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Sample records for broad spectrum microarray

  1. Broad spectrum microarray for fingerprint-based bacterial species identification

    Directory of Open Access Journals (Sweden)

    Frey Jürg E

    2010-02-01

    Full Text Available Abstract Background Microarrays are powerful tools for DNA-based molecular diagnostics and identification of pathogens. Most target a limited range of organisms and are based on only one or a very few genes for specific identification. Such microarrays are limited to organisms for which specific probes are available, and often have difficulty discriminating closely related taxa. We have developed an alternative broad-spectrum microarray that employs hybridisation fingerprints generated by high-density anonymous markers distributed over the entire genome for identification based on comparison to a reference database. Results A high-density microarray carrying 95,000 unique 13-mer probes was designed. Optimized methods were developed to deliver reproducible hybridisation patterns that enabled confident discrimination of bacteria at the species, subspecies, and strain levels. High correlation coefficients were achieved between replicates. A sub-selection of 12,071 probes, determined by ANOVA and class prediction analysis, enabled the discrimination of all samples in our panel. Mismatch probe hybridisation was observed but was found to have no effect on the discriminatory capacity of our system. Conclusions These results indicate the potential of our genome chip for reliable identification of a wide range of bacterial taxa at the subspecies level without laborious prior sequencing and probe design. With its high resolution capacity, our proof-of-principle chip demonstrates great potential as a tool for molecular diagnostics of broad taxonomic groups.

  2. Application of broad-spectrum resequencing microarray for genotyping rhabdoviruses.

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    Dacheux, Laurent; Berthet, Nicolas; Dissard, Gabriel; Holmes, Edward C; Delmas, Olivier; Larrous, Florence; Guigon, Ghislaine; Dickinson, Philip; Faye, Ousmane; Sall, Amadou A; Old, Iain G; Kong, Katherine; Kennedy, Giulia C; Manuguerra, Jean-Claude; Cole, Stewart T; Caro, Valérie; Gessain, Antoine; Bourhy, Hervé

    2010-09-01

    The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family Rhabdoviridae. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family Rhabdoviridae were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world.

  3. Application of Broad-Spectrum Resequencing Microarray for Genotyping Rhabdoviruses▿

    Science.gov (United States)

    Dacheux, Laurent; Berthet, Nicolas; Dissard, Gabriel; Holmes, Edward C.; Delmas, Olivier; Larrous, Florence; Guigon, Ghislaine; Dickinson, Philip; Faye, Ousmane; Sall, Amadou A.; Old, Iain G.; Kong, Katherine; Kennedy, Giulia C.; Manuguerra, Jean-Claude; Cole, Stewart T.; Caro, Valérie; Gessain, Antoine; Bourhy, Hervé

    2010-01-01

    The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family Rhabdoviridae. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family Rhabdoviridae were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world. PMID:20610710

  4. Broad spectrum bioactive sunscreens.

    Science.gov (United States)

    Velasco, Maria Valéria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, André Rolim

    2008-11-03

    The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm.

  5. See what you eat--broad GMO screening with microarrays.

    Science.gov (United States)

    von Götz, Franz

    2010-03-01

    Despite the controversy of whether genetically modified organisms (GMOs) are beneficial or harmful for humans, animals, and/or ecosystems, the number of cultivated GMOs is increasing every year. Many countries and federations have implemented safety and surveillance systems for GMOs. Potent testing technologies need to be developed and implemented to monitor the increasing number of GMOs. First, these GMO tests need to be comprehensive, i.e., should detect all, or at least the most important, GMOs on the market. This type of GMO screening requires a high degree of parallel tests or multiplexing. To date, DNA microarrays have the highest number of multiplexing capabilities when nucleic acids are analyzed. This trend article focuses on the evolution of DNA microarrays for GMO testing. Over the last 7 years, combinations of multiplex PCR detection and microarray detection have been developed to qualitatively assess the presence of GMOs. One example is the commercially available DualChip GMO (Eppendorf, Germany; http://www.eppendorf-biochip.com), which is the only GMO screening system successfully validated in a multicenter study. With use of innovative amplification techniques, promising steps have recently been taken to make GMO detection with microarrays quantitative.

  6. Broad Spectrum Sanitizing Wipes with Food Additives, Phase I

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    National Aeronautics and Space Administration — Microcide proposes to develop novel multipurpose non-toxic sanitizing wipes that are aqueous based, have shelf life of 3-5 years, have broad spectrum microbicidal...

  7. The precipitation synthesis of broad-spectrum UV absorber nanoceria

    International Nuclear Information System (INIS)

    Nurhasanah, Iis; Sutanto, Heri; Puspaningrum, Nurul Wahyu

    2013-01-01

    In this paper the possibility of nanoceria as broad-spectrum UV absorber was evaluated. Nanoceria were synthesized by precipitation process from cerium nitrate solution and ammonium hydroxide as precipitant agent. Isopropanol was mixed with water as solvent to prevent hard agglomeration. The structure of resulting nanoceria was characterized by x-ray diffractometer (XRD). The transparency in the visible light and efficiency of protection in UV A region were studied using ultraviolet-visible (UV - Vis) spectrophotometer. The results show that nanoceria possess good tranparency in visible light and high UV light absorption. The critical absorption wavelenght of 368 nm was obtained which is desirable for excellent broad-spectrum protection absorbers. Moreover, analysis of photodegradation nanoceria to methylene blue solution shows poor photocatalytic activity. It indicates that nanoceria suitable for used as UV absorber in personal care products

  8. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    2010-09-01

    Full Text Available Pathological neovascularization is a hallmark of late stage neovascular (wet age-related macular degeneration (AMD and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV, while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD.Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH, Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2. Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1. The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG assessing retinal and by histology.Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially beneficial for ophthalmic

  9. Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

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    Avi Raveh

    Full Text Available Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable

  10. A Broad-Spectrum Inhibitor of CRISPR-Cas9.

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    Harrington, Lucas B; Doxzen, Kevin W; Ma, Enbo; Liu, Jun-Jie; Knott, Gavin J; Edraki, Alireza; Garcia, Bianca; Amrani, Nadia; Chen, Janice S; Cofsky, Joshua C; Kranzusch, Philip J; Sontheimer, Erik J; Davidson, Alan R; Maxwell, Karen L; Doudna, Jennifer A

    2017-09-07

    CRISPR-Cas9 proteins function within bacterial immune systems to target and destroy invasive DNA and have been harnessed as a robust technology for genome editing. Small bacteriophage-encoded anti-CRISPR proteins (Acrs) can inactivate Cas9, providing an efficient off switch for Cas9-based applications. Here, we show that two Acrs, AcrIIC1 and AcrIIC3, inhibit Cas9 by distinct strategies. AcrIIC1 is a broad-spectrum Cas9 inhibitor that prevents DNA cutting by multiple divergent Cas9 orthologs through direct binding to the conserved HNH catalytic domain of Cas9. A crystal structure of an AcrIIC1-Cas9 HNH domain complex shows how AcrIIC1 traps Cas9 in a DNA-bound but catalytically inactive state. By contrast, AcrIIC3 blocks activity of a single Cas9 ortholog and induces Cas9 dimerization while preventing binding to the target DNA. These two orthogonal mechanisms allow for separate control of Cas9 target binding and cleavage and suggest applications to allow DNA binding while preventing DNA cutting by Cas9. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The broad spectrum revisited: evidence from plant remains.

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    Weiss, Ehud; Wetterstrom, Wilma; Nadel, Dani; Bar-Yosef, Ofer

    2004-06-29

    The beginning of agriculture is one of the most important developments in human history, with enormous consequences that paved the way for settled life and complex society. Much of the research on the origins of agriculture over the last 40 years has been guided by Flannery's [Flannery, K. V. (1969) in The Domestication and Exploitation of Plants and Animals, eds. Ucko, P. J. & Dimbleby, G. W. (Duckworth, London), pp. 73-100] "broad spectrum revolution" (BSR) hypothesis, which posits that the transition to farming in southwest Asia entailed a period during which foragers broadened their resource base to encompass a wide array of foods that were previously ignored in an attempt to overcome food shortages. Although these resources undoubtedly included plants, nearly all BSR hypothesis-inspired research has focused on animals because of a dearth of Upper Paleolithic archaeobotanical assemblages. Now, however, a collection of >90,000 plant remains, recently recovered from the Stone Age site Ohalo II (23,000 B.P.), Israel, offers insights into the plant foods of the late Upper Paleolithic. The staple foods of this assemblage were wild grasses, pushing back the dietary shift to grains some 10,000 years earlier than previously recognized. Besides the cereals (wild wheat and barley), small-grained grasses made up a large component of the assemblage, indicating that the BSR in the Levant was even broader than originally conceived, encompassing what would have been low-ranked plant foods. Over the next 15,000 years small-grained grasses were gradually replaced by the cereals and ultimately disappeared from the Levantine diet.

  12. Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among Enterobacter spp.

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    Kaye, Keith S.; Cosgrove, Sara; Harris, Anthony; Eliopoulos, George M.; Carmeli, Yehuda

    2001-01-01

    Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance. PMID:11502540

  13. Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit.

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    Wiens, Jenna; Snyder, Graham M; Finlayson, Samuel; Mahoney, Monica V; Celi, Leo Anthony

    2018-02-01

    The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile . The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

  14. Detection of broad ultraviolet Fe II lines in the spectrum of NGC 1068

    International Nuclear Information System (INIS)

    Snijders, M.A.J.; Netzer, Hagai; Boksenberg, A.

    1986-01-01

    Ultraviolet observations of the nucleus of NGC 1068, obtained by the IUE over a period of 5 yr, are combined to give a high signal-to-noise spectrum of this source. The ultraviolet stellar continuum, obtained by comparison with ground-based data, is subtracted to show the nuclear non-stellar component. The resulting spectrum shows clearly the presence of strong broad FeII emission bands similar to those observed in many broad-line objects. Broad profiles are also seen in other strong emission lines. These observations confirm the recent discovery of an optical Seyfert type 1 spectrum in NGC 1068. (author)

  15. Enhanced methanol production in plants provides broad spectrum insect resistance.

    Directory of Open Access Journals (Sweden)

    Sameer Dixit

    Full Text Available Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR and spectra showed up to 16 fold higher methanol as compared to control wild type (WT plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid and Bemisia tabaci (whitefly, respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.

  16. Enhanced Methanol Production in Plants Provides Broad Spectrum Insect Resistance

    Science.gov (United States)

    Dixit, Sameer; Upadhyay, Santosh Kumar; Singh, Harpal; Sidhu, Om Prakash; Verma, Praveen Chandra; K, Chandrashekar

    2013-01-01

    Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants. PMID:24223989

  17. Evaluation of an expanded microarray for detecting antibiotic resistance genes in a broad range of gram-negative bacterial pathogens.

    Science.gov (United States)

    Card, Roderick; Zhang, Jiancheng; Das, Priya; Cook, Charlotte; Woodford, Neil; Anjum, Muna F

    2013-01-01

    A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure.

  18. Narrowly versus Broadly Defined Autism Spectrum Disorders: Differences in Pre-and Perinatal Risk Factors

    Science.gov (United States)

    Visser, Janne C.; Rommelse, Nanda; Vink, Lianne; Schrieken, Margo; Oosterling, Iris J.; Gaag, Rutger J.; Buitelaar, Jan K.

    2014-01-01

    This study examined the differential contribution of pre-and perinatal risks in narrowly versus broadly defined autism spectrum disorder (ASD) and across core symptom domains, IQ and co-morbid problems. Children with a DSM-IV diagnosis of autistic disorder (AD) (n = 121) or pervasive developmental disorder not otherwise specified (PDD-NOS)…

  19. Observing broad-absorption line quasars with Spectrum-Rontgen-Gamma

    DEFF Research Database (Denmark)

    Singh, K.P.; Schnopper, H.W.; Westergaard, Niels Jørgen Stenfeldt

    1998-01-01

    Broad-absorption line quasars are found to have extremely weak soft X-ray emission when compared with other optically selected quasars. In the only example of PHL 5200 for which a detailed X-ray spectrum has been obtained with ASCA, strong absorption in the source appears to be responsible...

  20. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    DEFF Research Database (Denmark)

    Taylor, Jenny C; Martin, Hilary C; Lise, Stefano

    2015-01-01

    To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the numb...

  1. Novel water-based antiseptic lotion demonstrates rapid, broad-spectrum kill compared with alcohol antiseptic.

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    Czerwinski, Steven E; Cozean, Jesse; Cozean, Colette

    2014-01-01

    A novel alcohol-based antiseptic and a novel water-based antiseptic lotion, both with a synergistic combination of antimicrobial ingredients containing 0.2% benzethonium chloride, were evaluated using the standard time-kill method against 25 FDA-specified challenge microorganisms. The purpose of the testing was to determine whether a non-alcohol product could have equivalent rapid and broad-spectrum kill to a traditional alcohol sanitizer. Both the alcohol- and water-based products showed rapid and broad-spectrum antimicrobial activity. The average 15-s kill was 99.999% of the challenge organism for the alcohol-based antiseptic and 99.971% for the water-based antiseptic. The alcohol-based product demonstrated 100% of peak efficacy (60s) within the first 15s, whereas the water-based product showed 99.97%. The novel alcohol-based antiseptic reduced concentrations of 100% of organisms by 99.999%, whereas the water-based antiseptic lotion showed the same reduction for 96% of organisms. A novel water-based antiseptic product demonstrated equivalent rapid, broad-spectrum antimicrobial activity to an alcohol-based sanitizer and provided additional benefits of reduced irritation, persistent effect, and greater efficacy against common viruses. The combination of rapid, broad-spectrum immediate kill and persistent efficacy against pathogens may have significant clinical benefit in limiting the spread of disease. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  2. Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health Care-associated Pneumonia.

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    Buckel, Whitney R; Stenehjem, Edward; Sorensen, Jeff; Dean, Nathan; Webb, Brandon

    2017-02-01

    Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care-associated pneumonia, especially where no microbiological diagnosis is made. To compare outcomes between patients who were transitioned to broad- versus narrow-spectrum oral antibiotics after initially receiving broad-spectrum intravenous antibiotic coverage. We performed a secondary analysis of an existing database of adults with community-onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology-negative health care-associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow-spectrum (usually a β-lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB-65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy. Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30-day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30-day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P = 0.26) between narrow and broad oral antibiotic groups. On the basis of analysis of a limited number of patients

  3. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes

    DEFF Research Database (Denmark)

    Clausen, Tine D; Bergholt, Thomas; Bouaziz, Olivier

    2016-01-01

    of childhood type 1 diabetes and the potential effect-modification by mode of delivery. MATERIALS AND METHODS: A Danish nationwide cohort study including all singletons born during 1997-2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome...... and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox...... regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. RESULTS: Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years...

  4. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  5. Biological activity of sedaxane---a novel broad-spectrum fungicide for seed treatment.

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    Zeun, Ronald; Scalliet, Gabriel; Oostendorp, Michael

    2013-04-01

    Sedaxane is a new broad-spectrum seed treatment fungicide developed by Syngenta Crop Protection for control of seed- and soil-borne diseases in a broad range of crops. Its physicochemical properties and activity spectrum have been optimised for use as a seed treatment providing both local and systemic protection of the seed and roots of target crops. Sedaxane inhibits respiration by binding to the succinate dehydrogenase complex in the fungal mitochondrium. Its activity spectrum covers seed-borne fungi such as Ustilago nuda, Tilletia caries, Monographella nivalis and Pyrenophora graminea, as well as the soil-borne fungi Rhizoctonia solani, R. cerealis and Typhula incarnata. Under greenhouse conditions, sedaxane showed high levels and consistent protection against U. nuda, P. graminea and Rhizoctonia spp. Under field conditions, efficacy against Rhizoctonia spp. resulted in increased yield compared with the untreated check. Efficacy against snow mould has been shown under very high disease pressure conditions. The combination of sedaxane plus fludioxonil against snow mould can provide resistance management for sustainable use. The broad spectrum and high level of activity in combination with excellent crop tolerance allow the use of sedaxane as a seed treatment in a wide variety of crops. It is a potential tool for precautionary resistance management when combined with other fungicides, especially against pathogens showing a potential for resistance development, such as M. nivalis. © 2012 Society of Chemical Industry.

  6. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    OpenAIRE

    Taylor, Jenny C; Martin, Hilary C; Lise, Stefano; Broxholme, John; Cazier, Jean-Baptiste; Rimmer, Andy; Kanapin, Alexander; Lunter, Gerton; Fiddy, Simon; Allan, Chris; Aricescu, A. Radu; Attar, Moustafa; Babbs, Christian; Becq, Jennifer; Beeson, David

    2015-01-01

    To assess factors influencing the success of whole genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases across a broad spectrum of disorders in whom prior screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritisation. We found that jointly calling variants across samples, filtering against both local and e...

  7. Relationship between the Broad Autism Phenotype, Social Relationships and Mental Health for Mothers of Children with Autism Spectrum Disorder

    Science.gov (United States)

    Pruitt, Megan M.; Rhoden, Madeline; Ekas, Naomi V.

    2018-01-01

    This study aimed to examine the mechanisms responsible for the association between the broad autism phenotype and depressive symptoms in mothers of a child with autism spectrum disorder. A total of 98 mothers who had a child with autism spectrum disorder between the ages of 2 and 16 years completed assessments of maternal broad autism phenotype,…

  8. Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Karen S. Ho

    2016-12-01

    Full Text Available Copy number variants (CNVs detected by chromosomal microarray analysis (CMA significantly contribute to understanding the etiology of autism spectrum disorder (ASD and other related conditions. In recognition of the value of CMA testing and its impact on medical management, CMA is in medical guidelines as a first-tier test in the evaluation of children with these disorders. As CMA becomes adopted into routine care for these patients, it becomes increasingly important to report these clinical findings. This study summarizes the results of over 4 years of CMA testing by a CLIA-certified clinical testing laboratory. Using a 2.8 million probe microarray optimized for the detection of CNVs associated with neurodevelopmental disorders, we report an overall CNV detection rate of 28.1% in 10,351 consecutive patients, which rises to nearly 33% in cases without ASD, with only developmental delay/intellectual disability (DD/ID and/or multiple congenital anomalies (MCA. The overall detection rate for individuals with ASD is also significant at 24.4%. The detection rate and pathogenic yield of CMA vary significantly with the indications for testing, age, and gender, as well as the specialty of the ordering doctor. We note discrete differences in the most common recurrent CNVs found in individuals with or without a diagnosis of ASD.

  9. Particle acceleration model for the broad-band baseline spectrum of the Crab nebula

    Science.gov (United States)

    Fraschetti, F.; Pohl, M.

    2017-11-01

    We develop a simple one-zone model of the steady-state Crab nebula spectrum encompassing both the radio/soft X-ray and the GeV/multi-TeV observations. By solving the transport equation for GeV-TeV electrons injected at the wind termination shock as a log-parabola momentum distribution and evolved via energy losses, we determine analytically the resulting differential energy spectrum of photons. We find an impressive agreement with the observed spectrum of synchrotron emission, and the synchrotron self-Compton component reproduces the previously unexplained broad 200-GeV peak that matches the Fermi/Large Area Telescope (LAT) data beyond 1 GeV with the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) data. We determine the parameters of the single log-parabola electron injection distribution, in contrast with multiple broken power-law electron spectra proposed in the literature. The resulting photon differential spectrum provides a natural interpretation of the deviation from power law customarily fitted with empirical multiple broken power laws. Our model can be applied to the radio-to-multi-TeV spectrum of a variety of astrophysical outflows, including pulsar wind nebulae and supernova remnants, as well as to interplanetary shocks.

  10. Wavelength characteristics of chirped quantum dot superluminescent diodes for broad spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Hyung-Chul; Park, Hong-Lee [Yonsei University, Seoul (Korea, Republic of); You, Young-Chae [Sungkyunkwan University, Suwon (Korea, Republic of); Han, Il-Ki [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

    2006-04-15

    A chirped InAs quantum dot superluminescent diode both with and without a In{sub 0.15}Ga{sub 0.85}As cap layer was fabricated for a broad-band spectrum. This study shows that the cap layer reduces strain and operates as a carrier capturer and that carriers excited by lattice heating also affect the radiative recombination in the quantum dots (QDs) as well as the cap layer through the characteristic temperature (T{sub 0}). In addition, by surveying peaks of each QD layers, the characteristics of carriers in QDs, such as band-filling effect and the thermal effect, were analyzed, in QDs, and a more effective method for creating a wider spectrum is proposed.

  11. Gamma-irradiated scrub typhus immunogens: broad-spectrum immunity with combinations of rickettsial strains

    International Nuclear Information System (INIS)

    Eisenberg, G.H. Jr.; Osterman, J.V.

    1979-01-01

    Scrub typhus immunogens were prepared from Rickettsia tsutsugamushi strains Karp, Kato, Gilliam, Kostival, and Buie by exposing frozen infected yolk sac suspensions to 300 krad of gamma radiation. Mouse protection tests showed that each of the irradiated immunogens protected C3H/HeDub mice against high challenge levels of Karp and Gilliam, but that none of these single-strain immunogens were capable of protecting against all five of the challenge strains. Broad-spectrum protection was achieved by using combinations of three strains of irradiated rickettsiae in a vaccination regimen of three injections at 5-day intervals

  12. Leapfrog diagnostics: Demonstration of a broad spectrum pathogen identification platform in a resource-limited setting

    Directory of Open Access Journals (Sweden)

    Leski Tomasz A

    2012-07-01

    Full Text Available Abstract Background Resource-limited tropical countries are home to numerous infectious pathogens of both human and zoonotic origin. A capability for early detection to allow rapid outbreak containment and prevent spread to non-endemic regions is severely impaired by inadequate diagnostic laboratory capacity, the absence of a “cold chain” and the lack of highly trained personnel. Building up detection capacity in these countries by direct replication of the systems existing in developed countries is not a feasible approach and instead requires “leapfrogging” to the deployment of the newest diagnostic systems that do not have the infrastructure requirements of systems used in developed countries. Methods A laboratory for molecular diagnostics of infectious agents was established in Bo, Sierra Leone with a hybrid solar/diesel/battery system to ensure stable power supply and a satellite modem to enable efficient communication. An array of room temperature stabilization and refrigeration technologies for reliable transport and storage of reagents and biological samples were also tested to ensure sustainable laboratory supplies for diagnostic assays. Results The laboratory demonstrated its operational proficiency by conducting an investigation of a suspected avian influenza outbreak at a commercial poultry farm at Bo using broad range resequencing microarrays and real time RT-PCR. The results of the investigation excluded influenza viruses as a possible cause of the outbreak and indicated a link between the outbreak and the presence of Klebsiella pneumoniae. Conclusions This study demonstrated that by application of a carefully selected set of technologies and sufficient personnel training, it is feasible to deploy and effectively use a broad-range infectious pathogen detection technology in a severely resource-limited setting.

  13. Brevibacillus laterosporus, a Pathogen of Invertebrates and a Broad-Spectrum Antimicrobial Species

    Directory of Open Access Journals (Sweden)

    Luca Ruiu

    2013-09-01

    Full Text Available Brevibacillus laterosporus, a bacterium characterized by the production of a unique canoe-shaped lamellar body attached to one side of the spore, is a natural inhabitant of water, soil and insects. Its biopesticidal potential has been reported against insects in different orders including Coleoptera, Lepidoptera, Diptera and against nematodes and mollusks. In addition to its pathogenicity against invertebrates, different B. laterosporus strains show a broad-spectrum antimicrobial activity including activity against phytopathogenic bacteria and fungi. A wide variety of molecules, including proteins and antibiotics, have been associated with the observed pathogenicity and mode of action. Before being considered as a biological control agent against plant pathogens, the antifungal and antibacterial properties of certain B. laterosporus strains have found medical interest, associated with the production of antibiotics with therapeutic effects. The recent whole genome sequencing of this species revealed its potential to produce polyketides, nonribosomal peptides, and toxins. Another field of growing interest is the use of this bacterium for bioremediation of contaminated sites by exploiting its biodegradation properties. The aim of the present review is to gather and discuss all recent findings on this emerging entomopathogen, giving a wider picture of its complex and broad-spectrum biocontrol activity.

  14. Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections.

    Science.gov (United States)

    Jackman, Joshua A; Lee, Jaywon; Cho, Nam-Joon

    2016-03-02

    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Identification and Structural Characterization of Naturally-Occurring Broad-Spectrum Cyclic Antibiotics Isolated from Paenibacillus

    Science.gov (United States)

    Knolhoff, Ann M.; Zheng, Jie; McFarland, Melinda A.; Luo, Yan; Callahan, John H.; Brown, Eric W.; Croley, Timothy R.

    2015-08-01

    The rise of antimicrobial resistance necessitates the discovery and/or production of novel antibiotics. Isolated strains of Paenibacillus alvei were previously shown to exhibit antimicrobial activity against a number of pathogens, such as E. coli, Salmonella, and methicillin-resistant Staphylococcus aureus (MRSA). The responsible antimicrobial compounds were isolated from these Paenibacillus strains and a combination of low and high resolution mass spectrometry with multiple-stage tandem mass spectrometry was used for identification. A group of closely related cyclic lipopeptides was identified, differing primarily by fatty acid chain length and one of two possible amino acid substitutions. Variation in the fatty acid length resulted in mass differences of 14 Da and yielded groups of related MSn spectra. Despite the inherent complexity of MS/MS spectra of cyclic compounds, straightforward analysis of these spectra was accomplished by determining differences in complementary product ion series between compounds that differ in molecular weight by 14 Da. The primary peptide sequence assignment was confirmed through genome mining; the combination of these analytical tools represents a workflow that can be used for the identification of complex antibiotics. The compounds also share amino acid sequence similarity to a previously identified broad-spectrum antibiotic isolated from Paenibacillus. The presence of such a wide distribution of related compounds produced by the same organism represents a novel class of broad-spectrum antibiotic compounds.

  16. Surprises from a Deep ASCA Spectrum of the Broad Absorption Line Quasar PHL 5200

    Science.gov (United States)

    Mathur, Smita; Matt, G.; Green, P. J.; Elvis, M.; Singh, K. P.

    2002-01-01

    We present a deep (approx. 85 ks) ASCA observation of the prototype broad absorption line quasar (BALQSO) PHL 5200. This is the best X-ray spectrum of a BALQSO yet. We find the following: (1) The source is not intrinsically X-ray weak. (2) The line-of-sight absorption is very strong, with N(sub H) = 5 x 10(exp 23)/sq cm. (3) The absorber does not cover the source completely; the covering fraction is approx. 90%. This is consistent with the large optical polarization observed in this source, implying multiple lines of sight. The most surprising result of this observation is that (4) the spectrum of this BALQSO is not exactly similar to other radio-quiet quasars. The hard X-ray spectrum of PHL 5200 is steep, with the power-law spectral index alpha approx. 1.5. This is similar to the steepest hard X-ray slopes observed so far. At low redshifts, such steep slopes are observed in narrow-line Seyfert 1 (NLS1) galaxies, believed to be accreting at a high Eddington rate. This observation strengthens the analogy between BALQSOs and NLS1 galaxies and supports the hypothesis that BALQSOs represent an early evolutionary state of quasars. It is well accepted that the orientation to the line of sight determines the appearance of a quasar: age seems to play a significant role as well.

  17. Development of a broad-spectrum antiviral with activity against Ebola virus.

    Science.gov (United States)

    Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

    2009-09-01

    We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

  18. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    Science.gov (United States)

    Lise, Stefano; Broxholme, John; Cazier, Jean-Baptiste; Rimmer, Andy; Kanapin, Alexander; Lunter, Gerton; Fiddy, Simon; Allan, Chris; Aricescu, A. Radu; Attar, Moustafa; Babbs, Christian; Becq, Jennifer; Beeson, David; Bento, Celeste; Bignell, Patricia; Blair, Edward; Buckle, Veronica J; Bull, Katherine; Cais, Ondrej; Cario, Holger; Chapel, Helen; Copley, Richard R; Cornall, Richard; Craft, Jude; Dahan, Karin; Davenport, Emma E; Dendrou, Calliope; Devuyst, Olivier; Fenwick, Aimée L; Flint, Jonathan; Fugger, Lars; Gilbert, Rodney D; Goriely, Anne; Green, Angie; Greger, Ingo H.; Grocock, Russell; Gruszczyk, Anja V; Hastings, Robert; Hatton, Edouard; Higgs, Doug; Hill, Adrian; Holmes, Chris; Howard, Malcolm; Hughes, Linda; Humburg, Peter; Johnson, David; Karpe, Fredrik; Kingsbury, Zoya; Kini, Usha; Knight, Julian C; Krohn, Jonathan; Lamble, Sarah; Langman, Craig; Lonie, Lorne; Luck, Joshua; McCarthy, Davis; McGowan, Simon J; McMullin, Mary Frances; Miller, Kerry A; Murray, Lisa; Németh, Andrea H; Nesbit, M Andrew; Nutt, David; Ormondroyd, Elizabeth; Oturai, Annette Bang; Pagnamenta, Alistair; Patel, Smita Y; Percy, Melanie; Petousi, Nayia; Piazza, Paolo; Piret, Sian E; Polanco-Echeverry, Guadalupe; Popitsch, Niko; Powrie, Fiona; Pugh, Chris; Quek, Lynn; Robbins, Peter A; Robson, Kathryn; Russo, Alexandra; Sahgal, Natasha; van Schouwenburg, Pauline A; Schuh, Anna; Silverman, Earl; Simmons, Alison; Sørensen, Per Soelberg; Sweeney, Elizabeth; Taylor, John; Thakker, Rajesh V; Tomlinson, Ian; Trebes, Amy; Twigg, Stephen RF; Uhlig, Holm H; Vyas, Paresh; Vyse, Tim; Wall, Steven A; Watkins, Hugh; Whyte, Michael P; Witty, Lorna; Wright, Ben; Yau, Chris; Buck, David; Humphray, Sean; Ratcliffe, Peter J; Bell, John I; Wilkie, Andrew OM; Bentley, David; Donnelly, Peter; McVean, Gilean

    2015-01-01

    To assess factors influencing the success of whole genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases across a broad spectrum of disorders in whom prior screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritisation. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease causing variants in 21% of cases, rising to 34% (23/68) for Mendelian disorders and 57% (8/14) in trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, though only four were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis, but also highlight many outstanding challenges. PMID:25985138

  19. Impact of broad-spectrum antimicrobial treatment on the ecology of intestinal flora.

    Science.gov (United States)

    Yang, Jen-Jia; Wang, Jann-Tay; Cheng, Aristine; Chuang, Yu-Chung; Sheng, Wang-Huei

    2017-06-28

    Suppression of intestinal flora by broad-spectrum antimicrobial agents facilitated risk of colonization or infection with resistant pathogen. We aimed to investigate the changes in bowel carriage of target resistant microorganisms (TRO) among patients treated with three different classes of Pseudomonas-sparing broad-spectrum antimicrobial agents (ertapenem, moxifloxacin and flomoxef) with anaerobic coverage. Risk factors for developing colonization of TRO were also analyzed. We prospectively enrolled the adult hospitalized patients (>20 years old) who were indicated for at least 7-day course with either of ertapenem, moxifloxacin or flomoxef. Rectal swabs were performed for the patients who received at least 1-day course of study antibiotics during the treatment duration. The TROs included Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. MacConkey agars with study antibiotics were used to isolate the TROs and evaluate the antimicrobial resistance. The mean age of our study population was 61.6 years, and 58.8% were males. The rates of rectal colonization for Pseudomonas aeruginosa was similar among the study medications (ertapenem 13.2%, flomoxef 20%, moxifloxacin 14.3%, p = 0.809). Compared with ertapenem, flomoxef (odds ratio [OR], 4.30; 95% confidence interval [95% CI], 1.28-14.48, p = 0.019) and moxifloxacin (OR, 6.95; 95% CI, 1.36-35.52, p = 0.019) had higher risk for colonization of ertapenem-resistant Escherichiacoli colonization. The patients who received treatment of ertapenem may have a lower risk of rectal colonization for ertapenem resistant Escherichia coli than those who received flomoxef or moxifloxacin. The rate of Pseudomonas colonization did not differ between the three study Pseudomonas-sparing agents. Copyright © 2017. Published by Elsevier B.V.

  20. Broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model.

    Science.gov (United States)

    Strzępa, Anna; Majewska-Szczepanik, Monika; Lobo, Francis M; Wen, Li; Szczepanik, Marian

    2017-07-01

    Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Oral treatment with enrofloxacin suppresses CS and production of anti-trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides-Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  1. Isolation of a new broad spectrum antifungal polyene from Streptomyces sp. MTCC 5680.

    Science.gov (United States)

    Vartak, A; Mutalik, V; Parab, R R; Shanbhag, P; Bhave, S; Mishra, P D; Mahajan, G B

    2014-06-01

    A new polyene macrolide antibiotic PN00053 was isolated from the fermentation broth of Streptomyces sp. wild-type strain MTCC-5680. The producer strain was isolated from fertile mountain soil of Naldehra region, Himachal Pradesh, India. The compound PN00053 was purified through various steps of chromatographic techniques and bio-activity guided fractionation followed by its characterization using physiochemical properties, spectral data ((1) H-NMR, (13) C-NMR, HMBC, HSQC, and COSY) and MS analysis. PN00053 exhibited broad spectrum in vitro antifungal activity against strains of Aspergillus fumigatus (HMR), A. fumigatus ATCC 16424, Candida albicans (I.V.), C. albicans ATCC 14503, C. krusei GO6, C. glabrata HO4, Cryptococcus neoformans, Trichophyton sp. as well as fluconazole resistant strains C. krusei GO3 and C. glabrata HO5. It did not inhibit growth of gram positive and gram-negative bacteria, displaying its specificity against fungi. PN00053 is a novel polyene macrolide isolated from a wild strain of Streptomyces sp. PM0727240 (MTCC5680), an isolate from the mountainous rocky regions of Himachal Pradesh, India. The compound is a new derivative of the antibiotic Roflamycoin [32, 33-didehydroroflamycoin (DDHR)]. It displayed broad spectrum antifungal activity against yeast and filamentous fungi. However, it did not show any antibacterial activity. The in vitro study revealed that PN00053 has better potency as compared to clinical gold standard fluconazole. The development of pathogenic resistance against the polyenes has been seldom reported. Hence, we envisage PN00053 could be a potential antifungal lead. © 2014 The Society for Applied Microbiology.

  2. Surveillance of broad-spectrum antibiotic prescription in Singaporean hospitals: a 5-year longitudinal study.

    Directory of Open Access Journals (Sweden)

    Yi-Xin Liew

    Full Text Available BACKGROUND: Inappropriate prescription of antibiotics may contribute towards higher levels antimicrobial resistance. A key intervention for improving appropriate antibiotic prescription is surveillance of prescription. This paper presents the results of a longitudinal surveillance of broad-spectrum antibiotic prescription in 5 public-sector hospitals in Singapore from 2006 to 2010. METHODOLOGY/PRINCIPAL FINDINGS: Quarterly antibiotic prescription data were obtained and converted to defined daily doses (DDDs per 1,000 inpatient-days. The presence of significant trends in antibiotic prescription over time for both individual and combined hospitals was tested by regression analysis and corrected for autocorrelation between time-points. Excluding fluoroquinolones, there was a significant increase in prescription of all monitored antibiotics from an average of 233.12 defined daily doses (DDD/1,000 inpatient-days in 2006 to 254.38 DDD/1,000 inpatient-days in 2010 (Coefficient = 1.13, 95%CI: 0.16-2.09, p = 0.025. Increasing utilization of carbapenems, piperacillin/tazobactam, and Gram-positive agents were seen in the majority of the hospitals, while cephalosporins were less prescribed over time. The combined expenditure for 5 hospitals increased from USD9.9 million in 2006 to USD16.7 million in 2010. CONCLUSIONS/SIGNIFICANCE: The rate of prescription of broad-spectrum antibiotics in Singaporean hospitals is much higher compared to those of European hospitals. This may be due to high rates of antimicrobial resistance. The increase in expenditure on monitored antibiotics over the past 5 years outstripped the actual increase in DDD/1,000 inpatient-days of antibiotics prescribed. Longitudinal surveillance of antibiotic prescription on a hospital and countrywide level is important for detecting trends for formulating interventions or policies. Further research is needed to understand the causes for the various prescription trends and to act on these where

  3. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

    International Nuclear Information System (INIS)

    Benedictis, P. de; Minola, A.; Rota, E.; Aiello, R.; Zecchin, B.; Salomoni, A.; Foglierini, M.; Agatic, G.; Vanzetta, F.; Lavenir, R.; Lepelletier, A.; Bentley, E.; Weiss, R.; Cattoli, G.

    2016-01-01

    Full text: Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. (author)

  4. XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

    Science.gov (United States)

    Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

    2014-11-09

    The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE) associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from the wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113-amino acid protein that shares 50% identity to the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23, but differs in promoter region by lacking the TALE binding-element (EBE) for AvrXa23. XA23 can trigger strong hypersensitive response in rice, tobacco and tomato. Our results provide the first evidence that plant genomes have an executor R gene family in which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in pathogen. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  5. Parametric instability producing broad symmetrical structure in the spectrum of ionospheric heating-induced radiation

    International Nuclear Information System (INIS)

    Kuo, S.P.

    1997-01-01

    A four-wave interaction process in which an O-mode electromagnetic pump decays parametrically into a lower hybrid decay mode and two-electron Bernstein sidebands is analyzed. It is shown that the instability can be excited in a spatial region near the electron Bernstein/upper hybrid double resonance and in a narrow pump frequency range slightly below the third harmonic electron cyclotron resonance. The two electron Bernstein sidebands have about the same intensity and thus, produce Broad Symmetrical Structure (BSS) in the emission spectrum after being converted into electromagnetic radiation by scattering off background field-aligned density irregularities. The results also show that the size of the instability zone becomes very small as the pump frequency operates near a cyclotron harmonic higher than the third. Thus, the converted emission will be too weak to be detected. This explains why the BSS feature in the spectrum of stimulated electromagnetic emissions (SEEs) has only been observed in the third harmonic case. copyright 1997 American Institute of Physics

  6. Trends in broad-spectrum antibiotic prescribing for children with acute otitis media in the United States, 1998–2004

    Directory of Open Access Journals (Sweden)

    Gambler Angela S

    2009-06-01

    Full Text Available Abstract Background Overuse of broad-spectrum antibiotics is associated with antibiotic resistance. Acute otitis media (AOM is responsible for a large proportion of antibiotics prescribed for US children. Rates of broad-spectrum antibiotic prescribing for AOM are unknown. Methods Analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1998 to 2004 (N = 6,878. Setting is office-based physicians, hospital outpatient departments, and emergency departments. Patients are children aged 12 years and younger prescribed antibiotics for acute otitis media. Main outcome measure is percentage of broad-spectrum antibiotics, defined as amoxicillin/clavulanate, macrolides, cephalosporins and quinolones. Results Broad-spectrum prescribing for acute otitis media increased from 34% of visits in 1998 to 45% of visits in 2004 (P Conclusion Prescribing of broad-spectrum antibiotics for acute otitis media has steadily increased from 1998 to 2004. Associations with non-clinical factors suggest potential for improvement in prescribing practice.

  7. Designing a broad-spectrum integrative approach for cancer prevention and treatment.

    Science.gov (United States)

    Block, Keith I; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Amin, A R M Ruhul; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Ashraf, S Salman; Azmi, Asfar S; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan; Bishayee, Anupam; Blain, Stacy W; Block, Penny B; Boosani, Chandra S; Carey, Thomas E; Carnero, Amancio; Carotenuto, Marianeve; Casey, Stephanie C; Chakrabarti, Mrinmay; Chaturvedi, Rupesh; Chen, Georgia Zhuo; Chen, Helen; Chen, Sophie; Chen, Yi Charlie; Choi, Beom K; Ciriolo, Maria Rosa; Coley, Helen M; Collins, Andrew R; Connell, Marisa; Crawford, Sarah; Curran, Colleen S; Dabrosin, Charlotta; Damia, Giovanna; Dasgupta, Santanu; DeBerardinis, Ralph J; Decker, William K; Dhawan, Punita; Diehl, Anna Mae E; Dong, Jin-Tang; Dou, Q Ping; Drew, Janice E; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A; Felsher, Dean W; Ferguson, Lynnette R; Fimognari, Carmela; Firestone, Gary L; Frezza, Christian; Fujii, Hiromasa; Fuster, Mark M; Generali, Daniele; Georgakilas, Alexandros G; Gieseler, Frank; Gilbertson, Michael; Green, Michelle F; Grue, Brendan; Guha, Gunjan; Halicka, Dorota; Helferich, William G; Heneberg, Petr; Hentosh, Patricia; Hirschey, Matthew D; Hofseth, Lorne J; Holcombe, Randall F; Honoki, Kanya; Hsu, Hsue-Yin; Huang, Gloria S; Jensen, Lasse D; Jiang, Wen G; Jones, Lee W; Karpowicz, Phillip A; Keith, W Nicol; Kerkar, Sid P; Khan, Gazala N; Khatami, Mahin; Ko, Young H; Kucuk, Omer; Kulathinal, Rob J; Kumar, Nagi B; Kwon, Byoung S; Le, Anne; Lea, Michael A; Lee, Ho-Young; Lichtor, Terry; Lin, Liang-Tzung; Locasale, Jason W; Lokeshwar, Bal L; Longo, Valter D; Lyssiotis, Costas A; MacKenzie, Karen L; Malhotra, Meenakshi; Marino, Maria; Martinez-Chantar, Maria L; Matheu, Ander; Maxwell, Christopher; McDonnell, Eoin; Meeker, Alan K; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A; Mohammad, Ramzi M; Mohammed, Sulma I; Morre, D James; Muralidhar, Vinayak; Muqbil, Irfana; Murphy, Michael P; Nagaraju, Ganji Purnachandra; Nahta, Rita; Niccolai, Elena; Nowsheen, Somaira; Panis, Carolina; Pantano, Francesco; Parslow, Virginia R; Pawelec, Graham; Pedersen, Peter L; Poore, Brad; Poudyal, Deepak; Prakash, Satya; Prince, Mark; Raffaghello, Lizzia; Rathmell, Jeffrey C; Rathmell, W Kimryn; Ray, Swapan K; Reichrath, Jörg; Rezazadeh, Sarallah; Ribatti, Domenico; Ricciardiello, Luigi; Robey, R Brooks; Rodier, Francis; Rupasinghe, H P Vasantha; Russo, Gian Luigi; Ryan, Elizabeth P; Samadi, Abbas K; Sanchez-Garcia, Isidro; Sanders, Andrew J; Santini, Daniele; Sarkar, Malancha; Sasada, Tetsuro; Saxena, Neeraj K; Shackelford, Rodney E; Shantha Kumara, H M C; Sharma, Dipali; Shin, Dong M; Sidransky, David; Siegelin, Markus David; Signori, Emanuela; Singh, Neetu; Sivanand, Sharanya; Sliva, Daniel; Smythe, Carl; Spagnuolo, Carmela; Stafforini, Diana M; Stagg, John; Subbarayan, Pochi R; Sundin, Tabetha; Talib, Wamidh H; Thompson, Sarah K; Tran, Phuoc T; Ungefroren, Hendrik; Vander Heiden, Matthew G; Venkateswaran, Vasundara; Vinay, Dass S; Vlachostergios, Panagiotis J; Wang, Zongwei; Wellen, Kathryn E; Whelan, Richard L; Yang, Eddy S; Yang, Huanjie; Yang, Xujuan; Yaswen, Paul; Yedjou, Clement; Yin, Xin; Zhu, Jiyue; Zollo, Massimo

    2015-12-01

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us

  8. A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy

    Science.gov (United States)

    Block, Keith I.; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Amin, A.R.M. Ruhul; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Ashraf, S. Salman; Azmi, Asfar S.; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan; Bishayee, Anupam; Blain, Stacy W.; Block, Penny B.; Boosani, Chandra S.; Carey, Thomas E.; Carnero, Amancio; Carotenuto, Marianeve; Casey, Stephanie C.; Chakrabarti, Mrinmay; Chaturvedi, Rupesh; Chen, Georgia Zhuo; Chen, Helen; Chen, Sophie; Chen, Yi Charlie; Choi, Beom K.; Ciriolo, Maria Rosa; Coley, Helen M.; Collins, Andrew R.; Connell, Marisa; Crawford, Sarah; Curran, Colleen S.; Dabrosin, Charlotta; Damia, Giovanna; Dasgupta, Santanu; DeBerardinis, Ralph J.; Decker, William K.; Dhawan, Punita; Diehl, Anna Mae E.; Dong, Jin-Tang; Dou, Q. Ping; Drew, Janice E.; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A.; Felsher, Dean W.; Ferguson, Lynnette R; Fimognari, Carmela; Firestone, Gary L.; Frezza, Christian; Fujii, Hiromasa; Fuster, Mark M.; Generali, Daniele; Georgakilas, Alexandros G.; Gieseler, Frank; Gilbertson, Michael; Green, Michelle F.; Grue, Brendan; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Heneberg, Petr; Hentosh, Patricia; Hirschey, Matthew D.; Hofseth, Lorne J.; Holcombe, Randall F.; Honoki, Kanya; Hsu, Hsue-Yin; Huang, Gloria S.; Jensen, Lasse D.; Jiang, Wen G.; Jones, Lee W.; Karpowicz, Phillip A.; Keith, W Nicol; Kerkar, Sid P.; Khan, Gazala N.; Khatami, Mahin; Ko, Young H.; Kucuk, Omer; Kulathinal, Rob J.; Kumar, Nagi B.; Kumara, H.M.C. Shantha; Kwon, Byoung S.; Le, Anne; Lea, Michael A.; Lee, Ho-Young; Lichtor, Terry; Lin, Liang-Tzung; Locasale, Jason W.; Lokeshwar, Bal L.; Longo, Valter D.; Lyssiotis, Costas A.; MacKenzie, Karen L.; Malhotra, Meenakshi; Marino, Maria; Martinez-Chantar, Maria L.; Matheu, Ander; Maxwell, Christopher; McDonnell, Eoin; Meeker, Alan K.; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A.; Mohammad, Ramzi M.; Mohammed, Sulma I.; Morre, D. James; Muqbil, Irfana; Muralidhar, Vinayak; Murphy, Michael P.; Nagaraju, Ganji Purnachandra; Nahta, Rita; Niccolai, Elena; Nowsheen, Somaira; Panis, Carolina; Pantano, Francesco; Parslow, Virginia R.; Pawelec, Graham; Pedersen, Peter L.; Poore, Brad; Poudyal, Deepak; Prakash, Satya; Prince, Mark; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Rathmell, W. Kimryn; Ray, Swapan K.; Reichrath, Jörg; Rezazadeh, Sarallah; Ribatti, Domenico; Ricciardiello, Luigi; Robey, R. Brooks; Rodier, Francis; Rupasinghe, H.P. Vasantha; Russo, Gian Luigi; Ryan, Elizabeth P.; Samadi, Abbas K.; Sanchez-Garcia, Isidro; Sanders, Andrew J.; Santini, Daniele; Sarkar, Malancha; Sasada, Tetsuro; Saxena, Neeraj K.; Shackelford, Rodney E; Sharma, Dipali; Shin, Dong M.; Sidransky, David; Siegelin, Markus David; Signori, Emanuela; Singh, Neetu; Sivanand, Sharanya; Sliva, Daniel; Smythe, Carl; Spagnuolo, Carmela; Stafforini, Diana M.; Stagg, John; Subbarayan, Pochi R.; Sundin, Tabetha; Talib, Wamidh H.; Thompson, Sarah K.; Tran, Phuoc T.; Ungefroren, Hendrik; Vander Heiden, Matthew G.; Venkateswaran, Vasundara; Vinay, Dass S.; Vlachostergios, Panagiotis J.; Wang, Zongwei; Wellen, Kathryn E.; Whelan, Richard L.; Yang, Eddy S.; Yang, Huanjie; Yang, Xujuan; Yaswen, Paul; Yedjou, Clement; Yin, Xin; Zhu, Jiyue; Zollo, Massimo

    2016-01-01

    Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a

  9. THE ANXIETY SPECTRUM AND THE REFLEX PHYSIOLOGY OF DEFENSE: FROM CIRCUMSCRIBED FEAR TO BROAD DISTRESS

    Science.gov (United States)

    McTeague, Lisa M.; Lang, Peter J.

    2013-01-01

    Guided by the diagnostic nosology, anxiety patients are expected to show defensive hyperarousal during affective challenge, irrespective of the principal phenotype. In the current study, patients representing the whole spectrum of anxiety disorders (i.e., specific phobia, social phobia, panic disorder with or without agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder(PTSD)), and healthy community control participants, completed an imagery-based fear elicitation paradigm paralleling conventional intervention techniques. Participants imagined threatening and neutral narratives as physiological responses were recorded. Clear evidence emerged for exaggerated reactivity to clinically relevant imagery—most pronounced in startle reflex responding. However, defensive propensity varied across principal anxiety disorders. Disorders characterized by focal fear and impairment (e.g., specific phobia) showed robust fear potentiation. Conversely, for disorders of long-enduring, pervasive apprehension and avoidance with broad anxiety and depression comorbidity (e.g., PTSD secondary to cumulative trauma, GAD), startle responses were paradoxically diminished to all aversive contents. Patients whose expressed symptom profiles were intermediate between focal fearfulness and broad anxious-misery in both severity and chronicity exhibited a still heightened but more generalized physiological propensity to respond defensively. Importantly, this defensive physiological gradient—the inverse of self-reported distress—was evident not only between but also within disorders. These results highlight that fear circuitry could be dysregulated in chronic, pervasive anxiety, and preliminary functional neuroimaging findings suggest that deficient amygdala recruitment could underlie attenuated reflex responding. In summary, adaptive defensive engagement during imagery may be compromised by long-term dysphoria and stress—a phenomenon

  10. Broad-spectrum enhanced absorption of graphene-molybdenum disulfide photovoltaic cells in metal-mirror microcavity

    Science.gov (United States)

    Jiang-Tao, Liu; Yun-Kai, Cao; Hong, Tong; Dai-Qiang, Wang; Zhen-Hua, Wu

    2018-04-01

    The optical absorption of graphene-molybdenum disulfide photovoltaic cells (GM-PVc) in wedge-shaped metal-mirror microcavities (w-MMCs) combined with a spectrum-splitting structure was studied. Results showed that the combination of spectrum-splitting structure and w-MMC can enable the light absorption of GM-PVcs to reach about 65% in the broad spectrum. The influence of processing errors on the absorption of GM-PVcs in w-MMCs was 3-14 times lower than that of GM-PVcs in wedge photonic crystal microcavities. The light absorption of GM-PVcs reached 60% in the broad spectrum, even with the processing errors. The proposed structure is easy to implement and may have potentially important applications in the development of ultra-thin and high-efficiency solar cells and optoelectronic devices.

  11. Dissecting disease entities out of the broad spectrum of bipolar-disorders.

    Science.gov (United States)

    Levine, Joseph; Toker, Lilach; Agam, Galila

    2018-01-01

    The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  13. Ceftiofur sodium, a broad-spectrum cephalosporin: evaluation in vitro and in vivo in mice.

    Science.gov (United States)

    Yancey, R J; Kinney, M L; Roberts, B J; Goodenough, K R; Hamel, J C; Ford, C W

    1987-07-01

    Ceftiofur sodium, a broad-spectrum beta-lactamase-resistant cephalosporin, was evaluated in vitro and in vivo in mice. Ceftiofur is the sodium salt of (6R, 7R)-7[( 2-amino-4-thiazolyl)-Z- (methoxyimino)acetyl]amino)-3-[( (2-furanylcarbonyl)thio]methyl)-8-oxo-5- thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylate. Minimal inhibitory concentration values were obtained with 264 strains representing 9 genera and 17 species of bacterial pathogens from cattle, swine, sheep, horses, poultry, dogs, cats, and human beings. Ceftiofur was more active than was ampicillin against all strains tested including beta-lactamase-producing organisms. In mice with systemic infections, ceftiofur was more active than or equivalent to ampicillin, cephalothin, cefamandole, cloxacillin, cefoperazone, or pirlimycin. These protection tests included infections with Escherichia coli, Haemophilus pleuropneumoniae, H somnus, Pasteurella haemolytica, P multocida, Salmonella typhimurium, or Staphylococcus aureus. In infant mice with E coli-induced lethal diarrhea and in mice with S aureus and E coli-induced mastitis, ceftiofur was comparable or more active than was ampicillin.

  14. Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

    Science.gov (United States)

    Cagno, Valeria; Andreozzi, Patrizia; D'Alicarnasso, Marco; Jacob Silva, Paulo; Mueller, Marie; Galloux, Marie; Le Goffic, Ronan; Jones, Samuel T.; Vallino, Marta; Hodek, Jan; Weber, Jan; Sen, Soumyo; Janeček, Emma-Rose; Bekdemir, Ahmet; Sanavio, Barbara; Martinelli, Chiara; Donalisio, Manuela; Rameix Welti, Marie-Anne; Eleouet, Jean-Francois; Han, Yanxiao; Kaiser, Laurent; Vukovic, Lela; Tapparel, Caroline; Král, Petr; Krol, Silke; Lembo, David; Stellacci, Francesco

    2018-02-01

    Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (~190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

  15. Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens

    Directory of Open Access Journals (Sweden)

    de Rochefort Anna

    2009-10-01

    Full Text Available Abstract Background New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures. Results Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria. Conclusion This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool.

  16. Novel α-MSH peptide analogues with broad spectrum antimicrobial activity.

    Directory of Open Access Journals (Sweden)

    Paolo Grieco

    Full Text Available Previous investigations indicate that α-melanocyte-stimulating hormone (α-MSH and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2'-7, Phe-12]-MSH(6-13 sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of α-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.

  17. Antilisterial activity of a broad-spectrum bacteriocin, enterocin LR/6 from Enterococcus faecium LR/6.

    Science.gov (United States)

    Kumar, Manoj; Srivastava, Sheela

    2010-10-01

    Enterocin LR/6, a purified bacteriocin, exhibited broad inhibitory spectrum both against related as well as some food-borne pathogens such as Listeria monocytogenes, Yersinia enterocolitica, Aeromonas sp., Shigella sp., and Bacillus licheniformis. In this investigation, we have focused on L. monocytogenes as the target organism, as it is not only an important pathogen but can also survive over a wide range of environmental conditions such as refrigeration temperature, low pH, and high-salt concentration. This allows the pathogen to overcome many food preservation and safety barriers and poses a potential risk to human health. The enterocin LR/6 showed a bactericidal action against L. monocytogenes and completely inhibited the growth on agar plates, supplemented with 200 AU/ml of enterocin LR/6. The effectiveness of enterocin LR/6 in completely killing a population of acid-adapted (pH 5.2, 2 h) L. monocytogenes exposed to different temperatures (4-37 degrees C), pH (2.5-8.0), and osmotic (up to 30% NaCl) stress is reported here. This paper focuses on the key issue of killing of the acid-adapted L. monocytogenes cells under adverse environmental conditions.

  18. Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

    Directory of Open Access Journals (Sweden)

    Wai-Leung Ng

    Full Text Available Quorum sensing (QS is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.

  19. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Directory of Open Access Journals (Sweden)

    Pan Kyeom Kim

    Full Text Available Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC. Two kinds of chimeric human antibodies (chimeric #7 and #17 were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  20. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Science.gov (United States)

    Kim, Pan Kyeom; Keum, Sun Ju; Osinubi, Modupe O V; Franka, Richard; Shin, Ji Young; Park, Sang Tae; Kim, Man Su; Park, Mi Jung; Lee, Soo Young; Carson, William; Greenberg, Lauren; Yu, Pengcheng; Tao, Xiaoyan; Lihua, Wang; Tang, Qing; Liang, Guodong; Shampur, Madhusdana; Rupprecht, Charles E; Chang, Shin Jae

    2017-01-01

    Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  1. Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CL(pro)

    Energy Technology Data Exchange (ETDEWEB)

    Bacha,U.; Barilla, J.; Gabelli, S.; Kiso, Y.; Amzel, L.; Freire, E.

    2008-01-01

    Coronaviruses comprise a large group of RNA viruses with diverse host specificity. The emergence of highly pathogenic strains like the SARS coronavirus (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. For that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. This goal can be accomplished by designing inhibitors against a target, such as the main protease 3CLpro (Mpro), which is highly conserved among all coronaviruses. Here 3CLpro derived from the SARS-CoV was used as the primary target to identify a new class of inhibitors containing a halomethyl ketone warhead. The compounds are highly potent against SARS 3CLpro with Ki's as low as 300 nm. The crystal structure of the complex of one of the compounds with 3CLpro indicates that this inhibitor forms a thioether linkage between the halomethyl carbon of the warhead and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR) studies of these compounds have led to the identification of a pharmacophore that accurately defines the essential molecular features required for the high affinity.

  2. The effects of exogenous catalase on broad-spectrum near-UV (300-400nm) treated Escherichia coli cells

    International Nuclear Information System (INIS)

    Sammartano, L.J.; Tuveson, R.W.

    1984-01-01

    Catalase incorporated into plating medium protects against inactivation and mutagenesis by broad-spectrum near-ultraviolet wavelength (300-400nm) (NUV) radiation in strains of Escherichia coli. Plating medium containing catalase does not provide protection against inactivation by wavelengths in the FUV region. Catalase added to the cell suspension during or added immediately after NUV exposure also protects against inactivation. The protection provided by catalase suggests a possible role for hydrogen peroxide in the processes of inactivation and mutagenesis by broad-spectrum NUV. (author)

  3. Broad-Spectrum Inhibitors against 3C-Like Proteases of Feline Coronaviruses and Feline Caliciviruses

    Science.gov (United States)

    Shivanna, Vinay; Narayanan, Sanjeev; Prior, Allan M.; Weerasekara, Sahani; Hua, Duy H.; Kankanamalage, Anushka C. Galasiti; Groutas, William C.; Chang, Kyeong-Ok

    2015-01-01

    ABSTRACT Feline infectious peritonitis and virulent, systemic calicivirus infection are caused by certain types of feline coronaviruses (FCoVs) and feline caliciviruses (FCVs), respectively, and are important infectious diseases with high fatality rates in members of the Felidae family. While FCoV and FCV belong to two distinct virus families, the Coronaviridae and the Caliciviridae, respectively, they share a dependence on viral 3C-like protease (3CLpro) for their replication. Since 3CLpro is functionally and structurally conserved among these viruses and essential for viral replication, 3CLpro is considered a potential target for the design of antiviral drugs with broad-spectrum activities against these distinct and highly important viral infections. However, small-molecule inhibitors against the 3CLpro enzymes of FCoV and FCV have not been previously identified. In this study, derivatives of peptidyl compounds targeting 3CLpro were synthesized and evaluated for their activities against FCoV and FCV. The structures of compounds that showed potent dual antiviral activities with a wide margin of safety were identified and are discussed. Furthermore, the in vivo efficacy of 3CLpro inhibitors was evaluated using a mouse model of coronavirus infection. Intraperitoneal administration of two 3CLpro inhibitors in mice infected with murine hepatitis virus A59, a hepatotropic coronavirus, resulted in significant reductions in virus titers and pathological lesions in the liver compared to the findings for the controls. These results suggest that the series of 3CLpro inhibitors described here may have the potential to be further developed as therapeutic agents against these important viruses in domestic and wild cats. This study provides important insights into the structure and function relationships of 3CLpro for the design of antiviral drugs with broader antiviral activities. IMPORTANCE Feline infectious peritonitis virus (FIPV) is the leading cause of death in young cats

  4. Modified lysozymes as novel broad spectrum natural antimicrobial agents in foods.

    Science.gov (United States)

    Aminlari, Ladan; Hashemi, Marjan Mohammadi; Aminlari, Mahmoud

    2014-06-01

    In recent years much attention and interest have been directed toward application of natural antimicrobial agents in foods. Some naturally occurring proteins such as lactoperoxidase, lactoferrin, and lysozyme have received considerable attention and are being considered as potential antimicrobial agents in foods. Lysozyme kills bacteria by hydrolyzing the peptidoglycan layer of the cell wall of certain bacterial species, hence its application as a natural antimicrobial agent has been suggested. However, limitations in the action of lysozyme against only Gram-positive bacteria have prompted scientists to extend the antimicrobial effects of lysozyme by several types of chemical modifications. During the last 2 decades extensive research has been directed toward modification of lysozyme in order to improve its antimicrobial properties. This review will report on the latest information available on lysozyme modifications and examine the applicability of the modified lysozymes in controlling growth of Gram-positive and Gram-negative bacteria in foods. The results of modifications of lysozyme using its conjugation with different small molecule, polysaccharides, as well as modifications using proteolytic enzymes will be reviewed. These types of modifications have not only increased the functional properties of lysozyme (such as solubility and heat stability) but also extended the antimicrobial activity of lysozyme. Many examples will be given to show that modification can decrease the count of Gram-negative bacteria in bacterial culture and in foods by as much as 5 log CFU/mL and in some cases essentially eliminated Escherichia coli. In conclusion this review demonstrates that modified lysozymes are excellent natural food preservatives, which can be used in food industry. The subject described in this review article can lead to the development of methods to produce new broad-spectrum natural antimicrobial agents, based on modification of chicken egg white lysozyme, which

  5. Overexpression of NPR1 in Brassica juncea Confers Broad Spectrum Resistance to Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Sajad Ali

    2017-10-01

    Full Text Available Brassica juncea (Indian mustard is a commercially important oil seed crop, which is highly affected by many biotic stresses. Among them, Alternaria leaf blight and powdery mildew are the most devastating diseases leading to huge yield losses in B. juncea around the world. In this regard, genetic engineering is a promising tool that may possibly allow us to enhance the B. juncea disease resistance against these pathogens. NPR1 (non-expressor of pathogen-related gene 1 is a bonafide receptor of salicylic acid (SA which modulates multiple immune responses in plants especially activation of induced and systemic acquired resistance (SAR. Here, we report the isolation and characterization of new NPR1 homolog (BjNPR1 from B. juncea. The phylogenetic tree constructed based on the deduced sequence of BjNPR1 with homologs from other species revealed that BjNPR1 grouped together with other known NPR1 proteins of Cruciferae family, and was nearest to B. napus. Furthermore, expression analysis showed that BjNPR1 was upregulated after SA treatment and fungal infection but not by jasmonic acid or abscisic acid. To understand the defensive role of this gene, we generated B. juncea transgenic lines overexpressing BjNPR1, and further confirmed by PCR and Southern blotting. The transgenic lines showed no phenotypic abnormalities, and constitutive expression of BjNPR1 activates defense signaling pathways by priming the expression of antifungal PR genes. Moreover, BjNPR1 transgenic lines showed enhanced resistance to Alternaria brassicae and Erysiphe cruciferarum as there was delay in symptoms and reduced disease severity than non-transgenic plants. In addition, the rate of disease spreading to uninfected or distal parts was also delayed in transgenic plants thus suggesting the activation of SAR. Altogether, the present study suggests that BjNPR1 is involved in broad spectrum of disease resistance against fungal pathogens.

  6. Broad spectrum antimicrobial activity of melimine covalently bound to contact lenses.

    Science.gov (United States)

    Dutta, Debarun; Cole, Nerida; Kumar, Naresh; Willcox, Mark D P

    2013-01-07

    To develop a stable antimicrobial contact lens, which is effective against the International Organization for Standardization (ISO) panel microorganisms, Acanthamoeba castellanii and drug resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Melimine was covalently incorporated into etafilcon A lenses. The amount of peptide present on the lens surface was quantified using amino acid analysis. After coating, the heat stability (121°C), lens surface hydrophobicity (by captive bubble), and in vitro cytotoxicity to mouse L929 cells of the lenses were investigated. Antimicrobial activity against the micro-organisms was evaluated by viable plate count and fluorescence microscopy, measuring the proportion of cell death compared with control lenses with no melimine. The most effective concentration was determined to be 152 ± 44 μg lens(-1) melimine on the lens surface. After coating, lenses were relatively hydrophilic and were nontoxic to mammalian cells. The activity remained high after autoclaving (e.g., 3.1, 3.9, 1.2, and 1.0 log inhibition against P. aeruginosa, S. aureus, A. castellanii, and Fusarium solani, respectively). Fluorescence microscopy confirmed significantly reduced (P bacteria to melimine contact lenses. Viable count confirmed that lenses were active against all the bacteria and fungi from the ISO panel, Acanthamoeba and gave at least 2 log inhibition against all the multidrug resistant S. aureus and P. aeruginosa strains. Melimine may offer excellent potential for development as a broad spectrum antimicrobial coating for contact lenses, showing activity against all the bacterial and fungal ISO panel microorganisms, Acanthamoeba, and antibiotic resistant strains of P. aeruginosa and S. aureus.

  7. The use of inexpensive broad spectrum lower toxicity therapeutics in chronic lymphocytic leukemia.

    Science.gov (United States)

    Marjanovic, Goran

    2017-01-01

    The use of new and highly efficient targeted therapies for chronic lymphocytic leukemia (CLL) is costly and out of reach for many health care systems. On the other hand, in recent years, few inexpensive, broad-spectrum low-toxicity therapeutics have proven to be effective both in the preclinical and clinical settings. In early-stage CLL, the use of 2000 mg of epigallocatechin-3-gallate (EGCG) from the green tea extract twice a day was able to reduce the absolute leukocyte count. Supplementation of >2000 IU/day of Vitamin D in early low-risk CLL patients is able to delay disease progression and postpone the moment of initiation of the first treatment. The doses of both vitamin D and EGCG were shown to be safe in older patients. Vitamin D, EGCG and Curcumin, either as monotherapy or in combination, have additive and synergistic effects with conventional chemotherapy. Further observations have identified the improvement of response to rituximab-fludarabine-cyclophosphamide (R-FC) therapy with concomitant administration of statin and aspirin combination in relapsed/refractory CLL. Finally, high dose dexamethasone with 40mg/m 2 /day for 4 days, every 28 days, either alone or with monoclonal antibody, might be used as a salvage therapy or for debulking before transplantation in refractory/resistant cases. Dexamethasone therapy is followed by transient response and high rate of infections, but fluid retention and other toxicities are lower compared to high dose methylprednisolone schedules. The low cost therapeutics discussed in this review could not be a substitute for the more effective targeted therapies, but their use in every day practice might postpone the need for early implementation of new and costly medications.

  8. Isolation and Characterization of a Broad Spectrum Bacteriocin from Bacillus amyloliquefaciens RX7

    Directory of Open Access Journals (Sweden)

    Kong Boon Lim

    2016-01-01

    Full Text Available We isolated a Bacillus strain, RX7, with inhibitory activity against Listeria monocytogenes from soil and identified it as Bacillus amyloliquefaciens based on 16S rRNA gene sequencing. The inhibitory activity was stable over a wide range of pH and was fully retained after 30 min at 80°C, after which it decreased gradually at higher temperatures. The activity was sensitive to the proteolytic action of α-chymotrypsin, proteinase-K, and trypsin, indicating its proteinaceous nature. This bacteriocin was active against a broad spectrum of bacteria and the fungus Candida albicans. Direct detection of antimicrobial activity on a sodium dodecyl sulfate-polyacrylamide gel suggested an apparent molecular mass of approximately 5 kDa. Ammonium sulfate precipitation and anion-exchange and gel permeation chromatography integrated with reverse phase-high-performance liquid chromatography were used for bacteriocin purification. Automated N-terminal Edman degradation of the purified RX7 bacteriocin recognized the first 15 amino acids as NH2-X-Ala-Trp-Tyr-Asp-Ile-Arg-Lys-Leu-Gly-Asn-Lys-Gly-Ala, where the letter X in the sequence indicates an unknown or nonstandard amino acid. Based on BLAST similarity search and multiple alignment analysis, the obtained partial sequence showed high homology with the two-peptide lantibiotic haloduracin (HalA1 from Bacillus halodurans, although at least two amino acids differed between the sequences. A time-kill study demonstrated a bactericidal mode of action of RX7 bacteriocin.

  9. Characteristics of a broad lytic spectrum endolysin from phage BtCS33 of Bacillus thuringiensis

    Directory of Open Access Journals (Sweden)

    Yuan Yihui

    2012-12-01

    Full Text Available Abstract Background Endolysins produced by bacteriophages lyse bacteria, and are thus considered a novel type of antimicrobial agent. Several endolysins from Bacillus phages or prophages have previously been characterized and used to target Bacillus strains that cause disease in animals and humans. B. thuringiensis phage BtCS33 is a Siphoviridae family phage and its genome has been sequenced and analyzed. In the BtCS33 genome, orf18 was found to encode an endolysin protein (PlyBt33. Results Bioinformatic analyses showed that endolysin PlyBt33 was composed of two functional domains, the N-terminal catalytic domain and the C-terminal cell wall binding domain. In this study, the entire endolysin PlyBt33, and both the N- and C-termini,were expressed in Escherichia coli and then purified. The lytic activities of PlyBt33 and its N-terminus were tested on bacteria. Both regions exhibited lytic activity, although PlyBt33 showed a higher lytic activity than the N-terminus. PlyBt33 exhibited activity against all Bacillus strains tested from five different species, but was not active against Gram-negative bacteria. Optimal conditions for PlyBt33 reactivity were pH 9.0 and 50°C. PlyBt33 showed high thermostability, with 40% of initial activity remaining following 1 h of treatment at 60°C. The C-terminus of PlyBt33 bound to B. thuringiensis strain HD-73 and Bacillus subtilis strain 168. This cell wall binding domain might be novel, as its amino acid sequence showed little similarity to previously reported endolysins. Conclusions PlyBt33 showed potential as a novel antimicrobial agent at a relatively high temperature and had a broad lytic spectrum within the Bacillus genus. The C-terminus of PlyBt33 might be a novel kind of cell wall binding domain.

  10. Wild Coastline Birds as Reservoirs of Broad-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Miami Beach, Florida

    Science.gov (United States)

    Potron, Anaïs; De La Cuesta, Carolina; Cleary, Timothy; Nordmann, Patrice; Munoz-Price, L. Silvia

    2012-01-01

    A high rate of broad-spectrum-β-lactamase-producing Escherichia coli isolates was identified from seagull and pelican feces collected in the Miami Beach, Florida, area. The most commonly identified resistance determinants were CMY-2 and CTX-M-15. Those wild birds might be therefore considered vehicles for wide dissemination of multidrug-resistant Enterobacteriaceae in the United States. PMID:22314536

  11. Psychological Adjustment and Sibling Relationships in Siblings of Children with Autism Spectrum Disorders: Environmental Stressors and the Broad Autism Phenotype

    Science.gov (United States)

    Petalas, Michael A.; Hastings, Richard P.; Nash, Susie; Hall, Louise M.; Joannidi, Helen; Dowey, Alan

    2012-01-01

    Research with siblings of children with Autism Spectrum Disorders (ASD) suggests that they may be at increased risk for behavioural and emotional problems and relatively poor sibling relationships. This study investigated a diathesis-stress model, whereby the presence of Broad Autism Phenotype features in the typically developing siblings might…

  12. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

    2016-01-01

    with the resistance evolved after single-drug exposure. Combination therapy selected for mutants that displayed broad-spectrum resistance, and a major resistance mechanism was mutational inactivation of the repressor gene mexR that regulates the multidrug efflux operon mexAB–oprM. Deregulation of this operon led...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  13. Acute mastoiditis in children: Middle ear cultures may help in reducing use of broad spectrum antibiotics.

    Science.gov (United States)

    Garcia, Catarina; Salgueiro, Ana Bárbara; Luís, Catarina; Correia, Paula; Brito, Maria João

    2017-01-01

    Acute mastoiditis (AM) is a suppurative infection of the mastoid air cells, representing the most frequent complication of acute otitis media. AM remains an important entity in children due to its potential complications and sequelae. We aim to describe the cases of AM admitted at our department, identify risk factors potentially associated with complications and analyse the changes in clinical approach of AM over time. Case review of clinical files of children admitted with acute mastoiditis from June 1996 to May 2013 at a Lisbon metropolitan area hospital. Data was divided into two groups (prior and after May 2005) in order to evaluate changes in AM approach over the years. 135 AM episodes were included. The median age was 3.8 years and 42% children were less than 24 months of age. Symptoms at presentation included fever (69%), ear pain (56%) and otorrhea (40%). Complications occurred in 22% patients and were more common in children under 24 months (33% vs 15%, p ≤ 0.01). Leukocyte count was significantly higher in children with complications (16.7 vs 14.5 × 10 9 /μL, p ≤ 0.05) as was C-Reactive Protein value (13 vs 6.3 mg/dL, p ≤ 0.001). There was a significant association between the development of complications and C-Reactive Protein value at admission (OR 1.892; IC95%: 1.018-2.493, p ≤ 0.01). The optimal cut-off value was 7.21 mg/dL. Over time there was a significant increase in middle ear cultures obtained by tympanocentesis during surgery (2% vs 16%, p ≤ 0,01) and also a decrease in the use of broad spectrum antibiotherapy as initial treatment (52% vs 25%,p ≤ 0,001). Children under 24 months, with high leukocyte count or with high C-Reactive Protein value should be monitored closely since complications tend to be more frequent. A CRP value of 7.21 mg/dL at admission seems to be a good cut-off to monitor children for potential complications. Throughout the period analysed more cultures were performed allowing identification of

  14. Integrated DNA walking system to characterize a broad spectrum of GMOs in food/feed matrices.

    Science.gov (United States)

    Fraiture, Marie-Alice; Herman, Philippe; Lefèvre, Loic; Taverniers, Isabel; De Loose, Marc; Deforce, Dieter; Roosens, Nancy H

    2015-08-14

    In order to provide a system fully integrated with qPCR screening, usually used in GMO routine analysis, as well as being able to detect, characterize and identify a broad spectrum of GMOs in food/feed matrices, two bidirectional DNA walking methods targeting p35S or tNOS, the most common transgenic elements found in GM crops, were developed. These newly developed DNA walking methods are completing the previously implemented DNA walking method targeting the t35S pCAMBIA element. Food/feed matrices containing transgenic crops (Bt rice or MON863 maize) were analysed using the integrated DNA walking system. First, the newly developed DNA walking methods, anchored on the sequences used for the p35S or tNOS qPCR screening, were tested on Bt rice that contains these two transgenic elements. Second, the methods were assessed on a maize sample containing a low amount of the GM MON863 event, representing a more complex matrix in terms of genome size and sensitivity. Finally, to illustrate its applicability in GMO routine analysis by enforcement laboratories, the entire workflow of the integrated strategy, including qPCR screening to detect the potential presence of GMOs and the subsequent DNA walking methods to characterize and identify the detected GMOs, was applied on a GeMMA Scheme Proficiency Test matrix. Via the characterization of the transgene flanking region between the transgenic cassette and the plant genome as well as of a part of the transgenic cassette, the presence of GMOs was properly confirmed or infirmed in all tested samples. Due to their simple procedure and their short time-frame to get results, the developed DNA walking methods proposed here can be easily implemented in GMO routine analysis by the enforcement laboratories. In providing crucial information about the transgene flanking regions and/or the transgenic cassettes, this DNA walking strategy is a key molecular tool to prove the presence of GMOs in any given food/feed matrix.

  15. Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions.

    Science.gov (United States)

    Kidane, Yared H; Lawrence, Christopher; Murali, T M

    2013-10-07

    newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.

  16. Reverse engineering truncations of an antimicrobial peptide dimer to identify the origins of potency and broad spectrum of action.

    Science.gov (United States)

    Anantharaman, Aparna; Sahal, Dinkar

    2010-08-26

    Antimicrobial peptides hold promise against antibiotic resistant pathogens. Here, to find the physicochemical origins of potency and broad spectrum antimicrobial action, we report the structure-activity relationships of synthetic intermediates (peptides A-D) of a potent lysine branched dimeric antibacterial peptide DeltaFd. Our studies show that a tetracationic character in a weak helical fold (peptide C) elicits potent but narrow spectrum antimicrobial activity [Minimum inhibitory concentrations (MICs) E. coli 10 microM, S. aureus>100 microM]. In contrast, a hexacationic character in a strong, amphipathic helix (DeltaFd) confers potent and broad spectrum action [MICs E. coli 2.5 microM, S. aureus 5 microM]. While DeltaFd caused rapid and potent permeabilization of the E. coli membranes, the less helical intermediates (peptides A-D) showed slow and weak to no responses. Two seminal findings that may aid future drug design are (a) at identical helicity, increasing charge enhanced outer membrane permeabilization, and (b) at identical charge, increasing helicity stimulated rate of outer membrane permeabilization and kill kinetics besides enhancing potency leading to broad spectrum action.

  17. Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals

    Science.gov (United States)

    2011-01-01

    Background Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study. Methods During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics - that is second- and third-generation cephalosporins, carbapenems, and quinolones - in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs) for antibiotics were used as measurement units (WHO ATC/DDD classification). Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics. Results Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01) used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks), whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin) were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4-weeks interval

  18. Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals.

    Science.gov (United States)

    Haug, Jon B; Myhr, Randi; Reikvam, Asmund

    2011-12-13

    Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study. During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics--that is second- and third-generation cephalosporins, carbapenems, and quinolones--in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs) for antibiotics were used as measurement units (WHO ATC/DDD classification). Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics. Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01) used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks), whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin) were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4-weeks interval. There is a need for caution in

  19. The secreted fructose 1,6-bisphosphate aldolase as a broad spectrum vaccine candidate against pathogenic bacteria in aquaculture.

    Science.gov (United States)

    Sun, Zhongyang; Shen, Binbing; Wu, Haizhen; Zhou, Xiangyu; Wang, Qiyao; Xiao, Jingfan; Zhang, Yuanxing

    2015-10-01

    The development of aquaculture has been hampered by different aquatic pathogens that can cause edwardsiellosis, vibriosis, or other diseases. Therefore, developing a broad spectrum vaccine against different fish diseases is necessary. In this study, fructose 1,6-bisphosphate aldolase (FBA), a conserved enzyme in the glycolytic pathway, was demonstrated to be located in the non-cytoplasmic components of five aquatic pathogenic bacteria and exhibited remarkable protection and cross-protection against these pathogens in turbot and zebrafish. Further analysis revealed that sera sampled from vaccinated turbot had a high level of specific antibody and bactericidal activity against these pathogens. Meanwhile, the increased expressions of immune response-related genes associated with antigen recognition and presentation indicated that the adaptive immune response was effectively aroused. Taken together, our results suggest that FBA can be utilized as a broad-spectrum vaccine against various pathogenic bacteria of aquaculture in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Screening of broad spectrum natural pesticides against conserved target arginine kinase in cotton pests by molecular modeling.

    Science.gov (United States)

    Sakthivel, Seethalakshmi; Habeeb, S K M; Raman, Chandrasekar

    2018-03-12

    Cotton is an economically important crop and its production is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved target across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag profiling from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One target protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum target which are highly specific to invertebrates.

  1. 宽光谱太阳能电池%Broad-Spectrum Solar Cell

    Institute of Scientific and Technical Information of China (English)

    李承辉; 王锴; 郑玮; 王致祥; 刘建; 游效曾

    2012-01-01

    太阳能电池的光谱响应特性和光电转换效率与光伏材料的微观能带结构及其宏观组装方式密切相关。无论使用哪种光伏材料,普通单结或单层太阳能电池都只能对部分波段的太阳光进行有效利用。宽光谱研究的目标是要使太阳能电池更好地利用太阳光谱所覆盖的全部波段范围的能量,从而提高太阳能电池光电转换效率。本文从化学角度综述了实现宽光谱太阳能电池的基本方法和当前的研究进展,其中包括叠层太阳能电池、中间带太阳能电池、量子点太阳能电池、热光伏太阳能电池、上转换和下转换、分子基柔性太阳能电池等方法。%Due to the energy crisis, utilization of renewable energy sources has been intensively investigated in recent years. Among a variety of renewable energy sources, solar energy is a sustainable alternative option that can be utilized in various ways and can be used for many applications. Converting directly the sunlight to electricity through solar cells is the most common and effective way to use solar energy. The spectral response and overall photo-to-electric energy conversion efficiency of solar cells are closely correlated to the micro band-gap structure and macro assembly process of photovoltaie materials. A solar cell can effectively utilize photons with energy hu close to the semiconductor band gap E,. Photons with energy smaller than the band gap are not absorbed. On the other hand, photons with energy larger than the band gap are absorbed, but the excess energy hu - Eg is not used effectively due to thermalization. Therefore, a normal single junction or single layer solar cell can only use part of the solar radiation no matter what kind of photovoltaic materials are used. Broad-spectrum solar cell aims to use most of the solar energy effectively via several structures or methods: Tandem solar cells, intermediate-band solar cells, quantum dot solar cells

  2. Broad-spectrum physical fitness benefits of recreational football: a systematic review and meta-analysis.

    Science.gov (United States)

    Milanović, Zoran; Pantelić, Saša; Čović, Nedim; Sporiš, Goran; Mohr, Magni; Krustrup, Peter

    2018-01-25

    participants with mild hypertension (11 and 7 mm Hg decrease, respectively) and participants with prehypertension (10 and 7 mm Hg decrease, respectively). Meta-analysis of recreational football determined the impact on resting heart rate as most likely extremely largely beneficial (ES=6.03 beats/min; 95% CI 4.43 to 7.64) when compared with non-active groups. The observed recreational football effect on fat mass was most likely largely beneficial (ES=1.72 kg; 95% CI 0.86 to 2.58) and the effect on countermovement jump (CMJ) performance was most likely very largely beneficial (ES=2.27 cm; 95% CI 1.29 to 3.25) when compared with non-active groups. Possibly beneficial decreases were found in low-density lipoprotein levels (ES=0.21 mmol/L; 95% CI 0.06 to 0.36). Possibly largely beneficial effect was observed for DBP in comparison with continuous running training. Small harmful and unclear results were noted for SBP, fat and lean body mass, body mass index, as well as muscular fitness when compared with running and Zumba training. The present meta-analysis demonstrated multiple broad-spectrum benefits of recreational football on health-related physical fitness compared with no-exercise controls, including improvements in blood pressure, resting heart rate, fat mass, low-density lipoprotein cholesterol and CMJ performance. Additionally, recreational football is efficient and effective as Zumba and continuous running exercise regimens with highlighted social, motivational and competitive components. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Molecular detection of TEM broad spectrum β-lactamase in clinical ...

    African Journals Online (AJOL)

    Resistance to β-lactam antibiotics, along with clinical isolates, frequently results to production of β- lactamase enzymes. In recent years, the production of extended spectrum β-lactamases (ESBLs) among clinical isolates, especially Escherichia coli has greatly increased. On the other hand, β lactamase genes have several ...

  4. Broad spectrum detoxification: the major longevity assurance process regulated by insulin/IGF-1 signaling?

    Science.gov (United States)

    Gems, David; McElwee, Joshua J

    2005-03-01

    Our recent survey of genes regulated by insulin/IGF-1 signaling (IIS) in Caenorhabditis elegans suggests a role for a number of gene classes in longevity assurance. Based on these findings, we propose a model for the biochemistry of longevity assurance and ageing, which is as follows. Ageing results from molecular damage from highly diverse endobiotic toxins. These are stochastic by-products of diverse metabolic processes, of which reactive oxygen species (ROS) are likely to be only one component. Our microarray analysis suggests a major role in longevity assurance of the phase 1, phase 2 detoxification system involving cytochrome P450 (CYP), short-chain dehydrogenase/reductase (SDR) and UDP-glucuronosyltransferase (UGT) enzymes. Unlike superoxide and hydrogen peroxide detoxification, this system is energetically costly, and requires the excretion from the cell of its products. Given such costs, its activity may be selected against, as predicted by the disposable soma theory. CYP and UGT enzymes target lipophilic molecular species; insufficient activity of this system is consistent with age-pigment (lipofuscin) accumulation during ageing. We suggest that IIS-regulated longevity assurance involves: (a) energetically costly detoxification and excretion of molecular rubbish, and (b) conservation of existing proteins via molecular chaperones. Given the emphasis in this theory on investment in cellular waste disposal, and on protein conservation, we have dubbed it the green theory.

  5. Broad photoelectron spectrum and lowered electron affinity due to hydrogen in ZnOH: A joint experimental and theoretical study

    Science.gov (United States)

    Iordanov, I.; Gunaratne, K. D. D.; Harmon, C. L.; Sofo, J. O.; Castleman, A. W.

    2012-06-01

    We report a combined experimental and theoretical photoelectron spectroscopy study of ZnOH-. We find that the electron binding energy spectrum of ZnOH- reveals a broad and featureless peak between 1.4 and 2.4 eV in energy. The vertical detachment energy (VDE) of ZnOH- is determined to be 1.78 eV, which is lower than the 2.08 eV VDE of ZnO-. Our theoretical calculations match the VDE of ZnOH- accurately, but we find that the broadness of the peak cannot be explained by rotational or vibrational state excitation. The broadness of this peak is in strong contrast to the narrow and easily understood first peak of the ZnO spectrum, which features a well-resolved vibrational progression that can be readily explained by calculating the Franck-Condon transition factors. This study provides spectroscopic evidence of the effect of hydrogen on diatomic ZnO.

  6. Preclinical evaluation of novel triphenylphosphonium salts with broad-spectrum activity.

    Directory of Open Access Journals (Sweden)

    Melissa Millard

    Full Text Available BACKGROUND: Recently, there has been a surge of interest in developing compounds selectively targeting mitochondria for the treatment of neoplasms. The critical role of mitochondria in cellular metabolism and respiration supports this therapeutic rationale. Dysfunction in the processes of energy production and metabolism contributes to attenuation of response to pro-apoptotic stimuli and increased ROS production both of which are implicated in the initiation and progression of most human cancers. METHODOLOGY/PRINCIPAL FINDINGS: A high-throughput MTT-based screen of over 10,000 drug-like small molecules for anti-proliferative activity identified the phosphonium salts TP187, 197 and 421 as having IC₅₀ concentrations in the submicromolar range. TP treatment induced cell cycle arrest independent of p53 status, as determined by analysis of DNA content in propidium iodide stained cells. In a mouse model of human breast cancer, TP-treated mice showed significantly decreased tumor growth compared to vehicle or paclitaxel treated mice. No toxicities or organ damage were observed following TP treatment. Immunohistochemical staining of tissue sections from TP187-treated tumors demonstrated a decrease in cellular proliferation and increased caspase-3 cleavage. The fluorescent properties of analog TP421 were exploited to assess subcellular uptake of TP compounds, demonstrating mitochondrial localization. Following mitochondrial uptake cells exhibited decreased oxygen consumption and concomittant increase in mitochondrial superoxide production. Proteomics analysis of results from a 600 target antibody microarray demonstrated that TP compounds significantly affected signaling pathways relevant to growth and proliferation. CONCLUSIONS/SIGNIFICANCE: Through our continued interest in designing compounds targeting cancer-cell metabolism, the Warburg effect, and mitochondria we recently discovered a series of novel, small-molecule compounds containing a

  7. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

    Science.gov (United States)

    Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

    2017-12-19

    Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868

  8. Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen

    Science.gov (United States)

    Hohenadel, I; Kiworr, M; Genitsariotis, R; Zeidler, D; Lorenz, J

    2001-01-01

    BACKGROUND—In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR).
METHODS—With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography. All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites. Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated. We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR.
RESULTS—Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients. Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days. Pathologically relevant isolates were found in 65% of all patients. Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus). In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment. Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%).
CONCLUSIONS—Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL. BAL is a relatively safe

  9. The RF Probe: providing space situational awareness through broad-spectrum detection and characterization

    Science.gov (United States)

    Zenick, Raymond; Kohlhepp, Kimberly; Partch, Russell

    2004-09-01

    AeroAstro's patented RF Probe is a system designed to address the needs of spacecraft developers and operators interested in measuring and analyzing near-field RF emissions emanating from a nearby spacecraft of interest. The RF Probe consists of an intelligent spectrum analyzer with digital signal processing capabilities combined with a calibrated, wide-bandwidth antenna and RF front end that covers the 50 kHz to 18 GHz spectrum. It is capable of acquiring signal level and signal vector information, classifying signals, assessing the quality of a satellite"s transponders, and characterizing near-field electromagnetic emissions. The RF Probe is intended for either incorporation as part of a suite of spacecraft sensors, or as a stand-alone sensor on spacecraft or other platforms such as Unmanned Aerial Vehicles (UAVs). The RF Probe was initially conceived as a tool to detect and aid in diagnosis of malfunctions in a spacecraft of interest. However, the utility of the RF Probe goes far beyond this initial concept, spanning a wide range of military applications. Most importantly, the RF Probe can provide space situational awareness for critical on-orbit assets by detecting externally induced RF fields, aiding in protection against potentially devastating attacks.

  10. Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior.

    Science.gov (United States)

    Tielbeek, Jorim J; Johansson, Ada; Polderman, Tinca J C; Rautiainen, Marja-Riitta; Jansen, Philip; Taylor, Michelle; Tong, Xiaoran; Lu, Qing; Burt, Alexandra S; Tiemeier, Henning; Viding, Essi; Plomin, Robert; Martin, Nicholas G; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant; Beaver, Kevin M; Waldman, Irwin; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Perry, John R B; Munafò, Marcus; LoParo, Devon; Paunio, Tiina; Tiihonen, Jari; Mous, Sabine E; Pappa, Irene; de Leeuw, Christiaan; Watanabe, Kyoko; Hammerschlag, Anke R; Salvatore, Jessica E; Aliev, Fazil; Bigdeli, Tim B; Dick, Danielle; Faraone, Stephen V; Popma, Arne; Medland, Sarah E; Posthuma, Danielle

    2017-12-01

    Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation

  11. Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome.

    Science.gov (United States)

    Balci, Tugce B; Davila, Jorge; Lewis, Denice; Boafo, Addo; Sell, Erick; Richer, Julie; Nikkel, Sarah M; Armour, Christine M; Tomiak, Eva; Lines, Matthew A; Sawyer, Sarah L

    2018-01-01

    White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals. © 2017 Wiley Periodicals, Inc.

  12. Snake Venom PLA2, a Promising Target for Broad-Spectrum Antivenom Drug Development

    Directory of Open Access Journals (Sweden)

    Huixiang Xiao

    2017-01-01

    Full Text Available Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae. Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.

  13. Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

    Science.gov (United States)

    Tammimies, Kristiina; Marshall, Christian R; Walker, Susan; Kaur, Gaganjot; Thiruvahindrapuram, Bhooma; Lionel, Anath C; Yuen, Ryan K C; Uddin, Mohammed; Roberts, Wendy; Weksberg, Rosanna; Woodbury-Smith, Marc; Zwaigenbaum, Lonnie; Anagnostou, Evdokia; Wang, Zhuozhi; Wei, John; Howe, Jennifer L; Gazzellone, Matthew J; Lau, Lynette; Sung, Wilson W L; Whitten, Kathy; Vardy, Cathy; Crosbie, Victoria; Tsang, Brian; D'Abate, Lia; Tong, Winnie W L; Luscombe, Sandra; Doyle, Tyna; Carter, Melissa T; Szatmari, Peter; Stuckless, Susan; Merico, Daniele; Stavropoulos, Dimitri J; Scherer, Stephen W; Fernandez, Bridget A

    2015-09-01

    The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). All probands underwent CMA, with WES performed for 95 proband-parent trios. The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may

  14. Endophytic Paraconiothyrium sp. from Zingiber officinale Rosc. Displays Broad-Spectrum Antimicrobial Activity by Production of Danthron.

    Science.gov (United States)

    Anisha, C; Sachidanandan, P; Radhakrishnan, E K

    2018-03-01

    The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp. The bioactive compound produced by the isolate was separated by bioactivity-guided fractionation and was identified by GC-MS as danthron, an anthraquinone derivative. PCR amplification showed the presence of non-reducing polyketide synthase gene (NR-PKS) in the endophyte GFM13, which is reported to be responsible for the synthesis of anthraquinones in fungi. This is the first report of danthron being produced as the biologically active component of Paraconiothyrium sp. Danthron is reported to have wide pharmaceutical and agronomic applications which include its use as a fungicide in agriculture. The broad-spectrum antimicrobial activity of danthron and the endophytic origin of Paraconiothyrium sp. offer immense applications of the study.

  15. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    International Nuclear Information System (INIS)

    Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J.; Wood, T.E.; Croll, L.M.; Reynolds, J.H.; Dahn, J.R.

    2010-01-01

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO 3 ) 2 /0.04 M H 3 PO 4 .12MoO 3 /4 M HNO 3 solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  16. An aggregated perylene-based broad-spectrum, efficient and label-free quencher for multiplexed fluorescent bioassays.

    Science.gov (United States)

    Liu, Tao; Hu, Rong; Lv, Yi-Fan; Wu, Yuan; Liang, Hao; Huan, Shuang-Yan; Zhang, Xiao-Bing; Tan, Weihong; Yu, Ru-Qin

    2014-08-15

    Fluorescent sensing systems based on the quenching of fluorophores have found wide applications in bioassays. An efficient quencher will endow the sensing system a high sensitivity. The frequently used quenchers are based on organic molecules or nanomaterials, which usually need tedious synthesizing and modifying steps, and exhibit different quenching efficiencies to different fluorophores. In this work, we for the first time report that aggregated perylene derivative can serve as a broad-spectrum and label-free quencher that is able to efficiently quench a variety of fluorophores, such as green, red and far red dyes labeled on DNA. By choosing nucleases as model biomolecules, such a broad-spectrum quencher was then employed to construct a multiplexed bioassay platform through a label-free manner. Due to the high quenching efficiency of the aggregated perylene, the proposed platform could detect nuclease with high sensitivity, with a detection limit of 0.03U/mL for EcoRV, and 0.05U/mL for EcoRI. The perylene quencher does not affect the activity of nuclease, which makes it possible to design post-addition type bioassay platform. Moreover, the proposed platform allows simultaneous and multicolor analysis of nucleases in homogeneous solution, demonstrating its value of potential application in rapid screening of multiple bio-targets. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei.

    Science.gov (United States)

    Abdelbaqi, Suha; Deslouches, Berthony; Steckbeck, Jonathan; Montelaro, Ronald; Reed, Douglas S

    2016-02-01

    Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL-37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50% killing of F. tularensis at a concentration of 12.5 μM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections.

  18. Changes in Cell Viability of Wounded Fibroblasts following Laser Irradiation in Broad-Spectrum or Infrared Light

    International Nuclear Information System (INIS)

    Hawkins, D.; Abrahamse, H.

    2007-01-01

    Objective. This study aimed to establish if broad-spectrum or infrared (IR) light in combination with laser therapy can assist phototherapy to improve the cell function of wounded cells. Background. The effect of laser light may be partly or completely reduced by broad-spectrum light. Methods. Wounded human skin fibroblasts were irradiated with 5 J/cm2 using a helium-neon laser, a diode laser, or an Nd:YAG laser in the dark, in the light, or in IR. Changes in cell viability were evaluated by cell morphology, ATP cell viability, LDH membrane integrity, and caspase 3/7 as an early marker of apoptosis. Results. Wounded cells exposed to 5 J/cm2 using 632.8 nm in the dark or 830 nm in the light or 1064 nm in the dark showed an increase in ATP viability, an increase in cytokine expression, and a decrease in LDH cytotoxicity indicating that the metabolic activity of the wounded cells was stimulated. Conclusion. Wounded cells irradiated in IR light showed an undesirable thermal effect that was proportional to the duration of exposure.

  19. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J. [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Wood, T.E. [3M Company, St. Paul, MN, 55144 (United States); Croll, L.M.; Reynolds, J.H. [3M Canada Company, Brockville, Ontario, K6V 5V8 (Canada); Dahn, J.R., E-mail: jeff.dahn@dal.ca [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada)

    2010-08-15

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO{sub 3}){sub 2}/0.04 M H{sub 3}PO{sub 4}.12MoO{sub 3}/4 M HNO{sub 3} solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  20. Broad spectrum pesticide application alters natural enemy communities and may facilitate secondary pest outbreaks

    Science.gov (United States)

    Macfadyen, Sarina; Nash, Michael A.

    2017-01-01

    Background Pesticide application is the dominant control method for arthropod pests in broad-acre arable systems. In Australia, organophosphate pesticides are often applied either prophylactically, or reactively, including at higher concentrations, to control crop establishment pests such as false wireworms and earth mite species. Organophosphates are reported to be disruptive to beneficial species, such as natural enemies, but this has not been widely assessed in Australian systems. Neither has the risk that secondary outbreaks may occur if the natural enemy community composition or function is altered. Methods We examine the abundance of ground-dwelling invertebrate communities in an arable field over successive seasons under rotation; barley, two years of wheat, then canola. Two organophosphates (chlorpyrifos and methidathion) were initially applied at recommended rates. After no discernible impact on target pest species, the rate for chlorpyrifos was doubled to elicit a definitive response to a level used at establishment when seedling damage is observed. Invertebrates were sampled using pitfalls and refuge traps throughout the experiments. We applied measures of community diversity, principal response curves and multiple generalised linear modelling techniques to understand the changes in pest and natural enemy communities. Results There was large variability due to seasonality and crop type. Nevertheless, both pest (e.g., mites and aphids) and natural enemy (e.g., predatory beetles) invertebrate communities were significantly affected by application of organophosphates. When the rate of chlorpyrifos was increased there was a reduction in the number of beetles that predate on slug populations. Slugs displayed opposite trends to many of the other target pests, and actually increased in numbers under the higher rates of chlorpyrifos in comparison to the other treatments. Slug numbers in the final rotation of canola resulted in significant yield loss regardless

  1. Broad spectrum pesticide application alters natural enemy communities and may facilitate secondary pest outbreaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Hill

    2017-12-01

    Full Text Available Background Pesticide application is the dominant control method for arthropod pests in broad-acre arable systems. In Australia, organophosphate pesticides are often applied either prophylactically, or reactively, including at higher concentrations, to control crop establishment pests such as false wireworms and earth mite species. Organophosphates are reported to be disruptive to beneficial species, such as natural enemies, but this has not been widely assessed in Australian systems. Neither has the risk that secondary outbreaks may occur if the natural enemy community composition or function is altered. Methods We examine the abundance of ground-dwelling invertebrate communities in an arable field over successive seasons under rotation; barley, two years of wheat, then canola. Two organophosphates (chlorpyrifos and methidathion were initially applied at recommended rates. After no discernible impact on target pest species, the rate for chlorpyrifos was doubled to elicit a definitive response to a level used at establishment when seedling damage is observed. Invertebrates were sampled using pitfalls and refuge traps throughout the experiments. We applied measures of community diversity, principal response curves and multiple generalised linear modelling techniques to understand the changes in pest and natural enemy communities. Results There was large variability due to seasonality and crop type. Nevertheless, both pest (e.g., mites and aphids and natural enemy (e.g., predatory beetles invertebrate communities were significantly affected by application of organophosphates. When the rate of chlorpyrifos was increased there was a reduction in the number of beetles that predate on slug populations. Slugs displayed opposite trends to many of the other target pests, and actually increased in numbers under the higher rates of chlorpyrifos in comparison to the other treatments. Slug numbers in the final rotation of canola resulted in significant yield

  2. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies.

    Science.gov (United States)

    Brunner, Patrick M; Guttman-Yassky, Emma; Leung, Donald Y M

    2017-04-01

    Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of T H 22, T H 17/IL-23, and T H 1 cytokine pathways depending on the subtype of the disease. In this review we discuss our current understanding of the AD immune map in both patients with early-onset and those with chronic disease. Clinical studies with broad and targeted therapeutics have helped to elucidate the contribution of various immune axes to the disease phenotype. Importantly, immune activation extends well beyond lesional AD because nonlesional skin and the blood component harbor AD-specific inflammatory changes. For this reason, future therapeutics will need to focus on a systemic treatment approach, especially in patients with moderate-to-severe disease. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Broad Spectrum Microbicidal Activity of Photocatalysis by TiO2

    Directory of Open Access Journals (Sweden)

    Yoshinobu Kubota

    2013-03-01

    Full Text Available Photocatalytically active titanium dioxide (TiO2 is widely used as a self-cleaning and self-disinfecting material in many applications to keep environments biologically clean. Several studies on the inactivation of bacteria and viruses by photocatalytic reactions have also been reported; however, only few studies evaluated the spectrum of the microbicidal activity with photocatalysis for various species. There is a need to confirm the expected effectiveness of disinfection by photocatalysis against multidrug-resistant bacteria and viruses. In this study, microbicidal activity of photocatalysis was evaluated by comparing the inactivation of various species of bacteria and viruses when their suspensions were dropped on the surface of TiO2-coated glass. Gram-positive bacteria, e.g., methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae, were easily inactivated by photocatalysis, whereas some gram-negative bacteria, e.g., Escherichia coli and multidrug-resistant Pseudomonas aeruginosa, were gradually inactivated by photocatalysis. Influenza virus, an enveloped virus, was significantly inactivated by photocatalysis compared with feline calicivirus, a non-enveloped virus. The effectiveness of microbicidal activity by photocatalysis may depend on the surface structure. However, they are effectively inactivated by photocatalysis on the surface of TiO2-coated glass. Our data emphasize that effective cleaning and disinfection by photocatalysis in nosocomial settings prevents pathogen transmission.

  4. A Strategy for Generating a Broad-Spectrum Monoclonal Antibody and Soluble Single-Chain Variable Fragments against Plant Potyviruses

    Science.gov (United States)

    Liu, Han-Lin; Lin, Wei-Fang; Hu, Wen-Chi; Lee, Yung-An

    2015-01-01

    Potyviruses are major pathogens that often cause mixed infection in calla lilies. To reduce the time and cost of virus indexing, a detection method for the simultaneous targeting of multiple potyviruses was developed by generating a broad-spectrum monoclonal antibody (MAb) for detecting the greatest possible number of potyviruses. The conserved 121-amino-acid core regions of the capsid proteins of Dasheen mosaic potyvirus (DsMV), Konjak mosaic potyvirus (KoMV), and Zantedeschia mild mosaic potyvirus (ZaMMV) were sequentially concatenated and expressed as a recombinant protein for immunization. After hybridoma cell fusion and selection, one stable cell line that secreted a group-specific antibody, named C4 MAb, was selected. In the reaction spectrum test, the C4 MAb detected at least 14 potyviruses by indirect enzyme-linked immunosorbent assay (I-ELISA) and Western blot analysis. Furthermore, the variable regions of the heavy (VH) and light (VL) chains of the C4 MAb were separately cloned and constructed as single-chain variable fragments (scFvs) for expression in Escherichia coli. Moreover, the pectate lyase E (PelE) signal peptide of Erwinia chrysanthemi S3-1 was added to promote the secretion of C4 scFvs into the medium. According to Western blot analysis and I-ELISA, the soluble C4 scFv (VL-VH) fragment showed a binding specificity similar to that of the C4 MAb. Our results demonstrate that a recombinant protein derived from fusion of the conserved regions of viral proteins has the potential to produce a broad-spectrum MAb against a large group of viruses and that the PelE signal peptide can improve the secretion of scFvs in E. coli. PMID:26209665

  5. Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study

    NARCIS (Netherlands)

    van der Eerden, M. M.; Vlaspolder, F.; de Graaff, C. S.; Groot, T.; Bronsveld, W.; Jansen, H. M.; Boersma, W. G.

    2005-01-01

    Background: There is much controversy about the ideal approach to the management of community acquired pneumonia ( CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. Methods: In a prospective randomised open study performed

  6. Recognition of emotional facial expressions and broad autism phenotype in parents of children diagnosed with autistic spectrum disorder.

    Science.gov (United States)

    Kadak, Muhammed Tayyib; Demirel, Omer Faruk; Yavuz, Mesut; Demir, Türkay

    2014-07-01

    Research findings debate about features of broad autism phenotype. In this study, we tested whether parents of children with autism have problems recognizing emotional facial expression and the contribution of such an impairment to the broad phenotype of autism. Seventy-two parents of children with autistic spectrum disorder and 38 parents of control group participated in the study. Broad autism features was measured with Autism Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with the Emotion Recognition Test, consisting a set of photographs from Ekman & Friesen's. In a two-tailed analysis of variance of AQ, there was a significant difference for social skills (F(1, 106)=6.095; p<.05). Analyses of variance revealed significant difference in the recognition of happy, surprised and neutral expressions (F(1, 106)=4.068, p=.046; F(1, 106)=4.068, p=.046; F(1, 106)=6.064, p=.016). According to our findings, social impairment could be considered a characteristic feature of BAP. ASD parents had difficulty recognizing neutral expressions, suggesting that ASD parents may have impaired recognition of ambiguous expressions as do autistic children. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Applications of a broad-spectrum tool for conservation and fisheries analysis: aquatic gap analysis

    Science.gov (United States)

    McKenna, James E.; Steen, Paul J.; Lyons, John; Stewart, Jana S.

    2009-01-01

    . Aquatic gap analysis naturally focuses on aquatic habitats. The analytical tools are largely based on specification of the species-habitat relations for the system and organism group of interest (Morrison et al. 2003; McKenna et al. 2006; Steen et al. 2006; Sowa et al. 2007). The Great Lakes Regional Aquatic Gap Analysis (GLGap) project focuses primarily on lotic habitat of the U.S. Great Lakes drainage basin and associated states and has been developed to address fish and fisheries issues. These tools are unique because they allow us to address problems at a range of scales from the region to the stream segment and include the ability to predict species specific occurrence or abundance for most of the fish species in the study area. The results and types of questions that can be addressed provide better global understanding of the ecological context within which specific natural resources fit (e.g., neighboring environments and resources, and large and small scale processes). The geographic analysis platform consists of broad and flexible geospatial tools (and associated data) with many potential applications. The objectives of this article are to provide a brief overview of GLGap methods and analysis tools, and demonstrate conservation and planning applications of those data and tools. Although there are many potential applications, we will highlight just three: (1) support for the Eastern Brook Trout Joint Venture (EBTJV), (2) Aquatic Life classification in Wisconsin, and (3) an educational tool that makes use of Google Earth (use of trade or product names does not imply endorsement by the U.S. Government) and Internet accessibility.

  8. Carbohydrate microarrays

    DEFF Research Database (Denmark)

    Park, Sungjin; Gildersleeve, Jeffrey C; Blixt, Klas Ola

    2012-01-01

    In the last decade, carbohydrate microarrays have been core technologies for analyzing carbohydrate-mediated recognition events in a high-throughput fashion. A number of methods have been exploited for immobilizing glycans on the solid surface in a microarray format. This microarray...... of substrate specificities of glycosyltransferases. This review covers the construction of carbohydrate microarrays, detection methods of carbohydrate microarrays and their applications in biological and biomedical research....

  9. The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment

    Directory of Open Access Journals (Sweden)

    Ira Ekmekciu

    2017-05-01

    Full Text Available There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and

  10. Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-09-01

    Full Text Available Chemotherapy-induced nausea and vomiting (CINV is a complex pathophysiological condition and consists of two phases. The conventional CINV neurotransmitter hypothesis suggests that the immediate phase is mainly due to release of serotonin (5-HT from the enterochromaffin cells in the gastrointestinal tract (GIT, while the delayed phase is a consequence of release of substance P (SP in the brainstem. However, more recent findings argue against this simplistic neurotransmitter and anatomical view of CINV. Revision of the hypothesis advocates a more complex, differential and overlapping involvement of several emetic neurotransmitters/modulators (e.g. dopamine, serotonin, substance P, prostaglandins and related arachidonic acid derived metabolites in both phases of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous system (ENS [1]. No single antiemetic is currently available to completely prevent both phases of CINV. The standard antiemetic regimens include a 5-HT3 antagonist plus dexamethasone for the prevention of acute emetic phase, combined with an NK1 receptor antagonist (e.g. aprepitant for the delayed phase. Although NK1 antagonists behave in animals as broad-spectrum antiemetics against different emetogens including cisplatin-induced acute and delayed vomiting, by themselves they are not very effective against CINV in cancer patients. Cannabinoids such as D9-THC also behave as broad-spectrum antiemetics against diverse emetic stimuli as well as being effective against both phases of CINV in animals and patients. Potential side effects may limit the clinical utility of direct-acting cannabinoid agonists which could be avoided by the use of corresponding indirect-acting agonists. Cannabinoids (both phyto-derived and synthetic behave as agonist antiemetics via the activation of cannabinoid CB1 receptors in both the brainstem and the ENS emetic loci. An endocannabinoid antiemetic tone may exist since inverse CB1

  11. A novel alkaloid from marine-derived actinomycete Streptomyces xinghaiensis with broad-spectrum antibacterial and cytotoxic activities.

    Directory of Open Access Journals (Sweden)

    Wence Jiao

    Full Text Available Due to the increasing emergence of drug-resistant bacteria and tumor cell lines, novel antibiotics with antibacterial and cytotoxic activities are urgently needed. Marine actinobacteria are rich sources of novel antibiotics, and here we report the discovery of a novel alkaloid, xinghaiamine A, from a marine-derived actinomycete Streptomyces xinghaiensis NRRL B24674(T. Xinghaiamine A was purified from the fermentation broth, and its structure was elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR spectrum as well as mass spectrometry. Xinghaiamine A was identified to be a novel alkaloid with highly symmetric structure on the basis of sulfoxide functional group, and sulfoxide containing compound has so far never been reported in microorganisms. Biological assays revealed that xinghaiamine A exhibited broad-spectrum antibacterial activities to both Gram-negative persistent hospital pathogens (e.g. Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli and Gram-positive ones, which include Staphylococcus aureus and Bacillus subtilis. In addition, xinghaiamine A also exhibited potent cytotoxic activity to human cancer cell lines of MCF-7 and U-937 with the IC50 of 0.6 and 0.5 µM, respectively.

  12. Novel Hybrid Anticonvulsants Derived from Pyrrolidine-2,5-dione Scaffold with Broad Spectrum of Activity in the Preclinical Studies.

    Science.gov (United States)

    Kaminski, Krzysztof

    2017-01-01

    The multifunctional ligands application is an emerging approach in drug delivery, mainly in the treatment of diseases with complex pathology, such as Alzheimer's, cancer, and epilepsy. Using this method many biomolecules with different properties are combined to form a single unit that can provide a complex broad spectrum activity. Thus, a new type of hybrid anticonvulsants based on the pyrrolidine-2,5-dione frame are detailed with the aim of acquiring more effective antiepileptic drugs (AED) that could suppress various human convulsions. These hybrid molecules attach to the chemical particles of clinically relevant AEDs such as ethosuximide, levetiracetam, and lacosamide. As a result of this hybridization process the compounds obtained were effective in three most important animal epilepsy models, namely the maximal electroshock seizure (MES) test, the subcutaneous pentylenetetrazole (scPTZ) test, and the six-Hertz (6 Hz) model in mice. These substances displayed wider spectrum of protection, more potent efficacy, and better safety profile than the aforementioned AEDs. Several compounds were also active in the formalin model of persistent pain in mice. The in vitro ligand binding studies have proved that the most conceivable molecular mechanism of anticonvulsant and antinociceptive action was the influence on the neuronal voltage-sensitive sodium and L-type calcium channels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices.

    Science.gov (United States)

    Rakhi, N K; Tuwani, Rudraksh; Mukherjee, Jagriti; Bagler, Ganesh

    2018-01-01

    Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms.

  14. Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices

    Science.gov (United States)

    Mukherjee, Jagriti

    2018-01-01

    Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms. PMID:29813110

  15. Weak turbulence and broad-spectrum excitation in a nonmagnetized electron beam via second-harmonic generation

    International Nuclear Information System (INIS)

    Bogdanov, A.T.

    1990-01-01

    The nonlinear evolution of an initially monoenergetic [ν-bar(t = 0) = (0,0,u)] electron beam propagating in a nonmagnetized dielectric medium of permittivity ε > 1, with initial velocity u ≥ c/√ε (where c is the vacuum speed of light) is investigated. The specific instability of the beam under such conditions is the cause of the generation of a broad spectrum of transverse electromagnetic waves coupled to the simultaneous excitation of the second harmonic of the beam's oscillations, both at the expense of the beam's initial kinetic energy. The system of self-consistent nonlinear equations, describing the particle-field dynamics, is treated in the spirit of the weak-turbulence approach. The integrals of the resulting nonlinear system of equations for the amplitudes of the fields of the electron density are used to evaluate the spectral distribution of the amplitudes in the saturation phase, and hence the efficiency of the transformation of the beam's energy into electromagnetic radiation as a function of the width of the spectrum of the initially present electromagnetic fluctuations. A substantial increase in this efficiency is observed in comparison with the single-mode case. (author)

  16. Broad spectrum reactivity versus subtype specificity-trade-offs in serodiagnosis of influenza A virus infections by competitive ELISA.

    Science.gov (United States)

    Postel, A; Ziller, M; Rudolf, M; Letzel, T; Ehricht, Ralf; Pourquier, P; Dauber, M; Grund, C; Beer, Martin; Harder, T C

    2011-04-01

    Avian influenza viruses (AIVs) of the H5 and H7 subtypes can cause substantial economic losses in the poultry industry and are a potential threat to public health. Serosurveillance of poultry populations is an important monitoring tool and can also be used for control of vaccination campaigns. The purpose of this study was to develop broadly reactive, yet subtype-specific competitive ELISAs (cELISAs) for the specific detection of antibodies to the notifiable AIV subtypes H5 and H7 as an alternative to the gold standard haemagglutination inhibition assay (HI). Broadly reacting monoclonal competitor antibodies (mAbs) and genetically engineered subtype H5 or H7 haemagglutinin antigen, expressed and in vivo biotinylated in insect cells, were used to develop the cELISAs. Sera from galliform species and water fowl (n=793) were used to evaluate the performance characteristics of the cELISAs. For the H5 specific cELISA, 98.1% test sensitivity and 91.5% test specificity (97.7% and 90.2% for galliforms; 98.9% and 92.6% for waterfowl), and for the H7 cELISA 97.3% sensitivity and 91.8% specificity (95.3% and 98.9% for galliforms; 100% and 82.7% for waterfowl) were reached when compared to HI. The use of competitor mAbs with broad spectrum reactivity within an AIV haemagglutinin subtype allowed for homogenous detection with high sensitivity of subtype-specific antibodies induced by antigenically widely distinct isolates including antigenic drift variants. However, a trade-off regarding sensitivity versus nonspecific detection of interfering antibodies induced by phylo- and antigenically closely related subtypes, e.g., H5 versus H2 and H7 versus H15, must be considered. The observed intersubtype antibody cross-reactivity remains a disturbance variable in AIV subtype-specific serodiagnosis which negatively affects specificity. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. New insights into broad spectrum communities of the Early Holocene Near East: The birds of Hallan Çemi

    Science.gov (United States)

    Zeder, Melinda A.; Spitzer, Megan D.

    2016-11-01

    The Early Holocene in Near East was a pivotal transitional period that witnessed dramatic changes in climate and environment, human settlement, major changes in subsistence strategies focusing on a broad range of different plant and animal resources, and a radical restructuring of social relations. The remarkable corpus of avifauna from the Early Holocene site of Hallan Çemi in southeastern Turkey sheds new light on key issues about this dynamic period that has been termed the ;Broad Spectrum Revolution;. The avifauna from this important site demonstrate how Hallan Çemi occupants took advantage of the site's strategic location at the junction of multiple environmental zones by extracting a diverse range of seasonally available resources from both near-by and more distant eco-zones to cobble together a stable subsistence economy capable of supporting this small community throughout the year. They give testimony to the impacts of resource utilization over time, especially on species unable to rebound from sustained human hunting. At the same time, they show how Hallan Çemi residents mitigated these impacts by replacing depleted resources with alternative, more resilient ones that could be more sustainably harvested. They open a window onto the growing investment in feasting and ritual activity that helped bind this community together. In so doing they provide a means of empirically evaluating the efficacy of contrasting explanatory frameworks for the Broad Spectrum Revolution that gave rise to the subsequent domestication of plant and animals in the Near East. Contrary to frameworks that cast these developments as responses to resource depression, lessons learned from the Hallan Çemi avifauna lend support to frameworks that emphasize the human capacity to strategically target, capitalize, and improve upon circumscribed resource rich environments in a way that permits more permanent occupation of these niches. And they underscore the degree to which social and

  18. White LEDs as broad spectrum light sources for spectrophotometry: demonstration in the visible spectrum range in a diode-array spectrophotometric detector.

    Science.gov (United States)

    Piasecki, Tomasz; Breadmore, Michael C; Macka, Mirek

    2010-11-01

    Although traditional lamps, such as deuterium lamps, are suitable for bench-top instrumentation, their compatibility with the requirements of modern miniaturized instrumentation is limited. This study investigates the option of utilizing solid-state light source technology, namely white LEDs, as a broad band spectrum source for spectrophotometry. Several white light LEDs of both RGB and white phosphorus have been characterized in terms of their emission spectra and energy output and a white phosphorus Luxeon LED was then chosen for demonstration as a light source for visible-spectrum spectrophotometry conducted in CE. The Luxeon LED was fixed onto the base of a dismounted deuterium (D(2) ) lamp so that the light-emitting spot was geometrically positioned exactly where the light-emitting spot of the original D(2) lamp is placed. In this manner, the detector of a commercial CE instrument equipped with a DAD was not modified in any way. As the detector hardware and electronics remained the same, the change of the deuterium lamp for the Luxeon white LED allowed a direct comparison of their performances. Several anionic dyes as model analytes with absorption maxima between 450 and 600 nm were separated by CE in an electrolyte of 0.01 mol/L sodium tetraborate. The absorbance baseline noise as the key parameter was 5 × lower for the white LED lamp, showing clearly superior performance to the deuterium lamp in the available, i.e. visible part of the spectrum. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Transgenic cotton coexpressing Vip3A and Cry1Ac has a broad insecticidal spectrum against lepidopteran pests.

    Science.gov (United States)

    Chen, Wen-Bo; Lu, Guo-Qing; Cheng, Hong-Mei; Liu, Chen-Xi; Xiao, Yu-Tao; Xu, Chao; Shen, Zhi-Cheng; Wu, Kong-Ming

    2017-10-01

    Although farmers in China have grown transgenic Bt-Cry1Ac cotton to resist the major pest Helicoverpa armigera since 1997 with great success, many secondary lepidopteran pests that are tolerant to Cry1Ac are now reported to cause considerable economic damage. Vip3AcAa, a chimeric protein with the N-terminal part of Vip3Ac and the C-terminal part of Vip3Aa, has a broad insecticidal spectrum against lepidopteran pests and has no cross resistance to Cry1Ac. In the present study, we tested insecticidal activities of Vip3AcAa against Spodoptera litura, Spodoptera exigua, and Agrotis ipsilon, which are relatively tolerant to Cry1Ac proteins. The bioassay results showed that insecticidal activities of Vip3AcAa against these three pests are superior to Cry1Ac, and after an activation pretreatment, Vip3AcAa retained insecticidal activity against S. litura, S. exigua and A. ipsilon that was similar to the unprocessed protein. The putative receptor for this chimeric protein in the brush border membrane vesicle (BBMV) in the three pests was also identified using biotinylated Vip3AcAa toxin. To broaden Bt cotton activity against a wider spectrum of pests, we introduced the vip3AcAa and cry1Ac genes into cotton. Larval mortality rates for S. litura, A. ipsilon and S. exigua that had fed on this new cotton increased significantly compared with larvae fed on non-Bt cotton and Bt-Cry1Ac cotton in a laboratory experiment. These results suggested that the Vip3AcAa protein is an excellent option for a "pyramid" strategy for integrated pest management in China. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Efficient full-spectrum utilization, reception and conversion of solar energy by broad-band nanospiral antenna.

    Science.gov (United States)

    Zhao, Huaqiao; Gao, Huotao; Cao, Ting; Li, Boya

    2018-01-22

    In this work, the collection of solar energy by a broad-band nanospiral antenna is investigated in order to solve the low efficiency of the solar rectenna based on conventional nanoantennas. The antenna impedance, radiation, polarization and effective area are all considered in the efficiency calculation using the finite integral technique. The wavelength range investigated is 300-3000 nm, which corresponds to more than 98% of the solar radiation energy. It's found that the nanospiral has stronger field enhancement in the gap than a nanodipole counterpart. And a maximum harvesting efficiency about 80% is possible in principle for the nanospiral coupled to a rectifier resistance of 200 Ω, while about 10% for the nanodipole under the same conditions. Moreover, the nanospiral could be coupled to a rectifier diode of high resistance more easily than the nanodipole. These results indicate that the efficient full-spectrum utilization, reception and conversion of solar energy can be achieved by the nanospiral antenna, which is expected to promote the solar rectenna to be a promising technology in the clean, renewable energy application.

  1. A broad-spectrum, efficient and nontransgenic approach to control plant viruses by application of salicylic acid and jasmonic acid.

    Science.gov (United States)

    Shang, Jing; Xi, De-Hui; Xu, Fei; Wang, Shao-Dong; Cao, Sen; Xu, Mo-Yun; Zhao, Ping-Ping; Wang, Jian-Hui; Jia, Shu-Dan; Zhang, Zhong-Wei; Yuan, Shu; Lin, Hong-Hui

    2011-02-01

    Plant viruses cause many diseases that lead to significant economic losses. However, most of the approaches to control plant viruses, including transgenic processes or drugs are plant-species-limited or virus-species-limited, and not very effective. We introduce an application of jasmonic acid (JA) and salicylic acid (SA), a broad-spectrum, efficient and nontransgenic method, to improve plant resistance to RNA viruses. Applying 0.06 mM JA and then 0.1 mM SA 24 h later, enhanced resistance to Cucumber mosaic virus (CMV), Tobacco mosaic virus (TMV) and Turnip crinkle virus (TCV) in Arabidopsis, tobacco, tomato and hot pepper. The inhibition efficiency to virus replication usually achieved up to 80-90%. The putative molecular mechanism was investigated. Some possible factors affecting the synergism of JA and SA have been defined, including WRKY53, WRKY70, PDF1.2, MPK4, MPK2, MPK3, MPK5, MPK12, MPK14, MKK1, MKK2, and MKK6. All genes involving in the synergism of JA and SA were investigated. This approach is safe to human beings and environmentally friendly and shows potential as a strong tool for crop protection against plant viruses.

  2. Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry

    Science.gov (United States)

    2013-01-01

    Background We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. Results Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. Conclusions CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified. PMID:23924316

  3. A universal aptameric biosensor: Multiplexed detection of small analytes via aggregated perylene-based broad-spectrum quencher.

    Science.gov (United States)

    Hu, Rong; Zhang, Xi; Xu, Qiang; Lu, Dan-Qing; Yang, Yun-Hui; Xu, Quan-Qing; Ruan, Qiong; Mo, Liu-Ting; Zhang, Xiao-Bing

    2017-06-15

    A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Broad-spectrum detection of H5 subtype influenza A viruses with a new fluorescent immunochromatography system.

    Directory of Open Access Journals (Sweden)

    Akira Sakurai

    Full Text Available Immunochromatography (IC is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza virus because the protocol is short time and easy to use. Despite the usability of IC, the sensitivity is approximately 10(3 pfu per reaction. In addition, antigen-antibody interaction-based method cannot be used for the detection of influenza viruses with major antigenic change. In this study, we established the use of fluorescent immunochromatography (FLIC to detect a broad spectrum of H5 subtype influenza A viruses. This method has improved sensitivity 10-100 fold higher than traditional IC because of the use of fluorescent conjugated beads. Our Type-E FLIC kit detected all of the H5 subtype influenza viruses that were examined, as well as recombinant hemagglutinin (HA proteins (rHAs belonging to the Eurasian H5 subtype viruses and the Type-N diagnosed North American H5 subtype influenza A viruses. Thus, this kit has the improved potential to detect H5 subtype influenza viruses of different clades with both Type-E and Type-N FLIC kits. Compared with PCR-based diagnosis, FLIC has a strong advantage in usability, because the sample preparation required for FLIC is only mix-and-drop without any additional steps such as RNA extraction. Our results can provide new strategies against the spread and transmission of HPAI H5N1 viruses in birds and mammals including humans.

  5. Broad-spectrum health improvements with one year of soccer training in inactive mildly hypertensive middle-aged women.

    Science.gov (United States)

    Krustrup, P; Skoradal, M-B; Randers, M B; Weihe, P; Uth, J; Mortensen, J; Mohr, M

    2017-12-01

    The study tested the hypothesis that long-term soccer training has positive impact on cardiovascular profile, body composition, bone health, and physical capacity in inactive, pre-menopausal women with mild hypertension. The study applied a randomized controlled design in which physically inactive middle-aged women were separated into a soccer training group (n=19; SOC) and a control group (n=12; CON). SOC performed 128±29 (±SD) one-h small-sided soccer training sessions over one year. Blood pressure, body composition, blood lipid profile, and fitness level were determined pre- and post-intervention. Over one year, mean arterial pressure decreased more in SOC than in CON (-5±7 vs +4±5 mmHg; Pendurance level 1 (122±105 vs 2±21%) and 20-m sprint performance (6±6 vs -1±2%) increased more (Ptraining resulted in broad-spectrum improvements in the health profile of untrained, pre-menopausal women with mild hypertension, including cardiovascular, metabolic, and musculo-skeletal benefits. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

    Science.gov (United States)

    Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

    2016-06-01

    Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Marker-assisted introgression of broad-spectrum blast resistance genes into the cultivated MR219 rice variety.

    Science.gov (United States)

    Miah, Gous; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam B; Rahim, Harun A; Latif, Mohammad A

    2017-07-01

    The rice cultivar MR219 is famous for its better yield and long and fine grain quality; however, it is susceptible to blast disease. The main objective of this study was to introgress blast resistance genes into MR219 through marker-assisted selection (MAS). The rice cultivar MR219 was used as the recurrent parent, and Pongsu Seribu 1 was used as the donor. Marker-assisted foreground selection was performed using RM6836 and RM8225 to identify plants possessing blast resistance genes. Seventy microsatellite markers were used to estimate recurrent parent genome (RPG) recovery. Our analysis led to the development of 13 improved blast resistant lines with Piz, Pi2 and Pi9 broad-spectrum blast resistance genes and an MR219 genetic background. The RPG recovery of the selected improved lines was up to 97.70% with an average value of 95.98%. Selected improved lines showed a resistance response against the most virulent blast pathogen pathotype, P7.2. The selected improved lines did not express any negative effect on agronomic traits in comparison with MR219. The research findings of this study will be a conducive approach for the application of different molecular techniques that may result in accelerating the development of new disease-resistant rice varieties, which in turn will match rising demand and food security worldwide. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

    Full Text Available Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8, Vesicular Stomatitis Virus (VSV, Herpes Simplex Virus (HSV and Newcastle Disease Virus (NDV in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2. Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.

  9. Spectral properties of plant leaves pertaining to urban landscape design of broad-spectrum solar ultraviolet radiation reduction

    Science.gov (United States)

    Yoshimura, Haruka; Zhu, Hui; Wu, Yunying; Ma, Ruijun

    2010-03-01

    Human exposure to harmful ultraviolet (UV) radiation has important public health implications. Actual human exposure to solar UV radiation depends on ambient UV irradiance, and the latter is influenced by ground reflection. In urban areas with higher reflectivity, UV exposure occurs routinely. To discover the solar UV radiation regulation mechanism of vegetation, the spectral reflectance and transmittance of plant leaves were measured with a spectrophotometer. Typically, higher plants have low leaf reflectance (around 5%) and essentially zero transmittance throughout the UV region regardless of plant species and seasonal change. Accordingly, incident UV radiation decreases to 5% by being reflected and is reduced to zero by passing through a leaf. Therefore, stratified structures of vegetation are working as another terminator of UV rays, protecting whole terrestrial ecosystems, while vegetation at waterfronts contributes to protect aquatic ecosystems. It is possible to protect the human population from harmful UV radiation by urban landscape design of tree shade and the botanical environment. Even thin but uniformly distributed canopy is effective in attenuating UV radiation. To intercept diffuse radiation, UV screening by vertical structures such as hedges should be considered. Reflectivity of vegetation is around 2%, as foliage surfaces reduce incident UV radiation via reflection, while also eliminating it by transmittance. Accordingly, vegetation reduces incident UV radiation to around 2% by reflection. Vegetation influence on ambient UV radiation is broad-spectrum throughout the UV region. Only trees provide cool UV protective shade. Urban landscapes aimed at abating urban heat islands integrated with a reduction of human UV over-exposure would contribute to mitigation of climate change.

  10. In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin with a broad antibacterial spectrum.

    Science.gov (United States)

    Hata, K; Otsuki, M; Nishino, T

    1992-01-01

    E1077 is a new injectable cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria, including staphylococci and Pseudomonas aeruginosa. The in vitro activities of E1077 against clinical isolates of methicillin-susceptible Staphylococcus aureus (MIC of E1077 for 90% of the strains tested [MIC90], 0.78 microgram/ml) and methicillin-resistant S. aureus (MIC90, 50 micrograms/ml) were similar to those of cefpirome and flomoxef. Against Enterococcus faecalis (MIC90, 6.25 micrograms/ml), E1077 was the most active of the drugs tested and four times more active than cefpirome. The MIC90S of E1077 for streptococci, Haemophilus influenzae, and Neisseria gonorrhoeae ranged from 0.05 to 0.78 microgram/ml; E1077 was similar in activity to cefpirome. E1077 inhibited 90% of most species of the family Enterobacteriaceae at concentrations of less than or equal to 1.56 micrograms/ml, with the exception of Serratia marcescens and Proteus vulgaris (12.5 micrograms/ml). The activity of E1077 against P. aeruginosa (MIC90, 6.25 micrograms/ml) was comparable to that of ceftazidime. In vivo activity was evaluated with systemic infections in mice. E1077 showed a protective effect against systemic infections by gram-positive or gram-negative bacteria, as reflected by its in vitro activity. The protective effects of E1077 were higher than those of cefpirome against S. aureus and P. aeruginosa infections and similar to those of cefpirome against other bacterial infections. Morphological studies using differential interference and phase-contrast microscopy showed that low concentrations of E1077 caused swelling of S. aureus and spheroplast and bulge formation in P. aeruginosa. In general, the antibacterial profile of E1077 is similar to that of cefpirome. Images PMID:1416879

  11. Application of the broad-spectrum bacteriocin enterocin AS-48 to inhibit Bacillus coagulans in canned fruit and vegetable foods.

    Science.gov (United States)

    Lucas, R; Grande, M A J; Abriouel, H; Maqueda, M; Ben Omar, N; Valdivia, E; Martínez-Cañamero, M; Gálvez, A

    2006-10-01

    The enterococcal bacteriocin (enterocin) AS-48 is a broad-spectrum cyclic peptide. Enterocin AS-48 was tested against Bacillus coagulans in three vegetable canned foods: tomato paste (pH 4.64), syrup from canned peaches (pH 3.97), and juice from canned pineapple (pH 3.65). When vegetative cells of B. coagulans CECT (Spanish Type Culture Collection) 12 were inoculated in tomato paste supplemented with 6 microg/ml AS-48 and stored at different temperatures, viable cell counts were reduced by approximately 2.37 (4 degrees C), 4.3 (22 degrees C) and 3.0 (37 degrees C) log units within 24 h storage. After 15-days storage, no viable cells were detected in any sample. Strain B. coagulans CECT 561 showed a poor survival in tomato paste, but surviving cells were also killed by AS-48. The bacteriocin was also very active against B. coagulans CECT 12 vegetative cells in juice from canned pineapple stored at 22 degrees C, and slightly less active in syrup from canned peaches. In food samples supplemented with 1.5% lactic acid, enterocin AS-48 (6 microg/ml) rapidly reduced viable counts of vegetative cells below detection limits within 24 h storage. Addition of glucose and sucrose (10% and 20%) significantly increased bacteriocin activity against vegetative cells of B. coagulans CECT 12. Enterocin AS-48 had no significant effect on B. coagulans CECT 12 spores. However, the combined application of AS-48 and heat (80-95 degrees C for 5 min) significantly increased the effect of thermal treatments on spores.

  12. Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

    Science.gov (United States)

    Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

    2013-01-01

    Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

  13. Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

    Directory of Open Access Journals (Sweden)

    Debmalya Barh

    Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

  14. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

    Directory of Open Access Journals (Sweden)

    Yunjeong Kim

    2016-03-01

    Full Text Available Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP, can arise through mutation of FECV to FIP virus (FIPV. The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for

  15. Characterization of a broad host-spectrum virulent Salmonella bacteriophage fmb-p1 and its application on duck meat.

    Science.gov (United States)

    Wang, Changbao; Chen, Qiming; Zhang, Chong; Yang, Jie; Lu, Zhaoxin; Lu, Fengxia; Bie, Xiaomei

    2017-05-15

    The aim of this study was to find a virulent bacteriophage for the biocontrol of Salmonella in duck meat. A broad host-spectrum virulent phage, fmb-p1, was isolated and purified from an duck farm, and its host range was determined to include S. Typhimurium, S. Enteritidis, S. Saintpaul, S. Agona, S. Miami, S. Anatum, S. Heidelberg and S. Paratyphi-C. Electron microscopy and genome sequencing showed that fmb-p1 belongs to the family Siphoviridae. The genome of fmb-p1 is composed of a 43,327-bp double-stranded DNA molecule with 60 open reading frames and a total G+C content of 46.09%. There are no deleterious sequences or genes encoding known harmful products in the phage fmb-p1 genome. Phage fmb-p1 was stable under different temperature (40-75°C), pH (4-10) and NaCl solutions (1-11%). The phage treatment (9.9×10 9 PFU/cm 2 ) caused a peak reduction in S. Typhimurium of 4.52 log CFU/cm 2 in ready-to-eat (RTE) duck meat, whereas potassium sorbate treatment (PS, 2mg/cm 2 ) resulted in a 0.05-0.12 log reduction. Compared to PS treatment, there was significant difference in the S. Typhimurium reduction (P˂0.05) by phage treatment at both 4°C and 25°C. The results suggested that phage could be applied to reduce Salmonella, on commercial poultry products. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin

    International Nuclear Information System (INIS)

    Reinhardt, P.; Cybulski, M.; Miller, S.M.; Ferrarotto, C.; Wilkins, R.; Deslauriers, Y.

    2006-01-01

    The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm 2 UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1α levels increased with LOM concentration. The release of TNF-α and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 μmol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM. (author)

  17. X-ray Emitting GHz-Peaked Spectrum Galaxies: Testing a Dynamical-Radiative Model with Broad-Band Spectra

    International Nuclear Information System (INIS)

    Ostorero, L.; Moderski, R.; Stawarz, L.; Diaferio, A.; Kowalska, I.; Cheung, C.C.; Kataoka, J.; Begelman, M.C.; Wagner, S.J.

    2010-01-01

    In a dynamical-radiative model we recently developed to describe the physics of compact, GHz-Peaked-Spectrum (GPS) sources, the relativistic jets propagate across the inner, kpc-sized region of the host galaxy, while the electron population of the expanding lobes evolves and emits synchrotron and inverse-Compton (IC) radiation. Interstellar-medium gas clouds engulfed by the expanding lobes, and photoionized by the active nucleus, are responsible for the radio spectral turnover through free-free absorption (FFA) of the synchrotron photons. The model provides a description of the evolution of the GPS spectral energy distribution (SED) with the source expansion, predicting significant and complex high-energy emission, from the X-ray to the γ-ray frequency domain. Here, we test this model with the broad-band SEDs of a sample of eleven X-ray emitting GPS galaxies with Compact-Symmetric-Object (CSO) morphology, and show that: (i) the shape of the radio continuum at frequencies lower than the spectral turnover is indeed well accounted for by the FFA mechanism; (ii) the observed X-ray spectra can be interpreted as non-thermal radiation produced via IC scattering of the local radiation fields off the lobe particles, providing a viable alternative to the thermal, accretion-disk dominated scenario. We also show that the relation between the hydrogen column densities derived from the X-ray (N H ) and radio (N HI ) data of the sources is suggestive of a positive correlation, which, if confirmed by future observations, would provide further support to our scenario of high-energy emitting lobes.

  18. A Novel, Broad-Spectrum Inhibitor of Enterovirus Replication That Targets Host Cell Factor Phosphatidylinositol 4-Kinase IIIβ

    Science.gov (United States)

    van der Schaar, Hilde M.; Leyssen, Pieter; Thibaut, Hendrik J.; de Palma, Armando; van der Linden, Lonneke; Lanke, Kjerstin H. W.; Lacroix, Céline; Verbeken, Erik; Conrath, Katja; MacLeod, Angus M.; Mitchell, Dale R.; Palmer, Nicholas J.; van de Poël, Hervé; Andrews, Martin

    2013-01-01

    Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2-a]pyrazin-3-yl)phenol. This compound exhibited a broad spectrum of antiviral activity, as it inhibited all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM. After a lengthy resistance selection process, coxsackievirus mutants resistant to compound 1 were isolated that carried substitutions in their 3A protein. Remarkably, the same substitutions were recently shown to provide resistance to inhibitors of phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ), a lipid kinase that is essential for enterovirus replication, suggesting that compound 1 may also target this host factor. Accordingly, compound 1 directly inhibited PI4KIIIβ in an in vitro kinase activity assay. Furthermore, the compound strongly reduced the PI 4-phosphate levels of the Golgi complex in cells. Rescue of coxsackievirus replication in the presence of compound 1 by a mutant PI4KIIIβ carrying a substitution in its ATP-binding pocket revealed that the compound directly binds the kinase at this site. Finally, we determined that an analogue of compound 1, 3-(3-fluoro-4-methoxyphenyl)-2-methyl-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine, is well tolerated in mice and has a dose-dependent protective activity in a coxsackievirus serotype B4-induced pancreatitis model. PMID:23896472

  19. Complete Genome Sequence of Bacillus velezensis YJ11-1-4, a Strain with Broad-Spectrum Antimicrobial Activity, Isolated from Traditional Korean Fermented Soybean Paste.

    Science.gov (United States)

    Lee, Hyo Jung; Chun, Byung-Hee; Jeon, Hye Hee; Kim, Yeon Bee; Lee, Se Hee

    2017-11-30

    Bacillus velezensis YJ11-1-4 is a strain that exhibits broad-spectrum antimicrobial activity against various pathogens. It was isolated from doenjang, a traditional Korean fermented soybean paste. The genome comprises a single circular chromosome of 4,006,637 bp with 46.42% G+C content without plasmids. Copyright © 2017 Lee et al.

  20. Naturally occurring broad-spectrum powdery mildw resistance in a central American tomato accession is caused by loss of Mlo function

    NARCIS (Netherlands)

    Bai, Y.; Pavan, S.N.C.; Zheng, Z.; Zappel, N.F.; Reinstadler, A.; Lotti, C.; Giovanni, de C.; Ricciardi, L.; Lindhout, P.; Visser, R.G.F.; Theres, K.; Panstruga, R.

    2008-01-01

    The resistant cherry tomato (Solanum lycopersicum var. cerasiforme) line LC-95, derived from an accession collected in Ecuador, harbors a natural allele (ol-2) that confers broad-spectrum and recessively inherited resistance to powdery mildew (Oidium neolycopersici). As both the genetic and

  1. Durable broad-spectrum powdery mildew resistance in pea er1 plants is conferred by natural loss-of-function mutations in PsMLO1

    NARCIS (Netherlands)

    Humphry, M.; Reinstädler, A.; Ivanov, S.; Bisseling, T.; Panstruga, R.

    2011-01-01

    Loss-of-function alleles of plant-specific MLO (Mildew Resistance Locus O) genes confer broad-spectrum powdery mildew resistance in monocot (barley) and dicot (Arabidopsis thaliana, tomato) plants. Recessively inherited powdery mildew resistance in pea (Pisum sativum) er1 plants is, in many aspects,

  2. Draft Genome Sequence of Streptomyces sp. Strain Wb2n-11, a Desert Isolate with Broad-Spectrum Antagonism against Soilborne Phytopathogens

    Energy Technology Data Exchange (ETDEWEB)

    Köberl, Martina; White, Richard A.; Erschen, Sabine; El-Arabi, Tarek F.; Jansson, Janet K.; Berg, Gabriele

    2015-08-06

    Streptomyces sp. strain Wb2n-11, isolated from native desert soil, exhibited broad-spectrum antagonism against plant pathogenic fungi, bacteria and nematodes. The 8.2 Mb draft genome reveals genes putatively responsible for its promising biocontrol activity and genes which enable the soil bacterium to directly interact beneficially with plants.

  3. A highly sensitive, multiplex broad-spectrum PCR-DNA-enzyme immunoassay and reverse hybridization assay for rapid detection and identification of Chlamydia trachomatis serovars.

    NARCIS (Netherlands)

    Quint, K.D.; Doorn, L.J. van; Kleter, B.; Koning, M.N. de; Munckhof, H.A. van den; Morre, S.A.; Harmsel, B. ter; Weiderpass, E.; Harbers, G.; Melchers, W.J.G.; Quint, W.G.V.

    2007-01-01

    Chlamydia trachomatis (Ct) comprises distinct serogroups and serovars. The present study evaluates a novel Ct amplification, detection, and genotyping method (Ct-DT assay). The Ct-DT amplification step is a multiplex broad-spectrum PCR for the cryptic plasmid and the VD2-region of ompl. The Ct-DT

  4. Broad Energy Range Neutron Spectroscopy using a Liquid Scintillator and a Proportional Counter: Application to a Neutron Spectrum Similar to that from an Improvised Nuclear Device.

    Science.gov (United States)

    Xu, Yanping; Randers-Pehrson, Gerhard; Marino, Stephen A; Garty, Guy; Harken, Andrew; Brenner, David J

    2015-09-11

    A novel neutron irradiation facility at the Radiological Research Accelerator Facility (RARAF) has been developed to mimic the neutron radiation from an Improvised Nuclear Device (IND) at relevant distances (e.g. 1.5 km) from the epicenter. The neutron spectrum of this IND-like neutron irradiator was designed according to estimations of the Hiroshima neutron spectrum at 1.5 km. It is significantly different from a standard reactor fission spectrum, because the spectrum changes as the neutrons are transported through air, and it is dominated by neutron energies from 100 keV up to 9 MeV. To verify such wide energy range neutron spectrum, detailed here is the development of a combined spectroscopy system. Both a liquid scintillator detector and a gas proportional counter were used for the recoil spectra measurements, with the individual response functions estimated from a series of Monte Carlo simulations. These normalized individual response functions were formed into a single response matrix for the unfolding process. Several accelerator-based quasi-monoenergetic neutron source spectra were measured and unfolded to test this spectroscopy system. These reference neutrons were produced from two reactions: T(p,n) 3 He and D(d,n) 3 He, generating neutron energies in the range between 0.2 and 8 MeV. The unfolded quasi-monoenergetic neutron spectra indicated that the detection system can provide good neutron spectroscopy results in this energy range. A broad-energy neutron spectrum from the 9 Be(d,n) reaction using a 5 MeV deuteron beam, measured at 60 degrees to the incident beam was measured and unfolded with the evaluated response matrix. The unfolded broad neutron spectrum is comparable with published time-of-flight results. Finally, the pair of detectors were used to measure the neutron spectrum generated at the RARAF IND-like neutron facility and a comparison is made to the neutron spectrum of Hiroshima.

  5. Insight into the mechanism of action of temporin-SHa, a new broad-spectrum antiparasitic and antibacterial agent.

    Directory of Open Access Journals (Sweden)

    Zahid Raja

    Full Text Available Antimicrobial peptides (AMPs are promising drugs to kill resistant pathogens. In contrast to bacteria, protozoan parasites, such as Leishmania, were little studied. Therefore, the antiparasitic mechanism of AMPs is still unclear. In this study, we sought to get further insight into this mechanism by focusing our attention on temporin-SHa (SHa, a small broad-spectrum AMP previously shown to be active against Leishmania infantum. To improve activity, we designed analogs of SHa and compared the antibacterial and antiparasitic mechanisms. [K3]SHa emerged as a highly potent compound active against a wide range of bacteria, yeasts/fungi, and trypanosomatids (Leishmania and Trypanosoma, with leishmanicidal intramacrophagic activity and efficiency toward antibiotic-resistant strains of S. aureus and antimony-resistant L. infantum. Multipassage resistance selection demonstrated that temporins-SH, particularly [K3]SHa, are not prone to induce resistance in Escherichia coli. Analysis of the mode of action revealed that bacterial and parasite killing occur through a similar membranolytic mechanism involving rapid membrane permeabilization and depolarization. This was confirmed by high-resolution imaging (atomic force microscopy and field emission gun-scanning electron microscopy. Multiple combined techniques (nuclear magnetic resonance, surface plasmon resonance, differential scanning calorimetry allowed us to detail peptide-membrane interactions. [K3]SHa was shown to interact selectively with anionic model membranes with a 4-fold higher affinity (KD = 3 x 10-8 M than SHa. The amphipathic α-helical peptide inserts in-plane in the hydrophobic lipid bilayer and disrupts the acyl chain packing via a detergent-like effect. Interestingly, cellular events, such as mitochondrial membrane depolarization or DNA fragmentation, were observed in L. infantum promastigotes after exposure to SHa and [K3]SHa at concentrations above IC50. Our results indicate that these

  6. The broad-band X-ray spectrum of IC 4329A from a joint NuSTAR/Suzaku observation

    Energy Technology Data Exchange (ETDEWEB)

    Brenneman, L. W.; Elvis, M. [Harvard-Smithsonian CfA, 60 Garden St., MS-67, Cambridge, MA 02138 (United States); Madejski, G. [Kavli Institute for Particle Astrophysics and Cosmology, SLAC National Accelerator Laboratory, Menlo Park, CA 94025 (United States); Fuerst, F.; Harrison, F. A.; Grefenstette, B. W.; Madsen, K. K.; Rivers, E.; Walton, D. J. [Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Matt, G.; Marinucci, A. [Dipartimento di Matematica e Fisica, Università Roma Tre, via della Vasca Navale 84, I-00146 Roma (Italy); Ballantyne, D. R. [Center for Relativistic Astrophysics, School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Boggs, S. E. [Space Science Laboratory, University of California, Berkeley, CA 94720 (United States); Christensen, F. E.; Craig, W. W. [DTU Space-National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Fabian, A. C. [Institute of Astronomy, Madingley Road, Cambridge CB3 0HA (United Kingdom); Hailey, C. J. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Stern, D. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Zhang, W. W. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2014-06-10

    We have obtained a deep, simultaneous observation of the bright, nearby Seyfert galaxy IC 4329A with Suzaku and NuSTAR. Through a detailed spectral analysis, we are able to robustly separate the continuum, absorption, and distant reflection components in the spectrum. The absorbing column is found to be modest (∼6×10{sup 21} cm{sup −2} ), and does not introduce any significant curvature in the Fe K band. We are able to place a strong constraint on the presence of a broadened Fe Kα line (E{sub rest}=6.46{sub −0.07}{sup +0.08} keV with σ=0.33{sub −0.07}{sup +0.08} keV and EW=34{sub −7}{sup +8} eV), though we are not able to constrain any of the parameters of a relativistic reflection model. These results highlight the range in broad Fe K line strengths observed in nearby, bright, active galactic nuclei (roughly an order of magnitude), and imply a corresponding range in the physical properties of the inner accretion disk in these sources. We have also updated our previously reported measurement of the high-energy cutoff of the hard X-ray emission using both observatories rather than just NuSTAR alone: E {sub cut} = 186 ± 14 keV. This high-energy cutoff acts as a proxy for the temperature of the coronal electron plasma, enabling us to further separate this parameter from the plasma's optical depth and to update our results for these parameters as well. We derive kT=50{sub −3}{sup +6} keV with τ=2.34{sub −0.11}{sup +0.16} using a spherical geometry, kT = 61 ± 1 keV with τ = 0.68 ± 0.02 for a slab geometry, with both having an equivalent goodness-of-fit.

  7. Detection of a Mixed Infection in a Culture-Negative Brain Abscess by Broad-Spectrum Bacterial 16S rRNA Gene PCR ▿ †

    Science.gov (United States)

    Keller, Peter M.; Rampini, Silvana K.; Bloemberg, Guido V.

    2010-01-01

    We describe the identification of two bacterial pathogens from a culture-negative brain abscess by the use of broad-spectrum 16S rRNA gene PCR. Simultaneous detection of Fusobacterium nucleatum and Porphyromonas endodontalis was possible due to a 24-bp length difference of their partially amplified 16S rRNA genes, which allowed separation by high-resolution polyacrylamide gel electrophoresis. PMID:20392909

  8. A broad-spectrum sunscreen prevents cumulative damage from repeated exposure to sub-erythemal solar ultraviolet radiation representative of temperate latitudes.

    Science.gov (United States)

    Seité, S; Christiaens, F; Bredoux, C; Compan, D; Zucchi, H; Lombard, D; Fourtanier, A; Young, A R

    2010-02-01

    We have previously shown the detrimental effects of 19 sub-erythemal exposures to daily ultraviolet radiation (DUVR, which mimics non-extreme exposure conditions), delivered over 4 weeks to volunteers. This source had UVA (320-400 nm) to UVB (290-320 nm) irradiance ratio of 25, instead of that close to 10 that is typically the case with solar-simulated radiation (SSR) that represents summer global sunlight with a clear sky and quasi-zenith solar irradiance. Here, we report on an extension of this previous study, in which we evaluated the photoprotection afforded by a broad-spectrum daily-care product with a low-sun protection factor (SPF 8, UVA-PF 7 and 3* rated UVA protection). We assessed cellular and molecular markers of photodamage that are relevant to skin cancer and photoageing. This study shows that biological effects of repeated exposure to DUVR can be prevented by a broad-spectrum daily-care product and that the level of protection afforded varies with the studied endpoint. Efficient daily UVR protection, as provided by a broad-spectrum daily-care product, is necessary to prevent the 'silent' sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

  9. Effect of healthcare associated infections and broad spectrum antibiotic use in newborn period on development of asthma, allergic rhinitis and atopic dermatitis in early childhood

    Directory of Open Access Journals (Sweden)

    Hacer Yapicioglu Yildizdas

    2017-03-01

    Full Text Available Purpose: The iam of this study was to investigate the effect of healthcare associated infections (HAIs and broad spectrum antibiotic use in newborn period on asthma, allergic rhinitis and atopic dermatitis. Material and Methods: Seventy three children treated for HAIs in newborn period in Neonatal Intesive Care Unitin a 6 years period, and their 41 siblings who were healthy in newborn period were included in the study. Parents answered a detailed questionnaire, children were examined and complete blood count, serum total Ig E and specific Ig E levels were studied. Results: Ventilator associated pneumonia was observed in 32 (45.2%, blood stream infection in 28 (38.4% and clinic sepsis in 12 (16.4% of 73 children with HAIs. Asthma was significantly higher in HAIs group compared to sibling group (32.9% vs. 4.9, whereas there was no significant difference in allergic rhinitis (4.1% vs.2.4% and atopic dermatitis (6.8% vs. 0% among groups. When non-allergic 85 subjects and allergic 29 children compared, children who had been hospitalised and treated with broad-spectrum antibiotics in newborn period were almost 11.5 times as likely to have an allergic disease. Conclusion: Asthma was significantly higher in HAI group, and allergic disease risk seems to increase in children treated with broad-spectrum antibiotics for HAIs in newborn period. [Cukurova Med J 2017; 42(1.000: 132-139

  10. An Intrinsic Baldwin Effect in the H Beta Broad Emission Line in the Spectrum of NGC 5548

    Science.gov (United States)

    Gilbert, Karoline M.; Peterson, Bradley M.

    2003-01-01

    We investigate the possibility of an intrinsic Baldwin effect (i.e., nonlinear emission-line response to continuum variations) in the broad HP emission line of the active galaxy NGC 5548 using crosscorrelation techniques to remove light-travel time effects from the data. We find a nonlinear relationship between the HP emission line and continuum fluxes that is in good agreement with theoretical predictions. We suggest that similar analysis of multiple lines might provide a useful diagnostic of physical conditions in the broad-line region.

  11. Tricyclic GyrB/ParE (TriBE inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.

    Directory of Open Access Journals (Sweden)

    Leslie W Tari

    Full Text Available Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB and topoisomerase IV (ParE have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD, we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.

  12. Evaluation of a commercial microarray as a confirmation test for the presence of extended-spectrum beta-lactamases in isolates from the routine clinical setting.

    NARCIS (Netherlands)

    Platteel, T.N.; Stuart, J.W.; Voets, G.M.; Scharringa, J.; Sande, N. van de; Fluit, A.C.; Leverstein-van Hall, M.A.; Sturm, P.D.J.; et al.,

    2011-01-01

    Since the diagnostic characteristics of the Check-KPC ESBL microarray as a confirmation test on isolates obtained in a routine clinical setting have not been determined, we evaluated the microarray in a random selection of 346 clinical isolates with a positive ESBL screen test (MIC >1 mg/L for

  13. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Science.gov (United States)

    Burastero, Samuele E; Frigerio, Barbara; Lopalco, Lucia; Sironi, Francesca; Breda, Daniela; Longhi, Renato; Scarlatti, Gabriella; Canevari, Silvana; Figini, Mariangela; Lusso, Paolo

    2011-01-01

    To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs) directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env) bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ) was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  14. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Directory of Open Access Journals (Sweden)

    Samuele E Burastero

    Full Text Available To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  15. The broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.

    Science.gov (United States)

    Sandoz, Kelsi M; Valiant, William G; Eriksen, Steven G; Hruby, Dennis E; Allen, Robert D; Rockey, Daniel D

    2014-07-01

    Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates in Parents of Individuals with Autism Spectrum Disorders

    OpenAIRE

    Billeci, Lucia; Calderoni, Sara; Conti, Eugenia; Gesi, Camilla; Carmassi, Claudia; Dell'Osso, Liliana; Cioni, Giovanni; Muratori, Filippo; Guzzetta, Andrea

    2016-01-01

    Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the “Broader Autism Phenotype” (BAP). BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characteri...

  17. Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.

    Science.gov (United States)

    Horii, T; Arakawa, Y; Ohta, M; Ichiyama, S; Wacharotayankun, R; Kato, N

    1993-01-01

    Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam. Images PMID:8517725

  18. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    DEFF Research Database (Denmark)

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats

    2008-01-01

    ABSTRACT: Background Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined...... cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases...

  19. The broad-band X-ray spectrum of IC 4329A from a joint NuSTAR/Suzaku observation

    DEFF Research Database (Denmark)

    Brenneman, L. W.; Madejski, G.; Fuerst, F.

    2014-01-01

    We have obtained a deep, simultaneous observation of the bright, nearby Seyfert galaxy IC 4329A with Suzaku andNuSTAR. Through a detailed spectral analysis, we are able to robustly separate the continuum, absorption, and distant reflection components in the spectrum. The absorbing column is found...... also updated our previously reported measurement of the high-energy cutoff of the hard X-ray emission using both observatories rather than justNuSTAR alone: Ecut = 186±14 keV. This high-energy cutoff acts as a proxy for the temperature of the coronal electron plasma, enabling us to further separate...

  20. Influence of two-stream relativistic electron beam parameters on the space-charge wave with broad frequency spectrum formation

    Science.gov (United States)

    Alexander, LYSENKO; Iurii, VOLK

    2018-03-01

    We developed a cubic non-linear theory describing the dynamics of the multiharmonic space-charge wave (SCW), with harmonics frequencies smaller than the two-stream instability critical frequency, with different relativistic electron beam (REB) parameters. The self-consistent differential equation system for multiharmonic SCW harmonic amplitudes was elaborated in a cubic non-linear approximation. This system considers plural three-wave parametric resonant interactions between wave harmonics and the two-stream instability effect. Different REB parameters such as the input angle with respect to focusing magnetic field, the average relativistic factor value, difference of partial relativistic factors, and plasma frequency of partial beams were investigated regarding their influence on the frequency spectrum width and multiharmonic SCW saturation levels. We suggested ways in which the multiharmonic SCW frequency spectrum widths could be increased in order to use them in multiharmonic two-stream superheterodyne free-electron lasers, with the main purpose of forming a powerful multiharmonic electromagnetic wave.

  1. Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.

    Science.gov (United States)

    Fleeman, Renee; LaVoi, Travis M; Santos, Radleigh G; Morales, Angela; Nefzi, Adel; Welmaker, Gregory S; Medina-Franco, José L; Giulianotti, Marc A; Houghten, Richard A; Shaw, Lindsey N

    2015-04-23

    Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study, we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10000 and 750000 structural analogues for a total of >6 million compounds. From this, we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations development of resistance, and displayed almost no toxicity when tested against human lung cells and erythrocytes. Using a murine model of peritonitis, we also demonstrate that these agents are highly efficacious in vivo.

  2. Whole-genome sequencing of Bacillus velezensis LS69, a strain with a broad inhibitory spectrum against pathogenic bacteria.

    Science.gov (United States)

    Liu, Guoqiang; Kong, Yingying; Fan, Yajing; Geng, Ce; Peng, Donghai; Sun, Ming

    2017-05-10

    Bacillus velezensis LS69 was found to exhibit antagonistic activity against a diverse spectrum of pathogenic bacteria. It has one circular chromosome of 3,917,761bp with 3,643 open reading frames. Genome analysis identified ten gene clusters involved in nonribosomal synthesis of polyketides (macrolactin, bacillaene and difficidin), lipopeptides (surfactin, fengycin, bacilysin and iturin A) and bacteriocins (amylolysin and amylocyclicin). In addition, B. velezensis LS69 was found to contain a series of genes involved in enhancing plant growth and triggering plant immunity. Whole genome sequencing of Bacillus velezensis LS69 will provide a basis for elucidation of its biocontrol mechanisms and facilitate its applications in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Directory of Open Access Journals (Sweden)

    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  4. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Directory of Open Access Journals (Sweden)

    Johannsson Oskar

    2008-11-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations. Methods Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations. Results 10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA developed colon cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.

  5. Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses.

    Science.gov (United States)

    Hu, Yanmei; Zhang, Jiantao; Musharrafieh, Rami Ghassan; Ma, Chunlong; Hau, Raymond; Wang, Jun

    2017-09-01

    The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy. Mechanistic studies revealed that dapivirine inhibits the nuclear entry of viral ribonucleoproteins at the early stage of viral replication. As a result, viral RNA and protein synthesis were inhibited. Furthermore, dapivirine has a high in vitro genetic barrier to drug resistance, and its antiviral activity is synergistic with oseltamivir carboxylate. In summary, the in vitro antiviral results of dapivirine suggest it is a promising candidate for the development of the next generation of dual influenza and HIV antivirals. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Biogenic synthesis of Zinc oxide nanostructures from Nigella sativa seed: Prospective role as food packaging material inhibiting broad-spectrum quorum sensing and biofilm.

    Science.gov (United States)

    Al-Shabib, Nasser A; Husain, Fohad Mabood; Ahmed, Faheem; Khan, Rais Ahmad; Ahmad, Iqbal; Alsharaeh, Edreese; Khan, Mohd Shahnawaz; Hussain, Afzal; Rehman, Md Tabish; Yusuf, Mohammad; Hassan, Iftekhar; Khan, Javed Masood; Ashraf, Ghulam Md; Alsalme, Ali Mohammed; Al-Ajmi, Mohamed F; Tarasov, Vadim V; Aliev, Gjumrakch

    2016-12-05

    Bacterial spoilage of food products is regulated by density dependent communication system called quorum sensing (QS). QS control biofilm formation in numerous food pathogens and Biofilms formed on food surfaces act as carriers of bacterial contamination leading to spoilage of food and health hazards. Agents inhibiting or interfering with bacterial QS and biofilm are gaining importance as a novel class of next-generation food preservatives/packaging material. In the present study, Zinc nanostructures were synthesised using Nigella sativa seed extract (NS-ZnNPs). Synthesized nanostructures were characterized hexagonal wurtzite structure of size ~24 nm by UV-visible, XRD, FTIR and TEM. NS-ZnNPs demonstrated broad-spectrum QS inhibition in C. violaceum and P. aeruginosa biosensor strains. Synthesized nanostructures inhibited QS regulated functions of C. violaceum CVO26 (violacein) and elastase, protease, pyocyanin and alginate production in PAO1 significantly. NS-ZnNPs at sub-inhibitory concentrations inhibited the biofilm formation of four-food pathogens viz. C. violaceum 12472, PAO1, L. monocytogenes, E. coli. Moreover, NS-ZnNPs was found effective in inhibiting pre-formed mature biofilms of the four pathogens. Therefore, the broad-spectrum inhibition of QS and biofilm by biogenic Zinc oxide nanoparticles and it is envisaged that these nontoxic bioactive nanostructures can be used as food packaging material and/or as food preservative.

  7. The Freshwater Sponge Ephydatia fluviatilis Harbours Diverse Pseudomonas Species (Gammaproteobacteria, Pseudomonadales) with Broad-Spectrum Antimicrobial Activity

    Science.gov (United States)

    Keller-Costa, Tina; Jousset, Alexandre; van Overbeek, Leo; van Elsas, Jan Dirk; Costa, Rodrigo

    2014-01-01

    Bacteria are believed to play an important role in the fitness and biochemistry of sponges (Porifera). Pseudomonas species (Gammaproteobacteria, Pseudomonadales) are capable of colonizing a broad range of eukaryotic hosts, but knowledge of their diversity and function in freshwater invertebrates is rudimentary. We assessed the diversity, structure and antimicrobial activities of Pseudomonas spp. in the freshwater sponge Ephydatia fluviatilis. Polymerase Chain Reaction – Denaturing Gradient Gel Electrophoresis (PCR-DGGE) fingerprints of the global regulator gene gacA revealed distinct structures between sponge-associated and free-living Pseudomonas communities, unveiling previously unsuspected diversity of these assemblages in freshwater. Community structures varied across E. fluviatilis specimens, yet specific gacA phylotypes could be detected by PCR-DGGE in almost all sponge individuals sampled over two consecutive years. By means of whole-genome fingerprinting, 39 distinct genotypes were found within 90 fluorescent Pseudomonas isolates retrieved from E. fluviatilis. High frequency of in vitro antibacterial (49%), antiprotozoan (35%) and anti-oomycetal (32%) activities was found among these isolates, contrasting less-pronounced basidiomycetal (17%) and ascomycetal (8%) antagonism. Culture extracts of highly predation-resistant isolates rapidly caused complete immobility or lysis of cells of the protozoan Colpoda steinii. Isolates tentatively identified as P. jessenii, P. protegens and P. oryzihabitans showed conspicuous inhibitory traits and correspondence with dominant sponge-associated phylotypes registered by cultivation-independent analysis. Our findings suggest that E. fluviatilis hosts both transient and persistent Pseudomonas symbionts displaying antimicrobial activities of potential ecological and biotechnological value. PMID:24533086

  8. Genetic analysis of a novel broad-spectrum powdery mildew resistance gene from the wheat-Agropyron cristatum introgression line Pubing 74.

    Science.gov (United States)

    Lu, Yuqing; Yao, Miaomiao; Zhang, Jinpeng; Song, Liqiang; Liu, Weihua; Yang, Xinming; Li, Xiuquan; Li, Lihui

    2016-09-01

    A novel broad-spectrum powdery mildew resistance gene PmPB74 was identified in wheat- Agropyron cristatum introgression line Pubing 74. Development of wheat cultivars with broad-spectrum, durable resistance to powdery mildew has been restricted by lack of superior genetic resources. In this study, a wheat-A. cristatum introgression line Pubing 74, originally selected from a wide cross between the common wheat cultivar Fukuhokomugi (Fukuho) and Agropyron cristatum (L.) Gaertn (2n = 4x = 28; genome PPPP), displayed resistance to powdery mildew at both the seedling and adult stages. The putative alien chromosomal fragment in Pubing 74 was below the detection limit of genomic in situ hybridization (GISH), but evidence for other non-GISH-detectable introgressions was provided by the presence of three STS markers specific to A. cristatum. Genetic analysis indicated that Pubing 74 carried a single dominant gene for powdery mildew resistance, temporarily designated PmPB74. Molecular mapping showed that PmPB74 was located on wheat chromosome arm 5DS, and flanked by markers Xcfd81 and HRM02 at genetic distances of 2.5 and 1.7 cM, respectively. Compared with other lines with powdery mildew resistance gene(s) on wheat chromosome arm 5DS, Pubing 74 was resistant to all 28 Blumeria graminis f. sp tritici (Bgt) isolates from different wheat-producing regions of northern China. Allelism tests indicated that PmPB74 was not allelic to PmPB3558 or Pm2. Our work showed that PmPB74 is a novel gene with broad resistance to powdery mildew, and hence will be helpful in broadening the genetic basis of powdery mildew resistance in wheat.

  9. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites.

    Science.gov (United States)

    Kevin Ii, Dion A; Meujo, Damaris Af; Hamann, Mark T

    2009-02-01

    As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics.

  10. Dissemination and genetic support of broad-spectrum beta-lactam-resistant Escherichia coli strain isolated from two Tunisian hospitals during 2004-2012.

    Science.gov (United States)

    Ayari, Khaoula; Bourouis, Amel; Chihi, Hela; Mahrouki, Sihem; Naas, Thierry; Belhadj, Omrane

    2017-06-01

    The dissemination of extended-spectrum β-lactamase (ESBL)-producing bacteria presented a great concern worldwide. Gram-negative organisms such as Escherichia coli and Klebsiella pneumoniae are the most frequently isolated pathogens responsible for nosocomial infections. The aim of this study was to investigate and to follow the emergence of resistance and the characterization of Extended-Spectrum Beta-Lactamases (ESBL) among broad-spectrum beta-lactam- Escherichia coli clinical isolates recovered from the military hospital and Habib Thameur hospital in Tunisia. A total of 113 E.coli isolates obtained during the period 2004 through 2012 showed a significant degree of multi-resistance. Among these strains, the double-disk synergy test confirmed the ESBL phenotype in 46 isolates. These included 32(70%) strains from Hospital A and 14(30%) from Hospital B. The ESBL was identified as CTX-M-15. The ESBL resistance was transferred by a 60 kb plasmid CTXM-15-producing isolates were unrelated according to the PFGE analysis and characterization of the regions surrounding the blaCTX-M-15 showed the ISEcp1 elements located in the upstream region of the bla gene and 20 of them truncated by IS26. ESBL producing E. coli strains are a serious threat in the community in Tunisia and we should take into consideration any possible spread of such epidemiological resistance.

  11. A stably expressed llama single-domain intrabody targeting Rev displays broad-spectrum anti-HIV activity.

    Science.gov (United States)

    Boons, Eline; Li, Guangdi; Vanstreels, Els; Vercruysse, Thomas; Pannecouque, Christophe; Vandamme, Anne-Mieke; Daelemans, Dirk

    2014-12-01

    subtypes and groups. Altogether, our results indicate that Nb(190) may have broad potential as a gene therapeutic agent against HIV-1. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The Broad Autism (EndoPhenotype: Neurostructural And Neurofunctional Correlates In Parents Of Individuals With Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Lucia Billeci

    2016-07-01

    Full Text Available Autism Spectrum Disorders (ASD are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the Broader Autism Phenotype (BAP. BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characterizing brain profiles of relatives of autistic probands may help to understand ASD endophenotype. The aim of this review was to provide an up-to-date overview of research findings on the neurostructural and neurofunctional substrates in parents of individuals with ASD (pASD. The primary hypothesis was that, like for the behavioral profile, the pASD express an intermediate neurobiological pattern between ASD individuals and healthy controls.The 13 reviewed studies evaluated structural magnetic resonance imaging (MRI brain volumes, chemical signals using magnetic resonance spectroscopy (MRS, task-related functional activation by functional magnetic resonance imaging (fMRI, electroencephalography (EEG, or magnetoencephalography (MEG in pASD. The studies showed that pASD are generally different from healthy controls at a structural and functional level despite often not behaviorally impaired. More atypicalities in neural patterns of pASD seem to be associated with higher scores at BAP assessment. Some of the observed atypicalities are the same of the ASD probands. In addition, the pattern of neural correlates in pASD resembles that of adult individuals with ASD, or it is specific, possibly due to a compensatory mechanism are the same as those detected in ASD subjects. Future studies should ideally include a group of pASD and HC with their ASD and non-ASD probands respectively. They should subgrouping the pASD according to the BAP scores, considering gender as a

  13. Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.

    Science.gov (United States)

    Parker, Michael H; Smith-Swintosky, Virginia L; McComsey, David F; Huang, Yifang; Brenneman, Douglas; Klein, Brian; Malatynska, Ewa; White, H Steve; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Iannucci, Robert; Leclercq, Laurent; Cuyckens, Filip; Reitz, Allen B; Maryanoff, Bruce E

    2009-12-10

    In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.

  14. Bio-Inspired Wide-Angle Broad-Spectrum Cylindrical Lens Based on Reflections from Micro-Mirror Array on a Cylindrical Elastomeric Membrane

    Directory of Open Access Journals (Sweden)

    Chi-Chieh Huang

    2014-06-01

    Full Text Available We present a wide-angle, broad-spectrum cylindrical lens based on reflections from an array of three-dimensional, high-aspect-ratio micro-mirrors fabricated on a cylindrical elastomeric substrate, functionally inspired by natural reflecting superposition compound eyes. Our device can perform one-dimensional focusing and beam-shaping comparable to conventional refraction-based cylindrical lenses, while avoiding chromatic aberration. The focal length of our cylindrical lens is 1.035 mm, suitable for micro-optical systems. Moreover, it demonstrates a wide field of view of 152° without distortion, as well as modest spherical aberrations. Our work could be applied to diverse applications including laser diode collimation, barcode scanning, holography, digital projection display, microlens arrays, and optical microscopy.

  15. Spectrum

    DEFF Research Database (Denmark)

    Høgfeldt Hansen, Leif

    2016-01-01

    The publication functions as a proces description of the development and construction of an urban furniture SPECTRUM in the city of Gwangju, Republic of Korea. It is used as the cataloque for the exhibition of Spectrum.......The publication functions as a proces description of the development and construction of an urban furniture SPECTRUM in the city of Gwangju, Republic of Korea. It is used as the cataloque for the exhibition of Spectrum....

  16. Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs.

    Science.gov (United States)

    Cherkasov, Artem; Hilpert, Kai; Jenssen, Håvard; Fjell, Christopher D; Waldbrook, Matt; Mullaly, Sarah C; Volkmer, Rudolf; Hancock, Robert E W

    2009-01-16

    Increased multiple antibiotic resistance in the face of declining antibiotic discovery is one of society's most pressing health issues. Antimicrobial peptides represent a promising new class of antibiotics. Here we ask whether it is possible to make small broad spectrum peptides employing minimal assumptions, by capitalizing on accumulating chemical biology information. Using peptide array technology, two large random 9-amino-acid peptide libraries were iteratively created using the amino acid composition of the most active peptides. The resultant data was used together with Artificial Neural Networks, a powerful machine learning technique, to create quantitative in silico models of antibiotic activity. On the basis of random testing, these models proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models.

  17. Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

    Science.gov (United States)

    Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

    2015-06-01

    Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

  18. The sun protection factor (SPF) inadequately defines broad spectrum photoprotection: demonstration using skin reconstructed in vitro exposed to UVA, UVBor UV-solar simulated radiation.

    Science.gov (United States)

    Bernerd, Françoise; Vioux, Corinne; Lejeune, François; Asselineau, Daniel

    2003-01-01

    Wavelength specific biological damage has been previously identified in human skin reconstructed in vitro. Sunburn cell and pyrimidine dimers were found after UVB exposure, and alterations of dermal fibroblasts after UVA exposure. These damages permitted us to discriminate UVB and UVA single absorbers. The present study shows that these biological effects can be obtained simultaneously by a combined UVB + UVA exposure using ultraviolet solar simulated light (UV-SSR), which represents a relevant UV source. In addition, the protection afforded by two broad spectrum sunscreen complex formulations was assessed after topical application. These two formulations displayed the same sun protection factor but different UVA protection factors determined by the persistent pigment darkening (PPD) method. Dose response experiments of UVA or UV-SSR showed that the preparation with the highest PF-UVA provided a better protection with regard to dermal damage compared to the other formulation. Using an original UVB source to obtain the UVB portion of SSR spectrum, the preparations provided the same protection. This study strikingly illustrates the fact that the photoprotection afforded by two sunscreen formulations having similar SPF values is not equal with regard to dermal damage related to photoaging.

  19. A P25/(NH4)xWO3 hybrid photocatalyst with broad spectrum photocatalytic properties under UV, visible, and near-infrared irradiation.

    Science.gov (United States)

    Yang, Linfen; Liu, Bin; Liu, Tongyao; Ma, Xinlong; Li, Hao; Yin, Shu; Sato, Tsugio; Wang, Yuhua

    2017-04-03

    In this study, a series of hybrid nanostructured photocatalysts P25/(NH 4 ) x WO 3 nanocomposites with the average crystallite size of P25 and (NH 4 ) x WO 3 of the sample was calculated to be about 30 nm and 130 nm, were successfully synthesized via a simple one-step hydrothermal method. The as-obtained samples was characterized by transmission electron microscopy (TEM), which implies that the P25/(NH 4 ) x WO 3 nanocomposites are fabricated with favourable nanosizd interfacial. The XPS results confirmed that the obtained sample consists of mixed chemical valences of W 5+ and W 6+ , the low-valance W 5+ sites could be the origin of NIR absorption. As revealed by optical absorption results, P25/(NH 4 ) x WO 3 nanocomposites possess high optical absorption in the whole solar spectrum of 200-2500 nm. Benefiting from this unique photo-absorption property and the synergistic effect of P25 and (NH 4 ) x WO 3 , broad spectrum response photocatalytic activities covering UV, visible and near infrared regions on degradation of Rhodamine B have been realized by P25/(NH 4 ) x WO 3 nanocomposites. Meanwhile, the stability of photocatalysts was examined by the XRD and XPS of the photocatalysts after the reaction. The results show that P25/(NH 4 ) x WO 3 photocatalysts has a brilliant application prospect in the energy utilization to solve deteriorating environmental issues.

  20. INVESTIGATING THE COMPLEX X-RAY SPECTRUM OF A BROAD-LINE 2MASS RED QUASAR: XMM-NEWTON OBSERVATION OF FTM 0830+3759

    International Nuclear Information System (INIS)

    Piconcelli, Enrico; Nicastro, Fabrizio; Fiore, Fabrizio; Vignali, Cristian; Bianchi, Stefano; Miniutti, Giovanni

    2010-01-01

    We report results from a 50 ks XMM-Newton observation of the dust-reddened broad-line quasar FTM 0830+3759 (z = 0.413) selected from the Faint Images of the Radio Sky at Twenty cm/Two Micron All Sky Survey red quasar survey. For this active galactic nucleus (AGN), a very short 9 ks Chandra exposure had suggested a feature-rich X-ray spectrum and Hubble Space Telescope images revealed a very disturbed host galaxy morphology. Contrary to classical, optically selected quasars, the X-ray properties of red (i.e., with J - K s > 1.7 and R - K s > 4.0) broad-line quasars are still quite unexplored, although there is a growing consensus that, due to moderate obscuration, these objects can offer a unique view of spectral components typically swamped by the AGN light in normal, blue quasars. The XMM-Newton observation discussed here has definitely confirmed the complexity of the X-ray spectrum revealing the presence of a cold (or mildly ionized) absorber with N H ∼ 10 22 cm -2 along the line of sight to the nucleus and a Compton reflection component accompanied by an intense Fe Kα emission line in this quasar with a L 2-10 k eV ∼ 5 x 10 44 erg s -1 . A soft-excess component is also required by the data. The match between the column density derived by our spectral analysis and that expected on the basis of reddening due to the dust suggests the possibility that both absorptions occur in the same medium. FTM 0830+3759 is characterized by an extinction/absorption-corrected X-ray-to-optical flux ratio α ox = -2.3, which is steeper than expected on the basis of its UV luminosity. These findings indicate that the X-ray properties of FTM 0830+3759 differ from those typically observed for optically selected broad-line quasars with comparable hard X-ray luminosity.

  1. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, So Young; Park, Ji Hoon [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of); Kim, Young Ho; Kang, Jong Seong [College of Pharmacy, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Min, Ji-Young, E-mail: jiyoung.min@ip-korea.org [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of)

    2016-03-04

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  2. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    International Nuclear Information System (INIS)

    Chang, So Young; Park, Ji Hoon; Kim, Young Ho; Kang, Jong Seong; Min, Ji-Young

    2016-01-01

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  3. Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

    Science.gov (United States)

    Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

    2014-08-01

    The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  4. Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.

    Science.gov (United States)

    Chuck, Chi-Pang; Chen, Chao; Ke, Zhihai; Wan, David Chi-Cheong; Chow, Hak-Fun; Wong, Kam-Bo

    2013-01-01

    Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6-49 μM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~10x more potent than the other inhibitors tested. Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 μM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis.

    Science.gov (United States)

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-Aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-10-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action-inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.

  6. Broad Protein Spectrum in Stored Pollen of Three Stingless Bees from the Chaco Dry Forest in South America (Hymenoptera, Apidae, Meliponini and Its Ecological Implications

    Directory of Open Access Journals (Sweden)

    Favio Gerardo Vossler

    2015-01-01

    Full Text Available Protein content of pollen stored by three meliponine species was variable from 9.78% (less than half the value considered as optimal to brood development in Apis mellifera in type Capparis tweediana-C. speciosa to more than 26% in type Maytenus vitis-idaea and some Prosopis samples. This pollen of low protein value was occasionally foraged (only six out of 75 masses analyzed of G. argentina, but none in 86 masses of T. fiebrigi or in ten of M. orbignyi. However, it is likely that amino acid deficiencies of certain pollens are compensated by randomly foraging on a broad spectrum of pollen plants. The large amounts of pollen stored in their nests might also be important in compensating these deficiencies. The only sample studied for M. orbignyi showed a protein value greater than the one required for A. mellifera and was dominated by types Acacia praecox and Prosopis. As this species also prefers Solanum and other protein-rich pollen, more samples would need to be analyzed to establish whether protein requirements are high for this Melipona species. Pollen showing the highest protein content (>26% belonged to highly nectariferous plants well represented in meliponine and Apis honey such as Prosopis, Maytenus, and Ziziphus.

  7. Ectopic expression of Arabidopsis broad-spectrum resistance gene RPW8.2 improves the resistance to powdery mildew in grapevine (Vitis vinifera).

    Science.gov (United States)

    Hu, Yang; Li, Yajuan; Hou, Fengjuan; Wan, Dongyan; Cheng, Yuan; Han, Yongtao; Gao, Yurong; Liu, Jie; Guo, Ye; Xiao, Shunyuan; Wang, Yuejin; Wen, Ying-Qiang

    2018-02-01

    Powdery mildew is the most economically important disease of cultivated grapevines worldwide. Here, we report that the Arabidopsis broad-spectrum disease resistance gene RPW8.2 could improve resistance to powdery mildew in Vitis vinifera cv. Thompson Seedless. The RPW8.2-YFP fusion gene was stably expressed in grapevines from either the constitutive 35S promoter or the native promoter (NP) of RPW8.2. The grapevine shoots and plantlets transgenic for 35S::RPW8.2-YFP showed reduced rooting and reduced growth at later development stages in the absence of any pathogens. Infection tests with an adapted grapevine powdery mildew isolate En NAFU1 showed that hyphal growth and sporulation were significantly restricted in transgenic grapevines expressing either of the two constructs. The resistance appeared to be attributable to the ectopic expression of RPW8.2, and associated with the enhanced encasement of the haustorial complex (EHC) and onsite accumulation of H 2 O 2 . In addition, the RPW8.2-YFP fusion protein showed focal accumulation around the fungal penetration sites. Transcriptome analysis revealed that ectopic expression of RPW8.2 in grapevines not only significantly enhanced salicylic acid-dependent defense signaling, but also altered expression of other phytohormone-associated genes. Taken together, our results indicate that RPW8.2 could be utilized as a transgene for improving resistance against powdery mildew in grapevines. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Efficacy of Oral E1210, a New Broad-Spectrum Antifungal with a Novel Mechanism of Action, in Murine Models of Candidiasis, Aspergillosis, and Fusariosis▿

    Science.gov (United States)

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-01-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action—inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated. PMID:21788462

  9. An application in cheddar cheese manufacture for a strain of Lactococcus lactis producing a novel broad-spectrum bacteriocin, lacticin 3147.

    Science.gov (United States)

    Ryan, M P; Rea, M C; Hill, C; Ross, R P

    1996-01-01

    Lactococcus lactis DPC3147, a strain isolated from an Irish kefir grain, produces a bacteriocin with a broad spectrum of inhibition. The bacteriocin produced is heat stable, particularly at a low pH, and inhibits nisin-producing (Nip+) lactococci. On the basis of the observation that the nisin structural gene (nisA) does not hybridize to DPC3147 genomic DNA, the bacteriocin produced was considered novel and designated lacticin 3147. The genetic determinants which encode lacticin 3147 are contained on a 63-kb plasmid, which was conjugally mobilized to a commercial cheese starter, L. lactis subsp. cremoris DPC4268. The resultant transconjugant, DPC4275, both produces and is immune to lacticin 3147. The ability of lacticin 3147-producing lactococci to perform as cheddar cheese starters was subsequently investigated in cheesemaking trials. Bacteriocin-producing starters (which included the transconjugant strain DPC4275) produced acid at rates similar to those of commercial strains. The level of lacticin 3147 produced in cheese remained constant over 6 months of ripening and correlated with a significant reduction in the levels of nonstarter lactic acid bacteria. Such results suggest that these starters provide a means of controlling developing microflora in ripened fermented products. PMID:8593062

  10. CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor with antiproliferative and antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Cao, Z Alexander; Bass, Kathryn E; Balasubramanian, Sriram; Liu, Liang; Schultz, Brian; Verner, Erik; Dai, Yuqin; Molina, Rafael A; Davis, Jack R; Misialek, Shawn; Sendzik, Martin; Orr, Christine J; Leung, Ling; Callan, Ondine; Young, Peter; Dalrymple, Stacie A; Buggy, Joseph J

    2006-07-01

    CRA-026440 is a novel, broad-spectrum, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) that shows antitumor and antiangiogenic activities in vitro and in vivo preclinically. CRA-026440 inhibited pure recombinant isozymes HDAC1, HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range. Treatment of cultured tumor cell lines grown in vitro with CRA-026440 resulted in the accumulation of acetylated histone and acetylated tubulin, leading to an inhibition of tumor cell growth and the induction of apoptosis. CRA-026440 inhibited ex vivo angiogenesis in a dose-dependent manner. CRA-026440 parenterally given to mice harboring HCT116 or U937 human tumor xenografts resulted in a statistically significant reduction in tumor growth. CRA-026440, when used in combination with Avastin, achieved greater preclinical efficacy in HCT 116 colorectal tumor model. Inhibition of tumor growth was accompanied by an increase in the acetylation of alpha-tubulin in peripheral blood mononuclear cells and an alteration in the expression of many genes in the tumors, including several involved in angiogenesis, apoptosis, and cell growth. These results reveal CRA-026440 to be a novel HDAC inhibitor with potent antitumor activity.

  11. Oldest human occupation of Wallacea at Laili Cave, Timor-Leste, shows broad-spectrum foraging responses to late Pleistocene environments

    Science.gov (United States)

    Hawkins, Stuart; O'Connor, Sue; Maloney, Tim Ryan; Litster, Mirani; Kealy, Shimona; Fenner, Jack N.; Aplin, Ken; Boulanger, Clara; Brockwell, Sally; Willan, Richard; Piotto, Elena; Louys, Julien

    2017-09-01

    The Wallacea Archipelago provides an extraordinary laboratory for the study of human colonisation and adaptation, yet few detailed archaeological studies have been conducted in the region that span the earliest phase of human settlement. Laili Cave, in northern Timor-Leste, preserves the oldest human occupation in this insular region with a cultural sequence spanning 11,200 to 44,600 cal BP. Small-bodied vertebrates and invertebrates were recovered to the lowest excavated levels, associated with highly concentrated stone artefacts. We report on human behavioural adaptations within the context of Pleistocene environments and changing landscapes using zooarchaeological, stone artefact, bathymetric, and experimental isotopic analyses. Results indicate that Pleistocene humans used the abundant local chert liberally and engaged in mobile broad-spectrum exploitation of invertebrates and fishes from marine, estuarine, and freshwater environments within close proximity of Laili Cave. The faunal assemblage indicates heterogeneous but relatively stable environments during the late Pleistocene. Variability in subsistence strategies over time appears to be a response to changing landscapes and concomitant local resources. This record contrasts with marine specialisations evident from other sites in Timor-Leste and within the broader Wallacean region.

  12. Varespladib (LY315920 Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation

    Directory of Open Access Journals (Sweden)

    Matthew Lewin

    2016-08-01

    Full Text Available Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2 activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2 inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.

  13. Sunscreens with broad-spectrum absorption decrease the trans TO cis photoisomerization of urocanic acid in the human stratum corneum after multiple UV light exposures

    International Nuclear Information System (INIS)

    Krien, P.M.; Moyal, D.

    1994-01-01

    The trans to cis photoisomerization of urocanic acid (UCA) in skin is considered to play an important role in the mechanism of immunosuppression. We have investigated the effects of skin type and various sunscreens with low sun protection factor (SPF) on the UV-induced cis-UCA formation in human skin after exposure to artificial UV light. The rate of cis-UCA formation depends little on the skin type and is reduced by topical application of sunscreens. The rate of cis-UCA formation decreases with increasing SPF and only broad-spectrum, highly protective sunscreens offer protection against the UV-induced formation of cis-UCA, which accumulates in the stratum corneum after multiple UV exposures. A theoretical approach to estimate the distribution of cis-UCA after irradiation indicates that this compound may diffuse into the deeper layers of the epidermis with D ∼ 10 -17 m 2 /s, and that its elimination from the stratum corneum is mainly due to desquamation. (author)

  14. Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

    Science.gov (United States)

    Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

    2016-01-01

    Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

  15. A novel blast resistance gene, Pi54rh cloned from wild species of rice, Oryza rhizomatis confers broad spectrum resistance to Magnaporthe oryzae.

    Science.gov (United States)

    Das, Alok; Soubam, D; Singh, P K; Thakur, S; Singh, N K; Sharma, T R

    2012-06-01

    The dominant rice blast resistance gene, Pi54 confers resistance to Magnaporthe oryzae in different parts of India. In our effort to identify more effective forms of this gene, we isolated an orthologue of Pi54 named as Pi54rh from the blast-resistant wild species of rice, Oryza rhizomatis, using allele mining approach and validated by complementation. The Pi54rh belongs to CC-NBS-LRR family of disease resistance genes with a unique Zinc finger (C(3)H type) domain. The 1,447 bp Pi54rh transcript comprises of 101 bp 5'-UTR, 1,083 bp coding region and 263 bp 3'-UTR, driven by pathogen inducible promoter. We showed the extracellular localization of Pi54rh protein and the presence of glycosylation, myristoylation and phosphorylation sites which implicates its role in signal transduction process. This is in contrast to other blast resistance genes that are predicted to be intracellular NBS-LRR-type resistance proteins. The Pi54rh was found to express constitutively at basal level in the leaves, but upregulates 3.8-fold at 96 h post-inoculation with the pathogen. Functional validation of cloned Pi54rh gene using complementation test showed high degree of resistance to seven isolates of M. oryzae collected from different geographical locations of India. In this study, for the first time, we demonstrated that a rice blast resistance gene Pi54rh cloned from wild species of rice provides broad spectrum resistance to M. oryzae hence can be used in rice improvement breeding programme.

  16. Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

    Science.gov (United States)

    Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara

    2016-09-01

    The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.

  17. Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue Virus.

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2011-01-01

    Full Text Available The ultimate stage of the transmission of Dengue Virus (DENV to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti. Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598. Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide.

  18. Molecular characterisation of the broad-spectrum resistance to powdery mildew conferred by the Stpk-V gene from the wild species Haynaldia villosa.

    Science.gov (United States)

    Qian, C; Cui, C; Wang, X; Zhou, C; Hu, P; Li, M; Li, R; Xiao, J; Wang, X; Chen, P; Xing, L; Cao, A

    2017-11-01

    A key member of the Pm21 resistance gene locus, Stpk-V, derived from Haynaldia villosa, was shown to confer broad-spectrum resistance to wheat powdery mildew. The present study was planned to investigate the resistance mechanism mediated by Stpk-V. Transcriptome analysis was performed in Stpk-V transgenic plants and recipient Yangmai158 upon Bgt infection, and detailed histochemical observations were conducted. Chromosome location of Stpk-V orthologous genes in Triticeae species was conducted for evolutionary study and over-expression of Stpk-V both in barley and Arabidopsis was performed for functional study. The transcriptome results indicate, at the early infection stage, the ROS pathway, JA pathway and some PR proteins associated with the SA pathway were activated in both the resistant Stpk-V transgenic plants and susceptible Yangmai158. However, at the later infection stage, the genes up-regulated at the early stage were continuously held only in the transgenic plants, and a large number of new genes were also activated in the transgenic plants but not in Yangmai158. Results indicate that sustained activation of the early response genes combined with later-activated genes mediated by Stpk-V is critical for resistance in Stpk-V transgenic plants. Stpk-V orthologous genes in the representative grass species are all located on homologous group six chromosomes, indicating that Stpk-V is an ancient gene in the grasses. Over-expression of Stpk-V enhanced host resistance to powdery mildew in barley but not in Arabidopsis. Our results enable a better understanding of the resistance mechanism mediated by Stpk-V, and establish a solid foundation for its use in cereal breeding as a gene resource. © 2017 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

  19. Pentocin MQ1: A Novel, Broad-Spectrum, Pore-Forming Bacteriocin From Lactobacillus pentosus CS2 With Quorum Sensing Regulatory Mechanism and Biopreservative Potential

    Directory of Open Access Journals (Sweden)

    Samson B. Wayah

    2018-03-01

    Full Text Available Micrococcus luteus, Listeria monocytogenes, and Bacillus cereus are major food-borne pathogenic and spoilage bacteria. Emergence of antibiotic resistance and consumer demand for foods containing less of chemical preservatives led to a search for natural antimicrobials. A study aimed at characterizing, investigating the mechanism of action and regulation of biosynthesis and evaluating the biopreservative potential of pentocin from Lactobacillus pentosus CS2 was conducted. Pentocin MQ1 is a novel bacteriocin isolated from L. pentosus CS2 of coconut shake origin. The purification strategy involved adsorption-desorption of bacteriocin followed by RP-HPLC. It has a molecular weight of 2110.672 Da as determined by MALDI-TOF mass spectrometry and a molar extinction value of 298.82 M−1 cm−1. Pentocin MQ1 is not plasmid-borne and its biosynthesis is regulated by a quorum sensing mechanism. It has a broad spectrum of antibacterial activity, exhibited high chemical, thermal and pH stability but proved sensitive to proteolytic enzymes. It is potent against M. luteus, B. cereus, and L. monocytogenes at micromolar concentrations. It is quick-acting and exhibited a bactericidal mode of action against its targets. Target killing was mediated by pore formation. We report for the first time membrane permeabilization as a mechanism of action of the pentocin from the study against Gram-positive bacteria. Pentocin MQ1 is a cell wall-associated bacteriocin. Application of pentocin MQ1 improved the microbiological quality and extended the shelf life of fresh banana. This is the first report on the biopreservation of banana using bacteriocin. These findings place pentocin MQ1 as a potential biopreservative for further evaluation in food and medical applications.

  20. Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Weber, Daniela; Jenq, Robert R; Peled, Jonathan U; Taur, Ying; Hiergeist, Andreas; Koestler, Josef; Dettmer, Katja; Weber, Markus; Wolff, Daniel; Hahn, Joachim; Pamer, Eric G; Herr, Wolfgang; Gessner, André; Oefner, Peter J; van den Brink, Marcel R M; Holler, Ernst

    2017-05-01

    In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Phosphatase Inhibitors Function as Novel, Broad Spectrum Botulinum Neurotoxin Antagonists in Mouse and Human Embryonic Stem Cell-Derived Motor Neuron-Based Assays.

    Directory of Open Access Journals (Sweden)

    Erkan Kiris

    Full Text Available There is an urgent need to develop novel treatments to counter Botulinum neurotoxin (BoNT poisoning. Currently, the majority of BoNT drug development efforts focus on directly inhibiting the proteolytic components of BoNT, i.e. light chains (LC. Although this is a rational approach, previous research has shown that LCs are extremely difficult drug targets and that inhibiting multi-serotype BoNTs with a single LC inhibitor may not be feasible. An alternative approach would target neuronal pathways involved in intoxication/recovery, rather than the LC itself. Phosphorylation-related mechanisms have been implicated in the intoxication pathway(s of BoNTs. However, the effects of phosphatase inhibitors upon BoNT activity in the physiological target of BoNTs, i.e. motor neurons, have not been investigated. In this study, a small library of phosphatase inhibitors was screened for BoNT antagonism in the context of mouse embryonic stem cell-derived motor neurons (ES-MNs. Four inhibitors were found to function as BoNT/A antagonists. Subsequently, we confirmed that these inhibitors protect against BoNT/A in a dose-dependent manner in human ES-MNs. Additionally, these compounds provide protection when administered in post-intoxication scenario. Importantly, the inhibitors were also effective against BoNT serotypes B and E. To the best of our knowledge, this is the first study showing phosphatase inhibitors as broad-spectrum BoNT antagonists.

  2. Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N-Docosahexaenoyl 2′, 2′-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Youssef W. Naguib

    2016-01-01

    Full Text Available In this study, a new compound, 4-(N-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC, was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3 Da and a melting point of about 96°C. The activation energy for the degradation of DHA-dFdC in an aqueous Tween 80–based solution is 12.86 kcal/mol, whereas its stability is significantly higher in the presence of vitamin E. NCI-60 DTP Human Tumor Cell Line Screening revealed that DHA-dFdC has potent and broad-spectrum antitumor activity, especially in leukemia, renal, and central nervous system cancer cell lines. In human and murine pancreatic cancer cell lines, the IC50 value of DHA-dFdC was up to 105-fold lower than that of dFdC. The elimination of DHA-dFdC in mouse plasma appeared to follow a biexponential model, with a terminal phase t1/2 of about 58 minutes. DHA-dFdC significantly extended the survival of genetically engineered mice that spontaneously develop pancreatic ductal adenocarcinoma. In nude mice with subcutaneously implanted human Panc-1 pancreatic tumors, the antitumor activity of DHA-dFdC was significantly stronger than the molar equivalent of dFdC alone, DHA alone, or the physical mixture of them (1:1, molar ratio. DHA-dFdC also significantly inhibited the growth of Panc-1 tumors orthotopically implanted in the pancreas of nude mice, whereas the molar equivalent dose of dFdC alone did not show any significant activity. DHA-dFdC is a promising compound for the potential treatment of cancers in organs such as the pancreas.

  3. Detection and characterization of broad-spectrum antipathogen activity of novel rhizobacterial isolates and suppression of Fusarium crown and root rot disease of tomato.

    Science.gov (United States)

    Zhang, L; Khabbaz, S E; Wang, A; Li, H; Abbasi, P A

    2015-03-01

    To detect and characterize broad-spectrum antipathogen activity of indigenous bacterial isolates obtained from potato soil and soya bean leaves for their potential to be developed as biofungicides to control soilborne diseases such as Fusarium crown and root rot of tomato (FCRR) caused by Fusarium oxysporum f. sp. radicis-lycopersici (Forl). Thirteen bacterial isolates (Bacillus amyloliquefaciens (four isolates), Paenibacillus polymyxa (three isolates), Pseudomonas chlororaphis (two isolates), Pseudomonas fluorescens (two isolates), Bacillus subtilis (one isolate) and Pseudomonas sp. (one isolate)) or their volatiles showed antagonistic activity against most of the 10 plant pathogens in plate assays. Cell-free culture filtrates (CF) of five isolates or 1-butanol extracts of CFs also inhibited the growth of most pathogen mycelia in plate assays. PCR analysis confirmed the presence of most antibiotic biosynthetic genes such as phlD, phzFA, prnD and pltC in most Pseudomonas isolates and bmyB, bacA, ituD, srfAA and fenD in most Bacillus isolates. These bacterial isolates varied in the production of hydrogen cyanide (HCN), siderophores, β-1,3-glucanases, chitinases, proteases, indole-3-acetic acid, salicylic acid, and for nitrogen fixation and phosphate solubilization. Gas chromatography-mass spectrometry analysis identified 10 volatile compounds from 10 isolates and 18 compounds from 1-butanol extracts of CFs of five isolates. Application of irradiated peat formulation of six isolates to tomato roots prior to transplanting in a Forl-infested potting mix and field soil provided protection of tomato plants from FCRR disease and enhanced plant growth under greenhouse conditions. Five of the 13 indigenous bacterial isolates were antagonistic to eight plant pathogens, both in vitro and in vivo. Antagonistic and plant-growth promotion activities of these isolates might be related to the production of several types of antibiotics, lytic enzymes, phytohormones, secondary

  4. Comparison of a Broad-Based Screen versus Disorder-Specific Screen in Detecting Young Children with an Autism Spectrum Disorder

    OpenAIRE

    Wiggins, Lisa D.; Piazza, Vivian; Robins, Diana L.

    2012-01-01

    The goals of our study were to (a) compare agreement between autism spectrum disorder diagnosis and outcome of the Modified Checklist for Autism in Toddlers and Parents Evaluation of Developmental Status in a sample of toddlers and (b) examine specific concerns noted for toddlers who screened negative on the Modified Checklist for Autism in Toddlers or Parents Evaluation of Developmental Status but were later diagnosed with autism spectrum disorder. Participants were administered the Modified...

  5. Development of the Digital Health Literacy Instrument : Measuring a Broad Spectrum of Health 1.0 and Health 2.0 Skills

    NARCIS (Netherlands)

    van der Vaart, Rosalie; Drossaert, Constance

    2017-01-01

    Background: With the digitization of health care and the wide availability of Web-based applications, a broad set of skills is essential to properly use such facilities; these skills are called digital health literacy or eHealth literacy. Current instruments to measure digital health literacy focus

  6. Comparison of a Broad-Based Screen versus Disorder-Specific Screen in Detecting Young Children with an Autism Spectrum Disorder

    Science.gov (United States)

    Wiggins, Lisa D; Piazza, Vivian; Robins, Diana L

    2014-01-01

    The goals of our study were to (a) compare agreement between autism spectrum disorder diagnosis and outcome of the Modified Checklist for Autism in Toddlers and Parents Evaluation of Developmental Status in a sample of toddlers and (b) examine specific concerns noted for toddlers who screened negative on the Modified Checklist for Autism in…

  7. Characterization and modeling of broad spectrum InAs-GaAs quantum-dot superluminescent diodes emitting at 1.2-1.3 μm

    NARCIS (Netherlands)

    Rossetti, M.; Li, L.; Markus, A.; Fiore, A.; Occhi, L.; Velez, C.; Mikhrin, S.; Krestnikov, I.; Kovsh, A.

    2007-01-01

    High-power broadband superluminescent diodes (SLDs) emitting in the 1.2-1.3-?m region are demonstrated using InAs-GaAs quantum dots (QDs). The highest output powers of ?30-50 mW are achieved using 18 QD layers with p-doped GaAs spacers. At these high powers the device operates in a regime of broad

  8. Antimicrobial peptides effectively kill a broad spectrum of Listeria monocytogenes and Staphylococcus aureus strains independently of origin, sub-type, or virulence factor expression

    DEFF Research Database (Denmark)

    Gottlieb, Caroline Trebbien; Thomsen, L.E.; Ingmer, H.

    2008-01-01

    -type, and phenotypic behavior. Strains within each species were equally sensitive to HDPs and oxidative stress representing important components of the innate immune defense system. Four non-human peptides (protamine, plectasin, novicidin, and novispirin G10) were similar in activity profile (MIC value spectrum......Background Host defense peptides (HDPs), or antimicrobial peptides (AMPs), are important components of the innate immune system that bacterial pathogens must overcome to establish an infection and HDPs have been suggested as novel antimicrobial therapeutics in treatment of infectious diseases...... Caenorhabditis elegans. For L. monocytogenes, proliferation in whole blood was paralleled by high invasion in Caco-2 cells and fast killing of C. elegans, however, no such pattern in phenotypic behavior was observed for S. aureus and none of the phenotypic differences were correlated to sensitivity to HDPs...

  9. Fibre optic microarrays.

    Science.gov (United States)

    Walt, David R

    2010-01-01

    This tutorial review describes how fibre optic microarrays can be used to create a variety of sensing and measurement systems. This review covers the basics of optical fibres and arrays, the different microarray architectures, and describes a multitude of applications. Such arrays enable multiplexed sensing for a variety of analytes including nucleic acids, vapours, and biomolecules. Polymer-coated fibre arrays can be used for measuring microscopic chemical phenomena, such as corrosion and localized release of biochemicals from cells. In addition, these microarrays can serve as a substrate for fundamental studies of single molecules and single cells. The review covers topics of interest to chemists, biologists, materials scientists, and engineers.

  10. MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates

    Directory of Open Access Journals (Sweden)

    Katrina eBrudzynski

    2015-07-01

    Full Text Available The emergence of extended- spectrum β-lactamase (ESBL is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1 precursor that harbors three antimicrobial peptides: Jelleins 1, 2 and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised 3 MRSA, 4 Pseudomonas aeruginosa, 2 Klebsiella pneumoniae, 2 VRE and 5 Extended-spectrum beta-lactamase (ESBL identified as 1 Proteus mirabilis, 3 Escherichia coli and 1 Escherichia coli NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differred in their susceptibility to glps with MIC90 values ranging from 4.8μg/ml against B. subtilis to 14.4μg/ml against ESBL K. pneumoniae, Klebsiella spp ESBL and E. coli and up to 33μg/ml against highly resistant strains of P. aeruginosa. Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a their mode of action is distinct from other classes of β-lactams and that (b the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate.

  11. DNA Microarray Technology

    Science.gov (United States)

    Skip to main content DNA Microarray Technology Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features Funding Divisions Funding ...

  12. DNA Microarray Technology; TOPICAL

    International Nuclear Information System (INIS)

    WERNER-WASHBURNE, MARGARET; DAVIDSON, GEORGE S.

    2002-01-01

    Collaboration between Sandia National Laboratories and the University of New Mexico Biology Department resulted in the capability to train students in microarray techniques and the interpretation of data from microarray experiments. These studies provide for a better understanding of the role of stationary phase and the gene regulation involved in exit from stationary phase, which may eventually have important clinical implications. Importantly, this research trained numerous students and is the basis for three new Ph.D. projects

  13. A Sequential Statistical Approach towards an Optimized Production of a Broad Spectrum Bacteriocin Substance from a Soil Bacterium Bacillus sp. YAS 1 Strain

    Directory of Open Access Journals (Sweden)

    Amira M. Embaby

    2014-01-01

    Full Text Available Bacteriocins, ribosomally synthesized antimicrobial peptides, display potential applications in agriculture, medicine, and industry. The present study highlights integral statistical optimization and partial characterization of a bacteriocin substance from a soil bacterium taxonomically affiliated as Bacillus sp. YAS 1 after biochemical and molecular identifications. A sequential statistical approach (Plackett-Burman and Box-Behnken was employed to optimize bacteriocin (BAC YAS 1 production. Using optimal levels of three key determinants (yeast extract (0.48% (w/v, incubation time (62 hrs, and agitation speed (207 rpm in peptone yeast beef based production medium resulted in 1.6-fold enhancement in BAC YAS 1 level (470 AU/mL arbitrary units against Erwinia amylovora. BAC YAS 1 showed activity over a wide range of pH (1–13 and temperature (45–80°C. A wide spectrum antimicrobial activity of BAC YAS 1 against the human pathogens (Clostridium perfringens, Staphylococcus epidermidis, Campylobacter jejuni, Enterobacter aerogenes, Enterococcus sp., Proteus sp., Klebsiella sp., and Salmonella typhimurium, the plant pathogen (E. amylovora, and the food spoiler (Listeria innocua was demonstrated. On top and above, BAC YAS 1 showed no antimicrobial activity towards lactic acid bacteria (Lactobacillus bulgaricus, L. casei, L. lactis, and L. reuteri. Promising characteristics of BAC YAS 1 prompt its commercialization for efficient utilization in several industries.

  14. Evaluation of a Broad-Spectrum Partially Automated Adverse Event Surveillance System: A Potential Tool for Patient Safety Improvement in Hospitals With Limited Resources.

    Science.gov (United States)

    Saikali, Melody; Tanios, Alain; Saab, Antoine

    2017-11-21

    The aim of the study was to evaluate the sensitivity and resource efficiency of a partially automated adverse event (AE) surveillance system for routine patient safety efforts in hospitals with limited resources. Twenty-eight automated triggers from the hospital information system's clinical and administrative databases identified cases that were then filtered by exclusion criteria per trigger and then reviewed by an interdisciplinary team. The system, developed and implemented using in-house resources, was applied for 45 days of surveillance, for all hospital inpatient admissions (N = 1107). Each trigger was evaluated for its positive predictive value (PPV). Furthermore, the sensitivity of the surveillance system (overall and by AE category) was estimated relative to incidence ranges in the literature. The surveillance system identified a total of 123 AEs among 283 reviewed medical records, yielding an overall PPV of 52%. The tool showed variable levels of sensitivity across and within AE categories when compared with the literature, with a relatively low overall sensitivity estimated between 21% and 44%. Adverse events were detected in 23 of the 36 AE categories defined by an established harm classification system. Furthermore, none of the detected AEs were voluntarily reported. The surveillance system showed variable sensitivity levels across a broad range of AE categories with an acceptable PPV, overcoming certain limitations associated with other harm detection methods. The number of cases captured was substantial, and none had been previously detected or voluntarily reported. For hospitals with limited resources, this methodology provides valuable safety information from which interventions for quality improvement can be formulated.

  15. HLA-A2–Restricted Cytotoxic T Lymphocyte Epitopes from Human Heparanase as Novel Targets for Broad-Spectrum Tumor Immunotherapy

    Directory of Open Access Journals (Sweden)

    Ting Chen

    2008-09-01

    Full Text Available Peptide vaccination for cancer immunotherapy requires identification of peptide epitopes derived from antigenic proteins associated with tumors. Heparanase (Hpa is broadly expressed in various advanced tumors and seems to be an attractive new tumor-associated antigen. The present study was designed to predict and identify HLA-A2– restricted cytotoxic T lymphocyte (CTL epitopes in the protein of human Hpa. For this purpose, HLA-A2–restricted CTL epitopes were identified using the following four-step procedure: 1 a computer-based epitope prediction from the amino acid sequence of human Hpa, 2 a peptide-binding assay to determine the affinity of the predicted protein with the HLA-A2 molecule, 3 stimulation of the primary T-cell response against the predicted peptides in vitro, and 4 testing of the induced CTLs toward different kinds of carcinoma cells expressing Hpa antigens and/or HLA-A2. The results demonstrated that, of the tested peptides, effectors induced by peptides of human Hpa containing residues 525-533 (PAFSYSFFV, Hpa525, 277-285 (KMLKSFLKA, Hpa277, and 405-413 (WLSLLFKKL, Hpa405 could effectively lyse various tumor cell lines that were Hpa-positive and HLA-A2-matched. We also found that these peptide-specific CTLs could not lyse autologous lymphocytes with low Hpa activity. Further study revealed that Hpa525, Hpa277, and Hpa405 peptides increased the frequency of IFN-γ–producing T cells compared to a negative peptide. Our results suggest that Hpa525, Hpa277, and Hpa405 peptides are new HLA-A2–restricted CTL epitopes capable of inducing Hpa-specific CTLs in vitro. Because Hpa is expressed in most advanced malignant tumors, Hpa525, Hpa277, and Hpa405 peptide–based vaccines may be useful for the immunotherapy for patients with advanced tumors.

  16. Antimicrobial peptides effectively kill a broad spectrum of Listeria monocytogenes and Staphylococcus aureus strains independently of origin, sub-type, or virulence factor expression

    Directory of Open Access Journals (Sweden)

    Kristensen Hans-Henrik

    2008-11-01

    Full Text Available Abstract Background Host defense peptides (HDPs, or antimicrobial peptides (AMPs, are important components of the innate immune system that bacterial pathogens must overcome to establish an infection and HDPs have been suggested as novel antimicrobial therapeutics in treatment of infectious diseases. Hence it is important to determine the natural variation in susceptibility to HDPs to ensure a successful use in clinical treatment regimes. Results Strains of two human bacterial pathogens, Listeria monocytogenes and Staphylococcus aureus, were selected to cover a wide range of origin, sub-type, and phenotypic behavior. Strains within each species were equally sensitive to HDPs and oxidative stress representing important components of the innate immune defense system. Four non-human peptides (protamine, plectasin, novicidin, and novispirin G10 were similar in activity profile (MIC value spectrum to the human β-defensin 3 (HBD-3. All strains were inhibited by concentrations of hydrogen peroxide between 0.1% – 1.0%. Sub-selections of both species differed in expression of several virulence-related factors and in their ability to survive in human whole blood and kill the nematode virulence model Caenorhabditis elegans. For L. monocytogenes, proliferation in whole blood was paralleled by high invasion in Caco-2 cells and fast killing of C. elegans, however, no such pattern in phenotypic behavior was observed for S. aureus and none of the phenotypic differences were correlated to sensitivity to HDPs. Conclusion Strains of L. monocytogenes and S. aureus were within each species equally sensitive to a range of HDPs despite variations in subtype, origin, and phenotypic behavior. Our results suggest that therapeutic use of HDPs will not be hampered by occurrence of naturally tolerant strains of the two species investigated in the present study.

  17. Massively multiplexed microbial identification using resequencing DNA microarrays for outbreak investigation

    Science.gov (United States)

    Leski, T. A.; Ansumana, R.; Jimmy, D. H.; Bangura, U.; Malanoski, A. P.; Lin, B.; Stenger, D. A.

    2011-06-01

    Multiplexed microbial diagnostic assays are a promising method for detection and identification of pathogens causing syndromes characterized by nonspecific symptoms in which traditional differential diagnosis is difficult. Also such assays can play an important role in outbreak investigations and environmental screening for intentional or accidental release of biothreat agents, which requires simultaneous testing for hundreds of potential pathogens. The resequencing pathogen microarray (RPM) is an emerging technological platform, relying on a combination of massively multiplex PCR and high-density DNA microarrays for rapid detection and high-resolution identification of hundreds of infectious agents simultaneously. The RPM diagnostic system was deployed in Sierra Leone, West Africa in collaboration with Njala University and Mercy Hospital Research Laboratory located in Bo. We used the RPM-Flu microarray designed for broad-range detection of human respiratory pathogens, to investigate a suspected outbreak of avian influenza in a number of poultry farms in which significant mortality of chickens was observed. The microarray results were additionally confirmed by influenza specific real-time PCR. The results of the study excluded the possibility that the outbreak was caused by influenza, but implicated Klebsiella pneumoniae as a possible pathogen. The outcome of this feasibility study confirms that application of broad-spectrum detection platforms for outbreak investigation in low-resource locations is possible and allows for rapid discovery of the responsible agents, even in cases when different agents are suspected. This strategy enables quick and cost effective detection of low probability events such as outbreak of a rare disease or intentional release of a biothreat agent.

  18. Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

    Energy Technology Data Exchange (ETDEWEB)

    Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.; Yates, Christopher M.; Wawrzak, Zdzislaw; Rachakonda, Girish; Villalta, Fernando; Lepesheva, Galina I.

    2017-05-01

    ABSTRACT

    Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungusAspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatusCYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis ofA. fumigatusCYP51/voriconazole andCandida albicansCYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using twoA. fumigatusstrains (strains 32820 and 1022) displayed a direct

  19. Growing Escherichia coli mutants deficient in riboflavin biosynthesis with non-limiting riboflavin results in sensitization to inactivation by broad-spectrum near-ultraviolet light (320-400 nm)

    International Nuclear Information System (INIS)

    Lloyd, R.E.; Rinkenberger, J.L.; Hug, B.A.; Tuveson, R.W.

    1990-01-01

    Two mutants of Escherichia coli unable to synthesize riboflavin were grown with limiting (2 μg ml -1 ) and non-limiting (10 μg ml -1 ) concentrations of riboflavin. These riboflavin auxotrophs when grown to exponential phase with non-limiting riboflavin are more sensitive to broad spectrum near-ultraviolet light (NUV, 320-400 nm) inactivation than when they are grown with limiting riboflavin. Exponential phase cells of the riboflavin auxotrophs grown with limiting riboflavin are sensitized when irradiated in saline supplemented with riboflavin. This suggests that extracellular riboflavin is important as a NUV sensitizer when intracellular levels of riboflavin are reduced. The concentration of riboflavin in crude extracts from exponentially growing cells correlates well with the sensitivity of these mutants to NUV inactivation. The level of riboflavin supplementation has little effect on the NUV sensitivity of the parental strain. (author)

  20. Broad-spectrum antiviral properties of andrographolide.

    Science.gov (United States)

    Gupta, Swati; Mishra, K P; Ganju, Lilly

    2017-03-01

    Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.

  1. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO-associated bacteremia.This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012.It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP, and 57.3% were gram-negative (GN. GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias. Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms and Klebsiellapneumoniae(13.3% of total, 23.3% of GN organisms were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/ tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p value<0.05.

  2. Prevalence of quinolone resistance determinant qnrA6 among broad- and extended-spectrum beta-lactam-resistant Proteus mirabilis and Morganella morganii clinical isolates with sul1-type class 1 integron association in a Tunisian Hospital.

    Science.gov (United States)

    Mahrouki, Sihem; Perilli, Mariagrazia; Bourouis, Amel; Chihi, Hela; Ferjani, Mustapha; Ben Moussa, Mohamed; Amicosante, Gianfranco; Belhadj, Omrane

    2013-08-01

    The aim of this study was to investigate the prevalence and the emergence of plasmid-mediated quinolone resistance among broad-spectrum beta-lactam-resistant Proteus mirabilis and Morganella morganii clinical isolates recovered in the Military Hospital in Tunisia. Of 200 strains examined, 50 exhibited resistance to quinolones. Quinolone resistance determinants (qnr and aac(6')-Ib-cr) were characterized by multiplex PCR and sequencing. Chromosomal quinolone resistance mutations in the quinolone resistance-determining region (QRDR) and class 1 integron characterization were analysed by PCR and sequencing. The clonal relationship between the isolates was studied by pulsed-field gel electrophoresis (PFGE). Fourteen isolates harboured qnrA6 and among them 8 (57%) were extended-spectrum beta-lactamase (ESBL) producers, whilst 12 (85%) isolates harboured blaDHA-1. Mutations in the QRDR were detected in gyrA (Ser83Ile, Glu87Lys), gyrB (Ser464Phe), and parC (Ser80Ile). qnrA6 and blaDHA-1 genes were found embedded in complex sul1-type class 1 integrons. A gene cassette carrying aac(6')-Ib-cr was found located in the class 1 integron upstream of the qacEΔ1 gene. According to the PFGE analysis, the isolates were clonally unrelated. This is the first description in North Africa of class 1 integrons carrying blaDHA-1, qnrA6 gene, and aac(6')-Ib-cr determinants in clinical strains of Proteus mirabilis and Morganella morganii.

  3. A high-resolution map of the Grp1 locus on chromosome V of potato harbouring broad-spectrum resistance to the cyst nematode species Globodera pallida and Globodera rostochiensis.

    Science.gov (United States)

    Finkers-Tomczak, Anna; Danan, Sarah; van Dijk, Thijs; Beyene, Amelework; Bouwman, Liesbeth; Overmars, Hein; van Eck, Herman; Goverse, Aska; Bakker, Jaap; Bakker, Erin

    2009-06-01

    The Grp1 locus confers broad-spectrum resistance to the potato cyst nematode species Globodera pallida and Globodera rostochiensis and is located in the GP21-GP179 interval on the short arm of chromosome V of potato. A high-resolution map has been developed using the diploid mapping population RHAM026, comprising 1,536 genotypes. The flanking markers GP21 and GP179 have been used to screen the 1,536 genotypes for recombination events. Interval mapping of the resistances to G. pallida Pa2 and G. rostochiensis Ro5 resulted in two nearly identical LOD graphs with the highest LOD score just north of marker TG432. Detailed analysis of the 44 recombinant genotypes showed that G. pallida and G. rostochiensis resistance could not be separated and map to the same location between marker SPUD838 and TG432. It is suggested that the quantitative resistance to both nematode species at the Grp1 locus is mediated by one or more tightly linked R genes that might belong to the NBS-LRR class.

  4. Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112).

    Science.gov (United States)

    McComsey, David F; Smith-Swintosky, Virginia L; Parker, Michael H; Brenneman, Douglas E; Malatynska, Ewa; White, H Steve; Klein, Brian D; Wilcox, Karen S; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B; Maryanoff, Bruce E

    2013-11-27

    Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels and was effective as a K(+) channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.

  5. Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Johnsen, Anders H; Jurlander, Jesper

    2007-01-01

    virus (KSHV) encodes three chemokine-like proteins named vCCL1, vCCL2, and vCCL3. In this study vCCL3 was probed in parallel with vCCL1 and vCCL2 against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCCL1 acted as a selective CCR8 agonist, whereas vCCL2......Large DNA viruses such as herpesvirus and poxvirus encode proteins that target and exploit the chemokine system of their host. These proteins have the potential to block or change the orchestrated recruitment of leukocytes to sites of viral infection. The genome of Kaposi sarcoma-associated herpes...... was found to act as a broad spectrum chemokine antagonist of human chemokine receptors, including the lymphotactin receptor. In contrast vCCL3 was found to be a highly selective agonist for the human lymphotactin receptor XCR1. The potency of vCCL3 was found to be 10-fold higher than the endogenous human...

  6. Exploring Lactobacillus plantarum genome diversity by using microarrays

    NARCIS (Netherlands)

    Molenaar, D.; Bringel, F.; Schuren, F.H.; Vos, de W.M.; Siezen, R.J.; Kleerebezem, M.

    2005-01-01

    Lactobacillus plantarum is a versatile and flexible species that is encountered in a variety of niches and can utilize a broad range of fermentable carbon sources. To assess if this versatility is linked to a variable gene pool, microarrays containing a subset of small genomic fragments of L.

  7. Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial.

    Science.gov (United States)

    López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

    2017-06-09

    Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic 'real-practice' trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae . The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from

  8. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model.

    Directory of Open Access Journals (Sweden)

    Hongyu Qiu

    Full Text Available Clostridium difficile (C. difficile infection (CDI is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA, and cytotoxin, toxin B (TcdB, which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4 and anti-TcdB (CANmAbB4 and CANmAbB1 antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively in a hamster gastrointestinal infection (GI model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI.

  9. Runs 800, 813, 842 and physics runs from 18.1.77 to 21.5.77, Development of a new set-up for working line measurements including a Fast Fourier Transform Spectrum Analyser and using weak beam excitiation with broad-band noise

    CERN Document Server

    Borer, J

    1977-01-01

    Runs 800, 813, 842 and physics runs from 18.1.77 to 21.5.77, Development of a new set-up for working line measurements including a Fast Fourier Transform Spectrum Analyser and using weak beam excitiation with broad-band noise

  10. A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

    Science.gov (United States)

    Evans, Malkanthi; Antony, Joseph; Guthrie, Najla; Landes, Bernie; Aruoma, Okezie I

    2018-01-01

    The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

  11. DNA microarrays : a molecular cloning manual

    National Research Council Canada - National Science Library

    Sambrook, Joseph; Bowtell, David

    2002-01-01

    .... DNA Microarrays provides authoritative, detailed instruction on the design, construction, and applications of microarrays, as well as comprehensive descriptions of the software tools and strategies...

  12. The 2010 Broad Prize

    Science.gov (United States)

    Education Digest: Essential Readings Condensed for Quick Review, 2011

    2011-01-01

    A new data analysis, based on data collected as part of The Broad Prize process, provides insights into which large urban school districts in the United States are doing the best job of educating traditionally disadvantaged groups: African-American, Hispanics, and low-income students. Since 2002, The Eli and Edythe Broad Foundation has awarded The…

  13. Polyadenylation state microarray (PASTA) analysis.

    Science.gov (United States)

    Beilharz, Traude H; Preiss, Thomas

    2011-01-01

    Nearly all eukaryotic mRNAs terminate in a poly(A) tail that serves important roles in mRNA utilization. In the cytoplasm, the poly(A) tail promotes both mRNA stability and translation, and these functions are frequently regulated through changes in tail length. To identify the scope of poly(A) tail length control in a transcriptome, we developed the polyadenylation state microarray (PASTA) method. It involves the purification of mRNA based on poly(A) tail length using thermal elution from poly(U) sepharose, followed by microarray analysis of the resulting fractions. In this chapter we detail our PASTA approach and describe some methods for bulk and mRNA-specific poly(A) tail length measurements of use to monitor the procedure and independently verify the microarray data.

  14. Direct calibration of PICKY-designed microarrays

    Directory of Open Access Journals (Sweden)

    Ronald Pamela C

    2009-10-01

    Full Text Available Abstract Background Few microarrays have been quantitatively calibrated to identify optimal hybridization conditions because it is difficult to precisely determine the hybridization characteristics of a microarray using biologically variable cDNA samples. Results Using synthesized samples with known concentrations of specific oligonucleotides, a series of microarray experiments was conducted to evaluate microarrays designed by PICKY, an oligo microarray design software tool, and to test a direct microarray calibration method based on the PICKY-predicted, thermodynamically closest nontarget information. The complete set of microarray experiment results is archived in the GEO database with series accession number GSE14717. Additional data files and Perl programs described in this paper can be obtained from the website http://www.complex.iastate.edu under the PICKY Download area. Conclusion PICKY-designed microarray probes are highly reliable over a wide range of hybridization temperatures and sample concentrations. The microarray calibration method reported here allows researchers to experimentally optimize their hybridization conditions. Because this method is straightforward, uses existing microarrays and relatively inexpensive synthesized samples, it can be used by any lab that uses microarrays designed by PICKY. In addition, other microarrays can be reanalyzed by PICKY to obtain the thermodynamically closest nontarget information for calibration.

  15. Current Knowledge on Microarray Technology - An Overview

    African Journals Online (AJOL)

    Erah

    This paper reviews basics and updates of each microarray technology and serves to .... through protein microarrays. Protein microarrays also known as protein chips are nothing but grids that ... conditioned media, patient sera, plasma and urine. Clontech ... based antibody arrays) is similar to membrane-based antibody ...

  16. Diagnostic and analytical applications of protein microarrays

    DEFF Research Database (Denmark)

    Dufva, Hans Martin; Christensen, C.B.V.

    2005-01-01

    DNA microarrays have changed the field of biomedical sciences over the past 10 years. For several reasons, antibody and other protein microarrays have not developed at the same rate. However, protein and antibody arrays have emerged as a powerful tool to complement DNA microarrays during the post...

  17. Global microarray analysis of carbohydrate use in alkaliphilic hemicellulolytic bacterium Bacillus sp. N16-5.

    Directory of Open Access Journals (Sweden)

    Yajian Song

    Full Text Available The alkaliphilic hemicellulolytic bacterium Bacillus sp. N16-5 has a broad substrate spectrum and exhibits the capacity to utilize complex carbohydrates such as galactomannan, xylan, and pectin. In the monosaccharide mixture, sequential utilization by Bacillus sp. N16-5 was observed. Glucose appeared to be its preferential monosaccharide, followed by fructose, mannose, arabinose, xylose, and galactose. Global transcription profiles of the strain were determined separately for growth on six monosaccharides (glucose, fructose, mannose, galactose, arabinose, and xylose and four polysaccharides (galactomannan, xylan, pectin, and sodium carboxymethylcellulose using one-color microarrays. Numerous genes potentially related to polysaccharide degradation, sugar transport, and monosaccharide metabolism were found to respond to a specific substrate. Putative gene clusters for different carbohydrates were identified according to transcriptional patterns and genome annotation. Identification and analysis of these gene clusters contributed to pathway reconstruction for carbohydrate utilization in Bacillus sp. N16-5. Several genes encoding putative sugar transporters were highly expressed during growth on specific sugars, suggesting their functional roles. Two phosphoenolpyruvate-dependent phosphotransferase systems were identified as candidate transporters for mannose and fructose, and a major facilitator superfamily transporter was identified as a candidate transporter for arabinose and xylose. Five carbohydrate uptake transporter 1 family ATP-binding cassette transporters were predicted to participate in the uptake of hemicellulose and pectin degradation products. Collectively, microarray data improved the pathway reconstruction involved in carbohydrate utilization of Bacillus sp. N16-5 and revealed that the organism precisely regulates gene transcription in response to fluctuations in energy resources.

  18. Global Microarray Analysis of Carbohydrate Use in Alkaliphilic Hemicellulolytic Bacterium Bacillus sp. N16-5

    Science.gov (United States)

    Song, Yajian; Xue, Yanfen; Ma, Yanhe

    2013-01-01

    The alkaliphilic hemicellulolytic bacterium Bacillus sp. N16-5 has a broad substrate spectrum and exhibits the capacity to utilize complex carbohydrates such as galactomannan, xylan, and pectin. In the monosaccharide mixture, sequential utilization by Bacillus sp. N16-5 was observed. Glucose appeared to be its preferential monosaccharide, followed by fructose, mannose, arabinose, xylose, and galactose. Global transcription profiles of the strain were determined separately for growth on six monosaccharides (glucose, fructose, mannose, galactose, arabinose, and xylose) and four polysaccharides (galactomannan, xylan, pectin, and sodium carboxymethylcellulose) using one-color microarrays. Numerous genes potentially related to polysaccharide degradation, sugar transport, and monosaccharide metabolism were found to respond to a specific substrate. Putative gene clusters for different carbohydrates were identified according to transcriptional patterns and genome annotation. Identification and analysis of these gene clusters contributed to pathway reconstruction for carbohydrate utilization in Bacillus sp. N16-5. Several genes encoding putative sugar transporters were highly expressed during growth on specific sugars, suggesting their functional roles. Two phosphoenolpyruvate-dependent phosphotransferase systems were identified as candidate transporters for mannose and fructose, and a major facilitator superfamily transporter was identified as a candidate transporter for arabinose and xylose. Five carbohydrate uptake transporter 1 family ATP-binding cassette transporters were predicted to participate in the uptake of hemicellulose and pectin degradation products. Collectively, microarray data improved the pathway reconstruction involved in carbohydrate utilization of Bacillus sp. N16-5 and revealed that the organism precisely regulates gene transcription in response to fluctuations in energy resources. PMID:23326578

  19. Three-dimensional Ag2O/Bi5O7I p-n heterojunction photocatalyst harnessing UV-vis-NIR broad spectrum for photodegradation of organic pollutants.

    Science.gov (United States)

    Chen, Yannan; Zhu, Gangqiang; Hojamberdiev, Mirabbos; Gao, Jianzhi; Zhu, Runliang; Wang, Chenghui; Wei, Xiumei; Liu, Peng

    2018-02-15

    Ag 2 O nanoparticles-loaded Bi 5 O 7 I microspheres forming a three dimensional Ag 2 O/Bi 5 O 7 I p-n heterojunction photocatalyst with wide-spectrum response were synthesized in this study. The results of transmission electron microscopy observations revealed that the Ag 2 O nanoparticles with the diameter of ca. 10-20nm were distributed on the surfaces of Bi 5 O 7 I nanosheets. The as-synthesized Ag 2 O/Bi 5 O 7 I exhibited an excellent wide-spectrum response to wavelengths ranging from ultraviolet (UV) to near-infrared (NIR), indicating its potential for effective utilization of solar energy. Compared with pure Bi 5 O 7 I, the Ag 2 O/Bi 5 O 7 I composite also demonstrated excellent photocatalytic activity for the degradation of Bisphenol A and phenol in aqueous solution under visible LED light irradiation. Among samples, the 20% Ag 2 O/Bi 5 O 7 I composite photocatalyst showed the highest photocatalytic activity for the degradation of Bisphenol A and phenol in aqueous solution. In addition, the 20% Ag 2 O/Bi 5 O 7 I composite also exhibited a photocatalytic activity for the degradation of Bisphenol A under NIR light irradiation. The improved photocatalytic activity is attributed to the formation of a p-n heterojunction between Ag 2 O and Bi 5 O 7 I, allowing the efficient utilization of solar energy (from UV to NIR) and high separation efficiency of photogenerated electron-hole pairs. The present work is desirable to explore a possible avenue for the full utilization of solar energy. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Feleucin-BO1: a novel antimicrobial non-apeptide amide from the skin secretion of the toad, Bombina orientalis, and design of a potent broad-spectrum synthetic analogue, feleucin-K3.

    Science.gov (United States)

    Hou, Xiaojuan; Du, Qiang; Li, Renjie; Zhou, Mei; Wang, Hui; Wang, Lei; Guo, Can; Chen, Tianbao; Shaw, Chris

    2015-03-01

    Feleucins-BV1 and -BV2 are recently described prototypes of a novel antimicrobial non-apeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μm) but was inactive (> 250 μm) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly enhanced potency and spectrum of activity. The MICs of F-K3 against the reference micro-organisms were 7 μm (S. aureus), 14 μm (E. coli) and 7 μm (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility. © 2014 John Wiley & Sons A/S.

  1. Tumour auto-antibody screening: performance of protein microarrays using SEREX derived antigens

    International Nuclear Information System (INIS)

    Stempfer, René; Weinhäusel, Andreas; Syed, Parvez; Vierlinger, Klemens; Pichler, Rudolf; Meese, Eckart; Leidinger, Petra; Ludwig, Nicole; Kriegner, Albert; Nöhammer, Christa

    2010-01-01

    The simplicity and potential of minimal invasive testing using serum from patients make auto-antibody based biomarkers a very promising tool for use in diagnostics of cancer and auto-immune disease. Although several methods exist for elucidating candidate-protein markers, immobilizing these onto membranes and generating so called macroarrays is of limited use for marker validation. Especially when several hundred samples have to be analysed, microarrays could serve as a good alternative since processing macro membranes is cumbersome and reproducibility of results is moderate. Candidate markers identified by SEREX (serological identification of antigens by recombinant expression cloning) screenings of brain and lung tumour were used for macroarray and microarray production. For microarray production recombinant proteins were expressed in E. coli by autoinduction and purified His-tag (histidine-tagged) proteins were then used for the production of protein microarrays. Protein arrays were hybridized with the serum samples from brain and lung tumour patients. Methods for the generation of microarrays were successfully established when using antigens derived from membrane-based selection. Signal patterns obtained by microarrays analysis of brain and lung tumour patients' sera were highly reproducible (R = 0.92-0.96). This provides the technical foundation for diagnostic applications on the basis of auto-antibody patterns. In this limited test set, the assay provided high reproducibility and a broad dynamic range to classify all brain and lung samples correctly. Protein microarray is an efficient means for auto-antibody-based detection when using SEREX-derived clones expressing antigenic proteins. Protein microarrays are preferred to macroarrays due to the easier handling and the high reproducibility of auto-antibody testing. Especially when using only a few microliters of patient samples protein microarrays are ideally suited for validation of auto

  2. Microarray analyses of glucocorticoid and vitamin D3 target genes in differentiating cultured human podocytes.

    Directory of Open Access Journals (Sweden)

    Xiwen Cheng

    Full Text Available Glomerular podocytes are highly differentiated epithelial cells that are key components of the kidney filtration units. Podocyte damage or loss is the hallmark of nephritic diseases characterized by severe proteinuria. Recent studies implicate that hormones including glucocorticoids (ligand for glucocorticoid receptor and vitamin D3 (ligand for vitamin D receptor protect or promote repair of podocytes from injury. In order to elucidate the mechanisms underlying hormone-mediated podocyte-protecting activity from injury, we carried out microarray gene expression studies to identify the target genes and corresponding pathways in response to these hormones during podocyte differentiation. We used immortalized human cultured podocytes (HPCs as a model system and carried out in vitro differentiation assays followed by dexamethasone (Dex or vitamin D3 (VD3 treatment. Upon the induction of differentiation, multiple functional categories including cell cycle, organelle dynamics, mitochondrion, apoptosis and cytoskeleton organization were among the most significantly affected. Interestingly, while Dex and VD3 are capable of protecting podocytes from injury, they only share limited target genes and affected pathways. Compared to VD3 treatment, Dex had a broader and greater impact on gene expression profiles. In-depth analyses of Dex altered genes indicate that Dex crosstalks with a broad spectrum of signaling pathways, of which inflammatory responses, cell migration, angiogenesis, NF-κB and TGFβ pathways are predominantly altered. Together, our study provides new information and identifies several new avenues for future investigation of hormone signaling in podocytes.

  3. Fitting new technologies into the safety paradigm: use of microarrays in transfusion.

    Science.gov (United States)

    Fournier-Wirth, C; Coste, J

    2007-01-01

    Until the late 1990s, mandatory blood screening for transmissible infectious agents depended entirely on antigen/antibody-based detection assays. The recent emergence of Nucleic acid Amplification Technologies (NAT) has revolutionised viral diagnosis, not only by increasing the level of sensitivity but also by facilitating the detection of several viruses in parallel by multiplexing specific primers. In more complex biological situations, when a broad spectrum of pathogens must be screened, the limitations of these first generation technologies became apparent. High throughput systems, such as DNA Arrays, permit a conceptually new approach. These miniaturised micro systems allow the detection of hundreds of different targets simultaneously, inducing a dramatic decrease in reagent consumption, a reduction in the number of confirmation tests and a simplification of data interpretation. However, the systems currently available require additional instrumentation and reagents for sample preparation and target amplification prior to detection on the DNA array. A major challenge in the area of DNA detection is the development of methods that do not rely on target amplification systems. Likewise, the advances of protein microarrays have lagged because of poor stability of proteins, complex coupling chemistry and weak detection signals. Emerging technologies like Biosensors and nano-particle based DNA or Protein Bio-Barcode Amplification Assays are promising diagnostic tools for a wide range of clinical applications, including blood donation screening.

  4. "Harshlighting" small blemishes on microarrays

    Directory of Open Access Journals (Sweden)

    Wittkowski Knut M

    2005-03-01

    Full Text Available Abstract Background Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans show similar artefacts, which affect the analysis, particularly when one tries to detect subtle changes. However, most blemishes are hard to find by the unaided eye, particularly in high-density oligonucleotide arrays (HDONAs. Results We present a method that harnesses the statistical power provided by having several HDONAs available, which are obtained under similar conditions except for the experimental factor. This method "harshlights" blemishes and renders them evident. We find empirically that about 25% of our chips are blemished, and we analyze the impact of masking them on screening for differentially expressed genes. Conclusion Experiments attempting to assess subtle expression changes should be carefully screened for blemishes on the chips. The proposed method provides investigators with a novel robust approach to improve the sensitivity of microarray analyses. By utilizing topological information to identify and mask blemishes prior to model based analyses, the method prevents artefacts from confounding the process of background correction, normalization, and summarization.

  5. Parallel scan hyperspectral fluorescence imaging system and biomedical application for microarrays

    International Nuclear Information System (INIS)

    Liu Zhiyi; Ma Suihua; Liu Le; Guo Jihua; He Yonghong; Ji Yanhong

    2011-01-01

    Microarray research offers great potential for analysis of gene expression profile and leads to greatly improved experimental throughput. A number of instruments have been reported for microarray detection, such as chemiluminescence, surface plasmon resonance, and fluorescence markers. Fluorescence imaging is popular for the readout of microarrays. In this paper we develop a quasi-confocal, multichannel parallel scan hyperspectral fluorescence imaging system for microarray research. Hyperspectral imaging records the entire emission spectrum for every voxel within the imaged area in contrast to recording only fluorescence intensities of filter-based scanners. Coupled with data analysis, the recorded spectral information allows for quantitative identification of the contributions of multiple, spectrally overlapping fluorescent dyes and elimination of unwanted artifacts. The mechanism of quasi-confocal imaging provides a high signal-to-noise ratio, and parallel scan makes this approach a high throughput technique for microarray analysis. This system is improved with a specifically designed spectrometer which can offer a spectral resolution of 0.2 nm, and operates with spatial resolutions ranging from 2 to 30 μm . Finally, the application of the system is demonstrated by reading out microarrays for identification of bacteria.

  6. Advanced microarray technologies for clinical diagnostics

    NARCIS (Netherlands)

    Pierik, Anke

    2011-01-01

    DNA microarrays become increasingly important in the field of clinical diagnostics. These microarrays, also called DNA chips, are small solid substrates, typically having a maximum surface area of a few cm2, onto which many spots are arrayed in a pre-determined pattern. Each of these spots contains

  7. Carbohydrate Microarrays in Plant Science

    DEFF Research Database (Denmark)

    Fangel, Jonatan Ulrik; Pedersen, H.L.; Vidal-Melgosa, S.

    2012-01-01

    Almost all plant cells are surrounded by glycan-rich cell walls, which form much of the plant body and collectively are the largest source of biomass on earth. Plants use polysaccharides for support, defense, signaling, cell adhesion, and as energy storage, and many plant glycans are also important...... industrially and nutritionally. Understanding the biological roles of plant glycans and the effective exploitation of their useful properties requires a detailed understanding of their structures, occurrence, and molecular interactions. Microarray technology has revolutionized the massively high...... for plant research and can be used to map glycan populations across large numbers of samples to screen antibodies, carbohydrate binding proteins, and carbohydrate binding modules and to investigate enzyme activities....

  8. The EADGENE Microarray Data Analysis Workshop

    DEFF Research Database (Denmark)

    de Koning, Dirk-Jan; Jaffrézic, Florence; Lund, Mogens Sandø

    2007-01-01

    Microarray analyses have become an important tool in animal genomics. While their use is becoming widespread, there is still a lot of ongoing research regarding the analysis of microarray data. In the context of a European Network of Excellence, 31 researchers representing 14 research groups from...... 10 countries performed and discussed the statistical analyses of real and simulated 2-colour microarray data that were distributed among participants. The real data consisted of 48 microarrays from a disease challenge experiment in dairy cattle, while the simulated data consisted of 10 microarrays...... statistical weights, to omitting a large number of spots or omitting entire slides. Surprisingly, these very different approaches gave quite similar results when applied to the simulated data, although not all participating groups analysed both real and simulated data. The workshop was very successful...

  9. Testing and Validation of High Density Resequencing Microarray for Broad Range Biothreat Agents Detection

    Science.gov (United States)

    2009-08-11

    concentration of the virus was expressed in plaque forming units (pfu). For synthetic DNA templates, the DNA concentration was used to calculate the...cells ATCC Escherichia coli O157:H7 ATCC 43985 (CDC EDL933) Nucleic acid ATCC Francisella tularensis SHU4 Nucleic acid AFIP Leptospira interrogans ATCC...2% on the nucleotide level and 0.6% on the protein level. Similar strain discrimination was obtained in case of Machupo virus strains Carvallo and

  10. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds

    Directory of Open Access Journals (Sweden)

    Ixtepan-Turrent Liliana

    2011-08-01

    Full Text Available Abstract The advance in nanotechnology has enabled us to utilize particles in the size of the nanoscale. This has created new therapeutic horizons, and in the case of silver, the currently available data only reveals the surface of the potential benefits and the wide range of applications. Interactions between viral biomolecules and silver nanoparticles suggest that the use of nanosystems may contribute importantly for the enhancement of current prevention of infection and antiviral therapies. Recently, it has been suggested that silver nanoparticles (AgNPs bind with external membrane of lipid enveloped virus to prevent the infection. Nevertheless, the interaction of AgNPs with viruses is a largely unexplored field. AgNPs has been studied particularly on HIV where it was demonstrated the mechanism of antiviral action of the nanoparticles as well as the inhibition the transmission of HIV-1 infection in human cervix organ culture. This review discusses recent advances in the understanding of the biocidal mechanisms of action of silver Nanoparticles.

  11. Broad spectrum probiotic (Sakhabactisubtil recovered from Yakutia permafrost soil

    Directory of Open Access Journals (Sweden)

    Mikhail Petrovich Neustroev

    2011-10-01

    Full Text Available Probiotic “Sakhabactisubtil” has been developed, it has unique biological properties: frank antagonistic effect against pathogen and opportunistic microorganisms (bacteria, fungi and viruses, interferon-evoke activity, immune system enhancing effect, producing a range of ferments, beneficial microflora formation's stimulation, resistance to a number of antibiotics. [Vet. World 2011; 4(5.000: 222-224

  12. Broad Spectrum Photoelectrochemical Diodes for Solar Hydrogen Generation

    Energy Technology Data Exchange (ETDEWEB)

    Grimes, Craig A.

    2014-11-26

    Under program auspices we have investigated material chemistries suitable for the solar generation of hydrogen by water photoelectrolysis. We have built upon, and extended, our knowledge base on the synthesis and application of TiO2 nanotube arrays, a material architecture that appears ideal for water photoelectrolysis. To date we have optimized, refined, and greatly extended synthesis techniques suitable for achieving highly ordered TiO2 nanotube arrays of given length, wall thickness, pore diameter, and tube-to-tube spacing for use in water photoelectrolysis. We have built upon this knowledge based to achieve visible light responsive, photocorrosion stable n-type and p-type ternary oxide nanotube arrays for use in photoelectrochemical diodes.

  13. Probing Gallic Acid for Its Broad Spectrum Applications.

    Science.gov (United States)

    Choubey, Sneha; Goyal, Soniya; Varughese, Lesley Rachel; Kumar, Vinod

    2018-03-29

    Gallic acid and its derivatives not only exhibit excellent antioxidant, anticarcinogenic, antimutagenic, antimicrobial properties but also provide protection to the cells against oxidative stress. Gallic acid (3, 4, 5-trihydroxybenzoic acid), a low molecular triphenolic compound has arised as an efficient apoptosis inducing agent. The antimicrobial and other biological properties of gallic acid and its derivatives seemed to be linked with the hydrolysis of ester linkage between gallic acid and polyols like tannins hydrolyzed after ripening of many edible fruits. Gallic acid serves a natural defense mechanism against microbial infections and modulation of immune-responses. The current review updates us with the diverse roles played by gallic acid, its antioxidant potential, action mechanism and more importantly the diverse array of applications in therapeutic and pharmaceutical area. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Synthetic histatin analogues with broad-spectrum antimicrobial activity.

    OpenAIRE

    Helmerhorst, E J; Van't Hof, W; Veerman, E C; Simoons-Smit, I; Nieuw Amerongen, A V

    1997-01-01

    Histatins are salivary histidine-rich cationic peptides, ranging from 7 to 38 amino acid residues in length, that exert a potent killing effect in vitro on Candida albicans. Starting from the C-terminal fungicidal domain of histatin 5 (residues 11-24, called dh-5) a number of substitution analogues were chemically synthesized to study the effect of amphipathicity of the peptide in helix conformation on candidacidal activity. Single substitutions in dh-5 at several positions did not have any e...

  15. Studies on broad spectrum corrosion resistant oxide coatings

    Indian Academy of Sciences (India)

    Unknown

    Corrosion resistant coating materials and their application ... technology demand such corrosion resistant coatings having a ... mill additives used are as follows: China clay, 3⋅0–10⋅0; .... stage involves modification in processing of the deve-.

  16. The broad spectrum of preclinical radiobiology: British contributions

    International Nuclear Information System (INIS)

    Denekamp, Juliana

    1996-01-01

    British radiobiologists have often been at the forefront in taking clinical questions into the laboratory and in taking the results back into the clinic, i.e., what is nowadays labeled as Translational Research. They have published widely and have been very active in lectures, workshops, and discussions, forming an important component of the international communication web, both within the basic science aspects and in the translation from science to medicine, and back again. Major contributions have been made at the cellular and subcellular level, and at the level of multicellular structures, both normal and malignant. The common features of the response of cells to single doses in well-defined conditions have been used to interpret the much greater complexity of tissue and tumor responses treated with repeated small doses in a fractionated course, both of photons and other radiations, with and without chemical modifiers. The many contributions to the field of cell kinetics have provided the tools with which an understanding has been gained of the latency and evolution of radiation damage in different tissues. The prolonged interest in microenvironmental gradients and compensatory responses to injury have provided a framework for designing better radiotherapy schedules, and considerable spin-off to other branches of cancer therapy

  17. Antipneumococcal activity of ceftobiprole, a novel broad-spectrum cephalosporin.

    Science.gov (United States)

    Kosowska, Klaudia; Hoellman, Dianne B; Lin, Gengrong; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bozdogan, Bülent; Shapiro, Stuart; Appelbaum, Peter C

    2005-05-01

    Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC(50) and MIC(90) values (microg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1x and 2x the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2x the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2x the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole.

  18. Graduated diagnostics required. Broad spectrum of differential diagnoses

    International Nuclear Information System (INIS)

    Auer, I.O.

    1997-01-01

    The time lapse between initial symptoms and secured diagnosis of colitis ulcerosa still is 6-8 weeks, in case of M. Crohn even about 30 weeks. A graduated diagnostic approach is required: phase 1 relies on non-invasive methods such as anamnesis, physical examination, examination of stools, blood chemistry and sonography of the abdomen; phase 2 ecompasses endoscopy and radiological techniques, phase 3 computed tomography and MRI for detection of complications. The results of the leucodiagnosis by scintiscanning, for detection of inflammations of and out of the intestine, offer a still inhomogenous picture in terms of sensitivity and specificity. (orig./MG) [de

  19. Volatile aldehydes are promising broad-spectrum postharvest insecticides.

    Science.gov (United States)

    Hammond, D G; Rangel, S; Kubo, I

    2000-09-01

    A variety of naturally occurring aldehydes common in plants have been evaluated for their insecticidal activity and for phytotoxicity to postharvest fruits, vegetables, and grains. Twenty-nine compounds were initially screened for their activity against aphids on fava bean leaf disks. Application under reduced pressure (partial vacuum) for the first quarter of fumigation increased insecticidal activity severalfold. The 11 best aldehydes were assayed against aphids placed under the third leaf of whole heads of iceberg lettuce using the same two-tier reduced-pressure regime, which caused no additional detriment to the commodity over fumigation at atmospheric pressure. Phytotoxicity to naked and wrapped iceburg lettuce, green and red table grapes, lemon, grapefruit, orange, broccoli, avocado, cabbage, pinto bean, and rice at doses that killed 100% of aphids was recorded for three promising fumigants: propanal, (E)-2-pentenal, and 2-methyl-(E)-2-butenal. These three compounds have excellent potential as affordable postharvest insect control agents, killing 100% of the aphids with little or no detectable harm to a majority of the commodities tested. Preliminary assays indicate that similar doses are also effective against mealybugs, thrips, and whitefly.

  20. Broad-spectrum physical fitness benefits of recreational football

    DEFF Research Database (Denmark)

    Milanović, Zoran; Pantelić, Saša; Čović, Nedim

    2018-01-01

    , narrative reviews have demonstrated beneficial effects of recreational football on physical fitness and health status. OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the magnitude of effects of recreational football on blood pressure, body composition, lipid profile...... and muscular fitness with reference to age, gender and health status. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, PubMed, SPORTDiscus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Google Scholar were searched prior to 1 February 2017. In addition...... to a recreational football group or any other type of exercises or passive control group were included. Training programmes had to last at least 2 weeks to meet the inclusion criteria. The primary outcome measures were blood pressure, resting heart rate, body composition, muscular fitness, and blood lipids...

  1. MARS: Microarray analysis, retrieval, and storage system

    Directory of Open Access Journals (Sweden)

    Scheideler Marcel

    2005-04-01

    Full Text Available Abstract Background Microarray analysis has become a widely used technique for the study of gene-expression patterns on a genomic scale. As more and more laboratories are adopting microarray technology, there is a need for powerful and easy to use microarray databases facilitating array fabrication, labeling, hybridization, and data analysis. The wealth of data generated by this high throughput approach renders adequate database and analysis tools crucial for the pursuit of insights into the transcriptomic behavior of cells. Results MARS (Microarray Analysis and Retrieval System provides a comprehensive MIAME supportive suite for storing, retrieving, and analyzing multi color microarray data. The system comprises a laboratory information management system (LIMS, a quality control management, as well as a sophisticated user management system. MARS is fully integrated into an analytical pipeline of microarray image analysis, normalization, gene expression clustering, and mapping of gene expression data onto biological pathways. The incorporation of ontologies and the use of MAGE-ML enables an export of studies stored in MARS to public repositories and other databases accepting these documents. Conclusion We have developed an integrated system tailored to serve the specific needs of microarray based research projects using a unique fusion of Web based and standalone applications connected to the latest J2EE application server technology. The presented system is freely available for academic and non-profit institutions. More information can be found at http://genome.tugraz.at.

  2. Annotating breast cancer microarray samples using ontologies

    Science.gov (United States)

    Liu, Hongfang; Li, Xin; Yoon, Victoria; Clarke, Robert

    2008-01-01

    As the most common cancer among women, breast cancer results from the accumulation of mutations in essential genes. Recent advance in high-throughput gene expression microarray technology has inspired researchers to use the technology to assist breast cancer diagnosis, prognosis, and treatment prediction. However, the high dimensionality of microarray experiments and public access of data from many experiments have caused inconsistencies which initiated the development of controlled terminologies and ontologies for annotating microarray experiments, such as the standard microarray Gene Expression Data (MGED) ontology (MO). In this paper, we developed BCM-CO, an ontology tailored specifically for indexing clinical annotations of breast cancer microarray samples from the NCI Thesaurus. Our research showed that the coverage of NCI Thesaurus is very limited with respect to i) terms used by researchers to describe breast cancer histology (covering 22 out of 48 histology terms); ii) breast cancer cell lines (covering one out of 12 cell lines); and iii) classes corresponding to the breast cancer grading and staging. By incorporating a wider range of those terms into BCM-CO, we were able to indexed breast cancer microarray samples from GEO using BCM-CO and MGED ontology and developed a prototype system with web interface that allows the retrieval of microarray data based on the ontology annotations. PMID:18999108

  3. Simulation of microarray data with realistic characteristics

    Directory of Open Access Journals (Sweden)

    Lehmussola Antti

    2006-07-01

    Full Text Available Abstract Background Microarray technologies have become common tools in biological research. As a result, a need for effective computational methods for data analysis has emerged. Numerous different algorithms have been proposed for analyzing the data. However, an objective evaluation of the proposed algorithms is not possible due to the lack of biological ground truth information. To overcome this fundamental problem, the use of simulated microarray data for algorithm validation has been proposed. Results We present a microarray simulation model which can be used to validate different kinds of data analysis algorithms. The proposed model is unique in the sense that it includes all the steps that affect the quality of real microarray data. These steps include the simulation of biological ground truth data, applying biological and measurement technology specific error models, and finally simulating the microarray slide manufacturing and hybridization. After all these steps are taken into account, the simulated data has realistic biological and statistical characteristics. The applicability of the proposed model is demonstrated by several examples. Conclusion The proposed microarray simulation model is modular and can be used in different kinds of applications. It includes several error models that have been proposed earlier and it can be used with different types of input data. The model can be used to simulate both spotted two-channel and oligonucleotide based single-channel microarrays. All this makes the model a valuable tool for example in validation of data analysis algorithms.

  4. Radioactive cDNA microarray in neurospsychiatry

    International Nuclear Information System (INIS)

    Choe, Jae Gol; Shin, Kyung Ho; Lee, Min Soo; Kim, Meyoung Kon

    2003-01-01

    Microarray technology allows the simultaneous analysis of gene expression patterns of thousands of genes, in a systematic fashion, under a similar set of experimental conditions, thus making the data highly comparable. In some cases arrays are used simply as a primary screen leading to downstream molecular characterization of individual gene candidates. In other cases, the goal of expression profiling is to begin to identify complex regulatory networks underlying developmental processes and disease states. Microarrays were originally used with cell lines or other simple model systems. More recently, microarrays have been used in the analysis of more complex biological tissues including neural systems and the brain. The application of cDNA arrays in neuropsychiatry has lagged behind other fields for a number of reasons. These include a requirement for a large amount of input probe RNA in fluorescent-glass based array systems and the cellular complexity introduced by multicellular brain and neural tissues. An additional factor that impacts the general use of microarrays in neuropsychiatry is the lack of availability of sequenced clone sets from model systems. While human cDNA clones have been widely available, high quality rat, mouse, and drosophilae, among others are just becoming widely available. A final factor in the application of cDNA microarrays in neuropsychiatry is cost of commercial arrays. As academic microarray facilitates become more commonplace custom made arrays will become more widely available at a lower cost allowing more widespread applications. In summary, microarray technology is rapidly having an impact on many areas of biomedical research. Radioisotope-nylon based microarrays offer alternatives that may in some cases be more sensitive, flexible, inexpensive, and universal as compared to other array formats, such as fluorescent-glass arrays. In some situations of limited RNA or exotic species, radioactive membrane microarrays may be the most

  5. Radioactive cDNA microarray in neurospsychiatry

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Jae Gol; Shin, Kyung Ho; Lee, Min Soo; Kim, Meyoung Kon [Korea University Medical School, Seoul (Korea, Republic of)

    2003-02-01

    Microarray technology allows the simultaneous analysis of gene expression patterns of thousands of genes, in a systematic fashion, under a similar set of experimental conditions, thus making the data highly comparable. In some cases arrays are used simply as a primary screen leading to downstream molecular characterization of individual gene candidates. In other cases, the goal of expression profiling is to begin to identify complex regulatory networks underlying developmental processes and disease states. Microarrays were originally used with cell lines or other simple model systems. More recently, microarrays have been used in the analysis of more complex biological tissues including neural systems and the brain. The application of cDNA arrays in neuropsychiatry has lagged behind other fields for a number of reasons. These include a requirement for a large amount of input probe RNA in fluorescent-glass based array systems and the cellular complexity introduced by multicellular brain and neural tissues. An additional factor that impacts the general use of microarrays in neuropsychiatry is the lack of availability of sequenced clone sets from model systems. While human cDNA clones have been widely available, high quality rat, mouse, and drosophilae, among others are just becoming widely available. A final factor in the application of cDNA microarrays in neuropsychiatry is cost of commercial arrays. As academic microarray facilitates become more commonplace custom made arrays will become more widely available at a lower cost allowing more widespread applications. In summary, microarray technology is rapidly having an impact on many areas of biomedical research. Radioisotope-nylon based microarrays offer alternatives that may in some cases be more sensitive, flexible, inexpensive, and universal as compared to other array formats, such as fluorescent-glass arrays. In some situations of limited RNA or exotic species, radioactive membrane microarrays may be the most

  6. Metric learning for DNA microarray data analysis

    International Nuclear Information System (INIS)

    Takeuchi, Ichiro; Nakagawa, Masao; Seto, Masao

    2009-01-01

    In many microarray studies, gene set selection is an important preliminary step for subsequent main task such as tumor classification, cancer subtype identification, etc. In this paper, we investigate the possibility of using metric learning as an alternative to gene set selection. We develop a simple metric learning algorithm aiming to use it for microarray data analysis. Exploiting a property of the algorithm, we introduce a novel approach for extending the metric learning to be adaptive. We apply the algorithm to previously studied microarray data on malignant lymphoma subtype identification.

  7. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    blood glucose > 16.7 mmol/L were used as the model group and treated with Dendrobium mixture. (DEN ... Keywords: Diabetes, Gene expression, Dendrobium mixture, Microarray testing ..... homeostasis in airway smooth muscle. Am J.

  8. SLIMarray: Lightweight software for microarray facility management

    Directory of Open Access Journals (Sweden)

    Marzolf Bruz

    2006-10-01

    Full Text Available Abstract Background Microarray core facilities are commonplace in biological research organizations, and need systems for accurately tracking various logistical aspects of their operation. Although these different needs could be handled separately, an integrated management system provides benefits in organization, automation and reduction in errors. Results We present SLIMarray (System for Lab Information Management of Microarrays, an open source, modular database web application capable of managing microarray inventories, sample processing and usage charges. The software allows modular configuration and is well suited for further development, providing users the flexibility to adapt it to their needs. SLIMarray Lite, a version of the software that is especially easy to install and run, is also available. Conclusion SLIMarray addresses the previously unmet need for free and open source software for managing the logistics of a microarray core facility.

  9. Broad band exciplex dye lasers

    International Nuclear Information System (INIS)

    Dienes, A.; Shank, C.V.; Trozzolo, A.M.

    1975-01-01

    The disclosure is concerned with exciplex dye lasers, i.e., lasers in which the emitting species is a complex formed only from a constituent in an electronically excited state. Noting that an exciplex laser, favorable from the standpoint of broad tunability, results from a broad shift in the peak emission wavelength for the exciplex relative to the unreacted species, a desirable class resulting in such broad shift is described. Preferred classes of laser media utilizing specified resonant molecules are set forth. (auth)

  10. PATMA: parser of archival tissue microarray

    Directory of Open Access Journals (Sweden)

    Lukasz Roszkowiak

    2016-12-01

    Full Text Available Tissue microarrays are commonly used in modern pathology for cancer tissue evaluation, as it is a very potent technique. Tissue microarray slides are often scanned to perform computer-aided histopathological analysis of the tissue cores. For processing the image, splitting the whole virtual slide into images of individual cores is required. The only way to distinguish cores corresponding to specimens in the tissue microarray is through their arrangement. Unfortunately, distinguishing the correct order of cores is not a trivial task as they are not labelled directly on the slide. The main aim of this study was to create a procedure capable of automatically finding and extracting cores from archival images of the tissue microarrays. This software supports the work of scientists who want to perform further image processing on single cores. The proposed method is an efficient and fast procedure, working in fully automatic or semi-automatic mode. A total of 89% of punches were correctly extracted with automatic selection. With an addition of manual correction, it is possible to fully prepare the whole slide image for extraction in 2 min per tissue microarray. The proposed technique requires minimum skill and time to parse big array of cores from tissue microarray whole slide image into individual core images.

  11. Extended analysis of benchmark datasets for Agilent two-color microarrays

    Directory of Open Access Journals (Sweden)

    Kerr Kathleen F

    2007-10-01

    Full Text Available Abstract Background As part of its broad and ambitious mission, the MicroArray Quality Control (MAQC project reported the results of experiments using External RNA Controls (ERCs on five microarray platforms. For most platforms, several different methods of data processing were considered. However, there was no similar consideration of different methods for processing the data from the Agilent two-color platform. While this omission is understandable given the scale of the project, it can create the false impression that there is consensus about the best way to process Agilent two-color data. It is also important to consider whether ERCs are representative of all the probes on a microarray. Results A comparison of different methods of processing Agilent two-color data shows substantial differences among methods for low-intensity genes. The sensitivity and specificity for detecting differentially expressed genes varies substantially for different methods. Analysis also reveals that the ERCs in the MAQC data only span the upper half of the intensity range, and therefore cannot be representative of all genes on the microarray. Conclusion Although ERCs demonstrate good agreement between observed and expected log-ratios on the Agilent two-color platform, such an analysis is incomplete. Simple loess normalization outperformed data processing with Agilent's Feature Extraction software for accurate identification of differentially expressed genes. Results from studies using ERCs should not be over-generalized when ERCs are not representative of all probes on a microarray.

  12. Generalization of DNA microarray dispersion properties: microarray equivalent of t-distribution

    DEFF Research Database (Denmark)

    Novak, Jaroslav P; Kim, Seon-Young; Xu, Jun

    2006-01-01

    BACKGROUND: DNA microarrays are a powerful technology that can provide a wealth of gene expression data for disease studies, drug development, and a wide scope of other investigations. Because of the large volume and inherent variability of DNA microarray data, many new statistical methods have...

  13. Nanotechnology: moving from microarrays toward nanoarrays.

    Science.gov (United States)

    Chen, Hua; Li, Jun

    2007-01-01

    Microarrays are important tools for high-throughput analysis of biomolecules. The use of microarrays for parallel screening of nucleic acid and protein profiles has become an industry standard. A few limitations of microarrays are the requirement for relatively large sample volumes and elongated incubation time, as well as the limit of detection. In addition, traditional microarrays make use of bulky instrumentation for the detection, and sample amplification and labeling are quite laborious, which increase analysis cost and delays the time for obtaining results. These problems limit microarray techniques from point-of-care and field applications. One strategy for overcoming these problems is to develop nanoarrays, particularly electronics-based nanoarrays. With further miniaturization, higher sensitivity, and simplified sample preparation, nanoarrays could potentially be employed for biomolecular analysis in personal healthcare and monitoring of trace pathogens. In this chapter, it is intended to introduce the concept and advantage of nanotechnology and then describe current methods and protocols for novel nanoarrays in three aspects: (1) label-free nucleic acids analysis using nanoarrays, (2) nanoarrays for protein detection by conventional optical fluorescence microscopy as well as by novel label-free methods such as atomic force microscopy, and (3) nanoarray for enzymatic-based assay. These nanoarrays will have significant applications in drug discovery, medical diagnosis, genetic testing, environmental monitoring, and food safety inspection.

  14. Integrative missing value estimation for microarray data.

    Science.gov (United States)

    Hu, Jianjun; Li, Haifeng; Waterman, Michael S; Zhou, Xianghong Jasmine

    2006-10-12

    Missing value estimation is an important preprocessing step in microarray analysis. Although several methods have been developed to solve this problem, their performance is unsatisfactory for datasets with high rates of missing data, high measurement noise, or limited numbers of samples. In fact, more than 80% of the time-series datasets in Stanford Microarray Database contain less than eight samples. We present the integrative Missing Value Estimation method (iMISS) by incorporating information from multiple reference microarray datasets to improve missing value estimation. For each gene with missing data, we derive a consistent neighbor-gene list by taking reference data sets into consideration. To determine whether the given reference data sets are sufficiently informative for integration, we use a submatrix imputation approach. Our experiments showed that iMISS can significantly and consistently improve the accuracy of the state-of-the-art Local Least Square (LLS) imputation algorithm by up to 15% improvement in our benchmark tests. We demonstrated that the order-statistics-based integrative imputation algorithms can achieve significant improvements over the state-of-the-art missing value estimation approaches such as LLS and is especially good for imputing microarray datasets with a limited number of samples, high rates of missing data, or very noisy measurements. With the rapid accumulation of microarray datasets, the performance of our approach can be further improved by incorporating larger and more appropriate reference datasets.

  15. Integrative missing value estimation for microarray data

    Directory of Open Access Journals (Sweden)

    Zhou Xianghong

    2006-10-01

    Full Text Available Abstract Background Missing value estimation is an important preprocessing step in microarray analysis. Although several methods have been developed to solve this problem, their performance is unsatisfactory for datasets with high rates of missing data, high measurement noise, or limited numbers of samples. In fact, more than 80% of the time-series datasets in Stanford Microarray Database contain less than eight samples. Results We present the integrative Missing Value Estimation method (iMISS by incorporating information from multiple reference microarray datasets to improve missing value estimation. For each gene with missing data, we derive a consistent neighbor-gene list by taking reference data sets into consideration. To determine whether the given reference data sets are sufficiently informative for integration, we use a submatrix imputation approach. Our experiments showed that iMISS can significantly and consistently improve the accuracy of the state-of-the-art Local Least Square (LLS imputation algorithm by up to 15% improvement in our benchmark tests. Conclusion We demonstrated that the order-statistics-based integrative imputation algorithms can achieve significant improvements over the state-of-the-art missing value estimation approaches such as LLS and is especially good for imputing microarray datasets with a limited number of samples, high rates of missing data, or very noisy measurements. With the rapid accumulation of microarray datasets, the performance of our approach can be further improved by incorporating larger and more appropriate reference datasets.

  16. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

    Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

  17. The use of microarrays in microbial ecology

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, G.L.; He, Z.; DeSantis, T.Z.; Brodie, E.L.; Zhou, J.

    2009-09-15

    Microarrays have proven to be a useful and high-throughput method to provide targeted DNA sequence information for up to many thousands of specific genetic regions in a single test. A microarray consists of multiple DNA oligonucleotide probes that, under high stringency conditions, hybridize only to specific complementary nucleic acid sequences (targets). A fluorescent signal indicates the presence and, in many cases, the abundance of genetic regions of interest. In this chapter we will look at how microarrays are used in microbial ecology, especially with the recent increase in microbial community DNA sequence data. Of particular interest to microbial ecologists, phylogenetic microarrays are used for the analysis of phylotypes in a community and functional gene arrays are used for the analysis of functional genes, and, by inference, phylotypes in environmental samples. A phylogenetic microarray that has been developed by the Andersen laboratory, the PhyloChip, will be discussed as an example of a microarray that targets the known diversity within the 16S rRNA gene to determine microbial community composition. Using multiple, confirmatory probes to increase the confidence of detection and a mismatch probe for every perfect match probe to minimize the effect of cross-hybridization by non-target regions, the PhyloChip is able to simultaneously identify any of thousands of taxa present in an environmental sample. The PhyloChip is shown to reveal greater diversity within a community than rRNA gene sequencing due to the placement of the entire gene product on the microarray compared with the analysis of up to thousands of individual molecules by traditional sequencing methods. A functional gene array that has been developed by the Zhou laboratory, the GeoChip, will be discussed as an example of a microarray that dynamically identifies functional activities of multiple members within a community. The recent version of GeoChip contains more than 24,000 50mer

  18. 3D Biomaterial Microarrays for Regenerative Medicine

    DEFF Research Database (Denmark)

    Gaharwar, Akhilesh K.; Arpanaei, Ayyoob; Andresen, Thomas Lars

    2015-01-01

    Three dimensional (3D) biomaterial microarrays hold enormous promise for regenerative medicine because of their ability to accelerate the design and fabrication of biomimetic materials. Such tissue-like biomaterials can provide an appropriate microenvironment for stimulating and controlling stem...... for tissue engineering and drug screening applications....... cell differentiation into tissue-specifi c lineages. The use of 3D biomaterial microarrays can, if optimized correctly, result in a more than 1000-fold reduction in biomaterials and cells consumption when engineering optimal materials combinations, which makes these miniaturized systems very attractive...

  19. Multi-gene detection and identification of mosquito-borne RNA viruses using an oligonucleotide microarray.

    Directory of Open Access Journals (Sweden)

    Nathan D Grubaugh

    Full Text Available BACKGROUND: Arthropod-borne viruses are important emerging pathogens world-wide. Viruses transmitted by mosquitoes, such as dengue, yellow fever, and Japanese encephalitis viruses, infect hundreds of millions of people and animals each year. Global surveillance of these viruses in mosquito vectors using molecular based assays is critical for prevention and control of the associated diseases. Here, we report an oligonucleotide DNA microarray design, termed ArboChip5.1, for multi-gene detection and identification of mosquito-borne RNA viruses from the genera Flavivirus (family Flaviviridae, Alphavirus (Togaviridae, Orthobunyavirus (Bunyaviridae, and Phlebovirus (Bunyaviridae. METHODOLOGY/PRINCIPAL FINDINGS: The assay utilizes targeted PCR amplification of three genes from each virus genus for electrochemical detection on a portable, field-tested microarray platform. Fifty-two viruses propagated in cell-culture were used to evaluate the specificity of the PCR primer sets and the ArboChip5.1 microarray capture probes. The microarray detected all of the tested viruses and differentiated between many closely related viruses such as members of the dengue, Japanese encephalitis, and Semliki Forest virus clades. Laboratory infected mosquitoes were used to simulate field samples and to determine the limits of detection. Additionally, we identified dengue virus type 3, Japanese encephalitis virus, Tembusu virus, Culex flavivirus, and a Quang Binh-like virus from mosquitoes collected in Thailand in 2011 and 2012. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the described assay can be utilized in a comprehensive field surveillance program by the broad-range amplification and specific identification of arboviruses from infected mosquitoes. Furthermore, the microarray platform can be deployed in the field and viral RNA extraction to data analysis can occur in as little as 12 h. The information derived from the ArboChip5.1 microarray can help to establish

  20. Development and application of a microarray meter tool to optimize microarray experiments

    Directory of Open Access Journals (Sweden)

    Rouse Richard JD

    2008-07-01

    Full Text Available Abstract Background Successful microarray experimentation requires a complex interplay between the slide chemistry, the printing pins, the nucleic acid probes and targets, and the hybridization milieu. Optimization of these parameters and a careful evaluation of emerging slide chemistries are a prerequisite to any large scale array fabrication effort. We have developed a 'microarray meter' tool which assesses the inherent variations associated with microarray measurement prior to embarking on large scale projects. Findings The microarray meter consists of nucleic acid targets (reference and dynamic range control and probe components. Different plate designs containing identical probe material were formulated to accommodate different robotic and pin designs. We examined the variability in probe quality and quantity (as judged by the amount of DNA printed and remaining post-hybridization using three robots equipped with capillary printing pins. Discussion The generation of microarray data with minimal variation requires consistent quality control of the (DNA microarray manufacturing and experimental processes. Spot reproducibility is a measure primarily of the variations associated with printing. The microarray meter assesses array quality by measuring the DNA content for every feature. It provides a post-hybridization analysis of array quality by scoring probe performance using three metrics, a a measure of variability in the signal intensities, b a measure of the signal dynamic range and c a measure of variability of the spot morphologies.

  1. Development and application of an antibody-based protein microarray to assess physiological stress in grizzly bears (Ursus arctos).

    Science.gov (United States)

    Carlson, Ruth I; Cattet, Marc R L; Sarauer, Bryan L; Nielsen, Scott E; Boulanger, John; Stenhouse, Gordon B; Janz, David M

    2016-01-01

    A novel antibody-based protein microarray was developed that simultaneously determines expression of 31 stress-associated proteins in skin samples collected from free-ranging grizzly bears (Ursus arctos) in Alberta, Canada. The microarray determines proteins belonging to four broad functional categories associated with stress physiology: hypothalamic-pituitary-adrenal axis proteins, apoptosis/cell cycle proteins, cellular stress/proteotoxicity proteins and oxidative stress/inflammation proteins. Small skin samples (50-100 mg) were collected from captured bears using biopsy punches. Proteins were isolated and labelled with fluorescent dyes, with labelled protein homogenates loaded onto microarrays to hybridize with antibodies. Relative protein expression was determined by comparison with a pooled standard skin sample. The assay was sensitive, requiring 80 µg of protein per sample to be run in triplicate on the microarray. Intra-array and inter-array coefficients of variation for individual proteins were generally bears. This suggests that remotely delivered biopsy darts could be used in future sampling. Using generalized linear mixed models, certain proteins within each functional category demonstrated altered expression with respect to differences in year, season, geographical sampling location within Alberta and bear biological parameters, suggesting that these general variables may influence expression of specific proteins in the microarray. Our goal is to apply the protein microarray as a conservation physiology tool that can detect, evaluate and monitor physiological stress in grizzly bears and other species at risk over time in response to environmental change.

  2. Microarray Я US: a user-friendly graphical interface to Bioconductor tools that enables accurate microarray data analysis and expedites comprehensive functional analysis of microarray results.

    Science.gov (United States)

    Dai, Yilin; Guo, Ling; Li, Meng; Chen, Yi-Bu

    2012-06-08

    Microarray data analysis presents a significant challenge to researchers who are unable to use the powerful Bioconductor and its numerous tools due to their lack of knowledge of R language. Among the few existing software programs that offer a graphic user interface to Bioconductor packages, none have implemented a comprehensive strategy to address the accuracy and reliability issue of microarray data analysis due to the well known probe design problems associated with many widely used microarray chips. There is also a lack of tools that would expedite the functional analysis of microarray results. We present Microarray Я US, an R-based graphical user interface that implements over a dozen popular Bioconductor packages to offer researchers a streamlined workflow for routine differential microarray expression data analysis without the need to learn R language. In order to enable a more accurate analysis and interpretation of microarray data, we incorporated the latest custom probe re-definition and re-annotation for Affymetrix and Illumina chips. A versatile microarray results output utility tool was also implemented for easy and fast generation of input files for over 20 of the most widely used functional analysis software programs. Coupled with a well-designed user interface, Microarray Я US leverages cutting edge Bioconductor packages for researchers with no knowledge in R language. It also enables a more reliable and accurate microarray data analysis and expedites downstream functional analysis of microarray results.

  3. Spectrophotometry of six broad absorption line QSOs

    Science.gov (United States)

    Junkkarinen, Vesa T.; Burbidge, E. Margaret; Smith, Harding E.

    1987-01-01

    Spectrophotometric observations of six broad absorption-line QSOs (BALQSOs) are presented. The continua and emission lines are compared with those in the spectra of QSOs without BALs. A statistically significant difference is found in the emission-line intensity ratio for (N V 1240-A)/(C IV 1549-A). The median value of (N V)/(C IV) for the BALQSOs is two to three times the median for QSOs without BALs. The absorption features of the BALQSOs are described, and the column densities and limits on the ionization structure of the BAL region are discussed. If the dominant ionization mechanism is photoionization, then it is likely that either the ionizing spectrum is steep or the abundances are considerably different from solar. Collisional ionization may be a significant factor, but it cannot totally dominate the ionization rate.

  4. Principles of gene microarray data analysis.

    Science.gov (United States)

    Mocellin, Simone; Rossi, Carlo Riccardo

    2007-01-01

    The development of several gene expression profiling methods, such as comparative genomic hybridization (CGH), differential display, serial analysis of gene expression (SAGE), and gene microarray, together with the sequencing of the human genome, has provided an opportunity to monitor and investigate the complex cascade of molecular events leading to tumor development and progression. The availability of such large amounts of information has shifted the attention of scientists towards a nonreductionist approach to biological phenomena. High throughput technologies can be used to follow changing patterns of gene expression over time. Among them, gene microarray has become prominent because it is easier to use, does not require large-scale DNA sequencing, and allows for the parallel quantification of thousands of genes from multiple samples. Gene microarray technology is rapidly spreading worldwide and has the potential to drastically change the therapeutic approach to patients affected with tumor. Therefore, it is of paramount importance for both researchers and clinicians to know the principles underlying the analysis of the huge amount of data generated with microarray technology.

  5. Detection of selected plant viruses by microarrays

    OpenAIRE

    HRABÁKOVÁ, Lenka

    2013-01-01

    The main aim of this master thesis was the simultaneous detection of four selected plant viruses ? Apple mosaic virus, Plum pox virus, Prunus necrotic ringspot virus and Prune harf virus, by microarrays. The intermediate step in the process of the detection was optimizing of multiplex polymerase chain reaction (PCR).

  6. LNA-modified isothermal oligonucleotide microarray for ...

    Indian Academy of Sciences (India)

    2014-10-20

    Oct 20, 2014 ... the advent of DNA microarray techniques (Lee et al. 2007). ... atoms of ribose to form a bicyclic ribosyl structure. It is the .... 532 nm and emission at 570 nm. The signal ..... sis and validation using real-time PCR. Nucleic Acids ...

  7. Gene Expression Analysis Using Agilent DNA Microarrays

    DEFF Research Database (Denmark)

    Stangegaard, Michael

    2009-01-01

    Hybridization of labeled cDNA to microarrays is an intuitively simple and a vastly underestimated process. If it is not performed, optimized, and standardized with the same attention to detail as e.g., RNA amplification, information may be overlooked or even lost. Careful balancing of the amount ...

  8. Microarrays (DNA Chips) for the Classroom Laboratory

    Science.gov (United States)

    Barnard, Betsy; Sussman, Michael; BonDurant, Sandra Splinter; Nienhuis, James; Krysan, Patrick

    2006-01-01

    We have developed and optimized the necessary laboratory materials to make DNA microarray technology accessible to all high school students at a fraction of both cost and data size. The primary component is a DNA chip/array that students "print" by hand and then analyze using research tools that have been adapted for classroom use. The…

  9. Comparing transformation methods for DNA microarray data

    NARCIS (Netherlands)

    Thygesen, Helene H.; Zwinderman, Aeilko H.

    2004-01-01

    Background: When DNA microarray data are used for gene clustering, genotype/phenotype correlation studies, or tissue classification the signal intensities are usually transformed and normalized in several steps in order to improve comparability and signal/noise ratio. These steps may include

  10. Identifying Fishes through DNA Barcodes and Microarrays.

    Directory of Open Access Journals (Sweden)

    Marc Kochzius

    2010-09-01

    Full Text Available International fish trade reached an import value of 62.8 billion Euro in 2006, of which 44.6% are covered by the European Union. Species identification is a key problem throughout the life cycle of fishes: from eggs and larvae to adults in fisheries research and control, as well as processed fish products in consumer protection.This study aims to evaluate the applicability of the three mitochondrial genes 16S rRNA (16S, cytochrome b (cyt b, and cytochrome oxidase subunit I (COI for the identification of 50 European marine fish species by combining techniques of "DNA barcoding" and microarrays. In a DNA barcoding approach, neighbour Joining (NJ phylogenetic trees of 369 16S, 212 cyt b, and 447 COI sequences indicated that cyt b and COI are suitable for unambiguous identification, whereas 16S failed to discriminate closely related flatfish and gurnard species. In course of probe design for DNA microarray development, each of the markers yielded a high number of potentially species-specific probes in silico, although many of them were rejected based on microarray hybridisation experiments. None of the markers provided probes to discriminate the sibling flatfish and gurnard species. However, since 16S-probes were less negatively influenced by the "position of label" effect and showed the lowest rejection rate and the highest mean signal intensity, 16S is more suitable for DNA microarray probe design than cty b and COI. The large portion of rejected COI-probes after hybridisation experiments (>90% renders the DNA barcoding marker as rather unsuitable for this high-throughput technology.Based on these data, a DNA microarray containing 64 functional oligonucleotide probes for the identification of 30 out of the 50 fish species investigated was developed. It represents the next step towards an automated and easy-to-handle method to identify fish, ichthyoplankton, and fish products.

  11. Facilitating functional annotation of chicken microarray data

    Directory of Open Access Journals (Sweden)

    Gresham Cathy R

    2009-10-01

    Full Text Available Abstract Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO. However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and

  12. Microarray BASICA: Background Adjustment, Segmentation, Image Compression and Analysis of Microarray Images

    Directory of Open Access Journals (Sweden)

    Jianping Hua

    2004-01-01

    Full Text Available This paper presents microarray BASICA: an integrated image processing tool for background adjustment, segmentation, image compression, and analysis of cDNA microarray images. BASICA uses a fast Mann-Whitney test-based algorithm to segment cDNA microarray images, and performs postprocessing to eliminate the segmentation irregularities. The segmentation results, along with the foreground and background intensities obtained with the background adjustment, are then used for independent compression of the foreground and background. We introduce a new distortion measurement for cDNA microarray image compression and devise a coding scheme by modifying the embedded block coding with optimized truncation (EBCOT algorithm (Taubman, 2000 to achieve optimal rate-distortion performance in lossy coding while still maintaining outstanding lossless compression performance. Experimental results show that the bit rate required to ensure sufficiently accurate gene expression measurement varies and depends on the quality of cDNA microarray images. For homogeneously hybridized cDNA microarray images, BASICA is able to provide from a bit rate as low as 5 bpp the gene expression data that are 99% in agreement with those of the original 32 bpp images.

  13. A novel multifunctional oligonucleotide microarray for Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Chen Feng

    2010-10-01

    Full Text Available Abstract Background Microarrays are invaluable tools for genome interrogation, SNP detection, and expression analysis, among other applications. Such broad capabilities would be of value to many pathogen research communities, although the development and use of genome-scale microarrays is often a costly undertaking. Therefore, effective methods for reducing unnecessary probes while maintaining or expanding functionality would be relevant to many investigators. Results Taking advantage of available genome sequences and annotation for Toxoplasma gondii (a pathogenic parasite responsible for illness in immunocompromised individuals and Plasmodium falciparum (a related parasite responsible for severe human malaria, we designed a single oligonucleotide microarray capable of supporting a wide range of applications at relatively low cost, including genome-wide expression profiling for Toxoplasma, and single-nucleotide polymorphism (SNP-based genotyping of both T. gondii and P. falciparum. Expression profiling of the three clonotypic lineages dominating T. gondii populations in North America and Europe provides a first comprehensive view of the parasite transcriptome, revealing that ~49% of all annotated genes are expressed in parasite tachyzoites (the acutely lytic stage responsible for pathogenesis and 26% of genes are differentially expressed among strains. A novel design utilizing few probes provided high confidence genotyping, used here to resolve recombination points in the clonal progeny of sexual crosses. Recent sequencing of additional T. gondii isolates identifies >620 K new SNPs, including ~11 K that intersect with expression profiling probes, yielding additional markers for genotyping studies, and further validating the utility of a combined expression profiling/genotyping array design. Additional applications facilitating SNP and transcript discovery, alternative statistical methods for quantifying gene expression, etc. are also pursued at

  14. DNA Microarrays in Comparative Genomics and Transcriptomics

    DEFF Research Database (Denmark)

    Willenbrock, Hanni

    2007-01-01

    at identifying the exact breakpoints where DNA has been gained or lost. In this thesis, three popular methods are compared and a realistic simulation model is presented for generating artificial data with known breakpoints and known DNA copy number. By using simulated data, we obtain a realistic evaluation......During the past few years, innovations in the DNA sequencing technology has led to an explosion in available DNA sequence information. This has revolutionized biological research and promoted the development of high throughput analysis methods that can take advantage of the vast amount of sequence...... data. For this, the DNA microarray technology has gained enormous popularity due to its ability to measure the presence or the activity of thousands of genes simultaneously. Microarrays for high throughput data analyses are not limited to a few organisms but may be applied to everything from bacteria...

  15. Immobilization Techniques for Microarray: Challenges and Applications

    Directory of Open Access Journals (Sweden)

    Satish Balasaheb Nimse

    2014-11-01

    Full Text Available The highly programmable positioning of molecules (biomolecules, nanoparticles, nanobeads, nanocomposites materials on surfaces has potential applications in the fields of biosensors, biomolecular electronics, and nanodevices. However, the conventional techniques including self-assembled monolayers fail to position the molecules on the nanometer scale to produce highly organized monolayers on the surface. The present article elaborates different techniques for the immobilization of the biomolecules on the surface to produce microarrays and their diagnostic applications. The advantages and the drawbacks of various methods are compared. This article also sheds light on the applications of the different technologies for the detection and discrimination of viral/bacterial genotypes and the detection of the biomarkers. A brief survey with 115 references covering the last 10 years on the biological applications of microarrays in various fields is also provided.

  16. Mining meiosis and gametogenesis with DNA microarrays.

    Science.gov (United States)

    Schlecht, Ulrich; Primig, Michael

    2003-04-01

    Gametogenesis is a key developmental process that involves complex transcriptional regulation of numerous genes including many that are conserved between unicellular eukaryotes and mammals. Recent expression-profiling experiments using microarrays have provided insight into the co-ordinated transcription of several hundred genes during mitotic growth and meiotic development in budding and fission yeast. Furthermore, microarray-based studies have identified numerous loci that are regulated during the cell cycle or expressed in a germ-cell specific manner in eukaryotic model systems like Caenorhabditis elegans, Mus musculus as well as Homo sapiens. The unprecedented amount of information produced by post-genome biology has spawned novel approaches to organizing biological knowledge using currently available information technology. This review outlines experiments that contribute to an emerging comprehensive picture of the molecular machinery governing sexual reproduction in eukaryotes.

  17. Facilitating RNA structure prediction with microarrays.

    Science.gov (United States)

    Kierzek, Elzbieta; Kierzek, Ryszard; Turner, Douglas H; Catrina, Irina E

    2006-01-17

    Determining RNA secondary structure is important for understanding structure-function relationships and identifying potential drug targets. This paper reports the use of microarrays with heptamer 2'-O-methyl oligoribonucleotides to probe the secondary structure of an RNA and thereby improve the prediction of that secondary structure. When experimental constraints from hybridization results are added to a free-energy minimization algorithm, the prediction of the secondary structure of Escherichia coli 5S rRNA improves from 27 to 92% of the known canonical base pairs. Optimization of buffer conditions for hybridization and application of 2'-O-methyl-2-thiouridine to enhance binding and improve discrimination between AU and GU pairs are also described. The results suggest that probing RNA with oligonucleotide microarrays can facilitate determination of secondary structure.

  18. Plasmonically amplified fluorescence bioassay with microarray format

    Science.gov (United States)

    Gogalic, S.; Hageneder, S.; Ctortecka, C.; Bauch, M.; Khan, I.; Preininger, Claudia; Sauer, U.; Dostalek, J.

    2015-05-01

    Plasmonic amplification of fluorescence signal in bioassays with microarray detection format is reported. A crossed relief diffraction grating was designed to couple an excitation laser beam to surface plasmons at the wavelength overlapping with the absorption and emission bands of fluorophore Dy647 that was used as a label. The surface of periodically corrugated sensor chip was coated with surface plasmon-supporting gold layer and a thin SU8 polymer film carrying epoxy groups. These groups were employed for the covalent immobilization of capture antibodies at arrays of spots. The plasmonic amplification of fluorescence signal on the developed microarray chip was tested by using interleukin 8 sandwich immunoassay. The readout was performed ex situ after drying the chip by using a commercial scanner with high numerical aperture collecting lens. Obtained results reveal the enhancement of fluorescence signal by a factor of 5 when compared to a regular glass chip.

  19. Tissue Microarray Analysis Applied to Bone Diagenesis

    OpenAIRE

    Barrios Mello, Rafael; Regis Silva, Maria Regina; Seixas Alves, Maria Teresa; Evison, Martin; Guimarães, Marco Aurélio; Francisco, Rafaella Arrabaça; Dias Astolphi, Rafael; Miazato Iwamura, Edna Sadayo

    2017-01-01

    Taphonomic processes affecting bone post mortem are important in forensic, archaeological and palaeontological investigations. In this study, the application of tissue microarray (TMA) analysis to a sample of femoral bone specimens from 20 exhumed individuals of known period of burial and age at death is described. TMA allows multiplexing of subsamples, permitting standardized comparative analysis of adjacent sections in 3-D and of representative cross-sections of a large number of specimens....

  20. Image microarrays derived from tissue microarrays (IMA-TMA: New resource for computer-aided diagnostic algorithm development

    Directory of Open Access Journals (Sweden)

    Jennifer A Hipp

    2012-01-01

    Full Text Available Background: Conventional tissue microarrays (TMAs consist of cores of tissue inserted into a recipient paraffin block such that a tissue section on a single glass slide can contain numerous patient samples in a spatially structured pattern. Scanning TMAs into digital slides for subsequent analysis by computer-aided diagnostic (CAD algorithms all offers the possibility of evaluating candidate algorithms against a near-complete repertoire of variable disease morphologies. This parallel interrogation approach simplifies the evaluation, validation, and comparison of such candidate algorithms. A recently developed digital tool, digital core (dCORE, and image microarray maker (iMAM enables the capture of uniformly sized and resolution-matched images, with these representing key morphologic features and fields of view, aggregated into a single monolithic digital image file in an array format, which we define as an image microarray (IMA. We further define the TMA-IMA construct as IMA-based images derived from whole slide images of TMAs themselves. Methods: Here we describe the first combined use of the previously described dCORE and iMAM tools, toward the goal of generating a higher-order image construct, with multiple TMA cores from multiple distinct conventional TMAs assembled as a single digital image montage. This image construct served as the basis of the carrying out of a massively parallel image analysis exercise, based on the use of the previously described spatially invariant vector quantization (SIVQ algorithm. Results: Multicase, multifield TMA-IMAs of follicular lymphoma and follicular hyperplasia were separately rendered, using the aforementioned tools. Each of these two IMAs contained a distinct spectrum of morphologic heterogeneity with respect to both tingible body macrophage (TBM appearance and apoptotic body morphology. SIVQ-based pattern matching, with ring vectors selected to screen for either tingible body macrophages or apoptotic

  1. Geiger mode avalanche photodiodes for microarray systems

    Science.gov (United States)

    Phelan, Don; Jackson, Carl; Redfern, R. Michael; Morrison, Alan P.; Mathewson, Alan

    2002-06-01

    New Geiger Mode Avalanche Photodiodes (GM-APD) have been designed and characterized specifically for use in microarray systems. Critical parameters such as excess reverse bias voltage, hold-off time and optimum operating temperature have been experimentally determined for these photon-counting devices. The photon detection probability, dark count rate and afterpulsing probability have been measured under different operating conditions. An active- quench circuit (AQC) is presented for operating these GM- APDs. This circuit is relatively simple, robust and has such benefits as reducing average power dissipation and afterpulsing. Arrays of these GM-APDs have already been designed and together with AQCs open up the possibility of having a solid-state microarray detector that enables parallel analysis on a single chip. Another advantage of these GM-APDs over current technology is their low voltage CMOS compatibility which could allow for the fabrication of an AQC on the same device. Small are detectors have already been employed in the time-resolved detection of fluorescence from labeled proteins. It is envisaged that operating these new GM-APDs with this active-quench circuit will have numerous applications for the detection of fluorescence in microarray systems.

  2. Classification across gene expression microarray studies

    Directory of Open Access Journals (Sweden)

    Kuner Ruprecht

    2009-12-01

    Full Text Available Abstract Background The increasing number of gene expression microarray studies represents an important resource in biomedical research. As a result, gene expression based diagnosis has entered clinical practice for patient stratification in breast cancer. However, the integration and combined analysis of microarray studies remains still a challenge. We assessed the potential benefit of data integration on the classification accuracy and systematically evaluated the generalization performance of selected methods on four breast cancer studies comprising almost 1000 independent samples. To this end, we introduced an evaluation framework which aims to establish good statistical practice and a graphical way to monitor differences. The classification goal was to correctly predict estrogen receptor status (negative/positive and histological grade (low/high of each tumor sample in an independent study which was not used for the training. For the classification we chose support vector machines (SVM, predictive analysis of microarrays (PAM, random forest (RF and k-top scoring pairs (kTSP. Guided by considerations relevant for classification across studies we developed a generalization of kTSP which we evaluated in addition. Our derived version (DV aims to improve the robustness of the intrinsic invariance of kTSP with respect to technologies and preprocessing. Results For each individual study the generalization error was benchmarked via complete cross-validation and was found to be similar for all classification methods. The misclassification rates were substantially higher in classification across studies, when each single study was used as an independent test set while all remaining studies were combined for the training of the classifier. However, with increasing number of independent microarray studies used in the training, the overall classification performance improved. DV performed better than the average and showed slightly less variance. In

  3. Development of a Feature and Template-Assisted Assembler and Application to the Analysis of a Foot-and-Mouth Disease Virus Genotyping Microarray.

    Directory of Open Access Journals (Sweden)

    Roger W Barrette

    Full Text Available Several RT-PCR and genome sequencing strategies exist for the resolution of Foot-and-Mouth Disease virus (FMDV. While these approaches are relatively straightforward, they can be vulnerable to failure due to the unpredictable nature of FMDV genome sequence variations. Sequence independent single primer amplification (SISPA followed by genotyping microarray offers an attractive unbiased approach to FMDV characterization. Here we describe a custom FMDV microarray and a companion feature and template-assisted assembler software (FAT-assembler capable of resolving virus genome sequence using a moderate number of conserved microarray features. The results demonstrate that this approach may be used to rapidly characterize naturally occurring FMDV as well as an engineered chimeric strain of FMDV. The FAT-assembler, while applied to resolving FMDV genomes, represents a new bioinformatics approach that should be broadly applicable to interpreting microarray genotyping data for other viruses or target organisms.

  4. Evaluation of toxicity of the mycotoxin citrinin using yeast ORF DNA microarray and Oligo DNA microarray

    Directory of Open Access Journals (Sweden)

    Nobumasa Hitoshi

    2007-04-01

    Full Text Available Abstract Background Mycotoxins are fungal secondary metabolites commonly present in feed and food, and are widely regarded as hazardous contaminants. Citrinin, one of the very well known mycotoxins that was first isolated from Penicillium citrinum, is produced by more than 10 kinds of fungi, and is possibly spread all over the world. However, the information on the action mechanism of the toxin is limited. Thus, we investigated the citrinin-induced genomic response for evaluating its toxicity. Results Citrinin inhibited growth of yeast cells at a concentration higher than 100 ppm. We monitored the citrinin-induced mRNA expression profiles in yeast using the ORF DNA microarray and Oligo DNA microarray, and the expression profiles were compared with those of the other stress-inducing agents. Results obtained from both microarray experiments clustered together, but were different from those of the mycotoxin patulin. The oxidative stress response genes – AADs, FLR1, OYE3, GRE2, and MET17 – were significantly induced. In the functional category, expression of genes involved in "metabolism", "cell rescue, defense and virulence", and "energy" were significantly activated. In the category of "metabolism", genes involved in the glutathione synthesis pathway were activated, and in the category of "cell rescue, defense and virulence", the ABC transporter genes were induced. To alleviate the induced stress, these cells might pump out the citrinin after modification with glutathione. While, the citrinin treatment did not induce the genes involved in the DNA repair. Conclusion Results from both microarray studies suggest that citrinin treatment induced oxidative stress in yeast cells. The genotoxicity was less severe than the patulin, suggesting that citrinin is less toxic than patulin. The reproducibility of the expression profiles was much better with the Oligo DNA microarray. However, the Oligo DNA microarray did not completely overcome cross

  5. Spectrum Recombination.

    Science.gov (United States)

    Greenslade, Thomas B., Jr.

    1984-01-01

    Describes several methods of executing lecture demonstrations involving the recombination of the spectrum. Groups the techniques into two general classes: bringing selected portions of the spectrum together using lenses or mirrors and blurring the colors by rapid movement or foreshortening. (JM)

  6. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

    Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

  7. Broad-Application Test Reactor

    International Nuclear Information System (INIS)

    Motloch, C.G.

    1992-05-01

    This report is about a new, safe, and operationally efficient DOE reactor of nuclear research and testing proposed for the early to mid- 21st Century. Dubbed the Broad-Application Test Reactor (BATR), the proposed facility incorporates a multiple-application, multiple-mission design to support DOE programs such as naval reactors and space power and propulsion, as well as research in medical, science, isotope, and electronics arenas. DOE research reactors are aging, and implementing major replacement projects requires long lead times. Primary design drivers include safety, low risk, minimum operation cost, mission flexibility, waste minimization, and long life. Scientists and engineers at the Idaho National Engineering Laboratory are evaluating possible fuel forms, structural materials, reactor geometries, coolants, and moderators

  8. Extended -Regular Sequence for Automated Analysis of Microarray Images

    Directory of Open Access Journals (Sweden)

    Jin Hee-Jeong

    2006-01-01

    Full Text Available Microarray study enables us to obtain hundreds of thousands of expressions of genes or genotypes at once, and it is an indispensable technology for genome research. The first step is the analysis of scanned microarray images. This is the most important procedure for obtaining biologically reliable data. Currently most microarray image processing systems require burdensome manual block/spot indexing work. Since the amount of experimental data is increasing very quickly, automated microarray image analysis software becomes important. In this paper, we propose two automated methods for analyzing microarray images. First, we propose the extended -regular sequence to index blocks and spots, which enables a novel automatic gridding procedure. Second, we provide a methodology, hierarchical metagrid alignment, to allow reliable and efficient batch processing for a set of microarray images. Experimental results show that the proposed methods are more reliable and convenient than the commercial tools.

  9. Design of a covalently bonded glycosphingolipid microarray

    DEFF Research Database (Denmark)

    Arigi, Emma; Blixt, Klas Ola; Buschard, Karsten

    2012-01-01

    , the major classes of plant and fungal GSLs. In this work, a prototype "universal" GSL-based covalent microarray has been designed, and preliminary evaluation of its potential utility in assaying protein-GSL binding interactions investigated. An essential step in development involved the enzymatic release...... of the fatty acyl moiety of the ceramide aglycone of selected mammalian GSLs with sphingolipid N-deacylase (SCDase). Derivatization of the free amino group of a typical lyso-GSL, lyso-G(M1), with a prototype linker assembled from succinimidyl-[(N-maleimidopropionamido)-diethyleneglycol] ester and 2...

  10. Linking probe thermodynamics to microarray quantification

    International Nuclear Information System (INIS)

    Li, Shuzhao; Pozhitkov, Alexander; Brouwer, Marius

    2010-01-01

    Understanding the difference in probe properties holds the key to absolute quantification of DNA microarrays. So far, Langmuir-like models have failed to link sequence-specific properties to hybridization signals in the presence of a complex hybridization background. Data from washing experiments indicate that the post-hybridization washing has no major effect on the specifically bound targets, which give the final signals. Thus, the amount of specific targets bound to probes is likely determined before washing, by the competition against nonspecific binding. Our competitive hybridization model is a viable alternative to Langmuir-like models. (comment)

  11. Broad-band beam buncher

    International Nuclear Information System (INIS)

    Goldberg, D.A.; Flood, W.S.; Arthur, A.A.; Voelker, F.

    1986-01-01

    This patent describes a broad-band beam buncher. This beam buncher consists of: a housing adapted to be eacuated, an electron gun in the housing for producing a beam of electrons, buncher means in the housing forming a buncher cavity which has an entrance opening for receiving the electron beam and an exit opening through which the electron beam passes out of the buncher cavity, a drift tube electrode in the buncher cavity and disposed between the entrance opening and the exit opening with first and second gaps between the drift tube electrode and the entrance and exit openings, the drift tube electrode which has a first drift space through which the electron beam passes in traveling between the entrance and exit openings, modulating means for supplying an ultrahigh frequeny modulating signal to the drift tube electrode for producing velocity modulation of the electrons in the electron beam as the electrons pass through the buncher cavity and the drift tube electrode between the entrance opening and the exit opening, drift space means in the housing forming a second drift space for receiving the velocity modulated electron beam from the exit opening, the velocity modulated electron beam being bunched as it passes along the second drift space, the drift space means has a discharge opening through which the electron beam is discharged from the second drift space after being bunched therein, the modulating means containing a signal source for producing an ultrahigh frequency signal, a transmission line connected between the signal source and the drift tube electrode, and terminating means connected to the drift tube electrode for terminating the transmission line in approximately its characteristic impedance to afford a broad response band with minimum 6 variations therein

  12. Design of an Enterobacteriaceae Pan-genome Microarray Chip

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2010-01-01

    -density microarray chip has been designed, using 116 Enterobacteriaceae genome sequences, taking into account the enteric pan-genome. Probes for the microarray were checked in silico and performance of the chip, based on experimental strains from four different genera, demonstrate a relatively high ability...... to distinguish those strains on genus, species, and pathotype/serovar levels. Additionally, the microarray performed well when investigating which genes were found in a given strain of interest. The Enterobacteriaceae pan-genome microarray, based on 116 genomes, provides a valuable tool for determination...

  13. Development of a miniaturised microarray-based assay for the rapid identification of antimicrobial resistance genes in Gram-negative bacteria

    DEFF Research Database (Denmark)

    Batchelor, Miranda; Hopkins, Katie L; Liebana, Ernesto

    2008-01-01

    We describe the development of a miniaturised microarray for the detection of antimicrobial resistance genes in Gram-negative bacteria. Included on the array are genes encoding resistance to aminoglycosides, trimethoprim, sulphonamides, tetracyclines and beta-lactams, including extended-spectrum ...

  14. Comparing transformation methods for DNA microarray data

    Directory of Open Access Journals (Sweden)

    Zwinderman Aeilko H

    2004-06-01

    Full Text Available Abstract Background When DNA microarray data are used for gene clustering, genotype/phenotype correlation studies, or tissue classification the signal intensities are usually transformed and normalized in several steps in order to improve comparability and signal/noise ratio. These steps may include subtraction of an estimated background signal, subtracting the reference signal, smoothing (to account for nonlinear measurement effects, and more. Different authors use different approaches, and it is generally not clear to users which method they should prefer. Results We used the ratio between biological variance and measurement variance (which is an F-like statistic as a quality measure for transformation methods, and we demonstrate a method for maximizing that variance ratio on real data. We explore a number of transformations issues, including Box-Cox transformation, baseline shift, partial subtraction of the log-reference signal and smoothing. It appears that the optimal choice of parameters for the transformation methods depends on the data. Further, the behavior of the variance ratio, under the null hypothesis of zero biological variance, appears to depend on the choice of parameters. Conclusions The use of replicates in microarray experiments is important. Adjustment for the null-hypothesis behavior of the variance ratio is critical to the selection of transformation method.

  15. Calling Biomarkers in Milk Using a Protein Microarray on Your Smartphone

    Science.gov (United States)

    Ludwig, Susann K. J.; Tokarski, Christian; Lang, Stefan N.; van Ginkel, Leendert A.; Zhu, Hongying; Ozcan, Aydogan; Nielen, Michel W. F.

    2015-01-01

    Here we present the concept of a protein microarray-based fluorescence immunoassay for multiple biomarker detection in milk extracts by an ordinary smartphone. A multiplex immunoassay was designed on a microarray chip, having built-in positive and negative quality controls. After the immunoassay procedure, the 48 microspots were labelled with Quantum Dots (QD) depending on the protein biomarker levels in the sample. QD-fluorescence was subsequently detected by the smartphone camera under UV light excitation from LEDs embedded in a simple 3D-printed opto-mechanical smartphone attachment. The somewhat aberrant images obtained under such conditions, were corrected by newly developed Android-based software on the same smartphone, and protein biomarker profiles were calculated. The indirect detection of recombinant bovine somatotropin (rbST) in milk extracts based on altered biomarker profile of anti-rbST antibodies was selected as a real-life challenge. RbST-treated and untreated cows clearly showed reproducible treatment-dependent biomarker profiles in milk, in excellent agreement with results from a flow cytometer reference method. In a pilot experiment, anti-rbST antibody detection was multiplexed with the detection of another rbST-dependent biomarker, insulin-like growth factor 1 (IGF-1). Milk extract IGF-1 levels were found to be increased after rbST treatment and correlated with the results obtained from the reference method. These data clearly demonstrate the potential of the portable protein microarray concept towards simultaneous detection of multiple biomarkers. We envisage broad application of this ‘protein microarray on a smartphone’-concept for on-site testing, e.g., in food safety, environment and health monitoring. PMID:26308444

  16. Calling Biomarkers in Milk Using a Protein Microarray on Your Smartphone.

    Directory of Open Access Journals (Sweden)

    Susann K J Ludwig

    Full Text Available Here we present the concept of a protein microarray-based fluorescence immunoassay for multiple biomarker detection in milk extracts by an ordinary smartphone. A multiplex immunoassay was designed on a microarray chip, having built-in positive and negative quality controls. After the immunoassay procedure, the 48 microspots were labelled with Quantum Dots (QD depending on the protein biomarker levels in the sample. QD-fluorescence was subsequently detected by the smartphone camera under UV light excitation from LEDs embedded in a simple 3D-printed opto-mechanical smartphone attachment. The somewhat aberrant images obtained under such conditions, were corrected by newly developed Android-based software on the same smartphone, and protein biomarker profiles were calculated. The indirect detection of recombinant bovine somatotropin (rbST in milk extracts based on altered biomarker profile of anti-rbST antibodies was selected as a real-life challenge. RbST-treated and untreated cows clearly showed reproducible treatment-dependent biomarker profiles in milk, in excellent agreement with results from a flow cytometer reference method. In a pilot experiment, anti-rbST antibody detection was multiplexed with the detection of another rbST-dependent biomarker, insulin-like growth factor 1 (IGF-1. Milk extract IGF-1 levels were found to be increased after rbST treatment and correlated with the results obtained from the reference method. These data clearly demonstrate the potential of the portable protein microarray concept towards simultaneous detection of multiple biomarkers. We envisage broad application of this 'protein microarray on a smartphone'-concept for on-site testing, e.g., in food safety, environment and health monitoring.

  17. Extreme Variability in a Broad Absorption Line Quasar

    Energy Technology Data Exchange (ETDEWEB)

    Stern, Daniel; Jun, Hyunsung D. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Mail Stop 169-221, Pasadena, CA 91109 (United States); Graham, Matthew J.; Djorgovski, S. G.; Donalek, Ciro; Drake, Andrew J.; Mahabal, Ashish A.; Steidel, Charles C. [California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125 (United States); Arav, Nahum; Chamberlain, Carter [Department of Physics, Virginia Tech, Blacksburg, VA 24061 (United States); Barth, Aaron J. [Department of Physics and Astronomy, 4129 Frederick Reines Hall, University of California, Irvine, CA 92697 (United States); Glikman, Eilat, E-mail: daniel.k.stern@jpl.nasa.gov [Department of Physics, Middlebury College, Middlebury, VT 05753 (United States)

    2017-04-20

    CRTS J084133.15+200525.8 is an optically bright quasar at z = 2.345 that has shown extreme spectral variability over the past decade. Photometrically, the source had a visual magnitude of V ∼ 17.3 between 2002 and 2008. Then, over the following five years, the source slowly brightened by approximately one magnitude, to V ∼ 16.2. Only ∼1 in 10,000 quasars show such extreme variability, as quantified by the extreme parameters derived for this quasar assuming a damped random walk model. A combination of archival and newly acquired spectra reveal the source to be an iron low-ionization broad absorption line quasar with extreme changes in its absorption spectrum. Some absorption features completely disappear over the 9 years of optical spectra, while other features remain essentially unchanged. We report the first definitive redshift for this source, based on the detection of broad H α in a Keck/MOSFIRE spectrum. Absorption systems separated by several 1000 km s{sup −1} in velocity show coordinated weakening in the depths of their troughs as the continuum flux increases. We interpret the broad absorption line variability to be due to changes in photoionization, rather than due to motion of material along our line of sight. This source highlights one sort of rare transition object that astronomy will now be finding through dedicated time-domain surveys.

  18. Shared probe design and existing microarray reanalysis using PICKY

    Directory of Open Access Journals (Sweden)

    Chou Hui-Hsien

    2010-04-01

    Full Text Available Abstract Background Large genomes contain families of highly similar genes that cannot be individually identified by microarray probes. This limitation is due to thermodynamic restrictions and cannot be resolved by any computational method. Since gene annotations are updated more frequently than microarrays, another common issue facing microarray users is that existing microarrays must be routinely reanalyzed to determine probes that are still useful with respect to the updated annotations. Results PICKY 2.0 can design shared probes for sets of genes that cannot be individually identified using unique probes. PICKY 2.0 uses novel algorithms to track sharable regions among genes and to strictly distinguish them from other highly similar but nontarget regions during thermodynamic comparisons. Therefore, PICKY does not sacrifice the quality of shared probes when choosing them. The latest PICKY 2.1 includes the new capability to reanalyze existing microarray probes against updated gene sets to determine probes that are still valid to use. In addition, more precise nonlinear salt effect estimates and other improvements are added, making PICKY 2.1 more versatile to microarray users. Conclusions Shared probes allow expressed gene family members to be detected; this capability is generally more desirable than not knowing anything about these genes. Shared probes also enable the design of cross-genome microarrays, which facilitate multiple species identification in environmental samples. The new nonlinear salt effect calculation significantly increases the precision of probes at a lower buffer salt concentration, and the probe reanalysis function improves existing microarray result interpretations.

  19. A Critical Perspective On Microarray Breast Cancer Gene Expression Profiling

    NARCIS (Netherlands)

    Sontrop, H.M.J.

    2015-01-01

    Microarrays offer biologists an exciting tool that allows the simultaneous assessment of gene expression levels for thousands of genes at once. At the time of their inception, microarrays were hailed as the new dawn in cancer biology and oncology practice with the hope that within a decade diseases

  20. The Importance of Normalization on Large and Heterogeneous Microarray Datasets

    Science.gov (United States)

    DNA microarray technology is a powerful functional genomics tool increasingly used for investigating global gene expression in environmental studies. Microarrays can also be used in identifying biological networks, as they give insight on the complex gene-to-gene interactions, ne...

  1. The application of DNA microarrays in gene expression analysis

    NARCIS (Netherlands)

    Hal, van N.L.W.; Vorst, O.; Houwelingen, van A.M.M.L.; Kok, E.J.; Peijnenburg, A.A.C.M.; Aharoni, A.; Tunen, van A.J.; Keijer, J.

    2000-01-01

    DNA microarray technology is a new and powerful technology that will substantially increase the speed of molecular biological research. This paper gives a survey of DNA microarray technology and its use in gene expression studies. The technical aspects and their potential improvements are discussed.

  2. Uses of Dendrimers for DNA Microarrays

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Majoral

    2006-08-01

    Full Text Available Biosensors such as DNA microarrays and microchips are gaining an increasingimportance in medicinal, forensic, and environmental analyses. Such devices are based onthe detection of supramolecular interactions called hybridizations that occur betweencomplementary oligonucleotides, one linked to a solid surface (the probe, and the other oneto be analyzed (the target. This paper focuses on the improvements that hyperbranched andperfectly defined nanomolecules called dendrimers can provide to this methodology. Twomain uses of dendrimers for such purpose have been described up to now; either thedendrimer is used as linker between the solid surface and the probe oligonucleotide, or thedendrimer is used as a multilabeled entity linked to the target oligonucleotide. In the firstcase the dendrimer generally induces a higher loading of probes and an easier hybridization,due to moving away the solid phase. In the second case the high number of localized labels(generally fluorescent induces an increased sensitivity, allowing the detection of smallquantities of biological entities.

  3. 78 FR 20119 - Broad Stakeholder Survey

    Science.gov (United States)

    2013-04-03

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2012-0042] Broad Stakeholder Survey AGENCY... concerning the Broad Stakeholder Survey. DHS previously published this ICR in the Federal Register on August... across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on the...

  4. Bystander effect: Biological endpoints and microarray analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhry, M. Ahmad [Department of Medical Laboratory and Radiation Sciences, College of Nursing and Health Sciences, University of Vermont, 302 Rowell Building, Burlington, VT 05405 (United States) and DNA Microarray Facility, University of Vermont, Burlington, VT 05405 (United States)]. E-mail: mchaudhr@uvm.edu

    2006-05-11

    In cell populations exposed to ionizing radiation, the biological effects occur in a much larger proportion of cells than are estimated to be traversed by radiation. It has been suggested that irradiated cells are capable of providing signals to the neighboring unirradiated cells resulting in damage to these cells. This phenomenon is termed the bystander effect. The bystander effect induces persistent, long-term, transmissible changes that result in delayed death and neoplastic transformation. Because the bystander effect is relevant to carcinogenesis, it could have significant implications for risk estimation for radiation exposure. The nature of the bystander effect signal and how it impacts the unirradiated cells remains to be elucidated. Examination of the changes in gene expression could provide clues to understanding the bystander effect and could define the signaling pathways involved in sustaining damage to these cells. The microarray technology serves as a tool to gain insight into the molecular pathways leading to bystander effect. Using medium from irradiated normal human diploid lung fibroblasts as a model system we examined gene expression alterations in bystander cells. The microarray data revealed that the radiation-induced gene expression profile in irradiated cells is different from unirradiated bystander cells suggesting that the pathways leading to biological effects in the bystander cells are different from the directly irradiated cells. The genes known to be responsive to ionizing radiation were observed in irradiated cells. Several genes were upregulated in cells receiving media from irradiated cells. Surprisingly no genes were found to be downregulated in these cells. A number of genes belonging to extracellular signaling, growth factors and several receptors were identified in bystander cells. Interestingly 15 genes involved in the cell communication processes were found to be upregulated. The induction of receptors and the cell

  5. Bystander effect: Biological endpoints and microarray analysis

    International Nuclear Information System (INIS)

    Chaudhry, M. Ahmad

    2006-01-01

    In cell populations exposed to ionizing radiation, the biological effects occur in a much larger proportion of cells than are estimated to be traversed by radiation. It has been suggested that irradiated cells are capable of providing signals to the neighboring unirradiated cells resulting in damage to these cells. This phenomenon is termed the bystander effect. The bystander effect induces persistent, long-term, transmissible changes that result in delayed death and neoplastic transformation. Because the bystander effect is relevant to carcinogenesis, it could have significant implications for risk estimation for radiation exposure. The nature of the bystander effect signal and how it impacts the unirradiated cells remains to be elucidated. Examination of the changes in gene expression could provide clues to understanding the bystander effect and could define the signaling pathways involved in sustaining damage to these cells. The microarray technology serves as a tool to gain insight into the molecular pathways leading to bystander effect. Using medium from irradiated normal human diploid lung fibroblasts as a model system we examined gene expression alterations in bystander cells. The microarray data revealed that the radiation-induced gene expression profile in irradiated cells is different from unirradiated bystander cells suggesting that the pathways leading to biological effects in the bystander cells are different from the directly irradiated cells. The genes known to be responsive to ionizing radiation were observed in irradiated cells. Several genes were upregulated in cells receiving media from irradiated cells. Surprisingly no genes were found to be downregulated in these cells. A number of genes belonging to extracellular signaling, growth factors and several receptors were identified in bystander cells. Interestingly 15 genes involved in the cell communication processes were found to be upregulated. The induction of receptors and the cell

  6. Lipid Microarray Biosensor for Biotoxin Detection.

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.; Edel, Joshua B.; Meyer, Grant D.; Craighead, Harold G.

    2006-05-01

    We present the use of micron-sized lipid domains, patterned onto planar substrates and within microfluidic channels, to assay the binding of bacterial toxins via total internal reflection fluorescence microscopy (TIRFM). The lipid domains were patterned using a polymer lift-off technique and consisted of ganglioside-populated DSPC:cholesterol supported lipid bilayers (SLBs). Lipid patterns were formed on the substrates by vesicle fusion followed by polymer lift-off, which revealed micron-sized SLBs containing either ganglioside GT1b or GM1. The ganglioside-populated SLB arrays were then exposed to either Cholera toxin subunit B (CTB) or Tetanus toxin fragment C (TTC). Binding was assayed on planar substrates by TIRFM down to 1 nM concentration for CTB and 100 nM for TTC. Apparent binding constants extracted from three different models applied to the binding curves suggest that binding of a protein to a lipid-based receptor is strongly affected by the lipid composition of the SLB and by the substrate on which the bilayer is formed. Patterning of SLBs inside microfluidic channels also allowed the preparation of lipid domains with different compositions on a single device. Arrays within microfluidic channels were used to achieve segregation and selective binding from a binary mixture of the toxin fragments in one device. The binding and segregation within the microfluidic channels was assayed with epifluorescence as proof of concept. We propose that the method used for patterning the lipid microarrays on planar substrates and within microfluidic channels can be easily adapted to proteins or nucleic acids and can be used for biosensor applications and cell stimulation assays under different flow conditions. KEYWORDS. Microarray, ganglioside, polymer lift-off, cholera toxin, tetanus toxin, TIRFM, binding constant.4

  7. cDNA microarray screening in food safety

    International Nuclear Information System (INIS)

    Roy, Sashwati; Sen, Chandan K.

    2006-01-01

    The cDNA microarray technology and related bioinformatics tools presents a wide range of novel application opportunities. The technology may be productively applied to address food safety. In this mini-review article, we present an update highlighting the late breaking discoveries that demonstrate the vitality of cDNA microarray technology as a tool to analyze food safety with reference to microbial pathogens and genetically modified foods. In order to bring the microarray technology to mainstream food safety, it is important to develop robust user-friendly tools that may be applied in a field setting. In addition, there needs to be a standardized process for regulatory agencies to interpret and act upon microarray-based data. The cDNA microarray approach is an emergent technology in diagnostics. Its values lie in being able to provide complimentary molecular insight when employed in addition to traditional tests for food safety, as part of a more comprehensive battery of tests

  8. Versatile High Resolution Oligosaccharide Microarrays for Plant Glycobiology and Cell Wall Research

    DEFF Research Database (Denmark)

    Pedersen, Henriette Lodberg; Fangel, Jonatan Ulrik; McCleary, Barry

    2012-01-01

    Microarrays are powerful tools for high throughput analysis, and hundreds or thousands of molecular interactions can be assessed simultaneously using very small amounts of analytes. Nucleotide microarrays are well established in plant research, but carbohydrate microarrays are much less establish...

  9. A cell spot microarray method for production of high density siRNA transfection microarrays

    Directory of Open Access Journals (Sweden)

    Mpindi John-Patrick

    2011-03-01

    Full Text Available Abstract Background High-throughput RNAi screening is widely applied in biological research, but remains expensive, infrastructure-intensive and conversion of many assays to HTS applications in microplate format is not feasible. Results Here, we describe the optimization of a miniaturized cell spot microarray (CSMA method, which facilitates utilization of the transfection microarray technique for disparate RNAi analyses. To promote rapid adaptation of the method, the concept has been tested with a panel of 92 adherent cell types, including primary human cells. We demonstrate the method in the systematic screening of 492 GPCR coding genes for impact on growth and survival of cultured human prostate cancer cells. Conclusions The CSMA method facilitates reproducible preparation of highly parallel cell microarrays for large-scale gene knockdown analyses. This will be critical towards expanding the cell based functional genetic screens to include more RNAi constructs, allow combinatorial RNAi analyses, multi-parametric phenotypic readouts or comparative analysis of many different cell types.

  10. Zellweger Spectrum

    Science.gov (United States)

    ... severe defect, resulting in essentially nonfunctional peroxisomes. This phenomenon produces the range of severity of the disorders. How is the Zellweger Spectrum Diagnosed? The distinctive shape of the head and face of a child born with one of the diseases of the ...

  11. Broad-band spectrophotometry of HAT-P-32 b

    DEFF Research Database (Denmark)

    Mallonn, M.; Bernt, I.; Herrero, E.

    2016-01-01

    Multicolour broad-band transit observations offer the opportunity to characterize the atmosphere of an extrasolar planet with small- to medium-sized telescopes. One of the most favourable targets is the hot Jupiter HAT-P-32 b. We combined 21 new transit observations of this planet with 36 previou...... makes a recent tentative detection of a scattering feature less likely. Instead, the available spectral measurements of HAT-P-32 b favour a completely flat spectrum from the near-UV to the near-IR. A plausible interpretation is a thick cloud cover at high altitudes....

  12. Microintaglio Printing for Soft Lithography-Based in Situ Microarrays

    Directory of Open Access Journals (Sweden)

    Manish Biyani

    2015-07-01

    Full Text Available Advances in lithographic approaches to fabricating bio-microarrays have been extensively explored over the last two decades. However, the need for pattern flexibility, a high density, a high resolution, affordability and on-demand fabrication is promoting the development of unconventional routes for microarray fabrication. This review highlights the development and uses of a new molecular lithography approach, called “microintaglio printing technology”, for large-scale bio-microarray fabrication using a microreactor array (µRA-based chip consisting of uniformly-arranged, femtoliter-size µRA molds. In this method, a single-molecule-amplified DNA microarray pattern is self-assembled onto a µRA mold and subsequently converted into a messenger RNA or protein microarray pattern by simultaneously producing and transferring (immobilizing a messenger RNA or a protein from a µRA mold to a glass surface. Microintaglio printing allows the self-assembly and patterning of in situ-synthesized biomolecules into high-density (kilo-giga-density, ordered arrays on a chip surface with µm-order precision. This holistic aim, which is difficult to achieve using conventional printing and microarray approaches, is expected to revolutionize and reshape proteomics. This review is not written comprehensively, but rather substantively, highlighting the versatility of microintaglio printing for developing a prerequisite platform for microarray technology for the postgenomic era.

  13. The application of DNA microarrays in gene expression analysis.

    Science.gov (United States)

    van Hal, N L; Vorst, O; van Houwelingen, A M; Kok, E J; Peijnenburg, A; Aharoni, A; van Tunen, A J; Keijer, J

    2000-03-31

    DNA microarray technology is a new and powerful technology that will substantially increase the speed of molecular biological research. This paper gives a survey of DNA microarray technology and its use in gene expression studies. The technical aspects and their potential improvements are discussed. These comprise array manufacturing and design, array hybridisation, scanning, and data handling. Furthermore, it is discussed how DNA microarrays can be applied in the working fields of: safety, functionality and health of food and gene discovery and pathway engineering in plants.

  14. Tissue Microarray TechnologyA Brief Review

    Directory of Open Access Journals (Sweden)

    Ramya S Vokuda

    2018-01-01

    Full Text Available In this era of modern revolutionisation in the field of medical laboratory technology, everyone is aiming at taking the innovations from laboratory to bed side. One such technique that is most relevant to the pathologic community is Tissue Microarray (TMA technology. This is becoming quite popular amongst all the members of this family, right from laboratory scientists to clinicians and residents to technologists. The reason for this technique to gain popularity is attributed to its cost effectiveness and time saving protocols. Though, every technique is accompanied by disadvantages, the benefits out number them. This technique is very versatile as many downstream molecular assays such as immunohistochemistry, cytogenetic studies, Fluorescent In situ-Hybridisation (FISH etc., can be carried out on a single slide with multiple numbers of samples. It is a very practical approach that aids effectively to identify novel biomarkers in cancer diagnostics and therapeutics. It helps in assessing the molecular markers on a large scale very quickly. Also, the quality assurance protocols in pathological laboratory has exploited TMA to a great extent. However, the application of TMA technology is beyond oncology. This review shall focus on the different aspects of this technology such as construction of TMA, instrumentation, types, advantages and disadvantages and utilisation of the technique in various disease conditions.

  15. Tissue Microarray Analysis Applied to Bone Diagenesis.

    Science.gov (United States)

    Mello, Rafael Barrios; Silva, Maria Regina Regis; Alves, Maria Teresa Seixas; Evison, Martin Paul; Guimarães, Marco Aurelio; Francisco, Rafaella Arrabaca; Astolphi, Rafael Dias; Iwamura, Edna Sadayo Miazato

    2017-01-04

    Taphonomic processes affecting bone post mortem are important in forensic, archaeological and palaeontological investigations. In this study, the application of tissue microarray (TMA) analysis to a sample of femoral bone specimens from 20 exhumed individuals of known period of burial and age at death is described. TMA allows multiplexing of subsamples, permitting standardized comparative analysis of adjacent sections in 3-D and of representative cross-sections of a large number of specimens. Standard hematoxylin and eosin, periodic acid-Schiff and silver methenamine, and picrosirius red staining, and CD31 and CD34 immunohistochemistry were applied to TMA sections. Osteocyte and osteocyte lacuna counts, percent bone matrix loss, and fungal spheroid element counts could be measured and collagen fibre bundles observed in all specimens. Decalcification with 7% nitric acid proceeded more rapidly than with 0.5 M EDTA and may offer better preservation of histological and cellular structure. No endothelial cells could be detected using CD31 and CD34 immunohistochemistry. Correlation between osteocytes per lacuna and age at death may reflect reported age-related responses to microdamage. Methodological limitations and caveats, and results of the TMA analysis of post mortem diagenesis in bone are discussed, and implications for DNA survival and recovery considered.

  16. Transcriptome analysis of zebrafish embryogenesis using microarrays.

    Directory of Open Access Journals (Sweden)

    Sinnakaruppan Mathavan

    2005-08-01

    Full Text Available Zebrafish (Danio rerio is a well-recognized model for the study of vertebrate developmental genetics, yet at the same time little is known about the transcriptional events that underlie zebrafish embryogenesis. Here we have employed microarray analysis to study the temporal activity of developmentally regulated genes during zebrafish embryogenesis. Transcriptome analysis at 12 different embryonic time points covering five different developmental stages (maternal, blastula, gastrula, segmentation, and pharyngula revealed a highly dynamic transcriptional profile. Hierarchical clustering, stage-specific clustering, and algorithms to detect onset and peak of gene expression revealed clearly demarcated transcript clusters with maximum gene activity at distinct developmental stages as well as co-regulated expression of gene groups involved in dedicated functions such as organogenesis. Our study also revealed a previously unidentified cohort of genes that are transcribed prior to the mid-blastula transition, a time point earlier than when the zygotic genome was traditionally thought to become active. Here we provide, for the first time to our knowledge, a comprehensive list of developmentally regulated zebrafish genes and their expression profiles during embryogenesis, including novel information on the temporal expression of several thousand previously uncharacterized genes. The expression data generated from this study are accessible to all interested scientists from our institute resource database (http://giscompute.gis.a-star.edu.sg/~govind/zebrafish/data_download.html.

  17. Cell-Based Microarrays for In Vitro Toxicology

    Science.gov (United States)

    Wegener, Joachim

    2015-07-01

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

  18. High throughput screening of starch structures using carbohydrate microarrays

    DEFF Research Database (Denmark)

    Tanackovic, Vanja; Rydahl, Maja Gro; Pedersen, Henriette Lodberg

    2016-01-01

    In this study we introduce the starch-recognising carbohydrate binding module family 20 (CBM20) from Aspergillus niger for screening biological variations in starch molecular structure using high throughput carbohydrate microarray technology. Defined linear, branched and phosphorylated...

  19. Microarray of DNA probes on carboxylate functional beads surface

    Institute of Scientific and Technical Information of China (English)

    黄承志; 李原芳; 黄新华; 范美坤

    2000-01-01

    The microarray of DNA probes with 5’ -NH2 and 5’ -Tex/3’ -NH2 modified terminus on 10 um carboxylate functional beads surface in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) is characterized in the preseni paper. it was found that the microarray capacity of DNA probes on the beads surface depends on the pH of the aqueous solution, the concentra-tion of DNA probe and the total surface area of the beads. On optimal conditions, the minimum distance of 20 mer single-stranded DNA probe microarrayed on beads surface is about 14 nm, while that of 20 mer double-stranded DNA probes is about 27 nm. If the probe length increases from 20 mer to 35 mer, its microarray density decreases correspondingly. Mechanism study shows that the binding mode of DNA probes on the beads surface is nearly parallel to the beads surface.

  20. Microarray of DNA probes on carboxylate functional beads surface

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The microarray of DNA probes with 5′-NH2 and 5′-Tex/3′-NH2 modified terminus on 10 m m carboxylate functional beads surface in the presence of 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide (EDC) is characterized in the present paper. It was found that the microarray capacity of DNA probes on the beads surface depends on the pH of the aqueous solution, the concentration of DNA probe and the total surface area of the beads. On optimal conditions, the minimum distance of 20 mer single-stranded DNA probe microarrayed on beads surface is about 14 nm, while that of 20 mer double-stranded DNA probes is about 27 nm. If the probe length increases from 20 mer to 35 mer, its microarray density decreases correspondingly. Mechanism study shows that the binding mode of DNA probes on the beads surface is nearly parallel to the beads surface.

  1. Rapid Diagnosis of Bacterial Meningitis Using a Microarray

    Directory of Open Access Journals (Sweden)

    Ren-Jy Ben

    2008-06-01

    Conclusion: The microarray method provides a more accurate and rapid diagnostic tool for bacterial meningitis compared to traditional culture methods. Clinical application of this new technique may reduce the potential risk of delay in treatment.

  2. Variance estimation in the analysis of microarray data

    KAUST Repository

    Wang, Yuedong; Ma, Yanyuan; Carroll, Raymond J.

    2009-01-01

    Microarrays are one of the most widely used high throughput technologies. One of the main problems in the area is that conventional estimates of the variances that are required in the t-statistic and other statistics are unreliable owing

  3. Novel Protein Microarray Technology to Examine Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Lilja, Hans

    2005-01-01

    The authors developed a novel macro and nanoporous silicon surface for protein microarrays to facilitate high-throughput biomarker discovery, and high-density protein-chip array analyses of complex biological samples...

  4. Beyond the Spectrum: Rethinking Autism

    Directory of Open Access Journals (Sweden)

    Heather Thomas

    2017-03-01

    Full Text Available The "spectrum" has become the dominant metaphor for conceptualizing autism, with fundamental consequences for notions of disability, diversity, and normality. In this article, we draw on ethnographic research with autistic communities to explore how the notion of the autism spectrum has become a focus of explicit identification, reflection, and contestation. To further this inquiry, we place these debates into conversation with earlier debates regarding another spectrum—the Kinsey Scale, a "spectrum" for conceptualizing sexual orientation that first appeared in 1948 but has been critiqued since the 1970s. How might responses to the Kinsey Scale (like the Klein Grid contribute to rethinking the autism spectrum? This is a question about the cultural and political implications of metaphors and conceptual models. It is of broad importance because the spectrum metaphor is being extended to a range of conditions beyond autism itself. Our goal is thus to build on insights from sexuality studies as well as the insights of autistic persons, advocates, and researchers who wish to forestall the naturalization of "the spectrum." In doing so, we seek to contribute to a discussion of what alternative frameworks might bring to questions of social justice, ability, and human flourishing.

  5. Universal Reference RNA as a standard for microarray experiments

    Directory of Open Access Journals (Sweden)

    Fero Michael

    2004-03-01

    Full Text Available Abstract Background Obtaining reliable and reproducible two-color microarray gene expression data is critically important for understanding the biological significance of perturbations made on a cellular system. Microarray design, RNA preparation and labeling, hybridization conditions and data acquisition and analysis are variables difficult to simultaneously control. A useful tool for monitoring and controlling intra- and inter-experimental variation is Universal Reference RNA (URR, developed with the goal of providing hybridization signal at each microarray probe location (spot. Measuring signal at each spot as the ratio of experimental RNA to reference RNA targets, rather than relying on absolute signal intensity, decreases variability by normalizing signal output in any two-color hybridization experiment. Results Human, mouse and rat URR (UHRR, UMRR and URRR, respectively were prepared from pools of RNA derived from individual cell lines representing different tissues. A variety of microarrays were used to determine percentage of spots hybridizing with URR and producing signal above a user defined threshold (microarray coverage. Microarray coverage was consistently greater than 80% for all arrays tested. We confirmed that individual cell lines contribute their own unique set of genes to URR, arguing for a pool of RNA from several cell lines as a better configuration for URR as opposed to a single cell line source for URR. Microarray coverage comparing two separately prepared batches each of UHRR, UMRR and URRR were highly correlated (Pearson's correlation coefficients of 0.97. Conclusion Results of this study demonstrate that large quantities of pooled RNA from individual cell lines are reproducibly prepared and possess diverse gene representation. This type of reference provides a standard for reducing variation in microarray experiments and allows more reliable comparison of gene expression data within and between experiments and

  6. Addressable droplet microarrays for single cell protein analysis.

    Science.gov (United States)

    Salehi-Reyhani, Ali; Burgin, Edward; Ces, Oscar; Willison, Keith R; Klug, David R

    2014-11-07

    Addressable droplet microarrays are potentially attractive as a way to achieve miniaturised, reduced volume, high sensitivity analyses without the need to fabricate microfluidic devices or small volume chambers. We report a practical method for producing oil-encapsulated addressable droplet microarrays which can be used for such analyses. To demonstrate their utility, we undertake a series of single cell analyses, to determine the variation in copy number of p53 proteins in cells of a human cancer cell line.

  7. Microarrays for Universal Detection and Identification of Phytoplasmas

    DEFF Research Database (Denmark)

    Nicolaisen, Mogens; Nyskjold, Henriette; Bertaccini, Assunta

    2013-01-01

    Detection and identification of phytoplasmas is a laborious process often involving nested PCR followed by restriction enzyme analysis and fine-resolution gel electrophoresis. To improve throughput, other methods are needed. Microarray technology offers a generic assay that can potentially detect...... and differentiate all types of phytoplasmas in one assay. The present protocol describes a microarray-based method for identification of phytoplasmas to 16Sr group level....

  8. Emerging use of gene expression microarrays in plant physiology.

    Science.gov (United States)

    Wullschleger, Stan D; Difazio, Stephen P

    2003-01-01

    Microarrays have become an important technology for the global analysis of gene expression in humans, animals, plants, and microbes. Implemented in the context of a well-designed experiment, cDNA and oligonucleotide arrays can provide highthroughput, simultaneous analysis of transcript abundance for hundreds, if not thousands, of genes. However, despite widespread acceptance, the use of microarrays as a tool to better understand processes of interest to the plant physiologist is still being explored. To help illustrate current uses of microarrays in the plant sciences, several case studies that we believe demonstrate the emerging application of gene expression arrays in plant physiology were selected from among the many posters and presentations at the 2003 Plant and Animal Genome XI Conference. Based on this survey, microarrays are being used to assess gene expression in plants exposed to the experimental manipulation of air temperature, soil water content and aluminium concentration in the root zone. Analysis often includes characterizing transcript profiles for multiple post-treatment sampling periods and categorizing genes with common patterns of response using hierarchical clustering techniques. In addition, microarrays are also providing insights into developmental changes in gene expression associated with fibre and root elongation in cotton and maize, respectively. Technical and analytical limitations of microarrays are discussed and projects attempting to advance areas of microarray design and data analysis are highlighted. Finally, although much work remains, we conclude that microarrays are a valuable tool for the plant physiologist interested in the characterization and identification of individual genes and gene families with potential application in the fields of agriculture, horticulture and forestry.

  9. Emerging Use of Gene Expression Microarrays in Plant Physiology

    Directory of Open Access Journals (Sweden)

    Stephen P. Difazio

    2006-04-01

    Full Text Available Microarrays have become an important technology for the global analysis of gene expression in humans, animals, plants, and microbes. Implemented in the context of a well-designed experiment, cDNA and oligonucleotide arrays can provide highthroughput, simultaneous analysis of transcript abundance for hundreds, if not thousands, of genes. However, despite widespread acceptance, the use of microarrays as a tool to better understand processes of interest to the plant physiologist is still being explored. To help illustrate current uses of microarrays in the plant sciences, several case studies that we believe demonstrate the emerging application of gene expression arrays in plant physiology were selected from among the many posters and presentations at the 2003 Plant and Animal Genome XI Conference. Based on this survey, microarrays are being used to assess gene expression in plants exposed to the experimental manipulation of air temperature, soil water content and aluminium concentration in the root zone. Analysis often includes characterizing transcript profiles for multiple post-treatment sampling periods and categorizing genes with common patterns of response using hierarchical clustering techniques. In addition, microarrays are also providing insights into developmental changes in gene expression associated with fibre and root elongation in cotton and maize, respectively. Technical and analytical limitations of microarrays are discussed and projects attempting to advance areas of microarray design and data analysis are highlighted. Finally, although much work remains, we conclude that microarrays are a valuable tool for the plant physiologist interested in the characterization and identification of individual genes and gene families with potential application in the fields of agriculture, horticulture and forestry.

  10. Plant-pathogen interactions: what microarray tells about it?

    Science.gov (United States)

    Lodha, T D; Basak, J

    2012-01-01

    Plant defense responses are mediated by elementary regulatory proteins that affect expression of thousands of genes. Over the last decade, microarray technology has played a key role in deciphering the underlying networks of gene regulation in plants that lead to a wide variety of defence responses. Microarray is an important tool to quantify and profile the expression of thousands of genes simultaneously, with two main aims: (1) gene discovery and (2) global expression profiling. Several microarray technologies are currently in use; most include a glass slide platform with spotted cDNA or oligonucleotides. Till date, microarray technology has been used in the identification of regulatory genes, end-point defence genes, to understand the signal transduction processes underlying disease resistance and its intimate links to other physiological pathways. Microarray technology can be used for in-depth, simultaneous profiling of host/pathogen genes as the disease progresses from infection to resistance/susceptibility at different developmental stages of the host, which can be done in different environments, for clearer understanding of the processes involved. A thorough knowledge of plant disease resistance using successful combination of microarray and other high throughput techniques, as well as biochemical, genetic, and cell biological experiments is needed for practical application to secure and stabilize yield of many crop plants. This review starts with a brief introduction to microarray technology, followed by the basics of plant-pathogen interaction, the use of DNA microarrays over the last decade to unravel the mysteries of plant-pathogen interaction, and ends with the future prospects of this technology.

  11. Broad Prize: Do the Successes Spread?

    Science.gov (United States)

    Samuels, Christina A.

    2011-01-01

    When the Broad Prize for Urban Education was created in 2002, billionaire philanthropist Eli Broad said he hoped the awards, in addition to rewarding high-performing school districts, would foster healthy competition; boost the prestige of urban education, long viewed as dysfunctional; and showcase best practices. Over the 10 years the prize has…

  12. 77 FR 50144 - Broad Stakeholder Survey

    Science.gov (United States)

    2012-08-20

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2012-0042] Broad Stakeholder Survey AGENCY... Information Collection Request: 1670-NEW. SUMMARY: The Department of Homeland Security (DHS), National... (Pub. L. 104-13, 44 U.S.C. Chapter 35). NPPD is soliciting comments concerning the Broad Stakeholder...

  13. 76 FR 34087 - Broad Stakeholder Survey

    Science.gov (United States)

    2011-06-10

    ... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0027] Broad Stakeholder Survey AGENCY... Information Collection Request: 1670-NEW. SUMMARY: The Department of Homeland Security (DHS), National... (Pub. L. 104-13, 44 U.S.C. Chapter 35). NPPD is soliciting comments concerning the Broad Stakeholder...

  14. Protein microarray: sensitive and effective immunodetection for drug residues

    Directory of Open Access Journals (Sweden)

    Zer Cindy

    2010-02-01

    Full Text Available Abstract Background Veterinary drugs such as clenbuterol (CL and sulfamethazine (SM2 are low molecular weight ( Results The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g than the ci-ELISA (0.1 ng/g for detection of CL residues. Conclusions The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.

  15. A comparative analysis of DNA barcode microarray feature size

    Directory of Open Access Journals (Sweden)

    Smith Andrew M

    2009-10-01

    Full Text Available Abstract Background Microarrays are an invaluable tool in many modern genomic studies. It is generally perceived that decreasing the size of microarray features leads to arrays with higher resolution (due to greater feature density, but this increase in resolution can compromise sensitivity. Results We demonstrate that barcode microarrays with smaller features are equally capable of detecting variation in DNA barcode intensity when compared to larger feature sizes within a specific microarray platform. The barcodes used in this study are the well-characterized set derived from the Yeast KnockOut (YKO collection used for screens of pooled yeast (Saccharomyces cerevisiae deletion mutants. We treated these pools with the glycosylation inhibitor tunicamycin as a test compound. Three generations of barcode microarrays at 30, 8 and 5 μm features sizes independently identified the primary target of tunicamycin to be ALG7. Conclusion We show that the data obtained with 5 μm feature size is of comparable quality to the 30 μm size and propose that further shrinking of features could yield barcode microarrays with equal or greater resolving power and, more importantly, higher density.

  16. Assessing Bacterial Interactions Using Carbohydrate-Based Microarrays

    Directory of Open Access Journals (Sweden)

    Andrea Flannery

    2015-12-01

    Full Text Available Carbohydrates play a crucial role in host-microorganism interactions and many host glycoconjugates are receptors or co-receptors for microbial binding. Host glycosylation varies with species and location in the body, and this contributes to species specificity and tropism of commensal and pathogenic bacteria. Additionally, bacterial glycosylation is often the first bacterial molecular species encountered and responded to by the host system. Accordingly, characterising and identifying the exact structures involved in these critical interactions is an important priority in deciphering microbial pathogenesis. Carbohydrate-based microarray platforms have been an underused tool for screening bacterial interactions with specific carbohydrate structures, but they are growing in popularity in recent years. In this review, we discuss carbohydrate-based microarrays that have been profiled with whole bacteria, recombinantly expressed adhesins or serum antibodies. Three main types of carbohydrate-based microarray platform are considered; (i conventional carbohydrate or glycan microarrays; (ii whole mucin microarrays; and (iii microarrays constructed from bacterial polysaccharides or their components. Determining the nature of the interactions between bacteria and host can help clarify the molecular mechanisms of carbohydrate-mediated interactions in microbial pathogenesis, infectious disease and host immune response and may lead to new strategies to boost therapeutic treatments.

  17. ArrayMining: a modular web-application for microarray analysis combining ensemble and consensus methods with cross-study normalization

    Directory of Open Access Journals (Sweden)

    Krasnogor Natalio

    2009-10-01

    Full Text Available Abstract Background Statistical analysis of DNA microarray data provides a valuable diagnostic tool for the investigation of genetic components of diseases. To take advantage of the multitude of available data sets and analysis methods, it is desirable to combine both different algorithms and data from different studies. Applying ensemble learning, consensus clustering and cross-study normalization methods for this purpose in an almost fully automated process and linking different analysis modules together under a single interface would simplify many microarray analysis tasks. Results We present ArrayMining.net, a web-application for microarray analysis that provides easy access to a wide choice of feature selection, clustering, prediction, gene set analysis and cross-study normalization methods. In contrast to other microarray-related web-tools, multiple algorithms and data sets for an analysis task can be combined using ensemble feature selection, ensemble prediction, consensus clustering and cross-platform data integration. By interlinking different analysis tools in a modular fashion, new exploratory routes become available, e.g. ensemble sample classification using features obtained from a gene set analysis and data from multiple studies. The analysis is further simplified by automatic parameter selection mechanisms and linkage to web tools and databases for functional annotation and literature mining. Conclusion ArrayMining.net is a free web-application for microarray analysis combining a broad choice of algorithms based on ensemble and consensus methods, using automatic parameter selection and integration with annotation databases.

  18. Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

    Directory of Open Access Journals (Sweden)

    Andrzej Chruscinski

    Full Text Available Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen. Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient

  19. Cross-platform comparison of microarray data using order restricted inference

    Science.gov (United States)

    Klinglmueller, Florian; Tuechler, Thomas; Posch, Martin

    2013-01-01

    Motivation Titration experiments measuring the gene expression from two different tissues, along with total RNA mixtures of the pure samples, are frequently used for quality evaluation of microarray technologies. Such a design implies that the true mRNA expression of each gene, is either constant or follows a monotonic trend between the mixtures, applying itself to the use of order restricted inference procedures. Exploiting only the postulated monotonicity of titration designs, we propose three statistical analysis methods for the validation of high-throughput genetic data and corresponding preprocessing techniques. Results Our methods allow for inference of accuracy, repeatability and cross-platform agreement, with minimal required assumptions regarding the underlying data generating process. Therefore, they are readily applicable to all sorts of genetic high-throughput data independent of the degree of preprocessing. An application to the EMERALD dataset was used to demonstrate how our methods provide a rich spectrum of easily interpretable quality metrics and allow the comparison of different microarray technologies and normalization methods. The results are on par with previous work, but provide additional new insights that cast doubt on the utility of popular preprocessing techniques, specifically concerning the EMERALD projects dataset. Availability All datasets are available on EBI’s ArrayExpress web site (http://www.ebi.ac.uk/microarray-as/ae/) under accession numbers E-TABM-536, E-TABM-554 and E-TABM-555. Source code implemented in C and R is available at: http://statistics.msi.meduniwien.ac.at/float/cross_platform/. Methods for testing and variance decomposition have been made available in the R-package orQA, which can be downloaded and installed from CRAN http://cran.r-project.org. PMID:21317143

  20. Segment and fit thresholding: a new method for image analysis applied to microarray and immunofluorescence data.

    Science.gov (United States)

    Ensink, Elliot; Sinha, Jessica; Sinha, Arkadeep; Tang, Huiyuan; Calderone, Heather M; Hostetter, Galen; Winter, Jordan; Cherba, David; Brand, Randall E; Allen, Peter J; Sempere, Lorenzo F; Haab, Brian B

    2015-10-06

    Experiments involving the high-throughput quantification of image data require algorithms for automation. A challenge in the development of such algorithms is to properly interpret signals over a broad range of image characteristics, without the need for manual adjustment of parameters. Here we present a new approach for locating signals in image data, called Segment and Fit Thresholding (SFT). The method assesses statistical characteristics of small segments of the image and determines the best-fit trends between the statistics. Based on the relationships, SFT identifies segments belonging to background regions; analyzes the background to determine optimal thresholds; and analyzes all segments to identify signal pixels. We optimized the initial settings for locating background and signal in antibody microarray and immunofluorescence data and found that SFT performed well over multiple, diverse image characteristics without readjustment of settings. When used for the automated analysis of multicolor, tissue-microarray images, SFT correctly found the overlap of markers with known subcellular localization, and it performed better than a fixed threshold and Otsu's method for selected images. SFT promises to advance the goal of full automation in image analysis.

  1. Development of oligonucleotide microarrays for simultaneous multi-species identification of Phellinus tree-pathogenic fungi.

    Science.gov (United States)

    Tzean, Yuh; Shu, Po-Yao; Liou, Ruey-Fen; Tzean, Shean-Shong

    2016-03-01

    Polyporoid Phellinus fungi are ubiquitously present in the environment and play an important role in shaping forest ecology. Several species of Phellinus are notorious pathogens that can affect a broad variety of tree species in forest, plantation, orchard and urban habitats; however, current detection methods are overly complex and lack the sensitivity required to identify these pathogens at the species level in a timely fashion for effective infestation control. Here, we describe eight oligonucleotide microarray platforms for the simultaneous and specific detection of 17 important Phellinus species, using probes generated from the internal transcribed spacer regions unique to each species. The sensitivity, robustness and efficiency of this Phellinus microarray system was subsequently confirmed against template DNA from two key Phellinus species, as well as field samples collected from tree roots, trunks and surrounding soil. This system can provide early, specific and convenient detection of Phellinus species for forestry, arboriculture and quarantine inspection, and could potentially help to mitigate the environmental and economic impact of Phellinus-related diseases. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  2. Spectrum 101: An Introduction to Spectrum Management

    Science.gov (United States)

    2004-03-01

    produces a Joint Restricted Frequency List (JRFL). The JFRL consolidates and classifies the spectrum uses that are most critical to operations and to...Management Office JRFL Joint Restricted Frequency List JSC Joint Spectrum Center JSIR Joint Spectrum Interference Resolution JSME Joint Spectrum...Multifunctional Information Distribution System MILSATCOM Military Satellite Communications MOA Memorandum of Agreement MRFL Master Radio Frequency

  3. Expression microarray reproducibility is improved by optimising purification steps in RNA amplification and labelling

    Directory of Open Access Journals (Sweden)

    Brenton James D

    2004-01-01

    Full Text Available Abstract Background Expression microarrays have evolved into a powerful tool with great potential for clinical application and therefore reliability of data is essential. RNA amplification is used when the amount of starting material is scarce, as is frequently the case with clinical samples. Purification steps are critical in RNA amplification and labelling protocols, and there is a lack of sufficient data to validate and optimise the process. Results Here the purification steps involved in the protocol for indirect labelling of amplified RNA are evaluated and the experimentally determined best method for each step with respect to yield, purity, size distribution of the transcripts, and dye coupling is used to generate targets tested in replicate hybridisations. DNase treatment of diluted total RNA samples followed by phenol extraction is the optimal way to remove genomic DNA contamination. Purification of double-stranded cDNA is best achieved by phenol extraction followed by isopropanol precipitation at room temperature. Extraction with guanidinium-phenol and Lithium Chloride precipitation are the optimal methods for purification of amplified RNA and labelled aRNA respectively. Conclusion This protocol provides targets that generate highly reproducible microarray data with good representation of transcripts across the size spectrum and a coefficient of repeatability significantly better than that reported previously.

  4. Advanced spot quality analysis in two-colour microarray experiments

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    Vetter Guillaume

    2008-09-01

    Full Text Available Abstract Background Image analysis of microarrays and, in particular, spot quantification and spot quality control, is one of the most important steps in statistical analysis of microarray data. Recent methods of spot quality control are still in early age of development, often leading to underestimation of true positive microarray features and, consequently, to loss of important biological information. Therefore, improving and standardizing the statistical approaches of spot quality control are essential to facilitate the overall analysis of microarray data and subsequent extraction of biological information. Findings We evaluated the performance of two image analysis packages MAIA and GenePix (GP using two complementary experimental approaches with a focus on the statistical analysis of spot quality factors. First, we developed control microarrays with a priori known fluorescence ratios to verify the accuracy and precision of the ratio estimation of signal intensities. Next, we developed advanced semi-automatic protocols of spot quality evaluation in MAIA and GP and compared their performance with available facilities of spot quantitative filtering in GP. We evaluated these algorithms for standardised spot quality analysis in a whole-genome microarray experiment assessing well-characterised transcriptional modifications induced by the transcription regulator SNAI1. Using a set of RT-PCR or qRT-PCR validated microarray data, we found that the semi-automatic protocol of spot quality control we developed with MAIA allowed recovering approximately 13% more spots and 38% more differentially expressed genes (at FDR = 5% than GP with default spot filtering conditions. Conclusion Careful control of spot quality characteristics with advanced spot quality evaluation can significantly increase the amount of confident and accurate data resulting in more meaningful biological conclusions.

  5. Flexible hemispheric microarrays of highly pressure-sensitive sensors based on breath figure method.

    Science.gov (United States)

    Wang, Zhihui; Zhang, Ling; Liu, Jin; Jiang, Hao; Li, Chunzhong

    2018-05-30

    Recently, flexible pressure sensors featuring high sensitivity, broad sensing range and real-time detection have aroused great attention owing to their crucial role in the development of artificial intelligent devices and healthcare systems. Herein, highly sensitive pressure sensors based on hemisphere-microarray flexible substrates are fabricated via inversely templating honeycomb structures deriving from a facile and static breath figure process. The interlocked and subtle microstructures greatly improve the sensing characteristics and compressibility of the as-prepared pressure sensor, endowing it a sensitivity as high as 196 kPa-1 and a wide pressure sensing range (0-100 kPa), as well as other superior performance, including a lower detection limit of 0.5 Pa, fast response time (10 000 cycles). Based on the outstanding sensing performance, the potential capability of our pressure sensor in capturing physiological information and recognizing speech signals has been demonstrated, indicating promising application in wearable and intelligent electronics.

  6. A synthetic glycan microarray enables epitope mapping of plant cell wall glycan-directed antibodies

    DEFF Research Database (Denmark)

    Ruprecht, Colin; Bartetzko, Max P; Senf, Deborah

    2017-01-01

    In the last three decades, more than 200 monoclonal antibodies have been raised against most classes of plant cell wall polysaccharides by different laboratories world-wide. These antibodies are widely used to identify differences in plant cell wall components in mutants, organ and tissue types......, and developmental stages. Despite their importance and broad use, the precise binding epitope for only a few of these antibodies has been determined. Here, we use a plant glycan microarray equipped with 88 synthetic oligosaccharides to comprehensively map the epitopes of plant cell wall glycan-directed antibodies....... Our results reveal the binding epitopes for 78 arabinogalactan-, rhamnogalacturonan-, xylan-, and xyloglucan-directed antibodies. We demonstrate that, with knowledge of the exact epitopes recognized by individual antibodies, specific glycosyl hydrolases can be implemented into immunological cell wall...

  7. Broad-band near-field ground motion simulations in 3-dimensional scattering media

    KAUST Repository

    Imperatori, W.; Mai, Paul Martin

    2012-01-01

    examine scattering phenomena, related to the loss of radiation pattern and the directivity breakdown. We first simulate broad-band ground motions for a point-source characterized by a classic ω2 spectrum model. Fault finiteness is then introduced by means

  8. Significance analysis of lexical bias in microarray data

    Directory of Open Access Journals (Sweden)

    Falkow Stanley

    2003-04-01

    Full Text Available Abstract Background Genes that are determined to be significantly differentially regulated in microarray analyses often appear to have functional commonalities, such as being components of the same biochemical pathway. This results in certain words being under- or overrepresented in the list of genes. Distinguishing between biologically meaningful trends and artifacts of annotation and analysis procedures is of the utmost importance, as only true biological trends are of interest for further experimentation. A number of sophisticated methods for identification of significant lexical trends are currently available, but these methods are generally too cumbersome for practical use by most microarray users. Results We have developed a tool, LACK, for calculating the statistical significance of apparent lexical bias in microarray datasets. The frequency of a user-specified list of search terms in a list of genes which are differentially regulated is assessed for statistical significance by comparison to randomly generated datasets. The simplicity of the input files and user interface targets the average microarray user who wishes to have a statistical measure of apparent lexical trends in analyzed datasets without the need for bioinformatics skills. The software is available as Perl source or a Windows executable. Conclusion We have used LACK in our laboratory to generate biological hypotheses based on our microarray data. We demonstrate the program's utility using an example in which we confirm significant upregulation of SPI-2 pathogenicity island of Salmonella enterica serovar Typhimurium by the cation chelator dipyridyl.

  9. A Fisheye Viewer for microarray-based gene expression data.

    Science.gov (United States)

    Wu, Min; Thao, Cheng; Mu, Xiangming; Munson, Ethan V

    2006-10-13

    Microarray has been widely used to measure the relative amounts of every mRNA transcript from the genome in a single scan. Biologists have been accustomed to reading their experimental data directly from tables. However, microarray data are quite large and are stored in a series of files in a machine-readable format, so direct reading of the full data set is not feasible. The challenge is to design a user interface that allows biologists to usefully view large tables of raw microarray-based gene expression data. This paper presents one such interface--an electronic table (E-table) that uses fisheye distortion technology. The Fisheye Viewer for microarray-based gene expression data has been successfully developed to view MIAME data stored in the MAGE-ML format. The viewer can be downloaded from the project web site http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in Java so that it could run on multiple platforms. We implemented the E-table by adapting JTable, a default table implementation in the Java Swing user interface library. Fisheye views use variable magnification to balance magnification for easy viewing and compression for maximizing the amount of data on the screen. This Fisheye Viewer is a lightweight but useful tool for biologists to quickly overview the raw microarray-based gene expression data in an E-table.

  10. A fisheye viewer for microarray-based gene expression data

    Directory of Open Access Journals (Sweden)

    Munson Ethan V

    2006-10-01

    Full Text Available Abstract Background Microarray has been widely used to measure the relative amounts of every mRNA transcript from the genome in a single scan. Biologists have been accustomed to reading their experimental data directly from tables. However, microarray data are quite large and are stored in a series of files in a machine-readable format, so direct reading of the full data set is not feasible. The challenge is to design a user interface that allows biologists to usefully view large tables of raw microarray-based gene expression data. This paper presents one such interface – an electronic table (E-table that uses fisheye distortion technology. Results The Fisheye Viewer for microarray-based gene expression data has been successfully developed to view MIAME data stored in the MAGE-ML format. The viewer can be downloaded from the project web site http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in Java so that it could run on multiple platforms. We implemented the E-table by adapting JTable, a default table implementation in the Java Swing user interface library. Fisheye views use variable magnification to balance magnification for easy viewing and compression for maximizing the amount of data on the screen. Conclusion This Fisheye Viewer is a lightweight but useful tool for biologists to quickly overview the raw microarray-based gene expression data in an E-table.

  11. AN IMPROVED FUZZY CLUSTERING ALGORITHM FOR MICROARRAY IMAGE SPOTS SEGMENTATION

    Directory of Open Access Journals (Sweden)

    V.G. Biju

    2015-11-01

    Full Text Available An automatic cDNA microarray image processing using an improved fuzzy clustering algorithm is presented in this paper. The spot segmentation algorithm proposed uses the gridding technique developed by the authors earlier, for finding the co-ordinates of each spot in an image. Automatic cropping of spots from microarray image is done using these co-ordinates. The present paper proposes an improved fuzzy clustering algorithm Possibility fuzzy local information c means (PFLICM to segment the spot foreground (FG from background (BG. The PFLICM improves fuzzy local information c means (FLICM algorithm by incorporating typicality of a pixel along with gray level information and local spatial information. The performance of the algorithm is validated using a set of simulated cDNA microarray images added with different levels of AWGN noise. The strength of the algorithm is tested by computing the parameters such as the Segmentation matching factor (SMF, Probability of error (pe, Discrepancy distance (D and Normal mean square error (NMSE. SMF value obtained for PFLICM algorithm shows an improvement of 0.9 % and 0.7 % for high noise and low noise microarray images respectively compared to FLICM algorithm. The PFLICM algorithm is also applied on real microarray images and gene expression values are computed.

  12. Advanced Data Mining of Leukemia Cells Micro-Arrays

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    Richard S. Segall

    2009-12-01

    Full Text Available This paper provides continuation and extensions of previous research by Segall and Pierce (2009a that discussed data mining for micro-array databases of Leukemia cells for primarily self-organized maps (SOM. As Segall and Pierce (2009a and Segall and Pierce (2009b the results of applying data mining are shown and discussed for the data categories of microarray databases of HL60, Jurkat, NB4 and U937 Leukemia cells that are also described in this article. First, a background section is provided on the work of others pertaining to the applications of data mining to micro-array databases of Leukemia cells and micro-array databases in general. As noted in predecessor article by Segall and Pierce (2009a, micro-array databases are one of the most popular functional genomics tools in use today. This research in this paper is intended to use advanced data mining technologies for better interpretations and knowledge discovery as generated by the patterns of gene expressions of HL60, Jurkat, NB4 and U937 Leukemia cells. The advanced data mining performed entailed using other data mining tools such as cubic clustering criterion, variable importance rankings, decision trees, and more detailed examinations of data mining statistics and study of other self-organized maps (SOM clustering regions of workspace as generated by SAS Enterprise Miner version 4. Conclusions and future directions of the research are also presented.

  13. Spot detection and image segmentation in DNA microarray data.

    Science.gov (United States)

    Qin, Li; Rueda, Luis; Ali, Adnan; Ngom, Alioune

    2005-01-01

    Following the invention of microarrays in 1994, the development and applications of this technology have grown exponentially. The numerous applications of microarray technology include clinical diagnosis and treatment, drug design and discovery, tumour detection, and environmental health research. One of the key issues in the experimental approaches utilising microarrays is to extract quantitative information from the spots, which represent genes in a given experiment. For this process, the initial stages are important and they influence future steps in the analysis. Identifying the spots and separating the background from the foreground is a fundamental problem in DNA microarray data analysis. In this review, we present an overview of state-of-the-art methods for microarray image segmentation. We discuss the foundations of the circle-shaped approach, adaptive shape segmentation, histogram-based methods and the recently introduced clustering-based techniques. We analytically show that clustering-based techniques are equivalent to the one-dimensional, standard k-means clustering algorithm that utilises the Euclidean distance.

  14. Probe Selection for DNA Microarrays using OligoWiz

    DEFF Research Database (Denmark)

    Wernersson, Rasmus; Juncker, Agnieszka; Nielsen, Henrik Bjørn

    2007-01-01

    Nucleotide abundance measurements using DNA microarray technology are possible only if appropriate probes complementary to the target nucleotides can be identified. Here we present a protocol for selecting DNA probes for microarrays using the OligoWiz application. OligoWiz is a client-server appl......Nucleotide abundance measurements using DNA microarray technology are possible only if appropriate probes complementary to the target nucleotides can be identified. Here we present a protocol for selecting DNA probes for microarrays using the OligoWiz application. OligoWiz is a client......-server application that offers a detailed graphical interface and real-time user interaction on the client side, and massive computer power and a large collection of species databases (400, summer 2007) on the server side. Probes are selected according to five weighted scores: cross-hybridization, deltaT(m), folding...... computer skills and can be executed from any Internet-connected computer. The probe selection procedure for a standard microarray design targeting all yeast transcripts can be completed in 1 h....

  15. Microarray-based screening of heat shock protein inhibitors.

    Science.gov (United States)

    Schax, Emilia; Walter, Johanna-Gabriela; Märzhäuser, Helene; Stahl, Frank; Scheper, Thomas; Agard, David A; Eichner, Simone; Kirschning, Andreas; Zeilinger, Carsten

    2014-06-20

    Based on the importance of heat shock proteins (HSPs) in diseases such as cancer, Alzheimer's disease or malaria, inhibitors of these chaperons are needed. Today's state-of-the-art techniques to identify HSP inhibitors are performed in microplate format, requiring large amounts of proteins and potential inhibitors. In contrast, we have developed a miniaturized protein microarray-based assay to identify novel inhibitors, allowing analysis with 300 pmol of protein. The assay is based on competitive binding of fluorescence-labeled ATP and potential inhibitors to the ATP-binding site of HSP. Therefore, the developed microarray enables the parallel analysis of different ATP-binding proteins on a single microarray. We have demonstrated the possibility of multiplexing by immobilizing full-length human HSP90α and HtpG of Helicobacter pylori on microarrays. Fluorescence-labeled ATP was competed by novel geldanamycin/reblastatin derivatives with IC50 values in the range of 0.5 nM to 4 μM and Z(*)-factors between 0.60 and 0.96. Our results demonstrate the potential of a target-oriented multiplexed protein microarray to identify novel inhibitors for different members of the HSP90 family. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Atividade antimicrobiana in vitro da cefpiroma em comparação com outros beta-lactâmicos de amplo espectro contra 804 amostras clínicas de nove hospitais brasileiros Antimicrobial activity of Cefpirome compared to other broad-spectrum Beta-Lactam drugs against 804 clinical isolates from 9 Brazilian hospitals

    Directory of Open Access Journals (Sweden)

    H.S. Sader

    1998-12-01

    imipenem apresentou atividade um pouco superior. CONCLUSÃO: Os resultados desse estudo sugerem que, no Brasil, a cefpiroma apresenta espectro de ação superior ao das CTGs contra bactérias gram-negativas (Enterobacteriaceae e não-fermentadares e gram-positivas e semelhante ao do imipenem contra algumas espécies de enterobactérias e contra P. aeruginosa.OBJECTIVE: To evaluate the in vitro activity of the fourth-generation cephalosporin cefpirome in comparison to that of ceftazidime, ceftriaxone, cefotaxime and imipenem in a multicenter study involving nine hospitals from six cities (four States. MATERIAL AND METHOD: A total of 804 isolates from patients hospitalized in either intensive care units or Oncology/Hematology units was evaluated. The isolates were collected between June and November of 1995, i.e. before cefpirome became commercially available in Brazil, and susceptibility tested by broth microdilution following the NCCLS procedures. All isolates resistant to cefpirome were retested by E-test. RESULTS: Against Enterobacteriaceae (n=344, cefpirome demonstrated an activity 2 to 32-fold higher than that of the third-generation cephalosporins (TGCs and similar to that of imipenem. The percentages of Enterobacteriaceae susceptible were: 88%, 69% and 96% for cefpirome, TGCs and imipenem, respectively. The cefpirome spectrum was greater or equal than that of imipenem against Citrobacter freundii, Enterobacter aerogenes, Morganella morganii and Serratia marcescens. Against Acinetobacter sp. (n=77, cefpirome was slightly more active than ceftazidime; however, the percentages of isolates resistant to these compounds were high (84% and 88%, respectively. The activities of cefpirome, ceftazidime and imipenem were very similar against P. aeruginosa isolates (n=128, with MIC50(mg/ml/percent susceptible of 8/59%, 8/62% and 4/62% respectively. Against aerobic gram-positive bacteria, the cefpirome activity was 4 to 16-fold higher than that of TGCs but 2 to 8-fold lower than

  17. DNA microarray data and contextual analysis of correlation graphs

    Directory of Open Access Journals (Sweden)

    Hingamp Pascal

    2003-04-01

    Full Text Available Abstract Background DNA microarrays are used to produce large sets of expression measurements from which specific biological information is sought. Their analysis requires efficient and reliable algorithms for dimensional reduction, classification and annotation. Results We study networks of co-expressed genes obtained from DNA microarray experiments. The mathematical concept of curvature on graphs is used to group genes or samples into clusters to which relevant gene or sample annotations are automatically assigned. Application to publicly available yeast and human lymphoma data demonstrates the reliability of the method in spite of its simplicity, especially with respect to the small number of parameters involved. Conclusions We provide a method for automatically determining relevant gene clusters among the many genes monitored with microarrays. The automatic annotations and the graphical interface improve the readability of the data. A C++ implementation, called Trixy, is available from http://tagc.univ-mrs.fr/bioinformatics/trixy.html.

  18. MICROARRAY IMAGE GRIDDING USING GRID LINE REFINEMENT TECHNIQUE

    Directory of Open Access Journals (Sweden)

    V.G. Biju

    2015-05-01

    Full Text Available An important stage in microarray image analysis is gridding. Microarray image gridding is done to locate sub arrays in a microarray image and find co-ordinates of spots within each sub array. For accurate identification of spots, most of the proposed gridding methods require human intervention. In this paper a fully automatic gridding method which enhances spot intensity in the preprocessing step as per a histogram based threshold method is used. The gridding step finds co-ordinates of spots from horizontal and vertical profile of the image. To correct errors due to the grid line placement, a grid line refinement technique is proposed. The algorithm is applied on different image databases and results are compared based on spot detection accuracy and time. An average spot detection accuracy of 95.06% depicts the proposed method’s flexibility and accuracy in finding the spot co-ordinates for different database images.

  19. A Versatile Microarray Platform for Capturing Rare Cells

    Science.gov (United States)

    Brinkmann, Falko; Hirtz, Michael; Haller, Anna; Gorges, Tobias M.; Vellekoop, Michael J.; Riethdorf, Sabine; Müller, Volkmar; Pantel, Klaus; Fuchs, Harald

    2015-10-01

    Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs) - about one cell in a billion normal blood cells. After incubation with an antibody cocktail, targeted cells are extracted on a microarray in a microfluidic chip. The accessibility of our platform allows for subsequent recovery of targets for further analysis. The microarray facilitates exclusion of false positive capture events by co-localization allowing for detection without fluorescent labelling. Analyzing blood samples from cancer patients with our platform reached and partly outreached gold standard performance, demonstrating feasibility for clinical application. Clinical researchers free choice of antibody cocktail without need for altered chip manufacturing or incubation protocol, allows virtual arbitrary targeting of capture species and therefore wide spread applications in biomedical sciences.

  20. AMDA: an R package for the automated microarray data analysis

    Directory of Open Access Journals (Sweden)

    Foti Maria

    2006-07-01

    Full Text Available Abstract Background Microarrays are routinely used to assess mRNA transcript levels on a genome-wide scale. Large amount of microarray datasets are now available in several databases, and new experiments are constantly being performed. In spite of this fact, few and limited tools exist for quickly and easily analyzing the results. Microarray analysis can be challenging for researchers without the necessary training and it can be time-consuming for service providers with many users. Results To address these problems we have developed an automated microarray data analysis (AMDA software, which provides scientists with an easy and integrated system for the analysis of Affymetrix microarray experiments. AMDA is free and it is available as an R package. It is based on the Bioconductor project that provides a number of powerful bioinformatics and microarray analysis tools. This automated pipeline integrates different functions available in the R and Bioconductor projects with newly developed functions. AMDA covers all of the steps, performing a full data analysis, including image analysis, quality controls, normalization, selection of differentially expressed genes, clustering, correspondence analysis and functional evaluation. Finally a LaTEX document is dynamically generated depending on the performed analysis steps. The generated report contains comments and analysis results as well as the references to several files for a deeper investigation. Conclusion AMDA is freely available as an R package under the GPL license. The package as well as an example analysis report can be downloaded in the Services/Bioinformatics section of the Genopolis http://www.genopolis.it/

  1. Streetlights attract a broad array of beetle species

    Directory of Open Access Journals (Sweden)

    Bruno Augusto Souza de Medeiros

    2017-01-01

    Full Text Available Light pollution on ecosystems is a growing concern, and knowledge about the effects of outdoor lighting on organisms is crucial to understand and mitigate impacts. Here we build up on a previous study to characterize the diversity of all beetles attracted to different commonly used streetlight set ups. We find that lights attract beetles from a broad taxonomic and ecological spectrum. Lights that attract a large number of insect individuals draw an equally high number of insect species. While there is some evidence for heterogeneity in the preference of beetle species to different kinds of light, all species are more attracted to some light radiating ultraviolet. The functional basis of this heterogeneity, however, is not clear. Our results highlight that control of ultraviolet radiation in public lighting is important to reduce the number and diversity of insects attracted to lights. Keywords: Lighting, Coleoptera, Light pollution, Insects, Ultraviolet

  2. Spectral properties of a broad-area diode laser with off-axis external-cavity feedback

    DEFF Research Database (Denmark)

    Chi, Mingjun; Petersen, Paul Michael

    2013-01-01

    Spectral properties, both the optical spectrum and the intensity noise spectrum, of a broad-area diode laser with off-axis external-cavity feedback are presented. We show that the optical spectrum of the diode laser system is shifted to longer wavelengths due to the external-cavity feedback....... The intensity noise spectrum of the diode laser shows that the intensity noise is increased strongly by the external-cavity feedback. External-cavity modes are excited in the external cavity even in the off-axis configuration. The peak spacing of the intensity noise spectrum shows that single roundtrip external......-cavity modes are excited. We believe that the four-wave mixing process in the broad-area diode laser is responsible for the establishment of the external-cavity mode....

  3. Label and Label-Free Detection Techniques for Protein Microarrays

    Directory of Open Access Journals (Sweden)

    Amir Syahir

    2015-04-01

    Full Text Available Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano‑biological events.

  4. Advanced Data Mining of Leukemia Cells Micro-Arrays

    OpenAIRE

    Richard S. Segall; Ryan M. Pierce

    2009-01-01

    This paper provides continuation and extensions of previous research by Segall and Pierce (2009a) that discussed data mining for micro-array databases of Leukemia cells for primarily self-organized maps (SOM). As Segall and Pierce (2009a) and Segall and Pierce (2009b) the results of applying data mining are shown and discussed for the data categories of microarray databases of HL60, Jurkat, NB4 and U937 Leukemia cells that are also described in this article. First, a background section is pro...

  5. Fabrication of Biomolecule Microarrays for Cell Immobilization Using Automated Microcontact Printing.

    Science.gov (United States)

    Foncy, Julie; Estève, Aurore; Degache, Amélie; Colin, Camille; Cau, Jean Christophe; Malaquin, Laurent; Vieu, Christophe; Trévisiol, Emmanuelle

    2018-01-01

    Biomolecule microarrays are generally produced by conventional microarrayer, i.e., by contact or inkjet printing. Microcontact printing represents an alternative way of deposition of biomolecules on solid supports but even if various biomolecules have been successfully microcontact printed, the production of biomolecule microarrays in routine by microcontact printing remains a challenging task and needs an effective, fast, robust, and low-cost automation process. Here, we describe the production of biomolecule microarrays composed of extracellular matrix protein for the fabrication of cell microarrays by using an automated microcontact printing device. Large scale cell microarrays can be reproducibly obtained by this method.

  6. The Unusual Moessbauer Spectrum of Beryl

    International Nuclear Information System (INIS)

    Viana, R. R.; Costa, G. M. da; Grave, E. de; Evangelista, H. J.; Stern, W. B.

    2001-01-01

    The Moessbauer spectra of several aquamarine samples have been obtained in the temperature range of 4.2-500 K. A common feature observed in all room-temperature spectra is the presence of an asymmetric Fe 2+ doublet (ΔE Q ∼2.7 mm/s, δ∼1.1 mm/s), with a very broad low-velocity peak. This asymmetry is not caused by preferred orientation since the spectrum collected under the magic angle did not show any difference in the line intensities, nor is it caused by the superposition of a Fe 3+ doublet. At 4.2 K the spectrum of a deep-blue beryl could be well fitted with three symmetrical doublets, with the major Fe 2+ doublet accounting for 87% of the total spectral area. At 14 K the symmetry remains, but at 30 K the low-velocity peak is again broad. Surprisingly, the spectrum at 500 K also shows a broad, but symmetrical doublet, with a clear splitting of the lines indicating the presence of at least two Fe 2+ components. The room-temperature spectrum obtained after the 500 K run shows the same features as before the heating. A meaningful fit for the room-temperature spectrum, as well as an explanation for the temperature dependence of the Moessbauer spectra, are discussed

  7. Sensitivity and fidelity of DNA microarray improved with integration of Amplified Differential Gene Expression (ADGE

    Directory of Open Access Journals (Sweden)

    Ile Kristina E

    2003-07-01

    Full Text Available Abstract Background The ADGE technique is a method designed to magnify the ratios of gene expression before detection. It improves the detection sensitivity to small change of gene expression and requires small amount of starting material. However, the throughput of ADGE is low. We integrated ADGE with DNA microarray (ADGE microarray and compared it with regular microarray. Results When ADGE was integrated with DNA microarray, a quantitative relationship of a power function between detected and input ratios was found. Because of ratio magnification, ADGE microarray was better able to detect small changes in gene expression in a drug resistant model cell line system. The PCR amplification of templates and efficient labeling reduced the requirement of starting material to as little as 125 ng of total RNA for one slide hybridization and enhanced the signal intensity. Integration of ratio magnification, template amplification and efficient labeling in ADGE microarray reduced artifacts in microarray data and improved detection fidelity. The results of ADGE microarray were less variable and more reproducible than those of regular microarray. A gene expression profile generated with ADGE microarray characterized the drug resistant phenotype, particularly with reference to glutathione, proliferation and kinase pathways. Conclusion ADGE microarray magnified the ratios of differential gene expression in a power function, improved the detection sensitivity and fidelity and reduced the requirement for starting material while maintaining high throughput. ADGE microarray generated a more informative expression pattern than regular microarray.

  8. Cross-spectrum symbol synchronization

    Science.gov (United States)

    Mccallister, R. D.; Simon, M. K.

    1981-01-01

    A popular method of symbol synchronization exploits one aspect of generalized harmonic analysis, normally referred to as the cross-spectrum. Utilizing nonlinear techniques, the input symbol energy is effectively concentrated onto multiples of the symbol clock frequency, facilitating application of conventional phase lock synchronization techniques. A general treatment of the cross-spectrum technique is developed and shown to be applicable across a broad class of symbol modulation formats. An important specific symbol synchronization application is then treated, focusing the general development to provide both insight and quantitative measure of the performance impact associated with variation in these key synchronization parameters: symbol modulation format, symbol transition probability, symbol energy to noise density ratio, and symbol rate to filter bandwidth ratio.

  9. Spectrum of PG 1700 + 518

    International Nuclear Information System (INIS)

    Wampler, E.J.

    1985-01-01

    Observations of PG 1700 + 518 show that this bright quasar has a very rich Fe II emission spectrum. In addition, there is a broad dip in spectral intensity to the blue of Mg II lambda 2800. It is argued that this dip is due to detached Mg II lambda 2800 absorption rather than to a gap between Fe II emission lines. Fe II transitions from 8 eV levels seem to be present in the spectrum. Also present are weak multiplets with the same upper levels as the strong optical multiplets 27 and 42. These observational data support the belief that the resonance lines of Fe II are optically thick and that the 8 eV levels are populated, presumably by fluorescence. Forbidden lines are very weak or absent in PG 1700 + 518. 11 references

  10. The tissue microarray OWL schema: An open-source tool for sharing tissue microarray data

    Directory of Open Access Journals (Sweden)

    Hyunseok P Kang

    2010-01-01

    Full Text Available Background: Tissue microarrays (TMAs are enormously useful tools for translational research, but incompatibilities in database systems between various researchers and institutions prevent the efficient sharing of data that could help realize their full potential. Resource Description Framework (RDF provides a flexible method to represent knowledge in triples, which take the form Subject- Predicate-Object. All data resources are described using Uniform Resource Identifiers (URIs, which are global in scope. We present an OWL (Web Ontology Language schema that expands upon the TMA data exchange specification to address this issue and assist in data sharing and integration. Methods: A minimal OWL schema was designed containing only concepts specific to TMA experiments. More general data elements were incorporated from predefined ontologies such as the NCI thesaurus. URIs were assigned using the Linked Data format. Results: We present examples of files utilizing the schema and conversion of XML data (similar to the TMA DES to OWL. Conclusion: By utilizing predefined ontologies and global unique identifiers, this OWL schema provides a solution to the limitations of XML, which represents concepts defined in a localized setting. This will help increase the utilization of tissue resources, facilitating collaborative translational research efforts.

  11. Spectrum of pediatric neuromyelitis optica.

    Science.gov (United States)

    Lotze, Timothy E; Northrop, Jennifer L; Hutton, George J; Ross, Benjamin; Schiffman, Jade S; Hunter, Jill V

    2008-11-01

    Our goal was to describe the spectrum of clinical phenotypes, laboratory and imaging features, and treatment in pediatric patients with neuromyelitis optica. The study consisted of a retrospective chart review of patients followed in a pediatric multiple sclerosis center with a diagnosis of neuromyelitis optica spectrum disorder. Nine patients with neuromyelitis optica spectrum disorders were included, all of whom were female. There were 4 black children, 2 Latin American children, 2 white children, and 1 child of mixed Latin American/white heritage. Median age at initial attack was 14 years (range: 1.9-16 years). Median disease duration was 4 years (range: 0.6-9 years). Tests for neuromyelitis optica immunoglobulin G were positive for 7 patients. Eight patients had transverse myelitis and optic neuritis, and 1 patient had longitudinally extensive transverse myelitis without optic neuritis but had a positive neuromyelitis optica immunoglobulin G antibody titer. Cerebral involvement on MRI was found in all subjects, 5 of whom were symptomatic with encephalopathy, seizures, hemiparesis, aphasia, vomiting, or hiccups. Immunosuppressive therapy reduced attack frequency and progression of disability. Pediatric neuromyelitis optica has a diverse clinical presentation and may be difficult to distinguish from multiple sclerosis in the early stages of the disease. The recognition of the broad spectrum of this disease to include signs and symptoms of brain involvement is aided by the availability of a serum biomarker: neuromyelitis optica immunoglobulin G. Early diagnosis and immunosuppresive treatment may help to slow the accumulation of severe disability.

  12. Evidence for a Broad Autism Phenotype

    NARCIS (Netherlands)

    K. de Groot (Kristel); J.W. van Strien (Jan)

    2017-01-01

    textabstractThe broad autism phenotype implies the existence of a continuum ranging from individuals displaying almost no autistic traits to severely impaired diagnosed individuals. Recent studies have linked this variation in autistic traits to several domains of functioning. However, studies

  13. 33 CFR 117.921 - Broad River.

    Science.gov (United States)

    2010-07-01

    ... OPERATION REGULATIONS Specific Requirements South Carolina § 117.921 Broad River. (a) The draw of the S170 bridge, mile 14.0 near Beaufort, shall open on signal if at least 24 hours notice is given. (b) The draw...

  14. Education and Broad Concepts of Agency

    Science.gov (United States)

    Winch, Christopher

    2014-01-01

    Drawing on recent debates about the relationship between propositional and practical knowledge, this article is concerned with broad concepts of agency. Specifically, it is concerned with agency that involves the forming and putting into effect of intentions over relatively extended periods, particularly in work contexts (called, for want of a…

  15. Integrating Biological Perspectives:. a Quantum Leap for Microarray Expression Analysis

    Science.gov (United States)

    Wanke, Dierk; Kilian, Joachim; Bloss, Ulrich; Mangelsen, Elke; Supper, Jochen; Harter, Klaus; Berendzen, Kenneth W.

    2009-02-01

    Biologists and bioinformatic scientists cope with the analysis of transcript abundance and the extraction of meaningful information from microarray expression data. By exploiting biological information accessible in public databases, we try to extend our current knowledge over the plant model organism Arabidopsis thaliana. Here, we give two examples of increasing the quality of information gained from large scale expression experiments by the integration of microarray-unrelated biological information: First, we utilize Arabidopsis microarray data to demonstrate that expression profiles are usually conserved between orthologous genes of different organisms. In an initial step of the analysis, orthology has to be inferred unambiguously, which then allows comparison of expression profiles between orthologs. We make use of the publicly available microarray expression data of Arabidopsis and barley, Hordeum vulgare. We found a generally positive correlation in expression trajectories between true orthologs although both organisms are only distantly related in evolutionary time scale. Second, extracting clusters of co-regulated genes implies similarities in transcriptional regulation via similar cis-regulatory elements (CREs). Vice versa approaches, where co-regulated gene clusters are found by investigating on CREs were not successful in general. Nonetheless, in some cases the presence of CREs in a defined position, orientation or CRE-combinations is positively correlated with co-regulated gene clusters. Here, we make use of genes involved in the phenylpropanoid biosynthetic pathway, to give one positive example for this approach.

  16. Kernel Based Nonlinear Dimensionality Reduction and Classification for Genomic Microarray

    Directory of Open Access Journals (Sweden)

    Lan Shu

    2008-07-01

    Full Text Available Genomic microarrays are powerful research tools in bioinformatics and modern medicinal research because they enable massively-parallel assays and simultaneous monitoring of thousands of gene expression of biological samples. However, a simple microarray experiment often leads to very high-dimensional data and a huge amount of information, the vast amount of data challenges researchers into extracting the important features and reducing the high dimensionality. In this paper, a nonlinear dimensionality reduction kernel method based locally linear embedding(LLE is proposed, and fuzzy K-nearest neighbors algorithm which denoises datasets will be introduced as a replacement to the classical LLE’s KNN algorithm. In addition, kernel method based support vector machine (SVM will be used to classify genomic microarray data sets in this paper. We demonstrate the application of the techniques to two published DNA microarray data sets. The experimental results confirm the superiority and high success rates of the presented method.

  17. The microarray detecting six fruit-tree viruses

    Czech Academy of Sciences Publication Activity Database

    Lenz, Ondřej; Petrzik, Karel; Špak, Josef

    2009-01-01

    Roč. 148, July (2009), s. 27 ISSN 1866-590X. [International Conference on Virus and other Graft Transmissible Diseases of Fruit Crops /21./. 05.07.2009-10.07.2009, Neustadt] R&D Projects: GA MŠk OC 853.001 Institutional research plan: CEZ:AV0Z50510513 Keywords : microarray * detection * virus Subject RIV: EE - Microbiology, Virology

  18. A Customized DNA Microarray for Microbial Source Tracking ...

    Science.gov (United States)

    It is estimated that more than 160, 000 miles of rivers and streams in the United States are impaired due to the presence of waterborne pathogens. These pathogens typically originate from human and other animal fecal pollution sources; therefore, a rapid microbial source tracking (MST) method is needed to facilitate water quality assessment and impaired water remediation. We report a novel qualitative DNA microarray technology consisting of 453 probes for the detection of general fecal and host-associated bacteria, viruses, antibiotic resistance, and other environmentally relevant genetic indicators. A novel data normalization and reduction approach is also presented to help alleviate false positives often associated with high-density microarray applications. To evaluate the performance of the approach, DNA and cDNA was isolated from swine, cattle, duck, goose and gull fecal reference samples, as well as soiled poultry liter and raw municipal sewage. Based on nonmetric multidimensional scaling analysis of results, findings suggest that the novel microarray approach may be useful for pathogen detection and identification of fecal contamination in recreational waters. The ability to simultaneously detect a large collection of environmentally important genetic indicators in a single test has the potential to provide water quality managers with a wide range of information in a short period of time. Future research is warranted to measure microarray performance i

  19. Dimension reduction methods for microarray data: a review

    Directory of Open Access Journals (Sweden)

    Rabia Aziz

    2017-03-01

    Full Text Available Dimension reduction has become inevitable for pre-processing of high dimensional data. “Gene expression microarray data” is an instance of such high dimensional data. Gene expression microarray data displays the maximum number of genes (features simultaneously at a molecular level with a very small number of samples. The copious numbers of genes are usually provided to a learning algorithm for producing a complete characterization of the classification task. However, most of the times the majority of the genes are irrelevant or redundant to the learning task. It will deteriorate the learning accuracy and training speed as well as lead to the problem of overfitting. Thus, dimension reduction of microarray data is a crucial preprocessing step for prediction and classification of disease. Various feature selection and feature extraction techniques have been proposed in the literature to identify the genes, that have direct impact on the various machine learning algorithms for classification and eliminate the remaining ones. This paper describes the taxonomy of dimension reduction methods with their characteristics, evaluation criteria, advantages and disadvantages. It also presents a review of numerous dimension reduction approaches for microarray data, mainly those methods that have been proposed over the past few years.

  20. GenePublisher: automated analysis of DNA microarray data

    DEFF Research Database (Denmark)

    Knudsen, Steen; Workman, Christopher; Sicheritz-Ponten, T.

    2003-01-01

    GenePublisher, a system for automatic analysis of data from DNA microarray experiments, has been implemented with a web interface at http://www.cbs.dtu.dk/services/GenePublisher. Raw data are uploaded to the server together with aspecification of the data. The server performs normalization...

  1. Towards a programmable magnetic bead microarray in a microfluidic channel

    DEFF Research Database (Denmark)

    Smistrup, Kristian; Bruus, Henrik; Hansen, Mikkel Fougt

    2007-01-01

    to use larger currents and obtain forces of longer range than from thin current lines at a given power limit. Guiding of magnetic beads in the hybrid magnetic separator and the construction of a programmable microarray of magnetic beads in the microfluidic channel by hydrodynamic focusing is presented....

  2. Comparison of Comparative Genomic Hybridization Technologies across Microarray Platforms

    Science.gov (United States)

    In the 2007 Association of Biomolecular Resource Facilities (ABRF) Microarray Research Group (MARG) project, we analyzed HL-60 DNA with five platforms: Agilent, Affymetrix 500K, Affymetrix U133 Plus 2.0, Illumina, and RPCI 19K BAC arrays. Copy number variation (CNV) was analyzed ...

  3. CONFIRMING MICROARRAY DATA--IS IT REALLY NECESSARY?

    Science.gov (United States)

    The generation of corroborative data has become a commonly used approach for ensuring the veracity of microarray data. Indeed, the need to conduct corroborative studies has now become official editorial policy for at least two journals, and several more are considering introducin...

  4. Microarrays: Molecular allergology and nanotechnology for personalised medicine (II).

    Science.gov (United States)

    Lucas, J M

    2010-01-01

    Progress in nanotechnology and DNA recombination techniques have produced tools for the diagnosis and investigation of allergy at molecular level. The most advanced examples of such progress are the microarray techniques, which have been expanded not only in research in the field of proteomics but also in application to the clinical setting. Microarrays of allergic components offer results relating to hundreds of allergenic components in a single test, and using a small amount of serum which can be obtained from capillary blood. The availability of new molecules will allow the development of panels including new allergenic components and sources, which will require evaluation for clinical use. Their application opens the door to component-based diagnosis, to the holistic perception of sensitisation as represented by molecular allergy, and to patient-centred medical practice by allowing great diagnostic accuracy and the definition of individualised immunotherapy for each patient. The present article reviews the application of allergenic component microarrays to allergology for diagnosis, management in the form of specific immunotherapy, and epidemiological studies. A review is also made of the use of protein and gene microarray techniques in basic research and in allergological diseases. Lastly, an evaluation is made of the challenges we face in introducing such techniques to clinical practice, and of the future perspectives of this new technology. Copyright 2010 SEICAP. Published by Elsevier Espana. All rights reserved.

  5. Exploiting fluorescence for multiplex immunoassays on protein microarrays

    International Nuclear Information System (INIS)

    Herbáth, Melinda; Balogh, Andrea; Matkó, János; Papp, Krisztián; Prechl, József

    2014-01-01

    Protein microarray technology is becoming the method of choice for identifying protein interaction partners, detecting specific proteins, carbohydrates and lipids, or for characterizing protein interactions and serum antibodies in a massively parallel manner. Availability of the well-established instrumentation of DNA arrays and development of new fluorescent detection instruments promoted the spread of this technique. Fluorescent detection has the advantage of high sensitivity, specificity, simplicity and wide dynamic range required by most measurements. Fluorescence through specifically designed probes and an increasing variety of detection modes offers an excellent tool for such microarray platforms. Measuring for example the level of antibodies, their isotypes and/or antigen specificity simultaneously can offer more complex and comprehensive information about the investigated biological phenomenon, especially if we take into consideration that hundreds of samples can be measured in a single assay. Not only body fluids, but also cell lysates, extracted cellular components, and intact living cells can be analyzed on protein arrays for monitoring functional responses to printed samples on the surface. As a rapidly evolving area, protein microarray technology offers a great bulk of information and new depth of knowledge. These are the features that endow protein arrays with wide applicability and robust sample analyzing capability. On the whole, protein arrays are emerging new tools not just in proteomics, but glycomics, lipidomics, and are also important for immunological research. In this review we attempt to summarize the technical aspects of planar fluorescent microarray technology along with the description of its main immunological applications. (topical review)

  6. Development of DNA Microarrays for Metabolic Pathway and Bioprocess Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Gregory Stephanopoulos

    2004-07-31

    Transcriptional profiling experiments utilizing DNA microarrays to study the intracellular accumulation of PHB in Synechocystis has proved difficult in large part because strains that show significant differences in PHB which would justify global analysis of gene expression have not been isolated.

  7. SNP typing on the NanoChip electronic microarray

    DEFF Research Database (Denmark)

    Børsting, Claus; Sanchez Sanchez, Juan Jose; Morling, Niels

    2005-01-01

    We describe a single nucleotide polymorphism (SNP) typing protocol developed for the NanoChip electronic microarray. The NanoChip array consists of 100 electrodes covered by a thin hydrogel layer containing streptavidin. An electric currency can be applied to one, several, or all electrodes...

  8. Application of Microarray technology in research and diagnostics

    DEFF Research Database (Denmark)

    Helweg-Larsen, Rehannah Borup

    The overall purpose of this thesis is to evaluate the use of microarray analysis to investigate the transcriptome of human cancers and human follicular cells and define the correlation between expression of human genes and specific cancer types as well as the developmental competence of the oocyte...

  9. Bacterial identification and subtyping using DNA microarray and DNA sequencing.

    Science.gov (United States)

    Al-Khaldi, Sufian F; Mossoba, Magdi M; Allard, Marc M; Lienau, E Kurt; Brown, Eric D

    2012-01-01

    The era of fast and accurate discovery of biological sequence motifs in prokaryotic and eukaryotic cells is here. The co-evolution of direct genome sequencing and DNA microarray strategies not only will identify, isotype, and serotype pathogenic bacteria, but also it will aid in the discovery of new gene functions by detecting gene expressions in different diseases and environmental conditions. Microarray bacterial identification has made great advances in working with pure and mixed bacterial samples. The technological advances have moved beyond bacterial gene expression to include bacterial identification and isotyping. Application of new tools such as mid-infrared chemical imaging improves detection of hybridization in DNA microarrays. The research in this field is promising and future work will reveal the potential of infrared technology in bacterial identification. On the other hand, DNA sequencing by using 454 pyrosequencing is so cost effective that the promise of $1,000 per bacterial genome sequence is becoming a reality. Pyrosequencing technology is a simple to use technique that can produce accurate and quantitative analysis of DNA sequences with a great speed. The deposition of massive amounts of bacterial genomic information in databanks is creating fingerprint phylogenetic analysis that will ultimately replace several technologies such as Pulsed Field Gel Electrophoresis. In this chapter, we will review (1) the use of DNA microarray using fluorescence and infrared imaging detection for identification of pathogenic bacteria, and (2) use of pyrosequencing in DNA cluster analysis to fingerprint bacterial phylogenetic trees.

  10. Microarray-Based Identification of Transcription Factor Target Genes

    NARCIS (Netherlands)

    Gorte, M.; Horstman, A.; Page, R.B.; Heidstra, R.; Stromberg, A.; Boutilier, K.A.

    2011-01-01

    Microarray analysis is widely used to identify transcriptional changes associated with genetic perturbation or signaling events. Here we describe its application in the identification of plant transcription factor target genes with emphasis on the design of suitable DNA constructs for controlling TF

  11. Employing image processing techniques for cancer detection using microarray images.

    Science.gov (United States)

    Dehghan Khalilabad, Nastaran; Hassanpour, Hamid

    2017-02-01

    Microarray technology is a powerful genomic tool for simultaneously studying and analyzing the behavior of thousands of genes. The analysis of images obtained from this technology plays a critical role in the detection and treatment of diseases. The aim of the current study is to develop an automated system for analyzing data from microarray images in order to detect cancerous cases. The proposed system consists of three main phases, namely image processing, data mining, and the detection of the disease. The image processing phase performs operations such as refining image rotation, gridding (locating genes) and extracting raw data from images the data mining includes normalizing the extracted data and selecting the more effective genes. Finally, via the extracted data, cancerous cell is recognized. To evaluate the performance of the proposed system, microarray database is employed which includes Breast cancer, Myeloid Leukemia and Lymphomas from the Stanford Microarray Database. The results indicate that the proposed system is able to identify the type of cancer from the data set with an accuracy of 95.45%, 94.11%, and 100%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Microarray-based RNA profiling of breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Tan, Qihua

    2014-01-01

    analyzed the same 234 breast cancers on two different microarray platforms. One dataset contained known batch-effects associated with the fabrication procedure used. The aim was to assess the significance of correcting for systematic batch-effects when integrating data from different platforms. We here...

  13. Microarray expression profiling of human dental pulp from single subject.

    Science.gov (United States)

    Tete, Stefano; Mastrangelo, Filiberto; Scioletti, Anna Paola; Tranasi, Michelangelo; Raicu, Florina; Paolantonio, Michele; Stuppia, Liborio; Vinci, Raffaele; Gherlone, Enrico; Ciampoli, Cristian; Sberna, Maria Teresa; Conti, Pio

    2008-01-01

    Microarray is a recently developed simultaneous analysis of expression patterns of thousand of genes. The aim of this research was to evaluate the expression profile of human healthy dental pulp in order to find the presence of genes activated and encoding for proteins involved in the physiological process of human dental pulp. We report data obtained by analyzing expression profiles of human tooth pulp from single subjects, using an approach based on the amplification of the total RNA. Experiments were performed on a high-density array able to analyse about 21,000 oligonucleotide sequences of about 70 bases in duplicate, using an approach based on the amplification of the total RNA from the pulp of a single tooth. Obtained data were analyzed using the S.A.M. system (Significance Analysis of Microarray) and genes were merged according to their molecular functions and biological process by the Onto-Express software. The microarray analysis revealed 362 genes with specific pulp expression. Genes showing significant high expression were classified in genes involved in tooth development, protoncogenes, genes of collagen, DNAse, Metallopeptidases and Growth factors. We report a microarray analysis, carried out by extraction of total RNA from specimens of healthy human dental pulp tissue. This approach represents a powerful tool in the study of human normal and pathological pulp, allowing minimization of the genetic variability due to the pooling of samples from different individuals.

  14. Microarray analysis of the gene expression profile in triethylene ...

    African Journals Online (AJOL)

    Microarray analysis of the gene expression profile in triethylene glycol dimethacrylate-treated human dental pulp cells. ... Conclusions: Our results suggest that TEGDMA can change the many functions of hDPCs through large changes in gene expression levels and complex interactions with different signaling pathways.

  15. Comparison of gene coverage of mouse oligonucleotide microarray platforms

    Directory of Open Access Journals (Sweden)

    Medrano Juan F

    2006-03-01

    Full Text Available Abstract Background The increasing use of DNA microarrays for genetical genomics studies generates a need for platforms with complete coverage of the genome. We have compared the effective gene coverage in the mouse genome of different commercial and noncommercial oligonucleotide microarray platforms by performing an in-house gene annotation of probes. We only used information about probes that is available from vendors and followed a process that any researcher may take to find the gene targeted by a given probe. In order to make consistent comparisons between platforms, probes in each microarray were annotated with an Entrez Gene id and the chromosomal position for each gene was obtained from the UCSC Genome Browser Database. Gene coverage was estimated as the percentage of Entrez Genes with a unique position in the UCSC Genome database that is tested by a given microarray platform. Results A MySQL relational database was created to store the mapping information for 25,416 mouse genes and for the probes in five microarray platforms (gene coverage level in parenthesis: Affymetrix430 2.0 (75.6%, ABI Genome Survey (81.24%, Agilent (79.33%, Codelink (78.09%, Sentrix (90.47%; and four array-ready oligosets: Sigma (47.95%, Operon v.3 (69.89%, Operon v.4 (84.03%, and MEEBO (84.03%. The differences in coverage between platforms were highly conserved across chromosomes. Differences in the number of redundant and unspecific probes were also found among arrays. The database can be queried to compare specific genomic regions using a web interface. The software used to create, update and query the database is freely available as a toolbox named ArrayGene. Conclusion The software developed here allows researchers to create updated custom databases by using public or proprietary information on genes for any organisms. ArrayGene allows easy comparisons of gene coverage between microarray platforms for any region of the genome. The comparison presented here

  16. Workflows for microarray data processing in the Kepler environment

    Directory of Open Access Journals (Sweden)

    Stropp Thomas

    2012-05-01

    Full Text Available Abstract Background Microarray data analysis has been the subject of extensive and ongoing pipeline development due to its complexity, the availability of several options at each analysis step, and the development of new analysis demands, including integration with new data sources. Bioinformatics pipelines are usually custom built for different applications, making them typically difficult to modify, extend and repurpose. Scientific workflow systems are intended to address these issues by providing general-purpose frameworks in which to develop and execute such pipelines. The Kepler workflow environment is a well-established system under continual development that is employed in several areas of scientific research. Kepler provides a flexible graphical interface, featuring clear display of parameter values, for design and modification of workflows. It has capabilities for developing novel computational components in the R, Python, and Java programming languages, all of which are widely used for bioinformatics algorithm development, along with capabilities for invoking external applications and using web services. Results We developed a series of fully functional bioinformatics pipelines addressing common tasks in microarray processing in the Kepler workflow environment. These pipelines consist of a set of tools for GFF file processing of NimbleGen chromatin immunoprecipitation on microarray (ChIP-chip datasets and more comprehensive workflows for Affymetrix gene expression microarray bioinformatics and basic primer design for PCR experiments, which are often used to validate microarray results. Although functional in themselves, these workflows can be easily customized, extended, or repurposed to match the needs of specific projects and are designed to be a toolkit and starting point for specific applications. These workflows illustrate a workflow programming paradigm focusing on local resources (programs and data and therefore are close to

  17. Workflows for microarray data processing in the Kepler environment.

    Science.gov (United States)

    Stropp, Thomas; McPhillips, Timothy; Ludäscher, Bertram; Bieda, Mark

    2012-05-17

    Microarray data analysis has been the subject of extensive and ongoing pipeline development due to its complexity, the availability of several options at each analysis step, and the development of new analysis demands, including integration with new data sources. Bioinformatics pipelines are usually custom built for different applications, making them typically difficult to modify, extend and repurpose. Scientific workflow systems are intended to address these issues by providing general-purpose frameworks in which to develop and execute such pipelines. The Kepler workflow environment is a well-established system under continual development that is employed in several areas of scientific research. Kepler provides a flexible graphical interface, featuring clear display of parameter values, for design and modification of workflows. It has capabilities for developing novel computational components in the R, Python, and Java programming languages, all of which are widely used for bioinformatics algorithm development, along with capabilities for invoking external applications and using web services. We developed a series of fully functional bioinformatics pipelines addressing common tasks in microarray processing in the Kepler workflow environment. These pipelines consist of a set of tools for GFF file processing of NimbleGen chromatin immunoprecipitation on microarray (ChIP-chip) datasets and more comprehensive workflows for Affymetrix gene expression microarray bioinformatics and basic primer design for PCR experiments, which are often used to validate microarray results. Although functional in themselves, these workflows can be easily customized, extended, or repurposed to match the needs of specific projects and are designed to be a toolkit and starting point for specific applications. These workflows illustrate a workflow programming paradigm focusing on local resources (programs and data) and therefore are close to traditional shell scripting or R

  18. High quality protein microarray using in situ protein purification

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2009-08-01

    Full Text Available Abstract Background In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC. This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. Results Two slide surfaces were examined, chelated Cu2+ slides suspended on a polyethylene glycol (PEG coating and chelated Ni2+ slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu2+ slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents

  19. Workflows for microarray data processing in the Kepler environment

    Science.gov (United States)

    2012-01-01

    Background Microarray data analysis has been the subject of extensive and ongoing pipeline development due to its complexity, the availability of several options at each analysis step, and the development of new analysis demands, including integration with new data sources. Bioinformatics pipelines are usually custom built for different applications, making them typically difficult to modify, extend and repurpose. Scientific workflow systems are intended to address these issues by providing general-purpose frameworks in which to develop and execute such pipelines. The Kepler workflow environment is a well-established system under continual development that is employed in several areas of scientific research. Kepler provides a flexible graphical interface, featuring clear display of parameter values, for design and modification of workflows. It has capabilities for developing novel computational components in the R, Python, and Java programming languages, all of which are widely used for bioinformatics algorithm development, along with capabilities for invoking external applications and using web services. Results We developed a series of fully functional bioinformatics pipelines addressing common tasks in microarray processing in the Kepler workflow environment. These pipelines consist of a set of tools for GFF file processing of NimbleGen chromatin immunoprecipitation on microarray (ChIP-chip) datasets and more comprehensive workflows for Affymetrix gene expression microarray bioinformatics and basic primer design for PCR experiments, which are often used to validate microarray results. Although functional in themselves, these workflows can be easily customized, extended, or repurposed to match the needs of specific projects and are designed to be a toolkit and starting point for specific applications. These workflows illustrate a workflow programming paradigm focusing on local resources (programs and data) and therefore are close to traditional shell scripting or

  20. Spectrum estimation method based on marginal spectrum

    International Nuclear Information System (INIS)

    Cai Jianhua; Hu Weiwen; Wang Xianchun

    2011-01-01

    FFT method can not meet the basic requirements of power spectrum for non-stationary signal and short signal. A new spectrum estimation method based on marginal spectrum from Hilbert-Huang transform (HHT) was proposed. The procession of obtaining marginal spectrum in HHT method was given and the linear property of marginal spectrum was demonstrated. Compared with the FFT method, the physical meaning and the frequency resolution of marginal spectrum were further analyzed. Then the Hilbert spectrum estimation algorithm was discussed in detail, and the simulation results were given at last. The theory and simulation shows that under the condition of short data signal and non-stationary signal, the frequency resolution and estimation precision of HHT method is better than that of FFT method. (authors)

  1. Computational biology of genome expression and regulation--a review of microarray bioinformatics.

    Science.gov (United States)

    Wang, Junbai

    2008-01-01

    Microarray technology is being used widely in various biomedical research areas; the corresponding microarray data analysis is an essential step toward the best utilizing of array technologies. Here we review two components of the microarray data analysis: a low level of microarray data analysis that emphasizes the designing, the quality control, and the preprocessing of microarray experiments, then a high level of microarray data analysis that focuses on the domain-specific microarray applications such as tumor classification, biomarker prediction, analyzing array CGH experiments, and reverse engineering of gene expression networks. Additionally, we will review the recent development of building a predictive model in genome expression and regulation studies. This review may help biologists grasp a basic knowledge of microarray bioinformatics as well as its potential impact on the future evolvement of biomedical research fields.

  2. THE MAQC PROJECT: ESTABLISHING QC METRICS AND THRESHOLDS FOR MICROARRAY QUALITY CONTROL

    Science.gov (United States)

    Microarrays represent a core technology in pharmacogenomics and toxicogenomics; however, before this technology can successfully and reliably be applied in clinical practice and regulatory decision-making, standards and quality measures need to be developed. The Microarray Qualit...

  3. Translating microarray data for diagnostic testing in childhood leukaemia

    International Nuclear Information System (INIS)

    Hoffmann, Katrin; Firth, Martin J; Beesley, Alex H; Klerk, Nicholas H de; Kees, Ursula R

    2006-01-01

    Recent findings from microarray studies have raised the prospect of a standardized diagnostic gene expression platform to enhance accurate diagnosis and risk stratification in paediatric acute lymphoblastic leukaemia (ALL). However, the robustness as well as the format for such a diagnostic test remains to be determined. As a step towards clinical application of these findings, we have systematically analyzed a published ALL microarray data set using Robust Multi-array Analysis (RMA) and Random Forest (RF). We examined published microarray data from 104 ALL patients specimens, that represent six different subgroups defined by cytogenetic features and immunophenotypes. Using the decision-tree based supervised learning algorithm Random Forest (RF), we determined a small set of genes for optimal subgroup distinction and subsequently validated their predictive power in an independent patient cohort. We achieved very high overall ALL subgroup prediction accuracies of about 98%, and were able to verify the robustness of these genes in an independent panel of 68 specimens obtained from a different institution and processed in a different laboratory. Our study established that the selection of discriminating genes is strongly dependent on the analysis method. This may have profound implications for clinical use, particularly when the classifier is reduced to a small set of genes. We have demonstrated that as few as 26 genes yield accurate class prediction and importantly, almost 70% of these genes have not been previously identified as essential for class distinction of the six ALL subgroups. Our finding supports the feasibility of qRT-PCR technology for standardized diagnostic testing in paediatric ALL and should, in conjunction with conventional cytogenetics lead to a more accurate classification of the disease. In addition, we have demonstrated that microarray findings from one study can be confirmed in an independent study, using an entirely independent patient cohort

  4. Microarray analysis in the archaeon Halobacterium salinarum strain R1.

    Directory of Open Access Journals (Sweden)

    Jens Twellmeyer

    Full Text Available BACKGROUND: Phototrophy of the extremely halophilic archaeon Halobacterium salinarum was explored for decades. The research was mainly focused on the expression of bacteriorhodopsin and its functional properties. In contrast, less is known about genome wide transcriptional changes and their impact on the physiological adaptation to phototrophy. The tool of choice to record transcriptional profiles is the DNA microarray technique. However, the technique is still rarely used for transcriptome analysis in archaea. METHODOLOGY/PRINCIPAL FINDINGS: We developed a whole-genome DNA microarray based on our sequence data of the Hbt. salinarum strain R1 genome. The potential of our tool is exemplified by the comparison of cells growing under aerobic and phototrophic conditions, respectively. We processed the raw fluorescence data by several stringent filtering steps and a subsequent MAANOVA analysis. The study revealed a lot of transcriptional differences between the two cell states. We found that the transcriptional changes were relatively weak, though significant. Finally, the DNA microarray data were independently verified by a real-time PCR analysis. CONCLUSION/SIGNIFICANCE: This is the first DNA microarray analysis of Hbt. salinarum cells that were actually grown under phototrophic conditions. By comparing the transcriptomics data with current knowledge we could show that our DNA microarray tool is well applicable for transcriptome analysis in the extremely halophilic archaeon Hbt. salinarum. The reliability of our tool is based on both the high-quality array of DNA probes and the stringent data handling including MAANOVA analysis. Among the regulated genes more than 50% had unknown functions. This underlines the fact that haloarchaeal phototrophy is still far away from being completely understood. Hence, the data recorded in this study will be subject to future systems biology analysis.

  5. Washing scaling of GeneChip microarray expression

    Directory of Open Access Journals (Sweden)

    Krohn Knut

    2010-05-01

    Full Text Available Abstract Background Post-hybridization washing is an essential part of microarray experiments. Both the quality of the experimental washing protocol and adequate consideration of washing in intensity calibration ultimately affect the quality of the expression estimates extracted from the microarray intensities. Results We conducted experiments on GeneChip microarrays with altered protocols for washing, scanning and staining to study the probe-level intensity changes as a function of the number of washing cycles. For calibration and analysis of the intensity data we make use of the 'hook' method which allows intensity contributions due to non-specific and specific hybridization of perfect match (PM and mismatch (MM probes to be disentangled in a sequence specific manner. On average, washing according to the standard protocol removes about 90% of the non-specific background and about 30-50% and less than 10% of the specific targets from the MM and PM, respectively. Analysis of the washing kinetics shows that the signal-to-noise ratio doubles roughly every ten stringent washing cycles. Washing can be characterized by time-dependent rate constants which reflect the heterogeneous character of target binding to microarray probes. We propose an empirical washing function which estimates the survival of probe bound targets. It depends on the intensity contribution due to specific and non-specific hybridization per probe which can be estimated for each probe using existing methods. The washing function allows probe intensities to be calibrated for the effect of washing. On a relative scale, proper calibration for washing markedly increases expression measures, especially in the limit of small and large values. Conclusions Washing is among the factors which potentially distort expression measures. The proposed first-order correction method allows direct implementation in existing calibration algorithms for microarray data. We provide an experimental

  6. DNA microarray-based PCR ribotyping of Clostridium difficile.

    Science.gov (United States)

    Schneeberg, Alexander; Ehricht, Ralf; Slickers, Peter; Baier, Vico; Neubauer, Heinrich; Zimmermann, Stefan; Rabold, Denise; Lübke-Becker, Antina; Seyboldt, Christian

    2015-02-01

    This study presents a DNA microarray-based assay for fast and simple PCR ribotyping of Clostridium difficile strains. Hybridization probes were designed to query the modularly structured intergenic spacer region (ISR), which is also the template for conventional and PCR ribotyping with subsequent capillary gel electrophoresis (seq-PCR) ribotyping. The probes were derived from sequences available in GenBank as well as from theoretical ISR module combinations. A database of reference hybridization patterns was set up from a collection of 142 well-characterized C. difficile isolates representing 48 seq-PCR ribotypes. The reference hybridization patterns calculated by the arithmetic mean were compared using a similarity matrix analysis. The 48 investigated seq-PCR ribotypes revealed 27 array profiles that were clearly distinguishable. The most frequent human-pathogenic ribotypes 001, 014/020, 027, and 078/126 were discriminated by the microarray. C. difficile strains related to 078/126 (033, 045/FLI01, 078, 126, 126/FLI01, 413, 413/FLI01, 598, 620, 652, and 660) and 014/020 (014, 020, and 449) showed similar hybridization patterns, confirming their genetic relatedness, which was previously reported. A panel of 50 C. difficile field isolates was tested by seq-PCR ribotyping and the DNA microarray-based assay in parallel. Taking into account that the current version of the microarray does not discriminate some closely related seq-PCR ribotypes, all isolates were typed correctly. Moreover, seq-PCR ribotypes without reference profiles available in the database (ribotype 009 and 5 new types) were correctly recognized as new ribotypes, confirming the performance and expansion potential of the microarray. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Recommendations for the use of microarrays in prenatal diagnosis.

    Science.gov (United States)

    Suela, Javier; López-Expósito, Isabel; Querejeta, María Eugenia; Martorell, Rosa; Cuatrecasas, Esther; Armengol, Lluis; Antolín, Eugenia; Domínguez Garrido, Elena; Trujillo-Tiebas, María José; Rosell, Jordi; García Planells, Javier; Cigudosa, Juan Cruz

    2017-04-07

    Microarray technology, recently implemented in international prenatal diagnosis systems, has become one of the main techniques in this field in terms of detection rate and objectivity of the results. This guideline attempts to provide background information on this technology, including technical and diagnostic aspects to be considered. Specifically, this guideline defines: the different prenatal sample types to be used, as well as their characteristics (chorionic villi samples, amniotic fluid, fetal cord blood or miscarriage tissue material); variant reporting policies (including variants of uncertain significance) to be considered in informed consents and prenatal microarray reports; microarray limitations inherent to the technique and which must be taken into account when recommending microarray testing for diagnosis; a detailed clinical algorithm recommending the use of microarray testing and its introduction into routine clinical practice within the context of other genetic tests, including pregnancies in families with a genetic history or specific syndrome suspicion, first trimester increased nuchal translucency or second trimester heart malformation and ultrasound findings not related to a known or specific syndrome. This guideline has been coordinated by the Spanish Association for Prenatal Diagnosis (AEDP, «Asociación Española de Diagnóstico Prenatal»), the Spanish Human Genetics Association (AEGH, «Asociación Española de Genética Humana») and the Spanish Society of Clinical Genetics and Dysmorphology (SEGCyD, «Sociedad Española de Genética Clínica y Dismorfología»). Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  8. Integrated olfactory receptor and microarray gene expression databases

    Directory of Open Access Journals (Sweden)

    Crasto Chiquito J

    2007-06-01

    Full Text Available Abstract Background Gene expression patterns of olfactory receptors (ORs are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB, which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction. Description ORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data. Conclusion ORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.

  9. Seeded Bayesian Networks: Constructing genetic networks from microarray data

    Directory of Open Access Journals (Sweden)

    Quackenbush John

    2008-07-01

    Full Text Available Abstract Background DNA microarrays and other genomics-inspired technologies provide large datasets that often include hidden patterns of correlation between genes reflecting the complex processes that underlie cellular metabolism and physiology. The challenge in analyzing large-scale expression data has been to extract biologically meaningful inferences regarding these processes – often represented as networks – in an environment where the datasets are often imperfect and biological noise can obscure the actual signal. Although many techniques have been developed in an attempt to address these issues, to date their ability to extract meaningful and predictive network relationships has been limited. Here we describe a method that draws on prior information about gene-gene interactions to infer biologically relevant pathways from microarray data. Our approach consists of using preliminary networks derived from the literature and/or protein-protein interaction data as seeds for a Bayesian network analysis of microarray results. Results Through a bootstrap analysis of gene expression data derived from a number of leukemia studies, we demonstrate that seeded Bayesian Networks have the ability to identify high-confidence gene-gene interactions which can then be validated by comparison to other sources of pathway data. Conclusion The use of network seeds greatly improves the ability of Bayesian Network analysis to learn gene interaction networks from gene expression data. We demonstrate that the use of seeds derived from the biomedical literature or high-throughput protein-protein interaction data, or the combination, provides improvement over a standard Bayesian Network analysis, allowing networks involving dynamic processes to be deduced from the static snapshots of biological systems that represent the most common source of microarray data. Software implementing these methods has been included in the widely used TM4 microarray analysis package.

  10. Microarray Evaluation of Antimicrobial Resistance and Virulence of Escherichia coli Isolates from Portuguese Poultry

    Directory of Open Access Journals (Sweden)

    Nuno Mendonça

    2016-01-01

    Full Text Available The presence of antimicrobial resistance and virulence factors of 174 Escherichia coli strains isolated from healthy Portuguese Gallus gallus was evaluated. Resistance profiles were determined against 33 antimicrobials by microbroth dilution. Resistance was prevalent for tetracycline (70% and ampicillin (63%. Extended-spectrum beta-lactamase (ESBL phenotype was observed in 18% of the isolates. Multidrug resistance was found in 56% of isolates. A subset of 74 isolates were screened by DNA microarrays for the carriage of 88 antibiotic resistance genes and 62 virulence genes. Overall, 37 different resistance genes were detected. The most common were tet(A (72%, blaTEM (68%, and sul1 (47%, while 21% isolates harbored an ESBL gene (blaCTX-M group 1, group 2, or group 9. Of these, 96% carried the increased serum survival (iss virulence gene, while 89% presented the enterobactin siderophore receptor protein (iroN, 70% the temperature-sensitive hemagglutinin (tsh, and 68% the long polar fimbriae (lpfA virulence genes associated with extraintestinal pathogenic E. coli. In conclusion, prevalence of antibiotic resistant E. coli from the microbiota of Portuguese chickens was high, including to extended spectrum cephalosporins. The majority of isolates seems to have the potential to trigger extraintestinal human infection due to the presence of some virulence genes. However, the absence of genes specific for enteropathogenic E. coli reduces the risk for human intestinal infection.

  11. On the origin of gamma rays in Fermi blazars: beyond the broad line region.

    Science.gov (United States)

    Costamante, L.; Cutini, S.; Tosti, G.; Antolini, E.; Tramacere, A.

    2018-05-01

    The gamma-ray emission in broad-line blazars is generally explained as inverse Compton (IC) radiation of relativistic electrons in the jet scattering optical-UV photons from the Broad Line Region (BLR), the so-called BLR External Compton scenario. We test this scenario on the Fermi gamma-ray spectra of 106 broad-line blazars detected with the highest significance or largest BLR, by looking for cut-off signatures at high energies compatible with γ-γ interactions with BLR photons. We do not find evidence for the expected BLR absorption. For 2/3 of the sources, we can exclude any significant absorption (τmax 5). We conclude that for 9 out of 10 objects, the jet does not interact with BLR photons. Gamma-rays seem either produced outside the BLR most of the time, or the BLR is ˜100 × larger than given by reverberation mapping. This means that i) External Compton on BLR photons is disfavoured as the main gamma-ray mechanism, vs IC on IR photons from the torus or synchrotron self-Compton; ii) the Fermi gamma-ray spectrum is mostly intrinsic, determined by the interaction of the particle distribution with the seed-photons spectrum; iii) without suppression by the BLR, broad-line blazars can become copious emitters above 100 GeV, as demonstrated by 3C 454.3. We expect the CTA sky to be much richer of broad-line blazars than previously thought.

  12. Broad line regions in Seyfert-1 galaxies

    International Nuclear Information System (INIS)

    Groningen, E. van.

    1984-01-01

    To reproduce observed emission profiles of Seyfert galaxies, rotation in an accretion disk has been proposed. In this thesis, the profiles emitted by such an accretion disk are investigated. Detailed comparison with the observed profiles yields that a considerable fraction can be fitted with a power-law function, as predicted by the model. The author analyzes a series of high quality spectra of Seyfert galaxies, obtained with the 2.5m telescope at Las Campanas. He presents detailed analyses of two objects: Mkn335 and Akn120. In both cases, strong evidence is presented for the presence of two separate broad line zones. These zones are identified with an accretion disk and an outflowing wind. The disk contains gas with very high densities and emits predominantly the lower ionization lines. He reports on the discovery of very broad wings beneath the strong forbidden line 5007. (Auth.)

  13. Fourier evaluation of broad Moessbauer spectra

    International Nuclear Information System (INIS)

    Vincze, I.

    1981-01-01

    It is shown by the Fourier analysis of broad Moessbauer spectra that the even part of the distribution of the dominant hyperfine interaction (hyperfine field or quadrupole splitting) can be obtained directly without using least-square fitting procedures. Also the odd part of this distribution correlated with other hyperfine parameters (e.g. isomer shift) can be directly determined. Examples for amorphous magnetic and paramagnetic iron-based alloys are presented. (author)

  14. Fourier evaluation of broad Moessbauer spectra

    International Nuclear Information System (INIS)

    Vincze, I.

    1981-09-01

    It is shown by the Fourier analysis of broad Moessbauer spectra that the even part of the distribution of the dominant hyperfine interaction (hyperfine field or quadrupole splitting) can be obtained directly without using least-square fitting procedures. Also the odd part of this distribution correlated with other hyperfine parameters (e.g. isomer shift) can be directly determined. Examples covering the case of amorphous magnetic and paramagnetic iron-based alloys are presented. (author)

  15. Arbidol (Umifenovir): A broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses

    Czech Academy of Sciences Publication Activity Database

    Haviernik, J.; Štefánik, M.; Fojtíková, M.; Kali, S.; Tordo, N.; Rudolf, Ivo; Hubálek, Zdeněk; Eyer, Luděk; Růžek, Daniel

    2018-01-01

    Roč. 10, č. 4 (2018), č. článku 184. ISSN 1999-4915 R&D Projects: GA ČR(CZ) GA16-20054S Institutional support: RVO:68081766 ; RVO:60077344 Keywords : Antiviral activity * Arbidol * Cell-type dependent antiviral effect * Cytotoxicity * Flavivirus * Umifenovir Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 3.465, year: 2016

  16. Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

    International Nuclear Information System (INIS)

    Altmann, S.E.; Jones, J.C.; Schultz-Cherry, S.; Brandt, C.R.

    2009-01-01

    Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC 50 of 15 μM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC 50 > 200 μM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption was unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of β-galactosidase expression from an early viral promoter with an EC 50 of 45 μM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.

  17. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

    Directory of Open Access Journals (Sweden)

    Keiko Rausch

    2017-01-01

    Full Text Available Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested, including physiologically relevant primary cells. Nanchangmycin also was active against other medically relevant viruses, including West Nile, dengue, and chikungunya viruses that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis.

  18. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

    OpenAIRE

    Rausch, Keiko; Hackett, Brent A.; Weinbren, Nathan L.; Reeder, Sophia M.; Sadovsky, Yoel; Hunter, Christopher A.; Schultz, David C.; Coyne, Carolyn B.; Cherry, Sara

    2017-01-01

    Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from in...

  19. Self-esteem in a broad-spectrum approach for mental health promotion

    NARCIS (Netherlands)

    Mann, M.; Hosman, C.M.H.; Schaalma, H.P.; Vries, N.K. de

    2004-01-01

    Self-evaluation is crucial to mental and social well-being. It influences aspirations, personal goals and interaction with others. This paper stresses the importance of self-esteem as a protective factor and a non-specific risk factor in physical and mental health. Evidence is presented illustrating

  20. Identification of an antioxidant small-molecule with broad-spectrum antiviral activity.

    Science.gov (United States)

    Panchal, Rekha G; Reid, St Patrick; Tran, Julie P; Bergeron, Alison A; Wells, Jay; Kota, Krishna P; Aman, Javad; Bavari, Sina

    2012-01-01

    The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets. Published by Elsevier B.V.

  1. Novel Naja atra cardiotoxin 1 (CTX-1 derived antimicrobial peptides with broad spectrum activity.

    Directory of Open Access Journals (Sweden)

    Andrea Sala

    Full Text Available Naja atra subsp. atra cardiotoxin 1 (CTX-1, produced by Chinese cobra snakes, belonging to Elapidae family, is included in the three-finger toxin family and exerts high cytotoxicity and antimicrobial activity too. Using as template mainly the tip and the subsequent β-strand of the first "finger" of this toxin, different sequences of 20 amino acids linear peptides have been designed in order to avoid toxic effects but to maintain or even strengthen the partial antimicrobial activity already seen for the complete toxin. As a result, the sequence NCP-0 (Naja Cardiotoxin Peptide-0 was designed as ancestor and subsequently 4 other variant sequences of NCP-0 were developed. These synthesized variant sequences have shown microbicidal activity towards a panel of reference and field strains of Gram-positive and Gram-negative bacteria. The sequence named NCP-3, and its variants NCP-3a and NCP-3b, have shown the best antimicrobial activity, together with low cytotoxicity against eukaryotic cells and low hemolytic activity. Bactericidal activity has been demonstrated by minimum bactericidal concentration (MBC assay at values below 10 μg/ml for most of the tested bacterial strains. This potent antimicrobial activity was confirmed even for unicellular fungi Candida albicans, Candida glabrata and Malassezia pachydermatis (MBC 50-6.3 μg/ml, and against the fast-growing mycobacteria Mycobacterium smegmatis and Mycobacterium fortuitum. Moreover, NCP-3 has shown virucidal activity on Bovine Herpesvirus 1 (BoHV1 belonging to Herpesviridae family. The bactericidal activity is maintained even in a high salt concentration medium (125 and 250 mM NaCl and phosphate buffer with 20% Mueller Hinton (MH medium against E. coli, methicillin resistant Staphylococcus aureus (MRSA and Pseudomonas aeruginosa reference strains. Considering these in vitro obtained data, the search for active sequences within proteins presenting an intrinsic microbicidal activity could provide a new way for discovering a large number of novel and promising antimicrobial peptides families.

  2. Dissemination and genetic support of broad-spectrum beta-lactam ...

    African Journals Online (AJOL)

    Methods: A total of 113 E.coli isolates obtained during the period 2004 through 2012 showed a ... to the PFGE analysis and characterization of the regions surrounding the blaCTX-M-15 ... 240-Gly which increases its catalytic efficiency against.

  3. Sarcomas associated with hereditary nonpolyposis colorectal cancer: broad anatomical and morphological spectrum

    DEFF Research Database (Denmark)

    Nilbert, Mef; Therkildsen, Christina; Nissen, Anja

    2009-01-01

    -register to identify HNPCC families in which sarcomas had been diagnosed. Fourteen sarcomas were identified in families with mutations in MSH2, MSH6, and MLH1. The median age at sarcoma diagnosis was 43 (15-74) years. Soft tissue sarcomas predominated followed by uterine sarcomas and eight histopathological subtypes...

  4. A mutagenesis-derived broad-spectrum disease resistance locus in wheat

    Science.gov (United States)

    Wheat leaf rust, stem rust, stripe rust, and powdery mildew caused by the fungal pathogens Puccinia triticina, P. graminis f. sp. tritici, P. striiformis f. sp. tritici, and Blumeria graminis f. sp. tritici, respectively, are destructive diseases of wheat worldwide. The most effective and widely uti...

  5. Fungal Glucosylceramide-Specific Camelid Single Domain Antibodies Are Characterized by Broad Spectrum Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Barbara De Coninck

    2017-06-01

    Full Text Available Chemical crop protection is widely used to control plant diseases. However, the adverse effects of pesticide use on human health and environment, resistance development and the impact of regulatory requirements on the crop protection market urges the agrochemical industry to explore innovative and alternative approaches. In that context, we demonstrate here the potential of camelid single domain antibodies (VHHs generated against fungal glucosylceramides (fGlcCer, important pathogenicity factors. To this end, llamas were immunized with purified fGlcCer and a mixture of mycelium and spores of the fungus Botrytis cinerea, one of the most important plant pathogenic fungi. The llama immune repertoire was subsequently cloned in a phage display vector to generate a library with a diversity of at least 108 different clones. This library was incubated with fGlcCer to identify phages that bind to fGlcCer, and VHHs that specifically bound fGlcCer but not mammalian or plant-derived GlcCer were selected. They were shown to inhibit the growth of B. cinerea in vitro, with VHH 41D01 having the highest antifungal activity. Moreover, VHH 41D01 could reduce disease symptoms induced by B. cinerea when sprayed on tomato leaves. Based on all these data, anti-fGlcCer VHHs show the potential to be used as an alternative approach to combat fungal plant diseases.

  6. Self-Report and Brain Indicators of Impaired Emotion Regulation in the Broad Autism Spectrum

    NARCIS (Netherlands)

    de Groot, K. (Kristel); J.W. van Strien (Jan)

    2017-01-01

    textabstractAlthough not used as a diagnostic criterion, impaired emotion regulation is frequently observed in autism. The present study examined self-reported use of emotion regulation strategies in individuals scoring low or high on autistic traits. In addition, the late positive potential, which

  7. Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Ranu A., E-mail: ranu.dutta16@gmail.com [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); NanoeRA medicare Private Limited, Uttar Pradesh (India); Sharma, Prashant K. [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); Indian School of Mines, Dhanbad (India); Tiwari, Vandana [Department of Pathology, KGMU, Lucknow (India); Tiwari, Vivek; Patel, Anant B. [Centre for Cellular and Molecular Biology, Hyderabad (India); Pandey, Ravindra [Department of Physics, Michigan Technological University, Michigan 49931-1295 (United States); Pandey, Avinash C. [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); NanoeRA medicare Private Limited, Uttar Pradesh (India); Bundelkhand University, Jhansi (India)

    2014-01-13

    The engineering of the Gadolinium based nanostructures have been demonstrated in this paper. Nanostructures of α-Gd{sub 2}S{sub 3} exhibit a unique transition between ferromagnetic state and paramagnetic state of the system. It was demonstrated that their properties could be tuned for a wide range of applications ranging from hyperthermia to Magnetic Resonance Imaging, owing to their magnetic moments and large relaxivities. Metallic Gd nanoparticles obtained by reduction method were employed for cancer imaging in mice. The Gd nanoparticles were coated with Curcumin and their biomedical implications in the field of simultaneous diagnosis and therapy of cancer and related diseases has been discussed.

  8. POSACONAZOLE — NEW AZOLE BROAD-SPECTRUM ANTIFUNGAL AGENT FOR PREVENTION AND TREATMENT OF INVASIVE MYCOSES

    Directory of Open Access Journals (Sweden)

    N.N. Klimko

    2008-01-01

    Full Text Available Invasive mycoses are a common complication of various categories of immune depressed patients that are characterized with heavy clinical presentations and high lethal rate. Many causatives of invasive mycoses are resistant to currently applied antifungal medications, and some are polybresistant. Posaconazole (Noksafil is a new triazole antimycotic of second generation that is active both in vitro and in vivo against most causatives of invasive mycoses, including poly resistant microbmycets. Clinical study demonstrate high efficiency and safety of applying this medication. in russia posaconazole is allowed for prevention of invasive mycoses for hematological patients with longbrunning neutropenia resulting from chemical therapy, who are prescribed large doses of immune suppressors, recipients of transplants of hemapoietic stem cells, as well as for treatment of invasive candidoses, aspergillus, zigomicosys, criptococcosis, fuzariosis, chromomycosis and micetoma, as well as cocsidiodosis that are refractory towards other anti fungal medications, or in cases of intolerance.Key words: mycoses, posaconazole, treatment.

  9. Laboratory simulation of interplanetary ultraviolet radiation (broad spectrum) and its effects on Deinococcus radiodurans

    Science.gov (United States)

    Paulino-Lima, Ivan Gláucio; Pilling, Sérgio; Janot-Pacheco, Eduardo; de Brito, Arnaldo Naves; Barbosa, João Alexandre Ribeiro Gonçalves; Leitão, Alvaro Costa; Lage, Claudia de Alencar Santos

    2010-08-01

    The radiation-resistant bacterium Deinococcus radiodurans was exposed to a simulated interplanetary UV radiation at the Brazilian Synchrotron Light Laboratory (LNLS). Bacterial samples were irradiated on different substrates to investigate the influence of surface relief on cell survival. The effects of cell multi-layers were also investigated. The ratio of viable microorganisms remained virtually the same (average 2%) for integrated doses from 1.2 to 12 kJ m -2, corresponding to 16 h of irradiation at most. The asymptotic profiles of the curves, clearly connected to a shielding effect provided by multi-layering cells on a cavitary substrate (carbon tape), means that the inactivation rate may not change significantly along extended periods of exposure to radiation. Such high survival rates reinforce the possibility of an interplanetary transfer of viable microbes.

  10. Investigating AAK1-and GAK-Regulated Virus-Host Interactions Uncovers Broad-Spectrum Antivirals

    Science.gov (United States)

    2017-02-16

    AP1) and AP2M1 (AP2) were 527 selected from the Human ORFeome library of cDNA clones (65) (Open Biosystems) and 528 recombined into either pCherry...TSV01 Renilla reporter plasmid was a gift from Pei-Yong Shi (68). 534 Lentiviral constructs used for AP2 overexpression were cloned into the pRRLSIN...681 total of 10 days and observed daily for 28 days for lethality or clinical signs of disease. 682 683 Animal study approval/ Ethics Statement

  11. Broad-spectrum antibacterial properties of metal-ion doped borate bioactive glasses for clinical applications

    Science.gov (United States)

    Ottomeyer, Megan

    Bioactive glasses with antimicrobial properties can be implemented as coatings on medical devices and implants, as well as a treatment for tissue repair and prevention of common hospital-acquired infections such as MRSA. A borate-containing glass, B3, is also undergoing clinical trials to assess wound-healing properties. The sensitivities of various bacteria to B3, B3-Ag, B3-Ga, and B3-I bioactive glasses were tested. In addition, the mechanism of action for the glasses was studied by spectroscopic enzyme kinetics experiments, Live-Dead staining fluorescence microscopy, and luminescence assays using two gene fusion strains of Escherichia coli. It was found that gram-positive bacteria were more sensitive to all four glasses than gram negative bacteria, and that a single mechanism of action for the glasses is unlikely, as the rates of catalysis for metabolic enzymes as well as membrane permeability were altered after glass exposure.

  12. Chitosanase purified from bacterial isolate Bacillus licheniformis of ruined vegetables displays broad spectrum biofilm inhibition.

    Science.gov (United States)

    Muslim, Sahira Nsayef; Al-Kadmy, Israa M S; Hussein, Nadheema Hammood; Mohammed Ali, Alaa Naseer; Taha, Buthainah Mohammed; Aziz, Sarah Naji; Kheraif, Abdulaziz Abdullah Al; Divakar, Darshan Devang; Ramakrishnaiah, Ravikumar

    2016-11-01

    A number of bacterial species produces chitosanases which has variety of applications because of its high biodegradability, non-toxicity and antimicrobial assets. In the present study chitosanase is purified from new bacterial species Bacillus licheniformis from spoiled vegetable. This novel strain of Bacillus licheniformis isolated from spoilt cucumber and pepper samples has the ability to produce the chitosanase enzyme when grown on chitosan substrate. Study also examined its antibiofilm properties against diverse bacterial species with biofilm forming ability. The purified chitosanase inhibited the biofilm formation ability for all Gram-negative and Gram-positive biofilm-forming bacteria [biofilm producers] tested in this study in congo red agar and microtiter plate's methods. Highly antibiofilm activity of chitosanase was recorded against Pseudomonas aeruginosa followed by Klebsiella pneumoniae with reduction of biofilm formation upto 22 and 29%, respectively compared with [100] % of control. Biofilm formation has multiple role including ability to enhance resistance and self-protection from external stress. This chitosanase has promising benefit as antibiofilm agent against biofilm forming pathogenic bacteria and has promising application as alternative antibiofilm agents to combat the growing number of multidrug resistant pathogen-associated infections, especially in situation where biofilms are involved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The broad spectrum of unbearable suffering in end of life cancer studied in dutch primary care

    NARCIS (Netherlands)

    Ruijs, C.D.M.; Kerkhof, A.J.F.M.; van der Wal, G.; Onwuteaka-Philipsen, B.D.

    2012-01-01

    Background: Unbearable suffering most frequently is reported in end-of-life cancer patients in primary care. However, research seldom addresses unbearable suffering. The aim of this study was to comprehensively investigate the various aspects of unbearable suffering in end-of-life cancer patients

  14. Expansion of a recent class of broad-spectrum antifungal agents: the echinocandins

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2009-09-01

    Full Text Available The echinocandins show comparable efficacy in the treatment of candidemia and invasive candidiasis. Caspofungin and micafungin appear to be similarly efficacious in salvage therapy in aspergillosis; anidulafungin has excellent in vitro activity against Aspergillus species but as yet there are no sufficient clinical data for anidulafungin in this disease state. Each drug has minor advantages and disadvantages compared to the others of the same classe; however, there are large differences in the approved indications for the different drugs. The formulary selection process should consider the direct and indirect costs of the single agents; the characteristics of the patient population at risk for invasive mycosis, such as frequent use of interacting drugs and the burden of monitoring plasma drug levels of drugs; and the implications of using products for indications which have not been still approved (off-label indications.

  15. Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

    Czech Academy of Sciences Publication Activity Database

    Cagno, V.; Andreozzi, P.; D'Alicarnasso, M.; Silva, P. J.; Mueller, M.; Galloux, M.; Le Goffic, R.; Jones, S. T.; Vallino, M.; Hodek, Jan; Weber, Jan; Sen, S.; Janeček, E. R.; Bekdemir, A.; Sanavio, B.; Martinelli, C.; Donalisio, M.; Welti, M. A. R.; Eleouet, J. F.; Han, Y.; Kaiser, L.; Vukovic, L.; Tapparel, C.; Král, P.; Krol, S.; Lembo, D.; Stellacci, F.

    2018-01-01

    Roč. 17, č. 2 (2018), s. 195-203 ISSN 1476-1122 R&D Projects: GA MŠk(CZ) LK11207 Institutional support: RVO:61388963 Keywords : coli polysaccharide derivatives * multivalent gold nanoparticles * respiratory syncytial virus Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 39.737, year: 2016

  16. Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

    Czech Academy of Sciences Publication Activity Database

    Seydlová, G.; Pohl, Radek; Zborníková, Eva; Ehn, Marcel; Šimák, Ondřej; Panova, Natalya; Kolář, M.; Bogdanová, K.; Večeřová, R.; Fišer, R.; Šanderová, Hana; Vítovská, Dragana; Sudzinová, Petra; Pospíšil, Jiří; Benada, Oldřich; Křížek, T.; Sedlák, David; Bartůněk, Petr; Krásný, Libor; Rejman, Dominik

    2017-01-01

    Roč. 60, č. 14 (2017), s. 6098-6118 ISSN 0022-2623 R&D Projects: GA MŠk LO1220; GA MŠk LM2015063; GA ČR(CZ) GBP305/12/G034; GA MŠk(CZ) LM2015055; GA MZd(CZ) NV17-29680A Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:68378050 Keywords : resistant Staphylococcus aureus * cationic steroid antibiotics * antimicrobial peptides Subject RIV: EE - Microbiology, Virology; EE - Microbiology, Virology (MBU-M) OBOR OECD: Microbiology; Microbiology (MBU-M) Impact factor: 6.259, year: 2016

  17. Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance

    NARCIS (Netherlands)

    Pavan, S.N.C.; Jacobsen, E.; Visser, R.G.F.; Bai, Y.

    2010-01-01

    Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant

  18. The leaf size-twig size spectrum in evergreen broad- leaved forest of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-06-07

    Jun 7, 2010 ... al., 1998; Brouat and McKey, 2001; Preston and Ackerly,. 2003; Westoby and Wright, 2003), few studies have examined the scaling relationship in relation to environ- mental gradients. In order to examine the response of the leaf size-twig size relationship to environmental variations, we investi-.

  19. Broad spectrum antimicrobial activity of forest-derived soil actinomycete, Nocardia sp. PB-52

    Directory of Open Access Journals (Sweden)

    Priyanka eSharma

    2016-03-01

    Full Text Available A mesophilic actinomycete strain designated as PB-52 was isolated from soil samples of Pobitora Wildlife Sanctuary of Assam, India. Based on phenotypic and molecular characteristics, the strain was identified as Nocardia sp. which shares 99.7% sequence similarity with Nocardia niigatensis IFM 0330 (NR_112195. The strain is a Gram-positive filamentous bacterium with rugose spore surface which exhibited a wide range of antimicrobial activity against Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA, Gram-negative bacteria and yeasts. Optimization for the growth and antimicrobial metabolite production of the strain PB-52 was carried out in batch culture under shaking condition. The optimum growth and the antimicrobial metabolite production by the strain PB-52 was recorded in GLM medium at 28ºC, initial pH 7.4 of the medium and incubation period of eight days. Based on polyketide synthases (PKS and nonribosomal peptide synthetases (NRPS gene-targeted PCR amplification, the occurrence of both of these biosynthetic pathways was detected which might be involved in the production of antimicrobial metabolite in PB-52. Extract of the fermented broth culture of PB-52 was prepared with organic solvent extraction method using ethyl acetate. The ethyl acetate extract of PB-52 (EA-PB-52 showed lowest minimum inhibitory concentration (MIC against Staphylococcus aureus MTCC 96 (0.975 μg/ml whereas highest was recorded against Klebsiella pneumoniae ATCC 13883 (62.5 μg/ml. Scanning electron microscopy (SEM revealed that treatment of the test microorganisms with EA-PB-52 destroyed the targeted cells with prominent loss of cell shape and integrity. In order to determine the constituents responsible for its antimicrobial activity, EA-PB-52 was subjected to chemical analysis using gas chromatography-mass spectrometry (GC-MS. GC-MS analysis showed the presence of twelve different chemical constituents in the extract, some of which are reported to possess diverse biological activity. These results confirmed that the presence of bioactive constituents in EA-PB-52 could be a promising source for the development of potent antimicrobial agents effective against wide range of microbial pathogens including MRSA.

  20. Colostrum of Healthy Mothers Contains Broad Spectrum of Secretory IgA Autoantibodies

    Czech Academy of Sciences Publication Activity Database

    Přibylová, Jaroslava; Krausová, Klára; Kocourková, I.; Rossmann, Pavel; Klimešová, Klára; Kverka, Miloslav; Tlaskalová-Hogenová, Helena

    2012-01-01

    Roč. 32, č. 6 (2012), s. 1372-1380 ISSN 0271-9142 R&D Projects: GA ČR(CZ) GAP304/11/1252 Institutional support: RVO:61388971 Keywords : Autoantibodies * mucosal immunity * immunoglobulins Subject RIV: EC - Immunology Impact factor: 3.382, year: 2012

  1. Interfamily transfer of a plant pattern-recognition receptor confers broad-spectrum bacterial resistance

    NARCIS (Netherlands)

    Lacombe, S.; Rougon-Cardoso, A.; Sherwood, E.; Peeters, N.; Dahlbeck, D.; Esse, van H.P.; Smoker, M.; Rallapalli, G.; Thomma, B.P.H.J.; Staskawicz, B.; Jones, J.D.G.; Zipfel, C.

    2010-01-01

    Plant diseases cause massive losses in agriculture. Increasing the natural defenses of plants may reduce the impact of phytopathogens on agricultural productivity. Pattern-recognition receptors (PRRs) detect microbes by recognizing conserved pathogen-associated molecular patterns (PAMPs)1, 2, 3.

  2. Surface structures for enhancement of quantum yield in broad spectrum emission nanocrystals

    Science.gov (United States)

    Schreuder, Michael A.; McBride, James R.; Rosenthal, Sandra J.

    2014-07-22

    Disclosed are inorganic nanoparticles comprising a body comprising cadmium and/or zinc crystallized with selenium, sulfur, and/or tellurium; a multiplicity of phosphonic acid ligands comprising at least about 20% of the total surface ligand coverage; wherein the nanocrystal is capable of absorbing energy from a first electromagnetic region and capable of emitting light in a second electromagnetic region, wherein the maximum absorbance wavelength of the first electromagnetic region is different from the maximum emission wavelength of the second electromagnetic region, thereby providing a Stokes shift of at least about 20 nm, wherein the second electromagnetic region comprises an at least about 100 nm wide band of wavelengths, and wherein the nanoparticle exhibits has a quantum yield of at least about 10%. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  3. Broad spectrum screening of 463 organic contaminants in rivers in Macedonia.

    Science.gov (United States)

    Stipaničev, Draženka; Dragun, Zrinka; Repec, Siniša; Rebok, Katerina; Jordanova, Maja

    2017-01-01

    Target screening of 463 organic contaminants in surface water using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) with direct injection was performed in spring of 2015 in northern Macedonia, at six sampling sites in four rivers belonging to Vardar basin: Kriva, Zletovska, Bregalnica and Vardar. The aim of the study was to differentiate between various types of organic contamination characteristic for different types of anthropogenic activities, such as mining, agriculture, and urbanization. Depending on the studied river, 9-16% of analyzed compounds were detected. The highest total levels of organic contaminants were recorded in agriculturally impacted Bregalnica River (1839-1962ngL -1 ) and Vardar River downstream from the city of Skopje (1945ngL -1 ), whereas the lowest level was found in the mining impacted Zletovska River (989ngL -1 ). The principal organic contaminants of the Bregalnica River were herbicides (45-55% of all detected compounds; 838-1094ngL -1 ), with the highest concentrations of bentazone (407-530ngL -1 ) and molinate (84-549ngL -1 ), common herbicides in rice cultivation. The main organic contaminants in the other rivers were drugs (70-80% of all detected compounds), with antibiotics as a predominant drug class. The highest drug concentrations were measured in the Vardar River, downstream from Skopje (1544ngL -1 ). Screening of surface water by UHPLC-QTOF-MS was proven as a practical tool for fast collection of comprehensive preliminary information on organic contamination of natural waters, which can present a significant contribution in the monitoring and preservation of good ecological status of freshwater ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Legionella shows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase

    Directory of Open Access Journals (Sweden)

    Nicholas J. Tobias

    2016-11-01

    Full Text Available Several members of the genus Legionella cause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites from Legionella. Following whole genome sequencing, we assembled and annotated the Legionella parisiensis DSM 19216 genome. Together with 14 other members of the Legionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found that Legionella contains a huge variety of biosynthetic gene clusters (BGCs that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in all Legionella strains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis and secondary metabolism (polyketide and non-ribosomal peptide synthesis. Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential of Legionella.

  5. Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

    International Nuclear Information System (INIS)

    Dutta, Ranu A.; Sharma, Prashant K.; Tiwari, Vandana; Tiwari, Vivek; Patel, Anant B.; Pandey, Ravindra; Pandey, Avinash C.

    2014-01-01

    The engineering of the Gadolinium based nanostructures have been demonstrated in this paper. Nanostructures of α-Gd 2 S 3 exhibit a unique transition between ferromagnetic state and paramagnetic state of the system. It was demonstrated that their properties could be tuned for a wide range of applications ranging from hyperthermia to Magnetic Resonance Imaging, owing to their magnetic moments and large relaxivities. Metallic Gd nanoparticles obtained by reduction method were employed for cancer imaging in mice. The Gd nanoparticles were coated with Curcumin and their biomedical implications in the field of simultaneous diagnosis and therapy of cancer and related diseases has been discussed

  6. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.

    Science.gov (United States)

    Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

    2001-03-31

    Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

  7. Kidney failure related to broad-spectrum antibiotics in critically ill patients

    DEFF Research Database (Denmark)

    Jensen, Jens-Ulrik Stæhr; Hein, Lars; Lundgren, Bettina

    2012-01-01

    To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients.......To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients....

  8. A review on toxicological properties of thymoquinone a natural broad spectrum ingredient

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Nigella sativa is a delicate floral vegetable belonging to Ranunculaceae family. Thymoquinone (TQ is the dominant active component in Nigella sativa seed oil which has a variety of pharmacological properties such as antioxidant, anticancer, anti-inflammatory and analgesic activities. However, TQ is a quinone derivative, which may lead to the generation of reactive oxygen species and resulting intermediate toxicity with various adverse effects in vivo, including acute cytotoxicity, genotoxicity, immunotoxicity, and carcinogenesis. In this review we have mentioned several studies on the toxicity properties of thymoquinone and Nigella sativa. Methods: A literature search was conducted using the Web of Science, PubMed, MEDLINE and Scopus. The search included the following keywords: "thymoquinone", "hydroquinone"," quinone" and "Nigella sativa". Citations within articles were also reviewed to identify the relevant sources. We studied about 170 articles and put aside the articles that were performed on the effect of Nigella sativa and thymoquinone on cancer cell lines. Results:  Since TQ is a quinone derivative, we observed the generation of reactive oxygen species and the toxicity of this substance in some studies. LD50 of Thymoquinone was very higher than Nigella sativa and also LD50 of this substance in oral route was higher than intrapritoneal route of administration. Conclusion: The findings have provided approximate safety information for TQ, which will further help researchers.

  9. The effect of broad-spectrum antibiotics on warfarin excretion and metabolism in the rat

    International Nuclear Information System (INIS)

    Remmel, R.P.; Elmer, G.W.

    1981-01-01

    The excretion and metabolism of 14 C-warfarin in rats was examined in a crossover experiment, the first phase consisting of treatment with normal saline, the second phase using the same animals given neomycin, bacitracin, and tetracycline orally. Urine and feces were collected every 24 hours for 72 hours and examined for warfarin and its metabolites, both unconjugated and conjugated. Significantly more radioactivity was eliminated in th feces of antibiotic-treated rats. The feces of antibiotic-treated rats contained only trace amounts of beta-glucuronidase activity. Urine contained a similar ratio of unconjugated to conjugated radioactivity in both treatment groups, but the antibiotic-treated animals had significantly larger amount of conjugates in their feces. Examination of metabolic profiles of conjugated and unconjugated fractions revealed significantly fewer hydroxylated metabolites in antibiotic-treated rats, especially in the feces. The lower amount of hydroxylative metabolism in attributed to a reduction in gut flora-medicated interohepatic recycling caused by the antibiotics

  10. Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior

    NARCIS (Netherlands)

    Tielbeek, Jorim J; Johansson, Ada; Polderman, Tinca J C; Rautiainen, Marja-Riitta; Jansen, Philip; Taylor, Michelle; Tong, Xiaoran; Lu, Qing; Burt, Alexandra S; Tiemeier, Henning; Viding, Essi; Plomin, Robert; Martin, Nicholas G; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant; Beaver, Kevin M; Waldman, Irwin; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Perry, John R B; Munafò, Marcus; LoParo, Devon; Paunio, Tiina; Tiihonen, Jari; Mous, Sabine E; Pappa, Irene; de Leeuw, Christiaan; Watanabe, Kyoko; Hammerschlag, Anke R; Salvatore, Jessica E; Aliev, Fazil; Bigdeli, Tim B; Dick, Danielle; Faraone, Stephen V; Popma, Arne; Medland, Sarah E; Posthuma, Danielle

    2017-01-01

    Importance: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. Objectives: To estimate the single-nucleotide

  11. Synergistic effect of broad-spectrum Sunscreens and antihistamines in the control of idiopathic solar urticaria

    DEFF Research Database (Denmark)

    Faurschou, A.; Wulf, Hans Chr.

    2008-01-01

    . Observations: Three patients with idiopathic solar urticaria underwent phototesting with UV-B and UV-A radiation. The minimal urticarial dose (MUD) was determined 15 minutes after irradiation. The patients were subsequently tested with 5 times the MUD, and the reaction was graded every minute for 15 minutes...

  12. Broad-Spectrum Behavioral Treatment for Chronic Alcoholics: Effects of Training Controlled Drinking Skills.

    Science.gov (United States)

    Foy, David W.; And Others

    1984-01-01

    Assessed unique treatment effects of training controlled drinking skills in a chronic alcoholic population of veterans (N=62). Results of a six-month posttreatment follow-up revealed that subjects in the drinking skills condition had significantly fewer abstinent days and more abusive drinking days than subjects in the untrained condition. (LLL)

  13. Printing Proteins as Microarrays for High-Throughput Function Determination

    Science.gov (United States)

    MacBeath, Gavin; Schreiber, Stuart L.

    2000-09-01

    Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins. To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins. A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities. The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution. Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules.

  14. Bioinformatics and Microarray Data Analysis on the Cloud.

    Science.gov (United States)

    Calabrese, Barbara; Cannataro, Mario

    2016-01-01

    High-throughput platforms such as microarray, mass spectrometry, and next-generation sequencing are producing an increasing volume of omics data that needs large data storage and computing power. Cloud computing offers massive scalable computing and storage, data sharing, on-demand anytime and anywhere access to resources and applications, and thus, it may represent the key technology for facing those issues. In fact, in the recent years it has been adopted for the deployment of different bioinformatics solutions and services both in academia and in the industry. Although this, cloud computing presents several issues regarding the security and privacy of data, that are particularly important when analyzing patients data, such as in personalized medicine. This chapter reviews main academic and industrial cloud-based bioinformatics solutions; with a special focus on microarray data analysis solutions and underlines main issues and problems related to the use of such platforms for the storage and analysis of patients data.

  15. Analyses of Aloe polysaccharides using carbohydrate microarray profiling

    DEFF Research Database (Denmark)

    Isager Ahl, Louise; Grace, Olwen M; Pedersen, Henriette Lodberg

    2018-01-01

    As the popularity of Aloe vera extracts continues to rise, a desire to fully understand the individual polymer components of the leaf mesophyll, their relation to one another and the effects they have on the human body are increasing. Polysaccharides present in the leaf mesophyll have been...... identified as the components responsible for the biological activities of Aloe vera, and they have been widely studied in the past decades. However, the commonly used methods do not provide the desired platform to conduct large comparative studies of polysaccharide compositions as most of them require...... a complete or near-complete fractionation of the polymers. The objective for this study was to assess whether carbohydrate microarrays could be used for the high-throughput analysis of cell wall polysaccharides in Aloe leaf mesophyll. The method we chose is known as Comprehensive Microarray Polymer Profiling...

  16. DNA microarray technology in nutraceutical and food safety.

    Science.gov (United States)

    Liu-Stratton, Yiwen; Roy, Sashwati; Sen, Chandan K

    2004-04-15

    The quality and quantity of diet is a key determinant of health and disease. Molecular diagnostics may play a key role in food safety related to genetically modified foods, food-borne pathogens and novel nutraceuticals. Functional outcomes in biology are determined, for the most part, by net balance between sets of genes related to the specific outcome in question. The DNA microarray technology offers a new dimension of strength in molecular diagnostics by permitting the simultaneous analysis of large sets of genes. Automation of assay and novel bioinformatics tools make DNA microarrays a robust technology for diagnostics. Since its development a few years ago, this technology has been used for the applications of toxicogenomics, pharmacogenomics, cell biology, and clinical investigations addressing the prevention and intervention of diseases. Optimization of this technology to specifically address food safety is a vast resource that remains to be mined. Efforts to develop diagnostic custom arrays and simplified bioinformatics tools for field use are warranted.

  17. Homogeneous versus heterogeneous probes for microbial ecological microarrays.

    Science.gov (United States)

    Bae, Jin-Woo; Park, Yong-Ha

    2006-07-01

    Microbial ecological microarrays have been developed for investigating the composition and functions of microorganism communities in environmental niches. These arrays include microbial identification microarrays, which use oligonucleotides, gene fragments or microbial genomes as probes. In this article, the advantages and disadvantages of each type of probe are reviewed. Oligonucleotide probes are currently useful for probing uncultivated bacteria that are not amenable to gene fragment probing, whereas the functional gene fragments amplified randomly from microbial genomes require phylogenetic and hierarchical categorization before use as microbial identification probes, despite their high resolution for both specificity and sensitivity. Until more bacteria are sequenced and gene fragment probes are thoroughly validated, heterogeneous bacterial genome probes will provide a simple, sensitive and quantitative tool for exploring the ecosystem structure.

  18. Nanomedicine, microarrays and their applications in clinical microbiology

    Directory of Open Access Journals (Sweden)

    Özcan Deveci

    2010-12-01

    Full Text Available Growing interest in the future medical applications of nanotechnology is leading to the emergence of a new scientific field that called as “nanomedicine”. Nanomedicine may be defined as the investigating, treating, reconstructing and controlling human biology and health at the molecular level, using engineered nanodevices and nanostructures. Microarray technology is a revolutionary tool for elucidating roles of genes in infectious diseases, shifting from traditional methods of research to integrated approaches. This technology has great potential to provide medical diagnosis, monitor treatment and help in the development of new tools for infectious disease prevention and/or management. The aim of this paper is to provide an overview of the current application of microarray platforms and nanomedicine in the study of experimental microbiology and the impact of this technology in clinical settings.

  19. Fuzzy support vector machine for microarray imbalanced data classification

    Science.gov (United States)

    Ladayya, Faroh; Purnami, Santi Wulan; Irhamah

    2017-11-01

    DNA microarrays are data containing gene expression with small sample sizes and high number of features. Furthermore, imbalanced classes is a common problem in microarray data. This occurs when a dataset is dominated by a class which have significantly more instances than the other minority classes. Therefore, it is needed a classification method that solve the problem of high dimensional and imbalanced data. Support Vector Machine (SVM) is one of the classification methods that is capable of handling large or small samples, nonlinear, high dimensional, over learning and local minimum issues. SVM has been widely applied to DNA microarray data classification and it has been shown that SVM provides the best performance among other machine learning methods. However, imbalanced data will be a problem because SVM treats all samples in the same importance thus the results is bias for minority class. To overcome the imbalanced data, Fuzzy SVM (FSVM) is proposed. This method apply a fuzzy membership to each input point and reformulate the SVM such that different input points provide different contributions to the classifier. The minority classes have large fuzzy membership so FSVM can pay more attention to the samples with larger fuzzy membership. Given DNA microarray data is a high dimensional data with a very large number of features, it is necessary to do feature selection first using Fast Correlation based Filter (FCBF). In this study will be analyzed by SVM, FSVM and both methods by applying FCBF and get the classification performance of them. Based on the overall results, FSVM on selected features has the best classification performance compared to SVM.

  20. Genotyping microarray (gene chip) for the ABCR (ABCA4) gene.

    Science.gov (United States)

    Jaakson, K; Zernant, J; Külm, M; Hutchinson, A; Tonisson, N; Glavac, D; Ravnik-Glavac, M; Hawlina, M; Meltzer, M R; Caruso, R C; Testa, F; Maugeri, A; Hoyng, C B; Gouras, P; Simonelli, F; Lewis, R A; Lupski, J R; Cremers, F P M; Allikmets, R

    2003-11-01

    Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of ABCR variation and diagnostics have been complicated by substantial allelic heterogeneity and by differences in screening methods. To overcome these limitations, we designed a genotyping microarray (gene chip) for ABCR that includes all approximately 400 disease-associated and other variants currently described, enabling simultaneous detection of all known ABCR variants. The ABCR genotyping microarray (the ABCR400 chip) was constructed by the arrayed primer extension (APEX) technology. Each sequence change in ABCR was included on the chip by synthesis and application of sequence-specific oligonucleotides. We validated the chip by screening 136 confirmed STGD patients and 96 healthy controls, each of whom we had analyzed previously by single strand conformation polymorphism (SSCP) technology and/or heteroduplex analysis. The microarray was >98% effective in determining the existing genetic variation and was comparable to direct sequencing in that it yielded many sequence changes undetected by SSCP. In STGD patient cohorts, the efficiency of the array to detect disease-associated alleles was between 54% and 78%, depending on the ethnic composition and degree of clinical and molecular characterization of a cohort. In addition, chip analysis suggested a high carrier frequency (up to 1:10) of ABCR variants in the general population. The ABCR genotyping microarray is a robust, cost-effective, and comprehensive screening tool for variation in one gene in which mutations are responsible for a substantial fraction of retinal disease. The ABCR chip is a prototype for the next generation of screening and diagnostic tools in ophthalmic genetics, bridging clinical and scientific research. Copyright 2003 Wiley

  1. Xylella fastidiosa gene expression analysis by DNA microarrays

    OpenAIRE

    Travensolo,Regiane F.; Carareto-Alves,Lucia M.; Costa,Maria V.C.G.; Lopes,Tiago J.S.; Carrilho,Emanuel; Lemos,Eliana G.M.

    2009-01-01

    Xylella fastidiosa genome sequencing has generated valuable data by identifying genes acting either on metabolic pathways or in associated pathogenicity and virulence. Based on available information on these genes, new strategies for studying their expression patterns, such as microarray technology, were employed. A total of 2,600 primer pairs were synthesized and then used to generate fragments using the PCR technique. The arrays were hybridized against cDNAs labeled during reverse transcrip...

  2. Dynamic, electronically switchable surfaces for membrane protein microarrays.

    Science.gov (United States)

    Tang, C S; Dusseiller, M; Makohliso, S; Heuschkel, M; Sharma, S; Keller, B; Vörös, J

    2006-02-01

    Microarray technology is a powerful tool that provides a high throughput of bioanalytical information within a single experiment. These miniaturized and parallelized binding assays are highly sensitive and have found widespread popularity especially during the genomic era. However, as drug diagnostics studies are often targeted at membrane proteins, the current arraying technologies are ill-equipped to handle the fragile nature of the protein molecules. In addition, to understand the complex structure and functions of proteins, different strategies to immobilize the probe molecules selectively onto a platform for protein microarray are required. We propose a novel approach to create a (membrane) protein microarray by using an indium tin oxide (ITO) microelectrode array with an electronic multiplexing capability. A polycationic, protein- and vesicle-resistant copolymer, poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG), is exposed to and adsorbed uniformly onto the microelectrode array, as a passivating adlayer. An electronic stimulation is then applied onto the individual ITO microelectrodes resulting in the localized release of the polymer thus revealing a bare ITO surface. Different polymer and biological moieties are specifically immobilized onto the activated ITO microelectrodes while the other regions remain protein-resistant as they are unaffected by the induced electrical potential. The desorption process of the PLL-g-PEG is observed to be highly selective, rapid, and reversible without compromising on the integrity and performance of the conductive ITO microelectrodes. As such, we have successfully created a stable and heterogeneous microarray of biomolecules by using selective electronic addressing on ITO microelectrodes. Both pharmaceutical diagnostics and biomedical technology are expected to benefit directly from this unique method.

  3. Microarray analysis of gene expression profiles in ripening pineapple fruits.

    Science.gov (United States)

    Koia, Jonni H; Moyle, Richard L; Botella, Jose R

    2012-12-18

    Pineapple (Ananas comosus) is a tropical fruit crop of significant commercial importance. Although the physiological changes that occur during pineapple fruit development have been well characterized, little is known about the molecular events that occur during the fruit ripening process. Understanding the molecular basis of pineapple fruit ripening will aid the development of new varieties via molecular breeding or genetic modification. In this study we developed a 9277 element pineapple microarray and used it to profile gene expression changes that occur during pineapple fruit ripening. Microarray analyses identified 271 unique cDNAs differentially expressed at least 1.5-fold between the mature green and mature yellow stages of pineapple fruit ripening. Among these 271 sequences, 184 share significant homology with genes encoding proteins of known function, 53 share homology with genes encoding proteins of unknown function and 34 share no significant homology with any database accession. Of the 237 pineapple sequences with homologs, 160 were up-regulated and 77 were down-regulated during pineapple fruit ripening. DAVID Functional Annotation Cluster (FAC) analysis of all 237 sequences with homologs revealed confident enrichment scores for redox activity, organic acid metabolism, metalloenzyme activity, glycolysis, vitamin C biosynthesis, antioxidant activity and cysteine peptidase activity, indicating the functional significance and importance of these processes and pathways during pineapple fruit development. Quantitative real-time PCR analysis validated the microarray expression results for nine out of ten genes tested. This is the first report of a microarray based gene expression study undertaken in pineapple. Our bioinformatic analyses of the transcript profiles have identified a number of genes, processes and pathways with putative involvement in the pineapple fruit ripening process. This study extends our knowledge of the molecular basis of pineapple fruit

  4. Universal ligation-detection-reaction microarray applied for compost microbes

    Directory of Open Access Journals (Sweden)

    Romantschuk Martin

    2008-12-01

    Full Text Available Abstract Background Composting is one of the methods utilised in recycling organic communal waste. The composting process is dependent on aerobic microbial activity and proceeds through a succession of different phases each dominated by certain microorganisms. In this study, a ligation-detection-reaction (LDR based microarray method was adapted for species-level detection of compost microbes characteristic of each stage of the composting process. LDR utilises the specificity of the ligase enzyme to covalently join two adjacently hybridised probes. A zip-oligo is attached to the 3'-end of one probe and fluorescent label to the 5'-end of the other probe. Upon ligation, the probes are combined in the same molecule and can be detected in a specific location on a universal microarray with complementary zip-oligos enabling equivalent hybridisation conditions for all probes. The method was applied to samples from Nordic composting facilities after testing and optimisation with fungal pure cultures and environmental clones. Results Probes targeted for fungi were able to detect 0.1 fmol of target ribosomal PCR product in an artificial reaction mixture containing 100 ng competing fungal ribosomal internal transcribed spacer (ITS area or herring sperm DNA. The detection level was therefore approximately 0.04% of total DNA. Clone libraries were constructed from eight compost samples. The LDR microarray results were in concordance with the clone library sequencing results. In addition a control probe was used to monitor the per-spot hybridisation efficiency on the array. Conclusion This study demonstrates that the LDR microarray method is capable of sensitive and accurate species-level detection from a complex microbial community. The method can detect key species from compost samples, making it a basis for a tool for compost process monitoring in industrial facilities.

  5. DNA microarray technique for detecting food-borne pathogens

    Directory of Open Access Journals (Sweden)

    Xing GAO

    2012-08-01

    Full Text Available Objective To study the application of DNA microarray technique for screening and identifying multiple food-borne pathogens. Methods The oligonucleotide probes were designed by Clustal X and Oligo 6.0 at the conserved regions of specific genes of multiple food-borne pathogens, and then were validated by bioinformatic analyses. The 5' end of each probe was modified by amino-group and 10 Poly-T, and the optimized probes were synthesized and spotted on aldehyde-coated slides. The bacteria DNA template incubated with Klenow enzyme was amplified by arbitrarily primed PCR, and PCR products incorporated into Aminoallyl-dUTP were coupled with fluorescent dye. After hybridization of the purified PCR products with DNA microarray, the hybridization image and fluorescence intensity analysis was acquired by ScanArray and GenePix Pro 5.1 software. A series of detection conditions such as arbitrarily primed PCR and microarray hybridization were optimized. The specificity of this approach was evaluated by 16 different bacteria DNA, and the sensitivity and reproducibility were verified by 4 food-borne pathogens DNA. The samples of multiple bacteria DNA and simulated water samples of Shigella dysenteriae were detected. Results Nine different food-borne bacteria were successfully discriminated under the same condition. The sensitivity of genomic DNA was 102 -103pg/ μl, and the coefficient of variation (CV of the reproducibility of assay was less than 15%. The corresponding specific hybridization maps of the multiple bacteria DNA samples were obtained, and the detection limit of simulated water sample of Shigella dysenteriae was 3.54×105cfu/ml. Conclusions The DNA microarray detection system based on arbitrarily primed PCR can be employed for effective detection of multiple food-borne pathogens, and this assay may offer a new method for high-throughput platform for detecting bacteria.

  6. The broad utility of Trizac diamond tile

    Science.gov (United States)

    Gagliardi, John I.; Romero, Vincent D.; Sventek, Bruce; Zu, Lijun

    2017-10-01

    Sample finishing data from a broad range of materials — glasses, sapphire, silicon carbide, silicon, zirconium oxide, lithium tantalate, and flooring materials — are shown effectively processed with Trizact™ Diamond Tile (TDT). This data should provide the reader with an understanding of what to expect when using TDT on hard to grind or brittle materials. Keys to maintaining effective TDT pad wear rates, and therefore cost effect and stable processes, are described as managing 1) the proper lubricant flow rate for glasses and silicon-type materials and 2) the conditioning particle concentration for harder-to-grind materials

  7. DNA Microarray Technologies: A Novel Approach to Geonomic Research

    Energy Technology Data Exchange (ETDEWEB)

    Hinman, R.; Thrall, B.; Wong, K,

    2002-01-01

    A cDNA microarray allows biologists to examine the expression of thousands of genes simultaneously. Researchers may analyze the complete transcriptional program of an organism in response to specific physiological or developmental conditions. By design, a cDNA microarray is an experiment with many variables and few controls. One question that inevitably arises when working with a cDNA microarray is data reproducibility. How easy is it to confirm mRNA expression patterns? In this paper, a case study involving the treatment of a murine macrophage RAW 264.7 cell line with tumor necrosis factor alpha (TNF) was used to obtain a rough estimate of data reproducibility. Two trials were examined and a list of genes displaying either a > 2-fold or > 4-fold increase in gene expression was compiled. Variations in signal mean ratios between the two slides were observed. We can assume that erring in reproducibility may be compensated by greater inductive levels of similar genes. Steps taken to obtain results included serum starvation of cells before treatment, tests of mRNA for quality/consistency, and data normalization.

  8. MAGMA: analysis of two-channel microarrays made easy.

    Science.gov (United States)

    Rehrauer, Hubert; Zoller, Stefan; Schlapbach, Ralph

    2007-07-01

    The web application MAGMA provides a simple and intuitive interface to identify differentially expressed genes from two-channel microarray data. While the underlying algorithms are not superior to those of similar web applications, MAGMA is particularly user friendly and can be used without prior training. The user interface guides the novice user through the most typical microarray analysis workflow consisting of data upload, annotation, normalization and statistical analysis. It automatically generates R-scripts that document MAGMA's entire data processing steps, thereby allowing the user to regenerate all results in his local R installation. The implementation of MAGMA follows the model-view-controller design pattern that strictly separates the R-based statistical data processing, the web-representation and the application logic. This modular design makes the application flexible and easily extendible by experts in one of the fields: statistical microarray analysis, web design or software development. State-of-the-art Java Server Faces technology was used to generate the web interface and to perform user input processing. MAGMA's object-oriented modular framework makes it easily extendible and applicable to other fields and demonstrates that modern Java technology is also suitable for rather small and concise academic projects. MAGMA is freely available at www.magma-fgcz.uzh.ch.

  9. Surface defect assisted broad spectra emission from CdSe quantum dots for white LED application

    Science.gov (United States)

    Samuel, Boni; Mathew, S.; Anand, V. R.; Correya, Adrine Antony; Nampoori, V. P. N.; Mujeeb, A.

    2018-02-01

    This paper reports, broadband photoluminescence from CdSe quantum dots (QDs) under the excitation of 403 nm using fluorimeter and 403 nm CW laser excitation. The broad spectrum obtained from the colloidal quantum dots was ranges from 450 nm to 800 nm. The broadness of the spectra was attributed to the merging of band edge and defect driven emissions from the QDs. Six different sizes of particles were prepared via kinetic growth method by using CdO and elemental Se as sources of Cd and Se respectively. The particle sizes were measured from TEM images. The size dependent effect on broad emission was also studied and the defect state emission was found to be predominant in very small QDs. The defect driven emission was also observed to be redshifted, similar to the band edge emission, due to quantum confinement effect. The emission corresponding to different laser power was also studied and a linear relation was obtained. In order to study the colour characteristics of the emission, CIE chromaticity coordinate, CRI and CCT of the prepared samples were measured. It is observed that, these values were tunable by the addition of suitable intensity of blue light from the excitation source to yield white light of various colour temperatures. The broad photoluminescence spectrum of the QDs, were compared with that of a commercially available white LED. It was found that the prepared QDs are good alternatives for the phosphor in phosphor converted white LEDs, to provide good spectral tunability.

  10. Many channel spectrum unfolding

    International Nuclear Information System (INIS)

    Najzer, M.; Glumac, B.; Pauko, M.

    1980-01-01

    The principle of the ITER unfolding code as used for the many channel spectrum unfolding is described. Its unfolding ability is tested on seven typical neutron spectra. The effect of the initial spectrum approximation upon the solution is discussed

  11. Pulsar Emission Spectrum

    OpenAIRE

    Gruzinov, Andrei

    2013-01-01

    Emission spectrum is calculated for a weak axisymmetric pulsar. Also calculated are the observed spectrum, efficiency, and the observed efficiency. The underlying flow of electrons and positrons turns out to be curiously intricate.

  12. Autism Spectrum Disorder

    Science.gov (United States)

    ... Caregiver Education » Fact Sheets Autism Spectrum Disorder Fact Sheet What is autism spectrum disorder? What are some ... of mutations in individual genes but rather spontaneous coding mutations across many genes. De novo mutations may ...

  13. Broad ion beam serial section tomography

    Energy Technology Data Exchange (ETDEWEB)

    Winiarski, B., E-mail: b.winiarski@manchester.ac.uk [School of Materials, University of Manchester, Manchester M13 9PL (United Kingdom); Materials Division, National Physical Laboratory, Teddington TW11 0LW (United Kingdom); Gholinia, A. [School of Materials, University of Manchester, Manchester M13 9PL (United Kingdom); Mingard, K.; Gee, M. [Materials Division, National Physical Laboratory, Teddington TW11 0LW (United Kingdom); Thompson, G.E.; Withers, P.J. [School of Materials, University of Manchester, Manchester M13 9PL (United Kingdom)

    2017-01-15

    Here we examine the potential of serial Broad Ion Beam (BIB) Ar{sup +} ion polishing as an advanced serial section tomography (SST) technique for destructive 3D material characterisation for collecting data from volumes with lateral dimensions significantly greater than 100 µm and potentially over millimetre sized areas. Further, the associated low level of damage introduced makes BIB milling very well suited to 3D EBSD acquisition with very high indexing rates. Block face serial sectioning data registration schemes usually assume that the data comprises a series of parallel, planar slices. We quantify the variations in slice thickness and parallelity which can arise when using BIB systems comparing Gatan PECS and Ilion BIB systems for large volume serial sectioning and 3D-EBSD data acquisition. As a test case we obtain 3D morphologies and grain orientations for both phases of a WC-11%wt. Co hardmetal. In our case we have carried out the data acquisition through the manual transfer of the sample between SEM and BIB which is a very slow process (1–2 slice per day), however forthcoming automated procedures will markedly speed up the process. We show that irrespective of the sectioning method raw large area 2D-EBSD maps are affected by distortions and artefacts which affect 3D-EBSD such that quantitative analyses and visualisation can give misleading and erroneous results. Addressing and correcting these issues will offer real benefits when large area (millimetre sized) automated serial section BIBS is developed. - Highlights: • In this work we examine how microstructures can be reconstructed in three-dimensions (3D) by serial argon broad ion beam (BIB) milling, enabling much larger volumes (>250×250×100µm{sup 3}) to be acquired than by serial section focused ion beam-scanning electron microscopy (FIB-SEM). • The associated low level of damage introduced makes BIB milling very well suited to 3D-EBSD acquisition with very high indexing rates. • We explore

  14. Study on broad beam heavy ion CT

    International Nuclear Information System (INIS)

    Ohno, Yumiko; Kohno, Toshiyuki; Sasaki, Hitomi; Nanbu, S.; Kanai, Tatsuaki

    2003-01-01

    To achieve the heavy ion radiotherapy more precisely, it is important to know the distribution of the electron density in a human body, which is highly related to the range of charged particles. From a heavy ion CT image, we can directly obtain the 2-D distribution of the electron density in a sample. For this purpose, we have developed a broad beam heavy ion CT system. The electron density was obtained using some kinds of solutions targets. Also the dependence of the spatial resolution on the target size and the kinds of beams was estimated in this work using cylinders targets of 40, 60 and 80 mm in diameter, each of them has a hole of 10 mm in diameter at the center of it. (author)

  15. Broad Ligament Haematoma Following Normal Vaginal Delivery.

    Science.gov (United States)

    Ibrar, Faiza; Awan, Azra Saeed; Fatima, Touseef; Tabassum, Hina

    2017-01-01

    A 37-year-old, patient presented in emergency with history of normal vaginal delivery followed by development of abdominal distention, vomiting, constipation for last 3 days. She was para 4 and had normal vaginal delivery by traditional birth attendant at peripheral hospital 3 days back. Imaging study revealed a heterogeneous complex mass, ascites, pleural effusion, air fluid levels with dilatation gut loops. Based upon pelvic examination by senior gynaecologist in combination with ultrasound; a clinical diagnosis of broad ligament haematoma was made. However, vomiting and abdominal distention raised suspicion of intestinal obstruction. Due to worsening abdominal distention exploratory laparotomy was carried out. It was pseudo colonic obstruction and caecostomy was done. Timely intervention by multidisciplinary approach saved patient life with minimal morbidity.

  16. A broad view of model validation

    International Nuclear Information System (INIS)

    Tsang, C.F.

    1989-10-01

    The safety assessment of a nuclear waste repository requires the use of models. Such models need to be validated to ensure, as much as possible, that they are a good representation of the actual processes occurring in the real system. In this paper we attempt to take a broad view by reviewing step by step the modeling process and bringing out the need to validating every step of this process. This model validation includes not only comparison of modeling results with data from selected experiments, but also evaluation of procedures for the construction of conceptual models and calculational models as well as methodologies for studying data and parameter correlation. The need for advancing basic scientific knowledge in related fields, for multiple assessment groups, and for presenting our modeling efforts in open literature to public scrutiny is also emphasized. 16 refs

  17. Broad-lined Supernova 2016coi with a Helium Envelope

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Masayuki [Department of Physics, Faculty of Science and Engineering, Konan University, Okamoto, Kobe, Hyogo 658-8501 (Japan); Nakaoka, Tatsuya; Kawabata, Miho [Department of Physical Science, Hiroshima University, Kagamiyama 1-3-1, Higashi-Hiroshima 739-8526 (Japan); Tanaka, Masaomi [National Astronomical Observatory of Japan, National Institutes of Natural Sciences, Osawa, Mitaka, Tokyo 181-8588 (Japan); Maeda, Keiichi [Department of Astronomy, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan); Honda, Satoshi; Hosoya, Kensuke; Karita, Mayu; Morihana, Kumiko [Nishi-Harima Astronomical Observatory, Center for Astronomy, University of Hyogo, 407-2 Nishigaichi, Sayo-cho, Sayo, Hyogo 679-5313 (Japan); Hanayama, Hidekazu [Ishigakijima Astronomical Observatory, National Astronomical Observatory of Japan, National Institutes of Natural Sciences, 1024-1 Arakawa, Ishigaki, Okinawa 907-0024 (Japan); Morokuma, Tomoki [Institute of Astronomy, Graduate School of Science, The University of Tokyo, 2-21-1 Osawa, Mitaka, Tokyo 181-0015 (Japan); Imai, Masataka [Department of Cosmosciences, Graduate School of Science, Hokkaido University, Kita 10 Nishi8, Kita-ku, Sapporo 060-0810 (Japan); Kinugasa, Kenzo [Nobeyama Radio Observatory, National Astronomical Observatory of Japan, National Institutes of Natural Sciences, 462-2 Nobeyama, Minamimaki, Minamisaku, Nagano 384-1305 (Japan); Murata, Katsuhiro L. [Department of Astrophysics, Nagoya University, Chikusa-ku, Nagoya 464-8602 (Japan); Nishimori, Takefumi; Gima, Hirotaka; Ito, Ayano; Morikawa, Yuto; Murakami, Kotone [Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065 (Japan); Hashimoto, Osamu, E-mail: yamanaka@center.konan-u.ac.jp [Gunma Astronomical Observatory, Takayama, Gunma 377-0702 (Japan); and others

    2017-03-01

    We present the early-phase spectra and the light curves of the broad-lined (BL) supernova (SN) 2016coi from t = 7 to 67 days after the estimated explosion date. This SN was initially reported as a BL Type SN Ic (SN Ic-BL). However, we found that spectra up to t = 12 days exhibited the He i λ 5876, λ 6678, and λ 7065 absorption lines. We show that the smoothed and blueshifted spectra of normal SNe Ib are remarkably similar to the observed spectrum of SN 2016coi. The line velocities of SN 2016coi were similar to those of SNe Ic-BL and significantly faster than those of SNe Ib. Analyses of the line velocity and light curve suggest that the kinetic energy and the total ejecta mass of SN 2016coi are similar to those of SNe Ic-BL. Together with BL SNe 2009bb and 2012ap, for which the detection of He i was also reported, these SNe could be transitional objects between SNe Ic-BL and SNe Ib, and be classified as BL Type “Ib” SNe (SNe “Ib”-BL). Our work demonstrates the diversity of the outermost layer in BL SNe, which should be related to the variety of the evolutionary paths.

  18. Broad targeting of resistance to apoptosis in cancer

    Science.gov (United States)

    Mohammad, Ramzi M.; Muqbil, Irfana; Lowe, Leroy; Yedjou, Clement; Hsu, Hsue-Yin; Lin, Liang-Tzung; Siegelin, Markus David; Fimognari, Carmela; Kumar, Nagi B.; Dou, Q. Ping; Yang, Huanjie; Samadi, Abbas K.; Russo, Gian Luigi; Spagnuolo, Carmela; Ray, Swapan K.; Chakrabarti, Mrinmay; Morre, James D.; Coley, Helen M.; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, William G.; Yang, Xujuan; Boosani, Chandra S.; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Keith, W. Nicol; Bilsland, Alan; Halicka, Dorota; Nowsheen, Somaira; Azmi, Asfar S.

    2015-01-01

    Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer. PMID:25936818

  19. A method for the possible species discrimination of juvenile gadoids by broad-bandwidth backscattering spectra vs. angle of incidence

    DEFF Research Database (Denmark)

    Lundgren, Bo; Nielsen, J. Rasmus

    2008-01-01

    , alignment of acoustic and optical-reference frames, and automatic position-fitting of fish models to manually marked fix-points on fish images. The software also performs Fourier spectrum analysis and pulse-shape analysis of broad-bandwidth echoes. Therefore, several measurement series on free...

  20. Micro-Analyzer: automatic preprocessing of Affymetrix microarray data.

    Science.gov (United States)

    Guzzi, Pietro Hiram; Cannataro, Mario

    2013-08-01

    A current trend in genomics is the investigation of the cell mechanism using different technologies, in order to explain the relationship among genes, molecular processes and diseases. For instance, the combined use of gene-expression arrays and genomic arrays has been demonstrated as an effective instrument in clinical practice. Consequently, in a single experiment different kind of microarrays may be used, resulting in the production of different types of binary data (images and textual raw data). The analysis of microarray data requires an initial preprocessing phase, that makes raw data suitable for use on existing analysis platforms, such as the TIGR M4 (TM4) Suite. An additional challenge to be faced by emerging data analysis platforms is the ability to treat in a combined way those different microarray formats coupled with clinical data. In fact, resulting integrated data may include both numerical and symbolic data (e.g. gene expression and SNPs regarding molecular data), as well as temporal data (e.g. the response to a drug, time to progression and survival rate), regarding clinical data. Raw data preprocessing is a crucial step in analysis but is often performed in a manual and error prone way using different software tools. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of different microarray data are needed. The paper presents Micro-Analyzer (Microarray Analyzer), a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix gene expression and SNP binary data. It represents the evolution of the μ-CS tool, extending the preprocessing to SNP arrays that were not allowed in μ-CS. The Micro-Analyzer is provided as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data (gene expression and SNPs) by invoking TM4 platform. It avoids: (i) the manual invocation of external tools (e.g. the Affymetrix Power