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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. Broad-spectrum respiratory tract pathogen identification using resequencing DNA microarrays

    OpenAIRE

    Lin, Baochuan; Wang, Zheng; Vora, Gary J.; Jennifer A. Thornton; Schnur, Joel M.; Thach, Dzung C.; Blaney, Kate M.; Ligler, Adam G.; Malanoski, Anthony P.; Santiago, Jose; Walter, Elizabeth A.; Agan, Brian K.; Metzgar, David; Seto, Donald; Daum, Luke T.

    2006-01-01

    The exponential growth of pathogen nucleic acid sequences available in public domain databases has invited their direct use in pathogen detection, identification, and surveillance strategies. DNA microarray technology has offered the potential for the direct DNA sequence analysis of a broad spectrum of pathogens of interest. However, to achieve the practical attainment of this potential, numerous technical issues, especially nucleic acid amplification, probe specificity, and interpretation st...

  3. Broad spectrum antibiotic compounds and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Koglin, Alexander; Strieker, Matthias

    2016-07-05

    The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

  4. 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.

  5. Broad spectrum anthelmintic potential of Cassia plants

    Institute of Scientific and Technical Information of China (English)

    Suman Kundu; Saptarshi Roy; Larisha Mawkhleing Lyndem

    2014-01-01

    Objective: To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia(C. angustifolia) and Cassia occidentalis (C. occidentalis). angustifolia Methods: Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently.Results: C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33±2.07) h, treated worms lost their motility at (5.71±0.10) h, (6.60±0.86) h and (13.95±0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49±1.38) h in control, but with plant treatment, it lost its motility in just (0.57±0.08) h, (1.00±0.12) h and (1.47±0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively.Raillietina tetragona on the other hand became paralysed at (1.68±0.27) h, (2.95±0.29) h and (4.13±0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93±4.71) h.Conclusions:This present study indicated broad spectrum vermifugal activity of all plants tested.

  6. Broad-Spectrum Solution-Processed Photovoltaics

    Science.gov (United States)

    Ip, Alexander Halley

    High global demand for energy coupled with dwindling fossil fuel supply has driven the development of sustainable energy sources such as solar photovoltaics. Emerging solar technologies aim for low-cost, solution-processable materials which would allow wide deployment. Colloidal quantum dots (CQDs) are such a materials system which exhibits the ability to absorb across the entire solar spectrum, including in the infrared where many technologies cannot harvest photons. However, due to their nanocrystalline nature, CQDs are susceptible to surface-associated electronic traps which greatly inhibit performance. In this thesis, surface engineering of CQDs is presented through a combined ligand approach which improves the passivation of surface trap states. A metal halide treatment is found to passivate quantum dot surfaces in solution, while bifunctional organic ligands produce a dense film in solid state. This approach reduced midgap trap states fivefold compared with conventional passivation strategies and led to solar cells with a record certified 7.0% power conversion efficiency. The effect of this process on the electronic structure is studied through photoelectron spectroscopy. It is found that while the halide provides deep trap passivation, the nature of the metal cation on the CQD surface affects the density of band tail states. This effect is explored further through a wide survey of materials, and it is found that the coordination ability of the metal cation is responsible for the suppression of shallow traps. With this understanding of CQD surface passivation, broad spectral usage is then explored through a study of visible-absorbing organolead halide perovskite materials as well as narrow-bandgap CQD solar cells. Control over growth conditions and modification of electrode interfaces resulted in efficient perovskite devices with effective usages of visible photons. For infrared-absorbing CQDs, it is found that, in addition to providing surface trap

  7. Broad Spectrum Sanitizing Wipes with Food Additives Project

    Data.gov (United States)

    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...

  8. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    Full Text Available UNLABELLED: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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

  9. The broad spectrum revisited: Evidence from plant remains

    OpenAIRE

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

    2004-01-01

    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...

  10. Broad-spectrum antimicrobial polycarbonate hydrogels with fast degradability.

    Science.gov (United States)

    Pascual, Ana; Tan, Jeremy P K; Yuen, Alex; Chan, Julian M W; Coady, Daniel J; Mecerreyes, David; Hedrick, James L; Yang, Yi Yan; Sardon, Haritz

    2015-04-13

    In this study, a new family of broad-spectrum antimicrobial polycarbonate hydrogels has been successfully synthesized and characterized. Tertiary amine-containing eight-membered monofunctional and difunctional cyclic carbonates were synthesized, and chemically cross-linked polycarbonate hydrogels were obtained by copolymerizing these monomers with a poly(ethylene glycol)-based bifunctional initiator via organocatalyzed ring-opening polymerization using 1,8-diazabicyclo[5.4.0]undec-7-ene catalyst. The gels were quaternized using methyl iodide to confer antimicrobial properties. Stable hydrogels were obtained only when the bifunctional monomer concentration was equal to or higher than 12 mol %. In vitro antimicrobial studies revealed that all quaternized hydrogels exhibited broad-spectrum antimicrobial activity against Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), Pseudomonas aeruginosa (Gram-negative), and Candida albicans (fungus), while the antimicrobial activity of the nonquaternized hydrogels was negligible. Moreover, the gels showed fast degradation at room temperature (4-6 days), which makes them ideal candidates for wound healing and implantable biomaterials.

  11. Broad spectrum moderators and advanced reflector filters using 208Pb

    DEFF Research Database (Denmark)

    Schönfeldt, Troels; Batkov, K.; Klinkby, Esben Bryndt;

    2015-01-01

    thermalizing property of 208Pb to design a broad spectrum moderator, i.e. a moderator which emits thermal and cold neutrons from the same position. Using 208Pb as a reflector filter material is shown to be slightly less efficient than a conventional beryllium reflector filter. However, when surrounding......Cold and thermal neutrons used in neutrons scattering experiments are produced in nuclear reactors and spallation sources. The neutrons are cooled to thermal or cold temperatures in thermal and cold moderators, respectively. The present study shows that it is possible to exploit the poor...... the reflector filter by a cold moderator it is possible to regain the neutrons with wavelengths below the Bragg edge, which are suppressed in the beryllium reflector filter. In both the beryllium and lead case surrounding the reflector filter with a cold moderator increases the cold brightness significantly...

  12. Genetically Engineered Broad-Spectrum Disease Resistance in Tomato

    Science.gov (United States)

    Oldroyd, Giles E. D.; Staskawicz, Brian J.

    1998-08-01

    Resistance in tomato to the bacterial pathogen Pseudomonas syringae pathovar tomato requires Pto and Prf. Mutations that eliminate Prf show a loss of both Pto resistance and sensitivity to the organophosphate insecticide fenthion, suggesting that Prf controls both phenotypes. Herein, we report that the overexpression of Prf leads to enhanced resistance to a number of normally virulent bacterial and viral pathogens and leads to increased sensitivity to fenthion. These plants express levels of salicylic acid comparable to plants induced for systemic acquired resistance (SAR) and constitutively express pathogenesis related genes. These results suggest that the overexpression of Prf activates the Pto and Fen pathways in a pathogen-independent manner and leads to the activation of SAR. Transgene-induced SAR has implications for the generation of broad spectrum disease resistance in agricultural crop plants.

  13. Antibiofilm Peptides: Potential as Broad-Spectrum Agents.

    Science.gov (United States)

    Pletzer, Daniel; Hancock, Robert E W

    2016-10-01

    The treatment of bacterial diseases is facing twin threats, with increasing bacterial antibiotic resistance and relatively few novel compounds or strategies under development or entering the clinic. Bacteria frequently grow on surfaces as biofilm communities encased in a polymeric matrix. The biofilm mode of growth is associated with 65 to 80% of all clinical infections. It causes broad adaptive changes; biofilm bacteria are especially (10- to 1,000-fold) resistant to conventional antibiotics and to date no antimicrobials have been developed specifically to treat biofilms. Small synthetic peptides with broad-spectrum antibiofilm activity represent a novel approach to treat biofilm-related infections. Recent developments have provided evidence that these peptides can inhibit even developed biofilms, kill multiple bacterial species in biofilms (including the ESKAPE [Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species] pathogens), show strong synergy with several antibiotics, and act by targeting a universal stress response in bacteria. Thus, these peptides represent a promising alternative treatment to conventional antibiotics and work effectively in animal models of biofilm-associated infections. PMID:27068589

  14. Broad-spectrum identification and discrimination between biothreat agents and near-neighbor species

    Science.gov (United States)

    Malanoski, Anthony P.; Leski, Tomasz A.; Cheng, Luke; Wang, Zheng; Stenger, David A.; Lin, Baochuan

    2009-05-01

    A comprehensive resequencing microarray "Tropical and Emerging Infections (TessArray RPM-TEI 1.0 array)" has been developed to identify and distinguish between biothreat organisms of interest and genetically close related species. This array has undergone validation using an innovative approach where synthetic DNA fragments are used for organisms that it is not safe to work with outside a biosafety 3 facilities. The approach was confirmed from testing a subset of target organisms, such as Ebola viruses and Lassa viruses, at USAMRIID. Most potential biothreat organisms are actually endemic in some part of the world. Proper surveillance of biothreat agents will require some form of monitoring the evolution of the indigenous organisms under their natural environment, so when changes in the organisms occur, the diagnostic assays for these organisms can be reviewed to assure they still provide detection. Using the resequencing microarray (RPM) for detection in locations such as the Africa can support indigenous monitoring as it provides sequence information. An ongoing collaboration with Njala University aims to establish a broad-spectrum pathogen surveillance capability in the Republic of Sierra Leone, West Africa using RPM technology combined with a Geographic Information System. This has the potential to improve the public health efforts in an infected area as well as provide monitoring of the changes occurring to a biothreat organism, i.e. Lassa viruses, in its natural location.

  15. Characteristics of doripenem: a new broad-spectrum antibiotic

    Directory of Open Access Journals (Sweden)

    Francisco Alvarez-Lerma

    2009-05-01

    Full Text Available Francisco Alvarez-Lerma1, Santiago Grau2, Olivia Ferrández21Intensive Care Unit, 2Pharmacy Department, Hospital Del Mar, Barcelona, SpainAbstract: Doripenem (S-4661 is a new parenteral antibiotic from the carbapenem class; similarly to imipenem and meropenem, it has a broad-spectrum activity against Gram-positive, Gram-negative, and anaerobic bacteria. It is active against multiresistant Gram-negative bacilli such as extended-spectrum beta-lactamase-producing (ESBL Gram-negative Enterobacteriaceae and nonfermentative Gram-negative bacilli including some strains of Pseudomonas aeruginosa that are resistant to other carbapenems. Doripenem’s chemical structure is similar to that of meropenem (substitution of one sulfamoxil-aminomethyl chain for the dimethyl-carboxyl chain, and has one 1-beta-methyl chain which provides resistance to dehydropeptidase-I enzyme. The clinical trials conducted so far have focused on the treatment of severe infections such as complicated intra-abdominal infections, complicated urinary tract infections and pyelonephritis, nosocomial pneumonia, and ventilator-associated pneumonia. Given its activity profile and the results from the clinical trials, this antibiotic may be used for empirical treatment of multibacterial infections produced by potentially multiresistant Gram-negative bacilli. In 2007, the US Food and Drug Administration approved the use of doripenem for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. The European Medicines Agency has approved the use of doripenem for the same indications in addition to nosocomial pneumonia regardless of whether it is ventilator-associated or not.Keywords: doripenem, antimicrobial activity, clinical efficacy, pharmacokinetics, tolerability

  16. Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT-PCR DNA microarray system.

    Science.gov (United States)

    Huguenin, Antoine; Moutte, Lauryane; Renois, Fanny; Leveque, Nicolas; Talmud, Deborah; Abely, Michel; Nguyen, Yohan; Carrat, Fabrice; Andreoletti, Laurent

    2012-06-01

    Newly available molecular tools allow a sensitive detection of a broad panel of viruses in respiratory tract specimens. In the present study, the application of a multiplex RT-PCR DNA microarray in diagnosis and epidemiological survey of viral infections in infants hospitalized for bronchiolitis was assessed. One hundred and thirty-eight nasopharyngeal aspirates collected from October 2007 to September 2008 were tested by direct immunofluorescence and viral culture, a combination of referenced RT-PCRs and the DNA microarray. One or more viruses were detected in 96, 126 and 126 of the specimens by direct immunofluorescence and viral culture, RT-PCRs and DNA microarray, respectively (70 vs. 91 vs. 91%, P 0.1). In conclusion, the use of this DNA microarray in clinical virology practice allows rapid and accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. It should improve the clinical management, the epidemiological survey, and the prevention of the nosocomial transmission of respiratory viruses in pediatric wards. PMID:22499022

  17. Mucin biopolymers as broad-spectrum antiviral agents

    Science.gov (United States)

    Lieleg, Oliver; Lieleg, Corinna; Bloom, Jesse; Buck, Christopher B.; Ribbeck, Katharina

    2012-01-01

    Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system. PMID:22475261

  18. 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.

  19. The broad autism phenotype predicts child functioning in autism spectrum disorders

    OpenAIRE

    Maxwell, Christina R.; Parish-Morris, Julia; Hsin, Olivia; Bush, Jennifer C; Schultz, Robert T.

    2013-01-01

    Background Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connecti...

  20. Achievement of Narrow-Band CARS Signal by Manipulating Broad-band Laser Spectrum

    International Nuclear Information System (INIS)

    We theoretically demonstrate the achievement of narrow-band coherent anti-Stokes Raman scattering (CARS) signal by manipulating broad-band probe spectrum. The narrowing of the CARS signal depends on the spectrum bandwidth of the probe beam, and thus high-resolution CARS signal for a complicated quantum system can be obtained by the simple spectrum manipulation. Furthermore, the energy-level diagram for the complicated quantum system can also be labelled by measuring the CARS signal at a given frequency. (fundamental areas of phenomenology (including applications))

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

    Science.gov (United States)

    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.

  2. 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)…

  3. Draft Genome Sequence of the Broad-Spectrum Xenobiotic Degrader Achromobacter xylosoxidans ADAF13

    OpenAIRE

    Iyer, Rupa; Damania, Ashish

    2016-01-01

    Achromobacter xylosoxidans ADAF13, isolated from farmland soil, possesses a large number of putative degradation genes and pathways that break down a wide variety of aromatic hydrocarbons, pesticides, endocrine disruptors, and other high-impact xenobiotics. These properties make this strain an excellent candidate for further development as a broad-spectrum bioremediation agent.

  4. Are Broad-Spectrum Fluoroquinolones More Likely To Cause Clostridium difficile-Associated Disease?

    OpenAIRE

    Dhalla, Irfan A.; Muhammad M Mamdani; Simor, Andrew E; Kopp, Alex; Rochon, Paula A; Juurlink, David N.

    2006-01-01

    Limited evidence suggests that broad-spectrum fluoroquinolones such as gatifloxacin and moxifloxacin are more likely to cause Clostridium difficile-associated disease than levofloxacin. In a population-based case-control study of outpatients prescribed fluoroquinolones, we found no increased risk of C. difficile-associated disease requiring hospitalization among patients prescribed gatifloxacin or moxifloxacin compared to levofloxacin.

  5. Resistance of nanobacteria isolated from urinary and kidney stones to broad-spectrum antibiotics.

    Directory of Open Access Journals (Sweden)

    Hadi Sardarabadi

    2014-08-01

    Full Text Available Nanoscopic life forms called Nanobacteria or calcifying nanoparticles (CNP are unconventional agents. These novel organisms are very small (0.1 to 0.5 microns and possess unusual properties such as high resistance to heat and routine antimicrobial agents. Nanobacteria are 100 times smaller than bacteria and protected by a shell of apatite, so they could be as candidate for emerging and progress of in vivo pathological calcification. In this study, the inhibitory effect of broad-spectrum antibiotics on growth of these new forms of life has been investigated.Powdered urinary and kidney stones were demineralized with HCl and neutralized with appropriate buffers and became filtered. Finally suspension was incubated in DMEM medium with Fetal Bovine Serum (FBS and broad-spectrum antibiotics (100U/ml for penicillin and 100μg/ml for streptomycin for 60 days.In the presence of broad-spectrum antibiotics, Scanning Electron Micrographs (SEM showed a spherical shape of these nanobacteria. Also, Energy Dispersive X-ray spectroscopy (EDS showed a pick for calcium and phosphor. Transmission Electron Microscopy (TEM results illustrated cover around the nanobacteria.The growth of calcifying nanoparticles after adding the broad-spectrum antibiotics may be due to their apatite hard shells supporting them against penetration of the antibiotics.

  6. Draft Genome Sequence of the Broad-Spectrum Xenobiotic Degrader Achromobacter xylosoxidans ADAF13.

    Science.gov (United States)

    Iyer, Rupa; Damania, Ashish

    2016-01-01

    Achromobacter xylosoxidansADAF13, isolated from farmland soil, possesses a large number of putative degradation genes and pathways that break down a wide variety of aromatic hydrocarbons, pesticides, endocrine disruptors, and other high-impact xenobiotics. These properties make this strain an excellent candidate for further development as a broad-spectrum bioremediation agent. PMID:27081123

  7. 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...

  8. 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...

  9. Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population

    Science.gov (United States)

    Al-Mamari, Watfa; Al-Saegh, Abeer; Al-Kindy, Adila; Bruwer, Zandre; Al-Murshedi, Fathiya; Al-Thihli, Khalid

    2015-01-01

    Autism Spectrum Disorders are a complicated group of disorders characterized with heterogeneous genetic etiologies. The genetic investigations for this group of disorders have expanded considerably over the past decade. In our study we designed a tired approach and studied the diagnostic yield of chromosomal microarray analysis on patients…

  10. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study

    Science.gov (United States)

    Bergholt, Thomas; Bouaziz, Olivier; Arpi, Magnus; Eriksson, Frank; Rasmussen, Steen; Keiding, Niels; Løkkegaard, Ellen C.

    2016-01-01

    Background Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset 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 of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. Conclusions Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section. PMID:27560963

  11. 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.

  12. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.

    Science.gov (United States)

    Zasloff, Michael; Adams, A Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M; Weaver, Scott C; Wong, Gerard C L

    2011-09-20

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored. PMID:21930925

  13. Artificial TALE as a Convenient Protein Platform for Engineering Broad-Spectrum Resistance to Begomoviruses.

    Science.gov (United States)

    Cheng, Xiaofei; Li, Fangfang; Cai, Jianyu; Chen, Wei; Zhao, Nan; Sun, Yuqiang; Guo, Yushuang; Yang, Xiuling; Wu, Xiaoyun

    2015-08-01

    Transcription activator-like effectors (TALEs) are a class of sequence-specific DNA-binding proteins that utilize a simple and predictable modality to recognize target DNA. This unique characteristic allows for the rapid assembly of artificial TALEs, with high DNA binding specificity, to any target DNA sequences for the creation of customizable sequence-specific nucleases used in genome engineering. Here, we report the use of an artificial TALE protein as a convenient platform for designing broad-spectrum resistance to begomoviruses, one of the most destructive plant virus groups, which cause tremendous losses worldwide. We showed that artificial TALEs, which were assembled based on conserved sequence motifs within begomovirus genomes, could confer partial resistance in transgenic Nicotiana benthamiana to all three begomoviruses tested. Furthermore, the resistance was maintained even in the presence of their betasatellite. These results shed new light on the development of broad-spectrum resistance against DNA viruses, such as begomoviruses. PMID:26308041

  14. The Discussion about Truth Viewpoint and its Significance on the View of Broad-Spectrum Philosophy

    Directory of Open Access Journals (Sweden)

    Facheng Shang

    2012-11-01

    Full Text Available In this study, we have a discussion about truth viewpoint and its significance on the view of Broad-spectrum Philosophy, which inherit and develop the truth of Marxist philosophy Broad-spectrum. Philosophy provides a unique perspective; it introduces the concept of observocontrol mode, which regards the truth as an image in the equivalence class. By changing the observocontrol mode, it reveals “Multilobe” of the truth of the same objective. To answer the question on "how to test the truth", it constructs the procedures and criteria to knowledge the truth. These researches have an important revelation on the enrichment and development of the study of Marxism truth theory.

  15. Synthesis and Broad-Spectrum Antiviral Activity of Some Novel Benzo-Heterocyclic Amine Compounds

    Directory of Open Access Journals (Sweden)

    Da-Jun Zhang

    2014-01-01

    Full Text Available A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50 = 3.21–5.06 μM and 3g (IC50 = 0.71–34.87 μM showed potent activity towards both RNA viruses (influenza A, HCV and Cox B3 virus and a DNA virus (HBV at low micromolar concentrations. An SAR study showed that electron-withdrawing substituents located on the aromatic or heteroaromatic ring favored antiviral activity towards RNA viruses.

  16. 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 for the...... lack of soft Xray emission. Broad-band X-ray observations of a sample of BAL QSOs are proposed with a high throughput mission SPECTRUM-RONTGEN-GAMMA (SRG), to find out whether these sources are intrinsically weak over the entire bandwidth of X-rays or only in the soft X-rays due to absorption resulting...... from the line of sight passing through large column density clouds. Simultaneous UV observations will help to constrain the ionization state of the absorbers, and also improve the overall UV to X-ray continuum measurements in them....

  17. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential

    OpenAIRE

    Zasloff, Michael; Adams, A. Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M; Scott C Weaver; Wong, Gerard C. L.

    2011-01-01

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacit...

  18. Broad-spectrum transgenic resistance against distinct tospovirus species at the genus level.

    Directory of Open Access Journals (Sweden)

    Jui-Chu Peng

    Full Text Available Thrips-borne tospoviruses cause severe damage to crops worldwide. In this investigation, tobacco lines transgenic for individual WLm constructs containing the conserved motifs of the L RNA-encoded RNA-dependent RNA polymerase (L gene of Watermelon silver mottle virus (WSMoV were generated by Agrobacterium-mediated transformation. The WLm constructs included: (i translatable WLm in a sense orientation; (ii untranslatable WLmt with two stop codons; (iii untranslatable WLmts with stop codons and a frame-shift; (iv untranslatable antisense WLmA; and (v WLmhp with an untranslatable inverted repeat of WLm containing the tospoviral S RNA 3'-terminal consensus sequence (5'-ATTGCTCT-3' and an NcoI site as a linker to generate a double-stranded hairpin transcript. A total of 46.7-70.0% transgenic tobacco lines derived from individual constructs showed resistance to the homologous WSMoV; 35.7-100% plants of these different WSMoV-resistant lines exhibited broad-spectrum resistance against four other serologically unrelated tospoviruses Tomato spotted wilt virus, Groundnut yellow spot virus, Impatiens necrotic spot virus and Groundnut chlorotic fan-spot virus. The selected transgenic tobacco lines also exhibited broad-spectrum resistance against five additional tospoviruses from WSMoV and Iris yellow spot virus clades, but not against RNA viruses from other genera. Northern analyses indicated that the broad-spectrum resistance is mediated by RNA silencing. To validate the L conserved region resistance in vegetable crops, the constructs were also used to generate transgenic tomato lines, which also showed effective resistance against WSMoV and other tospoviruses. Thus, our approach of using the conserved motifs of tospoviral L gene as a transgene generates broad-spectrum resistance against tospoviruses at the genus level.

  19. Targeting an Essential GTPase Obg for the Development of Broad-Spectrum Antibiotics.

    Science.gov (United States)

    Bonventre, Josephine A; Zielke, Ryszard A; Korotkov, Konstantin V; Sikora, Aleksandra E

    2016-01-01

    A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from GC, ObgGC. The assay was validated with a pilot screen of 40,000 compounds and achieved an average Z' value of 0.58 ± 0.02, which suggests a robust assay amenable to high-throughput screening. We developed secondary assessments for identified lead compounds that utilize the interaction between ObgGC and fluorescent guanine nucleotide analogs, mant-GTP and mant-GDP, and an ObgGC variant with multiple alterations in the G-domains that prevent nucleotide binding. To evaluate the broad-spectrum potential of ObgGC inhibitors, Obg proteins of Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus were assessed using the colorimetric and fluorescence-based activity assays. These approaches can be useful in identifying broad-spectrum Obg inhibitors and advancing the therapeutic battle against multidrug resistant bacteria. PMID:26848972

  20. What Do Parents Think about Chromosomal Microarray Testing? A Qualitative Report from Parents of Children with Autism Spectrum Disorders

    OpenAIRE

    Xu, Lei; Mitchell, Linda Crane; Richman, Alice R.; Clawson, Kaitlyn

    2016-01-01

    Background. Chromosomal Microarray Analysis (CMA) is increasingly utilized to detect copy number variants among children and families affected with autism spectrum disorders (ASD). However, CMA is controversial due to possible ambiguous test findings, uncertain clinical implications, and other social and legal issues related to the test. Methods. Participants were parents of children with ASD residing in the North Eastern region of North Carolina, USA. We conducted individual, face-to-face in...

  1. Broad spectrum antiviral activity of favipiravir (T-705: protection from highly lethal inhalational Rift Valley Fever.

    Directory of Open Access Journals (Sweden)

    Amy L Caroline

    2014-04-01

    Full Text Available BACKGROUND: Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705, which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV. RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route. METHODOLOGY/PRINCIPAL FINDINGS: Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92% survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease. CONCLUSIONS/SIGNIFICANCE: Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug.

  2. An atypical kinase under balancing selection confers broad-spectrum disease resistance in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Carine Huard-Chauveau

    Full Text Available The failure of gene-for-gene resistance traits to provide durable and broad-spectrum resistance in an agricultural context has led to the search for genes underlying quantitative resistance in plants. Such genes have been identified in only a few cases, all for fungal or nematode resistance, and encode diverse molecular functions. However, an understanding of the molecular mechanisms of quantitative resistance variation to other enemies and the associated evolutionary forces shaping this variation remain largely unknown. We report the identification, map-based cloning and functional validation of QRX3 (RKS1, Resistance related KinaSe 1, conferring broad-spectrum resistance to Xanthomonas campestris (Xc, a devastating worldwide bacterial vascular pathogen of crucifers. RKS1 encodes an atypical kinase that mediates a quantitative resistance mechanism in plants by restricting bacterial spread from the infection site. Nested Genome-Wide Association mapping revealed a major locus corresponding to an allelic series at RKS1 at the species level. An association between variation in resistance and RKS1 transcription was found using various transgenic lines as well as in natural accessions, suggesting that regulation of RKS1 expression is a major component of quantitative resistance to Xc. The co-existence of long lived RKS1 haplotypes in A. thaliana is shared with a variety of genes involved in pathogen recognition, suggesting common selective pressures. The identification of RKS1 constitutes a starting point for deciphering the mechanisms underlying broad spectrum quantitative disease resistance that is effective against a devastating and vascular crop pathogen. Because putative RKS1 orthologous have been found in other Brassica species, RKS1 provides an exciting opportunity for plant breeders to improve resistance to black rot in crops.

  3. 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

    Combination therapy with several antibiotics is one strategy that has been applied in order to limit the spread of antimicrobial resistance. We compared the de novo evolution of resistance during combination therapy with the β-lactam ceftazidime and the fluoroquinolone ciprofloxacin...... 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...

  4. Bilogical and toxicological properties of econazole, a broad-spectrum antimycotic.

    Science.gov (United States)

    Thienpont, D; Van Cutsem, J; Van Nueten, J M; Niemegeers, C J; Marsboom, R

    1975-02-01

    The spectrum of activity of 1-(2,4-dichloro-beta-[(p-chlorobenzoyl)oxy]phenethyl)imidazole-nitrate (econazole, R 14827) was tested in vitro on various pathogenic fungi and bacteria, and also in vivo in guinea-pigs and rats experimentally infected with dermatophytes and C. albicans. The in vitro activity spectrum is very broad: the dermatophytes, the yeasts, the dimorphic fungi, the aspergilli, the mycetoma causing agents and the Gram-positive bacteria being most sensitive. Guinea-pigs infected with T. mentagrophytes, M. canis or C. albicans and treated topically or orally with econazole, were cured. In each of these tests the activity of econazole was compared with that of different reference drugs. Vaginal candidiasis in rats was cured after oral administration of econazole. Toxicity and teratogenicity studies in different laboratory animals indicate that econazole is well tolerated.

  5. Broad-spectrum sun-protective action of Porphyra-334 derived from Porphyra vietnamensis

    OpenAIRE

    Saurabh Bhatia; Sharma, K.; Namdeo, Ajay G.; B B Chaugule; Kavale, M.; Nanda, S

    2010-01-01

    There are enormous UV-protective compounds present in the current world market, out of which 98% give protection against UV-B range and the remaining 2% are potent against far UV-A range only. Furthermore, these synthetic compounds have various problems related to photo-stability and cross-stability. There is a vital need of sunscreen agents that will remain stable for prolonged periods and provide broad-spectrum protection against harmful UV range. The Indian Ocean contains large amounts of ...

  6. 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.

  7. Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity disorder: rationale and evidence to date.

    Science.gov (United States)

    Rucklidge, Julia J; Kaplan, Bonnie J

    2014-09-01

    Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric illness, which often co-occurs with other common psychiatric problems. Although empirical evidence supports the short-term efficacy of pharmacological and behavioural treatments, families often search for alternative treatment methods because of concerns about side effects and safety, cost and access, as well as fears about long-term exposure to psychotropic medications. This review presents the published evidence on use of broad-spectrum micronutrients to treat ADHD symptoms. This approach makes physiological sense in that nutrients are required for many critical biochemical reactions to occur, ranging from manufacturing neurotransmitters, to providing the mitochondria with essential nutrients for energy production, to assisting the gut to heal from inflammation. Multi-nutrient treatment approaches are an intriguing yet under-researched area; all but one of the trials conducted in the last decade have shown benefit for the treatment of ADHD symptoms, and the one negative trial likely used doses too low to effect change. However, the methodologies have varied widely from case-controlled studies to open-label trials to one randomized controlled trial. Sample sizes have typically been modest, although the effect sizes have tended to be medium to large. What is required now is replication, as well as investigation into the optimal ingredient range and optimal doses of nutrients. We discuss the proven and potential benefits of the broad-spectrum nutrient approach, considering the heterogeneous nature of ADHD. PMID:25056569

  8. 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

    2016-03-01

    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.

  9. 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

    2016-03-01

    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. PMID:26551316

  10. 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.

  11. Production, purification and characterization of bacteriocin from Lactobacillus murinus AU06 and its broad antibacterial spectrum

    Institute of Scientific and Technical Information of China (English)

    Sivaramasamy Elayaraja; Neelamegam Annamalai; Packiyam Mayavu; Thangavel Balasubramanian

    2014-01-01

    Objective: To study the production, purification and characterization of bacteriocin fromLactobacillus murinus against fish pathogens.Methods:AU06 isolated from marine sediments and its broad spectrum of inhibition bacteriocin. In addition, purified bacteriocin was tested for its antimicrobial activity against fish pathogens.Results:In the present study, the bacteriocin production was found to be higher at 35 °C, pH The selected strain was used in production, purification and characterized of 6.0 and was purified to 4.74 fold with 55. 38 U/mg of specific activity with the yield of 28.92%. The molecular weight of the purified bacteriocin was estimated as 21 kDa. The purified bacteriocin exhibited complete inactivation of antimicrobial activity when treated with proteinase K, pronase, chymotrypsin, trypsin, pepsin and papain. The purified bacteriocin exhibited broad inhibitory spectrum against both Gram positive and negative bacteria.Conclusions:It is concluded that the ability of bacteriocin in inhibiting a wide-range of pathogenic bacteria is of potential interest for food safety and may have future applications in food preservative.

  12. Mapping the Broad-band Spectrum of a New Candidate Intermediate Mass Black Hole

    Science.gov (United States)

    Farrell, Sean

    2014-10-01

    We request joint XMM-Newton & HST observations of a new intermediate mass black hole candidate in the galaxy LEDA 87326 to map the broad-band spectral energy distribution from X-ray to near-IR. Previous observations with the XMM-Newton EPIC and OM cameras detected an X-ray source with an observed 0.2-10 keV luminosity of 6E41 erg/s, with the X-ray spectrum dominated by a hard power law and the UV/optical data consistent with thermal emission from a cool (~0.08 keV) accretion disc. The high X-ray luminosity and low disc temperature imply a black hole mass > 4000 Msun. By observing this source simultaneously with XMM-Newton and the HST we will confirm that the observed optical emission is from an accretion disc and determine whether any reprocessing in the outer disc is present.

  13. Multilayer nanoparticle arrays for broad spectrum absorption enhancement in thin film solar cells

    CERN Document Server

    Krishnan, Aravind; Krishna, Siva Rama; Khan, Mohammed Zafar Ali

    2013-01-01

    In this paper, we present a theoretical study on the absorption efficiency enhancement of a thin film amorphous Silicon (a-Si) photovoltaic cell over a broad spectrum of wavelengths using multiple nanoparticle arrays. The light absorption efficiency is enhanced in the lower wavelengths by a nanoparticle array on the surface and in the higher wavelengths by another nanoparticle array embedded in the active region. The efficiency at intermediate wavelengths is enhanced by the constructive interference of plasmon coupled light. We optimize this design by tuning the radius of particles in both arrays, the period of the array and the distance between the two arrays. The optimization results in 61.44% increase in total quantum efficiency for a 500 nm thick a-Si substrate.

  14. Integrative therapies in cancer: modulating a broad spectrum of targets for cancer management.

    Science.gov (United States)

    Block, Keith I; Block, Penny B; Gyllenhaal, Charlotte

    2015-03-01

    Integrative medicine is an approach to health and healing that "makes use of all appropriate therapeutic approaches, health care professionals, and disciplines to achieve optimal health and healing." A comprehensive integrative medicine intervention for cancer patients typically includes nutritional counseling, biobehavioral strategies, and promotion of physical activity, as well as dietary supplements including herbs, nutraceuticals, and phytochemicals. A broad-spectrum intervention of this type may contribute uniquely to improvement in cancer outcomes through its impact on a wide variety of relevant molecular targets, including effects on multiple cancer hallmarks. Hallmarks that may be particularly affected include genetic instability, tumor-promoting inflammation, deregulated metabolism, and immune system evasion. Because of their susceptibility to manipulation by diet, exercise, and supplementation, these may be characterized as metabolic hallmarks. Research on the use of comprehensive integrative approaches can contribute to the development of systems of multitargeted treatment regimens and would help clarify the combined effect of these approaches on cancer outcomes. PMID:25601968

  15. Broad spectrum moderators and advanced reflector filters using 208Pb

    DEFF Research Database (Denmark)

    Schönfeldt, Troels; Batkov, K.; Klinkby, Esben Bryndt;

    2015-01-01

    Cold and thermal neutrons used in neutrons scattering experiments are produced in nuclear reactors and spallation sources. The neutrons are cooled to thermal or cold temperatures in thermal and cold moderators, respectively. The present study shows that it is possible to exploit the poor...... thermalizing property of 208Pb to design a broad spectrum moderator, i.e. a moderator which emits thermal and cold neutrons from the same position. Using 208Pb as a reflector filter material is shown to be slightly less efficient than a conventional beryllium reflector filter. However, when surrounding the...... reflector filter by a cold moderator it is possible to regain the neutrons with wavelengths below the Bragg edge, which are suppressed in the beryllium reflector filter. In both the beryllium and lead case surrounding the reflector filter with a cold moderator increases the cold brightness significantly...

  16. Analysis of mobile health applications for a broad spectrum of consumers: a user experience approach.

    Science.gov (United States)

    García-Gómez, Juan M; de la Torre-Díez, Isabel; Vicente, Javier; Robles, Montserrat; López-Coronado, Miguel; Rodrigues, Joel J

    2014-03-01

    Mobile health (m-health) apps can bring health prevention and promotion to the general population. The main purpose of this article is to analyze different m-health apps for a broad spectrum of consumers by means of three different experiences. This goal was defined following the strategic documents generated by the main prospective observatories of Information and Communications Technology for health. After a general exploration of the app markets, we analyze the entries of three specific themes focused in this article: type 2 diabetes, obesity, and breast-feeding. The user experiences reported in this study mostly cover the segments of (1) chronically monitored consumers through a Web mobile app for predicting type 2 diabetes (Diab_Alert app), (2) information seekers through a mobile app for maternity (Lactation app) and partially (3) the motivated healthy consumers through a mobile app for a dietetic monitoring and assessment (SapoFit app). These apps were developed by the authors of this work.

  17. 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

  18. Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health

    OpenAIRE

    Smet, Annemieke; Martel, An; Persoons, Davy; Dewulf, Jeroen; Heyndrickx, Marc; Herman, Lieve; Haesebrouck, Freddy; Butaye, Patrick

    2010-01-01

    Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals. This may pose a human health hazard since these genes may be present in zoonotic bacteria, which would cause a direct problem. They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and animals. Broad-spectrum β-lactamase genes ...

  19. Broad band X-ray spectrum of KS 1947+300 with BeppoSAX

    CERN Document Server

    Naik, S; Dotani, T; Paul, B

    2006-01-01

    We present results obtained from three BeppoSAX observations of the accretion-powered transient X-ray pulsar KS 1947+300 carried out during the declining phase of its 2000 November -- 2001 June outburst. A detailed spectral study of KS 1947+300 across a wide X-ray band (0.1--100.0 keV) is attempted for the first time here. Timing analysis of the data clearly shows a 18.7 s pulsation in the X-ray light curves in the above energy band. The pulse profile of KS 1947+300 is characterized by a broad peak with sharp rise followed by a narrow dip. The dip in the pulse profile shows a very strong energy dependence. Broad-band pulse-phase-averaged spectroscopy obtained with three of the BeppoSAX instruments shows that the energy spectrum in the 0.1--100 keV energy band has three components, a Comptonized component, a ~0.6 keV blackbody component, and a narrow and weak iron emission line at 6.7 keV with a low column density of material in the line of sight. We place an upper limit on the equivalent width of the iron K_\\...

  20. Locally Optimally Emitting Clouds and the Variable Broad Emission Line Spectrum of NGC 5548

    Science.gov (United States)

    Korista, Kirk T.; Goad, Michael R.

    2000-06-01

    In recent work Baldwin et al. proposed that in the geometrically extended broad-line regions (BLRs) of quasars and active galactic nuclei, a range in line-emitting gas properties (e.g., density, column density) might exist at each radius and showed that under these conditions the broad emission line spectra of these objects may be dominated by selection effects introduced by the atomic physics and general radiative transfer within the large pool of line-emitting entities. In this picture, the light we see originates in a vast amalgam of emitters but is dominated by those emitters best able to reprocess the incident continuum into a particular emission line. We test this ``locally optimally emitting clouds'' (LOC) model against the extensive spectroscopic database of the Seyfert 1 galaxy NGC 5548. The time-averaged, integrated-light UV broad emission line spectrum from the 1993 Hubble Space Telescope (HST) monitoring campaign is reproduced via the optimization of three global geometric parameters: the outer radius, the index controlling the radial cloud covering fraction of the continuum source, and the integrated cloud covering fraction. We make an ad hoc selection from the range of successful models, and for a simple spherical BLR geometry we simulate the emission-line light curves for the 1989 IUE and 1993 HST campaigns, using the respective observed UV continuum light curves as drivers. We find good agreement between the predicted and observed light curves and lags-a demonstration of the LOC picture's viability as a means to understanding the BLR environment. Finally, we discuss the next step in developing the LOC picture, which involves the marriage of echo-mapping techniques with spectral simulation grids such as those presented here, using the constraints provided by a high-quality, temporally well-sampled spectroscopic data set.

  1. Bloated stars as agn broad line clouds the emission line spectrum

    CERN Document Server

    Alexander, T; Tal Alexander; Hagai Netzer

    1994-01-01

    The `Bloated Stars Scenario' proposes that AGN broad line emission originates in the winds or envelopes of bloated stars (BS). Its main advantage over BLR cloud models is the gravitational confinement of the gas and its major difficulty the large estimated number of BSs and resulting high mass loss rate. We calculate the emission line spectrum by a detailed numerical photoionization code for a wide range of wind structures and a detailed QSO nucleus model with L(ion)=7E45 erg/s, M(bh)=8E7 Mo. The size and boundary density of the BS wind are determined by various processes: Comptonization by the central continuum source, calculated self consistently, tidal disruption by the black hole and the limit set by the wind's finite mass. We find that the emission spectrum is mainly determined by the conditions at the boundary of the line emitting fraction of the wind rather than by its internal structure. Comptonization results in very high ionization parameters at the boundary which produces an excess of unobserved br...

  2. 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.

  3. Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity.

    Directory of Open Access Journals (Sweden)

    Marie-Line Goulet

    Full Text Available The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5' triphosphate (5'ppp terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5'pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5'pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5'pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5'pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5'pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.

  4. Pyrodiversity and the anthropocene: the role of fire in the broad spectrum revolution.

    Science.gov (United States)

    Bird, Douglas W; Bliege Bird, Rebecca; Codding, Brian F

    2016-05-01

    The Anthropocene colloquially refers to a global regime of human-caused environmental modification of earth systems associated with profound changes in patterns of human mobility, as well as settlement and resource use compared with prior eras. Some have argued that the processes generating the Anthropocene are mainly associated with population growth and technological innovation, and thus began only in the late Holocene under conditions of dense sedentism and industrial agriculture.(1) However, it now seems clear that the roots of the Anthropocene lie in complex processes of intensification that significantly predate transitions to agriculture.(2,3) What intensification is remains less clear. For some it is increasing economic productivity that increases carrying capacity, the drivers of which may be too diverse and too local to generalize.(4,5) For others using Boserup's ideas about agrarian intensification, increasing density in hunter-gatherer populations can produce declines in subsistence efficiency that increase incentives for investing labor to boost yield per unit area, which then elevates Malthusian limits on carrying capacity.(6-8) As Morgan(9) demonstrates in a comprehensive review, the legacy of such Boserupian intensification is alive, well, and controversial in hunter-gatherer archeology. This is a result of its potential for illuminating processes involved in transformations of forager socio-political and economic systems, including those dominated by harvesting more immediate-return resources and high residential mobility as well as those characterized by more delayed-return material economies with reduced residential mobility, a broader spectrum of resources, degrees of storage, and greater social stratification. Here we detail hypotheses about the processes involved in such transitions and explore the way that anthropogenic disturbance of ecosystems, especially the use of landscape fire, could be fundamentally entangled with many broad-spectrum

  5. Pyrodiversity and the anthropocene: the role of fire in the broad spectrum revolution.

    Science.gov (United States)

    Bird, Douglas W; Bliege Bird, Rebecca; Codding, Brian F

    2016-05-01

    The Anthropocene colloquially refers to a global regime of human-caused environmental modification of earth systems associated with profound changes in patterns of human mobility, as well as settlement and resource use compared with prior eras. Some have argued that the processes generating the Anthropocene are mainly associated with population growth and technological innovation, and thus began only in the late Holocene under conditions of dense sedentism and industrial agriculture.(1) However, it now seems clear that the roots of the Anthropocene lie in complex processes of intensification that significantly predate transitions to agriculture.(2,3) What intensification is remains less clear. For some it is increasing economic productivity that increases carrying capacity, the drivers of which may be too diverse and too local to generalize.(4,5) For others using Boserup's ideas about agrarian intensification, increasing density in hunter-gatherer populations can produce declines in subsistence efficiency that increase incentives for investing labor to boost yield per unit area, which then elevates Malthusian limits on carrying capacity.(6-8) As Morgan(9) demonstrates in a comprehensive review, the legacy of such Boserupian intensification is alive, well, and controversial in hunter-gatherer archeology. This is a result of its potential for illuminating processes involved in transformations of forager socio-political and economic systems, including those dominated by harvesting more immediate-return resources and high residential mobility as well as those characterized by more delayed-return material economies with reduced residential mobility, a broader spectrum of resources, degrees of storage, and greater social stratification. Here we detail hypotheses about the processes involved in such transitions and explore the way that anthropogenic disturbance of ecosystems, especially the use of landscape fire, could be fundamentally entangled with many broad-spectrum

  6. Survey of pharmacists and physicians on drug interactions between combined oral contraceptives and broad-spectrum antibiotics

    Directory of Open Access Journals (Sweden)

    Masters KP

    2009-09-01

    Full Text Available Objective: To evaluate physician and pharmacist knowledge on potential drug interactions between combined oral contraceptives (COC and broad-spectrum antibiotics and determine if any difference exists between responses.Methods: Two hundred licensed retail pharmacists and 200 licensed family practice physicians in the states of Virginia, West Virginia, and Maryland were mailed an anonymous survey between August 2007 and November 2007. The survey consisted of 3 short questions asking practitioners about their current opinion on drug interactions with COCs and whether an alternative form of contraception is needed for patients taking COC and concomitant broad-spectrum antibiotics. The main outcome measure of the survey included: identifying how physicians and pharmacists handle prescribing or dispensing COCs along with broad-spectrum antibiotics. Gender, educational degree, and years in practice were also collected. Results: A total of 182 participants returned the surveys (57% were physicians and 43% were pharmacists. When asked if broad-spectrum antibiotics have a clinically significant interaction with COCs, 82.7% of physicians and 88.5% of pharmacists answered, “yes”. Of the respondents, 84.6% stated that the drug interaction warrants the patient to be advised to use back-up contraception. A total of 90.1% stated that they currently instruct patients to use back-up contraception when prescribing or dispensing antibiotics to a patient who is on COC, with no statistically significant difference existing between the responses of the pharmacists and the physicians.Conclusion: Physicians and pharmacists believe that broad-spectrum antibiotics decrease the effectiveness of COCs. These practitioners warn their patients of this interaction and advise the use of back-up contraception. More education should be provided to practitioners regarding the data concerning COCs and broad spectrum antibiotics and lack of a proven interaction.

  7. Broad-spectrum light versus blue light for phototherapy in neonatal hyperbilirubinemia: a randomized controlled trial.

    Science.gov (United States)

    Pratesi, Simone; Di Fabio, Sandra; Bresci, Cecilia; Di Natale, Cecilia; Bar, Shahar; Dani, Carlo

    2015-07-01

    Phototherapy is standard care for treatment of neonatal hyperbilirubinemia. Our aim was to compare the effectiveness of broad-spectrum light (BSL) to that of blue light emitting diodes (LED) phototherapy for the treatment of jaundiced late preterm and term infants. Infants with gestational age from 35(+0) to 41(+6) weeks of gestation and nonhemolytic hyperbilirubinemia were randomized to treatment with BSL phototherapy or blue LED phototherapy. A total of 20 infants were included in the blue LED phototherapy group and 20 in the BSL phototherapy group. The duration of phototherapy was lower in the BSL than in the blue LED phototherapy group (15.8 ± 4.9 vs. 20.6 ± 6.0 hours; p = 0.009), and infants in the former group had a lower probability (p = 0.015) of remaining in phototherapy than infants in the latter. We concluded that BSL phototherapy is more effective than blue LED phototherapy for the treatment of hyperbilirubinemia in late preterm and term infants. Our data suggest that these results are not due to the different irradiance of the two phototherapy systems, but probably depend on their different peak light emissions. PMID:25545446

  8. 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.

  9. 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.

  10. A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract.

    Science.gov (United States)

    Fünfgeld, E W

    1989-01-01

    The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long-term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings. PMID:2602410

  11. Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents.

    Science.gov (United States)

    Brai, Annalaura; Fazi, Roberta; Tintori, Cristina; Zamperini, Claudio; Bugli, Francesca; Sanguinetti, Maurizio; Stigliano, Egidio; Esté, José; Badia, Roger; Franco, Sandra; Martinez, Miguel A; Martinez, Javier P; Meyerhans, Andreas; Saladini, Francesco; Zazzi, Maurizio; Garbelli, Anna; Maga, Giovanni; Botta, Maurizio

    2016-05-10

    Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target. PMID:27118832

  12. Broad-spectrum resistance to Bacillus thuringiensis toxins by western corn rootworm (Diabrotica virgifera virgifera).

    Science.gov (United States)

    Jakka, Siva R K; Shrestha, Ram B; Gassmann, Aaron J

    2016-06-14

    The evolution of resistance and cross-resistance threaten the sustainability of genetically engineered crops that produce insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt). Western corn rootworm, Diabrotica virgifera virgifera LeConte, is a serious pest of maize and has been managed with Bt maize since 2003. We conducted laboratory bioassays with maize hybrids producing Bt toxins Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1, which represent all commercialized Bt toxins for management of western corn rootworm. We tested populations from fields where severe injury to Cry3Bb1 maize was observed, and populations that had never been exposed to Bt maize. Consistent with past studies, bioassays indicated that field populations were resistant to Cry3Bb1 maize and mCry3A maize, and that cross-resistance was present between these two types of Bt maize. Additionally, bioassays revealed resistance to eCry3.1Ab maize and cross-resistance among Cry3Bb1, mCry3A and eCry3.1Ab. However, no resistance or cross-resistance was detected for Cry34/35Ab1 maize. This broad-spectrum resistance illustrates the potential for insect pests to develop resistance rapidly to multiple Bt toxins when structural similarities are present among toxins, and raises concerns about the long-term durability of Bt crops for management of some insect pests.

  13. Locally Optimally-Emitting Clouds and the Variable Broad Emission Line Spectrum of NGC 5548

    CERN Document Server

    Korista, K T; Korista, Kirk T.; Goad, Michael R.

    2000-01-01

    [abridged] We test the ``locally optimally-emitting clouds'' (LOC) model against the extensive spectroscopic data base of the Seyfert~1, NGC 5548. The time-averaged, integrated-light UV broad emission line spectrum from the 1993 global geometric parameters: the outer radius, the index controlling the radial cloud covering fraction of the continuum source, and the integrated cloud covering fraction. We make an {\\em ad~hoc} selection from the range of successful models, and for a simple spherical BLR geometry we simulate the emission line light curves for the 1989 {\\em IUE} and 1993 {\\em HST} campaigns, using the respective observed UV continuum light curves as drivers. We find good agreement between the predicted and observed light curves and lags --- a demonstration of the LOC picture's viability as a means to understanding the BLR environment. Finally, we discuss the next step in developing the LOC picture which involves the marriage of echo-mapping techniques with spectral simulation grids such as those pre...

  14. L-carnitine esters as "soft", broad-spectrum antimicrobial amphiphiles.

    Science.gov (United States)

    Calvani, M; Critelli, L; Gallo, G; Giorgi, F; Gramiccioli, G; Santaniello, M; Scafetta, N; Tinti, M O; De Angelis, F

    1998-06-18

    A new class of antimicrobial, "soft", quaternary ammonium l-carnitine esters, of the type (CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-, has been designed, with R1 and R2 being in general long-chain alkyl substituents. The series shows good activity against a wide range of bacteria, yeasts, and fungi. Lipophilicity has been measured by RP-HPLC method to give the logarithm of the experimental capacity factor (log k'), and a quantitative relationship has been determined between log k' and the theoretical partition coefficient (CLOGP); also, bond-dipole descriptors have been introduced into calculations by accounting for polar moieties present within the apolar cores of the molecules, giving a more refined calculated capacity factor (log k'calcd). Finally the latter has been related to the antimicrobial activity (MIC values). The proposed models are predictive for the best broad-spectrum antimicrobial compound within the series. PMID:9632355

  15. Broad-spectrum sun-protective action of Porphyra-334 derived from Porphyra vietnamensis

    Directory of Open Access Journals (Sweden)

    Saurabh Bhatia

    2010-01-01

    Full Text Available There are enormous UV-protective compounds present in the current world market, out of which 98% give protection against UV-B range and the remaining 2% are potent against far UV-A range only. Furthermore, these synthetic compounds have various problems related to photo-stability and cross-stability. There is a vital need of sunscreen agents that will remain stable for prolonged periods and provide broad-spectrum protection against harmful UV range. The Indian Ocean contains large amounts of macro-algae which synthesize varied amount of mycosporine amino acids, "sun-protective compounds" by shikmic acid pathway. In the present study, we have evaluated the sunscreen protection provided by Porphyra-334, a mycosporine amino acid isolated from Indian sp. of Porphyra. Furthermore, the isolated compound was detected by high performance thin layer chromatography (HPTLC fingerprinting, high performance liquid chromatography (HPLC and ultraviolet (UV, whereas nuclear magnetic resonance (NMR spectroscopy and infrared spectrometry were used for its structural characterization. Stability studies were performed under different storage and pH conditions. Ultimately a sunscreen formulation was developed and its potential against marketed Aloe vera gel was evaluated by in vitro sunscreen protection method. It was observed that sunscreen potential of Porphyra-334 was 5.11-fold greater than that of the marketed Aloe vera gel preparation.

  16. Analysis of mobile health applications for a broad spectrum of consumers: a user experience approach.

    Science.gov (United States)

    García-Gómez, Juan M; de la Torre-Díez, Isabel; Vicente, Javier; Robles, Montserrat; López-Coronado, Miguel; Rodrigues, Joel J

    2014-03-01

    Mobile health (m-health) apps can bring health prevention and promotion to the general population. The main purpose of this article is to analyze different m-health apps for a broad spectrum of consumers by means of three different experiences. This goal was defined following the strategic documents generated by the main prospective observatories of Information and Communications Technology for health. After a general exploration of the app markets, we analyze the entries of three specific themes focused in this article: type 2 diabetes, obesity, and breast-feeding. The user experiences reported in this study mostly cover the segments of (1) chronically monitored consumers through a Web mobile app for predicting type 2 diabetes (Diab_Alert app), (2) information seekers through a mobile app for maternity (Lactation app) and partially (3) the motivated healthy consumers through a mobile app for a dietetic monitoring and assessment (SapoFit app). These apps were developed by the authors of this work. PMID:24550566

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

    Science.gov (United States)

    Ng, Wai-Leung; Perez, Lark; Cong, Jianping; Semmelhack, Martin F; Bassler, Bonnie L

    2012-01-01

    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. PMID:22761573

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

    OpenAIRE

    Hawkins, Denise; Abrahamse, Heidi

    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 ...

  19. Manganese Oxide Nanoarchitectures as Broad-Spectrum Sorbents for Toxic Gases.

    Science.gov (United States)

    Long, Jeffrey W; Wallace, Jean M; Peterson, Gregory W; Huynh, Kim

    2016-01-20

    We demonstrate that sol-gel-derived manganese oxide (MnOx) nanoarchitectures exhibit broad-spectrum filtration activity for three chemically diverse toxic gases: NH3, SO2, and H2S. Manganese oxides are synthesized via the reaction of NaMnO4 and fumaric acid to form monolithic gels of disordered, mixed-valent Na-MnOx; incorporated Na(+) is readily exchanged for H(+) by subsequent acid rinsing to form a more crystalline H-MnOx phase. For both Na-MnOx and H-MnOx forms, controlled pore-fluid removal yields either densified, yet still mesoporous, xerogels or low-density aerogels (prepared by drying from supercritical CO2). The performance of these MnOx nanoarchitectures as filtration media is assessed using dynamic-challenge microbreakthrough protocols. We observe technologically relevant sorption capacities under both dry conditions and wet (80% relative humidity) for each of the three toxic industrial chemicals investigated. The Na-MnOx xerogels and aerogels provide optimal performance with the aerogel exhibiting maximum sorption capacities of 39, 200, and 680 mg g(-1) for NH3, SO2, and H2S, respectively. Postbreakthrough characterization using X-ray photoelectron spectroscopy (XPS) and diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS) confirms that NH3 is captured and partially protonated within the MnOx structure, while SO2 undergoes oxidation by the redox-active oxide to form adsorbed sulfate at the MnOx surface. Hydrogen sulfide is also oxidized to form a combination of sulfate and sulfur/polysulfide products, concomitant with a decrease in the average Mn oxidation state from 3.43 to 2.94 and generation of a MnOOH phase. PMID:26741498

  20. Extensive sequence variation in rice blast resistance gene Pi54 makes it broad spectrum in nature

    Directory of Open Access Journals (Sweden)

    Shallu eThakur

    2015-05-01

    Full Text Available Rice blast resistant gene, Pi54 cloned from rice line, Tetep, is effective against diverse isolates of Magnaporthe oryzae. In this study, we prospected the allelic variants of the dominant blast resistance gene from a set of 92 rice lines to determine the nucleotide diversity, pattern of its molecular evolution, phylogenetic relationships and evolutionary dynamics, and to develop allele specific markers. High quality sequences were generated for homologs of Pi54 gene. Using comparative sequence analysis, InDels of variable sizes in all the alleles were observed. Profiling of the selected sites of SNP (Single Nucleotide Polymorphism and amino acids (N sites ≥ 10 exhibited constant frequency distribution of mutational and substitutional sites between the resistance and susceptible rice lines, respectively. A total of 50 new haplotypes based on the nucleotide polymorphism was also identified. A unique haplotype (H_3 was found to be linked to all the resistant alleles isolated from indica rice lines. Unique leucine zipper and tyrosine sulfation sites were identified in the predicted Pi54 proteins. Selection signals were observed in entire coding sequence of resistance alleles, as compared to LRR domains for susceptible alleles. This is a maiden report of extensive variability of Pi54 alleles in different landraces and cultivated varieties, possibly, attributing broad-spectrum resistance to Magnaporthe oryzae. The sequence variation in two consensus region: 163 bp and 144 bp were used for the development of allele specific DNA markers. Validated markers can be used for the selection and identification of better allele(s and their introgression in commercial rice cultivars employing marker assisted selection.

  1. Expression of mouse beta defensin 2 in Escherichia coli and its broad-spectrum antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Tianxiang Gong

    2011-09-01

    Full Text Available Mature mouse beta defensin 2 (mBD2 is a small cationic peptide with antimicrobial activity. Here we established a prokaryotic expression vector containing the cDNA of mature mBD2 fused with thioredoxin (TrxA, pET32a-mBD2. The vector was transformed into Escherichia Coli (E. coli Rosseta-gami (2 for expression fusion protein. Under the optimization of fermentation parameters: induce with 0.6 mM isopropylthiogalactoside (IPTG at 34ºC in 2×YT medium and harvest at 6 h postinduction, fusion protein TrxA-mBD2 was high expressed in the soluble fraction (>95%. After cleaved fusion protein by enterokinase, soluble mature mBD2 was achieved 6 mg/L with a volumetric productivity. Purified recombinant mBD2 demonstrated clear broad-spectrum antimicrobial activity for fungi, bacteria and virus. The MIC of antibacterial activity of against Staphylococcus aureus was 50 µg/ml. The MIC of against Candida albicans (C. albicans and Cryptococcus neoformans (C. neoformans was 12.5µg/ml and 25µg/ml, respectively. Also, the antimicrobial activity of mBD2 was effected by NaCl concentration. Additionally, mBD2 showed antiviral activity against influenza A virus (IAV, the protective rate for Madin-Darby canine kidney cells (MDCK was 93.86% at the mBD2 concentration of 100 µg/ml. These works might provide a foundation for the following research on the mBD2 as therapeutic agent for medical microbes.

  2. 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.

  3. Broad-spectrum resistance to Bacillus thuringiensis toxins by western corn rootworm (Diabrotica virgifera virgifera).

    Science.gov (United States)

    Jakka, Siva R K; Shrestha, Ram B; Gassmann, Aaron J

    2016-01-01

    The evolution of resistance and cross-resistance threaten the sustainability of genetically engineered crops that produce insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt). Western corn rootworm, Diabrotica virgifera virgifera LeConte, is a serious pest of maize and has been managed with Bt maize since 2003. We conducted laboratory bioassays with maize hybrids producing Bt toxins Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1, which represent all commercialized Bt toxins for management of western corn rootworm. We tested populations from fields where severe injury to Cry3Bb1 maize was observed, and populations that had never been exposed to Bt maize. Consistent with past studies, bioassays indicated that field populations were resistant to Cry3Bb1 maize and mCry3A maize, and that cross-resistance was present between these two types of Bt maize. Additionally, bioassays revealed resistance to eCry3.1Ab maize and cross-resistance among Cry3Bb1, mCry3A and eCry3.1Ab. However, no resistance or cross-resistance was detected for Cry34/35Ab1 maize. This broad-spectrum resistance illustrates the potential for insect pests to develop resistance rapidly to multiple Bt toxins when structural similarities are present among toxins, and raises concerns about the long-term durability of Bt crops for management of some insect pests. PMID:27297953

  4. Wild coastline birds as reservoirs of broad-spectrum-β-lactamase-producing Enterobacteriaceae in Miami Beach, Florida.

    Science.gov (United States)

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

    2012-05-01

    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.

  5. Successful five-item triage for the broad spectrum of mental disorders in pregnancy - A validation study

    NARCIS (Netherlands)

    C. Quispel (Chantal); T.A.J. Schneider (Tom); W.J.G. Hoogendijk (Witte); G.J. Bonsel (Gouke); M.P. Lambregtse-van den Berg (Mijke)

    2015-01-01

    textabstractBackground: Mental disorders are prevalent during pregnancy, affecting 10% of women worldwide. To improve triage of a broad spectrum of mental disorders, we investigated the decision impact validity of: 1) a short set of currently used psychiatric triage items, 2) this set with the inclu

  6. Competitive Interaction Between Phytophthora Infestans Effectors Leads to Increased Aggressiveness on Plants Containing Broad-spectrum Late Blight Resistance

    Science.gov (United States)

    The resistance (R) gene RB confers broad-spectrum resistance to potato late blight and belongs. The RB protein recognizes the presence of members of the Phytophthora infestans effector family IPI-O to elicit resistance. Most isolates of the pathogen contain IPI-O variants that are recognized by R...

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

    OpenAIRE

    Poirel, L.; Potron, A.; de la Cuesta, C.; Cleary, T.; Nordmann, P; Munoz-Price, L. S.

    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.

  8. The broad-spectrum cation channel blocker pinokalant (LOE 908 MS) reduces brain infarct volume in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Wienrich, Marion; Ensinger, Helmut A;

    2005-01-01

    Activation of cation channels conducting Ca2+, Na+ and K+ is involved in the pathogenesis of infarction in experimental focal cerebral ischaemia. Pinokalant (LOE 908 MS) is a novel broad-spectrum inhibitor of several subtypes of such channels and has previously been shown to improve the metabolic...

  9. A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion.

    Directory of Open Access Journals (Sweden)

    Frederic Vigant

    .01 delayed the time to death in a murine lethal challenge model of Rift Valley Fever Virus (RVFV. The viral membrane may be a viable target for broad-spectrum antivirals that target virus-cell fusion.

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

    Directory of Open Access Journals (Sweden)

    Haug Jon B

    2011-12-01

    Full Text Available Abstract 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

  11. Activation tagging of ATHB13 in Arabidopsis thaliana confers broad-spectrum disease resistance.

    Science.gov (United States)

    Gao, Dongli; Appiano, Michela; Huibers, Robin P; Chen, Xi; Loonen, Annelies E H M; Visser, Richard G F; Wolters, Anne-Marie A; Bai, Yuling

    2014-12-01

    Powdery mildew species Oidium neolycopersici (On) can cause serious yield losses in tomato production worldwide. Besides on tomato, On is able to grow and reproduce on Arabidopsis. In this study we screened a collection of activation-tagged Arabidopsis mutants and identified one mutant, 3221, which displayed resistance to On, and in addition showed a reduced stature and serrated leaves. Additional disease tests demonstrated that the 3221 mutant exhibited resistance to downy mildew (Hyaloperonospora arabidopsidis) and green peach aphid (Myzus persicae), but retained susceptibility to bacterial pathogen Pseudomonas syringae pv tomato DC3000. The resistance trait and morphological alteration were mutually linked in 3221. Identification of the activation tag insertion site and microarray analysis revealed that ATHB13, a homeodomain-leucine zipper (HD-Zip) transcription factor, was constitutively overexpressed in 3221. Silencing of ATHB13 in 3221 resulted in the loss of both the morphological alteration and resistance, whereas overexpression of the cloned ATHB13 in Col-0 and Col-eds1-2 backgrounds resulted in morphological alteration and resistance. Microarray analysis further revealed that overexpression of ATHB13 influenced the expression of a large number of genes. Previously, it was reported that ATHB13-overexpressing lines conferred tolerance to abiotic stress. Together with our results, it appears that ATHB13 is involved in the crosstalk between abiotic and biotic stress resistance pathways.

  12. Broad-band spectrophotometry of HAT-P-32 b: Search for a scattering signature in the planetary spectrum

    CERN Document Server

    Mallonn, M; Herrero, E; Hoyer, S; Kirk, J; Wheatley, P J; Seeliger, M; Mackebrandt, F; von Essen, C; Strassmeier, K G; Granzer, T; Künstler, A; Dhillon, V S; Marsh, T R; Gaitan, J

    2016-01-01

    Multi-colour broad-band transit observations offer the opportunity to characterise 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 previously published light curves for a homogeneous analysis of the broad-band transmission spectrum from the Sloan u' band to the Sloan z' band. Our results rule out cloud-free planetary atmosphere models of solar metallicity. Furthermore, a discrepancy at reddest wavelengths to previously published results 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.

  13. Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity

    OpenAIRE

    Chunli Liu; Ce Shi; Fei Mao; Yong Xu; Jinyan Liu; Bing Wei; Jin Zhu; Mingjie Xiang; Jian Li

    2014-01-01

    A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effect...

  14. NBS Proifling Identiifes Potential Novel Locus from Solanum demissum That Confers Broad-Spectrum Resistance to Phytophthora infestans

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kun; XU Jian-fei; DUAN Shao-guang; PANG Wan-fu; BIAN Chun-song; LIU Jie; JIN Li-ping

    2014-01-01

    Potato late blight, caused by the oomycete pathogen Phytophthora infestans, is the most serious disease of potato worldwide. The adoption of varieties with resistance genes, especially broad-spectrum resistance genes, is the most efifcient approach to control late blight. Solanum demissum is a well-known wild potato species from which 11 race-speciifc resistance genes have been identiifed, however, no broad-spectrum resistance genes like RB have been reported in this species. Here, we report a novel reisistance locus from S. demissum that potentially confer broad-spectrum resistance to late blight. A small segregating population of S. demissum were assessed for resistance to aggressive P. infestans isolates (race 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11). This coupled with nucleotide binding site (NBS) proifling analyses, led to the identiifcation of three fragments that linked to the potential candidate resistance gene(s). Cloning and sequence analysis of these fragments suggested that the identiifed resistance gene locus is located in the region containing R2 resistance gene at chromosome 4. Based on the sequences of the cloned fragments, a co-segregating sequence characterized ampliifed region (SCAR) marker, RDSP, was developed. The newly identiifed marker RDSP will be useful for marker assisted breeding and further cloning of this potential resistance gene locus.

  15. Overexpression of BSR1 confers broad-spectrum resistance against two bacterial diseases and two major fungal diseases in rice.

    Science.gov (United States)

    Maeda, Satoru; Hayashi, Nagao; Sasaya, Takahide; Mori, Masaki

    2016-06-01

    Broad-spectrum disease resistance against two or more types of pathogen species is desirable for crop improvement. In rice, Xanthomonas oryzae pv. oryzae (Xoo), the causal bacteria of rice leaf blight, and Magnaporthe oryzae, the fungal pathogen causing rice blast, are two of the most devastating pathogens. We identified the rice BROAD-SPECTRUM RESISTANCE 1 (BSR1) gene for a BIK1-like receptor-like cytoplasmic kinase using the FOX hunting system, and demonstrated that BSR1-overexpressing (OX) rice showed strong resistance to the bacterial pathogen, Xoo and the fungal pathogen, M. oryzae. Here, we report that BSR1-OX rice showed extended resistance against two other different races of Xoo, and to at least one other race of M. oryzae. In addition, the rice showed resistance to another bacterial species, Burkholderia glumae, which causes bacterial seedling rot and bacterial grain rot, and to Cochliobolus miyabeanus, another fungal species causing brown spot. Furthermore, BSR1-OX rice showed slight resistance to rice stripe disease, a major viral disease caused by rice stripe virus. Thus, we demonstrated that BSR1-OX rice shows remarkable broad-spectrum resistance to at least two major bacterial species and two major fungal species, and slight resistance to one viral pathogen. PMID:27436950

  16. What Do Parents Think about Chromosomal Microarray Testing? A Qualitative Report from Parents of Children with Autism Spectrum Disorders

    Science.gov (United States)

    Mitchell, Linda Crane; Richman, Alice R.; Clawson, Kaitlyn

    2016-01-01

    Background. Chromosomal Microarray Analysis (CMA) is increasingly utilized to detect copy number variants among children and families affected with autism spectrum disorders (ASD). However, CMA is controversial due to possible ambiguous test findings, uncertain clinical implications, and other social and legal issues related to the test. Methods. Participants were parents of children with ASD residing in the North Eastern region of North Carolina, USA. We conducted individual, face-to-face interviews with 45 parents and inquired about their perceptions of CMA. Results. Three major themes dominated parents' perceptions of CMA. None of the parents had ever heard of the test before and the majority of the parents postulated positive attitudes toward the test. Parents' motivations in undergoing the test were attributed to finding a potential cause of ASD, to being better prepared for having another affected child, and to helping with future reproductive decisions. Perceived barriers included the cost of testing, risk/pain of CMA testing, and fear of test results. Conclusion. This study contributes to the understanding of psychosocial aspects and cultural influences towards adoption of genetic testing for ASD in clinical practice. Genetic education can aid informed decision-making related to CMA genetic testing among parents of children with ASD. PMID:27413549

  17. Design of a broad spectrum multichannel optical filter based on FBG

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-tao; PAN Wei; YAN Lian-shan; LUO Bin; WEN Kun-hua; FENG Xian-gui

    2009-01-01

    To increase the channel number in the optic filter, the multiple-phase-shift (MPS) technology is adoped based on the multiple-reflection-spectrum-envelopes-concatenation (MRSEC) model which has a broadband flatness. The reflection spectra of the MPS digital concatenated sample gratings are simulated with transfer matrix method, the results show that wave band of the reflection spectrum is widened and the channel number is multiplied. What's more, the spectrum flatness is improved with the increasing of refraction index change. Moreover, to improve the extinction ratio and peak value when MPS is adopted in concatenated SFBG, an available designing method based on the cascaded unit is put forward and the optimized results are obtained.

  18. The Broad Autism Phenotype Questionnaire: Mothers versus Fathers of Children with an Autism Spectrum Disorder

    Science.gov (United States)

    Seidman, Ifat; Yirmiya, Nurit; Milshtein, Shahaf; Ebstein, Richard P.; Levi, Shlomit

    2012-01-01

    Parents of individuals with autism were examined using the Broad Autism Phenotype Questionnaire (BAPQ; Hurley et al. in "J Autism Dev Disord" 37:1679-1690, 2007) assessing BAP-related personality and language characteristics. The BAPQ was administered to parents as a self-report and as an informant (spouse)-based measure. Results indicated the…

  19. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities

    OpenAIRE

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-01-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypo...

  20. Effect of spectral range in surface inactivation of Listeria innocua using broad-spectrum pulsed light.

    Science.gov (United States)

    Woodling, Sarah E; Moraru, Carmen I

    2007-04-01

    Pulsed light (PL) treatment is an alternative to traditional thermal treatment that has the potential to achieve several log-cycle reductions in the concentration of microorganisms. One issue that is still debated is related to what specifically causes cell death after PL treatments. The main objective of this work was to elucidate which portions of the PL range are responsible for bacterial inactivation. Stainless steel coupons with controlled surface properties were inoculated with a known concentration of Listeria innocua in the stationary growth phase and treated with 1 to 12 pulses of light at a pulse rate of 3 pulses per s and a pulse width of 360 micros. The effects of the full spectrum (lambda = 180 to 1,100 nm) were compared with the effects obtained when only certain regions of UV, visible, and near-infrared light were used. The effectiveness of the treatments was determined in parallel by the standard plate count and most-probable-number techniques. At a fluence of about 6 J/cm(2), the full-spectrum PL treatment resulted in a 4.08-log reduction of L. innocua on a Mill finish surface, the removal of lambda 400 nm). This work provides additional supporting evidence that cell death in PL treatment is due to exposure to UV light. Additionally, it was shown that even a minor modification of the light path or the UV light spectrum in PL treatments can have a significant negative impact on the treatment intensity and effectiveness. PMID:17477260

  1. 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

  2. Anomalously Broad Diffuse Interstellar Bands and Excited CH+ Absorption in the Spectrum of Herschel 36

    Science.gov (United States)

    York, D. G.; Dahlstrom, J.; Welty, D. E.; Oka, T.; Hobbs, L. M.; Johnson, S.; Friedman, S. D.; Jiang, Z.; Rachford, B. L.; Snow, T. P.; Sherman, R.; Sonnentrucker, P.

    2014-02-01

    Anomalously broad diffuse interstellar bands (DIBs) at 5780.5, 5797.1, 6196.0, and 6613.6 Å are found in absorption along the line of sight to Herschel 36, an O star system next to the bright Hourglass nebula of the Hii region Messier 8. Excited lines of CH and CH+ are seen as well. We show that the region is very compact and itemize other anomalies of the gas. An infrared-bright star within 400 AU is noted. The combination of these effects produces anomalous DIBs, interpreted by Oka et al. (2013, see also this volume) as being caused predominantly by infrared pumping of rotational levels of relatively small molecules.

  3. The broad-band X-ray spectrum of Cygnus X-2

    Science.gov (United States)

    Pravdo, S. H.

    1983-01-01

    Cygnus X-2 was observed with the broad-band X-ray spectroscopy experiment, HEAO 1 A-2, in the energy range 0.4-18 keV for four intervals of approximately 31 s over the course of 5 days in 1977. The spectra can be adequately represented by single-temperature thermal bremmstrahlung continua with temperatures ranging from 3.7 x 10 to the 7th K to 6.4 x 10 to the 7th K. An examination of the spectra and the spectra-luminosity relationship effectively rules out one degenerate dwarf model for the X-ray emission. The far-UV continuum emission could be dominated by this continuum component during X-ray high states, an effect which would be detected in optical UV line observations. A Comptonized X-ray cloud around a neutron star remains a viable model for the observed X-ray spectra.

  4. Imipenem-cilastatin sodium, a broad-spectrum carbapenem antibiotic combination.

    Science.gov (United States)

    Pastel, D A

    1986-09-01

    The chemistry, antimicrobial spectrum, mechanism of action, pharmacology and pharmacokinetics, clinical use, adverse effects, dosage and administration, place in therapy, cost-effectiveness, and formulary considerations of imipenem-cilastatin sodium are reviewed. Imipenem is the first carbapenem antibiotic of the thienamycin class to be used clinically. Imipenem has the widest spectrum of antimicrobial activity of currently available beta-lactam agents and, in contrast to other beta-lactam antibiotics, lacks cross resistance with recently introduced extended-spectrum penicillins and third-generation cephalosporins. Against gram-positive and gram-negative aerobic and anaerobic organisms, imipenem demonstrates excellent activity. Pseudomonas maltophilia, some strains of Pseudomonas cepacia, and Streptococcus faecium are resistant. Strains of methicillin-resistant staphylococci should also be considered resistant to imipenem. For clinical use imipenem is coadministered in equal parts with cilastatin. Cilastatin is a renal dehydropeptidase inhibitor that inhibits the metabolism of imipenem by renal brush-border enzymes, thus increasing imipenem concentrations in urine. Imipenem-cilastatin is administered by the intravenous route only. The adverse reaction profile of imipenem-cilastatin is similar to t that of other beta-lactam antibiotics. Recommended dosage reductions appropriate for renal impairment should be guided by periodic assessments of renal function, with close adherence to recommended dosage schedules, particularly among patients who are predisposed to seizures or receiving anticonvulsant medication. Imipenem-cilastatin performed well in both comparative and noncomparative trials of clinical efficacy and safety. For infections with multiple organisms (e.g., pelvic, intra-abdominal, or soft-tissue infections), imipenem-cilastatin may be a cost-effective and less toxic single-agent alternative to "standard" combination (e.g., aminoglycoside-penicillin plus an

  5. Development of a broad spectrum polymer-released antimicrobial coating for the prevention of resistant strain bacterial infections.

    Science.gov (United States)

    Sinclair, K D; Pham, T X; Farnsworth, R W; Williams, D L; Loc-Carrillo, C; Horne, L A; Ingebretsen, S H; Bloebaum, R D

    2012-10-01

    More than 400,000 primary hip and knee replacement surgeries are performed each year in the United States. From these procedures, approximately 0.5-3% will become infected and when considering revision surgeries, this rate has been found to increase significantly. Antibiotic-resistant bacterial infections are a growing problem in patient care. This in vitro research investigated the antimicrobial potential of the polymer released, broad spectrum, Cationic Steroidal Antimicrobial-13 (CSA-13) for challenges against 5 × 10(8) colony forming units (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). It was hypothesized that a weight-to-weight (w/w) concentration of 18% CSA-13 in silicone would exhibit potent bactericidal potential when used as a controlled release device coating. When incorporated into a polymeric device coating, the 18% (w/w) broad-spectrum polymer released CSA-13 antimicrobial eliminated 5 × 10(8) CFU of MRSA within 8 h. In the future, these results will be utilized to develop a sheep model to assess CSA-13 for the prevention of perioperative device-related infections in vivo.

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

    International Nuclear Information System (INIS)

    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(NO3)2/0.04 M H3PO4.12MoO3/4 M HNO3 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.

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

    International Nuclear Information System (INIS)

    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.

  8. A multidisciplinary antimicrobial stewardship programme safely decreases the duration of broad-spectrum antibiotic prescription in Singaporean adult renal patients.

    Science.gov (United States)

    Cai, Yiying; Shek, Pui Ying; Teo, Isabelle; Tang, Sarah S L; Lee, Winnie; Liew, Yi Xin; Chlebicki, Piotr; Kwa, Andrea L

    2016-01-01

    Patients with chronic kidney disease have increased risk of infections. Thus, physicians may favour prolonged broad-spectrum antibiotic use. Studies focused on antimicrobial stewardship programmes (ASPs) in renal patients are currently lacking. Here we describe the role of a multidisciplinary ASP and the impact of ASP interventions in renal patients. A multidisciplinary ASP was initiated at a tertiary hospital in Singapore. Patients prescribed broad-spectrum parenteral antibiotics were identified daily and were subjected to prospective review with immediate concurrent feedback. ASP data from January 2010 to December 2011 were analysed for all renal patients. Outcome measures included the duration and appropriateness of antibiotics, intervention acceptance rates, cost savings and safety outcomes. A total of 2084 antibiotic courses were reviewed, of which 24% were inappropriate, with meropenem most commonly prescribed inappropriately (31.0%). The commonest reasons for inappropriate use were wrong choice (51.0%) and wrong duration (21.4%). In total, 634 recommendations were made, with high acceptance rates (73.3%). Recommendations to discontinue antibiotics (33.4%) and to optimise doses (17.2%) comprised the bulk of ASP work. A mean reduction of -1.28 days of antibiotic use was observed among patients with interventions accepted versus those rejected (Pantibiotic use without compromising safety in renal patients. Continued effort is needed to produce a long-term impact on antibiotic prescription and resistance.

  9. 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.

  10. Spectrum of broad resonances in anti pp → π-π+

    International Nuclear Information System (INIS)

    An amplitude analysis has been made of data on anti p p → π-π+ imposing crossing symmetry, and analyticity as a function of energy. The technique was to generate solutions for the invariant amplitudes along a sequence of hyperbolas in st space specified by a parameter 'a'. (These curves form a generalisation of that considered in backward dispersion relations.) The partial wave amplitudes, obtained by projection, thus only emerge at the end of the analysis, and consequently their energy dependence is not prejudged. On individual 'a-sections' more than one solution is obtained. However, as yet, only one acceptable family of solutions continuous in 'a' has been generated. For this solution the partial wave amplitudes exhibit smooth yet structured energy dependencies in which clear resonance signals may be discerned: firstly, states with J = 0, 1, 2 and 3, with well -defined masses in the range 2.1 to 2.3 GeV, and widths about 200 MeV; additional broad states with J = 0, 2 and 4, having masses around 2.43 GeV and widths about 400 MeV; and finally, a possible state with J = 5 at a mass of about 2.4 GeV, but whose width is poorly defined. Alternative solutions are being sought. (author)

  11. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities

    Science.gov (United States)

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-01-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials. PMID:24625321

  12. Broad spectrum of mimiviridae virophage allows its isolation using a mimivirus reporter.

    Directory of Open Access Journals (Sweden)

    Morgan Gaia

    Full Text Available The giant virus Mimiviridae family includes 3 groups of viruses: group A (includes Acanthamoeba polyphaga Mimivirus, group B (includes Moumouvirus and group C (includes Megavirus chilensis. Virophages have been isolated with both group A Mimiviridae (the Mamavirus strain and the related Cafeteria roenbergensis virus, and they have also been described by bioinformatic analysis of the Phycodnavirus. Here, we found that the first two strains of virophages isolated with group A Mimiviridae can multiply easily in groups B and C and play a role in gene transfer among these virus subgroups. To isolate new virophages and their Mimiviridae host in the environment, we used PCR to identify a sample with a virophage and a group C Mimiviridae that failed to grow on amoeba. Moreover, we showed that virophages reduce the pathogenic effect of Mimivirus (plaque formation, establishing its parasitic role on Mimivirus. We therefore developed a co-culture procedure using Acanthamoeba polyphaga and Mimivirus to recover the detected virophage and then sequenced the virophage's genome. We present this technique as a novel approach to isolating virophages. We demonstrated that the newly identified virophages replicate in the viral factories of all three groups of Mimiviridae, suggesting that the spectrum of virophages is not limited to their initial host.

  13. Novel gramicidin formulations in cationic lipid as broad-spectrum microbicidal agents

    Directory of Open Access Journals (Sweden)

    Ragioto DA

    2014-06-01

    Full Text Available Danielle AMT Ragioto, Letícia DM Carrasco, Ana M Carmona-Ribeiro Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil Abstract: Dioctadecyldimethylammonium bromide (DODAB is an antimicrobial lipid that can be dispersed as large closed bilayers (LV or bilayer disks (BF. Gramicidin (Gr is an antimicrobial peptide assembling as channels in membranes and increasing their permeability towards cations. In mammalian cells, DODAB and Gr have the drawbacks of Gram-positive resistance and high toxicity, respectively. In this study, DODAB bilayers incorporating Gr showed good antimicrobial activity and low toxicity. Techniques employed were spectroscopy, photon correlation spectroscopy for sizing and evaluation of the surface potential at the shear plane, turbidimetric detection of dissipation of osmotic gradients in LV/Gr, determination of bacterial cell lysis, and counting of colony-forming units. There was quantitative incorporation of Gr and development of functional channels in LV. Gr increased the bilayer charge density in LV but did not affect the BF charge density, with localization of Gr at the BF borders. DODAB/Gr formulations substantially reduce Gr toxicity against eukaryotic cells and advantageously broaden the antimicrobial activity spectrum, effectively killing Escherichia coli and Staphylococcus aureus bacteria with occurrence of cell lysis. Keywords: antimicrobial peptides, cationic bilayers, bilayer fragments, dioctadecyldimethylammonium bromide, gramicidin A, self-assembly

  14. 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.

  15. 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. PMID:21077241

  16. Broad spectrum analysis of polar and apolar organic compounds in submicron atmospheric particles.

    Science.gov (United States)

    Fontal, Marta; van Drooge, Barend L; López, Jordi F; Fernández, Pilar; Grimalt, Joan O

    2015-07-24

    A method for the quantitative analysis of organic compounds on submicron particulate matter (PM1) collected on quartz filters was developed. The compounds analyzed encompassed C22-C35 alkanes, polycyclic aromatic hydrocarbons (PAHs), quinones, levoglucosan, cis-pinonic acid and short chain dicarboxylic acids such as malonic, succinic, glutaric, adipic, suberic, azelaic, malic and phthalic acids. The method included extraction with a pressure liquid extraction system, sample filtration though glass fibre filter, fractionation by high performance liquid chromatography and subsequent analysis by gas chromatography coupled to mass spectrometry. The study of the extraction efficiency of different solvent mixtures showed that DCM:MeOH 1:1 was the one providing the highest recoveries for all compounds. Extraction temperatures of 100°C provided better results than 60°C or 80°C. This method provided comparable extraction efficiency and qualitative and quantitative data to those involving Soxhlet extraction. Method recoveries for alkanes, most PAH, quinones and polar compounds calculated from spiked real samples were 52-72%, 78-101%, 50-62% and 76-104%, respectively, reproducibilities were 2-28%, 7-29%, 10-27% and 5-28%, respectively, limits of quantification were 0.01-0.1ng/m(3), 0.01-0.27ng/m(3), 0.04ng/m(3) and 0.32-2.8ng/m(3), respectively, which affords the quantification of a broad number of primary and secondary organic constituents of submicron aerosols. PMID:26054559

  17. 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.

  18. Mussel-inspired synthesis of polydopamine-functionalized graphene oxide hydrogel as broad-spectrum antimicrobial material

    Science.gov (United States)

    Wang, Xinpeng; Liu, Zhiming; Zhong, Huiqing; Guo, Zhouyi; Yuan, Xiaochan

    2014-09-01

    Recently, three-dimensional GO-based hydrogels have attracted great attention due to the unique advantages. It is generally know that bacteria are everywhere and many of them could cause the diseases and threaten human health. However, developing new antibacterial materials with high-efficiency, low cost, broad-spectrum, and easy recycling is still a great challenge. Herein, inspired by mussel, we synthesized benzalkonium bromide/polydopamine/reduced graphene oxide hydrogel (BKB/PDA/rGOG). The as-prepared three-dimensional hydrogels were characterized by scanning eletron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. The resultant hydrogels exhibited strong antibacterial effects to both Gram-negative and Gram-positive bacteria due to the synergistic effect of graphene oxide and benzalkonium bromide. In addition, the resultant hydrogels could be removed easily from the resolution, which was undoubtedly good news for industry application.

  19. Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs.

    Science.gov (United States)

    Maianti, Juan Pablo; Kanazawa, Hiroki; Dozzo, Paola; Matias, Rowena D; Feeney, Lee Ann; Armstrong, Eliana S; Hildebrandt, Darin J; Kane, Timothy R; Gliedt, Micah J; Goldblum, Adam A; Linsell, Martin S; Aggen, James B; Kondo, Jiro; Hanessian, Stephen

    2014-09-19

    Aminoglycoside antibiotics are pseudosaccharides decorated with ammonium groups that are critical for their potent broad-spectrum antibacterial activity. Despite over three decades of speculation whether or not modulation of pKa is a viable strategy to curtail aminoglycoside kidney toxicity, there is a lack of methods to systematically probe amine-RNA interactions and resultant cytotoxicity trends. This study reports the first series of potent aminoglycoside antibiotics harboring fluorinated N1-hydroxyaminobutyryl acyl (HABA) appendages for which fluorine-RNA contacts are revealed through an X-ray cocrystal structure within the RNA A-site. Cytotoxicity in kidney-derived cells was significantly reduced for the derivative featuring our novel β,β-difluoro-HABA group, which masks one net charge by lowering the pKa without compromising antibacterial potency. This novel side-chain assists in evasion of aminoglycoside-modifying enzymes, and it can be easily transferred to impart these properties onto any number of novel analogs.

  20. 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.

  1. 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

  2. Reduced TiO2-Graphene Oxide Heterostructure As Broad Spectrum-Driven Efficient Water-Splitting Photocatalysts.

    Science.gov (United States)

    Li, Lihua; Yu, Lili; Lin, Zhaoyong; Yang, Guowei

    2016-04-01

    The reduced TiO2-graphene oxide heterostructure as an alternative broad spectrum-driven efficient water splitting photocatalyst has become a really interesting topic, however, its syntheses has many flaws, e.g., tedious experimental steps, time-consuming, small scale production, and requirement of various additives, for example, hydrazine hydrate is widely used as reductant to the reduction of graphene oxide, which is high toxicity and easy to cause the second pollution. For these issues, herein, we reported the synthesis of the reduced TiO2-graphene oxide heterostructure by a facile chemical reduction agent-free one-step laser ablation in liquid (LAL) method, which achieves extended optical response range from ultraviolet to visible and composites TiO2-x (reduced TiO2) nanoparticle and graphene oxide for promoting charge conducting. 30.64% Ti(3+) content in the reduced TiO2 nanoparticles induces the electronic reconstruction of TiO2, which results in 0.87 eV decrease of the band gap for the visible light absorption. TiO2-x-graphene oxide heterostructure achieved drastically increased photocatalytic H2 production rate, up to 23 times with respect to the blank experiment. Furthermore, a maximum H2 production rate was measured to be 16 mmol/h/g using Pt as a cocatalyst under the simulated sunlight irradiation (AM 1.5G, 135 mW/cm(2)), the quantum efficiencies were measured to be 5.15% for wavelength λ = 365 ± 10 nm and 1.84% for λ = 405 ± 10 nm, and overall solar energy conversion efficiency was measured to be 14.3%. These findings provided new insights into the broad applicability of this methodology for accessing fascinate photocatalysts. PMID:26986700

  3. Characterization of a type-I crustin with broad-spectrum antimicrobial activity from red swamp crayfish Procambarus clarkii.

    Science.gov (United States)

    Liu, Ning; Zhang, Ran-Ran; Fan, Zhen-Xu; Zhao, Xiao-Fan; Wang, Xian-Wei; Wang, Jin-Xing

    2016-08-01

    Crustins are a family of antimicrobial peptides mainly identified in crustaceans and characterized by a whey acidic protein (WAP) domain and an additional glycine-, cysteine-, or proline-rich region. In this study, we identified and characterized PcCru, a new crustin isolated from red swamp crayfish Procambarus clarkii. The open reading frame of PcCru was 333 base pairs long and encoded a 110-residue polypeptide, which contained a signal peptide, a cysteine-rich region, and a WAP domain. The architecture and phylogenetic analysis suggested that PcCru was a new member of the type-I crustin family. PcCru was highly expressed in hemocytes and was significantly induced by viral and bacterial stimulations at both the translational and transcriptional levels. The titer of PcCru in circulating plasma was also increased considerably by bacterial challenge. Recombinant PcCru from both prokaryotic and eukaryotic expression systems were generated, and the proteins exhibited broad-spectrum antimicrobial activity. Furthermore, PcCru protected crayfish from infection by pathogenic bacteria Aeromonas hydrophila in vivo. This study provided new information emphasizing the important role of the crustin family in the crustacean antibacterial immune response. PMID:27021077

  4. Silver Nanoparticles: Biosynthesis Using an ATCC Reference Strain of Pseudomonas aeruginosa and Activity as Broad Spectrum Clinical Antibacterial Agents

    Science.gov (United States)

    Quinteros, Melisa A.; Aiassa Martínez, Ivana M.; Dalmasso, Pablo R.; Páez, Paulina L.

    2016-01-01

    Currently, the biosynthesis of silver-based nanomaterials attracts enormous attention owing to the documented antimicrobial properties of these ones. This study reports the extracellular biosynthesis of silver nanoparticles (Ag-NPs) using a Pseudomonas aeruginosa strain from a reference culture collection. A greenish culture supernatant of P. aeruginosa incubated at 37°C with a silver nitrate solution for 24 h changed to a yellowish brown color, indicating the formation of Ag-NPs, which was confirmed by UV-vis spectroscopy, transmission electron microscopy, and X-ray diffraction. TEM analysis showed spherical and pseudospherical nanoparticles with a distributed size mainly between 25 and 45 nm, and the XRD pattern revealed the crystalline nature of Ag-NPs. Also it provides an evaluation of the antimicrobial activity of the biosynthesized Ag-NPs against human pathogenic and opportunistic microorganisms, namely, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Proteus mirabilis, Acinetobacter baumannii, Escherichia coli, P. aeruginosa, and Klebsiella pneumonia. Ag-NPs were found to be bioactive at picomolar concentration levels showing bactericidal effects against both Gram-positive and Gram-negative bacterial strains. This work demonstrates the first helpful use of biosynthesized Ag-NPs as broad spectrum bactericidal agents for clinical strains of pathogenic multidrug-resistant bacteria such as methicillin-resistant S. aureus, A. baumannii, and E. coli. In addition, these Ag-NPs showed negligible cytotoxic effect in human neutrophils suggesting low toxicity to the host. PMID:27340405

  5. The Broad-band X-ray Spectrum of IC 4329A from a Joint NuSTAR/Suzaku Observation

    CERN Document Server

    Brenneman, Laura; Fuerst, F; Matt, G; Elvis, M; Harrison, F A; Ballantyne, D R; Boggs, S E; Christensen, F E; Craig, W W; Fabian, A C; Grefenstette, B W; Hailey, C J; Madsen, K K; Marinucci, A; Rivers, E; Stern, D; Walton, D J; Zhang, W W

    2014-01-01

    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 at $N_H = 6 \\times 10^{21}$ cm$^2$, 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 K{\\alpha} line: $E = 6.46^{+0.08}_{-0.07}$ keV rest frame with ${\\sigma} = 0.33^{+0.08}_{-0.07}$ keV and $EW = 34^{+8}_{-7}$ 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{\\alpha} line strengths observed in nearby, bright AGN (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-ene...

  6. Broad-band transmission spectrum and K-band thermal emission of WASP-43b as observed from the ground

    CERN Document Server

    Chen, Guo; Wang, Hongchi; Nikolov, Nikolay; Fortney, Jonathan J; Seemann, Ulf; Wang, Wei; Mancini, Luigi; Henning, Thomas

    2014-01-01

    (Abridged) We observed one transit and one occultation of the hot Jupiter WASP-43b simultaneously in the g'r'i'z'JHK bands using the GROND instrument on the MPG/ESO 2.2-meter telescope. From the transit event, we have independently derived WASP-43's system parameters with high precision, and improved the period to be 0.81347437(13) days. No significant variation in transit depths is detected, with the largest deviations coming from the i', H, and K bands. Given the observational uncertainties, the broad-band transmission spectrum can be explained by either a flat featureless straight line that indicates thick clouds, synthetic spectra with absorption signatures of atomic Na/K or molecular TiO/VO that indicate cloud-free atmosphere, or a Rayleigh scattering profile that indicates high-altitude hazes. From the occultation event, we have detected planetary dayside thermal emission in the K-band with a flux ratio of 0.197 +/- 0.042%, which confirms previous detections obtained in the 2.09 micron narrow band and K...

  7. 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. PMID:26959835

  8. Structures of mammalian ER α-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals.

    Science.gov (United States)

    Caputo, Alessandro T; Alonzi, Dominic S; Marti, Lucia; Reca, Ida-Barbara; Kiappes, J L; Struwe, Weston B; Cross, Alice; Basu, Souradeep; Lowe, Edward D; Darlot, Benoit; Santino, Angelo; Roversi, Pietro; Zitzmann, Nicole

    2016-08-01

    The biosynthesis of enveloped viruses depends heavily on the host cell endoplasmic reticulum (ER) glycoprotein quality control (QC) machinery. This dependency exceeds the dependency of host glycoproteins, offering a window for the targeting of ERQC for the development of broad-spectrum antivirals. We determined small-angle X-ray scattering (SAXS) and crystal structures of the main ERQC enzyme, ER α-glucosidase II (α-GluII; from mouse), alone and in complex with key ligands of its catalytic cycle and antiviral iminosugars, including two that are in clinical trials for the treatment of dengue fever. The SAXS data capture the enzyme's quaternary structure and suggest a conformational rearrangement is needed for the simultaneous binding of a monoglucosylated glycan to both subunits. The X-ray structures with key catalytic cycle intermediates highlight that an insertion between the +1 and +2 subsites contributes to the enzyme's activity and substrate specificity, and reveal that the presence of d-mannose at the +1 subsite renders the acid catalyst less efficient during the cleavage of the monoglucosylated substrate. The complexes with iminosugar antivirals suggest that inhibitors targeting a conserved ring of aromatic residues between the α-GluII +1 and +2 subsites would have increased potency and selectivity, thus providing a template for further rational drug design. PMID:27462106

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

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, P.; Cybulski, M. [Lasers and Electro-Optics Div., Consumer and Clinical Radiation Protection Bureau, Product Safety Program, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario (Canada)], E-mail: pascale_reinhardt@hc-sc.gc.ca; Miller, S.M.; Ferrarotto, C.; Wilkins, R. [Radiobiology Div., Consumer and Clinical Radiation Protection Bureau, Product Safety Program, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario (Canada); Deslauriers, Y. [Lasers and Electro-Optics Div., Consumer and Clinical Radiation Protection Bureau, Product Safety Program, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario (Canada)

    2006-02-15

    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{sup 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-1{alpha} (IL-1{alpha}), interleukin-6 (IL-6), and tumour necrosis factor-{alpha} (TNF-{alpha}). 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-1{alpha} levels increased with LOM concentration. The release of TNF-{alpha} and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 {mu}mol/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)

  10. 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

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

    Science.gov (United States)

    Kim, Yunjeong; Liu, Hongwei; Galasiti Kankanamalage, Anushka C; Weerasekara, Sahani; Hua, Duy H; Groutas, William C; Chang, Kyeong-Ok; Pedersen, Niels C

    2016-03-01

    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 further

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ostorero, L.; /Turin U. /INFN, Turin; Moderski, R.; /Warsaw, Copernicus Astron. Ctr. /KIPAC, Menlo Park; Stawarz, L.; /KIPAC, Menlo Park /Jagiellonian U., Astron. Observ.; Diaferio, A.; /Turin U. /INFN, Turin; Kowalska, I.; /Warsaw U. Observ.; Cheung, C.C.; /NASA, Goddard /Naval Research Lab, Wash., D.C.; Kataoka, J.; /Waseda U., RISE; Begelman, M.C.; /JILA, Boulder; Wagner, S.J.; /Heidelberg Observ.

    2010-06-07

    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 {gamma}-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{sub H}) and radio (N{sub 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.

  14. Baulamycins A and B, broad-spectrum antibiotics identified as inhibitors of siderophore biosynthesis in Staphylococcus aureus and Bacillus anthracis.

    Science.gov (United States)

    Tripathi, Ashootosh; Schofield, Michael M; Chlipala, George E; Schultz, Pamela J; Yim, Isaiah; Newmister, Sean A; Nusca, Tyler D; Scaglione, Jamie B; Hanna, Philip C; Tamayo-Castillo, Giselle; Sherman, David H

    2014-01-29

    Siderophores are high-affinity iron chelators produced by microorganisms and frequently contribute to the virulence of human pathogens. Targeted inhibition of the biosynthesis of siderophores staphyloferrin B of Staphylococcus aureus and petrobactin of Bacillus anthracis hold considerable potential as a single or combined treatment for methicillin-resistant S. aureus (MRSA) and anthrax infection, respectively. The biosynthetic pathways for both siderophores involve a nonribosomal peptide synthetase independent siderophore (NIS) synthetase, including SbnE in staphyloferrin B and AsbA in petrobactin. In this study, we developed a biochemical assay specific for NIS synthetases to screen for inhibitors of SbnE and AsbA against a library of marine microbial-derived natural product extracts (NPEs). Analysis of the NPE derived from Streptomyces tempisquensis led to the isolation of the novel antibiotics baulamycins A (BmcA, 6) and B (BmcB, 7). BmcA and BmcB displayed in vitro activity with IC50 values of 4.8 μM and 19 μM against SbnE and 180 μM and 200 μM against AsbA, respectively. Kinetic analysis showed that the compounds function as reversible competitive enzyme inhibitors. Liquid culture studies with S. aureus , B. anthracis , E. coli , and several other bacterial pathogens demonstrated the capacity of these natural products to penetrate bacterial barriers and inhibit growth of both Gram-positive and Gram-negative species. These studies provide proof-of-concept that natural product inhibitors targeting siderophore virulence factors can provide access to novel broad-spectrum antibiotics, which may serve as important leads for the development of potent anti-infective agents. PMID:24401083

  15. Photomorphogenesis and photoassimilation in soybean and sorghum grown under broad spectrum or blue-deficient light sources

    Science.gov (United States)

    Britz, S. J.; Sager, J. C.; Knott, W. M. (Principal Investigator)

    1990-01-01

    The role of blue light in plant growth and development was investigated in soybean (Glycine max [L.] Merr. cv Williams) and sorghum (Sorghum bicolor [L.] Moench. cv Rio) grown under equal photosynthetic photon fluxes (approximately 500 micromoles per square meter per second) from broad spectrum daylight fluorescent or blue-deficient, narrow-band (589 nanometers) low pressure sodium (LPS) lamps. Between 14 and 18 days after sowing, it was possible to relate adaptations in photosynthesis and leaf growth to dry matter accumulation. Soybean development under LPS light was similar in several respects to that of shaded plants, consistent with an important role for blue light photoreceptors in regulation of growth response to irradiance. Thus, soybeans from LPS conditions partitioned relatively more growth to leaves and maintained higher average leaf area ratios (mean LAR) that compensated lower net assimilation rates (mean NAR). Relative growth rates were therefore comparable to plants from daylight fluorescent lamps. Reductions in mean NAR were matched by lower rates of net photosynthesis (A) on an area basis in the major photosynthetic source (first trifoliolate) leaf. Lower A in soybean resulted from reduced leaf dry matter per unit leaf area, but lower A under LPS conditions in sorghum correlated with leaf chlorosis and reduced total nitrogen (not observed in soybean). In spite of a lower A, mean NAR was larger in sorghum from LPS conditions, resulting in significantly greater relative growth rates (mean LAR was approximately equal for both light conditions). Leaf starch accumulation rate was higher for both species and starch content at the end of the dark period was elevated two- and three-fold for sorghum and soybean, respectively, under LPS conditions. Possible relations between starch accumulation, leaf export, and plant growth in response to spectral quality were considered.

  16. Controlled delivery of a new broad spectrum antibacterial agent against colitis: In vitro and in vivo performance.

    Science.gov (United States)

    Nieto-Bobadilla, M S; Siepmann, F; Djouina, M; Dubuquoy, L; Tesse, N; Willart, J-F; Dubreuil, L; Siepmann, J; Neut, C

    2015-10-01

    Coated pellets and mini-tablets were prepared containing a new broad spectrum antibacterial agent: CIN-102, a well-defined, synergistic blend of trans-cinnamaldehyde, trans-2-methoxycinnamaldehyde, cinnamyl acetate, linalool, β-caryophyllene, cineol and benzyl benzoate. The aim was to provide a new treatment method for colitis, especially for Inflammatory Bowel Disease (IBD) patients. Since the simple oral gavage of CIN-102 was not able to reduce the pathogenic bacteria involved in colitis (rat model), the drug was incorporated into multiparticulates. The idea was to minimize undesired drug release in the upper gastrointestinal tract and to control CIN-102 release in the colon, in order to optimize the resulting antibiotic concentration at the site of action. A particular challenge was the fact that CIN-102 is a volatile hydrophobic liquid. Pellet cores were prepared by extrusion-spheronization and coated with polymer blends, which are sensitive to colonic bacterial enzymes. Mini-tablets were prepared by direct compression. The release of the main compound of CIN-102 (cinnamaldehyde, 86.7% w/w) was monitored in vitro. Optimized coated pellets and mini-tablets were also tested in vivo: in seven-week-old, male mice suffering from dextran sodium sulfate induced colitis. Importantly, both types of multiparticulates were able: (i) to significantly reduce the number of luminal and mucosal enterobacteria in the mice (the levels of which are increased in the disease state), and (ii) to improve the clinical course of the intestinal inflammation (decrease in the percentages of mice with bloody stools and diarrhea). Thus, the proposed coated pellets and matrix mini-tablets allowing for controlled CIN-102 release show a promising potential for new treatment methods of colitis. PMID:26209123

  17. Comparison of nitroethane, 2-nitro-1-propanol, lauric acid, Lauricidin and the Hawaiian marine algae, Chaetoceros, for potential broad-spectrum control of anaerobically grown lactic acid bacteria

    Science.gov (United States)

    The gastrointestinal tract of bovines often contains bacteria that contribute to disorders of the rumen and may also contain foodborne or opportunistic human pathogens as well as bacteria capable of causing mastitis in cows. Thus, there is a need to develop broad-spectrum therapies that are effecti...

  18. Draft genome sequence of Streptomyces sp. strain Wb2n-11, a desert isolate with broad-spectrum antagonism against soilborne phytopathogens

    Energy Technology Data Exchange (ETDEWEB)

    Koeberl, 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.

  19. De Novo Whole-Genome Sequence of Micromonospora carbonacea JXNU-1 with Broad-Spectrum Antimicrobial Activity, Isolated from Soil Samples

    OpenAIRE

    Jiang, Yun; Huang, Yun-hong; Long, Zhong-er

    2015-01-01

    Micromonospora carbonacea JXNU-1 is an actinomycete with broad-spectrum antimicrobial activity, isolated from soil samples from the farmland in the area of Yaohu Lake in Nanchang, China. Here, we report the whole-genome sequence of M. carbonacea JXNU-1.

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yanping, E-mail: yx2132@cumc.columbia.edu; 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){sup 3}He and D(d,n){sup 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 {sup 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.

  1. 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.

    2015-09-01

    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)3He and D(d,n)3He, 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 9Be(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.

  2. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Vincent E de Meijer

    Full Text Available BACKGROUND: Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs. The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF-alpha-converting enzyme (TACE. We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4 administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4 was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-alpha receptors. Liver injury was quantified by alanine aminotransferase (ALT levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-alpha receptors exhibited an 80% reduction of serum ALT

  3. Newly isolated Paenibacillus tyrfis sp. nov., from Malaysian tropical peat swamp soil with broad spectrum antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Yoong Kit eAw

    2016-03-01

    Full Text Available Emergence of antimicrobial resistance coupled with the slowdown in discovery of new antimicrobial compounds points to serious consequences in human health. Therefore, scientists are looking for new antimicrobial compounds from unique and understudied ecosystem such as tropical peat swamp forests. Over the course of isolating antimicrobial producing bacteria from North Selangor tropical peat swamp forest, Malaysia, a Gram variable, rod shaped, endospore forming, facultative anaerobic novel strain MSt1T that exerts potent and broad spectrum antimicrobial activity was isolated. Phylogenetic analysis using 16S rRNA gene sequences showed that strain MSt1T belonged to the genus Paenibacillus with the highest similarity with Paenibacillus elgii SD17T (99.5%. Whole genome comparison between strain MSt1T with its closely related species using average nucleotide identity (ANI revealed that similarity between strain MSt1T with Paenibacillus elgii B69 (93.45% and Paenibacillus ehimensis A2 (90.42% was below the recommended threshold of 95%. Further analysis using in silico pairwise DDH also showed that similarity between strain MSt1T with P. elgii B69 (55.4% and P. ehimensis A2 (43.7% was below the recommended threshold of 70%. Strain MSt1T contained meso-diaminopilemic acid in the cell wall and MK-7 as the major menaquinone. The major fatty acids of strain MSt1T were anteiso-C15:0 (48.2% and C16:0 (29.0% whereas the polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unknown lipid, two unknown glycolipids and one unknown phospholipid. Total DNA G+C content of strain MSt1T was 51.5 mol%. Extract from strain MSt1T exerted strong antimicrobial activity against Escherichia coli ATCC 25922 (MIC = 1.5 µg/mL, MRSA ATCC 700699 (MIC = 25 µg/mL and Candida albicans IMR (MIC = 12.5 µg/mL. Partially purified active fraction exerted strong effect against Escherichia coli ATCC 25922 resulting in cell rupture

  4. Observation of a Broad Structure in the $\\pi^+\\pi^-J/\\psi$ Mass Spectrum around 4.26~GeV/$c^2$

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.; Barate, R.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Tisserand, V.; Zghiche, A.; /Annecy, LAPP; Grauges, E.; /Barcelona, IFAE; Palano, A.; Pappagallo, M.; Pompili, A.; /Bari U. /INFN, Bari; Chen, J.C.; Qi, N.D.; Rong, G.; Wang, P.; Zhu, Y.S.; /Beijing, Inst. High Energy Phys.; Eigen, G.; Ofte, I.; Stugu, B.

    2005-07-06

    The authors study initial-state radiation events, e{sup +}e{sup -} {yields} {gamma}{sub ISR} {pi}{sup +}{pi}{sup -} J/{psi}, with data collected with the BABAR detector. They observe an accumulation of events near 4.26 GeV/c{sup 2} in the invariant-mass spectrum of {pi}{sup +}{pi}{sup -} J/{psi}. Fits of the mass spectrum indicate that a broad resonance with a mass of about 4.26 GeV/c{sup 2} is required to describe the observed structure. The presence of additional narrow resonances cannot be excluded. The fitted width of the broad resonance is 50 to 90 MeV/c{sup 2}, depending on the fit hypothesis.

  5. Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity

    OpenAIRE

    Khedr MA

    2015-01-01

    Mohammed A KhedrDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, EgyptAbstract: Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were sy...

  6. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics - Fluoroquinolones

    OpenAIRE

    Qiming Li; Longxiang Xie; Quanxin Long; Jinxiao Mao; Hui Li; Mingliang Zhou; Jianping Xie

    2015-01-01

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoro...

  7. Rice RING protein OSBBI1 with E3 ligase activity confers broad-spectrum resistance against Magnaporthe oryzae by modifying the cell wall defence

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Zuhua He; Sihui Zhong; Guojun Li; Qun Li; Bizeng Mao; Yiwen Deng; Huijuan Zhang; Longjun Zeng; Fengming Song

    2011-01-01

    Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including innate immune responses in plants. However, the mechanism of the E3 ligase involvement in plant innate immunity is unclear.We report that a rice gene, OsBBI1, encoding a RING finger protein with E3 ligase activity, mediates broad-spectrum disease resistance. The expression of OSBBI1 was induced by rice blast fungus Magnaporthe oryzae, as well as chemical inducers, benzothiadiazole and salicylic acid. Biochemical analysis revealed that OsBBI1 protein possesses E3ubiquitin ligase activity in vitro. Genetic analysis revealed that the loss of OsBBI1 function in a Tos17-insertion line increased susceptibility, while the overexpression of OsBBI1 in transgenic plants conferred enhanced resistance to multiple races of M.oryzae. This indicates that OsBBI1 modulates broad-spectrum resistance against the blast fungus. The OsBBII-overexpressing plants showed higher levels of H,O, accumulation in cells and higher levels of phenolic compounds and cross-linking of proteins in cell walls at infection sites by M. Oryzae compared with wild-type(WT)plants. The cell walls were thicker in the OsBB11-overexpressing plants and thinner in the mutant plants than in the WT plants. Our results suggest that OsBBH modulates broad-spectrum resistance to blast fungus by modifying cell wall defence responses. The functional characterization of OsBBI1 provides insight into the E3 ligase-mediated innate immunity, and a practical tool for constructing broad-spectrum resistance against the most destructive disease in rice.

  8. The impact of pricing and patent expiration on the demand for pharmaceuticals: An examination of the use of broad-spectrum antimicrobials

    OpenAIRE

    Kaier, Klaus

    2010-01-01

    The aim of the analysis was to determine whether demand in Germany for antibiotics is driven by prices that drop considerably when generic substitutes become available. A time-series approach was therefore carried out to explore price elasticities of demand for two different classes of broad-spectrum antimicrobials (fluoroquinolones and cephalosporins) using data on ambulatory antibiotics prescribed on the German statutory health insurance scheme and data on in-hospital antibiotic use in a Ge...

  9. Anemia is associated with an increased central venous pressure and mortality in a broad spectrum of cardiovascular patients

    NARCIS (Netherlands)

    Kleijn, Lennaert; Westenbrink, B. Daan; van Deursen, Vincent M.; Damman, Kevin; de Boer, Rudolf A.; Hillege, Hans; van Veldhuisen, Dirk J.; Voors, Adriaan A.; van der Meer, Peter

    2014-01-01

    Background Anemia is frequently observed in patients with cardiovascular disease. Multiple factors have been associated with anemia, but the role of hemodynamics is largely unknown. Therefore, we investigated the association between hemoglobin (Hb) levels, hemodynamics and outcome in a broad spectru

  10. 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.

  11. The ASCA X-Ray Spectrum Of The Broad-Line Radio Galaxy Pictor A A Simple Power Law With No Fe K-$\\alpha$ Line

    CERN Document Server

    Eracleous, M; Eracleous, Michael; Halpern, Jules P.

    1998-01-01

    We present the X-ray spectrum of the broad-line radio galaxy Pictor A as observed by ASCA in 1996. The main objective of the observation was to detect and study the profiles of the Fe~K$\\alpha$ lines. The motivation was the fact that the Balmer lines of this object show well-separated displaced peaks, suggesting an origin in an accretion disk. The 0.5-10 keV X-ray spectrum is described very well by a model consisting of a power law of photon index 1.77 modified by interstellar photoelectric absorption. We find evidence for neither a soft nor a hard (Compton reflection) excess. More importantly, we do not detect an Fe K-alpha line, in marked contrast with the spectra of typical Seyfert galaxies and other broad-line radio galaxies observed by ASCA. The 99%-confidence upper limit on the equivalent width of an unresolved line at a rest energy of 6.4 keV is 100 eV, while for a broad line (FWHM of approximately 60,000 km/s) the corresponding upper limit is 135 eV. We discuss several possible explanations for the we...

  12. 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.

  13. 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. PMID:24777097

  14. 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

    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_5031ins......AA) 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....

  15. Broad-band radio circular polarization spectrum of the relativistic jet in PKS B2126-158

    Science.gov (United States)

    O'Sullivan, S. P.; McClure-Griffiths, N. M.; Feain, I. J.; Gaensler, B. M.; Sault, R. J.

    2013-10-01

    We present full Stokes radio polarization observations of the quasar PKS B2126-158 (z = 3.268) from 1 to 10 GHz using the Australia Telescope Compact Array. The source has large fractional circular polarization (CP), mc ≡ |V|/I, detected at high significance across the entire band (from 15 to 90σ per 128 MHz subband). This allows us to construct the most robust CP spectrum of an active galactic nucleus (AGN) jet to date. We find mc ∝ ν+0.60 ± 0.03 from 1.5 to 6.5 GHz, with a peak of mc ˜ 1 per cent before the spectrum turns over somewhere between 6.5 and 8 GHz, above which mc ∝ ν-3.0 ± 0.4. The fractional linear polarization (LP; p) varies from ≲0.2 to ˜1 per cent across our frequency range and is strongly anticorrelated with the fractional CP, with a best-fitting power law giving mc ∝ p-0.24 ± 0.03. This is the first clear relation between the observed LP and CP of an AGN jet, revealing the action of Faraday conversion of LP to CP within the jet. More detailed modelling in conjunction with high spatial resolution observations are required to determine the true driving force behind the conversion (i.e. magnetic twist or internal Faraday rotation). In particular determining whether the observed Faraday rotation is internal or entirely external to the jet is key to this goal. The simplest interpretation of our observations favours some internal Faraday rotation, implying that Faraday rotation-driven conversion of LP to CP is the dominant CP generation mechanism. In this case, a small amount of vector-ordered magnetic field along the jet axis is required, along with internal Faraday rotation from the low-energy end of the relativistic electron energy spectrum in an electron-proton-dominated jet.

  16. Design of a molecular imprinting biosensor with multi-scale roughness for detection across a broad spectrum of biomolecules.

    Science.gov (United States)

    Yu, Yingjie; Zhang, Qi; Chang, Chung-Chueh; Liu, Ying; Yang, Zhenhua; Guo, Yichen; Wang, Yantian; Galanakis, Dennis K; Levon, Kalle; Rafailovich, Miriam

    2016-10-01

    The molecular imprinting technique has tremendous applications in artificial enzymes, bioseparation, and sensor devices. In this study, a novel molecular imprinting (MI) biosensor platform was developed for the detection of a broad range of biomolecules with different sizes. Previously this method has been applied to 2D molecular imprinting, where the height of the self-assembled monolayer (SAM) of around 2 nm limited the maximum dimensions of the molecule that can be imprinted to create template-shaped cavities. In order to match the size of the imprinted molecules with the height of the SAM, we propose a model for 3D molecular imprinting where the analyte is sequestered within a niche created by the surface roughness. The SAM is assembled on the walls of the niche, forming a 3D pattern of the analyte uniquely molded to its contour. Surfaces with multi-scale roughness were prepared by evaporation of gold onto electropolished (smooth) and unpolished (rough) Si wafers, where the native roughness was found to have a normal distribution centered around 5 and 90 nm respectively. Our studies using molecules with size ranging on a nanometer scale, from proteins of a few nanometers to bacteria of hundreds of nanometers, showed that when the size of the analyte matched the roughness range of the gold surface, the molecular imprinting process was optimized for the best biosensing performance. After optimization, the MI biosensor platform enabled the identification and quantification of a broad range of biomolecules with great discrimination abilities. Hemoglobin under different pH values and several mutated fibrinogen molecules can also be well differentiated through the test.

  17. Broad-Spectrum Drug Screening Using Liquid Chromatography-Hybrid Triple-Quadrupole Linear Ion Trap Mass Spectrometry.

    Science.gov (United States)

    Stone, Judy

    2016-01-01

    Urine is processed with a simple C18 solid-phase extraction (SPE) and reconstituted in mobile phase. The liquid chromatography system (LC) injects 10 μL of extracted sample onto a reverse-phase LC column for gradient analysis with ammonium formate/acetonitrile mobile phases. Drugs in the column eluent become charged in the ion source using positive electrospray ionization (ESI). Pseudomolecular ions (M + H) are analyzed by a hybrid triple-quadrupole linear ion trap (QqQ and QqLIT) mass spectrometer using an SRM-IDA-EPI acquisition. An initial 125 compound selected ion monitoring (SRM) survey scan (triple quadrupole or QqQ mode) is processed by the information-dependent acquisition (IDA) algorithm. The IDA algorithm selects SRM signals from the survey scan with a peak height above the threshold (the three most abundant SRM signals above 1000 cps) to define precursor ions for subsequent dependent scanning. In the dependent QqLIT scan(s), selected precursor ion(s) are passed through the first quadrupole (Q1), fragmented with three different collision energies in the collision cell (Q2 or q), and product ions are collected in the third quadrupole (Q3), now operating as a linear ion trap (LIT). The ions are scanned out of the LIT in a mass dependent manner to produce a full-scan product ion spectrum (m/z 50-700) defined as an Enhanced (meaning acquired in LIT mode) Product Ion (EPI) spectrum (Mueller et al., Rapid Commun Mass Spectrom 19:1332-1338, 2005). Each EPI spectrum is linked to its precursor ion and to the associated SRM peak from the survey scan. EPI spectra are automatically searched against a 125 drug library of reference EPI spectra for identification. When the duty cycle is complete (one survey scan of 125 SRMs plus 0-3 dependent IDA-EPI scans) the mass spectrometer begins another survey scan of the 125 SRMs. PMID:26660183

  18. 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.

  19. 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

  20. Czech ethanol-free propolis extract displays inhibitory activity against a broad spectrum of bacterial and fungal pathogens.

    Science.gov (United States)

    Netíková, Ladislava; Bogusch, Petr; Heneberg, Petr

    2013-09-01

    Propolis acts primarily as a biocide against invasive bacteria and fungi in the hive, suggesting its potential for industrial applications. In food application, propolis is considered as a chemical preservative in meat products, extending shelf life of frozen meat and other food. The mechanism of action is still unclear due to the synergy of multiple compounds contained in propolis and due to parallel targeting of multiple pathways within each affected organism. Here, we examined the antimicrobial properties of dimethylsulfoxide (DMSO) Czech propolis extract. Until recently, DMSO was only rarely used in the propolis studies, although the other solvents tested (mostly ethanol) may significantly affect the observed inhibitory effects, notwithstanding the antimicrobial effects of ethanol itself. Here, we provide results of zone inhibition tests against Aspergillus fumigatus, Microsporum gypseum, Microsporum canis, Candida albicans, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis. Although we determined inhibitory effects against all the microorganisms tested, the dose-dependent response curves were not similar to each other. While inhibitory effects against C. albicans or S. aureus were strictly dose-dependent, responses of M. gypseum and E. faecalis displayed plateau across the broad range of concentrations tested. Interestingly, response of E. coli revealed the double-peak dose-dependent curve, and responses of M. canis and L. monocytogenes decreased at the highest concentrations tested. Suggested is evaluation of DMSO propolis extracts in experimental treatment of human and veterinary infections, preferably in multitherapy with antibiotics. PMID:23915150

  1. Czech ethanol-free propolis extract displays inhibitory activity against a broad spectrum of bacterial and fungal pathogens.

    Science.gov (United States)

    Netíková, Ladislava; Bogusch, Petr; Heneberg, Petr

    2013-09-01

    Propolis acts primarily as a biocide against invasive bacteria and fungi in the hive, suggesting its potential for industrial applications. In food application, propolis is considered as a chemical preservative in meat products, extending shelf life of frozen meat and other food. The mechanism of action is still unclear due to the synergy of multiple compounds contained in propolis and due to parallel targeting of multiple pathways within each affected organism. Here, we examined the antimicrobial properties of dimethylsulfoxide (DMSO) Czech propolis extract. Until recently, DMSO was only rarely used in the propolis studies, although the other solvents tested (mostly ethanol) may significantly affect the observed inhibitory effects, notwithstanding the antimicrobial effects of ethanol itself. Here, we provide results of zone inhibition tests against Aspergillus fumigatus, Microsporum gypseum, Microsporum canis, Candida albicans, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis. Although we determined inhibitory effects against all the microorganisms tested, the dose-dependent response curves were not similar to each other. While inhibitory effects against C. albicans or S. aureus were strictly dose-dependent, responses of M. gypseum and E. faecalis displayed plateau across the broad range of concentrations tested. Interestingly, response of E. coli revealed the double-peak dose-dependent curve, and responses of M. canis and L. monocytogenes decreased at the highest concentrations tested. Suggested is evaluation of DMSO propolis extracts in experimental treatment of human and veterinary infections, preferably in multitherapy with antibiotics.

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

    Science.gov (United States)

    Kevin, Dion A; Meujo, Damaris AF; Hamann, Mark T

    2016-01-01

    Background 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. Objective 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. Conclusion 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. PMID:23480512

  3. The broad pattern recognition spectrum of the Toll-like receptor in mollusk Zhikong scallop Chlamys farreri.

    Science.gov (United States)

    Wang, Mengqiang; Wang, Lingling; Guo, Ying; Sun, Rui; Yue, Feng; Yi, Qilin; Song, Linsheng

    2015-10-01

    Toll-like receptors (TLRs) are among the most studied pattern recognition receptors (PRRs) playing essential roles in innate immune defenses. In the present study, the basic features of CfTLR in mollusk Zhikong scallop Chlamys farreri, including sequence homology, tissue distribution, subcellular localization and ligands spectrum, were investigated to elucidate its pattern recognition. The elements of extracellular domains (ECD) in CfTLR displayed high homology to the corresponding parts of the ECDs in TLRs from Homo sapiens. CfTLR protein was detected in hemocytes, mantle, gills, hepatopancreas, kidney and gonad of the scallops, and it was localized in both the plasma membranes and the lysosomes in HEK293T cells. CfTLR could activate NFκB in response to multiple HsTLR ligands including Pam3CSK4, glucan (GLU), peptidoglycan (PGN), polyriboinosinic:polyribocytidylic acid (poly I:C), Imiquimod and three types of CpG. Additionally, the scallop serum could enhance the induction of NFκB in the CfTLR expressing cells elicited by most PAMPs, including GLU, PGN, Imiquimod and four types of CpG. It could be concluded that this primitive mollusk TLR shared a hybrid function in pattern recognition and could recognize broader ligands than mammalian TLRs, and its mosaic capability of pathogen associated molecular pattern (PAMP) recognition might be based on the basic features of its structure, ligand properties and the assistance of some components in scallop serum.

  4. Optimization design of hybrid Fresnel-based concentrator for generating uniformity irradiance with the broad solar spectrum

    Science.gov (United States)

    Zhuang, Zhenfeng; Yu, Feihong

    2014-08-01

    This paper presents a novel hybrid Fresnel-based concentrator with improved uniformity irradiance distribution on the solar cell without using secondary optical element (SOE) in the concentrator photovoltaic (CPV) system to overcome the Fresnel loss and to increase the solar cell conversion efficiency. The designed hybrid Fresnel-based concentrator is composed of two parts, the inner part and the outer part. The inner part is the conventional Fresnel lens, while the outer part is double total internal reflection (DTIR) lens. According to the simple geometrical relation, the profile of the proposed hybrid Fresnel-based concentrator is calculated as an initial design profile. To obtain good irradiance uniformity on the solar cell, optimal prism displacements are optimized by using a simplex algorithm for collimated incident sunlight based on different prism focus on different position principles. In addition, a Monte-Carlo ray-tracing simulation approach is utilized to verify the optical performance for the hybrid Fresnel-based concentrator. Results indicate that the hybrid Fresnel-based concentrator designed using this method can achieve spatial non-uniformity less than 16.2%, f-number less than 0.59 (focal length to entry aperture diameter ratio), geometrical concentrator ratio 1759.8×, and acceptance angle ±0.23°. Compared to the conventional Fresnel-based lens and the traditional hybrid Fresnel-based lens, the optimized concentrator yields a significant improvement in irradiance uniformity on the solar cell with a wide solar spectrum range. It also has good tolerance to the incident sunlight.

  5. Molecular epidemiology and antimicrobial susceptibility of extended- and broad-spectrum beta-lactamase-producing Klebsiella pneumoniae isolated in Portugal.

    Science.gov (United States)

    Mendonça, Nuno; Ferreira, Eugénia; Louro, Deolinda; Caniça, Manuela

    2009-07-01

    All 187 Klebsiella pneumoniae isolated over six consecutive months of 1999 in 17 Portuguese health institutions were studied: 89% were resistant to ampicillin, 31% to trimethoprim/sulfamethoxazole, 17% to aminoglycosides and 3% to fluoroquinolones; 16% were multidrug-resistant and 14% expressed an extended-spectrum beta-lactamase (ESBL) phenotype confirmed by genotyping. Molecular methods identified: 11 isolates possessing bla(ESBL-SHV) genes (bla(SHV-2A), bla(SHV-5), bla(SHV-12) and bla(SHV-55)), 9 isolates with bla(ESBL-TEM) (bla(TEM-3), bla(TEM-10) and bla(TEM-24)) and 7 isolates with bla(GES-1), encoding ESBL enzymes; and 160 isolates with bla(SHV-1) and bla(SHV-type) encoding non-ESBL enzymes. Overall, 15 new beta-lactamases were detected: SHV-60 to SHV-62, SHV-71 and SHV-73 to SHV-83. The genetic relatedness of 108 isolates was studied by pulsed-field gel electrophoresis (PFGE) analysis. The isolates were diverse and 18 clusters were defined, the largest including 12 isolates of different specimens, 6 of which expressed GES-1 enzymes. Twenty additional strains isolated during a second period (March-November 2006) in three of the participating hospitals contained ESBL-encoding genes, whereas none of the isolates in the same hospitals in 1999 carried such genes: bla(SHV-5), bla(SHV-12), bla(TEM-10), bla(TEM-52), bla(CTX-M-15), bla(CTX-M-32) and bla(CTX-M-61) (first described in the country). In this period, three new enzymes were detected: SHV-106 to SHV-108. We provide evidence that the genotypes of K. pneumoniae isolates is changing towards the emergence of ESBL enzymes. PMID:19272757

  6. "The Math You Need" When Faculty Need It: Enhancing Quantitative Skills at a Broad Spectrum of Higher Education Institutions

    Science.gov (United States)

    Baer, E. M.; Wenner, J. M.

    2014-12-01

    Implementation of "The Math You Need, When You Need It" (TMYN) modules at a wide variety of institutions suggests a broad need for faculty support in helping students develop quantitative skills necessary in introductory geoscience courses. Designed to support students in applying geoscience relevant quantitative skills, TMYN modules are web-based, self-paced and commonly assigned outside of class. They include topics such as calculating slope, rearranging equations, and unit conversions and provide several applications of the mathematical technique to geoscience problems. Each instructor chooses modules that are applicable to the content in his/her individual course and students typically work through the module immediately before the module topic is applied in lab or class. Instructors assigned TMYN modules in their courses at more than 40 diverse institutions, including four-year colleges and universities (4YCs) that vary from non-selective to highly selective and open-door two-year colleges (2YCs). Analysis of module topics assigned, frequency of module use, and institutional characteristics reveals similarities and differences among faculty perception of required quantitative skills and incoming student ability at variably selective institutions. Results indicate that institutional type and selectivity are not correlated with module topic; that is, faculty apply similar quantitative skills in all introductory geoscience courses. For example, nearly every instructor assigned the unit conversions module, whereas very few required the trigonometry module. However, differences in number of assigned modules and faculty expectations are observed between 2YCs and 4YCs (no matter the selectivity). Two-year college faculty typically assign a higher number of modules per course and faculty at 4YCs more often combine portions of multiple modules or cover multiple mathematical concepts in a single assignment. These observations suggest that quantitative skills required

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

    Science.gov (United States)

    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. 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. 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 possible confounding factor, and correlating these scores

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

    Science.gov (United States)

    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. 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. 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 possible confounding factor, and correlating these scores

  9. 网格蛋白介导型内吞作用与广谱抗病毒药%Clathrin-mediated endocytosis and broad-spectrum antivirals

    Institute of Scientific and Technical Information of China (English)

    周丽; 杨晓虹; 徐利保; 肖军海

    2013-01-01

    Viral disease is a serious threat for human health. Alhough plenty of antiviral agents have been used in clinical treatment, many viruses are resistant to them via virus mutation. And novel harmful viruses emerge in endlessly. So research and development of new antiviral drugs, especially the agents that are of broad-spectrum antiviral activity is particularly important. Clathrin-mediated endocytosis is the most common pathway used by viruses and pathogens for entering host cells. The inhibitors of clathrin-me-diated endocytosis may block the entry of viruses and pathogens, thus prevent viral infection. For the inhibitors do not directly act on the virus itself, it is hard to induce virus mutations which produce drug resistance. Clathrin-mediated endocytosis is the potential target of broad-spectrum antiviral agents in recent years. This review focuses on the mechanism of virus entry through clathrin-mediated endocytosis, the recent advances of clathrin-mediated endocytosis inhibitors and their potential applications in broad-spectrum antiviral therapeutics field.%病毒性疾病对人类的健康造成了巨大的威胁,虽然有很多药物用于临床治疗,但由于病毒的易变异性,对现有的抗病毒药物极易产生耐药性,而新发病毒又层出不穷,因此研发新的抗病毒药物尤其是广谱且不易产生耐药的抗病毒药物对于病毒性疾病的治疗就显得尤为重要.网格蛋白介导型内吞是许多病毒和病原体进入宿主细胞的主要途径,抑制此途径可阻断病毒进入宿主细胞,从而抑制病毒感染,由于其功能和机制与病毒自身无关,不易产生耐药,是近年来广谱抗病毒药物的潜在作用靶标.本文结合国内外最新研究报道,简要综述了病毒依赖网格蛋白介导型内吞入胞的机制,网格蛋白介导型内吞抑制剂的研究现状,及其在广谱抗病毒药物研发中的潜在应用前景.

  10. Facile synthesis of Fe3O4 nanoparticles decorated on 3D graphene aerogels as broad-spectrum sorbents for water treatment

    Science.gov (United States)

    Li, Yong; Zhang, Ruofang; Tian, Xike; Yang, Chao; Zhou, Zhaoxin

    2016-04-01

    In order to develop efficient and environment benign sorbents for water purification, the macroscopic multifunctional magnetite-reduced graphene oxides aerogels (M-RGOs) with strong interconnected networks were prepared via a one pot solvothermal method of graphene oxide sheets adsorbing iron ions and in situ simultaneous deposition of Fe3O4 nanoparticles in ethylene glycol or triethylene glycol solvents. Such M-RGOs exhibited excellent sorption capacity to different contaminants, including oils, organic solvents, arsenite ions, as well as dyes. In addition, it was demonstrated that the M-RGOs could be used as column packing materials to manufacture column for water purification by filtration. The method proposed was proved to be versatile to induce synergistic assembly of RGO sheets with other functional metal oxides nanoparticles and as a kind of broad-spectrum sorbents for removing different types of contaminants in water purification, simultaneously.

  11. 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.

  12. Molecular and Biochemical Characterization of a Novel β-N-Acetyl-D-Hexosaminidase with Broad Substrate-Spectrum from the Aisan Corn Borer, Ostrinia Furnacalis

    Directory of Open Access Journals (Sweden)

    Fengyi Liu, Tian Liu, Mingbo Qu, Qing Yang

    2012-01-01

    Full Text Available Insect β-N-acetyl-D-hexosaminidases with broad substrate-spectrum (IBS-Hex are the homologues of human β-N-acetyl-D-hexosaminidase A/B (HsHex A/ B. These enzymes are distributed in most insect species and vary in physiological roles. In this study, the gene encoding an IBS-Hex, OfHEX2, was cloned from the Asian corn borer, Ostrinia furnacalis. Recombinant OfHex2 was expressed in Pichia pastoris and purified to homogeneity. By structure-based sequence alignment, three sequence segments with high diversity among IBS-Hexs were firstly concluded. Furthermore, the residue pair N423-R424/ D452-L453 important for the specificity of human β-N-acetyl-D-hexosaminidase subunits α/β toward charged/ non-charged substrates was not conserved in OfHex2 and other IBS-Hexs. Unlike HsHex A, OfHex2 could not degrade charged substrates such as 4-methylumbelliferyl-6-sulfo-N-acetyl-β-D-glucosaminide, ganglioside GM2 and peptidoglycan. OfHex2 showed a broad substrate-spectrum by hydrolyzing β1-2 linked N-acetyl-D-glucosamines from both α3 and α6 branches of biantennary N-glycan and β1-4 linked GlcNAc from chitooligosaccharides as well as β1-3 linked or β1-4 linked N-acetyl-D-galactosamine from oligosaccharides of glycolipids. Real-time PCR analysis demonstrated that the expression of OfHEX2 was up-regulated in the intermolt stages (both larva and pupa, and mainly occurred in the carcass rather than in the midgut during the feeding stage of fifth (final instar larva. This study reported a novel IBS-Hex with specific biochemical properties, suggesting biodiversity of this class of enzymes.

  13. CaLecRK-S.5, a pepper L-type lectin receptor kinase gene, confers broad-spectrum resistance by activating priming

    Science.gov (United States)

    Woo, Joo Yong; Jeong, Kwang Ju; Kim, Young Jin; Paek, Kyung-Hee

    2016-01-01

    In Arabidopsis, several L-type lectin receptor kinases (LecRKs) have been identified as putative immune receptors. However, to date, there have been few analyses of LecRKs in crop plants. Virus-induced gene silencing of CaLecRK-S.5 verified the role of CaLecRK-S.5 in broad-spectrum resistance. Compared with control plants, CaLecRK-S.5-silenced plants showed reduced hypersensitive response, reactive oxygen species burst, secondary metabolite production, mitogen-activated protein kinase activation, and defense-related gene expression in response to Tobacco mosaic virus pathotype P0 (TMV-P0) infection. Suppression of CaLecRK-S.5 expression significantly enhanced the susceptibility to Pepper mild mottle virus pathotype P1,2,3, Xanthomonas campestris pv. vesicatoria, Phytophthora capsici, as well as TMV-P0. Additionally, β-aminobutyric acid treatment and a systemic acquired resistance assay revealed that CaLecRK-S.5 is involved in priming of plant immunity. Pre-treatment with β-aminobutyric acid before viral infection restored the reduced disease resistance phenotypes shown in CaLecRK-S.5-silenced plants. Systemic acquired resistance was also abolished in CaLecRK-S.5-silenced plants. Finally, RNA sequencing analysis indicated that CaLecRK-S.5 positively regulates plant immunity at the transcriptional level. Altogether, these results suggest that CaLecRK-S.5-mediated broad-spectrum resistance is associated with the regulation of priming. PMID:27647723

  14. Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity.

    Science.gov (United States)

    Acedo, Jeella Z; van Belkum, Marco J; Lohans, Christopher T; Towle, Kaitlyn M; Miskolzie, Mark; Vederas, John C

    2016-02-01

    Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively. These bacteriocins are characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four α-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 Å) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two-component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with broad-spectrum activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action.

  15. Chromosome Microarray.

    Science.gov (United States)

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  16. Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

    Science.gov (United States)

    Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

    2014-11-01

    Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered

  17. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety.

  18. Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

    Science.gov (United States)

    Król, Marek; Ufnal, Marcin; Szulczyk, Bartłomiej; Podsadni, Piotr; Drapała, Adrian; Turło, Jadwiga; Dawidowski, Maciej

    2016-01-01

    It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures. The compound displayed a broad spectrum of activity in the 'classical' models as well as in the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good therapeutic indices between the anticonvulsant activity and the motor impairment. On the contrary, no anticonvulsant effects but severe lethality were observed in the primary anticonvulsant testing of the parent DISO. By performing the whole-cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with an IC50 value in nM range. Moreover, the compound enhanced use-dependent block and decreased excitability in pyramidal neurons in the current-clamp experiments in cortical slices. Importantly, we found that ADD424042 possessed either no, or very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any apparent changes in electrocardiogram (ECG) and arterial blood pressure recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose which was 15 times higher than ED50 for the anticonvulsant effect in the MES model. Taken together, these data suggest that ADD424042 has the potential to become a lead structure for novel broadly acting AEDs with wide margin of cardiac safety. PMID:26441377

  19. Large scale multiplex PCR improves pathogen detection by DNA microarrays

    Directory of Open Access Journals (Sweden)

    Krönke Martin

    2009-01-01

    Full Text Available Abstract Background Medium density DNA microchips that carry a collection of probes for a broad spectrum of pathogens, have the potential to be powerful tools for simultaneous species identification, detection of virulence factors and antimicrobial resistance determinants. However, their widespread use in microbiological diagnostics is limited by the problem of low pathogen numbers in clinical specimens revealing relatively low amounts of pathogen DNA. Results To increase the detection power of a fluorescence-based prototype-microarray designed to identify pathogenic microorganisms involved in sepsis, we propose a large scale multiplex PCR (LSplex PCR for amplification of several dozens of gene-segments of 9 pathogenic species. This protocol employs a large set of primer pairs, potentially able to amplify 800 different gene segments that correspond to the capture probes spotted on the microarray. The LSplex protocol is shown to selectively amplify only the gene segments corresponding to the specific pathogen present in the analyte. Application of LSplex increases the microarray detection of target templates by a factor of 100 to 1000. Conclusion Our data provide a proof of principle for the improvement of detection of pathogen DNA by microarray hybridization by using LSplex PCR.

  20. 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.

  1. Tallow amphopolycarboxyglycinate-stabilized silver nanoparticles: new frontiers in development of plant protection products with a broad spectrum of action against phytopathogens

    Science.gov (United States)

    Krutyakov, Yurii A.; Kudrinskiy, Alexey A.; Zherebin, Pavel M.; Yapryntsev, Alexey D.; Pobedinskaya, Marina A.; Elansky, Sergey N.; Denisov, Albert N.; Mikhaylov, Dmitry M.; Lisichkin, Georgii V.

    2016-07-01

    Sustainable agriculture calls for minimal use of agrochemicals in order to protect the environment. It has caused an increase in the rate of nanoparticles use, in particular silver nanoparticles (AgNPs) due to their safety for mammals, unique biological activity and a broad spectrum of action against fungal and bacterial pathogens. Until now the use of AgNPs dispersions in the agricultural sector has been essentially limited due to many factors decreased their stability (mixing with other pesticides, presence of electrolytes). We present a versatile synthesis of polyampholyte surfactant (tallow amphopolycarboxyglycinate) stabilized AgNPs. We took a close look at unique aggregation behavior (via dynamic light scattering and UV-vis spectroscopy) and biocidal activity of obtained silver colloids. AgNPs are characterized by exclusively high aggregative stability in the presence of coagulating agents NaNO3 and NaSO4 (up to 1 M), during drying/redispergation, and frost/defrost cycles. The dispersion of AgNPs shows high biocidal activity (EC50 is ten times lower than commercial species ones) with respect to Phytophthora infestans and phytopathogenic fungi. This points to the possibility of successful application of silver preparations within agriculture with the goal of partial reduction of the use of toxic and expensive synthetic antibiotics and pesticides.

  2. Albendazole, a broad-spectrum anthelmintic, in the treatment of intestinal nematode and cestode infection: a multicenter study in 480 patients.

    Science.gov (United States)

    Jagota, S C

    1986-01-01

    The anthelmintic activity of and patient tolerance to albendazole, a broad-spectrum anthelmintic, were studied in a multicenter trial involving 480 patients ranging in age from 2 to 60 years. The patients had single or mixed infections caused by pinworms, roundworms, hookworms, whipworms, threadworms, or tapeworms. The stools were examined by the direct method, and ova were counted by means of the Kato-Katz technique. A Graham-Scotch test was also done in patients infected with Enterobius vermicularis. Most patients received a single 400-mg dose of albendazole; adults were given two tablets, and children were given a 2% suspension. All patients with Hymenolepis nana and about half of those with Taenia infections were treated for three successive days. Patients were carefully evaluated before and after treatment to assess the efficacy and safety of the drug. After a single dose of albendazole, the cure rate was 95.3% in ascariasis, 92.2% in ancylostomiasis, 90.5% in trichuriasis, 64.9% in taeniasis, and 100% in enterobiasis. Among patients receiving 400 mg of albendazole for three days, the cure rate was 63.4% in hymenolepiasis and 86.1% in taeniasis. The drug was well tolerated, and no significant side effects were reported. PMID:3516398

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

    Science.gov (United States)

    Lewin, Matthew; Samuel, Stephen; Merkel, Janie; Bickler, Philip

    2016-01-01

    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. PMID:27571102

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

    Science.gov (United States)

    Lewin, Matthew; Samuel, Stephen; Merkel, Janie; Bickler, Philip

    2016-01-01

    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. PMID:27571102

  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. Cloning and Expression of Synthetic Genes Encoding the Broad Antimicrobial Spectrum Bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by Recombinant Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Sara Arbulu

    2015-01-01

    Full Text Available We have evaluated the cloning and functional expression of previously described broad antimicrobial spectrum bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by recombinant Pichia pastoris. Synthetic genes, matching the codon usage of P. pastoris, were designed from the known mature amino acid sequence of these bacteriocins and cloned into the protein expression vector pPICZαA. The recombinant derived plasmids were linearized and transformed into competent P. pastoris X-33, and the presence of integrated plasmids into the transformed cells was confirmed by PCR and sequencing of the inserts. The antimicrobial activity, expected in supernatants of the recombinant P. pastoris producers, was purified using a multistep chromatographic procedure including ammonium sulfate precipitation, desalting by gel filtration, cation exchange-, hydrophobic interaction-, and reverse phase-chromatography (RP-FPLC. However, a measurable antimicrobial activity was only detected after the hydrophobic interaction and RP-FPLC steps of the purified supernatants. MALDI-TOF MS analysis of the antimicrobial fractions eluted from RP-FPLC revealed the existence of peptide fragments of lower and higher molecular mass than expected. MALDI-TOF/TOF MS analysis of selected peptides from eluted RP-FPLC samples with antimicrobial activity indicated the presence of peptide fragments not related to the amino acid sequence of the cloned bacteriocins.

  7. Cloning and Expression of Synthetic Genes Encoding the Broad Antimicrobial Spectrum Bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by Recombinant Pichia pastoris

    Science.gov (United States)

    Jiménez, Juan J.; Gútiez, Loreto; Cintas, Luis M.; Herranz, Carmen; Hernández, Pablo E.

    2015-01-01

    We have evaluated the cloning and functional expression of previously described broad antimicrobial spectrum bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by recombinant Pichia pastoris. Synthetic genes, matching the codon usage of P. pastoris, were designed from the known mature amino acid sequence of these bacteriocins and cloned into the protein expression vector pPICZαA. The recombinant derived plasmids were linearized and transformed into competent P. pastoris X-33, and the presence of integrated plasmids into the transformed cells was confirmed by PCR and sequencing of the inserts. The antimicrobial activity, expected in supernatants of the recombinant P. pastoris producers, was purified using a multistep chromatographic procedure including ammonium sulfate precipitation, desalting by gel filtration, cation exchange-, hydrophobic interaction-, and reverse phase-chromatography (RP-FPLC). However, a measurable antimicrobial activity was only detected after the hydrophobic interaction and RP-FPLC steps of the purified supernatants. MALDI-TOF MS analysis of the antimicrobial fractions eluted from RP-FPLC revealed the existence of peptide fragments of lower and higher molecular mass than expected. MALDI-TOF/TOF MS analysis of selected peptides from eluted RP-FPLC samples with antimicrobial activity indicated the presence of peptide fragments not related to the amino acid sequence of the cloned bacteriocins. PMID:25821820

  8. Tallow amphopolycarboxyglycinate-stabilized silver nanoparticles: new frontiers in development of plant protection products with a broad spectrum of action against phytopathogens

    Science.gov (United States)

    Krutyakov, Yurii A.; Kudrinskiy, Alexey A.; Zherebin, Pavel M.; Yapryntsev, Alexey D.; Pobedinskaya, Marina A.; Elansky, Sergey N.; Denisov, Albert N.; Mikhaylov, Dmitry M.; Lisichkin, Georgii V.

    2016-07-01

    Sustainable agriculture calls for minimal use of agrochemicals in order to protect the environment. It has caused an increase in the rate of nanoparticles use, in particular silver nanoparticles (AgNPs) due to their safety for mammals, unique biological activity and a broad spectrum of action against fungal and bacterial pathogens. Until now the use of AgNPs dispersions in the agricultural sector has been essentially limited due to many factors decreased their stability (mixing with other pesticides, presence of electrolytes). We present a versatile synthesis of polyampholyte surfactant (tallow amphopolycarboxyglycinate) stabilized AgNPs. We took a close look at unique aggregation behavior (via dynamic light scattering and UV–vis spectroscopy) and biocidal activity of obtained silver colloids. AgNPs are characterized by exclusively high aggregative stability in the presence of coagulating agents NaNO3 and NaSO4 (up to 1 M), during drying/redispergation, and frost/defrost cycles. The dispersion of AgNPs shows high biocidal activity (EC50 is ten times lower than commercial species ones) with respect to Phytophthora infestans and phytopathogenic fungi. This points to the possibility of successful application of silver preparations within agriculture with the goal of partial reduction of the use of toxic and expensive synthetic antibiotics and pesticides.

  9. Antimicrobial interactions (synergy) of teicoplanin with two broad-spectrum drugs (cefotaxime, ofloxacin) tested against gram-positive isolates from Germany and the United States.

    Science.gov (United States)

    Jones, R N; Marshall, S A; Grimm, H

    1997-10-01

    Teicoplanin, a glycopeptide, has been widely used in some nations alone and in empiric therapy combinations to address infections caused by Gram-positive cocci. However, glycopeptide resistance and the increasing incidence of oxacillin-resistant staphylococci have compromised contemporary chemotherapy. In this study, teicoplanin was tested in combinations with ampicillin, cefotaxime with and without desacetylcefotaxime, and ofloxacin against 151 Gram-positive cocci to assess the potential for enhanced action. The strains included recent isolates from the United States and Germany having well-characterized resistance mechanisms (oxacillin-resistant staphylococci, vancomycin-resistant enterococci), each tested by NCCLS methods, checkerboard synergy tests, and kill-curves. Teicoplanin alone was active (MIC90s, 0.25-2 micrograms/mL) against all species except vanA enterococci. Drug interactions of teicoplanin with beta-lactams revealed synergy and partial synergy versus oxacillin-resistant Staphylococcus spp. (67-100%) and vancomycin-resistant enterococci (70-100%), many at clinically achievable drug concentrations. However, confirming kill-curve experiments showed static action and no significant bactericidal effect. Combinations of ofloxacin with teicoplanin or cefotaxime plus desacetylcefotaxime showed a dominant additive and indifferent interaction. Teicoplanin continues to be a viable alternative to vancomycin, especially in combination therapy with selected broad-spectrum cephalosporins or fluoroquinolones. Many emerging pathogens that test resistant to individual drugs appear to be inhibited by tested combinations, extending their potential clinical utility.

  10. Characterization and Genetic Analysis of a Novel Rice Spotted-leaf Mutant HM47 with Broad-spectrum Resistance to Xanthomonas oryzae pv.oryzae(F)

    Institute of Scientific and Technical Information of China (English)

    Bao-Hua Feng; Yang Yang; Yong-Feng Shi; Hai-Chao Shen; Hui-Mei Wang; Qi-Na Huang; Xia Xu

    2013-01-01

    A stable inherited rice spotted-leaf mutant HM47 derived from an EMS-induced IR64 mutant bank was identified.The mutant expressed hypersensitive response (HR)-like symptoms throughout its whole life from the first leaf to the flag leaf,without pathogen invasion.Initiation of the lesions was induced by light under natural summer field conditions.Expression of pathogenesis-related genes including PAL,PO-C1,POX22.3 and PBZ1 was enhanced significantly in association with cell death and accumulation of H2O2 at and around the site of lesions in the mutant in contrast to that in the wild-type (WT).Disease reaction to Xanthomonas oryzae pv.oryzae from the Philippines and China showed that HM47 is a broad-spectrum disease-resistant mutant with enhanced resistance to multiple races of bacterial blight pathogens tested.An F2 progeny test showed that bacterial blight resistance to race HB-17 was cosegregated with the expression of lesions.Genetic analysis indicated that the spotted-leaf trait was controlled by a single recessive gene,tentatively named splHM47,flanked by two insertion/deletion markers in a region of approximately 74 kb on the long arm of chromosome 4.Ten open reading frames are predicted,and all of them are expressed proteins.Isolation and validation of the putative genes are currently underway.

  11. Natural herbicide resistance (HR) to broad-spectrum herbicide, glyphosate among traditional and inbred-cultivated rice (Oryza sativa L.) varieties in Sri Lanka.

    Science.gov (United States)

    Weerakoon, S R; Somaratne, S; Wijeratne, R G D; Ekanyaka, E M S I

    2013-08-15

    Weeds along with insect pests and plant diseases are sources of biotic stress in crop systems. Weeds are responsible for serious problems in rice worldwide affecting growth and causing a considerable reduction in quality and quantity in yield. High concentrations of pre-emergent-broad-spectrum systemic herbicide, Glyphosate is prevalently applied to control rice weeds which intern causes severe damages to cultivated rice varieties, susceptible to Glyphosate. However, there may be rice varieties with natural Herbicide Resistance (HR) which are so far, has not been evaluated. In this study Six traditional and eighteen developed-cultivated rice varieties (Bg, Bw, At and Ld series developed by Rice Research Development Institute, Sri Lanka) were used to screen their natural HR. RCBD with five replicates and three blocks in each treatment-combination was used as the experimental design. As observations, time taken-to seed germination, time taken to flowering; plant height and number of leaves at 12-weeks after sawing, leaf-length, breadth, panicle-length, number of seeds/panicle of resistant plants and controls were recorded. Plants with > or = 40% resistance were considered as resistant to Glyphosate. Ten inbred-cultivated rice varieties (Bg250, Bg94-1, Bg304, Bg359, Bg406, Bg379-2, Bg366, Bg300, Bw364, At362) and three traditional rice varieties ("Kalu Heenati", "Sudu Heenati", "Pachchaperumal") were naturally resistant to 0.25 g L(-1) Glyphosate concentration and when increased the concentration (0.5 g L(-1)) resistance was reduced. This study showed the usefulness of modern statistical method, classification and regression tree analysis (CART) in exploring and visualizing the patterns reflected by a large number of rice varieties (larger experimental database) on herbicide resistance in future.

  12. 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

    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.

  13. Broad-spectrum drug screening of meconium by liquid chromatography with tandem mass spectrometry and time-of-flight mass spectrometry.

    Science.gov (United States)

    Ristimaa, Johanna; Gergov, Merja; Pelander, Anna; Halmesmäki, Erja; Ojanperä, Ilkka

    2010-09-01

    Analysis of the major drugs of abuse in meconium has been established in clinical practice for detecting fetal exposure to illicit drugs, particularly for the ready availability of the sample and ease of collection from diapers, compared with neonatal hair and urine. Very little is known about the occurrence and detection possibilities of therapeutic and licit drugs in meconium. Meconium specimens (n = 209) were collected in delivery hospitals, from infants of mothers who were suspected to be drug abusers. A targeted analysis method by liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) was developed for abused drugs: amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, morphine, codeine, 6-monoacetylmorphine, oxycodone, methadone, tramadol, buprenorphine, and norbuprenorphine. A separate LC-MS/MS method was developed for 11-nor-∆(9)-tetrahydrocannabinol-9-carboxylic acid. A screening method based on LC coupled to time-of-flight MS was applied to a broad spectrum of drugs. As a result, a total of 77 different compounds were found. The main drug findings in meconium were as follows: local anesthetics 82.5% (n = 172), nicotine or its metabolites 61.5% (n = 129), opioids 48.5% (n = 101), stimulants 21.0% (n = 44), hypnotics and sedatives 19.0% (n = 40), antidepressants 18.0% (n = 38), antipsychotics 5.5% (n = 11), and cannabis 3.0% (n = 5). By revealing drugs and metabolites beyond the ordinary scope, the present procedure helps the pediatrician in cases where maternal denial is strong but the infant seems to suffer from typical drug-withdrawal symptoms. Intrapartum drug administration cannot be differentiated from gestational drug use by meconium analysis, which affects the interpretation of oxycodone, tramadol, fentanyl, pethidine, and ephedrine findings. PMID:20617307

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

    Science.gov (United States)

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

    2016-03-01

    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. PMID:26850850

  15. WRR4, a broad-spectrum TIR-NB-LRR gene from Arabidopsis thaliana that confers white rust resistance in transgenic oilseed Brassica crops.

    Science.gov (United States)

    Borhan, Mohammad Hossein; Holub, Eric B; Kindrachuk, Colin; Omidi, Mansour; Bozorgmanesh-Frad, Ghazaleh; Rimmer, S Roger

    2010-03-01

    White blister rust caused by Albugo candida (Pers.) Kuntze is a common and often devastating disease of oilseed and vegetable brassica crops worldwide. Physiological races of the parasite have been described, including races 2, 7 and 9 from Brassica juncea, B. rapa and B. oleracea, respectively, and race 4 from Capsella bursa-pastoris (the type host). A gene named WRR4 has been characterized recently from polygenic resistance in the wild brassica relative Arabidopsis thaliana (accession Columbia) that confers broad-spectrum white rust resistance (WRR) to all four of the above Al. candida races. This gene encodes a TIR-NB-LRR (Toll-like/interleukin-1 receptor-nucleotide binding-leucine-rich repeat) protein which, as with other known functional members in this subclass of intracellular receptor-like proteins, requires the expression of the lipase-like defence regulator, enhanced disease susceptibility 1 (EDS1). Thus, we used RNA interference-mediated suppression of EDS1 in a white rust-resistant breeding line of B. napus (transformed with a construct designed from the A. thaliana EDS1 gene) to determine whether defence signalling via EDS1 is functionally intact in this oilseed brassica. The eds1-suppressed lines were fully susceptible following inoculation with either race 2 or 7 isolates of Al. candida. We then transformed white rust-susceptible cultivars of B. juncea (susceptible to race 2) and B. napus (susceptible to race 7) with the WRR4 gene from A. thaliana. The WRR4-transformed lines were resistant to the corresponding Al. candida race for each host species. The combined data indicate that WRR4 could potentially provide a novel source of white rust resistance in oilseed and vegetable brassica crops.

  16. Development of a monoclonal antibody specific to envelope domain III with broad-spectrum detection of all four dengue virus serotypes.

    Science.gov (United States)

    Kim, Sae-Hae; Kim, Yu Na; Truong, Thang Thua; Thu Thuy, Nguyen Thi; Mai, Le Quynh; Jang, Yong-Suk

    2016-05-13

    Dengue virus (DENV) is a mosquito-borne pathogen that annually infects more than 390 million people in 100 different countries. Symptoms of the viral infection include a relatively weak dengue fever to severe dengue hemorrhagic fever/dengue shock syndrome, which are mortal infectious diseases. As of yet, there is no commercially available vaccine or therapeutic for DENV. Currently, passive immunotherapy using DENV-specific antibody (Ab) is a considered strategy to treat DENV infection. Here, we developed a monoclonal Ab (mAb), EDIIImAb-61, specific to the DENV domain III of the envelope glycoprotein (EDIII) with broad-spectrum detection ability to all four DENV serotypes (DENV-1∼4) to use as a therapeutic Ab. Although EDIII contains non-immunodominant epitopes compared to domains I and II, domain III plays a critical role in host receptor binding. EDIIImAb-61 exhibited cross-reactive binding affinity to all four DENV serotypes that had been isolated from infected humans. To further characterize EDIIImAb-61 and prepare genes for large-scale production using a heterologous expression system, the sequence of the complementarity determining regions was analyzed after cloning the full-length cDNA genes encoding the heavy and light chain of the mAb. Finally, we produced Ab from CHO-K1 cells transfected with the cloned EDIIImAb-61 heavy and light chain genes and confirmed the binding ability of the Ab. Collectively, we conclude that EDIIImAb-61 itself and the recombinant Ab produced using the cloned heavy and light chain gene of EDIIImAb-61 is a candidate for passive immunotherapy against DENV infection. PMID:27059141

  17. Natural herbicide resistance (HR) to broad-spectrum herbicide, glyphosate among traditional and inbred-cultivated rice (Oryza sativa L.) varieties in Sri Lanka.

    Science.gov (United States)

    Weerakoon, S R; Somaratne, S; Wijeratne, R G D; Ekanyaka, E M S I

    2013-08-15

    Weeds along with insect pests and plant diseases are sources of biotic stress in crop systems. Weeds are responsible for serious problems in rice worldwide affecting growth and causing a considerable reduction in quality and quantity in yield. High concentrations of pre-emergent-broad-spectrum systemic herbicide, Glyphosate is prevalently applied to control rice weeds which intern causes severe damages to cultivated rice varieties, susceptible to Glyphosate. However, there may be rice varieties with natural Herbicide Resistance (HR) which are so far, has not been evaluated. In this study Six traditional and eighteen developed-cultivated rice varieties (Bg, Bw, At and Ld series developed by Rice Research Development Institute, Sri Lanka) were used to screen their natural HR. RCBD with five replicates and three blocks in each treatment-combination was used as the experimental design. As observations, time taken-to seed germination, time taken to flowering; plant height and number of leaves at 12-weeks after sawing, leaf-length, breadth, panicle-length, number of seeds/panicle of resistant plants and controls were recorded. Plants with > or = 40% resistance were considered as resistant to Glyphosate. Ten inbred-cultivated rice varieties (Bg250, Bg94-1, Bg304, Bg359, Bg406, Bg379-2, Bg366, Bg300, Bw364, At362) and three traditional rice varieties ("Kalu Heenati", "Sudu Heenati", "Pachchaperumal") were naturally resistant to 0.25 g L(-1) Glyphosate concentration and when increased the concentration (0.5 g L(-1)) resistance was reduced. This study showed the usefulness of modern statistical method, classification and regression tree analysis (CART) in exploring and visualizing the patterns reflected by a large number of rice varieties (larger experimental database) on herbicide resistance in future. PMID:24498832

  18. 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.

  19. Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.

    Science.gov (United States)

    To, Kelvin K W; Mok, Ka-Yi; Chan, Andy S F; Cheung, Nam N; Wang, Pui; Lui, Yin-Ming; Chan, Jasper F W; Chen, Honglin; Chan, Kwok-Hung; Kao, Richard Y T; Yuen, Kwok-Yung

    2016-08-01

    Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo. PMID:27259985

  20. Inhibition of hemorrhagic and edematogenic activities of snake venoms by a broad-spectrum protease inhibitor, murinoglobulin; the effect on venoms from five different genera in Viperidae family.

    Science.gov (United States)

    Ribeiro Filho, Wilker; Sugiki, Masahiko; Yoshida, Etsuo; Maruyama, Masugi

    2003-08-01

    In order to obtain basic data on the effect of broad-spectrum protease inhibitor against local symptoms of Viperidae snake envenomation, inhibitory capacity of rat murinoglobulin on local hemorrhagic and edematogenic activities of venoms from Crotalus atrox, Bothrops jararaca, Lachesis muta muta, Trimeresurus flavoviridis and Echis carinatus sochureki were examined. Murinoglobulin, pre-incubated with the crude venoms at 37 degrees C for 15 min, inhibited hemorrhagic activity of all five venoms to various extents. The activity of C. atrox was almost completely inhibited at the murinoglobulin/venom ratio (w/w) of 20. The activity of B. jararaca, Lachesis muta muta and T. flavoviridis venoms was considerably inhibited at the ratio of 20 (77.2, 80.0 and 86.2% inhibition, respectively), however some of the activity still remained even at the ratio of 40 (84.2, 79.8 and 86.2% inhibition, respectively). Among the five venoms, E. c. sochureki venom is quite resistant to murinoglobulin treatment and statistically significant inhibition was only found at the ratio of 40 (64.1% inhibition). Fibrinolytic and gelatinase activities were more susceptible to murinoglobulin inhibition. The treatment at the ratios of 10 and 20 almost completely inhibited respectively the fibrinolytic and the gelatinase activities of all the venoms. Murinoglobulin treatment also significantly inhibited the edematogenic activity of L. muta muta, T. flavoviridis and Echis carinatus sochureki. The treatment of murinoglobulin at the ratio of 40 considerably suppressed the swelling up to 60 min after subcutaneous injection of L. muta muta and E. c. sochureki venoms, and up to 30 min after T. flavoviridis venom injection. Murinoglobulin is a potent inhibitor against local effects of multiple snake venoms in Viperidae family. PMID:12906888

  1. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models.

    Science.gov (United States)

    Zhao, Genshi; Li, Wei-Ying; Chen, Daohong; Henry, James R; Li, Hong-Yu; Chen, Zhaogen; Zia-Ebrahimi, Mohammad; Bloem, Laura; Zhai, Yan; Huss, Karen; Peng, Sheng-Bin; McCann, Denis J

    2011-11-01

    The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.

  2. DNA Microarrays

    Science.gov (United States)

    Nguyen, C.; Gidrol, X.

    Genomics has revolutionised biological and biomedical research. This revolution was predictable on the basis of its two driving forces: the ever increasing availability of genome sequences and the development of new technology able to exploit them. Up until now, technical limitations meant that molecular biology could only analyse one or two parameters per experiment, providing relatively little information compared with the great complexity of the systems under investigation. This gene by gene approach is inadequate to understand biological systems containing several thousand genes. It is essential to have an overall view of the DNA, RNA, and relevant proteins. A simple inventory of the genome is not sufficient to understand the functions of the genes, or indeed the way that cells and organisms work. For this purpose, functional studies based on whole genomes are needed. Among these new large-scale methods of molecular analysis, DNA microarrays provide a way of studying the genome and the transcriptome. The idea of integrating a large amount of data derived from a support with very small area has led biologists to call these chips, borrowing the term from the microelectronics industry. At the beginning of the 1990s, the development of DNA chips on nylon membranes [1, 2], then on glass [3] and silicon [4] supports, made it possible for the first time to carry out simultaneous measurements of the equilibrium concentration of all the messenger RNA (mRNA) or transcribed RNA in a cell. These microarrays offer a wide range of applications, in both fundamental and clinical research, providing a method for genome-wide characterisation of changes occurring within a cell or tissue, as for example in polymorphism studies, detection of mutations, and quantitative assays of gene copies. With regard to the transcriptome, it provides a way of characterising differentially expressed genes, profiling given biological states, and identifying regulatory channels.

  3. Environmental fate of herbicides trifluralin, metazachlor, metamitron and sulcotrione compared with that of glyphosate, a substitute broad spectrum herbicide for different glyphosate-resistant crops.

    Science.gov (United States)

    Mamy, Laure; Barriuso, Enrique; Gabrielle, Benoît

    2005-09-01

    The introduction of crops resistant to the broad spectrum herbicide glyphosate, N-(phosphonomethyl)glycine, may constitute an answer to increased contamination of the environment by herbicides, since it should reduce the total amount of herbicide needed and the number of active ingredients. However, there are few published data comparing the fate of glyphosate in the environment, particularly in soil, with that of substitute herbicides. The objective of this study is to compare the fate of glyphosate in three soils with that of four herbicides frequently used on crops that might be glyphosate resistant: trifluralin, alpha,alpha,alpha-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine, and metazachlor, 2-chloro-N-(pyrazol-1-ylmethyl)acet-2',6'-xylidide for oilseed rape, metamitron, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one for sugarbeet and sulcotrione, 2-(2-chloro-4-mesylbenzoyl)cyclohexane-1,3-dione for maize. The distribution of herbicides between the volatilized, mineralized, extractable and non-extractable fractions was studied, along with the formation of their metabolites in laboratory experiments using 14C-labelled herbicides, over a period of 140 days. The main dissipation pathways were mineralization for glyphosate and sulcotrione, volatilization for trifluralin and non-extractable residues formation for metazachlor and metamitron. The five herbicides had low persistence. Glyphosate had the shortest half-life, which varied with soil type, whereas trifluralin had the longest. The half-lives of metazachlor and sulcotrione were comparable, whereas that of metamitron was highly variable. Glyphosate, metazachlor and sulcotrione were degraded into persistent metabolites. Low amounts of trifluralin and metamitron metabolites were observed. At 140 days after herbicide applications, the amounts of glyphosate and its metabolite residues in soils were the lowest in two soils, but not in the third soil, a loamy sand with low pH. The environmental advantage

  4. The landscape of host transcriptional response programs commonly perturbed by bacterial pathogens: towards host-oriented broad-spectrum drug targets.

    Directory of Open Access Journals (Sweden)

    Yared H Kidane

    Full Text Available BACKGROUND: The emergence of drug-resistant pathogen strains and new infectious agents pose major challenges to public health. A promising approach to combat these problems is to target the host's genes or proteins, especially to discover targets that are effective against multiple pathogens, i.e., host-oriented broad-spectrum (HOBS drug targets. An important first step in the discovery of such drug targets is the identification of host responses that are commonly perturbed by multiple pathogens. RESULTS: In this paper, we present a methodology to identify common host responses elicited by multiple pathogens. First, we identified host responses perturbed by each pathogen using a gene set enrichment analysis of publicly available genome-wide transcriptional datasets. Then, we used biclustering to identify groups of host pathways and biological processes that were perturbed only by a subset of the analyzed pathogens. Finally, we tested the enrichment of each bicluster in human genes that are known drug targets, on the basis of which we elicited putative HOBS targets for specific groups of bacterial pathogens. We identified 84 up-regulated and three down-regulated statistically significant biclusters. Each bicluster contained a group of pathogens that commonly dysregulated a group of biological processes. We validated our approach by checking whether these biclusters correspond to known hallmarks of bacterial infection. Indeed, these biclusters contained biological process such as inflammation, activation of dendritic cells, pro- and anti- apoptotic responses and other innate immune responses. Next, we identified biclusters containing pathogens that infected the same tissue. After a literature-based analysis of the drug targets contained in these biclusters, we suggested new uses of the drugs Anakinra, Etanercept, and Infliximab for gastrointestinal pathogens Yersinia enterocolitica, Helicobacter pylori kx2 strain, and enterohemorrhagic Escherichia

  5. 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.

  6. Aptamer Microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Angel-Syrett, Heather; Collett, Jim; Ellington, Andrew D.

    2009-01-02

    In vitro selection can yield specific, high-affinity aptamers. We and others have devised methods for the automated selection of aptamers, and have begun to use these reagents for the construction of arrays. Arrayed aptamers have proven to be almost as sensitive as their solution phase counterparts, and when ganged together can provide both specific and general diagnostic signals for proteins and other analytes. We describe here technical details regarding the production and processing of aptamer microarrays, including blocking, washing, drying, and scanning. We will also discuss the challenges involved in developing standardized and reproducible methods for binding and quantitating protein targets. While signals from fluorescent analytes or sandwiches are typically captured, it has proven possible for immobilized aptamers to be uniquely coupled to amplification methods not available to protein reagents, thus allowing for protein-binding signals to be greatly amplified. Into the future, many of the biosensor methods described in this book can potentially be adapted to array formats, thus further expanding the utility of and applications for aptamer arrays.

  7. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    Science.gov (United States)

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    displayed anticonvulsant activity in the rat pilocarpine model of SE. Thirty minutes after the induction of SE, the calculated rat-ED50 for SPD against convulsive SE in this model was 84mg/kg. SPD was not neuroprotective in the organotypic hippocampal slice preparation; however, it did display hippocampal neuroprotection in both SE models and cognitive sparing in the MWM which was associated with its antiseizure effect against pilocarpine-induced SE. When administered 20 and 40min after SE onset, SPD (100-174mg/kg) produced long-lasting efficacy (e.g., 4-8hr) against soman-induced convulsive and electrographic SE in both rats and guinea pigs. SPD-ED50 values in guinea pigs were 67mg/kg and 92mg/kg at when administered at SE onset or 40min after SE onset, respectively. Assuming linear PK, the PK-PD results (rats) suggests that effective SPD plasma levels ranged between 8-40mg/L (20 min post onset of soman-induced seizures) and 12-50mg/L (40 min post onset of soman-induced seizures). The time to peak (tmax) pharmacodynamic effect (PD-tmax) occurred after the PK-tmax thereby suggesting that SPD undergoes slow distribution to extra-plasmatic sites likely responsible for SPD’s antiseizure activity. Significance The results demonstrate that SPD is a broad-spectrum antiseizure compound that blocks SE induced by pilocarpine and soman and affords in vivo neuroprotection that is associated with cognitive sparing. Its activity against SE is superior to diazepam in terms of rapid onset, potency and its effect on animal mortality and functional improvement. PMID:22150444

  8. 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...

  9. A strong and broad Fe line in the XMM-Newton spectrum of the new X-ray transient and black hole candidate XTEJ1652-453

    NARCIS (Netherlands)

    Hiemstra, Beike; Mendez, Mariano; Done, Chris; Diaz Trigo, Maria; Altamirano, Diego; Casella, Piergiorgio

    2011-01-01

    We observed the new X-ray transient and black hole candidate XTEJ1652-453 simultaneously with XMM-Newton and the Rossi X-ray Timing Explorer (RXTE). The observation was done during the decay of the 2009 outburst, when XTEJ1652-453 was in the hard-intermediate state. The spectrum shows a strong and b

  10. 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…

  11. Microarrays, Integrated Analytical Systems

    Science.gov (United States)

    Combinatorial chemistry is used to find materials that form sensor microarrays. This book discusses the fundamentals, and then proceeds to the many applications of microarrays, from measuring gene expression (DNA microarrays) to protein-protein interactions, peptide chemistry, carbodhydrate chemistry, electrochemical detection, and microfluidics.

  12. Essential Oils and Non-volatile Compounds Derived from Chamaecyparis obtusa: Broad Spectrum Antimicrobial Activity against Infectious Bacteria and MDR(multidrug resistant) Strains.

    Science.gov (United States)

    Bae, Min-Suk; Park, Dae-Hun; Choi, Chul-Yung; Kim, Gye-Yeop; Yoo, Jin-Cheol; Cho, Seung-Sik

    2016-05-01

    The aim of this study was to evaluate the antibacterial activity of essential oil from Chamaecyparis obtusa against general infectious microbes and drug resistant strains of clinical origin. The results indicate that both essential oil and non-volatile residue have broad inhibitory activity against test strains. Essential oil and non-volatile residues showed antimicrobial activity not only against general infectious bacteria, but also against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. PMID:27319153

  13. Microarray analysis in pulmonary hypertension.

    Science.gov (United States)

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  14. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants: A Propensity Score-matched Cohort Study.

    Science.gov (United States)

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-10-01

    Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants.A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases.A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171-11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365-27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to

  15. 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

    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......-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...

  16. Steps toward determination of the size and structure of the broad-line region in active nuclei. 7: Variability of the optical spectrum of NGC 5548 over years

    Science.gov (United States)

    Peterson, B. M.; Berlind, P.; Bertram, R.; Bochkarev, N. G.; Bond, D.; Brotherton, M. S.; Busler, J. R.; Chuvaev, K. K.; Cohen, R. D.; Dietrich, M.

    1994-01-01

    We report on the results of a continuation of a large monitoring program of optical spectroscopy of the Seyfert 1 galaxy NGC 5548. The new observations presented here were obtained between 1990 December and 1992 October, and extend the existing database to nearly 1400 days, dating back to 1988 December. The continuum variations are generally smooth and well-resolved, except during the third year of this 4 year project, when the variations were apparently more rapid and of lower amplitude than observed at other times. The broad H(beta) emission line is found to vary in response to the continuum variations with a lag of about 18 days, but with some changes from year to year. The H(beta) transfer functions for each of the 4 yr and for the entire 4 yr database are derived by using a maximum entropy method.

  17. 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.

  18. DNA Microarray Technique

    Directory of Open Access Journals (Sweden)

    Thakare SP

    2012-11-01

    Full Text Available DNA Microarray is the emerging technique in Biotechnology. The many varieties of DNA microarray or DNA chip devices and systems are described along with their methods for fabrication and their use. It also includes screening and diagnostic applications. The DNA microarray hybridization applications include the important areas of gene expression analysis and genotyping for point mutations, single nucleotide polymorphisms (SNPs, and short tandem repeats (STRs. In addition to the many molecular biological and genomic research uses, this review covers applications of microarray devices and systems for pharmacogenomic research and drug discovery, infectious and genetic disease and cancer diagnostics, and forensic and genetic identification purposes.

  19. The optical transmission spectrum of the hot Jupiter HAT-P-32b: clouds explain the absence of broad spectral features?

    CERN Document Server

    Gibson, N P; Barstow, J K; Evans, T M; Fletcher, L N; Irwin, P G J

    2013-01-01

    We report Gemini-North GMOS observations of the inflated hot Jupiter HAT-P-32b during two primary transits. We simultaneously observed two comparison stars and used differential spectro-photometry to produce multi-wavelength light curves. 'White' light curves and 29 'spectral' light curves were extracted for each transit and analysed to refine the system parameters and produce transmission spectra from 520-930nm in ~14nm bins. The light curves contain time-varying white noise as well as time-correlated noise, and we used a Gaussian process model to fit this complex noise model. Common mode corrections derived from the white light curve fits were applied to the spectral light curves which significantly improved our precision, reaching typical uncertainties in the transit depth of ~2x10^-4, corresponding to about half a pressure scale height. The low resolution transmission spectra are consistent with a featureless model, and we can confidently rule out broad features larger than about one scale height. The abs...

  20. Modelling the variable broad-band optical/UV/X-ray spectrum of PG1211+143: Implications for the ionized outflow

    CERN Document Server

    Papadakis, I E; Panagiotou, C

    2016-01-01

    We present the results from a detailed analysis of the 2007 Swift monitoring campaign of the quasar PG1211+143. We constructed broad-band, optical/UV/X-ray spectral energy distributions over three X-ray flux intervals. We fitted them with a model which accounts for the disc and the X-ray coronal emission and the warm absorber (well established in this source). The three flux spectra are well fitted by the model we considered. The disc inner temperature remains constant at ~2 eV, while X-rays are variable both in spectral slope and normalization. The absorber covers almost 90% of the central source. It is outflowing with a velocity less than 2.3*10^4 km/s (3sigma upper limit), and has a column density of ~10^23.2. Its ionization parameter varies by a factor of 1.6, and it is in photo-ionizing equilibrium with the ionizing flux. It is located at a distance of less than 0.35 pc from the central source and its relative thickness, DR/R is less than 0.1. The absorber' s ionization parameter variations can explain t...

  1. The quest for a universal density functional: The accuracy of density functionals across a broad spectrum of databases in chemistry and physics

    CERN Document Server

    Peverati, Roberto

    2012-01-01

    Kohn-Sham density functional theory is in principle an exact formulation of quantum mechanical electronic structure theory, but in practice we have to rely on approximate exchange-correlation (xc) functionals. The objective of our work has been to design an xc functional with broad accuracy across as wide an expanse of chemistry and physics as possible, leading-as a long-range goal-to a functional with good accuracy for all problems, i.e., a universal functional. To guide our path toward that goal and to measure our progress, we have developed-building on earlier work in our group-a set of databases of reference data for a variety of energetic and structural properties in chemistry and physics. These databases include energies of molecular processes such as atomization, complexation, proton addition, and ionization; they also include molecular geometries and solid-state lattice constants, chemical reaction barrier heights, and cohesive energies and band gaps of solids. For the present paper we gather many of ...

  2. TiO and VO broad band absorption features in the optical spectrum of the atmosphere of the hot-Jupiter HD209458b

    CERN Document Server

    Desert, J -M; Etangs, A Lecavelier des; Sing, D; Ehrenreich, D; Hébrard, G; Ferlet, R

    2008-01-01

    The presence of titanium oxide (TiO) and vanadium oxide (VO) gas phase species is searched for in the atmosphere of the hot Jupiter HD209458b. We compared a model for the planets transmitted spectrum to multi-wavelength eclipse-depth measurements (from 3000 to 10000 Angstrom), obtained by Sing et al. (2008a) using archived HST-STIS time series spectra. We make use of these observations to search for spectral signatures from extra absorbers in the planet atmosphere between 6000 and 8000 Angstrom. Along with sodium depletion and Rayleigh scattering recently published for this exoplanet atmosphere, an extra absorber of uncertain origin, redward of the sodium lines, resides in the atmosphere of the planet. Furthermore, this planet has a stratosphere experiencing a thermal inversion caused by the capture of optical stellar flux by absorbers that resides at altitude. Recent models have predicted that the presence of TiO and VO in the atmosphere of HD209458b may be responsible for this temperature inversion. Althoug...

  3. 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.

  4. A sequential statistical approach towards an optimized production of a broad spectrum bacteriocin substance from a soil bacterium Bacillus sp. YAS 1 strain.

    Science.gov (United States)

    Embaby, Amira M; Heshmat, Yasmin; Hussein, Ahmed; Marey, Heba S

    2014-01-01

    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.

  5. Broad spectrum and mode of action of an antibiotic produced by Scytonema sp. TISTR 8208 in a seaweed-type bioreactor.

    Science.gov (United States)

    Chetsumon, A; Umeda, F; Maeda, I; Yagi, K; Mizoguchi, T; Miura, Y

    1998-01-01

    A photobioreactor was constructed using anchored polyurethane foam strips (1 x 1 x 40 cm) fixed onto a stainless-steel ring to prevent flotation, as a biomass support material (BSM). This type of reactor was named a seaweed-type bioreactor. A filamentous cyanobacterium, Scytonema sp. TISTR 8208, which produces a novel cyclic dodecapeptide antibiotic, was immobilized in seaweed-type photobioreactor and cultivated with air containing 5% CO2 sparged at a gas flow rate of 250 mL/min under illumination at a light intensity of 200 mmol photon m-2 s-1. The antibiotic produced in the seaweed-type photobioreactor was purified by HPLC and examined regarding its spectrum and mode of action. The antibiotic effectively inhibited the growth of Gram-positive bacteria, pathogenic yeasts, and filamentous fungi, but it had only a weak effect on Gram-negative bacteria. Scanning electron micrograph analysis showed that the most characteristic change was swelling of the cells after exposure to the antibiotic. The antibiotic seems to alter the conformation of the microbial cell membrane, thereby changing its permeability, leading to osmotic shock. PMID:9627386

  6. Modelling the variable broad-band optical/UV/X-ray spectrum of PG1211+143: implications for the ionized outflow

    Science.gov (United States)

    Papadakis, I. E.; Nicastro, F.; Panagiotou, C.

    2016-06-01

    Context. We present the results from a detailed analysis of the 2007 Swift monitoring campaign of the quasar PG1211+143. Aims: We study its broad-band optical/UV-X-ray spectral energy distribution and its variations, with the use of physically motivated models. Methods: We constructed broad-band, optical/UV-X-ray spectral energy distributions over three X-ray flux intervals, and we fitted them with a model which accounts for the disc and the X-ray coronal emission. We also added a spectral model component to account for the presence of the warm absorber which has been well established from past observations of the source. Results: We detected no optical/UV variations over the two-month period of the monitoring campaign. On the other hand, the X-rays are highly variable in a correlated way in the soft and hard X-ray bands with an amplitude larger than has been commonly observed in nearby Seyferts, even on longer time scales. The three flux spectra are well fitted by the model we considered. The disc inner temperature remains constant at ~2 eV, while X-rays are variable in slope and normalization. The absorber covers almost 90% of the central source. It is outflowing with a velocity less than 2.3 × 104 km s-1 (3σ upper limit), and has a column density of log NH ~ 23.2. Its ionization parameter varies by a factor of 1.6, and it is in photo-ionizing equilibrium with the ionizing flux. It is located at a distance of less than 0.35 pc from the central source, and its relative thickness, ΔR/R, is less than 0.1. The absorber's ionization parameter variations can explain the larger than average amplitude of the X-ray variations. Conclusions: The absence of optical/UV variations are consistent with the high black hole mass estimate of ~108M⊙ for this object, which implies variability time scales longer than the period of the Swift observations. It argues against the presence of inward propagating fluctuations in the disc as the reason for the flux variability in this

  7. 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.

  8. Genes optimized by evolution for accurate and fast translation encode in Archaea and Bacteria a broad and characteristic spectrum of protein functions

    Directory of Open Access Journals (Sweden)

    Merkl Rainer

    2010-11-01

    Full Text Available Abstract Background In many microbial genomes, a strong preference for a small number of codons can be observed in genes whose products are needed by the cell in large quantities. This codon usage bias (CUB improves translational accuracy and speed and is one of several factors optimizing cell growth. Whereas CUB and the overrepresentation of individual proteins have been studied in detail, it is still unclear which high-level metabolic categories are subject to translational optimization in different habitats. Results In a systematic study of 388 microbial species, we have identified for each genome a specific subset of genes characterized by a marked CUB, which we named the effectome. As expected, gene products related to protein synthesis are abundant in both archaeal and bacterial effectomes. In addition, enzymes contributing to energy production and gene products involved in protein folding and stabilization are overrepresented. The comparison of genomes from eleven habitats shows that the environment has only a minor effect on the composition of the effectomes. As a paradigmatic example, we detailed the effectome content of 37 bacterial genomes that are most likely exposed to strongest selective pressure towards translational optimization. These effectomes accommodate a broad range of protein functions like enzymes related to glycolysis/gluconeogenesis and the TCA cycle, ATP synthases, aminoacyl-tRNA synthetases, chaperones, proteases that degrade misfolded proteins, protectants against oxidative damage, as well as cold shock and outer membrane proteins. Conclusions We made clear that effectomes consist of specific subsets of the proteome being involved in several cellular functions. As expected, some functions are related to cell growth and affect speed and quality of protein synthesis. Additionally, the effectomes contain enzymes of central metabolic pathways and cellular functions sustaining microbial life under stress situations. These

  9. Multiplex component-based allergen microarray in recent clinical studies.

    Science.gov (United States)

    Patelis, A; Borres, M P; Kober, A; Berthold, M

    2016-08-01

    During the last decades component-resolved diagnostics either as singleplex or multiplex measurements has been introduced into the field of clinical allergology, providing important information that cannot be obtained from extract-based tests. Here we review recent studies that demonstrate clinical applications of the multiplex microarray technique in the diagnosis and risk assessment of allergic patients, and its usefulness in studies of allergic diseases. The usefulness of ImmunoCAP ISAC has been validated in a wide spectrum of allergic diseases like asthma, allergic rhinoconjunctivitis, atopic dermatitis, eosinophilic esophagitis, food allergy and anaphylaxis. ISAC provides a broad picture of a patient's sensitization profile from a single test, and provides information on specific and cross-reactive sensitizations that facilitate diagnosis, risk assessment, and disease management. Furthermore, it can reveal unexpected sensitizations which may explain anaphylaxis previously categorized as idiopathic and also display for the moment clinically non-relevant sensitizations. ISAC can facilitate a better selection of relevant allergens for immunotherapy compared with extract testing. Microarray technique can visualize the allergic march and molecular spreading in the preclinical stages of allergic diseases, and may indicate that the likelihood of developing symptomatic allergy is associated with specific profiles of sensitization to allergen components. ISAC is shown to be a useful tool in routine allergy diagnostics due to its ability to improve risk assessment, to better select relevant allergens for immunotherapy as well as detecting unknown sensitization. Multiplex component testing is especially suitable for patients with complex symptomatology. PMID:27196983

  10. Microarray Analysis in Glioblastomas

    Science.gov (United States)

    Bhawe, Kaumudi M.; Aghi, Manish K.

    2016-01-01

    Microarray analysis in glioblastomas is done using either cell lines or patient samples as starting material. A survey of the current literature points to transcript-based microarrays and immunohistochemistry (IHC)-based tissue microarrays as being the preferred methods of choice in cancers of neurological origin. Microarray analysis may be carried out for various purposes including the following: To correlate gene expression signatures of glioblastoma cell lines or tumors with response to chemotherapy (DeLay et al., Clin Cancer Res 18(10):2930–2942, 2012)To correlate gene expression patterns with biological features like proliferation or invasiveness of the glioblastoma cells (Jiang et al., PLoS One 8(6):e66008, 2013)To discover new tumor classificatory systems based on gene expression signature, and to correlate therapeutic response and prognosis with these signatures (Huse et al., Annu Rev Med 64(1):59–70, 2013; Verhaak et al., Cancer Cell 17(1):98–110, 2010) While investigators can sometimes use archived tumor gene expression data available from repositories such as the NCBI Gene Expression Omnibus to answer their questions, new arrays must often be run to adequately answer specific questions. Here, we provide a detailed description of microarray methodologies, how to select the appropriate methodology for a given question, and analytical strategies that can be used. Experimental methodology for protein microarrays is outside the scope of this chapter, but basic sample preparation techniques for transcript-based microarrays are included here. PMID:26113463

  11. Broad-spectrum pollination of Plectranthus neochilus

    Directory of Open Access Journals (Sweden)

    C. H. Stirton

    1977-12-01

    Full Text Available The pollination ecology of Plectranthus neochilus Schltr. is discussed and compared with that of another garden plant,  Plectranthus barbatus Andr.. Pollinators and flower visitors of P. neochilus include members of  the Megachilidae, Anthophoridae, Syrphidae, Bombyliidae, Sphingidae, Apidae.

  12. 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.

  13. 贵州铜仁产广谱抑菌作用细菌素乳酸菌的筛选及鉴定%On the Sift and Identification of the Broad-spectrum Antibacterial Bacteriocin Produced in Tongren, Guizhou

    Institute of Scientific and Technical Information of China (English)

    胡美忠; 张新卓; 刘芸

    2014-01-01

    从贵州铜仁产发酵食品中分离纯化出70余株乳酸菌,采用Agar-spot-test初筛与排除酸、过氧化氢抑制后复筛出一株能产广谱抑菌作用细菌素的乳酸菌(编号G55),经生理生化及16S rDNA鉴定可知G55为植物乳杆菌。抑菌谱实验表明,G55产生的细菌素能抑制革兰阳性菌及革兰阴性菌的生长;蛋白酶实验表明,G55产生的细菌素对胃蛋白酶、蛋白酶K敏感,对胰蛋白酶、α凝乳蛋白酶部分敏感。%More than 70 strains of lactic acid bacteria are separated and purified from the fermented foods made in Tongren, Guizhou. First, they are preliminarily sifted by means of agar-spot-test and then excluded from the inhibition of the acid and hydrogen peroxide. After a second sift, a strain of lactic acid bacteria named G55 which can produce broad-spectrum antibacterial bacteriocin is chosen from them. After the physiobiochemical experiment and the 16SrDNA identification, it is concluded that G55 is an actobacillus plantarum. According to the antibacterial spectrum experiment, it shows that the bacteriocin produced by G55 can inhibit the growth of both gram-positive bacteria and gram-negative bacteria. Meanwhile, the experiment of protease shows that the bacteriorin is sensitive to pepsin and proteinase K and is partially sensitive to trypsin andαcurd protease.

  14. Phylloseptin-PBa—A Novel Broad-Spectrum Antimicrobial Peptide from the Skin Secretion of the Peruvian Purple-Sided Leaf Frog (Phyllomedusa Baltea Which Exhibits Cancer Cell Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Yuantai Wan

    2015-12-01

    Full Text Available Antimicrobial peptides from amphibian skin secretion display remarkable broad-spectrum antimicrobial activity and are thus promising for the discovery of new antibiotics. In this study, we report a novel peptide belonging to the phylloseptin family of antimicrobial peptides, from the skin secretion of the purple-sided leaf frog, Phyllomedusa baltea, which was named Phylloseptin-PBa. Degenerate primers complementary to putative signal peptide sites of frog skin peptide precursor-encoding cDNAs were designed to interrogate a skin secretion-derived cDNA library from this frog. Subsequently, the peptide was isolated and identified using reverse phase HPLC and MS/MS fragmentation. The synthetic replicate was demonstrated to have activity against S. aureus, E. coli and C. albicans at concentrations of 8, 128 and 8 mg/L, respectively. In addition, it exhibited anti-proliferative activity against the human cancer cell lines, H460, PC3 and U251MG, but was less active against a normal human cell line (HMEC. Furthermore, a haemolysis assay was performed to assess mammalian cell cytotoxicity of Phylloseptin-PBa. This peptide contained a large proportion of α-helical domain, which may explain its antimicrobial and anticancer activities.

  15. Combining Affymetrix microarray results

    Directory of Open Access Journals (Sweden)

    Doerge RW

    2005-03-01

    Full Text Available Abstract Background As the use of microarray technology becomes more prevalent it is not unusual to find several laboratories employing the same microarray technology to identify genes related to the same condition in the same species. Although the experimental specifics are similar, typically a different list of statistically significant genes result from each data analysis. Results We propose a statistically-based meta-analytic approach to microarray analysis for the purpose of systematically combining results from the different laboratories. This approach provides a more precise view of genes that are significantly related to the condition of interest while simultaneously allowing for differences between laboratories. Of particular interest is the widely used Affymetrix oligonucleotide array, the results of which are naturally suited to a meta-analysis. A simulation model based on the Affymetrix platform is developed to examine the adaptive nature of the meta-analytic approach and to illustrate the usefulness of such an approach in combining microarray results across laboratories. The approach is then applied to real data involving a mouse model for multiple sclerosis. Conclusion The quantitative estimates from the meta-analysis model tend to be closer to the "true" degree of differential expression than any single lab. Meta-analytic methods can systematically combine Affymetrix results from different laboratories to gain a clearer understanding of genes' relationships to specific conditions of interest.

  16. Protein microarrays for systems biology

    Institute of Scientific and Technical Information of China (English)

    Lina Yang; Shujuan Guo; Yang Li; Shumin Zhou; Shengce Tao

    2011-01-01

    Systems biology holds the key for understanding biological systems on a system level. It eventually holds the key for the treatment and cure of complex diseases such as cancer,diabetes, obesity, mental disorders, and many others. The '-omics' technologies, such as genomics, transcriptomics,proteomics, and metabonomics, are among the major driving forces of systems biology. Featured as highthroughput, miniaturized, and capable of parallel analysis,protein microarrays have already become an important technology platform for systems biology, In this review, we will focus on the system level or global analysis of biological systems using protein microarrays. Four major types of protein microarrays will be discussed: proteome microarrays, antibody microarrays, reverse-phase protein arrays,and lectin microarrays. We will also discuss the challenges and future directions of protein microarray technologies and their applications for systems biology. We strongly believe that protein microarrays will soon become an indispensable and invaluable tool for systems biology.

  17. Microarray technology and its applications

    CERN Document Server

    Müller, UR

    2006-01-01

    It presents detailed overviews of the different techniques of fabricating microarrays, of the chemistries and preparative steps involved, of the different types of microarrays, and of the instrumentation and optical issues involved.

  18. 不同品种香蕉内生菌分离及广谱拮抗菌的筛选%Endophytes Isolation and Broad-spectrum Antagonistic Bacterias Screening from Banana

    Institute of Scientific and Technical Information of China (English)

    王梦颖; 周登博; 井涛; 胡一凤; 高祝芬; 谢晴宜; 张锡炎; 戚春林

    2014-01-01

    In order to determine the main distribution of endophytes and their broad-spectrum antimicrobial activity, endophytes were obtained from healthy and diseased tissues of two disease-resistant and one disease susceptible banana cultivars. Endophytes were separated from roots, corms, pseudostems, leaves and store in the ultra-low on Luria-Bertani(LB), Yeast Extract with supplements(YE), and Potato Dextrose Agar(PDA)strain store medium. Then screened broad-spectrum antagonistic bacteria which against Fusarium oxysporum f. sp. Cubense, Curvularia lunata, Curvularia fallax, Corynespora cassiicola(Berk&Curt)Wei, Alternaria musae, Deightoniella troulosa, Colletotrichum musae, Pestalogiopsis sp., Btoryosphaeria dothidea. Taxonomy identification of 041, 04-1, 19-1, 03A-1 was conducted by evaluating morphologic characteristics and 16S rDNA gene sequences for phylogenetic analysis. After purification, total of 438 endophytes were obtained. The total of isolates showed that we obtained 240 strains bacteria, followed by 142 strains actinomycetes, and 56 strains fungi. The richest number of endophytes that isolated from diseased NanTian banana cultivars(128). Ten actinomyces and two bacterias were determined to possess antibiotic activity against Ten banana pathogens. Isolates 041 was the most effective and had 28.13±1.89 mm width of inhibition zone. Isolated 041, 04-1, 19-1, 034-1 were identified as Streptomyces misionensis.%旨在探究抗病品种与易感品种香蕉的健康株和病株内生菌与其中广谱拮抗菌的主要分布规律,并对广谱拮抗菌进行拮抗活性的测定。以样品根、球茎、假茎、叶为材料分离培养内生菌,在实验室条件下,筛选对供试的10种香蕉致病菌均有良好拮抗活性的菌株并测定它们的拮抗活性,对活性最强的菌株进行形态学、16S rDNA序列同源性分析。结果显示,分离得到内生菌438株,其中细菌240株,放线菌142株,真菌56株。抗病品种南天

  19. 严重烧伤患者早期短程应用高效抗生素的研究%Clinical study on the early and short - term use of antibiotics with broad spectrum in severely burned patients

    Institute of Scientific and Technical Information of China (English)

    宗光全; 张茂红; 章冠东; 杜庆安

    2001-01-01

    Objective To investigate the prevention and treatment effects of early and short - term use of antibiotics with broad spectrum on postburn severe infection in severely burned patients . Methods Thirty - five burn patients with TBSA from 50% to 95% were enrolled in the study. The patients were divided into early prevention[ 20 cases, antibiotics were used started from 6 postburn hours (PBH)] and delayed prevention( 15 cases,antibiotics were applied after 48 PBH )groups. Plasma levels of LPS,TNFa and IL -8 were dynamically monitored with the concomitant observation of clinical signs of postburn sepsis.Results After major burns,the plasma levels of LPS,TNFα and IL -8 increased evidently and reached the peak values on 3 ~5 postburn days(PBD). But the levels of all above factors in the early group were obviously lower than those in the delayed group( P < 0. 05 ~0. 01 ). The incidencies of sepsis and internal organ complications within 2 postburn weeks were much lower in the early group than those in the delayed group (P < 0. 05). The subeschar bacterial quantification on 4 ~ 7 PBD was evidently lower in the early group than that in the delayed group ( P < 0. 01 ) . Conclusion Early and short - term use of antibiotics with broad spectrum in severely burned patients could effectively prevent postburn severe infection and lower down the incidence of internal organ complications.%目的探讨早期短程应用高效抗生素对严重烧伤后患者感染的防治效果。方法烧伤患者35例,烧伤面积50%~95%。根据高效抗生素使用时机分为早防组(20例,伤后6 h内开始)和迟防组(15例,伤后48 h开始)。动态检测血浆内毒素( lipopolysaccharide, LPS ) 、肿瘤坏死因子(TNFα)和白细胞介素-8(IL-8)的变化,严密观察脓毒症各项指标。结果大面积烧伤后血LPS、TNFα和IL-8明显升高,于伤后3~5 d达高峰,但早防组明显低于迟防组(P<0.05~0.001)。伤后2周内脓毒症、内

  20. 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

    Science.gov (United States)

    Qiu, Hongyu; Cassan, Robyn; Johnstone, Darrell; Han, Xiaobing; Joyee, Antony George; McQuoid, Monica; Masi, Andrea; Merluza, John; Hrehorak, Bryce; Reid, Ross; Kennedy, Kieron; Tighe, Bonnie; Rak, Carla; Leonhardt, Melanie; Dupas, Brian; Saward, Laura; Berry, Jody D.; Nykiforuk, Cory L.

    2016-01-01

    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. PMID:27336843

  1. 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.

  2. Crx broadly modulates the pineal transcriptome

    OpenAIRE

    Rovsing, Louise; Clokie, Samuel; Bustos, Diego M.; Rohde, Kristian; Steven L Coon; Litman, Thomas; Rath, Martin F.; Møller, Morten; Klein, David C.

    2011-01-01

    Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. Here, the influence of Crx on the mammalian pineal gland was studied by light and electron microscopy and by use of microarray and qRTPCR technology, thereby extending previous studies on selected genes (Furukawa et al. 1999). Deletion of Crx was not found to alter pineal morphology, but was found to broadly modulate the mouse p...

  3. 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

  4. Navigating public microarray databases.

    Science.gov (United States)

    Penkett, Christopher J; Bähler, Jürg

    2004-01-01

    With the ever-escalating amount of data being produced by genome-wide microarray studies, it is of increasing importance that these data are captured in public databases so that researchers can use this information to complement and enhance their own studies. Many groups have set up databases of expression data, ranging from large repositories, which are designed to comprehensively capture all published data, through to more specialized databases. The public repositories, such as ArrayExpress at the European Bioinformatics Institute contain complete datasets in raw format in addition to processed data, whilst the specialist databases tend to provide downstream analysis of normalized data from more focused studies and data sources. Here we provide a guide to the use of these public microarray resources. PMID:18629145

  5. Design, construction, characterization, and application of a hyperspectral microarray scanner.

    Science.gov (United States)

    Sinclair, Michael B; Timlin, Jerilyn A; Haaland, David M; Werner-Washburne, Margaret

    2004-04-01

    We describe the design, construction, and operation of a hyperspectral microarray scanner for functional genomic research. The hyperspectral instrument operates with spatial resolutions ranging from 3 to 30 microm and records the emission spectrum between 490 and 900 nm with a spectral resolution of 3 nm for each pixel of the microarray. This spectral information, when coupled with multivariate data analysis techniques, allows for identification and elimination of unwanted artifacts and greatly improves the accuracy of microarray experiments. Microarray results presented in this study clearly demonstrate the separation of fluorescent label emission from the spectrally overlapping emission due to the underlying glass substrate. We also demonstrate separation of the emission due to green fluorescent protein expressed by yeast cells from the spectrally overlapping autofluorescence of the yeast cells and the growth media.

  6. Storing, linking, and mining microarray databases using SRS.

    NARCIS (Netherlands)

    A. Veldhoven (Antoine); D. de Lange (Don); M. Smid (Marcel); V. de Jager (Victor); J.A. Kors (Jan); G.W. Jenster (Guido)

    2005-01-01

    textabstractBACKGROUND: SRS (Sequence Retrieval System) has proven to be a valuable platform for storing, linking, and querying biological databases. Due to the availability of a broad range of different scientific databases in SRS, it has become a useful platform to incorporate and mine microarray

  7. 葡萄球菌肠毒素超抗原广谱抑制性多肽的功能研究%Study on the function of a broad-spectrum inhibitory peptide against SEs superantigen

    Institute of Scientific and Technical Information of China (English)

    王思雄; 李亚斐; 马惠文; 邵江河; 余慧青; 王东林

    2012-01-01

    目的 在前期筛选出针对SEA、SEB、SEC具有广谱抑制性的多肽P72基础上,通过竞争结合实验和动物模型对多肽P72的抑制机制进行探讨.方法 采用竞争结合实验检测多肽P72与MHCⅡ类分子的亲合力;利用“两次攻击(two-hit)法”建立的动物模型研究P72对SEs的体内抑制活性.结果 P72不能与FITC-SEs有效竞争结合Raji细胞上的MHCⅡ类分子,P72对SEA、SEB和SEC致Balb/c小鼠休克效应具有显著的保护作用.结论 P72可能不是与MHCⅡ类分子结合而产生的抑制作用,P72能够在体内抑制SEs的超抗原活性,其具体的抑制机制有待深入研究.%This study aims lo investigate the mechanism of the broad-spectrum inhibitory activity of synthetic peptide P72 against SEA, SEB and SEC based on the previous research of competition assay and animal experiments. We detected the binding ability of the peptide P72 to MHC class Ⅱ molecules by competition assay and assessed the in vivo biological activity of peptide P72 against SEs by the "two-hit animal model. The results indicated that the peptide P72 could not bind to MHC class Ⅱ molecules, while P72 can completely protect most of the Balb/c mice against toxic shock induced by SEA, SEB and SEC. In conclusion, our study demonstrates that the inhibitory activity of peptide P72 may not due lo binding to MHC Ⅱ . And peptide P72 can inhibit the biological activity of SEs in vivo. But the exact mechanism of inhibitory activity of P72 still needs studies.

  8. Health status, infection and disease in California sea lions (Zalophus californianus) studied using a canine microarray platform and machine-learning approaches.

    Science.gov (United States)

    Mancia, Annalaura; Ryan, James C; Chapman, Robert W; Wu, Qingzhong; Warr, Gregory W; Gulland, Frances M D; Van Dolah, Frances M

    2012-04-01

    Conservation biologists face many challenges in assessing health, immune status and infectious diseases in protected species. These challenges include unpredictable sample populations, diverse genetic and environmental backgrounds of the animals, as well as the practical, legal and ethical issues involved in experimentation. The use of whole genome scale transcriptomics with animal samples obtained in a minimally invasive manner is an approach that shows promise for health assessment. In this study we assessed the utility of a microarray to identify changes in gene expression predictive of health status by interrogating blood samples from California sea lions (Zalophus californianus) in rehabilitation. A custom microarray was developed from the commercially available dog microarray (Canis familiaris) by selecting probes that demonstrated reliable cross-hybridization with RNA in sea lion blood. This custom microarray was used for the analysis of RNA from 73 sea lion blood samples, from animals with a broad spectrum of health changes. Both traditional classifying techniques and newer artificial neural network approaches correctly classified sea lions with respect to health status, primarily distinguishing between leptospirosis infection and domoic acid exposure. Real time PCR validation for a small set of genes, followed by sequencing, showed good correlation with array results and high identity (96-98%) between the dog and sea lion sequences. This approach to health status classification shows promise for disease identification in a clinical setting, and assessment of health status of wildlife. PMID:22067742

  9. Compressive Sensing DNA Microarrays

    Directory of Open Access Journals (Sweden)

    Richard G. Baraniuk

    2009-01-01

    Full Text Available Compressive sensing microarrays (CSMs are DNA-based sensors that operate using group testing and compressive sensing (CS principles. In contrast to conventional DNA microarrays, in which each genetic sensor is designed to respond to a single target, in a CSM, each sensor responds to a set of targets. We study the problem of designing CSMs that simultaneously account for both the constraints from CS theory and the biochemistry of probe-target DNA hybridization. An appropriate cross-hybridization model is proposed for CSMs, and several methods are developed for probe design and CS signal recovery based on the new model. Lab experiments suggest that in order to achieve accurate hybridization profiling, consensus probe sequences are required to have sequence homology of at least 80% with all targets to be detected. Furthermore, out-of-equilibrium datasets are usually as accurate as those obtained from equilibrium conditions. Consequently, one can use CSMs in applications in which only short hybridization times are allowed.

  10. Granulometric Analysis of Spots in DNA Microarray Images

    Institute of Scientific and Technical Information of China (English)

    Behara Latha; Balasubramanian Venkatesh

    2004-01-01

    As the topological properties of each spot in DNA microarray images may vary from one another, we employed granulometries to understand the shape-size con tent contributed due to a significant intensity value within a spot. Analysis was performed on the microarray image that consisted of 240 spots by using concepts from mathematical morphology. In order to find out indices for each spot and to further classify them, we adopted morphological multiscale openings, which provided microarrays at multiple scales. Successive opened microarrays were subtracted to identify the protrusions that were smaller than the size of structuring element. Spot-wise details, in terms of probability of these observed protrusions,were computed by placing a regularly spaced grid on microarray such that each spot was centered in each grid. Based on the probability of size distribution functions of these protrusions isolated at each level, we estimated the mean size and texture index for each spot. With these characteristics, we classified the spots in a microarray image into bright and dull categories through pattern spectrum and shape-size complexity measures. These segregated spots can be compared with those of hybridization levels.

  11. DNA Microarray-Based Diagnostics.

    Science.gov (United States)

    Marzancola, Mahsa Gharibi; Sedighi, Abootaleb; Li, Paul C H

    2016-01-01

    The DNA microarray technology is currently a useful biomedical tool which has been developed for a variety of diagnostic applications. However, the development pathway has not been smooth and the technology has faced some challenges. The reliability of the microarray data and also the clinical utility of the results in the early days were criticized. These criticisms added to the severe competition from other techniques, such as next-generation sequencing (NGS), impacting the growth of microarray-based tests in the molecular diagnostic market.Thanks to the advances in the underlying technologies as well as the tremendous effort offered by the research community and commercial vendors, these challenges have mostly been addressed. Nowadays, the microarray platform has achieved sufficient standardization and method validation as well as efficient probe printing, liquid handling and signal visualization. Integration of various steps of the microarray assay into a harmonized and miniaturized handheld lab-on-a-chip (LOC) device has been a goal for the microarray community. In this respect, notable progress has been achieved in coupling the DNA microarray with the liquid manipulation microsystem as well as the supporting subsystem that will generate the stand-alone LOC device.In this chapter, we discuss the major challenges that microarray technology has faced in its almost two decades of development and also describe the solutions to overcome the challenges. In addition, we review the advancements of the technology, especially the progress toward developing the LOC devices for DNA diagnostic applications. PMID:26614075

  12. DNA Microarray-Based Diagnostics.

    Science.gov (United States)

    Marzancola, Mahsa Gharibi; Sedighi, Abootaleb; Li, Paul C H

    2016-01-01

    The DNA microarray technology is currently a useful biomedical tool which has been developed for a variety of diagnostic applications. However, the development pathway has not been smooth and the technology has faced some challenges. The reliability of the microarray data and also the clinical utility of the results in the early days were criticized. These criticisms added to the severe competition from other techniques, such as next-generation sequencing (NGS), impacting the growth of microarray-based tests in the molecular diagnostic market.Thanks to the advances in the underlying technologies as well as the tremendous effort offered by the research community and commercial vendors, these challenges have mostly been addressed. Nowadays, the microarray platform has achieved sufficient standardization and method validation as well as efficient probe printing, liquid handling and signal visualization. Integration of various steps of the microarray assay into a harmonized and miniaturized handheld lab-on-a-chip (LOC) device has been a goal for the microarray community. In this respect, notable progress has been achieved in coupling the DNA microarray with the liquid manipulation microsystem as well as the supporting subsystem that will generate the stand-alone LOC device.In this chapter, we discuss the major challenges that microarray technology has faced in its almost two decades of development and also describe the solutions to overcome the challenges. In addition, we review the advancements of the technology, especially the progress toward developing the LOC devices for DNA diagnostic applications.

  13. Oral microbiome profiles: 16S rRNA pyrosequencing and microarray assay comparison.

    Directory of Open Access Journals (Sweden)

    Jiyoung Ahn

    Full Text Available OBJECTIVES: The human oral microbiome is potentially related to diverse health conditions and high-throughput technology provides the possibility of surveying microbial community structure at high resolution. We compared two oral microbiome survey methods: broad-based microbiome identification by 16S rRNA gene sequencing and targeted characterization of microbes by custom DNA microarray. METHODS: Oral wash samples were collected from 20 individuals at Memorial Sloan-Kettering Cancer Center. 16S rRNA gene survey was performed by 454 pyrosequencing of the V3-V5 region (450 bp. Targeted identification by DNA microarray was carried out with the Human Oral Microbe Identification Microarray (HOMIM. Correlations and relative abundance were compared at phylum and genus level, between 16S rRNA sequence read ratio and HOMIM hybridization intensity. RESULTS: The major phyla, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria were identified with high correlation by the two methods (r = 0.70∼0.86. 16S rRNA gene pyrosequencing identified 77 genera and HOMIM identified 49, with 37 genera detected by both methods; more than 98% of classified bacteria were assigned in these 37 genera. Concordance by the two assays (presence/absence and correlations were high for common genera (Streptococcus, Veillonella, Leptotrichia, Prevotella, and Haemophilus; Correlation = 0.70-0.84. CONCLUSION: Microbiome community profiles assessed by 16S rRNA pyrosequencing and HOMIM were highly correlated at the phylum level and, when comparing the more commonly detected taxa, also at the genus level. Both methods are currently suitable for high-throughput epidemiologic investigations relating identified and more common oral microbial taxa to disease risk; yet, pyrosequencing may provide a broader spectrum of taxa identification, a distinct sequence-read record, and greater detection sensitivity.

  14. Microarray Scanner for Fluorescence Detection

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel pseudo confocal microarray scanner is introduced, in which one dimension scanning is performed by a galvanometer optical scanner and a telecentric objective, another dimension scanning is performed by a stepping motor.

  15. Recent advances of protein microarrays

    OpenAIRE

    Hultschig, Claus; Kreutzberger, Jürgen; Seitz, Harald; Konthur, Zoltán; Büssow, Konrad; Lehrach, Hans

    2006-01-01

    Technological innovations and novel applications have greatly advanced the field of protein microarrays. Over the past two years, different types of protein microarrays have been used for serum profiling, protein abundance determinations, and identification of proteins that bind DNA or small compounds. However, considerable development is still required to ensure common quality standards and to establish large content repertoires. Here, we summarize applications available to date and discuss ...

  16. 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…

  17. Broad resonances and beta-decay

    DEFF Research Database (Denmark)

    Riisager, K.; Fynbo, H. O. U.; Hyldegaard, S.;

    2015-01-01

    Beta-decay into broad resonances gives a distorted lineshape in the observed energy spectrum. Part of the distortion arises from the phase space factor, but we show that the beta-decay matrix element may also contribute. Based on a schematic model for p-wave continuum neutron states it is argued...

  18. The Stanford Tissue Microarray Database.

    Science.gov (United States)

    Marinelli, Robert J; Montgomery, Kelli; Liu, Chih Long; Shah, Nigam H; Prapong, Wijan; Nitzberg, Michael; Zachariah, Zachariah K; Sherlock, Gavin J; Natkunam, Yasodha; West, Robert B; van de Rijn, Matt; Brown, Patrick O; Ball, Catherine A

    2008-01-01

    The Stanford Tissue Microarray Database (TMAD; http://tma.stanford.edu) is a public resource for disseminating annotated tissue images and associated expression data. Stanford University pathologists, researchers and their collaborators worldwide use TMAD for designing, viewing, scoring and analyzing their tissue microarrays. The use of tissue microarrays allows hundreds of human tissue cores to be simultaneously probed by antibodies to detect protein abundance (Immunohistochemistry; IHC), or by labeled nucleic acids (in situ hybridization; ISH) to detect transcript abundance. TMAD archives multi-wavelength fluorescence and bright-field images of tissue microarrays for scoring and analysis. As of July 2007, TMAD contained 205 161 images archiving 349 distinct probes on 1488 tissue microarray slides. Of these, 31 306 images for 68 probes on 125 slides have been released to the public. To date, 12 publications have been based on these raw public data. TMAD incorporates the NCI Thesaurus ontology for searching tissues in the cancer domain. Image processing researchers can extract images and scores for training and testing classification algorithms. The production server uses the Apache HTTP Server, Oracle Database and Perl application code. Source code is available to interested researchers under a no-cost license. PMID:17989087

  19. Study of broad-spectrum antibiotics and antiseptics resistance genes in Acinetobacter baumannii strains isolated from burned patients%鲍曼不动杆菌烧伤分离株广谱抗生素及消毒剂耐药基因研究

    Institute of Scientific and Technical Information of China (English)

    程华莉; 潘宇红; 黄璇; 吕国忠; 朱婕; 糜祖煌; 张烽

    2011-01-01

    目的 研究鲍曼不动杆菌烧伤分离株对广谱抗生素的耐药性及所携带的广谱抗生素及消毒剂耐药基因.方法 测定20株分离自烧伤患者的鲍曼不动杆菌对四环素、米诺环素、氯霉素、利福平、复方磺胺甲噁唑5种广谱抗生素的敏感性,PCR检测catB、cmlA、arr-2/3、tetA、tetB、smr-2、emrE、dfrA1、dfrA5、dfrA7、dfrA12、dfrA17、dfrB5、qacE△l-sull和intI 共15种基因.结果 20株细菌对5种抗生素的敏感率分别为10%、100%、0、0和5%.tetB、qacE△l-sull和intl基因检出率均为95%(19/20),其余12种基因为阴性,且一株静脉导管分离株携带了上述3种基因.结论 本组鲍曼不动杆菌烧伤分离株对除米诺环素外的广谱抗生素耐药严重,并携带了四环素类和消毒剂耐药基因.应规范此类抗生素在养殖业中的使用,同时采取措施防止多重耐药菌株利用静脉导管在烧伤科传播.%Objective To investigate the broad-spectrum antibiotics resistance and broad-spectrum antibiotics and antiseptics resistance genes of Acinetobacter baumannii strains isolated from burned patients.Methods Susceptibilities to tetracycline, minocycline, chloramphenicol, rifampicin and trimethoprim-sulfamethoxazole were tested.Subsequently, catB, cmlA, arr-2/3, tetA, tetB, smr-2, emrE, dfrA1, dfrA5, dfr4 7, dfr412, dfrA17, dfrB5, qacE⊿l-sull and intI were detected by PCR.Results Susceptibilities to five broad-spectrum antibiotics were 10%, 100%, 0, 0 and 5% respectively.19/20(95%) isolates carried tetB, qacE⊿l-sull and intI genes while other 12 genes were not detected.Notably, an isolate colonising a central venous catheter carried all three genes mentioned above.Conclusions Acinetobacter baumannii strains isolated from burned patients we studied had serious resistances to broad-spectrum antibiotics except minocycline and carried tetracyclines and antiseptics resistance genes.Accordingly, broad-spectrum antibiotics should be

  20. Screen and Preliminary Identification of Lactic acid bacteria to Produce Broad-Spectrum Bacteriocin%产广谱细菌素乳酸菌CW3的筛选和初步鉴定

    Institute of Scientific and Technical Information of China (English)

    吕好新; 王巍东; 谈重芳; 杨飞飞; 焦迎春; 王雁萍; 李宗伟

    2013-01-01

    [Objective] CW3 strain was screened and preliminarily identified.[Method] Oxford cup double plate method was adopted to primarily screen spectrum bacteriocin,then excluding acid and hydrogen peroxide disturbance,the protein property of anti-bacteria material was detected,the strain of rescreening was identified.[Result] The supernatant of CW3 strain can inhibit the growth of indicator strains excluded hydrogen peroxide and organic acid.The inhibitive activity decreased largely after treatment with trpsin and pepsin,which can draw that the anti-microbial substances were bacteriocin.The results of identification of physiology and biochemistry preliminarily identified that CW3 strain was a Lactobacillus plantarum.[Conclusion] CW3 strain was a Lactobacillus plantarum,which can generate spectrum bacteriocin.%[目的]对CW3菌株进行筛选,并且进行初步鉴定.[方法]首先采用牛津杯双层平板法进行产广谱细菌素菌株的初筛,再将初筛得到的菌株进行排除酸和过氧化氢干扰,并检测抑菌物质的蛋白质性质,最终对复筛得到的菌株进行鉴定.[结果]试验得出,排除有机酸、过氧化氢等干扰因素后,发酵液仍有抑菌作用;用胰蛋白酶和胃蛋白酶处理后,发酵液抑菌活性急剧下降,确定产生的抑菌物质具有蛋白质性质,是一类细菌素.经过生理生化试验初步鉴定菌株CW3为植物乳杆菌.[结论]菌株CW3是一种能产广谱细菌素的植物乳杆菌.

  1. Electrostatic readout of DNA microarrays with charged microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Clack, Nathan G. [Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group; Salaita, Khalid [Univ. of California, Berkeley, CA (United States). Department of Chemistry; Groves, Jay T. [Univ. of California, Berkeley, CA (United States). Biophysics Graduate Group and Department of Chemistry

    2008-06-29

    DNA microarrays are used for gene-expression profiling, single-nucleotide polymorphism detection and disease diagnosis. A persistent challenge in this area is the lack of microarray screening technology suitable for integration into routine clinical care. In this paper, we describe a method for sensitive and label-free electrostatic readout of DNA or RNA hybridization on microarrays. The electrostatic properties of the microarray are measured from the position and motion of charged microspheres randomly dispersed over the surface. We demonstrate nondestructive electrostatic imaging with 10-μm lateral resolution over centimeter-length scales, which is four-orders of magnitude larger than that achievable with conventional scanning electrostatic force microscopy. Changes in surface charge density as a result of specific hybridization can be detected and quantified with 50-pM sensitivity, single base-pair mismatch selectivity and in the presence of complex background. Lastly, because the naked eye is sufficient to read out hybridization, this approach may facilitate broad application of multiplexed assays.

  2. Chromosome microarrays in diagnostic testing: interpreting the genomic data.

    Science.gov (United States)

    Peters, Greg B; Pertile, Mark D

    2014-01-01

    DNA-based Chromosome MicroArrays (CMAs) are now well established as diagnostic tools in clinical genetics laboratories. Over the last decade, the primary application of CMAs has been the genome-wide detection of a particular class of mutation known as copy number variants (CNVs). Since 2010, CMA testing has been recommended as a first-tier test for detection of CNVs associated with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies…in the post-natal setting. CNVs are now regarded as pathogenic in 14-18 % of patients referred for these (and related) disorders.Through consideration of clinical examples, and several microarray platforms, we attempt to provide an appreciation of microarray diagnostics, from the initial inspection of the microarray data, to the composing of the patient report. In CMA data interpretation, a major challenge comes from the high frequency of clinically irrelevant CNVs observed within "patient" and "normal" populations. As might be predicted, the more common and clinically insignificant CNVs tend to be the smaller ones resolution, and some miscalling of CNVs is unavoidable. In this, there is no ideal solution, but various strategies for handling noise are available. Even without solutions, consideration of these diagnostic problems per se is informative, as they afford critical insights into the biological and technical underpinnings of CNV discovery. These are indispensable to any clinician or scientist practising within the field of genome diagnostics. PMID:24870134

  3. Screening and performance test of efficient broad - spectrum composite sunscreen agent from traditional Chinese herbal medicines%中草药高效广谱复合防晒组分的筛选和性能测试

    Institute of Scientific and Technical Information of China (English)

    俞晨秀; 潘武

    2011-01-01

    通过对201种中草药在防晒光区(290~400 nm)紫外吸收能力的研究,选取紫外吸收强、吸收波段互补、调配着色浅的苦丁茶和槐米两种生药萃取液复配制得复合防晒剂.结果表明:复合防晒剂在水剂中的用量≤0.3 g/L,乳剂中的用量≤0.7 g/L时的使用色度合适,累积日照20h下稳定,50℃下热稳定,pH =4~7之间稳定,室内存放1 a稳定,具有广谱、高效的防晒效果.%Through UV (with spectrum of 290 ~400 nm) absorption capacity study of 201 kinds of traditional Chinese herbal medicine, Ilex kudingcha extract and Sophora japonica extract were selected to formulate a composite sunscreen agent based upon their strong UV absorption capacity, complementary absorption bands and light coloration. Experiment results showed that the composite sunscreen agent has the appropriate color when the mass concentration is below 0. 3 g/L in aqueous formulation and below 0. 7 g/L in emulsion formulation. The sunscreen agent is stable under cumulative sunshine of 20 h, temperature of 50 t ,and pH of 4 ~ 7. Under ambient condition, it can be stable for one year.

  4. 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.

  5. Comparison of gene expression microarray data with count-based RNA measurements informs microarray interpretation

    OpenAIRE

    Richard, Arianne C.; Lyons, Paul A.; Peters, James E.; Biasci, Daniele; Flint, Shaun M; James C Lee; McKinney, Eoin F; Siegel, Richard M.; Smith, Kenneth GC

    2014-01-01

    Background Although numerous investigations have compared gene expression microarray platforms, preprocessing methods and batch correction algorithms using constructed spike-in or dilution datasets, there remains a paucity of studies examining the properties of microarray data using diverse biological samples. Most microarray experiments seek to identify subtle differences between samples with variable background noise, a scenario poorly represented by constructed datasets. Thus, microarray u...

  6. 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...

  7. 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.

  8. Microarray results: how accurate are they?

    Directory of Open Access Journals (Sweden)

    Mane Shrikant

    2002-08-01

    Full Text Available Abstract Background DNA microarray technology is a powerful technique that was recently developed in order to analyze thousands of genes in a short time. Presently, microarrays, or chips, of the cDNA type and oligonucleotide type are available from several sources. The number of publications in this area is increasing exponentially. Results In this study, microarray data obtained from two different commercially available systems were critically evaluated. Our analysis revealed several inconsistencies in the data obtained from the two different microarrays. Problems encountered included inconsistent sequence fidelity of the spotted microarrays, variability of differential expression, low specificity of cDNA microarray probes, discrepancy in fold-change calculation and lack of probe specificity for different isoforms of a gene. Conclusions In view of these pitfalls, data from microarray analysis need to be interpreted cautiously.

  9. Optimisation algorithms for microarray biclustering.

    Science.gov (United States)

    Perrin, Dimitri; Duhamel, Christophe

    2013-01-01

    In providing simultaneous information on expression profiles for thousands of genes, microarray technologies have, in recent years, been largely used to investigate mechanisms of gene expression. Clustering and classification of such data can, indeed, highlight patterns and provide insight on biological processes. A common approach is to consider genes and samples of microarray datasets as nodes in a bipartite graphs, where edges are weighted e.g. based on the expression levels. In this paper, using a previously-evaluated weighting scheme, we focus on search algorithms and evaluate, in the context of biclustering, several variations of Genetic Algorithms. We also introduce a new heuristic "Propagate", which consists in recursively evaluating neighbour solutions with one more or one less active conditions. The results obtained on three well-known datasets show that, for a given weighting scheme, optimal or near-optimal solutions can be identified. PMID:24109756

  10. How Can Microarrays Unlock Asthma?

    Directory of Open Access Journals (Sweden)

    Alen Faiz

    2012-01-01

    Full Text Available Asthma is a complex disease regulated by the interplay of a large number of underlying mechanisms which contribute to the overall pathology. Despite various breakthroughs identifying genes related to asthma, our understanding of the importance of the genetic background remains limited. Although current therapies for asthma are relatively effective, subpopulations of asthmatics do not respond to these regimens. By unlocking the role of these underlying mechanisms, a source of novel and more effective treatments may be identified. In the new age of high-throughput technologies, gene-expression microarrays provide a quick and effective method of identifying novel genes and pathways, which would be impossible to discover using an individual gene screening approach. In this review we follow the history of expression microarray technologies and describe their contributions to advancing our current knowledge and understanding of asthma pathology.

  11. Gene expression alterations during HGF-induced dedifferentiation of a renal tubular epithelial cell line (MDCK) using a novel canine DNA microarray.

    Science.gov (United States)

    Balkovetz, Daniel F; Gerrard, Edward R; Li, Shixiong; Johnson, David; Lee, James; Tobias, John W; Rogers, Katherine K; Snyder, Richard W; Lipschutz, Joshua H

    2004-04-01

    Hepatocyte growth factor (HGF) elicits a broad spectrum of biological activities, including epithelial cell dedifferentiation. One of the most widely used and best-studied polarized epithelial cell lines is the Madin-Darby canine kidney (MDCK) cell line. Here, we describe and validate the early response of polarized monolayers of MDCK cells stimulated with recombinant HGF using a novel canine DNA microarray designed to query 12,473 gene sequences. In our survey, eight genes previously implicated in the HGF signaling pathway were differentially regulated, demonstrating that the system was responsive to HGF. Also identified were 117 genes not previously known to be involved in the HGF pathway. The results were confirmed by real-time PCR or Western blot analysis for 38 genes. Of particular interest were the large number of differentially regulated genes encoding small GTPases, proteins involved in endoplasmic reticulum translation, proteins involved in the cytoskeleton, the extracellular matrix, and the hematopoietic and prostaglandin systems.

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. Ontology-Based Analysis of Microarray Data.

    Science.gov (United States)

    Giuseppe, Agapito; Milano, Marianna

    2016-01-01

    The importance of semantic-based methods and algorithms for the analysis and management of biological data is growing for two main reasons. From a biological side, knowledge contained in ontologies is more and more accurate and complete, from a computational side, recent algorithms are using in a valuable way such knowledge. Here we focus on semantic-based management and analysis of protein interaction networks referring to all the approaches of analysis of protein-protein interaction data that uses knowledge encoded into biological ontologies. Semantic approaches for studying high-throughput data have been largely used in the past to mine genomic and expression data. Recently, the emergence of network approaches for investigating molecular machineries has stimulated in a parallel way the introduction of semantic-based techniques for analysis and management of network data. The application of these computational approaches to the study of microarray data can broad the application scenario of them and simultaneously can help the understanding of disease development and progress.

  15. Construction of metastatic spinal cancer tissue microarrays

    Institute of Scientific and Technical Information of China (English)

    Yang Xinghai; Chen Huajiang; Xiao Jianru; Yuan Wen; Jia Lianshun

    2009-01-01

    Objective: To explore the construction of metastatic spinal cancer (MSC) tissue microarrays and validate its value in immunohistochemical study of MSC. Methods: Paraffin-embedded specimens from 71 MSC cases and 6 primary tumor cases were selected as donor blocks and prepared into MSC tissue microarrays by tissue array arrangement, the steps of which included location, punching, sampling, sample seeding, and re-diagnosis by hematoxylin-eosin (HE) as well as MMP-9 and MMP-14 immunohistochemical staining. Results: The MSC tissue microarrays thus constructed were intact and crackless, containing 154 complete and well arranged microarray points. None of the sectioned tissue microarrays was lost, and the results of HE staining was consistent with the primary pathologic diagnoses. Immunohistochemical staining was also good without non-specific or marginal effect. Conclusion: The MSC tissue microarrays have a high value in the immunohistochemical study of MSC.

  16. Broad-spectrum antimicrobial activity of human intestinal defensin 5.

    OpenAIRE

    Porter, E M; van Dam, E; Valore, E V; Ganz, T

    1997-01-01

    Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia ...

  17. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    Science.gov (United States)

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  18. 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.

  19. The broad spectrum of celiac disease and gluten sensitive enteropathy.

    Science.gov (United States)

    Mocan, Oana; Dumitraşcu, Dan L

    2016-01-01

    The celiac disease is an immune chronic condition with genetic transmission, caused by the intolerance to gluten. Gluten is a protein from cereals containing the following soluble proteins: gliadine, which is the most toxic, and the prolamins. The average prevalence is about 1% in USA and Europe, but high in Africa: 5.6% in West Sahara. In the pathogenesis several factors are involved: gluten as external trigger, genetic predisposition (HLA, MYO9B), viral infections, abnormal immune reaction to gluten. Severity is correlated with the number of intraepithelial lymphocytes, cryptic hyperplasia and villous atrophy, as well as with the length of intestinal involvement. The severity is assessed according to the Marsh-Oberhuber staging. Diagnostic criteria are: positive serological tests, intestinal biopsy, the reversal after gluten free diet (GFD). Beside refractory forms, new conditions have been described, like the non celiac gluten intolerance. In a time when more and more people adhere to GFD for nonscientific reasons, practitioners should be updated with the progress in celiac disease knowledge. PMID:27547052

  20. 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.

  1. Studies on broad spectrum corrosion resistant oxide coatings

    Indian Academy of Sciences (India)

    Someswar Datta

    2001-12-01

    The corrosion resistant oxide coatings, developed and applied by the conventional vitreous enamelling techniques, showed superior resistance to a range of mineral acids at various strengths and temperatures, alkaline solutions, boiling water and chrome plating solutions. These coatings possess considerable abrasion and impact resistance as well as high thermal shock resistance. The properties of the coating system have been studied in detail and found to be strongly dependent on composition and processing parameters. These coatings have been characterized by X-ray diffraction analysis and SEM studies. Some of the coating materials have been found to be biocompatible.

  2. Laser-based patterning for transfected cell microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Andrew L; Creasey, Rhiannon; Voelcker, Nicolas H [Flinders University, GPO Box 2100, Bedford Park, SA 5042 (Australia); Hayes, Jason P [MiniFAB, 1 Dalmore Drive, Caribbean Park, Scoresby VIC 3179 (Australia); Thissen, Helmut, E-mail: Nico.Voelcker@flinders.edu.a [CSIRO Molecular and Health Technologies, Bayview Avenue, Clayton VIC 3168 (Australia)

    2009-12-15

    The spatial control over biomolecule- and cell-surface interactions is of great interest to a broad range of biomedical applications, including sensors, implantable devices and cell microarrays. Microarrays in particular require precise spatial control and the formation of patterns with microscale features. Here, we have developed an approach specifically designed for transfected cell microarray (TCM) applications that allows microscale spatial control over the location of both DNA and cells on highly doped p-type silicon substrates. This was achieved by surface modification, involving plasma polymerization of allylamine, grafting of poly(ethylene glycol) and subsequent excimer laser ablation. DNA could be delivered in a spatially defined manner using ink-jet printing. In addition, electroporation was investigated as an approach to transfect attached cells with adsorbed DNA and good transfection efficiencies of approximately 20% were observed. The ability of the microstructured surfaces to spatially direct both DNA adsorption and cell attachment was demonstrated in a functional TCM, making this system an exciting platform for chip-based functional genomics.

  3. Comprehensive comparison of six microarray technologies

    OpenAIRE

    Yauk, Carole L.; Berndt, M. Lynn; Williams, Andrew; Douglas, George R

    2004-01-01

    Microarray technology is extensively used in biological research. The applied technologies vary greatly between laboratories, and outstanding questions remain regarding the degree of correlation among approaches. Recently, there has been a drive toward ensuring high-quality microarray data by the implementation of MIAME (Minimal Information About a Microarray Experiment) guidelines and an emphasis on ensuring public-availability to all datasets. However, despite its current widespread use and...

  4. MICROARRAYS AND THEIR POTENTIAL IN MEDICINE

    Institute of Scientific and Technical Information of China (English)

    Erick Ling; Jie Xu

    2003-01-01

    Advancement in microarray technology can revolutionize many aspects of medicine. Microarrays have applications in gene expression profiling, genotyping, mutation analysis, gene identification, and pharmacology. This paper provides a brief review on the use of microarrays in studies of cancer, infectious diseases, chromosome disorders, neurological/mental disorders, and drugs, along with a prospect on its great potential in diagnosis, prognosis and the treatment of human diseases.

  5. "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.

  6. Development and Clinical Evaluation of a Highly Sensitive DNA Microarray for Detection and Genotyping of Human Papillomaviruses

    Science.gov (United States)

    Oh, TaeJeong; Kim, ChangJin; Woo, SukKyung; Kim, TaeSeung; Jeong, DongJun; Kim, MyungSoon; Lee, Sunwoo; Cho, HyunSill; An, Sungwhan

    2004-01-01

    Human papillomavirus (HPV) has been found in cervical cancer, tonsillar cancer, and certain types of head and neck cancers. We report on a DNA microarray-based method for the simultaneous detection and typing of HPVs. The genotype spectrum discriminated by this HPV DNA microarray includes 15 high-risk HPV genotypes and 12 low-risk HPV genotypes. The HPV DNA microarray showed high degrees of specificity and reproducibility. We evaluated the performance of the HPV DNA microarray by application to three HPV-positive cell lines (HeLa, Caski, and SiHa cells) and two HPV-negative cell lines (C33A and A549 cells). The HPV DNA microarray successfully identified the known types of HPV present in the cell lines. The detection limit of the HPV DNA microarray was at least 100-fold higher than that of PCR. To assess the clinical applicability of the HPV DNA microarray, we performed the HPV genotyping assay with 73 nonmalignant and malignant samples from 39 tonsillar cancer patients. Twenty-five of the 39 (64.1%) malignant samples were positive for HPV, whereas 3 of 34 (8.8%) nonmalignant samples were positive for HPV. This result shows a preferential association of HPV with tonsillar carcinomas. The correlations of the presence of HPV with the grade of differentiation and risk factors were not significant. Our data show that the HPV DNA microarray may be useful for the diagnosis and typing of HPV in large-scale epidemiological studies. PMID:15243092

  7. Application of microarray technology in pulmonary diseases

    OpenAIRE

    Patlakas George; Tzouvelekis Argyris; Bouros Demosthenes

    2004-01-01

    Abstract Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives.

  8. Broad iron lines in Active Galactic Nuclei

    CERN Document Server

    Fabian, A C; Reynolds, C S; Young, A J

    2000-01-01

    An intrinsically narrow line emitted by an accretion disk around a black hole appears broadened and skewed as a result of the Doppler effect and gravitational redshift. The fluorescent iron line in the X-ray band at 6.4-6.9keV is the strongest such line and is seen in the X-ray spectrum of many active galactic nuclei and, in particular, Seyfert galaxies. It is an important diagnostic with which to study the geometry and other properties of the accretion flow very close to the central black hole. The broad iron line indicates the presence of a standard thin accretion disk in those objects, often seen at low inclination. The broad iron line has opened up strong gravitational effects around black holes to observational study with wide-reaching consequences for both astrophysics and physics.

  9. 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...

  10. 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....

  11. DNA Microarrays for Identifying Fishes

    Science.gov (United States)

    Nölte, M.; Weber, H.; Silkenbeumer, N.; Hjörleifsdottir, S.; Hreggvidsson, G. O.; Marteinsson, V.; Kappel, K.; Planes, S.; Tinti, F.; Magoulas, A.; Garcia Vazquez, E.; Turan, C.; Hervet, C.; Campo Falgueras, D.; Antoniou, A.; Landi, M.; Blohm, D.

    2008-01-01

    In many cases marine organisms and especially their diverse developmental stages are difficult to identify by morphological characters. DNA-based identification methods offer an analytically powerful addition or even an alternative. In this study, a DNA microarray has been developed to be able to investigate its potential as a tool for the identification of fish species from European seas based on mitochondrial 16S rDNA sequences. Eleven commercially important fish species were selected for a first prototype. Oligonucleotide probes were designed based on the 16S rDNA sequences obtained from 230 individuals of 27 fish species. In addition, more than 1200 sequences of 380 species served as sequence background against which the specificity of the probes was tested in silico. Single target hybridisations with Cy5-labelled, PCR-amplified 16S rDNA fragments from each of the 11 species on microarrays containing the complete set of probes confirmed their suitability. True-positive, fluorescence signals obtained were at least one order of magnitude stronger than false-positive cross-hybridisations. Single nontarget hybridisations resulted in cross-hybridisation signals at approximately 27% of the cases tested, but all of them were at least one order of magnitude lower than true-positive signals. This study demonstrates that the 16S rDNA gene is suitable for designing oligonucleotide probes, which can be used to differentiate 11 fish species. These data are a solid basis for the second step to create a “Fish Chip” for approximately 50 fish species relevant in marine environmental and fisheries research, as well as control of fisheries products. PMID:18270778

  12. 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.

  13. DNA Microarrays in Herbal Drug Research

    Directory of Open Access Journals (Sweden)

    Preeti Chavan

    2006-01-01

    Full Text Available Natural products are gaining increased applications in drug discovery and development. Being chemically diverse they are able to modulate several targets simultaneously in a complex system. Analysis of gene expression becomes necessary for better understanding of molecular mechanisms. Conventional strategies for expression profiling are optimized for single gene analysis. DNA microarrays serve as suitable high throughput tool for simultaneous analysis of multiple genes. Major practical applicability of DNA microarrays remains in DNA mutation and polymorphism analysis. This review highlights applications of DNA microarrays in pharmacodynamics, pharmacogenomics, toxicogenomics and quality control of herbal drugs and extracts.

  14. Screening of Broad-spectrum Bacteriocin-producing Lactic Acid Bacteria Strain and Characteristics of Antibacterial Compounds%1株产广谱细菌素乳酸菌的筛选及其抑菌物质的特性

    Institute of Scientific and Technical Information of China (English)

    曹珂珂; 王娣; 李妍

    2012-01-01

    By A broad spectrum bacteriocin producing strain was screened by plant punching and its antibacterial characteristics was studied. The results showed that one baeteriocin-producing Lactic acid bacteria strain isolated from plant materials exhibited strong inhibition activity against the E. coil. The supernatant of this strain could still inhibit the growth of indicator strain strongly after eliminating hydrogen peroxide and organic acid. After treatment with pep- sin, the strain' s inhibitory activity decreased sharply, which showed the inhibitory substance possessed the character- istic of protein, and it could be named bacterioein. The strain was identified as Laetobacillus plantarum through detec- tion of its appearance, physiological and biochemical characteristics. The inhibitory activity of strain fermentation su- pernatant was not affected by high temperature, 1% Tween-80, SDS, EDTA and the low pH. However, its inhibitory activity revealed an obvious decrease after treatment with protease K and trypsin than with pepsin. The bacterial inhi- bition spectrum showed that this was a kind of bacteriocin with wide inhibition soectrum.%从植物性材料中筛选到1株对大肠杆菌有明显抑制作用的乳酸菌,在排除有机酸和过氧化氢的干扰后,该菌株的发酵上清液仍有较强的抑菌性;胃蛋白酶处理后,抑菌活性明显降低,说明其抑菌物质为蛋白质类物质,是一种细菌素。通过形态学和生理生化分析,初步鉴定该菌株为植物乳杆菌。生物学特性研究表明,该菌株发酵上清液经高温、吐温-80、SDS、EDTA处理后,仍保持较好的抑菌活性;在酸性条件下稳定;对蛋白酶K和胰蛋白酶较胃蛋白酶敏感。抑菌谱显示,该菌株的发酵上清液具有广谱抑菌性。

  15. Fluconazole prophylaxis for fungal infection in high risk preterm infants receiving broad-spectrum antibiotics over 10 days%氟康唑预防高危因素早产儿广谱抗生素使用后真菌感染的效果及安全性

    Institute of Scientific and Technical Information of China (English)

    陈涵强; 杨文庆; 杨长仪

    2010-01-01

    Objective To evaluate the benefits of fluconazole prophylaxis in preventing fungal infection in high risk premature infants using broad-spectrum antibiotics consecutively more than 10 days. Methods From October 2007 to September 2009, 164 preterm infants in high risk of fungal infection using broad-spectrum antibiotics consecutively more than 10 days were eligible for the study. Eighty-five infants,hospitalized from October 2008 to September 2009, were in the fluconazole group and were administered intravenously 3 mg/kg fluconazole every day for three days since the 11th day of antibiotic course. The other 79 infants, hospitalized from October 2007 to September 2008, were in the control group with no fluconazole administration. Fungal infection and colonizations and common complications were observed in the two groups. Results Fungal infection occured in six infants in the control group and none in the fluconazole group(χ2 = 4. 719,P = 0.03). There were no significant differences between the two groups in fungal colonization(χ2 =0. 175,P = 0. 675). No adverse effects of fluconazole therapy were documented. Conclusions Fluconazole prophylaxis may reduce the risk for fungal infection in high risk preterm infants.%目的 评估氟康唑对连续使用广谱抗生素10 d以上,且具有高危因素的早产儿发生侵袭性真菌感染的预防作用.方法 以2007年10月至2009年9月间入院,具有真菌感染高危因素并连续使用广谱抗生素10 d以上的164例早产儿为研究对象,将2008年10月至2009年9月入院的符合条件的85例早产儿作为预防组.予氟康唑3 mg/(kg·次)静脉滴注,每天1次,连续用3 d;将2007年10月至2008年9月入院的符合条件的79例早产儿作为对照组,不应用氟康唑预防.观察两组真菌感染和定植情况,以及常见并发症.结果 预防组无一例发生侵袭性真菌感染,对照组发生6例深部真菌感染,差异有统计学意义(χ2=4.719,P=0.03);预防组真菌定植11

  16. Integrating Hot and Cool Intelligences: Thinking Broadly about Broad Abilities

    Directory of Open Access Journals (Sweden)

    W. Joel Schneider

    2016-01-01

    Full Text Available Although results from factor-analytic studies of the broad, second-stratum abilities of human intelligence have been fairly consistent for decades, the list of broad abilities is far from complete, much less understood. We propose criteria by which the list of broad abilities could be amended and envision alternatives for how our understanding of the hot intelligences (abilities involving emotionally-salient information and cool intelligences (abilities involving perceptual processing and logical reasoning might be integrated into a coherent theoretical framework.

  17. 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...

  18. 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.

  19. Loss of glyphosate efficacy: a changing weed spectrum in Georgia cotton

    Science.gov (United States)

    Introduction of glyphosate resistance into crops through genetic modification has revolutionized crop protection. Glyphosate, the proverbial silver bullet, is a broad spectrum herbicide with favorable environmental characteristics and effective broad-spectrum weed control that has greatly improved ...

  20. Polymer microarrays for cell based applications

    OpenAIRE

    Hansen, Anne Klara Brigitte

    2012-01-01

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

  1. Text Mining Perspectives in Microarray Data Mining

    OpenAIRE

    Natarajan, Jeyakumar

    2013-01-01

    Current microarray data mining methods such as clustering, classification, and association analysis heavily rely on statistical and machine learning algorithms for analysis of large sets of gene expression data. In recent years, there has been a growing interest in methods that attempt to discover patterns based on multiple but related data sources. Gene expression data and the corresponding literature data are one such example. This paper suggests a new approach to microarray data mining as ...

  2. 肺炎克雷伯菌中超广谱β-内酰胺酶基因分布及转移研究%The distribution and transfer of genes of duper broad-spectrumβ-lactamase in klebsiella pneumoniae

    Institute of Scientific and Technical Information of China (English)

    卢锋

    2014-01-01

    目的:研究肺炎克雷伯菌中超广谱β-内酰胺酶(ESBLs)基因类型及转移方式。方法回顾性分析该院2011年1月至2013年1月收集的460例住院患者菌株的临床资料,并对其ESBLs基因进行分型和研究耐药性。结果460株β-内酰胺酶的KPN检出6种β-内酰胺酶基因,其中bla TEM占总数的5%,bla SHV占总数的20%, bla CTX-M-1群占总数的5%,bla CTX-M-9群占总数的25%,bla OXA-1群占总数的10%,bla DHA 占总数的30%等;本研究共发现322种菌株耐药谱,菌株耐药在9种抗菌药物以上。阿莫西林/替卡西林/头孢噻吩等、阿莫西林/克拉维酸和头孢西丁、哌拉西林/克拉维酸、亚胺培南的耐药性分别为100%、60%、45%、35%和0。结论肺炎克雷伯菌中ESBLs基因类型主要是bla TEM和bla CTX-M-1,并具有较为严重的耐药性。%Objective To study the distribution and transfer of genes of super broad-spectrum β-lactamase (ESBL s) in klebsiella pneumoniae .Methods The information of 460 strains of hospitalized patients who had been treated in our hospital from January 2011 to January 2013 were retrospectively analyzed .Results 460 β-lactamase KPN detected six kinds of β-lactamase gene ,which bla TEM of the total 5% ,bla SHV accounted for 20% ,bla CTX-M-1 group accounted for 5% ,bla CTX-M-9 group accounted for 25% ,bla OXA-1 group accounted for 10% ,bla DHA 30% of the total ,etc .;this study found that 322 strains resistant spectrum ,strains resistant to antibiotics in 9 above .Amoxicillin/ticarcillin/cephalosporin thiophene ,amoxicillin/clavulanic acid ,cefoxitin ,piperacillin/clavulanic acid ,imipenem were 100% ,60% ,45% ,35% and 0 .Conclusion Klebsiella pneumoniae Super spectrum β-lactamase gene type are primarily bla TEM and bla CTX-M-1 ,they have more serious resistance .

  3. The Impact of Photobleaching on Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Marcel von der Haar

    2015-09-01

    Full Text Available DNA-Microarrays have become a potent technology for high-throughput analysis of genetic regulation. However, the wide dynamic range of signal intensities of fluorophore-based microarrays exceeds the dynamic range of a single array scan by far, thus limiting the key benefit of microarray technology: parallelization. The implementation of multi-scan techniques represents a promising approach to overcome these limitations. These techniques are, in turn, limited by the fluorophores’ susceptibility to photobleaching when exposed to the scanner’s laser light. In this paper the photobleaching characteristics of cyanine-3 and cyanine-5 as part of solid state DNA microarrays are studied. The effects of initial fluorophore intensity as well as laser scanner dependent variables such as the photomultiplier tube’s voltage on bleaching and imaging are investigated. The resulting data is used to develop a model capable of simulating the expected degree of signal intensity reduction caused by photobleaching for each fluorophore individually, allowing for the removal of photobleaching-induced, systematic bias in multi-scan procedures. Single-scan applications also benefit as they rely on pre-scans to determine the optimal scanner settings. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the lab-to-lab comparability of microarray experiment results.

  4. Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens

    Directory of Open Access Journals (Sweden)

    Xuejun eMa

    2015-05-01

    Full Text Available A large number of viral and bacterial organisms are responsible for community-acquired pneumonia (CAP which contributes to substantial burden on health management. A new resequencing microarray (RPM-IVDC1 associated with targeted multiplex PCR was recently developed and validated for multiple respiratory viruses detection and discrimination. In this study, we evaluated the capability of RPM-IVDC1 for simultaneous identification of multiple viral and bacterial organisms. The nasopharyngeal aspirates (NPAs of 110 consecutive CAP patients, aged from 1 month to 96 years old, were collected from 5 distinct general hospitals in Beijing during 1-year period. The samples were subjected to the RPM-IVDC1 established protocol as compared to a real-time PCR (qRT-PCR, which was used as standard. The results of virus detection were consistent with those previously described. A total of 37 of Streptococcus pneumoniae, 14 of Haemophilus influenzae, 10 of Mycoplasma pneumoniae, 2 of Klebsiella pneumoniae and 1 of Moraxella catarrhalis were detected by RPM-IVDC1. The sensitivities and specificities were compared with those of qRT-PCR for S. pneumoniae (100%, 100%, respectively, H. influenzae (92.3%, 97.9%, respectively, M. pneumoniae (69.2%, 99.0%, respectively, K. pneumoniae (100%, 100%, respectively and M. catarrhalis (100%, 100%, respectively. Additional 22 of Streptococcus spp., 24 of Haemophilus spp. and 16 of Neisseria spp. were identified. In addition, methicillin-resistant and carbapenemases allele were also found in 9 of Staphylococcus spp. and 1 of K. pneumoniae, respectively. These results demonstrated the capability of RPM-IVDC1 for simultaneous detection of broad-spectrum respiratory pathogens in complex backgrounds and the advantage of accessing to the actual sequences, showing great potential use of epidemic outbreak investigation. The detection results should be carefully interpreted when introducing this technique in the clinical diagnostics.

  5. Consensus Statement : Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

    NARCIS (Netherlands)

    Miller, David T.; Adam, Margaret P.; Aradhya, Swaroop; Biesecker, Leslie G.; Brothman, Arthur R.; Carter, Nigel P.; Church, Deanna M.; Crolla, John A.; Eichler, Evan E.; Epstein, Charles J.; Faucett, W. Andrew; Feuk, Lars; Friedman, Jan M.; Hamosh, Ada; Jackson, Laird; Kaminsky, Erin B.; Kok, Klaas; Krantz, Ian D.; Kuhn, Robert M.; Lee, Charles; Ostell, James M.; Rosenberg, Carla; Scherer, Stephen W.; Spinner, Nancy B.; Stavropoulos, Dimitri J.; Tepperberg, James H.; Thorland, Erik C.; Vermeesch, Joris R.; Waggoner, Darrel J.; Watson, Michael S.; Martin, Christa Lese; Ledbetter, David H.

    2010-01-01

    Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantial

  6. rapmad: Robust analysis of peptide microarray data

    Directory of Open Access Journals (Sweden)

    Rothermel Andrée

    2011-08-01

    Full Text Available Abstract Background Peptide microarrays offer an enormous potential as a screening tool for peptidomics experiments and have recently seen an increased field of application ranging from immunological studies to systems biology. By allowing the parallel analysis of thousands of peptides in a single run they are suitable for high-throughput settings. Since data characteristics of peptide microarrays differ from DNA oligonucleotide microarrays, computational methods need to be tailored to these specifications to allow a robust and automated data analysis. While follow-up experiments can ensure the specificity of results, sensitivity cannot be recovered in later steps. Providing sensitivity is thus a primary goal of data analysis procedures. To this end we created rapmad (Robust Alignment of Peptide MicroArray Data, a novel computational tool implemented in R. Results We evaluated rapmad in antibody reactivity experiments for several thousand peptide spots and compared it to two existing algorithms for the analysis of peptide microarrays. rapmad displays competitive and superior behavior to existing software solutions. Particularly, it shows substantially improved sensitivity for low intensity settings without sacrificing specificity. It thereby contributes to increasing the effectiveness of high throughput screening experiments. Conclusions rapmad allows the robust and sensitive, automated analysis of high-throughput peptide array data. The rapmad R-package as well as the data sets are available from http://www.tron-mz.de/compmed.

  7. 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

  8. 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.

  9. DNA Microarrays in Comparative Genomics and Transcriptomics

    DEFF Research Database (Denmark)

    Willenbrock, Hanni

    2007-01-01

    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...... 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...... of various strains of the bacteria, e.g. Escherichia coli, with regard to genes involved in pathogenesis. Finally, this thesis present results demonstrating that the gene expression level is sequence dependent, that is, it depends on both DNA structure and codon usage bias. Here, microarray data was used...

  10. Finding consistent disease subnetworks across microarray datasets

    Directory of Open Access Journals (Sweden)

    Soh Donny

    2011-11-01

    Full Text Available Abstract Background While contemporary methods of microarray analysis are excellent tools for studying individual microarray datasets, they have a tendency to produce different results from different datasets of the same disease. We aim to solve this reproducibility problem by introducing a technique (SNet. SNet provides both quantitative and descriptive analysis of microarray datasets by identifying specific connected portions of pathways that are significant. We term such portions within pathways as “subnetworks”. Results We tested SNet on independent datasets of several diseases, including childhood ALL, DMD and lung cancer. For each of these diseases, we obtained two independent microarray datasets produced by distinct labs on distinct platforms. In each case, our technique consistently produced almost the same list of significant nontrivial subnetworks from two independent sets of microarray data. The gene-level agreement of these significant subnetworks was between 51.18% to 93.01%. In contrast, when the same pairs of microarray datasets were analysed using GSEA, t-test and SAM, this percentage fell between 2.38% to 28.90% for GSEA, 49.60% tp 73.01% for t-test, and 49.96% to 81.25% for SAM. Furthermore, the genes selected using these existing methods did not form subnetworks of substantial size. Thus it is more probable that the subnetworks selected by our technique can provide the researcher with more descriptive information on the portions of the pathway actually affected by the disease. Conclusions These results clearly demonstrate that our technique generates significant subnetworks and genes that are more consistent and reproducible across datasets compared to the other popular methods available (GSEA, t-test and SAM. The large size of subnetworks which we generate indicates that they are generally more biologically significant (less likely to be spurious. In addition, we have chosen two sample subnetworks and validated them with

  11. 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

  12. Design of a covalently bonded glycosphingolipid microarray

    DEFF Research Database (Denmark)

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

    2012-01-01

    , a monoclonal antibody to sulfatide, Sulph 1; and a polyclonal antiserum reactive to asialo-G(M2)). Preliminary evaluation of the method indicated successful immobilization of the GSLs, and selective binding of test probes. The potential utility of this methodology for designing covalent microarrays......, 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...

  13. 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

  14. Prominent feature selection of microarray data

    Institute of Scientific and Technical Information of China (English)

    Yihui Liu

    2009-01-01

    For wavelet transform, a set of orthogonal wavelet basis aims to detect the localized changing features contained in microarray data. In this research, we investigate the performance of the selected wavelet features based on wavelet detail coefficients at the second level and the third level. The genetic algorithm is performed to optimize wavelet detail coefficients to select the best discriminant features. Exper-iments are carried out on four microarray datasets to evaluate the performance of classification. Experimental results prove that wavelet features optimized from detail coefficients efficiently characterize the differences between normal tissues and cancer tissues.

  15. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  16. 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

    Directory of Open Access Journals (Sweden)

    Dai Yilin

    2012-06-01

    Full Text Available Abstract Background 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. Findings 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. Conclusion 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.

  17. Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays.

    Science.gov (United States)

    Albrecht, Valérie; Chevallier, Anne; Magnone, Virginie; Barbry, Pascal; Vandenbos, Fanny; Bongain, André; Lefebvre, Jean-Claude; Giordanengo, Valérie

    2006-11-01

    Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types. Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities. PMID:16879879

  18. Microarray data mining with visual programming

    OpenAIRE

    Xu, Qikai; Curk, Tomaž; Shaulsky, Gad; Petrovič, Uroš; Bratko, Ivan; Zupan, Blaž; Demšar, Janez; Leban, Gregor

    2005-01-01

    Visual programming offers an intuitive means of combining known analysis and visualization methods into powerful applications. The system presented here enables users who are not programmers to manage microarray and genomic data flow and to customize their analyses by combining common data analysis tools to fit their needs.

  19. Shrinkage covariance matrix approach for microarray data

    Science.gov (United States)

    Karjanto, Suryaefiza; Aripin, Rasimah

    2013-04-01

    Microarray technology was developed for the purpose of monitoring the expression levels of thousands of genes. A microarray data set typically consists of tens of thousands of genes (variables) from just dozens of samples due to various constraints including the high cost of producing microarray chips. As a result, the widely used standard covariance estimator is not appropriate for this purpose. One such technique is the Hotelling's T2 statistic which is a multivariate test statistic for comparing means between two groups. It requires that the number of observations (n) exceeds the number of genes (p) in the set but in microarray studies it is common that n Hotelling's T2 statistic with the shrinkage approach is proposed to estimate the covariance matrix for testing differential gene expression. The performance of this approach is then compared with other commonly used multivariate tests using a widely analysed diabetes data set as illustrations. The results across the methods are consistent, implying that this approach provides an alternative to existing techniques.

  20. Diagnostic Oligonucleotide Microarray Fingerprinting of Bacillus Isolates

    OpenAIRE

    Chandler, Darrell P.; Alferov, Oleg; Chernov, Boris; Daly, Don S; Golova, Julia; Perov, Alexander; Protic, Miroslava; Robison, Richard; Schipma, Matthew; White, Amanda; Willse, Alan

    2006-01-01

    A genome-independent microarray and new statistical techniques were used to genotype Bacillus strains and quantitatively compare DNA fingerprints with the known taxonomy of the genus. A synthetic DNA standard was used to understand process level variability and lead to recommended standard operating procedures for microbial forensics and clinical diagnostics.

  1. Single-species microarrays and comparative transcriptomics.

    Directory of Open Access Journals (Sweden)

    Frédéric J J Chain

    Full Text Available BACKGROUND: Prefabricated expression microarrays are currently available for only a few species but methods have been proposed to extend their application to comparisons between divergent genomes. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that the hybridization intensity of genomic DNA is a poor basis on which to select unbiased probes on Affymetrix expression arrays for studies of comparative transcriptomics, and that doing so produces spurious results. We used the Affymetrix Xenopus laevis microarray to evaluate expression divergence between X. laevis, X. borealis, and their F1 hybrids. When data are analyzed with probes that interrogate only sequences with confirmed identity in both species, we recover results that differ substantially analyses that use genomic DNA hybridizations to select probes. CONCLUSIONS/SIGNIFICANCE: Our findings have implications for the experimental design of comparative expression studies that use single-species microarrays, and for our understanding of divergent expression in hybrid clawed frogs. These findings also highlight important limitations of single-species microarrays for studies of comparative transcriptomics of polyploid species.

  2. Role of Permutations in Significance Analysis of Microarray and Clustering of Significant Microarray Gene list

    Directory of Open Access Journals (Sweden)

    Tejashree Damle

    2012-03-01

    Full Text Available Microarray is the gene expression data that represent gene in different biological states. Methods are needed to determine the significance of these changes while accounting for the enormous number of genes. Significance analysis of microarrays (SAM is a statistical technique for determining whether changes in gene expression are statistically significant. During the SAM procedure permutation of microarray data is considered to observe the changes in the overall expression level of data. With increasing number of permutations false discovery rate for gene set varies. In our work we took microarray data of Normal Glucose Tolerance (NGT, and Diabetes Mellitus (DM Type II. In this paper we proposed the result of permutations during execution of SAM algorithm. The hierarchical clustering is applied for observing expression levels of significant data and visualize it with heat map.

  3. 炎症及炎症耐受模型筛选广谱趋化因子抑制肽%Screening for a Peptide That Inhibits Expression of a Broad-spectrum of Chemokines Using Models of Endotoxin Tolerance and LPS-induced Pro-inflammation

    Institute of Scientific and Technical Information of China (English)

    苏焱; 孙晗笑; 李秀英; 莫雪梅; 张光

    2013-01-01

    The goal of this study was to screen bioactive peptides to identify an efficient antagonist of multiple pro-inflammatory chemokines that inhibits the pathological process of inflammatory diseases.A phage display library was sequentially screened by binding phages.The binding properties of individual phage clones to LPS-activated PBMCs were determined using cell-based ELISAs.The positive clones were selected and determined by chemotaxis assays.A high-activity peptide was determined to inhibit carrageenan-induced paw oedema and formaldehyde-induced arthritis in Wistar rats in vivo.A possible mechanism of inflammation inhibition involving chemokine mRNA by the peptide was determined by analyzing mRNA expression levels of chemokines and tristetraprolin (TTP) by SqRT-PCR.Nineteen phage clones were selected after four rounds of biopanning with a cut-off of 3-fold higher binding to LPS-activated PBMCs than to normal PBMCs.Nine of the phage clones inhibited IL-8,MCP-1,and MIP-1 β production in vitro.Five clones displayed the same peptide(CI-S5)most robustly inhibited the chemotactic activity in vitro and reduced paw oedema and arthritis in Wistar rats in vivo.SqRT-PCR results indicated that mRNA expression of IL-8,MCP-1,and MIP-1 β were reduced and TTP mRNA expression was increased in the CI-S5 treatment group.Our data demonstrate that CI-S5 is a broad-spectrum antagonist of pro-inflammatory chemokines as it enhances the expression of TTP to reduce chemokine mRNA expression.This study provides a basis for the development of new peptide-based therapies for the treatment of inflammatory diseases.%通过减少炎性组织或细胞趋化因子及炎性因子的表达量能将炎症性病理过程抑制在起始阶段.我们通过体外构建人外周血单个核细胞LPS激活的急性炎症模型及内毒素耐受模型,进行噬菌体肽库亲和筛选,ELISA检测与炎性PBMC的结合能力,分泌抑制实验筛选抑制性噬菌体克隆,经趋化抑制、竞争结合

  4. ISOLATION AND IDENTIFICATION OF ROT-CAUSING FUNGI OF WINTER JUJUBE IN STORAGE PERIOD AND SCREENING OF BROAD SPECTRUM ANTAGONIST%冬枣储藏期致腐真菌分离鉴定及广谱拮抗菌株的筛选

    Institute of Scientific and Technical Information of China (English)

    李静琴; 陈亮; 岳贵龙; 蔡静平

    2013-01-01

    Four rot-causing fungi were isolated from the rotten tissues of winter jujube and identified as Rhizomorpha Roth.ex FT, Alternaria tenuissima, Coniothyrium olivaceum and Penicillium expansum. 142 bacteria strains were isolated from different samples by dilution method, and 7 strains with remarkable antagonistic effect against the four rot-causing fungi were screened from the 142 bacteria strains by antagonistic cultivation method, strain LM2303 had the best broad spectrum antagonistic effect, and the inhibition zone widths of strain LM2303 to the four rot-causing fungi were respectively (8.5± 0.5) mm, (8.0± 0.3) mm, (10.3± 0.6) mm and (7.5± 0.9) mm. Based on morphologic observation, physiological-biochemical characteristic analysis and 16S rDNA sequence comparison, strain LM2303 should be Bacillus subtilis. Accordingly, strain LM2303 has significant antagonistic effect against the main rot-causing fungi of winter jujube, thereby laying the foundation for biocontrol of rot-causing fungi on winter jujube during storage.%从不同腐烂病症的冬枣中分离得到致腐真菌4株,经鉴定分别为根菌索菌(Rhizomorpha Roth.ex Fr)、细极链格孢(Alternaria tenuissima)、橄榄色盾壳霉(Coniothyrium olivaceum)、扩展青霉(Penicillium expansum);采用稀释分离法从样品中分离得到细菌菌株142株,采用对峙培养法从中筛选到对4种致腐真菌均具有明显拮抗作用的细菌菌株7株,其中菌株LM2303的广谱拮抗效果最佳,其对上述4种致腐真菌的抑菌带宽度分别为(8.5±0.5) mm、(8.0±0.3)mm、(10.3±0.6) mm和(7.5±0.9) mm;通过形态学观察、生理生化特性分析及16S rDNA序列比对,菌株LM2303应为枯草芽孢杆菌(Bacillus subtilis).菌株LM2303对冬枣主要致腐真菌均具有显著的拮抗作用,为冬枣储藏期致腐真菌生物防控奠定了基础.

  5. A comparative analysis of DNA barcode microarray feature size

    OpenAIRE

    Ammar, Ron; SMITH, ANDREW M.; Heisler, Lawrence E.; Giaever, Guri; Nislow, Corey

    2009-01-01

    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 platfor...

  6. 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

  7. Identifying Fishes through DNA Barcodes and Microarrays

    Science.gov (United States)

    Kochzius, Marc; Seidel, Christian; Antoniou, Aglaia; Botla, Sandeep Kumar; Campo, Daniel; Cariani, Alessia; Vazquez, Eva Garcia; Hauschild, Janet; Hervet, Caroline; Hjörleifsdottir, Sigridur; Hreggvidsson, Gudmundur; Kappel, Kristina; Landi, Monica; Magoulas, Antonios; Marteinsson, Viggo; Nölte, Manfred; Planes, Serge; Tinti, Fausto; Turan, Cemal; Venugopal, Moleyur N.; Weber, Hannes; Blohm, Dietmar

    2010-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID

  8. Identifying Fishes through DNA Barcodes and Microarrays.

    Directory of Open Access Journals (Sweden)

    Marc Kochzius

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  9. Broad Diphotons from Narrow States

    CERN Document Server

    An, Haipeng; Zhang, Yue

    2015-01-01

    ATLAS and CMS have each reported a modest diphoton excess consistent with the decay of a broad resonance at ~ 750 GeV. We show how this signal can arise in a weakly coupled theory comprised solely of narrow width particles. In particular, if the decaying particle is produced off-shell, then the associated diphoton resonance will have a broad, adjustable width. We present simplified models which explain the diphoton excess through the three-body decay of a scalar or fermion. Our minimal ultraviolet completion is a weakly coupled and renormalizable theory of a singlet scalar plus a heavy vector-like quark and lepton. The smoking gun of this mechanism is an asymmetric diphoton peak recoiling against missing transverse energy, jets, or leptons.

  10. Background Adjustment for DNA Microarrays Using a Database of Microarray Experiments

    OpenAIRE

    Sui, Yunxia; Zhao, Xiaoyue; Speed, Terence P.; Wu, Zhijin

    2009-01-01

    DNA microarrays have become an indispensable technique in biomedical research. The raw measurements from microarrays undergo a number of preprocessing steps before the data are converted to the genomic level for further analysis. Background adjustment is an important step in preprocessing. Estimating background noise has been challenging because background levels vary a lot from probe to probe, yet there are limited observations on each probe. Most current methods have used the empirical Baye...

  11. Cochlear microphonic broad tuning curves

    Science.gov (United States)

    Ayat, Mohammad; Teal, Paul D.; Searchfield, Grant D.; Razali, Najwani

    2015-12-01

    It is known that the cochlear microphonic voltage exhibits much broader tuning than does the basilar membrane motion. The most commonly used explanation for this is that when an electrode is inserted at a particular point inside the scala media, the microphonic potentials of neighbouring hair cells have different phases, leading to cancelation at the electrodes location. In situ recording of functioning outer hair cells (OHCs) for investigating this hypothesis is exceptionally difficult. Therefore, to investigate the discrepancy between the tuning curves of the basilar membrane and those of the cochlear microphonic, and the effect of phase cancellation of adjacent hair cells on the broadness of the cochlear microphonic tuning curves, we use an electromechanical model of the cochlea to devise an experiment. We explore the effect of adjacent hair cells (i.e., longitudinal phase cancellation) on the broadness of the cochlear microphonic tuning curves in different locations. The results of the experiment indicate that active longitudinal coupling (i.e., coupling with active adjacent outer hair cells) only slightly changes the broadness of the CM tuning curves. The results also demonstrate that there is a π phase difference between the potentials produced by the hair bundle and the soma near the place associated with the characteristic frequency based on place-frequency maps (i.e., the best place). We suggest that the transversal phase cancellation (caused by the phase difference between the hair bundle and the soma) plays a far more important role than longitudinal phase cancellation in the broadness of the cochlear microphonic tuning curves. Moreover, by increasing the modelled longitudinal resistance resulting the cochlear microphonic curves exhibiting sharper tuning. The results of the simulations suggest that the passive network of the organ of Corti determines the phase difference between the hair bundle and soma, and hence determines the sharpness of the

  12. 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

  13. Identification of the Broad Solar Emission Features Near 117 nm

    CERN Document Server

    Avrett, E H; Loeser, R; Avrett, Eugene H.; Kurucz, Robert L.; Loeser, Rudolf

    2006-01-01

    Wilhelm et al. have recently called attention to the unidentified broad emission features near 117 nm in the solar spectrum. They discuss the observed properties of these features in detail but do not identify the source of this emission. We show that the broad autoionizing transitions of neutral sulfur are responsible for these emission features. Autoionizing lines of \\ion{S}{i} occur throughout the spectrum between Lyman alpha and the Lyman limit. Sulfur is a normal contributor to stellar spectra. We use non-LTE chromospheric model calculations with line data from the Kurucz 2004 \\ion{S}{i} line list to simulate the solar spectrum in the range 116 to 118 nm. We compare the results with SUMER disk-center observations from Curdt et al. and limb observations from Wilhelm et al. Our calculations generally agree with the SUMER observations of the broad autoionizing \\ion{S}{i} emission features, the narrow \\ion{S}{i} emission lines, and the continuum in this wavelength region, and agree with basic characteristics...

  14. Viral diagnosis in Indian livestock using customized microarray chips.

    Science.gov (United States)

    Yadav, Brijesh S; Pokhriyal, Mayank; Ratta, Barkha; Kumar, Ajay; Saxena, Meeta; Sharma, Bhaskar

    2015-01-01

    Viral diagnosis in Indian livestock using customized microarray chips is gaining momentum in recent years. Hence, it is possible to design customized microarray chip for viruses infecting livestock in India. Customized microarray chips identified Bovine herpes virus-1 (BHV-1), Canine Adeno Virus-1 (CAV-1), and Canine Parvo Virus-2 (CPV-2) in clinical samples. Microarray identified specific probes were further confirmed using RT-PCR in all clinical and known samples. Therefore, the application of microarray chips during viral disease outbreaks in Indian livestock is possible where conventional methods are unsuitable. It should be noted that customized application requires a detailed cost efficiency calculation.

  15. 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

  16. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  17. A Gene Expression Barcode for Microarray Data

    OpenAIRE

    Zilliox, Michael J.; Irizarry, Rafael A.

    2007-01-01

    The ability to measure genome-wide expression holds great promise for characterizing cells and distinguishing diseased from normal tissues. Thus far, microarray technology has only been useful for measuring relative expression between two or more samples, which has handicapped its ability to classify tissue types. This paper presents the first method that can successfully predict tissue type based on data from a single hybridization. A preliminary web-tool is available at http://rafalab.jhsph...

  18. Pineal Function: Impact of Microarray Analysis

    OpenAIRE

    Klein, David C.; Bailey, Michael J; Carter, David A.; Kim, Jong-So; Shi, Qiong; Ho, Anthony; Chik, Constance; Gaildrat, Pascaline; Morin, Fabrice; Ganguly, Surajit; Rath, Martin F.; Møller, Morten; Sugden, David; Rangel, Zoila G.; Peter J Munson

    2009-01-01

    Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-hour schedule. This effort has highlighted surprising similarity to the retina and has provided reason to explore new avenues of study including intracellular signaling, signal transduction, transcriptional cascades, thyroid/retinoic acid hormone signaling, metal biology...

  19. Linking microarray reporters with protein functions

    Directory of Open Access Journals (Sweden)

    Gaj Stan

    2007-09-01

    Full Text Available Abstract Background The analysis of microarray experiments requires accurate and up-to-date functional annotation of the microarray reporters to optimize the interpretation of the biological processes involved. Pathway visualization tools are used to connect gene expression data with existing biological pathways by using specific database identifiers that link reporters with elements in the pathways. Results This paper proposes a novel method that aims to improve microarray reporter annotation by BLASTing the original reporter sequences against a species-specific EMBL subset, that was derived from and crosslinked back to the highly curated UniProt database. The resulting alignments were filtered using high quality alignment criteria and further compared with the outcome of a more traditional approach, where reporter sequences were BLASTed against EnsEMBL followed by locating the corresponding protein (UniProt entry for the high quality hits. Combining the results of both methods resulted in successful annotation of > 58% of all reporter sequences with UniProt IDs on two commercial array platforms, increasing the amount of Incyte reporters that could be coupled to Gene Ontology terms from 32.7% to 58.3% and to a local GenMAPP pathway from 9.6% to 16.7%. For Agilent, 35.3% of the total reporters are now linked towards GO nodes and 7.1% on local pathways. Conclusion Our methods increased the annotation quality of microarray reporter sequences and allowed us to visualize more reporters using pathway visualization tools. Even in cases where the original reporter annotation showed the correct description the new identifiers often allowed improved pathway and Gene Ontology linking. These methods are freely available at http://www.bigcat.unimaas.nl/public/publications/Gaj_Annotation/.

  20. Tissue Microarrays for Analysis of Expression Patterns

    OpenAIRE

    Lindskog Bergström, Cecilia

    2013-01-01

    Proteins are essential building blocks in every living cell, and since the complete human genome was sequenced in 2004, researchers have attempted to map the human proteome, which is the functional representation of the genome. One such initiative is the Human Protein Atlas programme (HPA), which generates monospecific antibodies towards all human proteins and uses these for high-throughput tissue profiling on tissue microarrays (TMAs). The results are publically available at the website www....

  1. Metadata Management and Semantics in Microarray Repositories

    Science.gov (United States)

    Kocabaş, F; Can, T; Baykal, N

    2011-01-01

    The number of microarray and other high-throughput experiments on primary repositories keeps increasing as do the size and complexity of the results in response to biomedical investigations. Initiatives have been started on standardization of content, object model, exchange format and ontology. However, there are backlogs and inability to exchange data between microarray repositories, which indicate that there is a great need for a standard format and data management. We have introduced a metadata framework that includes a metadata card and semantic nets that make experimental results visible, understandable and usable. These are encoded in syntax encoding schemes and represented in RDF (Resource Description Frame-word), can be integrated with other metadata cards and semantic nets, and can be exchanged, shared and queried. We demonstrated the performance and potential benefits through a case study on a selected microarray repository. We concluded that the backlogs can be reduced and that exchange of information and asking of knowledge discovery questions can become possible with the use of this metadata framework. PMID:24052712

  2. Microarrays for rapid identification of plant viruses.

    Science.gov (United States)

    Boonham, Neil; Tomlinson, Jenny; Mumford, Rick

    2007-01-01

    Many factors affect the development and application of diagnostic techniques. Plant viruses are an inherently diverse group that, unlike cellular pathogens, possess no nucleotide sequence type (e.g., ribosomal RNA sequences) in common. Detection of plant viruses is becoming more challenging as globalization of trade, particularly in ornamentals, and the potential effects of climate change enhance the movement of viruses and their vectors, transforming the diagnostic landscape. Techniques for assessing seed, other propagation materials and field samples for the presence of specific viruses include biological indexing, electron microscopy, antibody-based detection, including enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and microarray detection. Of these, microarray detection provides the greatest capability for parallel yet specific testing, and can be used to detect individual, or combinations of viruses and, using current approaches, to do so with a sensitivity comparable to ELISA. Methods based on PCR provide the greatest sensitivity among the listed techniques but are limited in parallel detection capability even in "multiplexed" applications. Various aspects of microarray technology, including probe development, array fabrication, assay target preparation, hybridization, washing, scanning, and interpretation are presented and discussed, for both current and developing technology.

  3. Chicken sperm transcriptome profiling by microarray analysis.

    Science.gov (United States)

    Singh, R P; Shafeeque, C M; Sharma, S K; Singh, R; Mohan, J; Sastry, K V H; Saxena, V K; Azeez, P A

    2016-03-01

    It has been confirmed that mammalian sperm contain thousands of functional RNAs, and some of them have vital roles in fertilization and early embryonic development. Therefore, we attempted to characterize transcriptome of the sperm of fertile chickens using microarray analysis. Spermatozoal RNA was pooled from 10 fertile males and used for RNA preparation. Prior to performing the microarray, RNA quality was assessed using a bioanalyzer, and gDNA and somatic cell RNA contamination was assessed by CD4 and PTPRC gene amplification. The chicken sperm transcriptome was cross-examined by analysing sperm and testes RNA on a 4 × 44K chicken array, and results were verified by RT-PCR. Microarray analysis identified 21,639 predominantly nuclear-encoded transcripts in chicken sperm. The majority (66.55%) of the sperm transcripts were shared with the testes, while surprisingly, 33.45% transcripts were detected (raw signal intensity greater than 50) only in the sperm and not in the testes. The greatest proportion of up-regulated transcripts were responsible for signal transduction (63.20%) followed by embryonic development (56.76%) and cell structure (56.25%). Of the 20 most abundant transcripts, 18 remain uncharacterized, whereas the least abundant genes were mostly associated with the ribosome. These findings lay a foundation for more detailed investigations on sperm RNAs in chickens to identify sperm-based biomarkers for fertility.

  4. Integrating data from heterogeneous DNA microarray platforms.

    Science.gov (United States)

    Valente, Eduardo; Rocha, Miguel

    2015-01-01

    DNA microarrays are one of the most used technologies for gene expression measurement. However, there are several distinct microarray platforms, from different manufacturers, each with its own measurement protocol, resulting in data that can hardly be compared or directly integrated. Data integration from multiple sources aims to improve the assertiveness of statistical tests, reducing the data dimensionality problem. The integration of heterogeneous DNA microarray platforms comprehends a set of tasks that range from the re-annotation of the features used on gene expression, to data normalization and batch effect elimination. In this work, a complete methodology for gene expression data integration and application is proposed, which comprehends a transcript-based re-annotation process and several methods for batch effect attenuation. The integrated data will be used to select the best feature set and learning algorithm for a brain tumor classification case study. The integration will consider data from heterogeneous Agilent and Affymetrix platforms, collected from public gene expression databases, such as The Cancer Genome Atlas and Gene Expression Omnibus. PMID:26673932

  5. Expanding the clinical spectrum of the 16p11.2 chromosomal rearrangements: three patients with syringomyelia.

    Science.gov (United States)

    Schaaf, Christian P; Goin-Kochel, Robin P; Nowell, Kerri P; Hunter, Jill V; Aleck, Kirk A; Cox, Sarah; Patel, Ankita; Bacino, Carlos A; Shinawi, Marwan

    2011-02-01

    16p11.2 rearrangements are associated with developmental delay, cognitive impairment, autism spectrum disorder, behavioral problems (especially attention-deficit hyperactivity disorder), seizures, obesity, dysmorphic features, and abnormal head size. In addition, congenital anomalies and abnormal brain findings were frequently observed in patients with these rearrangements. We identified and performed a detailed microarray, phenotypic, and radiological characterization of three new patients with 16p11.2 rearrangements: two deletion patients and one patient with the reciprocal duplication. All patients have a heterozygous loss (deletion) or gain (duplication) corresponding to chromosomal coordinates (chr16: 29 528 190-30 107 184) with a minimal size of 579 kb. The deletion patients had language delay and learning disabilities and one met criteria for pervasive developmental disorder not otherwise specified. The duplication patient received a diagnosis of autism and had academic deficits and behavioral problems. The patients with deletion had long cervicothoracic syringomyelia and the duplication patient had long thoracolumbar syringomyelia. The syringomyelia in one patient with deletion was associated with Chiari malformation. Our findings highlight the broad spectrum of clinical and neurological manifestations in patients with 16p11.2 rearrangements. Our observation suggests that genes (or a single gene) within the implicated interval have significant roles in the pathogenesis of syringomyelia. A more comprehensive and systematic research is warranted to study the frequency and spectrum of malformations in the central nervous system in these patients.

  6. Photoionisation modelling of the broad line region

    Science.gov (United States)

    King, Anthea

    2016-08-01

    Two of the most fundamental questions regarding the broad line region (BLR) are "what is its structure?" and "how is it moving?" Baldwin et al. (1995) showed that by summing over an ensemble of clouds at differing densities and distances from the ionising source we can easily and naturally produce a spectrum similar to what is observed for AGN. This approach is called the `locally optimally emitting clouds' (LOC) model. This approach can also explain the well-observed stratification of emission lines in the BLR (e.g. Clavel et al. 1991, Peterson et al. 1991, Kollatschny et al. 2001) and `breathing' of BLR with changes in the continuum luminosity (Netzer & Mor 1990, Peterson et al. 2014) and is therefore a generally accepted model of the BLR. However, LOC predictions require some assumptions to be made about the distribution of the clouds within the BLR. By comparing photoionization predictions, for a distribution of cloud properties, with observed spectra we can infer something about the structure of the BLR and distribution of clouds. I use existing reverberation mapping data to constrain the structure of the BLR by observing how individual line strengths and ratios of different lines change in high and low luminosity states. I will present my initial constraints and discuss the challenges associated with the method.

  7. Ghost imaging with broad distance

    Institute of Scientific and Technical Information of China (English)

    段德洋; 张路; 杜少将; 夏云杰

    2015-01-01

    We present a scheme that is able to achieve the ghost imaging with broad distance. The physical nature of our scheme is that the different wavelength beams are separated in free space by an optical media according to the slow light or dispersion principle. Meanwhile, the equality of the optical distance of the two light arms is not violated. The photon correlation is achieved by the rotating ground glass plate (RGGP) and spatial light modulator (SLM), respectively. Our work shows that a monochromic ghost image can be obtained in the case of RGGP. More importantly, the position (or distance) of the object can be ascertained by the color of the image. Thus, the imaging and ranging processes are combined as one process for the first time to the best of our knowledge. In the case of SLM, we can obtain a colored image regardless of where the object is.

  8. 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

  9. 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...... technology give "true" representation of physical processes, involved in measurement of RNA abundance. REVIEWERS: This article was reviewed by Yoav Gilad (nominated by Doron Lancet), Sach Mukherjee (nominated by Sandrine Dudoit) and Amir Niknejad and Shmuel Friedland (nominated by Neil Smalheiser)....

  10. Application of broad-spectrum PCR amplification and direct sequencing for identification of the infrequent bacterial cultures from clinical sources, targeting the bacterial 16S rRNA gene with universal primes%基于细菌16S rRNA基因的PCR扩增与测序分析在临床不常见菌鉴定中的应用

    Institute of Scientific and Technical Information of China (English)

    陈茶; 鄂顺梅; 叶金艳; 唐小龙; 蓝锴; 罗强; 戴小波; 袁慧; 屈平华; 顾全; 黄彬; 张伟铮; 穆小萍; 张磊; 陈默蕊; 王露霞

    2012-01-01

    Objectives To identify the infrequent strains in clinical isolates by broad-spectrum PCR amplification and direct sequencing targeting the bacterial 16S rRNA gene.Methods Total 48 clinical isolates and 7 false-positive blood culture samples were collected from 7 different hospitals or institutions from Decemler 2010 to September 201 1.The bacterial 16S rRNA gene were amplified and sequenced by universal prime sets of 27f-1492r and 27f-1525r,and MicroSeq 500 16S rRNA gene kit.The homology analysis was used by the Basic Local Alignment Search Tool,and comparing to gene sequence of the type strain.provided by the List of Prokaryotic names with Standing in Nomenclature.The criteria for the bacterial identification was interpreted according to the Clinical and Laboratory Standards Institute (CLSI) M M 18-A.Results All of the 48 cultured strains were succeeded amplifying and sequencing the targeted 16S rRNA genes.According to the criteria of CLSI MM18-A,total 35 strains were specified to the species level,11 strains were specified to the genus level,and the other 2 strains were specified to possible novel genus and species.Combining the analysis the sequence of other housekeeping gene with the results of biochemical results,total 42 strains can be specified to the species level,including some clinical important pathogens,such as Streptobacillus,Capnocytophaga,Nocardia,Mycobacterium,Roseomonas and Campylobacter.Two false-positive blood culture samples were managed to amplify 16S rRNA genes and finally identified as Streptococcus pneumoniae.We also identified one novel subspecies of Campylobacter fetus,and some new valid-published species,such as Acinetobacter parvus,Mycobacterium phocaicum,Roseomonas mucosa and Halomonas johnsoniae.Conclusions The 16S rRNA gene sequence based identification has unique advantages over the phenotypic methods.It is universal to almost of all the bacteria,and can provide the genetic classified information.It is very suitable for the clinical

  11. Fission Spectrum

    Science.gov (United States)

    Bloch, F.; Staub, H.

    1943-08-18

    Measurements of the spectrum of the fission neutrons of 25 are described, in which the energy of the neutrons is determined from the ionization produced by individual hydrogen recoils. The slow neutrons producing fission are obtained by slowing down the fast neutrons from the Be-D reaction of the Stanford cyclotron. In order to distinguish between fission neutrons and the remaining fast cyclotron neutrons both the cyclotron current and the pusle amplifier are modulated. A hollow neutron container, in which slow neutrons have a lifetime of about 2 milliseconds, avoids the use of large distances. This method results in much higher intensities than the usual modulation arrangement. The results show a continuous distribution of neutrons with a rather wide maximum at about 0.8 MV falling off to half of its maximum value at 2.0 MV. The total number of netrons is determined by comparison with the number of fission fragments. The result seems to indicate that only about 30% of the neutrons have energies below .8 MV. Various tests are described which were performed in order to rule out modification of the spectrum by inelastic scattering. Decl. May 4, 1951

  12. Formation and characterization of DNA microarrays at silicon nitride substrates.

    Science.gov (United States)

    Manning, Mary; Redmond, Gareth

    2005-01-01

    A versatile method for direct, covalent attachment of DNA microarrays at silicon nitride layers, previously deposited by chemical vapor deposition at silicon wafer substrates, is reported. Each microarray fabrication process step, from silicon nitride substrate deposition, surface cleaning, amino-silanation, and attachment of a homobifunctional cross-linking molecule to covalent immobilization of probe oligonucleotides, is defined, characterized, and optimized to yield consistent probe microarray quality, homogeneity, and probe-target hybridization performance. The developed microarray fabrication methodology provides excellent (high signal-to-background ratio) and reproducible responsivity to target oligonucleotide hybridization with a rugged chemical stability that permits exposure of arrays to stringent pre- and posthybridization wash conditions through many sustained cycles of reuse. Overall, the achieved performance features compare very favorably with those of more mature glass based microarrays. It is proposed that this DNA microarray fabrication strategy has the potential to provide a viable route toward the successful realization of future integrated DNA biochips.

  13. 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.

  14. Ghost imaging with broad distance

    Science.gov (United States)

    Duan, De-Yang; Zhang, Lu; Du, Shao-Jiang; Xia, Yun-Jie

    2015-10-01

    We present a scheme that is able to achieve the ghost imaging with broad distance. The physical nature of our scheme is that the different wavelength beams are separated in free space by an optical media according to the slow light or dispersion principle. Meanwhile, the equality of the optical distance of the two light arms is not violated. The photon correlation is achieved by the rotating ground glass plate (RGGP) and spatial light modulator (SLM), respectively. Our work shows that a monochromic ghost image can be obtained in the case of RGGP. More importantly, the position (or distance) of the object can be ascertained by the color of the image. Thus, the imaging and ranging processes are combined as one process for the first time to the best of our knowledge. In the case of SLM, we can obtain a colored image regardless of where the object is. Project supported by the National Natural Science Foundation of China (Grant Nos. 61178012, 11204156, 11304179, and 11247240), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant Nos. 20133705110001 and 20123705120002), the Scientific Research Foundation for Outstanding Young Scientists of Shandong Province, China (Grant No. BS2013DX034), and the Natural Science Foundation of Shandong Province, China (Grant No. ZR2012FQ024).

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

    NARCIS (Netherlands)

    Batchelor, M.; Hopkins, K.L.; Liebana, E.; Slickers, P.; Ehricht, R.; Mafura, M.; Aerestrup, F.; Mevius, D.J.; Clifton-Hadley, F.A.; Woodward, M.; Davies, R.; Threlfall, J.; Anjum, F.M.

    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 ß-lactams, including extended-spectrum ß-lact

  16. Determination of B-Cell Epitopes in Patients with Celiac Disease: Peptide Microarrays.

    Directory of Open Access Journals (Sweden)

    Rok Seon Choung

    Full Text Available Most antibodies recognize conformational or discontinuous epitopes that have a specific 3-dimensional shape; however, determination of discontinuous B-cell epitopes is a major challenge in bioscience. Moreover, the current methods for identifying peptide epitopes often involve laborious, high-cost peptide screening programs. Here, we present a novel microarray method for identifying discontinuous B-cell epitopes in celiac disease (CD by using a silicon-based peptide array and computational methods.Using a novel silicon-based microarray platform with a multi-pillar chip, overlapping 12-mer peptide sequences of all native and deamidated gliadins, which are known to trigger CD, were synthesized in situ and used to identify peptide epitopes.Using a computational algorithm that considered disease specificity of peptide sequences, 2 distinct epitope sets were identified. Further, by combining the most discriminative 3-mer gliadin sequences with randomly interpolated3- or 6-mer peptide sequences, novel discontinuous epitopes were identified and further optimized to maximize disease discrimination. The final discontinuous epitope sets were tested in a confirmatory cohort of CD patients and controls, yielding 99% sensitivity and 100% specificity.These novel sets of epitopes derived from gliadin have a high degree of accuracy in differentiating CD from controls, compared with standard serologic tests. The method of ultra-high-density peptide microarray described here would be broadly useful to develop high-fidelity diagnostic tests and explore pathogenesis.

  17. 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...... of labeled cDNA added to each slide reduces dye-bias and slide to slide variation. Efficient mixing of the hybridization solution throughout the hybridization reaction increases signals several fold. The amount of near perfect target-probe hybrids may be reduced by efficient stringency washes...

  18. Biocompatible polymer microarrays for cellular high-content screening

    OpenAIRE

    Pernagallo, Salvatore

    2010-01-01

    The global aim of this thesis was to study the use of microarray technology for the screening and identification of biocompatible polymers, to understand physiological phenomena, and the design of biomaterials, implant surfaces and tissue-engineering scaffolds. This work was based upon the polymer microarray platform developed by the Bradley group. Polymer microarrays were successfully applied to find the best polymer supports for: (i) mouse fibroblast cells and used to eval...

  19. DNA Microarray Assessment of Putative Borrelia burgdorferi Lipoprotein Genes

    OpenAIRE

    Liang, Fang Ting; Nelson, F. Kenneth; Fikrig, Erol

    2002-01-01

    A DNA microarray containing fragments of 137 Borrelia burgdorferi B31 putative lipoprotein genes was used to examine Lyme disease spirochetes. DNA from B. burgdorferi sensu stricto B31, 297, and N40; Borrelia garinii IP90; and Borrelia afzelii P/Gau was fluorescently labeled and hybridized to the microarray, demonstrating the degree to which the individual putative lipoprotein genes were conserved among the genospecies. These data show that a DNA microarray can globally examine the genes enco...

  20. Miniaturised Spotter-Compatible Multicapillary Stamping Tool for Microarray Printing

    CERN Document Server

    Drobyshev, A L; Zasedatelev, A S; Drobyshev, Alexei L; Verkhodanov, Nikolai N; Zasedatelev, Alexander S

    2007-01-01

    Novel microstamping tool for microarray printing is proposed. The tool is capable to spot up to 127 droplets of different solutions in single touch. It is easily compatible with commercially available microarray spotters. The tool is based on multichannel funnel with polypropylene capillaries inserted into its channels. Superior flexibility is achieved by ability to replace any printing capillary of the tool. As a practical implementation, hydrogel-based microarrays were stamped and successfully applied to identify the Mycobacterium tuberculosis drug resistance.

  1. Novel R pipeline for analyzing biolog phenotypic microarray data.

    OpenAIRE

    Minna Vehkala; Mikhail Shubin; Connor, Thomas R; Thomson, Nicholas R.; Jukka Corander

    2015-01-01

    Data produced by Biolog Phenotype MicroArrays are longitudinal measurements of cells' respiration on distinct substrates. We introduce a three-step pipeline to analyze phenotypic microarray data with novel procedures for grouping, normalization and effect identification. Grouping and normalization are standard problems in the analysis of phenotype microarrays defined as categorizing bacterial responses into active and non-active, and removing systematic errors from the experimental data, resp...

  2. A comparative analysis of DNA barcode microarray feature size

    OpenAIRE

    Smith Andrew M; Ammar Ron; Heisler Lawrence E; Giaever Guri; Nislow Corey

    2009-01-01

    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 microarra...

  3. Innovative DNA microarray design for bacterial flora composition evaluation

    OpenAIRE

    Huyghe, Antoine

    2009-01-01

    During the past decade, the advent of new molecular techniques has led to enormous progress in biology, notably with the development of DNA microarray technology. This technology allows monitoring simultaneously the expression of thousands of genes from a given organism. DNA microarrays have been used in a variety of applications, including the characterization of bacteria in biological samples. In this thesis, two distinct DNA microarray approaches for the characterization of bacterial flora...

  4. Chemiluminescence microarrays in analytical chemistry: a critical review.

    Science.gov (United States)

    Seidel, Michael; Niessner, Reinhard

    2014-09-01

    Multi-analyte immunoassays on microarrays and on multiplex DNA microarrays have been described for quantitative analysis of small organic molecules (e.g., antibiotics, drugs of abuse, small molecule toxins), proteins (e.g., antibodies or protein toxins), and microorganisms, viruses, and eukaryotic cells. In analytical chemistry, multi-analyte detection by use of analytical microarrays has become an innovative research topic because of the possibility of generating several sets of quantitative data for different analyte classes in a short time. Chemiluminescence (CL) microarrays are powerful tools for rapid multiplex analysis of complex matrices. A wide range of applications for CL microarrays is described in the literature dealing with analytical microarrays. The motivation for this review is to summarize the current state of CL-based analytical microarrays. Combining analysis of different compound classes on CL microarrays reduces analysis time, cost of reagents, and use of laboratory space. Applications are discussed, with examples from food safety, water safety, environmental monitoring, diagnostics, forensics, toxicology, and biosecurity. The potential and limitations of research on multiplex analysis by use of CL microarrays are discussed in this review.

  5. Spectrum war

    DEFF Research Database (Denmark)

    Henten, Anders; Tadayoni, Reza; Windekilde, Iwona Maria

    The digital dividend discussion represents an obvious conflict of interest between on the one hand the traditional broadcasters and market players from other mobile communication sectors and on the other hand between the stake holders within the mobile communication sector. The first one being...... communications sector, including commercial mobile operators and the stake holders representing specific uses like Public Safety and Emergency (PSE), Intelligent Traffic System (ITS), etc in getting access to these resources. The paper gives an analysis of the digital dividend and discusses relevant new...... a conflict in accessing to the valuable spectrum resources allocated to TV broadcast that has been there for many years and which has been intensified in different phases of technological development and the second being an obvious conflict of interest between the different stake holders within the mobile...

  6. 78 FR 20119 - Broad Stakeholder Survey

    Science.gov (United States)

    2013-04-03

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 30-day... soliciting comments concerning the Broad Stakeholder Survey. DHS previously published this ICR in the Federal... responders across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on...

  7. 77 FR 50144 - Broad Stakeholder Survey

    Science.gov (United States)

    2012-08-20

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 60-day... comments concerning the Broad Stakeholder Survey. DATES: Comments are encouraged and will be accepted until... across the Nation. The Broad Stakeholder Survey is designed to gather stakeholder feedback on...

  8. 76 FR 34087 - Broad Stakeholder Survey

    Science.gov (United States)

    2011-06-10

    ... SECURITY Broad Stakeholder Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 60-day... comments concerning the Broad Stakeholder Survey. DATES: Comments are encouraged and will be accepted until.... The Broad Stakeholder Survey is designed to gather stakeholder feedback on the effectiveness of...

  9. Intensity-based segmentation of microarray images.

    Science.gov (United States)

    Nagarajan, Radhakrishnan

    2003-07-01

    The underlying principle in microarray image analysis is that the spot intensity is a measure of the gene expression. This implicitly assumes the gene expression of a spot to be governed entirely by the distribution of the pixel intensities. Thus, a segmentation technique based on the distribution of the pixel intensities is appropriate for the current problem. In this paper, clustering-based segmentation is described to extract the target intensity of the spots. The approximate boundaries of the spots in the microarray are determined by manual adjustment of rectilinear grids. The distribution of the pixel intensity in a grid containing a spot is assumed to be the superposition of the foreground and the local background. The k-means clustering technique and the partitioning around medoids (PAM) were used to generate a binary partition of the pixel intensity distribution. The median (k-means) and the medoid (PAM) of the cluster members are chosen as the cluster representatives. The effectiveness of the clustering-based segmentation techniques was tested on publicly available arrays generated in a lipid metabolism experiment (Callow et al., 2000). The results are compared against those obtained using the region-growing approach (SPOT) (Yang et al., 2001). The effect of additive white Gaussian noise is also investigated. PMID:12906242

  10. Microarray analysis of the developing cortex.

    Science.gov (United States)

    Semeralul, Mawahib O; Boutros, Paul C; Likhodi, Olga; Okey, Allan B; Van Tol, Hubert H M; Wong, Albert H C

    2006-12-01

    Abnormal development of the prefrontal cortex (PFC) is associated with a number of neuropsychiatric disorders that have an onset in childhood or adolescence. Although the basic laminar structure of the PFC is established in utero, extensive remodeling continues into adolescence. To map the overall pattern of changes in cortical gene transcripts during postnatal development, we made serial measurements of mRNA levels in mouse PFC using oligonucleotide microarrays. We observed changes in mRNA transcripts consistent with known postnatal morphological and biochemical events. Overall, most transcripts that changed significantly showed a progressive decrease in abundance after birth, with the majority of change between postnatal weeks 2 and 4. Genes with cell proliferative, cytoskeletal, extracellular matrix, plasma membrane lipid/transport, protein folding, and regulatory functions had decreases in mRNA levels. Quantitative PCR verified the microarray results for six selected genes: DNA methyltransferase 3A (Dnmt3a), procollagen, type III, alpha 1 (Col3a1), solute carrier family 16 (monocarboxylic acid transporters), member 1 (Slc16a1), MARCKS-like 1 (Marcksl1), nidogen 1 (Nid1) and 3-hydroxybutyrate dehydrogenase (heart, mitochondrial) (Bdh).

  11. 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.

  12. 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

  13. Spectral Decomposition of Broad-Line AGNs and Host Galaxies

    CERN Document Server

    Vanden Berk, Daniel E; Yip, C W; Schneider, D P; Connolly, A J; Burton, R E; Jester, S; Hall, P B; Szalay, A S; Brinkmann, J; Berk, Daniel E. Vanden; Shen, Jiajian; Yip, Ching-Wa; Schneider, Donald P.; Connolly, Andrew J.; Burton, Ross E.; Jester, Sebastian; Hall, Patrick B.; Szalay, Alex S.; Brinkmann, John

    2005-01-01

    Using an eigenspectrum decomposition technique, we separate the host galaxy from the broad line active galactic nucleus (AGN) in a set of 4666 spectra from the Sloan Digital Sky Survey (SDSS), from redshifts near zero up to about 0.75. The decomposition technique uses separate sets of galaxy and quasar eigenspectra to efficiently and reliably separate the AGN and host spectroscopic components. The technique accurately reproduces the host galaxy spectrum, its contributing fraction, and its classification. We show how the accuracy of the decomposition depends upon S/N, host galaxy fraction, and the galaxy class. Based on the eigencoefficients, the sample of SDSS broad-line AGN host galaxies spans a wide range of spectral types, but the distribution differs significantly from inactive galaxies. In particular, post-starburst activity appears to be much more common among AGN host galaxies. The luminosities of the hosts are much higher than expected for normal early-type galaxies, and their colors become increasing...

  14. Mining microarray datasets aided by knowledge stored in literature

    NARCIS (Netherlands)

    R. Jelier (Rob); G.W. Jenster (Guido); L.C.J. Dorssers (Lambert); E.M. van Mulligen (Erik); B. Mons (Barend); J.A. Kors (Jan)

    2003-01-01

    textabstractDNA microarray technology produces large amounts of data. For data mining of these datasets, background information on genes can be helpful. Unfortunately most information is stored in free text. Here, we present an approach to use this information for DNA microarray da

  15. 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.

  16. Near-optimal designs for dual channel microarray studies

    NARCIS (Netherlands)

    Wit, Ernst; Nobile, Agostino; Khanin, Raya

    2005-01-01

    Much biological and medical research employs microarray studies to monitor gene expression levels across a wide range of organisms and under many experimental conditions. Dual channel microarrays are a common platform and allow two samples to be measured simultaneously. A frequently used design uses

  17. Defining best practice for microarray analyses in nutrigenomic studies

    NARCIS (Netherlands)

    Garosi, P.; Filippo, C. de; Erk, M. van; Rocca-Serra, P.; Sansone, S.A.; Elliott, R.

    2005-01-01

    Microarrays represent a powerful tool for studies of diet-gene interactions. Their use is, however, associated with a number of technical challenges and potential pitfalls. The cost of microarrays continues to drop but is still comparatively high. This, coupled with the complex logistical issues ass

  18. 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...

  19. Mathematical design of prokaryotic clone-based microarrays

    NARCIS (Netherlands)

    Pieterse, B.; Quirijns, E.J.; Schuren, F.H.J.; Werf, M.J. van der

    2005-01-01

    Background: Clone-based microarrays, on which each spot represents a random genomic fragment, are a good alternative to open reading frame-based microarrays, especially for microorganisms for which the complete genome sequence is not available. Since the generation of a genomic DNA library is a rand

  20. Hyperactivity of the Ero1α Oxidase Elicits Endoplasmic Reticulum Stress but No Broad Antioxidant Response

    DEFF Research Database (Denmark)

    Hansen, Henning Gram; Schmidt, Jonas Damgard; Soltoft, Cecilie Lutzen;

    2012-01-01

    Oxidizing equivalents for the process of oxidative protein folding in the endoplasmic reticulum (ER) of mammalian cells are mainly provided by the Ero1α oxidase. The molecular mechanisms that regulate Ero1α activity in order to harness its oxidative power are quite well understood. However...... are compromised. Using microarray analysis, we demonstrate that the cell reacts to the oxidative challenge caused by Ero1α hyperactivity by turning on the UPR. Moreover, this analysis allowed the identification of two new targets of the mammalian UPR, CRELD1 and c18orf45. Interestingly, a broad antioxidant...

  1. cDNA microarray screening in food safety

    International Nuclear Information System (INIS)

    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

  2. DNA microarray-based mutation discovery and genotyping.

    Science.gov (United States)

    Gresham, David

    2011-01-01

    DNA microarrays provide an efficient means of identifying single-nucleotide polymorphisms (SNPs) in DNA samples and characterizing their frequencies in individual and mixed samples. We have studied the parameters that determine the sensitivity of DNA probes to SNPs and found that the melting temperature (T (m)) of the probe is the primary determinant of probe sensitivity. An isothermal-melting temperature DNA microarray design, in which the T (m) of all probes is tightly distributed, can be implemented by varying the length of DNA probes within a single DNA microarray. I describe guidelines for designing isothermal-melting temperature DNA microarrays and protocols for labeling and hybridizing DNA samples to DNA microarrays for SNP discovery, genotyping, and quantitative determination of allele frequencies in mixed samples.

  3. 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...

  4. 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.

  5. Digital microarray analysis for digital artifact genomics

    Science.gov (United States)

    Jaenisch, Holger; Handley, James; Williams, Deborah

    2013-06-01

    We implement a Spatial Voting (SV) based analogy of microarray analysis for digital gene marker identification in malware code sections. We examine a famous set of malware formally analyzed by Mandiant and code named Advanced Persistent Threat (APT1). APT1 is a Chinese organization formed with specific intent to infiltrate and exploit US resources. Manidant provided a detailed behavior and sting analysis report for the 288 malware samples available. We performed an independent analysis using a new alternative to the traditional dynamic analysis and static analysis we call Spatial Analysis (SA). We perform unsupervised SA on the APT1 originating malware code sections and report our findings. We also show the results of SA performed on some members of the families associated by Manidant. We conclude that SV based SA is a practical fast alternative to dynamics analysis and static analysis.

  6. Differential splicing using whole-transcript microarrays

    Directory of Open Access Journals (Sweden)

    Robinson Mark D

    2009-05-01

    Full Text Available Abstract Background The latest generation of Affymetrix microarrays are designed to interrogate expression over the entire length of every locus, thus giving the opportunity to study alternative splicing genome-wide. The Exon 1.0 ST (sense target platform, with versions for Human, Mouse and Rat, is designed primarily to probe every known or predicted exon. The smaller Gene 1.0 ST array is designed as an expression microarray but still interrogates expression with probes along the full length of each well-characterized transcript. We explore the possibility of using the Gene 1.0 ST platform to identify differential splicing events. Results We propose a strategy to score differential splicing by using the auxiliary information from fitting the statistical model, RMA (robust multichip analysis. RMA partitions the probe-level data into probe effects and expression levels, operating robustly so that if a small number of probes behave differently than the rest, they are downweighted in the fitting step. We argue that adjacent poorly fitting probes for a given sample can be evidence of differential splicing and have designed a statistic to search for this behaviour. Using a public tissue panel dataset, we show many examples of tissue-specific alternative splicing. Furthermore, we show that evidence for putative alternative splicing has a strong correspondence between the Gene 1.0 ST and Exon 1.0 ST platforms. Conclusion We propose a new approach, FIRMAGene, to search for differentially spliced genes using the Gene 1.0 ST platform. Such an analysis complements the search for differential expression. We validate the method by illustrating several known examples and we note some of the challenges in interpreting the probe-level data. Software implementing our methods is freely available as an R package.

  7. Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (Review)

    OpenAIRE

    MÖHLER, HANS; PFIRMAN, ROLF W.; Frei, Karl

    2014-01-01

    Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the...

  8. 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.

  9. Microarray-based sketches of the HERV transcriptome landscape.

    Science.gov (United States)

    Pérot, Philippe; Mugnier, Nathalie; Montgiraud, Cécile; Gimenez, Juliette; Jaillard, Magali; Bonnaud, Bertrand; Mallet, François

    2012-01-01

    Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA) and revealed that (i) autonomous active LTRs are broadly subjected to operational determinism (ii) the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii) the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects.

  10. Microarray-based sketches of the HERV transcriptome landscape.

    Directory of Open Access Journals (Sweden)

    Philippe Pérot

    Full Text Available Human endogenous retroviruses (HERVs are spread throughout the genome and their long terminal repeats (LTRs constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA and revealed that (i autonomous active LTRs are broadly subjected to operational determinism (ii the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects.

  11. DISCOVERY OF THE TRANSITION OF A MINI-BROAD ABSORPTION LINE INTO A BROAD ABSORPTION LINE IN THE SDSS QUASAR J115122.14+020426.3

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, Paola Rodriguez; Eracleous, Michael; Charlton, Jane [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Hamann, Fred [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Murphy, Michael T. [Center for Astrophysics and Supercomputing, Swinburne University of Technology, P.O. Box 218, Hawthorn, Victoria 3122 (Australia); Nestor, Daniel [Department of Physics and Astronomy, University of California, 430 Portola Plaza, Box 951547, Los Angeles, CA 90095 (United States)

    2013-09-20

    We present the detection of a rare case of dramatic strengthening in the UV absorption profiles in the spectrum of the quasar J115122.14+020426.3 between observations {approx}2.86 yr apart in the quasar rest frame. A spectrum obtained in 2001 by the Sloan Digital Sky Survey shows a C IV ''mini-broad'' absorption line (FWHM = 1220 km s{sup -1}) with a maximum blueshift velocity of {approx}9520 km s{sup -1}, while a later spectrum from the Very Large Telescope shows a significantly broader and stronger absorption line, with a maximum blueshift velocity of {approx}12, 240 km s{sup -1} that qualifies as a broad absorption line. A similar variability pattern is observed in two additional systems at lower blueshifted velocities and in the Ly{alpha} and N V transitions as well. One of the absorption systems appears to be resolved and shows evidence for partial covering of the quasar continuum source (C{sub f} {approx} 0.65), indicating a transverse absorber size of, at least, {approx}6 Multiplication-Sign 10{sup 16} cm. In contrast, a cluster of narrower C IV lines appears to originate in gas that fully covers the continuum and broad emission line sources. There is no evidence for changes in the centroid velocity of the absorption troughs. This case suggests that at least some of the absorbers that produce ''mini-broad'' and broad absorption lines in quasar spectra do not belong to intrinsically separate classes. Here, the ''mini-broad'' absorption line is most likely interpreted as an intermediate phase before the appearance of a broad absorption line due to their similar velocities. While the current observations do not provide enough constraints to discern among the possible causes for this variability, future monitoring of multiple transitions at high resolution will help achieve this goal.

  12. Microarray Bioinformatics and Applications in Oncology

    NARCIS (Netherlands)

    J.K. Peeters (Justine Kate)

    2008-01-01

    textabstractBioinformatics’ is one of the newest fields of biological research, and should be viewed broadly as the use of mathematical, statistical, and computational methods for the processing and analysis of biologic data [1]. Over the last decade, the rapid growth of information and technology i

  13. A graph spectrum based geometric biclustering algorithm.

    Science.gov (United States)

    Wang, Doris Z; Yan, Hong

    2013-01-21

    Biclustering is capable of performing simultaneous clustering on two dimensions of a data matrix and has many applications in pattern classification. For example, in microarray experiments, a subset of genes is co-expressed in a subset of conditions, and biclustering algorithms can be used to detect the coherent patterns in the data for further analysis of function. In this paper, we present a graph spectrum based geometric biclustering (GSGBC) algorithm. In the geometrical view, biclusters can be seen as different linear geometrical patterns in high dimensional spaces. Based on this, the modified Hough transform is used to find the Hough vector (HV) corresponding to sub-bicluster patterns in 2D spaces. A graph can be built regarding each HV as a node. The graph spectrum is utilized to identify the eigengroups in which the sub-biclusters are grouped naturally to produce larger biclusters. Through a comparative study, we find that the GSGBC achieves as good a result as GBC and outperforms other kinds of biclustering algorithms. Also, compared with the original geometrical biclustering algorithm, it reduces the computing time complexity significantly. We also show that biologically meaningful biclusters can be identified by our method from real microarray gene expression data. PMID:23079285

  14. 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.

  15. A perspective on microarrays: current applications, pitfalls, and potential uses

    Directory of Open Access Journals (Sweden)

    Betenbaugh Michael

    2007-01-01

    Full Text Available Abstract With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.

  16. 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…

  17. AFM 4.0: a toolbox for DNA microarray analysis

    OpenAIRE

    Breitkreutz, Bobby-Joe; Jorgensen, Paul; Breitkreutz, Ashton; Tyers, Mike

    2001-01-01

    We have developed a series of programs, collectively packaged as Array File Maker 4.0 (AFM), that manipulate and manage DNA microarray data. AFM 4.0 is simple to use, applicable to any organism or microarray, and operates within the familiar confines of Microsoft Excel. Given a database of expression ratios, AFM 4.0 generates input files for clustering, helps prepare colored figures and Venn diagrams, and can uncover aneuploidy in yeast microarray data. AFM 4.0 should be especially useful to ...

  18. Towards standardization of microarray-based genotyping of Salmonella

    DEFF Research Database (Denmark)

    Löfström, Charlotta; Grønlund, Hugo Ahlm; Riber, Leise;

    2010-01-01

    Genotyping is becoming an increasingly important tool to improve risk assessments of Salmonella. DNA microarray technology is a promising diagnostic tool that can provide high resolution genomic profile of many genes simultaneously. However, standardization of DNA microarray analysis is needed...... of Salmonella at two different laboratories. The low-density array contained 281 of 57-60-mer oligonucleotide probes for detecting a wide range of specific genomic markers associated with antibiotic resistance, cell envelope structures, mobile genetic elements and pathogenicity. Several test parameters...... for a decentralized and simple-to-implement DNA microarray as part of a pan-European source-attribution model for risk assessment of Salmonella....

  19. Imaging combined autoimmune and infectious disease microarrays

    Science.gov (United States)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark

    2006-09-01

    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

  20. SAMMD: Staphylococcus aureus Microarray Meta-Database

    Directory of Open Access Journals (Sweden)

    Elasri Mohamed O

    2007-10-01

    Full Text Available Abstract Background Staphylococcus aureus is an important human pathogen, causing a wide variety of diseases ranging from superficial skin infections to severe life threatening infections. S. aureus is one of the leading causes of nosocomial infections. Its ability to resist multiple antibiotics poses a growing public health problem. In order to understand the mechanism of pathogenesis of S. aureus, several global expression profiles have been developed. These transcriptional profiles included regulatory mutants of S. aureus and growth of wild type under different growth conditions. The abundance of these profiles has generated a large amount of data without a uniform annotation system to comprehensively examine them. We report the development of the Staphylococcus aureus Microarray meta-database (SAMMD which includes data from all the published transcriptional profiles. SAMMD is a web-accessible database that helps users to perform a variety of analysis against and within the existing transcriptional profiles. Description SAMMD is a relational database that uses MySQL as the back end and PHP/JavaScript/DHTML as the front end. The database is normalized and consists of five tables, which holds information about gene annotations, regulated gene lists, experimental details, references, and other details. SAMMD data is collected from the peer-reviewed published articles. Data extraction and conversion was done using perl scripts while data entry was done through phpMyAdmin tool. The database is accessible via a web interface that contains several features such as a simple search by ORF ID, gene name, gene product name, advanced search using gene lists, comparing among datasets, browsing, downloading, statistics, and help. The database is licensed under General Public License (GPL. Conclusion SAMMD is hosted and available at http://www.bioinformatics.org/sammd/. Currently there are over 9500 entries for regulated genes, from 67 microarray

  1. 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.

  2. Robust Model Selection for Classification of Microarrays

    Directory of Open Access Journals (Sweden)

    Ikumi Suzuki

    2009-01-01

    Full Text Available Recently, microarray-based cancer diagnosis systems have been increasingly investigated. However, cost reduction and reliability assurance of such diagnosis systems are still remaining problems in real clinical scenes. To reduce the cost, we need a supervised classifier involving the smallest number of genes, as long as the classifier is sufficiently reliable. To achieve a reliable classifier, we should assess candidate classifiers and select the best one. In the selection process of the best classifier, however, the assessment criterion must involve large variance because of limited number of samples and non-negligible observation noise. Therefore, even if a classifier with a very small number of genes exhibited the smallest leave-one-out cross-validation (LOO error rate, it would not necessarily be reliable because classifiers based on a small number of genes tend to show large variance. We propose a robust model selection criterion, the min-max criterion, based on a resampling bootstrap simulation to assess the variance of estimation of classification error rates. We applied our assessment framework to four published real gene expression datasets and one synthetic dataset. We found that a state- of-the-art procedure, weighted voting classifiers with LOO criterion, had a non-negligible risk of selecting extremely poor classifiers and, on the other hand, that the new min-max criterion could eliminate that risk. These finding suggests that our criterion presents a safer procedure to design a practical cancer diagnosis system.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. A measurement error model for microarray data analysis

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yiming; CHENG Jing

    2005-01-01

    Microarray technology has been widely used to analyze the gene expression levels by detecting fluorescence intensity in a high throughput fashion. However, since the measurement error produced from various sources in microarray experiments is heterogeneous and too large to be ignored, we propose here a measurement error model for microarray data processing, by which the standard deviation of the measurement error is demonstrated to be linearly increased with fluorescence intensity. A robust algorithm, which estimates the parameters of the measurement error model from a single microarray without replicated spots, is provided. The model and algorithm for estimating of the parameters from a given data set are tested on both the real data set and the simulated data set, and the result has been proven satisfactory. And, combining the measurement error model with traditional Z-test method, a full statistical model has been developed. It can significantly improve the statistical inference for identifying differentially expressed genes.

  8. Investigation into the interchangeability of generic formulations using immunosuppressants and a broad selection of medicines

    NARCIS (Netherlands)

    Yu, Y.; Teerenstra, S.; Neef, C.; Burger, D.M.; Maliepaard, M.

    2015-01-01

    PURPOSE: To date, the interchangeability of generic drugs has only been investigated for a limited number of medicines. The objective of this study was to investigate generic-generic drug interchangeability in a large subset of generic formulations in order to cover a broad spectrum of drugs. METHOD

  9. Feature extraction and signal processing for nylon DNA microarrays

    OpenAIRE

    Bertucci F; Loï L; Bourgeois A.; Loriod B; Rougemont J; Lopez F; Hingamp P; Houlgatte R; Granjeaud S

    2004-01-01

    Abstract Background High-density DNA microarrays require automatic feature extraction methodologies and softwares. These can be a potential source of non-reproducibility of gene expression measurements. Variation in feature location or in signal integration methodology may be a significant contribution to the observed variance in gene expression levels. Results We explore sources of variability in feature extraction from DNA microarrays on Nylon membrane with radioactive detection. We introdu...

  10. Emerging Use of Gene Expression Microarrays in Plant Physiology

    OpenAIRE

    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 e...

  11. DNA Microarray Data Analysis: A Novel Biclustering Algorithm Approach

    OpenAIRE

    Tewfik Ahmed H; Tchagang Alain B

    2006-01-01

    Biclustering algorithms refer to a distinct class of clustering algorithms that perform simultaneous row-column clustering. Biclustering problems arise in DNA microarray data analysis, collaborative filtering, market research, information retrieval, text mining, electoral trends, exchange analysis, and so forth. When dealing with DNA microarray experimental data for example, the goal of biclustering algorithms is to find submatrices, that is, subgroups of genes and subgroups of conditions, w...

  12. Biclustering of microarray data with MOSPO based on crowding distance

    OpenAIRE

    Liu, Junwan; Li, Zhoujun; Hu, Xiaohua; Chen, Yiming

    2009-01-01

    Background High-throughput microarray technologies have generated and accumulated massive amounts of gene expression datasets that contain expression levels of thousands of genes under hundreds of different experimental conditions. The microarray datasets are usually presented in 2D matrices, where rows represent genes and columns represent experimental conditions. The analysis of such datasets can discover local structures composed by sets of genes that show coherent expression patterns unde...

  13. Microarrays meet the Voltaire challenge: Drug discovery on a chip?

    Science.gov (United States)

    Jackson, David B; Stein, Martin A; Merino, Alejandro; Eils, Roland

    2006-01-01

    The co-emergence of microarray technologies with systems oriented approaches to discovery is testament to the technological and conceptual advancements of recent years. By providing a platform for massively parallelized reductionism, microarrays are enabling us to examine the functional features of diverse classes of bio-system components in a contextually meaningful manner. Yet, to provide economic impact, future development of these technologies demands intimate alignment with the goal of producing safer and more efficacious drugs.: PMID:24980402

  14. Cluster stability scores for microarray data in cancer studies

    OpenAIRE

    Ghosh Debashis; Smolkin Mark

    2003-01-01

    Abstract Background A potential benefit of profiling of tissue samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Hierarchical clustering has been the primary analytical tool used to define disease subtypes from microarray experiments in cancer settings. Assessing cluster reliability poses a major complication in analyzing output from clustering procedures. While most work has focused on estimating the number of clusters in a dataset, t...

  15. High performance protein microarrays based on glycidyl methacrylate-modified polyethylene terephthalate plastic substrate.

    Science.gov (United States)

    Liu, Yingshuai; Li, Chang Ming; Hu, Weihua; Lu, Zhisong

    2009-01-15

    There is a great challenge to immobilize high density of probe molecules for high performance protein microarrays, and this is achieved in this work by using polyethylene terephthalate (PET) plastic substrate onto which glycidyl methacrylate (GMA) photopolymer is grafted under mild conditions to introduce high density of epoxy groups for covalent immobilization of proteins. The poly(GMA)-grafted PET (PGMA-PET) surface was characterized with atomic force microscope (AFM) and attenuated total reflectance Fourier transform infra-red (ATR-FTIR) spectroscopy. For high density of protein immobilization and good quality of microspots, experiments were conducted to optimize the printing buffer, and an optimal buffer was found out to be PBS with 10% glycerol+0.003% triton X-100. According to the studies of loading capacity and immobilization kinetics, the optimal protein probe concentration and incubation time for the efficient immobilization are 200 microg mL(-1) and 8h, respectively. The performance of the PGMA-PET-based protein microarrays is evaluated with sandwich immunoassay using rat IgG and anti-rat IgG as model proteins, demonstrating a limit of detection (LOD) of 10 pg mL(-1) and a dynamic range of five orders of magnitude which are better than or very comparable with the reported or commercially available immunoassays, while providing a high-throughput approach. The work renders a simple and economic method to manufacture high performance protein microarrays and is expected to have great potentials in broad applications related to clinic diagnosis, drug discovery and proteomic research. PMID:19064107

  16. 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.

  17. 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.

  18. AN INTELLIGENT SEGMENTATION ALGORITHM FOR MICROARRAY IMAGE PROCESSING

    Directory of Open Access Journals (Sweden)

    P.Rajkumar

    2013-06-01

    Full Text Available Microarray technology consists of an array of thousands of microscopic spots of DNA oligonucleotides attached to a solid surface. It is a very powerful technique for analyzing gene expressions as well as to explore the underlying genetic causes of many human diseases. There are numerous applications of this technology, including environmental health research, drug design and discovery, clinical diagnosis and treatment and in cancer detection. The spots, which represent genes in microarray experiment contains the quantitative information that needs to be extracted accurately. For this process, preprocessing of microarray plays an essential role and it is also influential in future steps of the analysis. The three microarray preprocessing steps include gridding, segmentation and quantification. The first step is gridding, refers to the identification of the centre coordinates of each spot. The second step is segmentation, refers to the process of separating foreground and background fluorescence intensities. Segmentation is very important step as it directly affects the accuracy of gene expression analysis in the data mining process that follows. Accurate segmentation is one of the vital steps in microarray image processing. A novel method for segmentation of microarray image is proposed which accurately segment the spots from background when compared with adaptive threshold, combined global and local thresholdand fuzzy c-means clustering methods. Experimental results show that our proposed method provides better segmentation and improved intensity values than the above existing methods.

  19. Inferring gene regulatory networks from asynchronous microarray data with AIRnet

    Directory of Open Access Journals (Sweden)

    Lai Chun Wan J

    2010-11-01

    Full Text Available Abstract Background Modern approaches to treating genetic disorders, cancers and even epidemics rely on a detailed understanding of the underlying gene signaling network. Previous work has used time series microarray data to infer gene signaling networks given a large number of accurate time series samples. Microarray data available for many biological experiments is limited to a small number of arrays with little or no time series guarantees. When several samples are averaged to examine differences in mean value between a diseased and normal state, information from individual samples that could indicate a gene relationship can be lost. Results Asynchronous Inference of Regulatory Networks (AIRnet provides gene signaling network inference using more practical assumptions about the microarray data. By learning correlation patterns for the changes in microarray values from all pairs of samples, accurate network reconstructions can be performed with data that is normally available in microarray experiments. Conclusions By focussing on the changes between microarray samples, instead of absolute values, increased information can be gleaned from expression data.

  20. 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.

  1. Design and analysis of mismatch probes for long oligonucleotide microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Ye; He, Zhili; Van Nostrand, Joy D.; Zhou, Jizhong

    2008-08-15

    Nonspecific hybridization is currently a major concern with microarray technology. One of most effective approaches to estimating nonspecific hybridizations in oligonucleotide microarrays is the utilization of mismatch probes; however, this approach has not been used for longer oligonucleotide probes. Here, an oligonucleotide microarray was constructed to evaluate and optimize parameters for 50-mer mismatch probe design. A perfect match (PM) and 28 mismatch (MM) probes were designed for each of ten target genes selected from three microorganisms. The microarrays were hybridized with synthesized complementary oligonucleotide targets at different temperatures (e.g., 42, 45 and 50 C). In general, the probes with evenly distributed mismatches were more distinguishable than those with randomly distributed mismatches. MM probes with 3, 4 and 5 mismatched nucleotides were differentiated for 50-mer oligonucleotide probes hybridized at 50, 45 and 42 C, respectively. Based on the experimental data generated from this study, a modified positional dependent nearest neighbor (MPDNN) model was constructed to adjust the thermodynamic parameters of matched and mismatched dimer nucleotides in the microarray environment. The MM probes with four flexible positional mismatches were designed using the newly established MPDNN model and the experimental results demonstrated that the redesigned MM probes could yield more consistent hybridizations. Conclusions: This study provides guidance on the design of MM probes for long oligonucleotides (e.g., 50 mers). The novel MPDNN model has improved the consistency for long MM probes, and this modeling method can potentially be used for the prediction of oligonucleotide microarray hybridizations.

  2. Measuring Prevention More Broadly, An Empirical...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Measuring Prevention More Broadly, An Empirical Assessment of CHIPRA Core Measures Differences in CHIP design and structure, across states and over time, may limit...

  3. H5N1型禽流感病毒广谱中和单克隆抗体的筛选及其中和机制初步研究%Broad-spectrum Neutralizing Monoclonal Antibodies Against H5N1 Avian Influenza A Viruses and Primary Research on The Mechanism

    Institute of Scientific and Technical Information of China (English)

    张晓; 曾晓燕; 刘哲; 金秋; 徐言; 冯振卿; 焦永军

    2011-01-01

    Avian influenza is a highly contagious disease of birds caused by A influenza viruses. The circulation in humans by the highly pathogenic H5N1 avian flu in the past few years have caused most pandemics and have heightened fear that the next influenza pandemic is due. Antibodies could be used as an efficient anti-virus agent in clinical therapy. The full-length HA of the A/Jiangsu/1/2007(H5N 1) about 1.7 kb was amplified, subcloned to the pFastBac vector and recombinant bacmid DNA was selected. The recombinant HA was expressed and purified HA about 70 ku was used as the antigen to immunize Balb/c mice. The whole H5N1 virus was used to select 5 mono-antibodies (mAbs), and all of them were tested using microneutralization assays. 8G10D7, one of the antibodies, had broad neutralizing effect against clade 2 and clade 9 H5N1 avian influenza A viruses, and the IC50 was from 1 : 256 to I ' 64. When detected with 8G10D7, all 4 viruses showed 70 ku and 43 ku protein band,which confirms that the binding site of the scFv antibodies were located at the HA1 domain. The nucleuses of MDCK cells infected by 4 viruses were colored purple, and red around the nucleus. 8Gl 0D7 showed HI activity to the 4 viruses, the HI has a positive correlation with neutralization concentration IC50, which also further confirms that the binding site of the scFv antibodies were located at the HA1 domain. When the mAb 8Gl 0D7 was used for the study of prophylaxis and therapeutic effect on influenza A viruses infection in an embryonated chicken eggs model. It had a complete 100% protection effect on the H5N1 viruses in avian host in the prophylactic and therapeutic groups. The 100% preventive protection effect could be reached when challenged with H5N1 avian influenza A viruse in human host in the prophylactic groups, and there is also a 87.5% protection effect with H5N1 viruses in human host in the therapeutic groups. Thereby, the study suggests that the mAb 8G10D7 could be used in therapies to

  4. Photopatterning of Hydrogel Microarrays in Closed Microchips.

    Science.gov (United States)

    Gumuscu, Burcu; Bomer, Johan G; van den Berg, Albert; Eijkel, Jan C T

    2015-12-14

    To date, optical lithography has been extensively used for in situ patterning of hydrogel structures in a scale range from hundreds of microns to a few millimeters. The two main limitations which prevent smaller feature sizes of hydrogel structures are (1) the upper glass layer of a microchip maintains a large spacing (typically 525 μm) between the photomask and hydrogel precursor, leading to diffraction of UV light at the edges of mask patterns, (2) diffusion of free radicals and monomers results in irregular polymerization near the illumination interface. In this work, we present a simple approach to enable the use of optical lithography to fabricate hydrogel arrays with a minimum feature size of 4 μm inside closed microchips. To achieve this, we combined two different techniques. First, the upper glass layer of the microchip was thinned by mechanical polishing to reduce the spacing between the photomask and hydrogel precursor, and thereby the diffraction of UV light at the edges of mask patterns. The polishing process reduces the upper layer thickness from ∼525 to ∼100 μm, and the mean surface roughness from 20 to 3 nm. Second, we developed an intermittent illumination technique consisting of short illumination periods followed by relatively longer dark periods, which decrease the diffusion of monomers. Combination of these two methods allows for fabrication of 0.4 × 10(6) sub-10 μm sized hydrogel patterns over large areas (cm(2)) with high reproducibility (∼98.5% patterning success). The patterning method is tested with two different types of photopolymerizing hydrogels: polyacrylamide and polyethylene glycol diacrylate. This method enables in situ fabrication of well-defined hydrogel patterns and presents a simple approach to fabricate 3-D hydrogel matrices for biomolecule separation, biosensing, tissue engineering, and immobilized protein microarray applications.

  5. Pipeline for macro- and microarray analyses

    Directory of Open Access Journals (Sweden)

    R. Vicentini

    2007-05-01

    Full Text Available The pipeline for macro- and microarray analyses (PMmA is a set of scripts with a web interface developed to analyze DNA array data generated by array image quantification software. PMmA is designed for use with single- or double-color array data and to work as a pipeline in five classes (data format, normalization, data analysis, clustering, and array maps. It can also be used as a plugin in the BioArray Software Environment, an open-source database for array analysis, or used in a local version of the web service. All scripts in PMmA were developed in the PERL programming language and statistical analysis functions were implemented in the R statistical language. Consequently, our package is a platform-independent software. Our algorithms can correctly select almost 90% of the differentially expressed genes, showing a superior performance compared to other methods of analysis. The pipeline software has been applied to 1536 expressed sequence tags macroarray public data of sugarcane exposed to cold for 3 to 48 h. PMmA identified thirty cold-responsive genes previously unidentified in this public dataset. Fourteen genes were up-regulated, two had a variable expression and the other fourteen were down-regulated in the treatments. These new findings certainly were a consequence of using a superior statistical analysis approach, since the original study did not take into account the dependence of data variability on the average signal intensity of each gene. The web interface, supplementary information, and the package source code are available, free, to non-commercial users at http://ipe.cbmeg.unicamp.br/pub/PMmA.

  6. Pipeline for macro- and microarray analyses.

    Science.gov (United States)

    Vicentini, R; Menossi, M

    2007-05-01

    The pipeline for macro- and microarray analyses (PMmA) is a set of scripts with a web interface developed to analyze DNA array data generated by array image quantification software. PMmA is designed for use with single- or double-color array data and to work as a pipeline in five classes (data format, normalization, data analysis, clustering, and array maps). It can also be used as a plugin in the BioArray Software Environment, an open-source database for array analysis, or used in a local version of the web service. All scripts in PMmA were developed in the PERL programming language and statistical analysis functions were implemented in the R statistical language. Consequently, our package is a platform-independent software. Our algorithms can correctly select almost 90% of the differentially expressed genes, showing a superior performance compared to other methods of analysis. The pipeline software has been applied to 1536 expressed sequence tags macroarray public data of sugarcane exposed to cold for 3 to 48 h. PMmA identified thirty cold-responsive genes previously unidentified in this public dataset. Fourteen genes were up-regulated, two had a variable expression and the other fourteen were down-regulated in the treatments. These new findings certainly were a consequence of using a superior statistical analysis approach, since the original study did not take into account the dependence of data variability on the average signal intensity of each gene. The web interface, supplementary information, and the package source code are available, free, to non-commercial users at http://ipe.cbmeg.unicamp.br/pub/PMmA. PMID:17464422

  7. Analysis of porcine MHC using microarrays.

    Science.gov (United States)

    Gao, Yu; Wahlberg, Per; Marthey, Sylvain; Esquerré, Diane; Jaffrézic, Florence; Lecardonnel, Jérome; Hugot, Karine; Rogel-Gaillard, Claire

    2012-07-15

    The major histocompatibility complex (MHC) in Mammals is one of the most gene dense regions of the genome and contains the polymorphic histocompatibility gene families known to be involved in pathogen response and control of auto-immunity. The MHC is a complex genetic system that provides an interesting model system to study genome expression regulation and genetic diversity at the megabase scale. The pig MHC or SLA (Swine Leucocyte Antigen) complex spans 2.4 megabases and 151 loci have been annotated. We will review key results from previous RNA expression studies using microarrays containing probes specific to annotated loci within SLA and in addition present novel data obtained using high-density tiling arrays encompassing the whole SLA complex. We have focused on transcriptome modifications of porcine peripheral blood mononuclear cells stimulated with a mixture of phorbol myristate acetate and ionomycin known to activate B and T cell proliferation. Our results show that numerous loci mapping to the SLA complex are affected by the treatment. A general decreased level of expression for class I and II genes and an up-regulation of genes involved in peptide processing and transport were observed. Tiling array-based experiments contributed to refined gene annotations as presented for one SLA class I gene referred to as SLA-11. In conclusion, high-density tiling arrays can serve as an excellent tool to draw comprehensive transcription maps, and improve genome annotations for the SLA complex. We are currently studying their relevance to characterize SLA genetic diversity in combination with high throughput next generation sequencing. PMID:21561666

  8. Mycobacterium Tuberculosis Proteome Microarray for Global Studies of Protein Function and Immunogenicity

    Directory of Open Access Journals (Sweden)

    Jiaoyu Deng

    2014-12-01

    Full Text Available Poor understanding of the basic biology of Mycobacterium tuberculosis (MTB, the etiological agent of tuberculosis, hampers development of much-needed drugs, vaccines, and diagnostic tests. Better experimental tools are needed to expedite investigations of this pathogen at the systems level. Here, we present a functional MTB proteome microarray covering most of the proteome and an ORFome library. We demonstrate the broad applicability of the microarray by investigating global protein-protein interactions, small-molecule-protein binding, and serum biomarker discovery, identifying 59 PknG-interacting proteins, 30 bis-(3′-5′-cyclic dimeric guanosine monophosphate (c-di-GMP binding proteins, and 14 MTB proteins that together differentiate between tuberculosis (TB patients with active disease and recovered individuals. Results suggest that the MTB rhamnose pathway is likely regulated by both the serine/threonine kinase PknG and c-di-GMP. This resource has the potential to generate a greater understanding of key biological processes in the pathogenesis of tuberculosis, possibly leading to more effective therapies for the treatment of this ancient disease.

  9. 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

    2015-10-01

    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. PMID:26339978

  10. 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.

  11. 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

    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......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......-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....

  12. The Broad Line Radio Galaxy J2114+820

    CERN Document Server

    Lara, L; Cotton, W D; Feretti, L; Giovannini, G; Marcaide, J M; Venturi, T

    1998-01-01

    In the frame of the study of a new sample of large angular size radio galaxies selected from the NRAO VLA Sky Survey, we have made radio observations of J2114+820, a low power radio galaxy with an angular size of 6'. Its radio structure basically consists of a prominent core, a jet directed in north-west direction and two extended S-shaped lobes. We have also observed the optical counterpart of J2114+820, a bright elliptical galaxy with a strong unresolved central component. The optical spectrum shows broad emission lines. This fact, together with its low radio power and FR-I type morphology, renders J2114+820 a non-trivial object from the point of view of the current unification schemes of radio loud active galactic nuclei.

  13. SPECTROSCOPY OF BROAD-LINE BLAZARS FROM 1LAC

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Michael S.; Romani, Roger W.; Healey, Stephen E.; Michelson, Peter F. [Department of Physics/KIPAC, Stanford University, Stanford, CA 94305 (United States); Cotter, Garret; Potter, William J. [Department of Astrophysics, University of Oxford, Oxford OX1 3RH (United Kingdom); Readhead, Anthony C. S.; Richards, Joseph L.; Max-Moerbeck, Walter; King, Oliver G. [Department of Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States)

    2012-03-20

    We report on optical spectroscopy of 165 flat spectrum radio quasars (FSRQs) in the Fermi 1LAC sample, which have helped allow a nearly complete study of this population. Fermi FSRQs show significant evidence for non-thermal emission even in the optical; the degree depends on the {gamma}-ray hardness. They also have smaller virial estimates of hole mass than the optical quasar sample. This appears to be largely due to a preferred (axial) view of the {gamma}-ray FSRQ and non-isotropic (H/R {approx} 0.4) distribution of broad-line velocities. Even after correction for this bias, the Fermi FSRQs show higher mean Eddington ratios than the optical population. A comparison of optical spectral properties with Owens Valley Radio Observatory radio flare activity shows no strong correlation.

  14. Advanced spot quality analysis in two-colour microarray experiments

    Directory of Open Access Journals (Sweden)

    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.

  15. BROAD PHONEME CLASSIFICATION USING SIGNAL BASED FEATURES

    Directory of Open Access Journals (Sweden)

    Deekshitha G

    2014-12-01

    Full Text Available Speech is the most efficient and popular means of human communication Speech is produced as a sequence of phonemes. Phoneme recognition is the first step performed by automatic speech recognition system. The state-of-the-art recognizers use mel-frequency cepstral coefficients (MFCC features derived through short time analysis, for which the recognition accuracy is limited. Instead of this, here broad phoneme classification is achieved using features derived directly from the speech at the signal level itself. Broad phoneme classes include vowels, nasals, fricatives, stops, approximants and silence. The features identified useful for broad phoneme classification are voiced/unvoiced decision, zero crossing rate (ZCR, short time energy, most dominant frequency, energy in most dominant frequency, spectral flatness measure and first three formants. Features derived from short time frames of training speech are used to train a multilayer feedforward neural network based classifier with manually marked class label as output and classification accuracy is then tested. Later this broad phoneme classifier is used for broad syllable structure prediction which is useful for applications such as automatic speech recognition and automatic language identification.

  16. Giant Broad Line Regions in Dwarf Seyferts

    CERN Document Server

    Devereux, Nick

    2015-01-01

    High angular resolution spectroscopy obtained with the Hubble Space Telescope (HST) has revealed a remarkable population of galaxies hosting dwarf Seyfert nuclei with an unusually large broad-line region (BLR). These objects are remarkable for two reasons. Firstly, the size of the BLR can, in some cases, rival those seen in the most luminous quasars. Secondly, the size of the BLR is not correlated with the central continuum luminosity, an observation that distinguishes them from their reverberating counterparts. Collectively, these early results suggest that non-reverberating dwarf Seyferts are a heterogeneous group and not simply scaled versions of each other. Careful inspection reveals broad H Balmer emission lines with single peaks, double peaks, and a combination of the two, suggesting that the broad emission lines are produced in kinematically distinct regions centered on the black hole (BH). Because the gravitational field strength is already known for these objects, by virtue of knowing their BH mass, ...

  17. 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.

  18. 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.

  19. A novel method for preparation of tissue microarray

    Institute of Scientific and Technical Information of China (English)

    Han-Lei Dan; Yan-Qing Ding; Chun-Hai Guo; Dian-Yuan Zhou; Ya-Li Zhang; Yan Zhang; Ya-Dong Wang; Zuo-Sheng Lai; Yu-Jie Yang; Hai-Hong Cui; Yan-Ting Jian; Jian Geng

    2004-01-01

    AIM: To improve the technique of tissue microarray (tissue chip).METHODS: A new tissue microarraying method was invented with a common microscope installed with a special holing needle, a sampling needle, and a special box fixing paraffin blocks on the microscope slide carrier. With the movement of microscope tube and objective stage on vertical and cross dimensions respectively, the holing procedure on the recipient paraffin blocks and sampling procedure of core tissue biopsies taken from the donor blocks were performed with the refitted microscope on the same platform. The precise observation and localization of representative regions in the donor blocks were also performed with the microscope equipped with a stereoscope.RESULTS: Highly-qualified tissue chips of colorectal tumors were produced by a new method, which simplified the conventional microarraying procedure, and was more convenient and accurate than that employing the existing tissue microarraying instruments.CONCLUSION: Using the refitted common microscope to produce tissue microarray is a simple, reliable, cost-effective and well-applicable technique.

  20. Advanced Data Mining of Leukemia Cells Micro-Arrays

    Directory of Open Access Journals (Sweden)

    Ryan M. Pierce

    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.

  1. Spectral decomposition of broad-line agns and host galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Vanden Berk, Daniel E.; Shen, Jiajian; /Penn State U., Astron. Astrophys.; Yip, Ching-Wa; /Pittsburgh U.; Schneider, Donald P.; /Penn State U., Astron. Astrophys.; Connolly,; /Pittsburgh U.; Burton, Ross E.; /Pittsburgh U. /Case Western Reserve U.; Jester, Sebastian; /Fermilab; Hall, Patrick B.; /York U., Canada; Szalay, Alex S.; /Johns Hopkins; Brinkmann, John; /Apache Point Observ.

    2005-09-01

    Using an eigenspectrum decomposition technique, we separate the host galaxy from the broad line active galactic nucleus (AGN) in a set of 4666 spectra from the Sloan Digital Sky Survey (SDSS), from redshifts near zero up to about 0.75. The decomposition technique uses separate sets of galaxy and quasar eigenspectra to efficiently and reliably separate the AGN and host spectroscopic components. The technique accurately reproduces the host galaxy spectrum, its contributing fraction, and its classification. We show how the accuracy of the decomposition depends upon S/N, host galaxy fraction, and the galaxy class. Based on the eigencoefficients, the sample of SDSS broad-line AGN host galaxies spans a wide range of spectral types, but the distribution differs significantly from inactive galaxies. In particular, post-starburst activity appears to be much more common among AGN host galaxies. The luminosities of the hosts are much higher than expected for normal early-type galaxies, and their colors become increasingly bluer than early-type galaxies with increasing host luminosity. Most of the AGNs with detected hosts are emitting at between 1% and 10% of their estimated Eddington luminosities, but the sensitivity of the technique usually does not extend to the Eddington limit. There are mild correlations among the AGN and host galaxy eigencoefficients, possibly indicating a link between recent star formation and the onset of AGN activity. The catalog of spectral reconstruction parameters is available as an electronic table.

  2. Silicon micromachined broad band light source

    Science.gov (United States)

    George, Thomas (Inventor); Jones, Eric (Inventor); Tuma, Margaret L. (Inventor); Eastwood, Michael (Inventor); Hansler, Richard (Inventor)

    2004-01-01

    A micro electromechanical system (MEMS) broad band incandescent light source includes three layers: a top transmission window layer; a middle filament mount layer; and a bottom reflector layer. A tungsten filament with a spiral geometry is positioned over a hole in the middle layer. A portion of the broad band light from the heated filament is reflective off the bottom layer. Light from the filament and the reflected light of the filament are transmitted through the transmission window. The light source may operate at temperatures of 2500 K or above. The light source may be incorporated into an on board calibrator (OBC) for a spectrometer.

  3. Autism Spectrum Disorder

    Science.gov (United States)

    Autism spectrum disorder (ASD) is a neurological and developmental disorder that begins early in childhood and lasts throughout a person's life. ... be known as Asperger syndrome and pervasive developmental disorders. It is called a "spectrum" disorder because people ...

  4. [Wilson's disease: clinical spectrum of liver disease].

    Science.gov (United States)

    Ochoa Palominos, Alejandra; Ibáñez Samaniego, Luis; Catalina Rodríguez, María-Vega; Pajares Díaz, José; Clemente Ricote, Gerardo

    2013-02-01

    Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism,characterized by copper accumulation in the liver and brain. This rare entity, which has a broad clinical spectrum, is often difficult to diagnose and should therefore always be suspected in patients with liver disease of unclear cause. We describe two types of manifestation of liver disease in two patients; the first developed fulminant hepatic failure requiring urgent liver transplantation and the second showed advanced chronic liver disease and received standard medical treatment. The objective of this clinical observation is to analyze the diagnosis of Wilson's disease in two patients with distinct onset, illustrating the broad clinical spectrum of the disease, and its treatment.

  5. Comparative analysis of genomic signal processing for microarray data clustering.

    Science.gov (United States)

    Istepanian, Robert S H; Sungoor, Ala; Nebel, Jean-Christophe

    2011-12-01

    Genomic signal processing is a new area of research that combines advanced digital signal processing methodologies for enhanced genetic data analysis. It has many promising applications in bioinformatics and next generation of healthcare systems, in particular, in the field of microarray data clustering. In this paper we present a comparative performance analysis of enhanced digital spectral analysis methods for robust clustering of gene expression across multiple microarray data samples. Three digital signal processing methods: linear predictive coding, wavelet decomposition, and fractal dimension are studied to provide a comparative evaluation of the clustering performance of these methods on several microarray datasets. The results of this study show that the fractal approach provides the best clustering accuracy compared to other digital signal processing and well known statistical methods.

  6. A Protein Microarray ELISA for Screening Biological Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Woodbury, Ronald L.; Zangar, Richard C.

    2004-02-01

    Protein microarrays permit the simultaneous measurement of many proteins in a small sample volume and therefore provide an attractive approach for the quantitative measurement of proteins in biological fluids, including serum. This chapter describes a microarray ELISA assay. Capture antibodies are immobilized onto a glass surface, the covalently attached antibodies bind a specific antigen from a sample overlaying the array. A second, biotinylated antibody that recognizes the same antigen as the first antibody but at a different epitope is then used for detection. Detection is based upon an enzymatic signal enhancement method known as tyramide signal amplification (TSA). By coupling a microarray-ELISA format with the signal amplification of tyramide deposition, the assay sensitivity is as low as sub-pg/ml.

  7. The GREGOR Broad-Band Imager

    Science.gov (United States)

    von der Lühe, O.; Volkmer, R.; Kentischer, T. J.; Geißler, R.

    2012-11-01

    The design and characteristics of the Broad-Band Imager (BBI) of GREGOR are described. BBI covers the visible spectral range with two cameras simultaneously for a large field and with critical sampling at 390 nm, and it includes a mode for observing the pupil in a Foucault configuration. Samples of first-light observations are shown.

  8. D-MaPs - DNA-microarray projects: web-based software for multi-platform microarray analysis

    Directory of Open Access Journals (Sweden)

    Marcelo F. Carazzolle

    2009-01-01

    Full Text Available The web application D-Maps provides a user-friendly interface to researchers performing studies based on microarrays. The program was developed to manage and process one- or two-color microarray data obtained from several platforms (currently, GeneTAC, ScanArray, CodeLink, NimbleGen and Affymetrix. Despite the availability of many algorithms and many software programs designed to perform microarray analysis on the internet, these usually require sophisticated knowledge of mathematics, statistics and computation. D-maps was developed to overcome the requirement of high performance computers or programming experience. D-Maps performs raw data processing, normalization and statistical analysis, allowing access to the analyzed data in text or graphical format. An original feature presented by D-Maps is GEO (Gene Expression Omnibus submission format service. The D-MaPs application was already used for analysis of oligonucleotide microarrays and PCR-spotted arrays (one- and two-color, laser and light scanner. In conclusion, D-Maps is a valuable tool for microarray research community, especially in the case of groups without a bioinformatic core.

  9. 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/

  10. A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

    OpenAIRE

    Patrick Ymele-Leki; Shugeng Cao; Jared Sharp; Kathleen G Lambert; McAdam, Alexander J.; Husson, Robert N.; Giselle Tamayo; Jon Clardy; Watnick, Paula I.

    2012-01-01

    Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms t...

  11. A BROAD-SPECTRUM ANTAGONISTIC ACTIVITY OF THE BIOCONTROL AGENT PSEUDOMONAS SYNXANTHA BG33R

    Science.gov (United States)

    Pseudomonas synxantha strain BG33R was previously reported to be effective in controlling the Peach Tree Short Life (PTSL) syndrome by suppressing the ring nematode (Mesocriconema xenoplax) through terminating the eggs of the second juvenile stage from further development. In this research the spec...

  12. A crustin isoform from black tiger shrimp, Penaeus monodon exhibits broad spectrum anti-bacterial activity

    Directory of Open Access Journals (Sweden)

    Debashis Banerjee

    2015-11-01

    Full Text Available Crustaceans have a powerful non-specific immune mechanism that responds to pathogen invasion and together with cellular responses, generates powerful humoral factors such as antimicrobial peptides. Crustins are a diverse class of antimicrobial peptides that are expressed by the circulating haemocytes of crustaceans. Several isoforms of this molecule are reported and in this study, one isoform from the black tiger shrimp, Penaeus monodon was cloned and expressed in Escherichia coli SG 13009. The purified recombinant crustin peptide had a molecular weight of 22 kDa and exhibited potent anti-bacterial activity in vitro against several Gram positive and Gram negative bacteria that included pathogens of aquatic animals and humans. The recombinant crustin showed a minimal inhibitory concentration of 0.5 μg ml−1 against the vibrio pathogens of shrimp, which suggests its promise for application in aquaculture.

  13. Characterization of broad-spectrum antibiotic resistance genes in wastewater treatment reactors through metagenomic approaches

    OpenAIRE

    Yang, Ying; 楊穎

    2014-01-01

    The spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have attracted great concerns worldwide. Wastewater treatment plants (WWTPs) are reservoirs of ARGs while wastewater/sludge treatment processes are considered as important means to control these emerging biological pollutants. However, the full profiles of ARGs in WWTPs or the removal efficiency of ARGs by wastewater/sludge treatment process was not well characterized yet. Thus, the major tasks in this st...

  14. A Broad-Spectrum Antimicrobial Activity of Bacillus subtilis RLID 12.1

    Directory of Open Access Journals (Sweden)

    Ramya Ramachandran

    2014-01-01

    Full Text Available In the present study, an attempt was made to biochemically characterize the antimicrobial substance from the soil isolate designated as RLID 12.1 and explore its potential applications in biocontrol of drug-resistant pathogens. The antimicrobial potential of the wild-type isolate belonging to the genus Bacillus was determined by the cut-well agar assay. The production of antimicrobial compound was recorded maximum at late exponential growth phase. The ultrafiltered concentrate was insensitive to organic solvents, metal salts, surfactants, and proteolytic and nonproteolytic enzymes. The concentrate was highly heat stable and active over a wide range of pH values. Partial purification, zymogram analysis, and TLC were performed to determine the preliminary biochemical nature. The molecular weight of the antimicrobial peptide was determined to be less than 2.5 kDa in 15% SDS-PAGE and in zymogram analysis against Streptococcus pyogenes. The N-terminal amino acid sequence by Edman degradation was partially determined to be T-P-P-Q-S-X-L-X-X-G, which shows very insignificant identity to other antimicrobial peptides from bacteria. The minimum inhibitory concentrations of dialysed and partially purified ion exchange fractions were determined against some selected gram-positive and gram-negative bacteria and some pathogenic yeasts. The presence of three important antimicrobial peptide biosynthesis genes ituc, fend, and bmyb was determined by PCR.

  15. Fibroblast growth factors: An epigenetic mechanism of broad spectrum resistance to anticancer drugs

    OpenAIRE

    Song, SaeHeum; Wientjes, M. Guillaume; Gan, Yuebo; Au, Jessie L. -S.

    2000-01-01

    Based on the observation that removal of tumors from metastatic organs reversed their chemoresistance, we hypothesized that chemoresistance is induced by extracellular factors in tumor-bearing organs. By comparing chemosensitivity and proteins in different tumors (primary vs. metastases) and different culture systems (tumor fragment histocultures vs. monolayer cultures derived from the same tumor), we found elevated levels of acidic (aFGF) and basic (bFGF) fibroblast growth factors in the con...

  16. Beyond Exposure for Posttraumatic Stress Disorder (PTSD) Symptoms: Broad-Spectrum PTSD Treatment Strategies

    Science.gov (United States)

    Lombardo, Thomas W.; Gray, Matt J.

    2005-01-01

    Although cases of posttraumatic stress disorder (PTSD) with comorbid disorders are common, the first generation of PTSD treatment approaches, including exposure and cognitive-behavioral therapy, generally ignore symptoms beyond those specific to PTSD. Optimum PTSD treatment outcome requires more comprehensive strategies, and the development and…

  17. Broad-Spectrum Antimicrobial Star Polycarbonates Functionalized with Mannose for Targeting Bacteria Residing inside Immune Cells.

    Science.gov (United States)

    Yang, Chuan; Krishnamurthy, Sangeetha; Liu, Jie; Liu, Shaoqiong; Lu, Xiaohua; Coady, Daniel J; Cheng, Wei; De Libero, Gennaro; Singhal, Amit; Hedrick, James L; Yang, Yi Yan

    2016-06-01

    In this study, a series of star-shaped polycarbonates are synthesized by metal-free organocatalytic ring-opening polymerization of benzyl chloride (BnCl) and mannose-functionalized cyclic carbonate monomers (MTC-BnCl and MTC-ipman) with heptakis-(2,3-di-O-acetyl)-β-cyclodextrin (DA-β-CD) as macroinitiator. The distributions and compositions of pendent benzyl chloride and protected mannose group (ipman) units are facilely modulated by varying the polymerization sequence and feed ratio of the monomers, allowing precise control over the molecular composition, and the resulting polymers have narrow molecular weight distribution. After deprotection of ipman groups and quaternization with various N,N-dimethylalkylamines, these star polymers with optimized compositions of cationic and mannose groups in block and random forms exhibit strong bactericidal activity and low hemolysis. Furthermore, the optimal mannose-functionalized polymer demonstrates mannose receptor-mediated intracellular bactericidal activity against BCG mycobacteria without inducing cytotoxicity on mammalian cells at the effective dose. Taken together, the materials designed in this study have potential use as antimicrobial agents against diseases such as tuberculosis, which is caused by intracellular bacteria.

  18. Functionalization of electrospun {beta}-cyclodextrin/polyacrylonitrile (PAN) with silver nanoparticles: Broad-spectrum antibacterial property

    Energy Technology Data Exchange (ETDEWEB)

    Wang Shan [Chemical Engineering College, Inner Mongolia University of Technology, Hohhot, 010051 (China); Bai Jie, E-mail: baijie@imut.edu.cn [Chemical Engineering College, Inner Mongolia University of Technology, Hohhot, 010051 (China); Li Chunping; Zhang Jianbin [Chemical Engineering College, Inner Mongolia University of Technology, Hohhot, 010051 (China)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer Novel PAN nanofibers contained {beta}-cyclodextrin and Ag nanoparticles. Black-Right-Pointing-Pointer The composite nanofibers as antibacterial material. Black-Right-Pointing-Pointer The composite nanofibers showed stronger antibacterial activity. - Abstract: Polyacrylonitrile (PAN) nanofibers containing {beta}-cyclodextrin ({beta}-CD) and Ag nanoparticles have been prepared by electrospinning technology. The silver nanoparticles were obtained from the AgNO{sub 3}/PAN/DMF solution, in which AgNO{sub 3} acted as the precursor, DMF as reducing reagent, and PAN as protective agent. Then, {beta}-CD was added to above solution and the resultant Ag/{beta}-CD-PAN/DMF solution was directly electrospun to prepare Ag/{beta}-CD-PAN nanofibers. The morphology of the nanofibers has been characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The antimicrobial properties were investigated by Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria, and the results indicated that the composite nanofibers showed stronger antibacterial activity.

  19. A Broad-Spectrum Microbicide with Virucidal Activity against Sexually Transmitted Viruses

    OpenAIRE

    Howett, M K; Neely, E. B.; Christensen, N D; Wigdahl, B; Krebs, F. C.; Malamud, D; Patrick, S D; Pickel, M. D.; Welsh, P. A.; Reed, C. A.; Ward, M. G.; Budgeon, L. R.; Kreider, J W

    1999-01-01

    Sodium dodecyl sulfate (SDS), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. In preliminary experiments, we demonstrated that SDS is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. We hypothesized that SDS might be capable of denaturing the capsid proteins of none...

  20. Broad spectrum activity of a lectin-like bacterial serine protease family on human leukocytes.

    Directory of Open Access Journals (Sweden)

    Jorge Luis Ayala-Lujan

    Full Text Available The serine protease autotransporter from Enterobacteriaceae (SPATE family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system.

  1. Childhood psychosocial stressors and adult onset arthritis: Broad spectrum risk factors and allostatic load

    OpenAIRE

    Von Korff, Michael; Alonso, Jordi; Ormel, Johan; Angermeyer, Matthais; Bruffaerts, Ronny; Fleiz, Clara; de Girolamo, Giovanni; Ronald C. Kessler; Kovess-Masfety, Viviane; Posada-Villa, Jose; Scott, Kate M.; Uda, Hidenori

    2009-01-01

    Neural, endocrine, and immune stress mediators are hypothesized to increase risks of diverse chronic diseases, including arthritis. Retrospective data from the World Mental Health Surveys (N = 18,309) were employed to assess whether adult onset of arthritis was associated with childhood adversities and early onset psychological disorder. Cox proportional hazard models assessed the association of number of childhood adversities and the presence of early onset psychological disorder with arthri...

  2. 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....

  3. Broad spectrum drug screening using electron-ionization gas chromatography-mass spectrometry (EI-GCMS).

    Science.gov (United States)

    Stone, Judy

    2010-01-01

    A liquid-liquid extraction (LLE) of drugs and internal standard (promazine) is performed by mixing urine at basic pH with 1-chlorobutane. There are no hydrolysis or derivatization steps. After centrifugation the organic (upper) layer is transferred to another tube and evaporated. The dried extract is reconstituted with ethyl acetate and 1 microL is injected onto the GCMS. Drugs are volatilized in the GC inlet and separated on a capillary column. In the EI source drugs become positively charged and fragment. Mass analysis of ionized fragments occurs with a single quadrupole. The resulting full scan mass spectra are automatically searched against three libraries. PMID:20077071

  4. Broad spectrum drug screening using liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry.

    Science.gov (United States)

    Stone, Judy

    2010-01-01

    Centrifuged urine, internal standard (promazine), and ammonium formate buffer are mixed in an autosampler vial to achieve a 10-fold dilution of the specimen. Without additional pretreatment, 10 microL of the sample is injected onto a C18 reverse phase column for gradient analysis with ammonium formate/acetonitrile mobile phases. Drugs in the column eluent become charged in the ion source using positive electrospray atmospheric pressure ionization. Pseudomolecular drug ions are analyzed by a hybrid triple quadrupole linear ion trap mass spectrometer operated with a 264-drug selected ion monitoring (SRM) acquisition method that includes an information-dependant acquisition (IDA) algorithm. PMID:20077072

  5. E-Learning: A Broad-Spectrum View toward Benefits and Pitfalls

    Science.gov (United States)

    Ebrahimi, Pouria

    2010-01-01

    In a world on the move, the need for technology in any of its form is desired every minute of every day. For any type of technology to stay in vogue, real-time information is to be delivered to the applicants; otherwise, it is doomed to fall. The process of updating information and delivering it to the applicants needs education--with no doubt.…

  6. MICROBIAL TRANSFORMATION OF GALLOTANNINS TO GALLIC ACID, AN INTERMEDIATE PRODUCT OF TRIMETHOPRIM, A BROAD SPECTRUM ANTIBOITIC

    Directory of Open Access Journals (Sweden)

    C. AYYANNA

    2006-01-01

    Full Text Available A method for producing Gallic acid by microbiological hydrolysis of the tannins of tripods powder is described in the present work. Hydrolysis of gallotanins of the substrate to Gallic acid by aspergilus niger MTCC 282 was studied. A simple extraction procedure is used. Fungal mycelia pre-induced with 5 g/l gallotanin was used as inocolums. Optimal values for various physico-chemical parameters including substrate concentration, inocolum levels, pH, temperature, fermentation, inocolum age, agitatioin, gallotanin concentration nultritional source and metal ion were determined. The yield of Gallic acide with respect to gallotannins present in the substrate is estimated. Yield of Gallic acid are about 82% with respect to gallotannin concentration, which suggests that this method ix exploitable industrially for manufacturing Trimethoprim drug.Currnet total requirment of Gallic acid is around 8,000 tones per year all over the world. Conventionally Gallic acid is being produced by acid hydrolysis of tannin rich source. But this technology has serval disadvantages regarding cost, yield and purity of the product. This technology alos causes a lot of environmental pollution being a chemical process. The present technique of conversion of teri tannins to Gallic acid using fungal mycelia viz, aspergillus niger MTCC 282, being purely a bioconversion is free from pollution with more purity of product.

  7. Inflammation and anaemia in a broad spectrum of patients with heart failure

    NARCIS (Netherlands)

    Kleijn, Lennaert; Belonje, Anne M. S.; Voors, Adriaan A.; De Boer, Rudolf A.; Jaarsma, Tiny; Ghosh, Sudip; Kim, Joseph; Hillege, Hans L.; Van Gilst, Wiek H.; van Veldhuisen, Dirk J.; van der Meer, Peter

    2012-01-01

    Aims Anaemia in heart failure (HF) is associated with a poor prognosis. Although inflammation is assumed to be an important cause of anaemia, the association between anaemia and inflammatory markers in patients with HF has not been well established. Methods Data from a multicentre randomised clinica

  8. Broad spectrum anti-microbial compounds producing bacteria from coast of Qingdao bays.

    Science.gov (United States)

    Khan, Muhammad Naseem; Li, Meng; Mirani, Zulfiqar Ali; Wang, Jingxue; Lin, Hong; Buzdar, Muhammad Aslam

    2015-03-01

    Anti-microbial resistance burden and hazard associated with chemical treatment of infections demanded for new anti-microbial natural products. Marine associated microorganisms are the enormous source of bioactive compounds. In this study we have isolated 272 marine bacteria among them 136 (50%) were antagonistic to at least one of the four pathogenic strains Listeria monocytogenes, Vibrio cholerae, E. coli and S. aureus. Only two strains exhibited antibacterial activity against all four test strains, which were identified by 16S rDNA sequencing as Bacillus sp. DK1-SA11 and Vibrio sp. DK6-SH8. Marine isolate DK1-SA11 has potential to resist boiling temperature and pH 2-12. Furthermore cell free extract (CFE) inhibited all test organisms including superbug MRSA and pathogenic yeast Candida albicans. Marine isolate Bacillus sp. DK1-SA11 could be a potential combatant for the battle of drugs and bugs. PMID:25730803

  9. The effect of broad-spectrum antibiotics on warfarin excretion and metabolism in the rat

    International Nuclear Information System (INIS)

    The excretion and metabolism of 14C-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. 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.

  11. Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate

    Science.gov (United States)

    Dinicola, Simona

    2016-01-01

    Inositols (myo-inositol and inositol hexakisphosphate) exert a wide range of critical activities in both physiological and pathological settings. Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways. Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle. Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation. Upstream of that pathway, inositols disrupt the ligand interaction between FGF and its receptor as well as with the EGF-transduction processes involving IGF-II receptor and AP-1 complexes. Additionally, Akt activation is severely impaired upon inositol addition. Downregulation of both Akt and ERK leads consequently to NF-kB inhibition and reduced expression of inflammatory markers (COX-2 and PGE2). Remarkably, inositol-induced downregulation of presenilin-1 interferes with the epithelial-mesenchymal transition and reduces Wnt-activation, β-catenin translocation, Notch-1, N-cadherin, and SNAI1 release. Inositols interfere also with the cytoskeleton by upregulating Focal Adhesion Kinase and E-cadherin and decreasing Fascin and Cofilin, two main components of pseudopodia, leading hence to invasiveness impairment. This effect is reinforced by the inositol-induced inhibition on metalloproteinases and ROCK1/2 release. Overall, these effects enable inositols to remodel the cytoskeleton architecture. PMID:27795708

  12. 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.

  13. 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......Background: It can be difficult to provide patients with idiopathic solar urticaria adequate protection from sunlight. In a nonrandomized controlled trial, we used a standardized phototest procedure to determine the effects of using sunscreen and antihistamine to control idiopathic solar urticaria......). Antihistamine use did not increase the patients' MUD but did suppress wheal formation and itch, and only immediate erythema sharply located in the irradiated areas occurred. The combination of sunscreen and antihistamine acted synergistically and increased the tolerance to UV radiation markedly (80-267 times...

  14. Rational design of berberine-based FtsZ inhibitors with broad-spectrum antibacterial activity.

    Directory of Open Access Journals (Sweden)

    Ning Sun

    Full Text Available Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 µg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 µg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.

  15. The broad spectrum of Trichinella hosts: from cold- to warm-blooded animals.

    Science.gov (United States)

    Pozio, E

    2005-09-01

    In recent years, studies on Trichinella have shown that the host range is wider than previously believed and new Trichinella species and genotypes have been described. Three classes of vertebrates are known to act as hosts, mammals, birds and reptiles, and infected vertebrates have been detected on all continents but Antarctica. Mammals represent the most important hosts and all Trichinella species are able to develop in this vertebrate class. Natural infections with Trichinella have been described in more than 150 mammalian species belonging to 12 orders (i.e., Marsupialia, Insectivora, Edentata, Chiroptera, Lagomorpha, Rodentia, Cetacea, Carnivora, Perissodactyla, Artiodactyla, Tylopoda and Primates). The epidemiology of the infection greatly varies by species relative to characteristics, such as diet, life span, distribution, behaviour, and relationships with humans. The non-encapsulated species Trichinella pseudospiralis, detected in both mammals (14 species) and birds (13 species), shows a cosmopolitan distribution with three distinguishable populations in the Palearctic, Nearctic and Australian regions. Two additional non-encapsulated species, Trichinella papuae, detected in wild pigs and saltwater crocodiles of Papua New Guinea, and Trichinella zimbabwensis, detected in farmed Nile crocodiles of Zimbabwe, can complete their life cycle in both mammals and reptiles. To the best of our knowledge, T. papuae and T. zimbabwensis are the only two parasites known to complete their entire life cycle independently of whether the host is warm-blooded or cold-blooded. This suggests that these two Trichinella species are capable of activating different physiological mechanisms, according to the specific vertebrate class hosting them. PMID:15970384

  16. Graduated diagnostics required. Broad spectrum of differential diagnoses; Stufendiagnostik erforderlich. Breites Spektrum an Differentialdiagnosen

    Energy Technology Data Exchange (ETDEWEB)

    Auer, I.O. [Medizinische Klinik Juliusspital, Schwerpunkt Gastroenterologie/Rheumatologie, Wuerzburg (Germany)

    1997-10-01

    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) [Deutsch] Noch immer betraegt die Zeitspanne von den ersten Symptomen bis zur Diagnose bei Colitis ulcerosa 6 bis 8 Wochen, bei M. Crohn sogar etwa 30 Wochen. Eine Stufendiagnostik ist gefordert: Stufe 1 umfasst nicht-invasive Methoden wie Anamnese, koerperliche Untersuchung, Stuhluntersuchung, Blutchemie und Abdomen-Sonographie, Stufe 2 die Endoskopie und radiologische Methoden, Stufe 3 die CT und die MRT zur Erkennung von Komplikationen. Die Ergebnisse der Leukozytenszintigraphie zum Nachweis entzuendlicher Veraenderungen am und ausserhalb des Darms sind hinsichtlich Spezifitaet und Sensitivitaet noch sehr uneinheitlich. (orig./MG)

  17. Broad Spectrum Activity of a Lectin-Like Bacterial Serine Protease Family on Human Leukocytes

    Science.gov (United States)

    Ayala-Lujan, Jorge Luis; Vijayakumar, Vidhya; Gong, Mei; Smith, Rachel; Santiago, Araceli E.; Ruiz-Perez, Fernando

    2014-01-01

    The serine protease autotransporter from Enterobacteriaceae (SPATE) family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system. PMID:25251283

  18. Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs.

    Science.gov (United States)

    McTier, Tom L; Chubb, Nathan; Curtis, Michael P; Hedges, Laura; Inskeep, Gregory A; Knauer, Christopher S; Menon, Sanjay; Mills, Brian; Pullins, Aleah; Zinser, Erich; Woods, Debra J; Meeus, Patrick

    2016-05-30

    The novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea (Ctenocephalides felis) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata. Efficacious compounds which were confirmed safe in rodents at doses up to 30mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro sarolaner demonstrated an LC80 of 0.3μg/mL against C. felis and an LC100 of 0.003μg/mL against O. turicata. In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, sarolaner demonstrated safety in dogs≥8 weeks of age upon repeated monthly dosing at up to 20mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for sarolaner was calculated at 11-12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25-5mg/kg, and these same doses provided robust efficacy (>99%) for ≥35days against both fleas (C. felis) and multiple species of ticks (Rhipicephalus sanguineus, Ixodes ricinus and Dermacentor reticulatus) after oral administration to dogs. As a result of these exploratory investigations, sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs. PMID:26961590

  19. 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.

  20. Novel gramicidin formulations in cationic lipid as broad-spectrum microbicidal agents

    OpenAIRE

    Ragioto DA; Carrasco LD; Carmona-Ribeiro AM

    2014-01-01

    Danielle AMT Ragioto, Letícia DM Carrasco, Ana M Carmona-Ribeiro Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil Abstract: Dioctadecyldimethylammonium bromide (DODAB) is an antimicrobial lipid that can be dispersed as large closed bilayers (LV) or bilayer disks (BF). Gramicidin (Gr) is an antimicrobial peptide assembling as channels in membranes and increasing their permeability towards ca...

  1. 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.

  2. New broad-spectrum resistance to septoria tritici blotch derived from synthetic hexaploid wheat

    NARCIS (Netherlands)

    Tabib Ghaffary, M.S.; Faris, J.D.; Friesen, T.L.; Visser, R.G.F.; Lee, van der T.A.J.; Robert, O.; Kema, G.H.J.

    2012-01-01

    Septoria tritici blotch (STB), caused by the ascomycete Mycosphaerella graminicola, is one of the most devastating foliar diseases of wheat. We screened five synthetic hexaploid wheats (SHs), 13 wheat varieties that represent the differential set of cultivars and two susceptible checks with a global

  3. Synthesis and antimicrobial evaluation of nitazoxanide-based analogues: identification of selective and broad spectrum activity.

    Science.gov (United States)

    Ballard, T Eric; Wang, Xia; Olekhnovich, Igor; Koerner, Taylor; Seymour, Craig; Salamoun, Joseph; Warthan, Michelle; Hoffman, Paul S; Macdonald, Timothy L

    2011-02-01

    A library composed of nitazoxanide-based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate-ferredoxin oxidoreductase (PFOR) using microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt the PFOR enzyme directly. The library was also screened for activity against staphylococci and resulted in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations with low toxicity to human foreskin cells. PMID:21275058

  4. Broad-spectrum anti-biofilm peptide that targets a cellular stress response.

    Directory of Open Access Journals (Sweden)

    César de la Fuente-Núñez

    2014-05-01

    Full Text Available Bacteria form multicellular communities known as biofilms that cause two thirds of all infections and demonstrate a 10 to 1000 fold increase in adaptive resistance to conventional antibiotics. Currently, there are no approved drugs that specifically target bacterial biofilms. Here we identified a potent anti-biofilm peptide 1018 that worked by blocking (pppGpp, an important signal in biofilm development. At concentrations that did not affect planktonic growth, peptide treatment completely prevented biofilm formation and led to the eradication of mature biofilms in representative strains of both Gram-negative and Gram-positive bacterial pathogens including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus, Salmonella Typhimurium and Burkholderia cenocepacia. Low levels of the peptide led to biofilm dispersal, while higher doses triggered biofilm cell death. We hypothesized that the peptide acted to inhibit a common stress response in target species, and that the stringent response, mediating (pppGpp synthesis through the enzymes RelA and SpoT, was targeted. Consistent with this, increasing (pppGpp synthesis by addition of serine hydroxamate or over-expression of relA led to reduced susceptibility to the peptide. Furthermore, relA and spoT mutations blocking production of (pppGpp replicated the effects of the peptide, leading to a reduction of biofilm formation in the four tested target species. Also, eliminating (pppGpp expression after two days of biofilm growth by removal of arabinose from a strain expressing relA behind an arabinose-inducible promoter, reciprocated the effect of peptide added at the same time, leading to loss of biofilm. NMR and chromatography studies showed that the peptide acted on cells to cause degradation of (pppGpp within 30 minutes, and in vitro directly interacted with ppGpp. We thus propose that 1018 targets (pppGpp and marks it for degradation in cells. Targeting (pppGpp represents a new approach against biofilm-related drug resistance.

  5. 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.

  6. 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 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...

  7. Compressió de microarrays d'ADN

    OpenAIRE

    Pueyo Navarro, Iván

    2015-01-01

    La tecnologia relacionada amb la creació d'imatges de microarray d'ADN és una eina de gran importància en el descobriment de l'estructura i funcionament de la nostra informació genètica. Dins d'aquest camp, la detecció del comportament de determinats gens sota condicions especifiques adquireix una gran rellevància. La grandària de les imatges de microarray sol ser de mitjana elevada, a causa de la gran quantitat de gens que s'analitzen i al fet que s'intenta mantenir en les imatges el major c...

  8. Fluorescence Lifetime Imaging of Quantum Dot Labeled DNA Microarrays

    Directory of Open Access Journals (Sweden)

    Jonathan G. Terry

    2009-04-01

    Full Text Available Quantum dot (QD labeling combined with fluorescence lifetime imaging microscopy is proposed as a powerful transduction technique for the detection of DNA hybridization events. Fluorescence lifetime analysis of DNA microarray spots of hybridized QD labeled target indicated a characteristic lifetime value of 18.8 ns, compared to 13.3 ns obtained for spots of free QD solution, revealing that QD labels are sensitive to the spot microenvironment. Additionally, time gated detection was shown to improve the microarray image contrast ratio by 1.8, achieving femtomolar target sensitivity. Finally, lifetime multiplexing based on Qdot525 and Alexa430 was demonstrated using a single excitation-detection readout channel.

  9. 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.

  10. Broad line regions in Seyfert-1 galaxies

    International Nuclear Information System (INIS)

    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.)

  11. Fourier evaluation of broad Moessbauer spectra

    International Nuclear Information System (INIS)

    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)

  12. A Broad View of Macroeconomic Stability

    OpenAIRE

    José Antonio Ocampo

    2005-01-01

    This paper recommends a broad concept of macroeconomic stability, whereby “sound macroeconomic frameworks” include not only price stability and sound fiscal policies, but also a well-functioning real economy, sustainable debt ratios and healthy public and private sector balance sheets. These multiple dimensions imply using multiple policy instruments. The paper elaborates a framework for developing countries that involves active use of counter-cyclical macroeconomic policies (exchange rate, m...

  13. Relativistic redshifts in quasar broad lines

    CERN Document Server

    Tremaine, Scott; Liu, Xin; Loeb, Abraham

    2014-01-01

    The broad emission lines commonly seen in quasar spectra have velocity widths of a few per cent of the speed of light, so special- and general-relativistic effects have a significant influence on the line profile. We have determined the redshift of the broad H-beta line in the quasar rest frame (determined from the core component of the [OIII] line) for over 20,000 quasars from the Sloan Digital Sky Survey DR7 quasar catalog. The mean redshift as a function of line width is approximately consistent with the relativistic redshift that is expected if the line originates in a randomly oriented Keplerian disk that is obscured when the inclination of the disk to the line of sight exceeds ~30-45 degrees, consistent with simple AGN unification schemes. This result also implies that the net line-of-sight inflow/outflow velocities in the broad-line region are much less than the Keplerian velocity when averaged over a large sample of quasars with a given line width.

  14. The intestinal lesion of autistic spectrum disorder.

    Science.gov (United States)

    Jass, Jeremy R

    2005-08-01

    This editorial briefly reviews the significance of lymphoid nodular hyperplasia in the intestinal tract of children with autistic spectrum disorder. The distinction between physiological and pathological lymphoid hyperplasia of the intestinal tract is of importance in the context of a possible causative link with autism. A primary intestinal lesion may occur as part of the broad spectrum of immunological disorders to which autistic children are prone. This could result in increased intestinal permeability to peptides of dietary origin which may then lead to disruption of neuroregulatory mechanisms required for normal brain development. Alternatively, there could be a primary defect in the translocation and processing of factors derived from the intestinal lumen. These possibilities deserve further investigation and should not be lost in the fog of the controversy regarding the role of measles/mumps/rubella vaccination in the aetiology of autistic spectrum disorder.

  15. 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.

  16. 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.

  17. 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...

  18. Thermodynamics of competitive surface adsorption on DNA microarrays

    International Nuclear Information System (INIS)

    Gene microarrays provide a powerful functional genomics technology which permits the expression profiling of tens of thousands of genes in parallel. The basic idea of their functioning is based on the sequence specificity of probe-target interactions combined with fluorescence detection. In reality, this straightforward principle is opposed by the complexity of the experimental system due to imperfections of chip fabrication and RNA preparation, due to the non-linearity of the probe response and especially due to competitive interactions which are inherently connected with the high throughput character of the method. We theoretically analysed aspects of the hybridization of DNA oligonucleotide probes with a complex multicomponent mixture of RNA fragments, such as the effect of different interactions between nucleotide strands competing with the formation of specific duplexes, electrostatic and entropic blocking, the fragmentation of the RNA, the incomplete synthesis of the probes and 'zipping' effects in the oligonucleotide duplexes. The effective hybridization affinities of microarray probes are considerably smaller than those for bulk hybridization owing to the effects discussed, but they correlate well with the bulk data on a relative scale. In general, the hybridization isotherms of microarray probes are shown to deviate from a Langmuir-type behaviour. Nevertheless isotherms of the Langmuir or Sips type are predicted to provide a relatively simple description of the non-linear, probe-specific concentration dependence of the signal intensity of microarray probes

  19. A microarray immunoassay for simultaneous detection of proteins and bacteria

    Science.gov (United States)

    Delehanty, James B.; Ligler, Frances S.

    2002-01-01

    We report the development and characterization of an antibody microarray biosensor for the rapid detection of both protein and bacterial analytes under flow conditions. Using a noncontact microarray printer, biotinylated capture antibodies were immobilized at discrete locations on the surface of an avidin-coated glass microscope slide. Preservation of capture antibody function during the deposition process was accomplished with the use of a low-salt buffer containing sucrose and bovine serum albumin. The slide was fitted with a six-channel flow module that conducted analyte-containing solutions over the array of capture antibody microspots. Detection of bound analyte was subsequently achieved using fluorescent tracer antibodies. The pattern of fluorescent complexes was interrogated using a scanning confocal microscope equipped with a 635-nm laser. This microarray system was employed to detect protein and bacterial analytes both individually and in samples containing mixtures of analytes. Assays were completed in 15 min, and detection of cholera toxin, staphylococcal enterotoxin B, ricin, and Bacillus globigii was demonstrated at levels as low as 8 ng/mL, 4 ng/mL, 10 ng/mL, and 6.2 x 10(4) cfu/mL, respectively. The assays presented here are very fast, as compared to previously published methods for measuring antibody-antigen interactions using microarrays (minutes versus hours).

  20. 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...