. This probe is used to demonstrate beamlet focusing to a diameter about one hundreth of the screen grid extraction aperture diameter. Additional testing is suggested to define an optimally contoured mesh that could yield well focused beamlets at net-to-total accelerating voltage ratios below about 0.1.

Eye closure helps memory by reducing cognitive load and enhancing visualisation.

PubMed

Vredeveldt, Annelies; Hitch, Graham J; Baddeley, Alan D

2011-10-01

Closing the eyes helps memory. We investigated the mechanisms underlying the eyeclosure effect by exposing 80 eyewitnesses to different types of distraction during the witness interview: blank screen (control), eyes closed, visual distraction, and auditory distraction. We examined the cognitive load hypothesis by comparing any type of distraction (visual or auditory) with minimal distraction (blank screen or eyes closed). We found recall to be significantly better when distraction was minimal, providing evidence that eyeclosure reduces cognitive load. We examined the modality-specific interference hypothesis by comparing the effects of visual and auditory distraction on recall of visual and auditory information. Visual and auditory distraction selectively impaired memory for information presented in the same modality, supporting the role of visualisation in the eyeclosure effect. Analysis of recall in terms of grain size revealed that recall of basic information about the event was robust, whereas recall of specific details was prone to both general and modality-specific disruptions.

System for monitoring the growth of crystalline films on stationary substrates

DOEpatents

Sheldon, Peter

1995-01-01

A system for monitoring the growth of crystalline films on stationary or rotating substrates includes a combination of some or all of the elements including a photodiode sensor for detecting the intensity of incoming light and converting it to a measurable current, a lens for focusing the RHEED pattern emanating from the phosphor screen onto the photodiode, an interference filter for filtering out light other than that which emanates from the phosphor screen, a current amplifier for amplifying and converting the current produced by the photodiode into a voltage, a computer for receiving the amplified photodiode current for RHEED data analysis, and a graphite impregnated triax cable for improving the signal to noise ratio obtained while sampling a stationary or rotating substrate. A rotating stage for supporting the substrate with diametrically positioned electron beam apertures and an optically encoded shaft can also be used to accommodate rotation of the substrate during measurement.

System for monitoring the growth of crystalline films on stationary substrates

DOEpatents

Sheldon, Peter

1996-01-01

A system for monitoring the growth of crystalline films on stationary or rotating substrates includes a combination of some or all of the elements including a photodiode sensor for detecting the intensity of incoming light and converting it to a measurable current, a lens for focusing the RHEED pattern emanating from the phosphor screen onto the photodiode, an interference filter for filtering out light other than that which emanates from the phosphor screen, a current amplifier for amplifying and convening the current produced by the photodiode into a voltage, a computer for receiving the amplified photodiode current for RHEED data analysis, and a graphite impregnated triax cable for improving the signal to noise ratio obtained while sampling a stationary or rotating substrate. A rotating stage for supporting the substrate with diametrically positioned electron beam apertures and an optically encoded shaft can also be used to accommodate rotation of the substrate during measurement.

Evaluation of hydrate-screening methods.

PubMed

Cui, Yong; Yao, Erica

2008-07-01

The purpose of this work is to evaluate the effectiveness and reliability of several common hydrate-screening techniques, and to provide guidelines for designing hydrate-screening programs for new drug candidates. Ten hydrate-forming compounds were selected as model compounds and six hydrate-screening approaches were applied to these compounds in an effort to generate their hydrate forms. The results prove that no screening approach is universally effective in finding hydrates for small organic compounds. Rather, a combination of different methods should be used to improve screening reliability. Among the approaches tested, the dynamic water vapor sorption/desorption isotherm (DVI) method and storage under high humidity (HH) yielded 60-70% success ratios, the lowest among all techniques studied. The risk of false negatives arises in particular for nonhygroscopic compounds. On the other hand, both slurry in water (Slurry) and temperature cycling of aqueous suspension (TCS) showed high success rates (90%) with some exceptions. The mixed solvent systems (MSS) procedure also achieved high success rates (90%), and was found to be more suitable for water-insoluble compounds. For water-soluble compounds, MSS may not be the best approach because recrystallization is difficult in solutions with high water activity. Finally, vapor diffusion (VD) yielded a reasonably high success ratio in finding hydrates (80%). However, this method suffers from experimental difficulty and unreliable results for either highly water-soluble or water-insoluble compounds. This study indicates that a reliable hydrate-screening strategy should take into consideration the solubility and hygroscopicity of the compounds studied. A combination of the Slurry or TCS method with the MSS procedure could provide a screening strategy with reasonable reliability.

RNAi screening comes of age: improved techniques and complementary approaches

PubMed Central

Mohr, Stephanie E.; Smith, Jennifer A.; Shamu, Caroline E.; Neumüller, Ralph A.; Perrimon, Norbert

2014-01-01

Gene silencing through sequence-specific targeting of mRNAs by RNAi has enabled genome-wide functional screens in cultured cells and in vivo in model organisms. These screens have resulted in the identification of new cellular pathways and potential drug targets. Considerable progress has been made to improve the quality of RNAi screen data through the development of new experimental and bioinformatics approaches. The recent availability of genome-editing strategies, such as the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system, when combined with RNAi, could lead to further improvements in screen data quality and follow-up experiments, thus promoting our understanding of gene function and gene regulatory networks. PMID:25145850

Applications of chemogenomic library screening in drug discovery.

PubMed

Jones, Lyn H; Bunnage, Mark E

2017-04-01

The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype. In this Review, we describe opportunities for chemogenomic screening to considerably expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Other applications are explored, including drug repositioning, predictive toxicology and the discovery of novel pharmacological modalities.

Personalized drug discovery: HCA approach optimized for rare diseases at Tel Aviv University.

PubMed

Solmesky, Leonardo J; Weil, Miguel

2014-03-01

The Cell screening facility for personalized medicine (CSFPM) at Tel Aviv University in Israel is devoted to screening small molecules libraries for finding new drugs for rare diseases using human cell based models. The main strategy of the facility is based on smartly reducing the size of the compounds collection in similarity clusters and at the same time keeping high diversity of pharmacophores. This strategy allows parallel screening of several patient derived - cells in a personalized screening approach. The tested compounds are repositioned drugs derived from collections of phase III and FDA approved small molecules. In addition, the facility carries screenings using other chemical libraries and toxicological characterizations of nanomaterials.

Laser interference microscopy: a novel approach to the visualization of structural changes in myelin during the propagation of nerve impulses

NASA Astrophysics Data System (ADS)

Yusipovich, A. I.; Cherkashin, A. A.; Verdiyan, E. E.; Sogomonyan, I. A.; Maksimov, G. V.

2016-08-01

We used 3D phase images obtained by laser interference microscopy (LIM) for ex vivo evaluation of changes in the structure of myelin during repetitive stimulation. In this work we propose a simple model of myelinated nerve fiber (mNF), which describes phase images as a result of different geometry and membrane-to-cytoplasm ratio in various regions, particularly, the internode and paranodal-nodal-paranodal region, including the node of Ranvier. Application of this model provides clear interpretation of the phase images and also demonstrates that repetitive action potentials are accompanied by structural changes in myelin in the internode and cytoplasmic modification in the node of Ranvier. The first 20 min of stimulation did not induce significant changes in the measured parameters, but then the optical path difference at the periphery of mNF and at the node of Ranvier declined reversibly. We believe that our model is also applicable to other modifications of interference and non-interference imaging.

Application of the correlation constrained multivariate curve resolution alternating least-squares method for analyte quantitation in the presence of unexpected interferences using first-order instrumental data.

PubMed

Goicoechea, Héctor C; Olivieri, Alejandro C; Tauler, Romà

2010-03-01

Correlation constrained multivariate curve resolution-alternating least-squares is shown to be a feasible method for processing first-order instrumental data and achieve analyte quantitation in the presence of unexpected interferences. Both for simulated and experimental data sets, the proposed method could correctly retrieve the analyte and interference spectral profiles and perform accurate estimations of analyte concentrations in test samples. Since no information concerning the interferences was present in calibration samples, the proposed multivariate calibration approach including the correlation constraint facilitates the achievement of the so-called second-order advantage for the analyte of interest, which is known to be present for more complex higher-order richer instrumental data. The proposed method is tested using a simulated data set and two experimental data systems, one for the determination of ascorbic acid in powder juices using UV-visible absorption spectral data, and another for the determination of tetracycline in serum samples using fluorescence emission spectroscopy.

Drilling Deeper into tooth brushing skills: Is proactive interference an under-recognized factor in oral hygiene behavior change?

PubMed

Thavarajah, Rooban; Kumar, Madan; Mohandoss, Anusa Arunachalam; Vernon, Lance T

2015-09-01

Proper tooth brushing is a seemingly simple motor activity that can promote oral health. Applying health theories, such as the Information-Motivation-Behavioral Skills (IMB) model, Motivational Interviewing (MI) and Integrated Health Coaching (IHC), may help optimize tooth brushing technique in those with suboptimal skills. Some motor activities, including tooth brushing, may over time become rote and unconscious actions, such that an existing habit can inhibit new learning, i.e., exert proactive interference on learning the new skill. Proactive interference may impede the acquisition of new tooth brushing skills; thus, in this report, we: (1) Review how the habit of tooth brushing is formed; (2) Postulate how proactive interference could impede the establishment of proper tooth brushing retraining; (3) Discuss the merits of this hypothesis; and (4) Provide guidance for future work in this topic within the context of an approach to behavior change that integrates IMB, MI and IHC methodology.

Drilling Deeper into tooth brushing skills: Is proactive interference an under-recognized factor in oral hygiene behavior change?

PubMed Central

Thavarajah, Rooban; Kumar, Madan; Mohandoss, Anusa Arunachalam

2015-01-01

Proper tooth brushing is a seemingly simple motor activity that can promote oral health. Applying health theories, such as the Information-Motivation-Behavioral Skills (IMB) model, Motivational Interviewing (MI) and Integrated Health Coaching (IHC), may help optimize tooth brushing technique in those with suboptimal skills. Some motor activities, including tooth brushing, may over time become rote and unconscious actions, such that an existing habit can inhibit new learning, i.e., exert proactive interference on learning the new skill. Proactive interference may impede the acquisition of new tooth brushing skills; thus, in this report, we: (1) Review how the habit of tooth brushing is formed; (2) Postulate how proactive interference could impede the establishment of proper tooth brushing retraining; (3) Discuss the merits of this hypothesis; and (4) Provide guidance for future work in this topic within the context of an approach to behavior change that integrates IMB, MI and IHC methodology. PMID:26457238

On-chip interference of single photons from an embedded quantum dot and an external laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prtljaga, N., E-mail: n.prtljaga@sheffield.ac.uk; Bentham, C.; O'Hara, J.

2016-06-20

In this work, we demonstrate the on-chip two-photon interference between single photons emitted by a single self-assembled InGaAs quantum dot and an external laser. The quantum dot is embedded within one arm of an air-clad directional coupler which acts as a beam-splitter for incoming light. Photons originating from an attenuated external laser are coupled to the second arm of the beam-splitter and then combined with the quantum dot photons, giving rise to two-photon quantum interference between dissimilar sources. We verify the occurrence of on-chip Hong-Ou-Mandel interference by cross-correlating the optical signal from the separate output ports of the directional coupler.more » This experimental approach allows us to use a classical light source (laser) to assess in a single step the overall device performance in the quantum regime and probe quantum dot photon indistinguishability on application realistic time scales.« less

Memory Reconsolidation Interference as an Emerging Treatment for Emotional Disorders: Strengths, Limitations, Challenges and Opportunities

PubMed Central

Beckers, Tom; Kindt, Merel

2016-01-01

Experimental research on emotional memory reconsolidation interference, or the induction of amnesia for previously established emotional memory, has a long tradition, but the potential of that research for the development of novel interventions to treat psychological disorders has been recognized only recently. Here we provide an overview of basic research and clinical studies on emotional memory reconsolidation interference. We point out specific advantages of interventions based on memory reconsolidation interference over traditional treatment for emotional disorders. We also explain how findings from basic research suggest limitations and challenges to clinical translation that may help to understand why clinical trials have met with mixed success so far and how their success can be increased. In closing, we preview new intervention approaches beyond the induction of amnesia that the phenomenon of memory reconsolidation may afford for alleviating the burden imposed by emotional memories and comment on theoretical controversies regarding the nature of memory reconsolidation. PMID:28375725

The use of Hemastix and the subsequent lack of DNA recovery using the Promega DNA IQ system.

PubMed

Poon, Hiron; Elliott, Jim; Modler, Jeff; Frégeau, Chantal

2009-11-01

Following implementation of our automated process incorporating the Promega DNA IQ system as a DNA extraction method, a large number of blood-containing exhibits failed to produce DNA. These exhibits had been tested with the Hemastix reagent strip, commonly used by police investigators and forensic laboratories as a screening test for blood. Some exhibits were even tainted green following transfer of the presumptive test reagents onto the samples. A series of experiments were carried out to examine the effect of the Hemastix chemistries on the DNA IQ system. Our results indicate that one or more chemicals imbedded in the Hemastix reagent strip severely reduce the ability to recover DNA from any suspected stain using the DNA IQ magnetic bead technology. The 3,3',5,5'-tetramethylbenzidine (TMB) used as the reporting dye appears to interact with the magnetic beads to prevent DNA recovery. Hydrogen peroxide does not seem to be involved. The Hemastix chemistries do not interfere in any way with DNA extraction performed using phenol-chloroform. The incompatibility of the Hemastix chemistries on the DNA IQ system forced us to adopt an indirect approach using filter paper to carry out the presumptive test.

Efficient IDUA Gene Mutation Detection with Combined Use of dHPLC and Dried Blood Samples

PubMed Central

Duarte, Ana Joana; Vieira, Luis

2013-01-01

Objectives. Development of a simple mutation directed method in order to allow lowering the cost of mutation testing using an easily obtainable biological material. Assessment of the feasibility of such method was tested using a GC-rich amplicon. Design and Methods. A method of denaturing high-performance liquid chromatography (dHPLC) was improved and implemented as a technique for the detection of variants in exon 9 of the IDUA gene. The optimized method was tested in 500 genomic DNA samples obtained from dried blood spots (DBS). Results. With this dHPLC approach it was possible to detect different variants, including the common p.Trp402Ter mutation in the IDUA gene. The high GC content did not interfere with the resolution and reliability of this technique, and discrimination of G-C transversions was also achieved. Conclusion. This PCR-based dHPLC method is proved to be a rapid, a sensitive, and an excellent option for screening numerous samples obtained from DBS. Furthermore, it resulted in the consistent detection of clearly distinguishable profiles of the common p.Trp402Ter IDUA mutation with an advantageous balance of cost and technical requirements. PMID:27335677

Radiography for intensive care: participatory process analysis in a PACS-equipped and film/screen environment

NASA Astrophysics Data System (ADS)

Peer, Regina; Peer, Siegfried; Sander, Heike; Marsolek, Ingo; Koller, Wolfgang; Pappert, Dirk; Hierholzer, Johannes

2002-05-01

If new technology is introduced into medical practice it must prove to make a difference. However traditional approaches of outcome analysis failed to show a direct benefit of PACS on patient care and economical benefits are still in debate. A participatory process analysis was performed to compare workflow in a film based hospital and a PACS environment. This included direct observation of work processes, interview of involved staff, structural analysis and discussion of observations with staff members. After definition of common structures strong and weak workflow steps were evaluated. With a common workflow structure in both hospitals, benefits of PACS were revealed in workflow steps related to image reporting with simultaneous image access for ICU-physicians and radiologists, archiving of images as well as image and report distribution. However PACS alone is not able to cover the complete process of 'radiography for intensive care' from ordering of an image till provision of the final product equals image + report. Interference of electronic workflow with analogue process steps such as paper based ordering reduces the potential benefits of PACS. In this regard workflow modeling proved to be very helpful for the evaluation of complex work processes linking radiology and the ICU.

The Stroop color-word test: influence of age, sex, and education; and normative data for a large sample across the adult age range.

PubMed

Van der Elst, Wim; Van Boxtel, Martin P J; Van Breukelen, Gerard J P; Jolles, Jelle

2006-03-01

The Stroop Color-Word Test was administered to 1,856 cognitively screened, healthy Dutch speaking participants aged 24 to 81 years. The effects of age, gender, and education on Stroop test performance were investigated to adequately stratify the normative data. The results showed that especially the speed-dependent Stroop scores (time to complete a subtest), rather than the accuracy measures (the errors made per Stroop sub-task), were profoundly affected by the demographic variables. In addition to the main effects of the demographic variables, an Age Low Level of Education interaction was found for the Error III and the Stroop Interference scores. This suggests that executive function, as measured by the Stroop test, declines with age and that the decline is more pronounced in people with a low level of education. This is consistent with the reserve hypothesis of brain aging (i.e., that education generates reserve capacity against the damaging effects of aging on brain functions). Normative Stroop data were established using both a regression-based and traditional approach, and the appropriateness of both methods for generating normative data is discussed.

No Menstrual Cyclicity in Mood and Interpersonal Behaviour in Nine Women with Self-Reported Premenstrual Syndrome.

PubMed

Bosman, Renske C; Albers, Casper J; de Jong, Jettie; Batalas, Nikolaos; Aan Het Rot, Marije

2018-06-06

Before diagnosing premenstrual dysphoric disorder (PMDD), 2 months of prospective assessment are required to confirm menstrual cyclicity in symptoms. For a diagnosis of premenstrual syndrome (PMS), this is not required. Women with PMDD and PMS often report that their symptoms interfere with mood and social functioning, and are said to show cyclical changes in interpersonal behaviour, but this has not been examined using a prospective approach. We sampled cyclicity in mood and interpersonal behaviour for 2 months in women with self- reported PMS. Participants met the criteria for PMS on the Premenstrual Symptoms Screening Tool (PSST), a retrospective questionnaire. For 2 menstrual cycles, after each social interaction, they used the online software TEMPEST to record on their smartphones how they felt and behaved. We examined within-person variability in negative affect, positive affect, quarrelsomeness, and agreeableness. Participants evaluated TEMPEST as positive. However, we found no evidence for menstrual cyclicity in mood and interpersonal behaviour in any of the individual women (n = 9). Retrospective questionnaires such as the PSST may lead to oversampling of PMS. The diagnosis of PMS, like that of PMDD, might require 2 months of prospective assessment. © 2018 S. Karger AG, Basel.

Thin Fresnel zone plate lenses for focusing underwater sound

NASA Astrophysics Data System (ADS)

Calvo, David C.; Thangawng, Abel L.; Nicholas, Michael; Layman, Christopher N.

2015-07-01

A Fresnel zone plate (FZP) lens of the Soret type creates a focus by constructive interference of waves diffracted through open annular zones in an opaque screen. For underwater sound below MHz frequencies, a large FZP that blocks sound using high-impedance, dense materials would have practical disadvantages. We experimentally and numerically investigate an alternative approach of creating a FZP with thin (0.4λ) acoustically opaque zones made of soft silicone rubber foam attached to a thin (0.1λ) transparent rubber substrate. An ultra-thin (0.0068λ) FZP that achieves higher gain is also proposed and simulated which uses low-volume fraction, bubble-like resonant air ring cavities to construct opaque zones. Laboratory measurements at 200 kHz indicate that the rubber foam can be accurately modeled as a lossy fluid with an acoustic impedance approximately 1/10 that of water. Measured focal gains up to 20 dB agree with theoretical predictions for normal and oblique incidence. The measured focal radius of 0.68λ (peak-to-null) agrees with the Rayleigh diffraction limit prediction of 0.61 λ/NA (NA = 0.88) for a low-aberration lens.

Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment?

PubMed Central

Gloeckl, Rainer; Vogiatzis, Ioannis; Kenn, Klaus

2017-01-01

Cognitive impairment is highly prevalent in patients with COPD and demonstrates multiple detrimental effects on many aspects of patient state and therapeutic outcomes. It is attributed to several overlapping pathophysiological factors, with the most common being the low level of oxygen saturation due to respiratory insufficiency. Despite the impact of cognitive impairment on clinical outcomes, the screening for coexisting cognitive deficits which may interfere with the successful progress of respiratory treatment is yet neglected. There is a special consideration that cognitive deficits should be taken into account when developing respiratory therapy plans. Cognitively impaired patients are likely to require more support and have need of an individualised respiratory care plan which can also be beneficial for their cognitive deficits. Pulmonary rehabilitation as a multidisciplinary approach could be prioritised for COPD patients with cognitive impairment. Educational aims To illustrate the common signs of cognitive impairment and define potential associations between lung and cognitive dysfunction. To illustrate the potential influence of cognitive deficits on the optimal progress of respiratory therapy. To illustrate the importance of cognitive evaluation as part of a comprehensive clinical assessment for patients suspected of suffering cognitive impairment. PMID:29184593

Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors

PubMed Central

Bonomo, Silvia; Hansen, Cecilie H.; Petrunak, Elyse M.; Scott, Emily E.; Styrishave, Bjarne; Jørgensen, Flemming Steen; Olsen, Lars

2016-01-01

Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells. PMID:27406023

Thin Fresnel zone plate lenses for focusing underwater sound

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calvo, David C., E-mail: david.calvo@nrl.navy.mil; Thangawng, Abel L.; Nicholas, Michael

A Fresnel zone plate (FZP) lens of the Soret type creates a focus by constructive interference of waves diffracted through open annular zones in an opaque screen. For underwater sound below MHz frequencies, a large FZP that blocks sound using high-impedance, dense materials would have practical disadvantages. We experimentally and numerically investigate an alternative approach of creating a FZP with thin (0.4λ) acoustically opaque zones made of soft silicone rubber foam attached to a thin (0.1λ) transparent rubber substrate. An ultra-thin (0.0068λ) FZP that achieves higher gain is also proposed and simulated which uses low-volume fraction, bubble-like resonant air ringmore » cavities to construct opaque zones. Laboratory measurements at 200 kHz indicate that the rubber foam can be accurately modeled as a lossy fluid with an acoustic impedance approximately 1/10 that of water. Measured focal gains up to 20 dB agree with theoretical predictions for normal and oblique incidence. The measured focal radius of 0.68λ (peak-to-null) agrees with the Rayleigh diffraction limit prediction of 0.61 λ/NA (NA = 0.88) for a low-aberration lens.« less

Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells.

PubMed

Carreras Puigvert, Jordi; von Stechow, Louise; Siddappa, Ramakrishnaiah; Pines, Alex; Bahjat, Mahnoush; Haazen, Lizette C J M; Olsen, Jesper V; Vrieling, Harry; Meerman, John H N; Mullenders, Leon H F; van de Water, Bob; Danen, Erik H J

2013-01-22

In pluripotent stem cells, DNA damage triggers loss of pluripotency and apoptosis as a safeguard to exclude damaged DNA from the lineage. An intricate DNA damage response (DDR) signaling network ensures that the response is proportional to the severity of the damage. We combined an RNA interference screen targeting all kinases, phosphatases, and transcription factors with global transcriptomics and phosphoproteomics to map the DDR in mouse embryonic stem cells treated with the DNA cross-linker cisplatin. Networks derived from canonical pathways shared in all three data sets were implicated in DNA damage repair, cell cycle and survival, and differentiation. Experimental probing of these networks identified a mode of DNA damage-induced Wnt signaling that limited apoptosis. Silencing or deleting the p53 gene demonstrated that genotoxic stress elicited Wnt signaling in a p53-independent manner. Instead, this response occurred through reduced abundance of Csnk1a1 (CK1α), a kinase that inhibits β-catenin. Together, our findings reveal a balance between p53-mediated elimination of stem cells (through loss of pluripotency and apoptosis) and Wnt signaling that attenuates this response to tune the outcome of the DDR.

Chronic Heart Failure: We Are Fighting the Battle, but Are We Winning the War?

PubMed Central

Atherton, John J.

2012-01-01

Heart failure represents an end-stage phenotype of a number of cardiovascular diseases and is generally associated with a poor prognosis. A number of organized battles fought over the last two to three decades have resulted in considerable advances in treatment including the use of drugs that interfere with neurohormonal activation and device-based therapies such as implantable cardioverter defibrillators and cardiac resynchronization therapy. Despite this, the prevalence of heart failure continues to rise related to both the aging population and better survival in patients with cardiovascular disease. Registries have identified treatment gaps and variation in the application of evidenced-based practice, including the use of echocardiography and prescribing of disease-modifying drugs. Quality initiatives often coupled with multidisciplinary, heart failure disease management promote self-care and minimize variation in the application of evidenced-based practice leading to better long-term clinical outcomes. However, to address the rising prevalence of heart failure and win the war, we must also turn our attention to disease prevention. A combined approach is required that includes public health measures applied at a population level and screening strategies to identify individuals at high risk of developing heart failure in the future. PMID:24278681

Retroactive interference in short-term memory and the word-length effect.

PubMed

Campoy, Guillermo

2011-09-01

Two experiments investigated the possibility that the word-length effect in short-term memory (STM) is a consequence of long words generating a greater level of retroactive interference than shorter words. In Experiment 1, six-word lists were auditorily presented under articulatory suppression for immediate serial reconstruction of only the first three words. These three words were always drawn from a single set of middle-length words, whereas the last three positions were occupied by either short or long interfering words. The results showed worse memory performance when the to-be-remembered words were followed by long words. In Experiment 2, a recent-probes task was used, in which recent negative probes matched a target word in trial n-2. The results showed lower levels of proactive interference when trial n-1 involved long words instead of short words, suggesting that long words displaced previous STM content to a greater extent. By two different experimental approaches, therefore, this study shows that long words produce more retroactive interference than short words, supporting an interference-based account for the word-length effect. Copyright © 2011 Elsevier B.V. All rights reserved.

Fast interaction of atoms with crystal surfaces: coherent lighting

NASA Astrophysics Data System (ADS)

Gravielle, M. S.

2017-11-01

Quantum coherence of incident waves results essential for the observation of interference patterns in grazing incidence fast atom diffraction (FAD). In this work we investigate the influence of the impact energy and projectile mass on the transversal length of the surface area that is coherently illuminated by the atomic beam, after passing through a collimating aperture. Such a transversal coherence length controls the general features of the interference structures, being here derived by means of the Van Cittert-Zernike theorem. The coherence length is then used to build the initial coherent wave packet within the Surface Initial Value Representation (SIVR) approximation. The SIVR approach is applied to fast He and Ne atoms impinging grazingly on a LiF(001) surface along a low-indexed crystallographic direction. We found that with the same collimating setup, by varying the impact energy we would be able to control the interference mechanism that prevails in FAD patterns, switching between inter-cell and unit-cell interferences. These findings are relevant to use FAD spectra adequately as a surface analysis tool, as well as to choose the appropriate collimating scheme for the observation of interference effects in a given collision system.

Reduction of polyatomic interferences in ICP-MS by collision/reaction cell (CRC-ICP-MS) techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eiden, Greg C; Barinaga, Charles J; Koppenaal, David W

2012-05-01

Polyatomic and other spectral interferences in plasma source mass spectrometry (PSMS) can be dramatically reduced using collision and reaction cells (CRC). These devices have been used for decades in fundamental studies of ion-molecule chemistry, but have only recently been applied to PSMS. Benefits of this approach as applied in inductively coupled plasma MS (ICP-MS) include interference reduction, isobar separation, and thermalization/focusing of ions. Novel ion-molecule chemistry schemes are now routinely designed and empirically evaluated with relative ease. These “chemical resolution” techniques can avert interferences requiring mass spectral resolutions of >600,000 (m/m). Purely physical ion beam processes, including collisional dampening andmore » collisional dissociation, are also employed to provide improved sensitivity, resolution, and spectral simplicity. CRC techniques are now firmly entrenched in current-day ICP-MS technology, enabling unprecedented flexibility and freedom from many spectral interferences. A significant body of applications has now been reported in the literature. CRC techniques are found to be most useful for specialized or difficult analytical needs and situations, and are employed in both single- and multi-element determination modes.« less

Population newborn screening for inherited metabolic disease: current UK perspectives.

PubMed

Green, A; Pollitt, R J

1999-06-01

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

A practical approach to screen for authorised and unauthorised genetically modified plants.

PubMed

Waiblinger, Hans-Ulrich; Grohmann, Lutz; Mankertz, Joachim; Engelbert, Dirk; Pietsch, Klaus

2010-03-01

In routine analysis, screening methods based on real-time PCR are most commonly used for the detection of genetically modified (GM) plant material in food and feed. In this paper, it is shown that the combination of five DNA target sequences can be used as a universal screening approach for at least 81 GM plant events authorised or unauthorised for placing on the market and described in publicly available databases. Except for maize event LY038, soybean events DP-305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of the five genetic elements has been inserted in these GM plants and is targeted by this screening approach. For the detection of these sequences, fully validated real-time PCR methods have been selected. A screening table is presented that describes the presence or absence of the target sequences for most of the listed GM plants. These data have been verified either theoretically according to available databases or experimentally using available reference materials. The screening table will be updated regularly by a network of German enforcement laboratories.

Point-of-care urine tests for smoking status and isoniazid treatment monitoring in adult patients.

PubMed

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference.

Point-of-Care Urine Tests for Smoking Status and Isoniazid Treatment Monitoring in Adult Patients

PubMed Central

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Background Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. Methodology/Principal Findings 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. Conclusions IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference. PMID:23029310

Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence.

PubMed

Disney, Matthew D; Angelbello, Alicia J

2016-12-20

The discovery of RNA catalysis in the 1980s and the dissemination of the human genome sequence at the start of this century inspired investigations of the regulatory roles of noncoding RNAs in biology. In fact, the Encyclopedia of DNA Elements (ENCODE) project has shown that only 1-2% of the human genome encodes protein, yet 75% is transcribed into RNA. Functional studies both preceding and following the ENCODE project have shown that these noncoding RNAs have important roles in regulating gene expression, developmental timing, and other critical functions. RNA's diverse roles are often a consequence of the various folds that it adopts. The single-stranded nature of the biopolymer enables it to adopt intramolecular folds with noncanonical pairings to lower its free energy. These folds can be scaffolds to bind proteins or to form frameworks to interact with other RNAs. Not surprisingly, dysregulation of certain noncoding RNAs has been shown to be causative of disease. Given this as the background, it is easy to see why it would be useful to develop methods that target RNA and manipulate its biology in rational and predictable ways. The antisense approach has afforded strategies to target RNAs via Watson-Crick base pairing and has typically focused on targeting partially unstructured regions of RNA. Small molecule strategies to target RNA would be desirable not only because compounds could be lead optimized via medicinal chemistry but also because structured regions within an RNA of interest could be targeted to directly interfere with RNA folds that contribute to disease. Additionally, small molecules have historically been the most successful drug candidates. Until recently, the ability to design small molecules that target non-ribosomal RNAs has been elusive, creating the perception that they are "undruggable". In this Account, approaches to demystify targeting RNA with small molecules are described. Rather than bulk screening for compounds that bind to singular targets, which is the purview of the pharmaceutical industry and academic institutions with high throughput screening facilities, we focus on methods that allow for the rational design of small molecules toward biological RNAs. One enabling and foundational technology that has been developed is two-dimensional combinatorial screening (2DCS), a library-versus-library selection approach that allows the identification of the RNA motif binding preferences of small molecules from millions of combinations. A landscape map of the 2DCS-defined and annotated RNA motif-small molecule interactions is then placed into Inforna, a computational tool that allows one to mine these interactions against an RNA of interest or an entire transcriptome. Indeed, this approach has been enabled by tools to annotate RNA structure from sequence, an invaluable asset to the RNA community and this work, and has allowed for the rational identification of "druggable" RNAs in a target agnostic fashion.

Adaptive Gaussian mixture models for pre-screening in GPR data

NASA Astrophysics Data System (ADS)

Torrione, Peter; Morton, Kenneth, Jr.; Besaw, Lance E.

2011-06-01

Due to the large amount of data generated by vehicle-mounted ground penetrating radar (GPR) antennae arrays, advanced feature extraction and classification can only be performed on a small subset of data during real-time operation. As a result, most GPR based landmine detection systems implement "pre-screening" algorithms to processes all of the data generated by the antennae array and identify locations with anomalous signatures for more advanced processing. These pre-screening algorithms must be computationally efficient and obtain high probability of detection, but can permit a false alarm rate which might be higher than the total system requirements. Many approaches to prescreening have previously been proposed, including linear prediction coefficients, the LMS algorithm, and CFAR-based approaches. Similar pre-screening techniques have also been developed in the field of video processing to identify anomalous behavior or anomalous objects. One such algorithm, an online k-means approximation to an adaptive Gaussian mixture model (GMM), is particularly well-suited to application for pre-screening in GPR data due to its computational efficiency, non-linear nature, and relevance of the logic underlying the algorithm to GPR processing. In this work we explore the application of an adaptive GMM-based approach for anomaly detection from the video processing literature to pre-screening in GPR data. Results with the ARA Nemesis landmine detection system demonstrate significant pre-screening performance improvements compared to alternative approaches, and indicate that the proposed algorithm is a complimentary technique to existing methods.

GNSS Space-Time Interference Mitigation and Attitude Determination in the Presence of Interference Signals

PubMed Central

Daneshmand, Saeed; Jahromi, Ali Jafarnia; Broumandan, Ali; Lachapelle, Gérard

2015-01-01

The use of Space-Time Processing (STP) in Global Navigation Satellite System (GNSS) applications is gaining significant attention due to its effectiveness for both narrowband and wideband interference suppression. However, the resulting distortion and bias on the cross correlation functions due to space-time filtering is a major limitation of this technique. Employing the steering vector of the GNSS signals in the filter structure can significantly reduce the distortion on cross correlation functions and lead to more accurate pseudorange measurements. This paper proposes a two-stage interference mitigation approach in which the first stage estimates an interference-free subspace before the acquisition and tracking phases and projects all received signals into this subspace. The next stage estimates array attitude parameters based on detecting and employing GNSS signals that are less distorted due to the projection process. Attitude parameters enable the receiver to estimate the steering vector of each satellite signal and use it in the novel distortionless STP filter to significantly reduce distortion and maximize Signal-to-Noise Ratio (SNR). GPS signals were collected using a six-element antenna array under open sky conditions to first calibrate the antenna array. Simulated interfering signals were then added to the digitized samples in software to verify the applicability of the proposed receiver structure and assess its performance for several interference scenarios. PMID:26016909

Testing complex animal cognition: Concept learning, proactive interference, and list memory.

PubMed

Wright, Anthony A

2018-01-01

This article describes an approach for assessing and comparing complex cognition in rhesus monkeys and pigeons by training them in a sequence of synergistic tasks, each yielding a whole function for enhanced comparisons. These species were trained in similar same/different tasks with expanding training sets (8, 16, 32, 64, 128 … 1024 pictures) followed by novel-stimulus transfer eventually resulting in full abstract-concept learning. Concept-learning functions revealed better rhesus transfer throughout and full concept learning at the 128 set, versus pigeons at the 256 set. They were then tested in delayed same/different tasks for proactive interference by inserting occasional tests within trial-unique sessions where the test stimulus matched a previous sample stimulus (1, 2, 4, 8, 16 trials prior). Proactive-interference functions revealed time-based interference for pigeons (1, 10 s delays), but event-based interference for rhesus (no effect of 1, 10, 20 s delays). They were then tested in list-memory tasks by expanding the sample to four samples in trial-unique sessions (minimizing proactive interference). The four-item, list-memory functions revealed strong recency memory at short delays, gradually changing to strong primacy memory at long delays over 30 s for rhesus, and 10 s for pigeons. Other species comparisons and future directions are discussed. © 2018 Society for the Experimental Analysis of Behavior.