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Sample records for voltage-induced broad-spectrum reflectivity

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

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    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.

  2. Broad-spectrum antiviral agents

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    Jun-Da eZhu

    2015-05-01

    Full Text Available Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents.

  3. Broad-spectrum antiviral therapeutics.

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    Todd H Rider

    Full Text Available Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA Activated Caspase Oligomerizer (DRACO that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.

  4. 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.

  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. On the Operational Meaning of Broad-Spectrum Philosophy Methodology

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    Miao Yi

    2012-06-01

    Full Text Available This study analyze the Broad-spectrum Philosophy Methodology on the operational meaning, and discusses three relatively primary methods of Broad-spectrum Philosophy Methodologies. The methodology of Broad-spectrum philosophy cannot pursuit of accuracy of numerical sense, but it pursuits of the exact nature of the research questions, the accuracy of the sense of set theory and sums up the experience which we solve problems in real life and make it up to the generalized quantization and procedural level and thus the methodology of Broad-spectrum philosophy has a general guide and it is a broad operations research. We gets the results that along with deep exploration and development of Broad-spectrum Philosophy Methodology, its function as generalized operation research can be more powerful.

  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.

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    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. Multivalent dendritic molecules as broad spectrum bacteria agglutination agents.

    Science.gov (United States)

    Xiao, Shuzhang; Abu-Esba, Lica; Turkyilmaz, Serhan; White, Alexander G; Smith, Bradley D

    2013-01-01

    This study reports the first set of synthetic molecules that act as broad spectrum agglutination agents and thus are complementary to the specific targeting of antibodies. The molecules have dendritic architecture and contain multiple copies of zinc(II)-dipicolylamine (ZnDPA) units that have selective affinity for the bacterial cell envelope. A series of molecular structures were evaluated, with the number of appended ZnDPA units ranging from four to thirty-two. Agglutination assays showed that the multivalent probes rapidly cross-linked ten different strains of bacteria, regardless of Gram-type and cell morphology. Fluorescence microscopy studies using probes with four ZnDPA units indicated a high selectivity for bacteria agglutination in the presence of mammalian cells and no measurable effect on the health of the cells. The high bacterial selectivity was confirmed by conducting in vivo optical imaging studies of a mouse leg infection model. The results suggest that multivalent ZnDPA molecular probes with dendritic structures have great promise as selective, broad spectrum bacterial agglutination agents for infection imaging and theranostic applications.

  11. 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.

  12. Rufinamide: a novel broad-spectrum antiepileptic drug.

    Science.gov (United States)

    Wheless, James W; Vazquez, Blanca

    2010-01-01

    The last 20 years have witnessed a tremendous explosion in the number of antiepileptic drugs (AEDs) as well as the introduction of AEDS developed for specific epilepsy syndromes. The study of the efficacy and side effect profile of AEDs for unique epilepsy syndromes has allowed neurologists to utilize evidence-based medicine when treating patients. In late 2008, the Food and Drug Administration approved rufinamide for adjunctive use in the treatment of seizures associated with Lennox-Gastaut syndrome. This unique chemical compound is also the first new AED to reach the market in the United States having a pediatric indication prior to approval for adults. Rufinamide appears to have a broad spectrum of efficacy, is well tolerated, and may be rapidly initiated--properties that will likely extend its use outside of Lennox-Gastaut syndrome.

  13. Clinical evaluation of clotrimazole. A broad-spectrum antifungal agent.

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    Spiekermann, P H; Young, M D

    1976-03-01

    The efficacy and safety of the broad-spectrum, topically applied antifungal agent clotrimazole were evaluated in two double-blind, multicentric trials. Ten investigators reported on a total of 1,361 cases in which a 1% solution or a 1% cream formulation was compared with its respective vehicle. Clotrimazole was therapeutically effective, as confirmed by mycological cure (negative microscopy and culture) and clinical improvement, in tinea pedis, tinea cruris, tinea corporis, pityriasis versicolor, and cutaneous candidasis. Furthermore, species identification established the efficacy of clotrimazole against Trichophyton rubrum, T mentagrophytes, Epidermophyton floccosum, Microsporum canis, Malassezia furfur (Pityrosporum orbiculare), and Candida albicans. Safety was demonstrated by the low incidence of possibly drug-related adverse experiences, namely, 19 (2.7%) of 699 patients who were treated with clotrimazole, of whom four (0.6%) discontinued treatment.

  14. 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...... 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......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...

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

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    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.

  16. 5-Alkyloxytryptamines are membrane-targeting, broad-spectrum antibiotics.

    Science.gov (United States)

    Faulkner, Katherine C; Hurley, Katherine A; Weibel, Douglas B

    2016-11-15

    Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants. We synthesized 5-alkyloxytryptamine analogs and found that an alkyl chain length of 6-12 carbons and a primary ammonium group are necessary for the antibacterial activity of the compounds, and an alkyl chain length of 6-10 carbons increased the membrane permeability of Gram-positive and Gram-negative bacteria. Although several of the most potent analogs also have activity against the membranes of human embryonic kidney cells, we demonstrate that below the minimum inhibitory concentration (MIC)-where mammalian cell toxicity is low-these compounds may be successfully used as adjuvants for chloramphenicol, tetracycline, ciprofloxacin, and rifampicin against clinical strains of Salmonella typhimurium, Acinetobacter baumannii and Staphylococcus aureus, reducing MIC values by as much as several logs.

  17. The broad spectrum revisited: Evidence from plant remains

    Science.gov (United States)

    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 transition to farming in southwest Asia entailed a period during which foragers broadened their resource base to encompass a wide array of foods that were previously ignored in an attempt to overcome food shortages. Although these resources undoubtedly included plants, nearly all BSR hypothesis-inspired research has focused on animals because of a dearth of Upper Paleolithic archaeobotanical assemblages. Now, however, a collection of >90,000 plant remains, recently recovered from the Stone Age site Ohalo II (23,000 B.P.), Israel, offers insights into the plant foods of the late Upper Paleolithic. The staple foods of this assemblage were wild grasses, pushing back the dietary shift to grains some 10,000 years earlier than previously recognized. Besides the cereals (wild wheat and barley), small-grained grasses made up a large component of the assemblage, indicating that the BSR in the Levant was even broader than originally conceived, encompassing what would have been low-ranked plant foods. Over the next 15,000 years small-grained grasses were gradually replaced by the cereals and ultimately disappeared from the Levantine diet. PMID:15210984

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

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    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

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

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    Avi Raveh

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

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

    Science.gov (United States)

    Raveh, Avi; Delekta, Phillip C; Dobry, Craig J; Peng, Weiping; Schultz, Pamela J; Blakely, Pennelope K; Tai, Andrew W; Matainaho, Teatulohi; Irani, David N; Sherman, David H; Miller, David J

    2013-01-01

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

  1. 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.

  2. Voltage-induced reduction of graphene oxide

    Science.gov (United States)

    Faucett, Austin C.

    Graphene Oxide (GO) is being widely researched as a precursor for the mass production of graphene, and as a versatile material in its own right for flexible electronics, chemical sensors, and energy harvesting applications. Reduction of GO, an electrically insulating material, into reduced graphene oxide (rGO) restores electrical conductivity via removal of oxygen-containing functional groups. Here, a reduction method using an applied electrical bias, known as voltage-induced reduction, is explored. Voltage-induced reduction can be performed under ambient conditions and avoids the use of hazardous chemicals or high temperatures common with standard methods, but little is known about the reduction mechanisms and the quality of rGO produced with this method. This work performs extensive structural and electrical characterization of voltage-reduced GO (V-rGO) and shows that it is competitive with standard methods. Beyond its potential use as a facile and eco-friendly processing approach, V-rGO reduction also offers record high-resolution patterning capabilities. In this work, the spatial resolution limits of voltage-induced reduction, performed using a conductive atomic force microscope probe, are explored. It is shown that arbitrary V-rGO conductive features can be patterned into insulating GO with nanoscale resolution. The localization of voltage-induced reduction to length scales < 10 nm allows studies of reduction reaction kinetics, using electrical current obtained in-situ, with statistical robustness. Methods for patterning V-rGO nanoribbons are then developed. After presenting sub-10nm patterning of V-rGO nanoribbons in GO single sheets and films, the performance of V-rGO nanoribbon field effect transistors (FETs) are demonstrated. Preliminary measurements show an increase in electrical current on/off ratios as compared to large-area rGO FETs, indicating transport gap modulation that is possibly due to quantum confinement effects.

  3. In vitro studies of BMY-28142, a new broad-spectrum cephalosporin.

    OpenAIRE

    Bodey, G.P.; Ho, D H; Leblanc, B.

    1985-01-01

    BMY-28142 was compared with other broad-spectrum antibiotics against gram-positive cocci and gram-negative bacilli. BMY-28142 was highly active against all gram-negative bacilli and especially against Enterobacter cloacae, Serratia marcescens, and Morganella morganii. Its in vitro activity suggests that BMY-28142 should prove to be useful for the treatment of gram-negative bacillary infections.

  4. Control of helminthosis in lambs by strategic treatment with closantel and broad-spectrum anthelmintics.

    Science.gov (United States)

    Dash, K M

    1986-01-01

    Treatment of ewes with broad-spectrum anthelmintic in August (pre-lambing) and early November, and of lambs in early November and early February, was effective in controlling infections with Trichostrongylus spp in lambs reared on contaminated pastures under set-stocked conditions. It was ineffective in controlling infections with Haemonchus contortus; 82% of lambs had to be withdrawn from the experiment because of severe haemonchosis. Treatment with closantel (7.5 mg/kg) at the same times was very effective against H. contortus but ineffective against Trichostrongylus spp; 25% of lambs had to be withdrawn because of severe trichostrongylosis. The same schedule using broad spectrum anthelmintic and closantel administered concurrently was effective against both parasites; no lambs had to be withdrawn and the bodyweight gain of lambs was higher than in lambs treated with broad-spectrum anthelmintic or closantel alone. The results provide a basis on which to develop a preventive anthelmintic treatment program to control haemonchosis and trichostrongylosis in sheep which will allow the current high frequency of treatment with broad-spectrum anthelmintics to be reduced. Such a program may retard selection for anthelmintic resistance in Trichostrongylus spp.

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

    Science.gov (United States)

    Iyer, Rupa; Damania, Ashish

    2016-04-14

    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.

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. Broad-spectrum antimicrobial epiphytic and endophytic fungi from marine organisms: isolation, bioassay and taxonomy.

    Science.gov (United States)

    Zhang, Yi; Mu, Jun; Feng, Yan; Kang, Yue; Zhang, Jia; Gu, Peng-Juan; Wang, Yu; Ma, Li-Fang; Zhu, Yan-Hua

    2009-04-17

    In the search for new marine derived antibiotics, 43 epi- and endophytic fungal strains were isolated from the surface or the inner tissue of different marine plants and invertebrates. Through preliminary and secondary screening, 10 of them were found to be able to produce broad-spectrum antimicrobial metabolites. By morphological and molecular biological methods, three active strains were characterized to be Penicillium glabrum, Fusarium oxysporum, and Alternaria alternata.

  14. Broad-Spectrum Antimicrobial Epiphytic and Endophytic Fungi from Marine Organisms: Isolation, Bioassay and Taxonomy

    Directory of Open Access Journals (Sweden)

    Yan-Hua Zhu

    2009-04-01

    Full Text Available In the search for new marine derived antibiotics, 43 epi- and endophytic fungal strains were isolated from the surface or the inner tissue of different marine plants and invertebrates. Through preliminary and secondary screening, 10 of them were found to be able to produce broad-spectrum antimicrobial metabolites. By morphological and molecular biological methods, three active strains were characterized to be Penicillium glabrum, Fusarium oxysporum, and Alternaria alternata.

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

    OpenAIRE

    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...

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

    OpenAIRE

    Luca Ruiu

    2013-01-01

    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 inc...

  17. Broad-Spectrum Antimicrobial Epiphytic and Endophytic Fungi from Marine Organisms: Isolation, Bioassay and Taxonomy

    OpenAIRE

    2009-01-01

    In the search for new marine derived antibiotics, 43 epi- and endophytic fungal strains were isolated from the surface or the inner tissue of different marine plants and invertebrates. Through preliminary and secondary screening, 10 of them were found to be able to produce broad-spectrum antimicrobial metabolites. By morphological and molecular biological methods, three active strains were characterized to be Penicillium glabrum, Fusarium oxysporum, and Alternaria alternata.

  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. Broad spectrum moderators and advanced reflector filters using 208Pb

    OpenAIRE

    Schönfeldt, Troels; Batkov, K.; Klinkby, Esben Bryndt; Lauritzen, Bent; F.Mezei; Muhrer, G.; PITCHER, E; Takibayev, A.; Willendrup, Peter Kjær; Zanini, L.

    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 sl...

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

    Science.gov (United States)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L; Clasen, Julie; Jochumsen, Nicholas; Molin, Søren; Jelsbak, Lars; Ingmer, Hanne; Folkesson, Anders

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

  1. A comparison of effects of broad-spectrum antibiotics and biosurfactants on established bacterial biofilms.

    Science.gov (United States)

    Quinn, Gerry A; Maloy, Aaron P; Banat, Malik M; Banat, Ibrahim M

    2013-11-01

    Current antibiofilm solutions based on planktonic bacterial physiology have limited efficacy in clinical and occasionally environmental settings. This has prompted a search for suitable alternatives to conventional therapies. This study compares the inhibitory properties of two biological surfactants (rhamnolipids and a plant-derived surfactant) against a selection of broad-spectrum antibiotics (ampicillin, chloramphenicol and kanamycin). Testing was carried out on a range of bacterial physiologies from planktonic and mixed bacterial biofilms. Rhamnolipids (Rhs) have been extensively characterised for their role in the development of biofilms and inhibition of planktonic bacteria. However, there are limited direct comparisons with antimicrobial substances on established biofilms comprising single or mixed bacterial strains. Baseline measurements of inhibitory activity using planktonic bacterial assays established that broad-spectrum antibiotics were 500 times more effective at inhibiting bacterial growth than either Rhs or plant surfactants. Conversely, Rhs and plant biosurfactants reduced biofilm biomass of established single bacterial biofilms by 74-88 and 74-98 %, respectively. Only kanamycin showed activity against biofilms of Bacillus subtilis and Staphylococcus aureus. Broad-spectrum antibiotics were also ineffective against a complex biofilm of marine bacteria; however, Rhs and plant biosurfactants reduced biofilm biomass by 69 and 42 %, respectively. These data suggest that Rhs and plant-derived surfactants may have an important role in the inhibition of complex biofilms.

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

    Science.gov (United States)

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

    2010-03-01

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

  3. 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.

  4. In vitro assessment of the broad-spectrum ultraviolet protection of sunscreen products.

    Science.gov (United States)

    Diffey, B L; Tanner, P R; Matts, P J; Nash, J F

    2000-12-01

    There are considerable data to suggest that protection from solar ultraviolet (UV) radiation will reduce the risk of acute and chronic skin damage in humans. Whereas the sun protection factor (SPF) provides an index of protection against erythemally effective solar UV, largely confined to the UVB (290-320 nm) and short-wavelength UVA (320-340 nm) region, there is currently no agreed-upon method to measure broad-spectrum protection against long-wavelength UVA (340-400 nm). The objective of these studies was to assess the potential of in vitro UV substrate spectrophotometry and subsequent calculation of the "critical wavelength" value as a measure of broad-spectrum UV protection and as a routine, practical procedure for classification of sunscreen products. The spectral absorption of 59 commercially available sunscreen products and multiple experimental formulas with one or more UV filters was measured. Sunscreen product, 1 mg/cm(2), was applied to a hydrated synthetic collagen substrate, preirradiated with a solar simulator, and then subjected to UV substrate spectrophotometry. Multiple determinations from 5 independent samples per product were used to calculate the critical wavelength value, defined as the wavelength at which the integral of the spectral absorbance curve reached 90% of the integral from 290 to 400 nm. We found that a recognized long-wave UVA active ingredient such as titanium dioxide, zinc oxide, or avobenzone is a necessary but insufficient product requirement for achieving the highest proposed broad-spectrum classification, that is, critical wavelength of 370 nm or more. Although SPF and critical wavelength are largely independent of each other, UVA absorbance must increase commensurate with SPF to maintain the same critical wavelength value. Substrate spectrophotometry and the calculation of critical wavelength can readily account for sunscreen photostability by UV preirradiation. Finally, there is also a strong positive relationship between

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

    Science.gov (United States)

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

    2016-03-02

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

  6. Towards establishing broad-spectrum disease resistance in plants: silicon leads the way.

    Science.gov (United States)

    Van Bockhaven, Jonas; De Vleesschauwer, David; Höfte, Monica

    2013-03-01

    Plants are constantly threatened by a wide array of microbial pathogens. Pathogen invasion can lead to vast yield losses and the demand for sustainable plant-protection strategies has never been greater. Chemical plant activators and selected strains of rhizobacteria can increase resistance against specific types of pathogens but these treatments are often ineffective or even cause susceptibility against others. Silicon application is one of the scarce examples of a treatment that effectively induces broad-spectrum disease resistance. The prophylactic effect of silicon is considered to be the result of both passive and active defences. Although the phenomenon has been known for decades, very little is known about the molecular basis of silicon-afforded disease control. By combining knowledge on how silicon interacts with cell metabolism in diatoms and plants, this review describes silicon-induced regulatory mechanisms that might account for broad-spectrum plant disease resistance. Priming of plant immune responses, alterations in phytohormone homeostasis, regulation of iron homeostasis, silicon-driven photorespiration and interaction with defence signalling components all are potential mechanisms involved in regulating silicon-triggered resistance responses. Further elucidating how silicon exerts its beneficial properties may create new avenues for developing plants that are better able to withstand multiple attackers.

  7. 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.

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

    Science.gov (United States)

    Ruiu, Luca

    2013-09-05

    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.

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

    Science.gov (United States)

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

    2015-08-01

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

  10. 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.

  11. Synergistic effect of broad-spectrum Sunscreens and antihistamines in the control of idiopathic solar urticaria

    DEFF Research Database (Denmark)

    Faurschou, A.; Wulf, Hans Chr.

    2008-01-01

    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....... The patients were then treated with a high-protection, broad-spectrum sunscreen and a nonsedative antihistamine alone and in combination and underwent similar phototesting. The use of sunscreen allowed the patients to tolerate much higher doses of UV radiation (32-38 times the MUD on untreated skin......). 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...

  12. 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.

  13. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases

    Science.gov (United States)

    Dinarello, Charles A.; Simon, Anna; van der Meer, Jos W. M.

    2013-01-01

    Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials. PMID:22850787

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Interfamily transfer of a plant pattern-recognition receptor confers broad-spectrum bacterial resistance.

    Science.gov (United States)

    Lacombe, Séverine; Rougon-Cardoso, Alejandra; Sherwood, Emma; Peeters, Nemo; Dahlbeck, Douglas; van Esse, H Peter; Smoker, Matthew; Rallapalli, Ghanasyam; Thomma, Bart P H J; Staskawicz, Brian; Jones, Jonathan D G; Zipfel, Cyril

    2010-04-01

    Plant diseases cause massive losses in agriculture. Increasing the natural defenses of plants may reduce the impact of phytopathogens on agricultural productivity. Pattern-recognition receptors (PRRs) detect microbes by recognizing conserved pathogen-associated molecular patterns (PAMPs). Although the overall importance of PAMP-triggered immunity for plant defense is established, it has not been used to confer disease resistance in crops. We report that activity of a PRR is retained after its transfer between two plant families. Expression of EFR (ref. 4), a PRR from the cruciferous plant Arabidopsis thaliana, confers responsiveness to bacterial elongation factor Tu in the solanaceous plants Nicotiana benthamiana and tomato (Solanum lycopersicum), making them more resistant to a range of phytopathogenic bacteria from different genera. Our results in controlled laboratory conditions suggest that heterologous expression of PAMP recognition systems could be used to engineer broad-spectrum disease resistance to important bacterial pathogens, potentially enabling more durable and sustainable resistance in the field.

  16. The Arabidopsis NPR1 gene confers broad-spectrum disease resistance in strawberry.

    Science.gov (United States)

    Silva, Katchen Julliany P; Brunings, Asha; Peres, Natalia A; Mou, Zhonglin; Folta, Kevin M

    2015-08-01

    Although strawberry is an economically important fruit crop worldwide, production of strawberry is limited by its susceptibility to a wide range of pathogens and the lack of major commercial cultivars with high levels of resistance to multiple pathogens. The objective of this study is to ectopically express the Arabidopsis thaliana NPR1 gene (AtNPR1) in the diploid strawberry Fragaria vesca L. and to test transgenic plants for disease resistance. AtNPR1 is a key positive regulator of the long-lasting broad-spectrum resistance known as systemic acquired resistance (SAR) and has been shown to confer resistance to a number of pathogens when overexpressed in Arabidopsis or ectopically expressed in several crop species. We show that ectopic expression of AtNPR1 in strawberry increases resistance to anthracnose, powdery mildew, and angular leaf spot, which are caused by different fungal or bacterial pathogens. The increased resistance is related to the relative expression levels of AtNPR1 in the transgenic plants. In contrast to Arabidopsis plants overexpressing AtNPR1, which grow normally and do not constitutively express defense genes, the strawberry transgenic plants are shorter than non-transformed controls, and most of them fail to produce runners and fruits. Consistently, most of the transgenic lines constitutively express the defense gene FvPR5, suggesting that the SAR activation mechanisms in strawberry and Arabidopsis are different. Nevertheless, our results indicate that overexpression of AtNPR1 holds the potential for generation of broad-spectrum disease resistance in strawberry.

  17. Immune Responses to Broad-Spectrum Antibiotic Treatment and Fecal Microbiota Transplantation in Mice

    Science.gov (United States)

    Ekmekciu, Ira; von Klitzing, Eliane; Fiebiger, Ulrike; Escher, Ulrike; Neumann, Christian; Bacher, Petra; Scheffold, Alexander; Kühl, Anja A.; Bereswill, Stefan; Heimesaat, Markus M.

    2017-01-01

    Compelling evidence demonstrates the pivotal role of the commensal intestinal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. Aim of this study was to investigate the impact of antibiotics induced depletion and subsequent restoration of the intestinal microbiota composition on the murine mucosal and systemic immunity. To address this, conventional C57BL/6j mice were subjected to broad-spectrum antibiotic treatment for 8 weeks. Restoration of the intestinal microbiota by peroral fecal microbiota transplantation (FMT) led to reestablishment of small intestinal CD4+, CD8+, and B220+ as well as of colonic CD4+ cell numbers as early as 7 days post-FMT. However, at d28 following FMT, colonic CD4+ and B220+ cell numbers were comparable to those in secondary abiotic (ABx) mice. Remarkably, CD8+ cell numbers were reduced in the colon upon antibiotic treatment, and FMT was not sufficient to restore this immune cell subset. Furthermore, absence of gut microbial stimuli resulted in decreased percentages of memory/effector T cells, regulatory T cells, and activated dendritic cells in the small intestine, colon, mesenteric lymph nodes (MLN), and spleen. Concurrent antibiotic treatment caused decreased cytokine production (IFN-γ, IL-17, IL-22, and IL-10) of CD4+ cells in respective compartments. These effects were, however, completely restored upon FMT. In summary, broad-spectrum antibiotic treatment resulted in profound local (i.e., small and large intestinal), peripheral (i.e., MLN), and systemic (i.e., splenic) changes in the immune cell repertoire that could, at least in part, be restored upon FMT. Further studies need to unravel the distinct molecular mechanisms underlying microbiota-driven changes in immune homeostasis subsequently providing novel therapeutic or even preventive approaches in human immunopathologies. PMID:28469619

  18. A robust, single-injection method for targeted, broad-spectrum plasma metabolomics.

    Science.gov (United States)

    Li, Kefeng; Naviaux, Jane C; Bright, A Taylor; Wang, Lin; Naviaux, Robert K

    2017-01-01

    Metabolomics is a powerful emerging technology for studying the systems biology and chemistry of health and disease. Current targeted methods are often limited by the number of analytes that can be measured, and/or require multiple injections. We developed a single-injection, targeted broad-spectrum plasma metabolomic method on a SCIEX Qtrap 5500 LC-ESI-MS/MS platform. Analytical validation was conducted for the reproducibility, linearity, carryover and blood collection tube effects. The method was also clinically validated for its potential utility in the diagnosis of chronic fatigue syndrome (CFS) using a cohort of 22 males CFS and 18 age- and sex-matched controls. Optimization of LC conditions and MS/MS parameters enabled the measurement of 610 key metabolites from 63 biochemical pathways and 95 stable isotope standards in a 45-minute HILIC method using a single injection without sacrificing sensitivity. The total imprecision (CVtotal) of peak area was 12% for both the control and CFS pools. The 8 metabolites selected in our previous study (PMID: 27573827) performed well in a clinical validation analysis even when the case and control samples were analyzed 1.5 years later on a different instrument by a different investigator, yielding a diagnostic accuracy of 95% (95% CI 85-100%) measured by the area under the ROC curve. A reliable and reproducible, broad-spectrum, targeted metabolomic method was developed, capable of measuring over 600 metabolites in plasma in a single injection. The method might be a useful tool in helping the diagnosis of CFS or other complex diseases.

  19. 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

  20. 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.

  1. Pharmacokinetics and pharmacodynamics of ceftobiprole, an anti-MRSA cephalosporin with broad-spectrum activity.

    Science.gov (United States)

    Murthy, Bindu; Schmitt-Hoffmann, Anne

    2008-01-01

    Ceftobiprole, a beta-lactam, is the first of a new generation of broad-spectrum cephalosporins in late-stage development with activity against methicillin-resistant Staphylococcus aureus (MRSA) in addition to broad-spectrum bactericidal activity against other Gram-positive and Gram-negative pathogens. The prodrug, ceftobiprole medocaril, is converted rapidly and almost completely to the active drug, ceftobiprole, upon infusion by type A esterases. In humans, ceftobiprole binds minimally (16%) to plasma proteins, and binding is independent of the drug and protein concentrations. Its steady-state volume of distribution (18.4 L) approximates the extracellular fluid volume in humans. Ceftobiprole undergoes minimal hepatic metabolism, and the primary metabolite is the beta-lactam ring-opened hydrolysis product (open-ring metabolite). Systemic exposure of the open-ring metabolite accounts for 4% of ceftobiprole exposure following single-dose administration; approximately 5% of the dose is excreted in the urine as the metabolite. Ceftobiprole does not significantly induce or inhibit relevant cytochrome P450 enzymes and is neither a substrate nor an inhibitor of P-glycoprotein. Ceftobiprole is rapidly eliminated, primarily unchanged, by renal excretion, with a terminal elimination half-life of 3 hours; the predominant mechanism responsible for elimination is glomerular filtration, with approximately 89% of the dose being excreted as the prodrug, active drug (ceftobiprole) and open-ring metabolite. The pharmacokinetics of ceftobiprole are linear following single and multiple infusions of 125-1000 mg. Steady-state drug concentrations are attained on the first day of dosing, with no appreciable accumulation when administered three times daily (every 8 hours) and twice daily (every 12 hours) in subjects with normal renal function. Low intersubject variability has been seen across studies. Ceftobiprole exposure is slightly higher (~15%) in females than in males; this difference

  2. Development of broad-spectrum antimicrobial latex paint surfaces employing active amphiphilic compounds.

    Science.gov (United States)

    Fulmer, Preston A; Wynne, James H

    2011-08-01

    With the increase in antibiotic-resistant microbes, the production of self-decontaminating surfaces has become an area of research that has seen a surge of interest in recent years. Such surfaces, when incorporated into commercial products such as children's toys, medical devices and hospital surfaces could reduce the number of infections caused by pathogenic microorganisms. A number of active components for self-decontaminating surfaces have been investigated, including common antibiotics, metal ions, quaternary ammonium salts (QAS), and antimicrobial peptides (AMP). A recent research focus has been development of a wide range of amphiphilic antimicrobial additives that when combined with modern low volatile organic compound (VOC), water-based paints leads to a surface concentration of the active compounds as the coating cures. Herein we report the development of antimicrobial coatings containing a variety of additives, both QAS and AMP that are active against a broad-spectrum of potentially pathogenic bacteria (1-7 log kill), as well as enveloped viruses (2-7 log kill) and fungi (1-2 log kill). Additionally, these additives were compatible with water-dispersed acrylate coatings (latex paint) which have a broad range of real world applicability, and remained active for multiple challenges and when exposed to various cleaning scenarios in which they might encounter in real world situations.

  3. 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.

  4. Tempered mlo broad-spectrum resistance to barley powdery mildew in an Ethiopian landrace.

    Science.gov (United States)

    Ge, Xintian; Deng, Weiwei; Lee, Zheng Zhou; Lopez-Ruiz, Francisco J; Schweizer, Patrick; Ellwood, Simon R

    2016-07-12

    Recessive mutations in the Mlo gene confer broad spectrum resistance in barley (Hordeum vulgare) to powdery mildew (Blumeria graminis f. sp. hordei), a widespread and damaging disease. However, all alleles discovered to date also display deleterious pleiotropic effects, including the naturally occurring mlo-11 mutant which is widely deployed in Europe. Recessive resistance was discovered in Eth295, an Ethiopian landrace, which was developmentally controlled and quantitative without spontaneous cell wall appositions or extensive necrosis and loss of photosynthetic tissue. This resistance is determined by two copies of the mlo-11 repeat units, that occur upstream to the wild-type Mlo gene, compared to 11-12 in commonly grown cultivars and was designated mlo-11 (cnv2). mlo-11 repeat unit copy number-dependent DNA methylation corresponded with cytological and macroscopic phenotypic differences between copy number variants. Sequence data indicated mlo-11 (cnv2) formed via recombination between progenitor mlo-11 repeat units and the 3' end of an adjacent stowaway MITE containing region. mlo-11 (cnv2) is the only example of a moderated mlo variant discovered to date and may have arisen by natural selection against the deleterious effects of the progenitor mlo-11 repeat unit configuration.

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

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

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

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

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    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.

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

    Science.gov (United States)

    Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G.; McAdam, Alexander J.; Husson, Robert N.; Tamayo, Giselle; Clardy, Jon; 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 that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

  8. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses.

    Science.gov (United States)

    Sui, Jianhua; Hwang, William C; Perez, Sandra; Wei, Ge; Aird, Daniel; Chen, Li-mei; Santelli, Eugenio; Stec, Boguslaw; Cadwell, Greg; Ali, Maryam; Wan, Hongquan; Murakami, Akikazu; Yammanuru, Anuradha; Han, Thomas; Cox, Nancy J; Bankston, Laurie A; Donis, Ruben O; Liddington, Robert C; Marasco, Wayne A

    2009-03-01

    Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.

  9. 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.

  10. Growth and characterization of broad spectrum infrared emitting GaInAsP/InP heterostructures

    Science.gov (United States)

    Rakovics, V.; Nádas, J.; Réti, I.; Dücső, Cs.; Battistig, G.

    2017-06-01

    Broad spectrum InGaAsP/InP light emitting heterostructures were grown by low temperature liquid phase epitaxy (LPE). The structure of the LED wafers was investigated by optical transmission measurements, and the layer thicknesses were also measured by electron microscopy. Two quaternary light emitting layers of different composition were built in one device structure in order to broaden the usable wavelength range of the emission spectrum. One of the layers is electrically, whereas the other is optically excited as a result of internal absorption and re-emission of the LED light. As a result of this absorption and re-emission process the modified LED chips have substantially broader emission spectra and higher radiance than the conventional surface emitting multi-wavelength NIR LED structures. The two emission peaks of the spectrum were designed for matching the first and second harmonic wavelength of the fundamental absorption band of C-H bonds. The internal quantum efficiency of the wavelength conversion in this type of LEDs is nearly 100%.

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

    Science.gov (United States)

    Lim, Kong Boon; Balolong, Marilen P; Kim, Sang Hoon; Oh, Ju Kyoung; Lee, Ji Yoon; Kang, Dae-Kyung

    2016-01-01

    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.

  12. 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

  13. 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.

  14. Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei.

    Science.gov (United States)

    Arrighi, Romanico B G; Ebikeme, Charles; Jiang, Yang; Ranford-Cartwright, Lisa; Barrett, Michael P; Langel, Ulo; Faye, Ingrid

    2008-09-01

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  15. 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

  16. 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...

  17. Microbiome disruption and recovery in the fish Gambusia affinis following exposure to broad-spectrum antibiotic

    Directory of Open Access Journals (Sweden)

    Carlson JM

    2017-05-01

    Full Text Available Jeanette M Carlson,1 Annie B Leonard,1 Embriette R Hyde,2,3 Joseph F Petrosino,2,3 Todd P Primm1 1Department of Biological Sciences, Sam Houston State University, Huntsville, 2Alkek Center for Metagenomics and Microbiome Research, 3Integrative Molecular and Biomedical Sciences Training Program, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA Abstract: Antibiotics are a relatively common disturbance to the normal microbiota of humans and agricultural animals, sometimes resulting in severe side effects such as antibiotic-associated enterocolitis. Gambusia affinis was used as a vertebrate model for effects of a broad-spectrum antibiotic, rifampicin, on the skin and gut mucosal microbiomes. The fish were exposed to the antibiotic in the water column for 1 week, and then monitored during recovery. As observed via culture, viable counts from the skin microbiome dropped strongly yet returned to pretreatment levels by 1.6 days and became >70% resistant. The gut microbiome counts dropped and took longer to recover (2.6 days, and became >90% drug resistant. The resistance persisted at ~20% of skin counts in the absence of antibiotic selection for 2 weeks. A community biochemical analysis measuring the presence/absence of 31 activities observed a 39% change in results after 3 days of antibiotic treatment. The antibiotic lowered the skin and gut microbiome community diversity and altered taxonomic composition, observed by 16S rRNA profiling. A 1-week recovery period did not return diversity or composition to pretreatment levels. The genus Myroides dominated both the microbiomes during the treatment, but was not stable and declined in abundance over time during recovery. Rifampicin selected for members of the family Comamonadaceae in the skin but not the gut microbiome. Consistent with other studies, this tractable animal model shows lasting effects on mucosal microbiomes following antibiotic exposure, including

  18. 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

    2016-05-06

    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

  19. 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.

  20. Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke

    Science.gov (United States)

    Winek, Katarzyna; Engel, Odilo; Koduah, Priscilla; Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Dames, Claudia; Kershaw, Olivia; Gruber, Achim D.; Curato, Caterina; Oyama, Naoki; Meisel, Christian; Meisel, Andreas

    2016-01-01

    Background and Purpose— Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain–gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke. Methods— We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry. Results— We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups. Conclusions— Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome. PMID:27056982

  1. 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.

  2. Activities of ceftobiprole, a novel broad-spectrum cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis.

    Science.gov (United States)

    Bogdanovich, Tatiana; Clark, Catherine; Ednie, Lois; Lin, Gengrong; Smith, Kathy; Shapiro, Stuart; Appelbaum, Peter C

    2006-06-01

    Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cephem currently in phase III clinical trials, had MICs between 0.008 microg/ml and 8.0 microg/ml for 321 clinical isolates of Haemophilus influenzae and between Ceftobiprole MIC(50) and MIC(90) values for H. influenzae were 0.06 microg/ml and 0.25 microg/ml for beta-lactamase-positive strains (n = 262), 0.03 microg/ml and 0.25 microg/ml for beta-lactamase-negative strains (n = 40), and 0.5 microg/ml and 2.0 microg/ml for beta-lactamase-negative ampicillin-resistant strains (n = 19), respectively. Ceftobiprole MIC(50) and MIC(90) values for beta-lactamase-positive M. catarrhalis strains (n = 40) were 0.12 microg/ml and 0.5 microg/ml, respectively, whereas the ceftobiprole MIC range for beta-lactamase-negative M. catarrhalis strains (n = 9) was ceftobiprole, whereas amoxicillin-clavulanate MICs usually were higher than those of ceftobiprole. Azithromycin and telithromycin had unimodal MIC distributions against H. influenzae, with MIC(90) values of azithromycin and telithromycin of 2 microg/ml and 4 microg/ml, respectively. Except for selected quinolone-nonsusceptible H. influenzae strains, moxifloxacin proved highly active, with MIC(90) values of 0.12 microg/ml. Time-kill analyses showed that ceftobiprole, ceftriaxone, cefpodoxime, amoxicillin-clavulanate, azithromycin, telithromycin, and moxifloxacin were bactericidal at 2x MIC by 24 h against all 10 H. influenzae strains surveyed. Only modest increases in MICs were found for H. influenzae or M. catarrhalis clones after 50 serial passages in the presence of subinhibitory concentrations of ceftobiprole, and single-passage selection showed that the selection frequency of H. influenzae or M. catarrhalis clones with elevated ceftobiprole MICs is quite low.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. 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.

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

    National Research Council Canada - National Science Library

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

    2015-01-01

    .... 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...

  6. 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.

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

    Science.gov (United States)

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

    2015-08-14

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

  8. 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

  9. Ceftobiprole: a review of a broad-spectrum and anti-MRSA cephalosporin.

    Science.gov (United States)

    Zhanel, George G; Lam, Ashley; Schweizer, Frank; Thomson, Kristjan; Walkty, Andrew; Rubinstein, Ethan; Gin, Alfred S; Hoban, Daryl J; Noreddin, Ayman M; Karlowsky, James A

    2008-01-01

    Ceftobiprole, an investigational cephalosporin, is currently in phase III clinical development. Ceftobiprole is a broad-spectrum cephalosporin with demonstrated in vitro activity against Gram-positive cocci, including meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant S. epidermidis, penicillin-resistant S. pneumoniae, Enterococcus faecalis, Gram-negative bacilli including AmpC-producing Escherichia coli and Pseudomonas aeruginosa, but excluding extended-spectrum beta-lactamase-producing strains. Like cefotaxime, ceftriaxone, ceftazidime, and cefepime, ceftobiprole demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. In single-step and serial passage in vitro resistance development studies, ceftobiprole demonstrated a low propensity to select for resistant subpopulations. Ceftobiprole, like cefepime, is a weak inducer and a poor substrate for AmpC beta-lactamases.Ceftobiprole medocaril, the prodrug of ceftobiprole, is converted by plasma esterases to ceftobiprole in ceftobiprole observed at the end of a single 30-minute infusion were 35.5 mug/mL for a 500-mg dose and 59.6 mug/mL for a 750-mg dose. The volume of distribution of ceftobiprole is 0.26 L/kg ( approximately 18 L), protein binding is 16%, and its serum half-life is approximately 3.5 hours. Ceftobiprole is renally excreted ( approximately 70% in the active form) and systemic clearance correlates with creatinine clearance, meaning that dosage adjustment is required in patients with renal dysfunction. Ceftobiprole has a modest post-antibiotic effect (PAE) of approximately 0.5 hours for MRSA and a longer PAE of approximately 2 hours for penicillin-resistant pneumococci. Ceftobiprole, when administered intravenously at 500 mg once every 8 hours (2-hour infusion), has a >90% probability of achieving f T(>MIC) (free drug concentration exceeds the minimum inhibitory concentration [MIC]) for 40% and 60%, respectively, of the dosing

  10. 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.

  11. Targeting Class A and C Serine β-Lactamases with a Broad-Spectrum Boronic Acid Derivative

    Science.gov (United States)

    2015-01-01

    Production of β-lactamases (BLs) is the most widespread resistance mechanism adopted by bacteria to fight β-lactam antibiotics. The substrate spectrum of BLs has become increasingly broad, posing a serious health problem. Thus, there is an urgent need for novel BL inhibitors. Boronic acid transition-state analogues are able to reverse the resistance conferred by class A and C BLs. We describe a boronic acid analogue possessing interesting and potent broad-spectrum activity vs class A and C serine-based BLs. Starting from benzo(b)thiophene-2-boronic acid (BZBTH2B), a nanomolar non-β-lactam inhibitor of AmpC that can potentiate the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria, we designed a novel broad-spectrum nanomolar inhibitor of class A and C BLs. Structure-based drug design (SBDD), synthesis, enzymology data, and X-ray crystallography results are discussed. We clarified the inhibitor binding geometry responsible for broad-spectrum activity vs serine-active BLs using double mutant thermodynamic cycle studies. PMID:24882105

  12. 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.

  13. Pinellia ternata agglutinin expression in chloroplasts confers broad spectrum resistance against aphid, whitefly, Lepidopteran insects, bacterial and viral pathogens.

    Science.gov (United States)

    Jin, Shuangxia; Zhang, Xianlong; Daniell, Henry

    2012-04-01

    Broad spectrum protection against different insects and pathogens requires multigene engineering. However, such broad spectrum protection against biotic stress is provided by a single protein in some medicinal plants. Therefore, tobacco chloroplasts were transformed with the agglutinin gene from Pinellia ternata (pta), a widely cultivated Chinese medicinal herb. Pinellia ternata agglutinin (PTA) was expressed up to 9.2% of total soluble protein in mature leaves. Purified PTA showed similar hemagglutination activity as snowdrop lectin. Artificial diet with purified PTA from transplastomic plants showed marked and broad insecticidal activity. In planta bioassays conducted with T0 or T1 generation PTA lines showed that the growth of aphid Myzus persicae (Sulzer) was reduced by 89%-92% when compared with untransformed (UT) plants. Similarly, the larval survival and total population of whitefly (Bemisia tabaci) on transplastomic lines were reduced by 91%-93% when compared with UT plants. This is indeed the first report of lectin controlling whitefly infestation. When transplastomic PTA leaves were fed to corn earworm (Helicoverpa zea), tobacco budworm (Heliothis virescens) or the beet armyworm (spodoptera exigua), 100% mortality was observed against all these three insects. In planta bioassays revealed Erwinia population to be 10,000-fold higher in control than in PTA lines. Similar results were observed with tobacco mosaic virus (TMV) challenge. Therefore, broad spectrum resistance to homopteran (sap-sucking), Lepidopteran insects as well as anti-bacterial or anti-viral activity observed in PTA lines provides a new option to engineer protection against biotic stress by hyper-expression of an unique protein that is naturally present in a medicinal plant.

  14. Broad-spectrum acquired resistance in barley induced by the Pseudomonas pathosystem shares transcriptional components with Arabidopsis systemic acquired resistance.

    Science.gov (United States)

    Colebrook, E H; Creissen, G; McGrann, G R D; Dreos, R; Lamb, C; Boyd, L A

    2012-05-01

    Inducible resistance responses play a central role in the defense of plants against pathogen attack. Acquired resistance (AR) is induced alongside defense toward primary attack, providing broad-spectrum protection against subsequent pathogen challenge. The localization and molecular basis of AR in cereals is poorly understood, in contrast with the well-characterized systemic acquired resistance (SAR) response in Arabidopsis. Here, we use Pseudomonas syringae as a biological inducer of AR in barley, providing a clear frame of reference to the Arabidopsis-P. syringae pathosystem. Inoculation of barley leaf tissue with the nonadapted P. syringae pv. tomato avrRpm1 (PstavrRpm1) induced an active local defense response. Furthermore, inoculation of barley with PstavrRpm1 resulted in the induction of broad-spectrum AR at a distance from the local lesion, "adjacent" AR, effective against compatible isolates of P. syringae and Magnaporthe oryzae. Global transcriptional profiling of this adjacent AR revealed similarities with the transcriptional profile of SAR in Arabidopsis, as well as transcripts previously associated with chemically induced AR in cereals, suggesting that AR in barley and SAR in Arabidopsis may be mediated by analogous pathways.

  15. Design of a photostabilizer having built-in antioxidant functionality and its utility in obtaining broad-spectrum sunscreen formulations.

    Science.gov (United States)

    Chaudhuri, Ratan K; Lascu, Zoia; Puccetti, Germain; Deshpande, Anant A; Paknikar, Sashikumar K

    2006-01-01

    Di-2,2'-diethylhexyl-3,5-dimethoxy-4-hydroxy-benzylidenemalonate (INCI name diethylhexyl syringylidene malonate, DESM), the target photostabilizer, was synthesized in one step by condensation of 3,5-dimethoxy-4-hydroxy benzaldehyde (Syringaldehyde) with di-2,2'-diethylhexyl malonate. Photostability data in sunscreen formulations showed that DESM is photostable and improves the photostability of avobenzone significantly when compared to control (without a photostabilizer). Photostable broad-spectrum sunscreen formulations with high SPF (>30) have been achieved by combining avobenzone, DESM and UV-B sunscreens, such as homosalate, octisalate or other UV-B sunscreens. It seems that (a) triplet-state energy transfer from avobenzone to DESM and (b) scavenging of reactive species are responsible for the observed stabilization of avobenzone. In vitro study of the two formulations containing DESM clearly showed critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens. DESM does not have any contribution to in vivo SPF; instead it boosts SPF by about 5 units in high-SPF products. DESM was found to be an excellent singlet-oxygen quencher, thereby reducing photodegradation of avobenzone caused by singlet oxygen. In short, the multiplicity of effects and formulation benefits seen with DESM makes it an ideal choice as a unique antioxidant photostabilizer for a variety of cosmetic products targeting young and mature skin alike.

  16. 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.

  17. A novel Pro197Glu substitution in acetolactate synthase (ALS) confers broad-spectrum resistance across ALS inhibitors.

    Science.gov (United States)

    Liu, Weitang; Yuan, Guohui; Du, Long; Guo, Wenlei; Li, Lingxu; Bi, Yaling; Wang, Jinxin

    2015-01-01

    Water chickweed (Myosoton aquaticum L.), a competitive broadleaf weed, is widespread in wheat fields in China. Tribenuron and pyroxsulam failed to control water chickweed in the same field in Qiaotian Village in 2011 and 2012, respectively. An initial tribenuron resistance confirmation test identified a resistant population (AH02). ALS gene sequencing revealed a previously unreported substitution of Glu for Pro at amino acid position 197 in resistant individuals. A purified subpopulation (WRR04) that was individually homozygous for the Pro197Glu substitution was generated and characterized in terms of its response to different classes of ALS inhibitors. A whole-plant experiment showed that the WRR04 population exhibited broad-spectrum resistance to tribenuron (SU, 318-fold), pyrithiobac sodium (PTB, > 197-fold), pyroxsulam (TP, 81-fold), florasulam (TP, > 36-fold) and imazethapyr (IMI, 11-fold). An in vitro ALS assay confirmed that the ALS from WRR04 showed high resistance to all the tested ALS inhibitors. These results established that the Pro197Glu substitution endows broad-spectrum resistance across ALS inhibitors in water chickweed. In addition, molecular markers were developed to rapidly identify the Pro197Glu mutation.

  18. Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling.

    Science.gov (United States)

    McCaskill, Jana L; Ressel, Sarah; Alber, Andreas; Redford, Jane; Power, Ultan F; Schwarze, Jürgen; Dutia, Bernadette M; Buck, Amy H

    2017-06-16

    The majority of antiviral therapeutics target conserved viral proteins, however, this approach confers selective pressure on the virus and increases the probability of antiviral drug resistance. An alternative therapeutic strategy is to target the host-encoded factors that are required for virus infection, thus minimizing the opportunity for viral mutations that escape drug activity. MicroRNAs (miRNAs) are small noncoding RNAs that play diverse roles in normal and disease biology, and they generally operate through the post-transcriptional regulation of mRNA targets. We have previously identified cellular miRNAs that have antiviral activity against a broad range of herpesvirus infections, and here we extend the antiviral profile of a number of these miRNAs against influenza and respiratory syncytial virus. From these screening experiments, we identified broad-spectrum antiviral miRNAs that caused >75% viral suppression in all strains tested, and we examined their mechanism of action using reverse-phase protein array analysis. Targets of lead candidates, miR-124, miR-24, and miR-744, were identified within the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and this work identified MAPK-activated protein kinase 2 as a broad-spectrum antiviral target required for both influenza and respiratory syncytial virus (RSV) infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Synthesis of 2,3,6-trideoxy sugar triazole hybrids as potential new broad spectrum antimicrobial agents.

    Science.gov (United States)

    Sharma, Smriti; Saquib, Mohammad; Verma, Saroj; Mishra, Nripendra N; Shukla, Praveen K; Srivastava, Ranjana; Prabhakar, Yenamandra S; Shaw, Arun K

    2014-08-18

    Here, we describe a molecular hybridization inspired design and synthesis of novel 6-triazolyl 2,3,6-trideoxy sugars as promising new broad-spectrum antimicrobial agents using click chemistry in key step. These compounds showed MIC between 0.39 and 50 μg/mL against different native and resistant bacteria and fungi with no toxicity. Among them, compound 29 was the most active molecule with MIC 0.78 μg/mL against Staphylococcus aureus and Klebsiella pneumoniae and 3.12 μg/mL against methicillin- and vancomycin-resistant S. aureus. Compound 26 was the most potent anti-fungal candidate with MIC 0.39 μg/mL against Trichophyton mentagrophytes. Compound 46 was found to be promising with broad-spectrum activity against both bacterial and fungal strains. The bioinformatic studies involving bacteria's protein co-crystals prompted penicillin binding protein-2 as the most likely target of these compounds.

  20. 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.

  1. Occurrence of bacteria producing broad-spectrum beta-lactamases and qnr genes in hospital and urban wastewater samples.

    Science.gov (United States)

    Röderová, Magdaléna; Sedláková, Miroslava Htoutou; Pudová, Vendula; Hricová, Kristýna; Silová, Romana; Imwensi, Peter Eghonghon Odion; Bardoň, Jan; Kolář, Milan

    2016-04-01

    The aims were to investigate the level of antibiotic-resistant bacteria in hospital and urban wastewater and to determine the similarity of isolates obtained from wastewater and hospitalized patients. Wastewater samples were collected in September 2013 and 2014. After identification using MALDI-TOF MS, beta-lactamase production was determined by relevant phenotypic tests. Genes responsible for the production of single beta-lactamase groups and Qnr proteins were established. The epidemiological relationship of the isolates from wastewater and hospitalized patients was determined by PFGE. A total of 51 isolates of enterobacteria were obtained. Overall, 45.1% of them produced broad-spectrum beta-lactamases. Genes encoding TEM, SHV, CTX-M, CIT, DHA and EBC types of enzymes and Qnr proteins were detected. No broad-spectrum beta-lactamase production was confirmed in the urban wastewater treatment plant. The most important finding was the detection of two identical isolates of K. pneumoniae in 2013, one from a patient's urinary catheter and the other from a wastewater sample.

  2. Potential Broad Spectrum Inhibitors of the Coronavirus 3CLpro: A Virtual Screening and Structure-Based Drug Design Study.

    Science.gov (United States)

    Berry, Michael; Fielding, Burtram C; Gamieldien, Junaid

    2015-12-15

    Human coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CL(pro) provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodologies. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds is bioactive is excellent. Additionally, the compounds segregate into 15 significantly dissimilar (p < 0.05) clusters based on shape and features, which represent valuable scaffolds that can be used as a basis for future anti-coronaviral inhibitor discovery experiments. Importantly though, the enriched subset of 19 compounds identified from the larger library has to be validated experimentally.

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

    Science.gov (United States)

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

    2016-02-01

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

  4. Broad Spectrum Anti-Quorum Sensing Activity of Tannin-Rich Crude Extracts of Indian Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Varsha Shukla

    2016-01-01

    Full Text Available Quorum sensing (QS mechanisms have been demonstrated to have significance in expression of pathogenicity in infectious bacteria. In Gram negative bacteria the autoinducer molecules that mediate QS are acyl homoserine lactones (AHL and in Gram positive bacteria they are peptides called autoinducing peptides (AIP. A screening of tannin-rich medicinal plants was attempted to identify extracts that could interrupt the QS mechanisms in both Gram positive and Gram negative bacteria over a wide range of concentrations and therefore potentially be potent agents that could act as broad spectrum QS inhibitors. Six out of the twelve Indian medicinal plant extracts that were analyzed exhibited anti-QS activity in Chromobacterium violaceum 12472 and in S. aureus strain with agr:blaZ fusion over a broad range of subinhibitory concentrations, indicating that the extracts contain high concentration of molecules that can interfere with the QS mechanisms mediated by AHL as well as AIP.

  5. 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.

  6. 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.

  7. “If it’s a broad spectrum, it can shoot better”: inappropriate antibiotic prescribing in Cambodia

    Directory of Open Access Journals (Sweden)

    Chhorvoin Om

    2016-12-01

    Full Text Available Abstract Background Cambodia is affected by antibiotic resistance but interventions to reduce the level of resistance require knowledge of the phenomena that lead to inappropriate prescribing. We interviewed physicians working in public hospitals to explore the drivers of inappropriate antibiotic prescribing. Methods Hospitals participating in a knowledge, attitudes and practices survey prior to this study were purposively selected and physicians were randomly recruited to participate in focus group discussions. Nvivo version 10 was used to inductively code the qualitative transcripts and manage thematic data analysis. Results Inappropriate antibiotic prescribing was a common practice and driven by seven factors: prescribing habit, limited diagnostic capacity, lack of microbiology evidence, non-evidence-based clinical guidelines, perceived patient demand, poor hygiene and infection control, and perceived bacterial resistance to narrow spectrum antibiotics. “Every day, doctors are not performing appropriately. We have made lots of mistakes with our antibiotic prescribing.” When a patient’s clinical condition was not responsive to empiric treatment, physicians changed to a broader spectrum antibiotic and microbiology services were sought only after failure of a treatment with a broad-spectrum antibiotic. This habitual empirical prescribing was a common practice regardless of microbiology service accessibility. Poor hygiene and infection control practices were commonly described as reasons for ‘preventive’ prescribing with full course of antibiotics while perception of bacterial resistance to narrow-spectrum antibiotics due to unrestricted access in the community resulted in unnecessary prescribing of broad spectrum antibiotics in private practices. Conclusions The practice of prescribing antibiotics by Cambodian physicians is inappropriate and based on prescribing habit rather than microbiology evidence. Improvement in prescribing

  8. Vancomycin and Five Broad-spectrum Antibiotic Utilization Evaluation in an Educational Medical Center in One Year

    Directory of Open Access Journals (Sweden)

    SiminDokht Shoaei

    2015-10-01

    Full Text Available  Background: Antibiotics can be life saving if they are used correctly, and can have unwanted side effects specially resistance with incorrect use. Unfortunately in fear of no response, physicians use broad spectrum antibiotics meticulously. In this Drug Utilization Evaluation (DUE, improper use of Vancomycin and five broad-spectrum antibiotics are studied to find faults and solution for this problem. Methods:This descriptive cross-sectional study performed during the March of 2012 to March of 2013.DUE of Imipenem, Meropenem, Piperacillin-Tazobactam, Cefepime, Ciprofloxacin and Vancomycin was done in 6 wards of Imam Hossein Hospital in Tehran. Demographic, clinical, laboratory, imaging and treatment data were looked for in medical records of 686 patients. Evaluation was done by three infectious disease specialist based on reference text book of Mandell’s Principles and Practice of Infectious Diseases 2010 and IDSA Guidelines. Results:This study showed 38.5% of prescriptions were correct and the remained 61.5% were incorrect with different faults predominantly incorrect overuse in 51.1%.Ciprofloxacin was the most common incorrect used drug in 74.8% cases and Piperacillin-Tazobactam with 48.7% cases had the least common incorrect use. There was no fault in prescription of antibiotics observing age and sex (pregnancy, breast feeding factors. Conclusions:Our results reveal a significant high level of the inappropriate use of Antibiotics mostly as overuse and empirically without culture results. It is needed to establish continuing medical education (CME courses and a locally conformable guideline of antibiotic use based on antibiogram results.

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

    Science.gov (United States)

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

    2015-10-01

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

  10. Voltage-Induced Buckling of Dielectric Films using Fluid Electrodes

    CERN Document Server

    Tavakol, Behrouz

    2016-01-01

    Accurate and integrable control of different flows within microfluidic channels is crucial to further development of lab-on-a-chip and fully integrated adaptable structures. Here we introduce a flexible microactuator that buckles at a high deformation rate and alters the downstream fluid flow. The microactuator consists of a confined, thin, dielectric film that buckles into the microfluidic channel when exposed to voltage supplied through conductive fluid electrodes. We estimate the critical buckling voltage, and characterize the buckled shape of the actuator. Finally, we investigate the effects of frequency, flow rate, and the pressure differences on the behavior of the buckling structure and the resulting fluid flow. These results demonstrate that the voltage--induced buckling of embedded microstructures using fluid electrodes provides a means for high speed attenuation of microfluidic flow.

  11. A multicenter comparative study of cefepime versus broad-spectrum antibacterial therapy in moderate and severe bacterial infections

    Directory of Open Access Journals (Sweden)

    Badaró Roberto

    2002-01-01

    Full Text Available The safety and efficacy of cefepime empiric monotherapy compared with standard broad-spectrum combination therapy for hospitalized adult patients with moderate to severe community-acquired bacterial infections were evaluated. In an open-label, multicenter study, 317 patients with an Acute Physiology and Chronic Health Evaluation (APACHE II score ranging from >5 to =19 were enrolled with documented pneumonia (n=196, urinary tract infection (n=65, intra-abdominal infection (n=38, or sepsis (n=18. Patients were randomly assigned 1:1 to receive cefepime 1 to 2 g IV twice daily or three times a day or IV ampicillin, cephalothin, or ceftriaxone ± aminoglycoside therapy for 3 to 21 days. For both treatment groups, metronidazole, vancomycin, or macrolide therapy was added as deemed necessary. The primary efficacy variable was clinical response at the end of therapy. Two hundred ninety-six (93% patients met evaluation criteria and were included in the efficacy analysis. Diagnoses included the following: 180 pneumonias (90 cefepime, 90 comparator, 62 urinary tract infections (29 cefepime, 33 comparator, 37 intra-abdominal infections (19 cefepime, 18 comparator, and 17 sepses (8 cefepime, 9 comparator. At the end of therapy, overall clinical success rates were 131/146 (90% for patients treated with cefepime vs 125/150 (83% for those treated with comparator (95% confidence interval [CI]: - 2.6% to 16.3%. The clinical success rate for patients with community-acquired pneumonia, the most frequent infection, was 86% for both treatment groups. Among the patients clinically evaluated, 162 pathogens were isolated and identified before therapy. The most commonly isolated pathogens were Escherichia coli (n=49, Streptococcus pneumoniae (n=29, Haemophilus influenzae (n=14, and Staphylococcus aureus (n=11. Bacteriologic eradication/presumed eradication was 97% for cefepime vs 94% for comparator-treated patients. Drug-related adverse events were reported in 16% of

  12. 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

  13. The broad-spectrum metalloproteinase inhibitor BB-94 inhibits growth, HER3 and Erk activation in fulvestrant-resistant breast cancer cell lines

    DEFF Research Database (Denmark)

    Kirkegaard, Tove; Yde, Christina Westmose; Kveiborg, Marie

    2014-01-01

    cells. This was prevented by treatment of resistant cells with the metalloproteinase inhibitor TAPI-2. Only the broad-spectrum metalloproteinase inhibitor BB-94, and not the more selective inhibitors GM6001 or TAPI-2, which inhibited shedding of the HER ligands produced by the fulvestrant...... of ligands. Only the broad-spectrum metalloproteinase inhibitor BB-94 could abrogate HER3 and Erk activation in the resistant cells, which stresses the complexity of the resistance mechanisms and the requirement of targeting signaling from HER receptors by multiple strategies....

  14. The Tortoise and the Hare. Small-Game Use, the Broad-Spectrum Revolution, and Paleolithic Demography.

    Science.gov (United States)

    Stiner; Munro; Surovell

    2000-02-01

    This study illustrates the potential of small-game data for identifying and dating Paleolithic demographic pulses such as those associated with modern human origins and the later evolution of food-producing economies. Archaeofaunal series from Israel and Italy serve as our examples. Three important implications of this study are that (1) early Middle Paleolithic populations were exceptionally small and highly dispersed, (2) the first major population growth pulse in the eastern Mediterranean probably occurred before the end of the Middle Paleolithic, and (3) subsequent demographic pulses in the Upper and Epi-Paleolithic greatly reshaped the conditions of selection that operated on human subsistence ecology, technology, and society. The findings of this study are consistent with the main premise of Flannery's broad-spectrum-revolution hypothesis. However, ranking small prey in terms of work of capture (in the absence of special harvesting tools) proved far more effective in this investigation of human diet breadth than have the taxonomic-diversity analyses published previously.

  15. The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

    Science.gov (United States)

    Safronetz, David; Rosenke, Kyle; Westover, Jonna B; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W; Feldmann, Heinz; Gowen, Brian B

    2015-10-12

    With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

  16. Sedaxane, Isopyrazam and Solatenol™: Novel Broad-spectrum Fungicides Inhibiting Succinate Dehydrogenase (SDH) - Synthesis Challenges and Biological Aspects.

    Science.gov (United States)

    Walter, Harald; Tobler, Hans; Gribkov, Denis; Corsi, Camilla

    2015-01-01

    Sedaxane (SDX) 1, isopyrazam (IZM) 2 and Solatenol™ (STL) 3 are broad-spectrum pyrazole carboxamides, which originate from novel chemical classes of fungicides. Their mode of action (MoA) is inhibition of succinate dehydrogenase (SDH), which was recognized for a long time to deliver only compounds with a narrow biological spectrum. This view changed with the market introduction of BASF's boscalid in 2003. All major agro-companies subsequently worked in parallel on this MoA successfully and recently introduced new compounds to the market. Syngenta entered the SDHI area in 1998 and was able to introduce three complementary compounds to the market between 2010 and 2012. In this short review some synthesis challenges and biological effects of SDX 1, IZM 2 and STL 3 will be covered. New cost-efficient synthesis strategies for the preparation of o-biscyclopropyl-aniline, new benzonorbornene intermediates and the key pyrazole carboxylic acid intermediate which is essential for all three Syngenta SDHIs, will be in the focus of this review.

  17. 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.

  18. Expression and post-translational processing of a broad-spectrum organophosphorus-neurotoxin-degrading enzyme in insect tissue culture

    Energy Technology Data Exchange (ETDEWEB)

    Dave, K.I.; Phillips, L.; Luckow, V.A.; Wild, J.R.

    1994-12-31

    A recombinant baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV), has been utilized to express the opd (organophosphate-degrading) gene from Pseudomonas diminuta in insect tissue-culture cells (Sf9) of the fall armyworm (Spodoptera frugiperda). The broad-spectrum organophosphate hydrolase (EC 3.1.8.1) encoded by this gene is a member of a general class of enzymes (organophosphate (OP) anhyorolases) that include parathion hydrolases, di-isopropyl-fluorophosphatases (DFpases), somanases, and OP phosphotrlesterases. This particular enzyme possesses the ability to hydrolyse paraoxon (P-O bond), DFP, sarin (P-F bond), VX (P-S bond) and tabun (P-CN bond), as well as a number of other extensively used organophosphorus pesticides. The enzyme produced in infected Sf9 cells is post-translationally processed and resembles the mature form of the enzyme expressed in various bacterial cells as identified by immunoprecipitation on Western blots. N-terminal sequence analysis of enzyme expressed in insect cells revealed Gly-29 as the terminal residue, whereas expression in Escherichia coli removes this residue, exposing Ser-30 at the N-terminus. Conditions for optimal expression of the enzyme in this system are described. Furthermore, hydrolytic efficiency of some OPs with purified enzyme from this system is discussed in relation to the in situ activity of Pseudomonas diminuta MG cells.

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

    Science.gov (United States)

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

    2011-02-01

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

  20. Broad-spectrum multi-modality image registration: from PET, CT, and MRI to autoradiography, microscopy, and beyond.

    Science.gov (United States)

    Zanzonico, P B

    2006-01-01

    Image registration and fusion are increasingly important components of both clinical and small-animal imaging and have lead to the development of a variety of pertinent hardware and software tools, including multi-modality, e.g. PET-CT, devices. At the same time, advances in microscopic imaging, including phosphor-plate digital autoradiography and immunohistochemistry, now allow ultra-high (sub-100 microm)-resolution molecular characterization of tissue sections. To date, however, in vivo imaging of intact subjects and ex vivo imaging of harvested tissues sections have remained separate and distinct, making it difficult to reliably inter-compare the former and the latter. The Department of Medical Physics and the Radiation Biophysics Laboratory at Memorial Sloan-Kettering Cancer Center, under the direction of Dr. Clifton Ling, has now designed, fabricated, and tested a stereotactic imaging system for so-called "broad-spectrum" image registration, from coarser-resolution in vivo imaging modalities such as PET, CT, and MRI to ultra-high-resolution ex vivo imaging techniques such as histology, autoradiography, and immunohistochemistry.

  1. Rational design of broad spectrum antibacterial activity based on a clinically relevant enoyl-acyl carrier protein (ACP) reductase inhibitor.

    Science.gov (United States)

    Schiebel, Johannes; Chang, Andrew; Shah, Sonam; Lu, Yang; Liu, Li; Pan, Pan; Hirschbeck, Maria W; Tareilus, Mona; Eltschkner, Sandra; Yu, Weixuan; Cummings, Jason E; Knudson, Susan E; Bommineni, Gopal R; Walker, Stephen G; Slayden, Richard A; Sotriffer, Christoph A; Tonge, Peter J; Kisker, Caroline

    2014-06-06

    Determining the molecular basis for target selectivity is of particular importance in drug discovery. The ideal antibiotic should be active against a broad spectrum of pathogenic organisms with a minimal effect on human targets. CG400549, a Staphylococcus-specific 2-pyridone compound that inhibits the enoyl-acyl carrier protein reductase (FabI), has recently been shown to possess human efficacy for the treatment of methicillin-resistant Staphylococcus aureus infections, which constitute a serious threat to human health. In this study, we solved the structures of three different FabI homologues in complex with several pyridone inhibitors, including CG400549. Based on these structures, we rationalize the 65-fold reduced affinity of CG400549 toward Escherichia coli versus S. aureus FabI and implement concepts to improve the spectrum of antibacterial activity. The identification of different conformational states along the reaction coordinate of the enzymatic hydride transfer provides an elegant visual depiction of the relationship between catalysis and inhibition, which facilitates rational inhibitor design. Ultimately, we developed the novel 4-pyridone-based FabI inhibitor PT166 that retained favorable pharmacokinetics and efficacy in a mouse model of S. aureus infection with extended activity against Gram-negative and mycobacterial organisms. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Rational Design of Broad Spectrum Antibacterial Activity Based on a Clinically Relevant Enoyl-Acyl Carrier Protein (ACP) Reductase Inhibitor*

    Science.gov (United States)

    Schiebel, Johannes; Chang, Andrew; Shah, Sonam; Lu, Yang; Liu, Li; Pan, Pan; Hirschbeck, Maria W.; Tareilus, Mona; Eltschkner, Sandra; Yu, Weixuan; Cummings, Jason E.; Knudson, Susan E.; Bommineni, Gopal R.; Walker, Stephen G.; Slayden, Richard A.; Sotriffer, Christoph A.; Tonge, Peter J.; Kisker, Caroline

    2014-01-01

    Determining the molecular basis for target selectivity is of particular importance in drug discovery. The ideal antibiotic should be active against a broad spectrum of pathogenic organisms with a minimal effect on human targets. CG400549, a Staphylococcus-specific 2-pyridone compound that inhibits the enoyl-acyl carrier protein reductase (FabI), has recently been shown to possess human efficacy for the treatment of methicillin-resistant Staphylococcus aureus infections, which constitute a serious threat to human health. In this study, we solved the structures of three different FabI homologues in complex with several pyridone inhibitors, including CG400549. Based on these structures, we rationalize the 65-fold reduced affinity of CG400549 toward Escherichia coli versus S. aureus FabI and implement concepts to improve the spectrum of antibacterial activity. The identification of different conformational states along the reaction coordinate of the enzymatic hydride transfer provides an elegant visual depiction of the relationship between catalysis and inhibition, which facilitates rational inhibitor design. Ultimately, we developed the novel 4-pyridone-based FabI inhibitor PT166 that retained favorable pharmacokinetics and efficacy in a mouse model of S. aureus infection with extended activity against Gram-negative and mycobacterial organisms. PMID:24739388

  3. Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas.

    Science.gov (United States)

    Wood, Laura D; Noë, Michaël; Hackeng, Wenzel; Brosens, Lodewijk A A; Bhaijee, Feriyl; Debeljak, Marija; Yu, Jun; Suenaga, Masaya; Singhi, Aatur D; Zaheer, Atif; Boyce, Alison; Robinson, Cemre; Eshleman, James R; Goggins, Michael G; Hruban, Ralph H; Collins, Michael T; Lennon, Anne Marie; Montgomery, Elizabeth A

    2017-02-10

    McCune-Albright Syndrome (MAS) is a rare sporadic syndrome caused by post-zygotic mutations in the GNAS oncogene, leading to constitutional mosaicism for these alterations. Somatic activating GNAS mutations also commonly occur in several gastrointestinal and pancreatic neoplasms, but the spectrum of abnormalities in these organs in patients with MAS has yet to be systematically described. We report comprehensive characterization of the upper gastrointestinal tract in seven patients with MAS and identify several different types of polyps, including gastric heterotopia/metaplasia (7/7), gastric hyperplastic polyps (5/7), fundic gland polyps (2/7), and a hamartomatous polyp (1/7). In addition, one patient had an unusual adenomatous lesion at the gastroesophageal junction with high-grade dysplasia. In the pancreas, all patients had endoscopic ultrasound findings suggestive of intraductal papillary mucinous neoplasm (IPMN), but only two patients met the criteria for surgical intervention. Both of these patients had IPMNs at resection, one with low-grade dysplasia and one with high-grade dysplasia. GNAS mutations were identified in the majority of lesions analyzed, including both IPMNs and the adenomatous lesion from the gastroesophageal junction. These studies suggest that there is a broad spectrum of abnormalities in the gastrointestinal tract and pancreas in patients with MAS and that patients with MAS should be evaluated for gastrointestinal pathology, some of which may warrant clinical intervention due to advanced dysplasia.

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

    Science.gov (United States)

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

    2017-07-01

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

  5. ICF syndrome mutations cause a broad spectrum of biochemical defects in DNMT3B-mediated de novo DNA methylation.

    Science.gov (United States)

    Moarefi, Amir H; Chédin, Frédéric

    2011-06-24

    The DNMT3B de novo DNA methyltransferase (DNMT) plays a major role in establishing DNA methylation patterns in early mammalian development, but its catalytic mechanism remains poorly characterized. Here, we provide a comprehensive biochemical analysis of human DNMT3B function through the characterization of a series of site-directed DNMT3B variants associated with immunodeficiency, centromere instability, and facial anomalies (ICF) syndrome. Our data reveal several novel and important aspects of DNMT3B function. First, DNMT3B, unlike DNMT3A, requires a DNA cofactor in order to stably bind to S-adenosyl-l-methionine (SAM), suggesting that it proceeds according to an ordered catalytic scheme. Second, ICF mutations cause a broad spectrum of biochemical defects in DNMT3B function, including defects in homo-oligomerization, SAM binding, SAM utilization, and DNA binding. Third, all tested ICF mutations, including the A766P and R840Q variants, result in altered catalytic properties without interfering with DNMT3L-mediated stimulation; this indicates that DNMT3L is not involved in the pathogenesis of ICF syndrome. Finally, our study reveals a novel level of coupling between substrate binding, oligomerization, and catalysis that is likely conserved within the DNMT3 family of enzymes.

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

    Science.gov (United States)

    Kaminski, Krzysztof

    2017-01-01

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

  7. 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.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  9. 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...

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-06

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

  12. Broad spectrum late blight resistance in potato differential set plants MaR8 and MaR9 is conferred by multiple stacked R genes

    NARCIS (Netherlands)

    Kim, H.I.; Lee, H.; Jo, K.R.; Mortazavian, S.M.M.; Huigen, D.J.; Evenhuis, A.; Kessel, G.J.T.; Visser, R.G.F.; Vossen, J.H.; Jacobsen, E.

    2012-01-01

    Phytophthora infestans is the causal agent of late blight in potato. The Mexican species Solanum demissum is well known as a good resistance source. Among the 11 R gene differentials, which were introgressed from S. demissum, especially R8 and R9 differentials showed broad spectrum resistance both u

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  14. Characterization of the UVA protection provided by avobenzone, zinc oxide, and titanium dioxide in broad-spectrum sunscreen products.

    Science.gov (United States)

    Beasley, Donathan G; Meyer, Thomas A

    2010-12-01

    Solar UV radiation (UVR) is composed of UVB (290-320 nm) and UVA (320-400 nm) wavelengths. Only two sunscreen active ingredients approved in the US, avobenzone (butylmethoxydibenzoylmethane) and zinc oxide (ZnO), provide true broad-spectrum protection against UVA wavelengths >360 nm. Although effective against shorter UVR wavelengths avobenzone. To sustain its absorption capacity within a sunscreen film during UVR exposure, avobenzone needs to be formulated into sunscreen products using sound formulation strategies. To characterize the efficacy of avobenzone, ZnO, and TiO(2) in terms of their abilities to provide broad UVA protection and to demonstrate the effectiveness of the different formulation strategies used today to maintain the efficacy of avobenzone even during prolonged exposures to UVR. UVA efficacy was assessed by measuring absorbance profiles in vitro using Vitro Skin® (IMS Inc., Orange, CT, USA) as an inert substrate and by determining UVA protection factors (PFA) on human skin. The impact of avobenzone loss on sun protection factor (SPF) and PFA values was evaluated by serially reducing avobenzone concentrations in an otherwise photostable product. The photostabilizing influence of specific formulation ingredients was monitored by measuring the extent to which they prevented UVR-induced degradation of avobenzone, whereas photostability of commercial sunscreen products was quantified by measuring the percentage change in absorbance within the UVB and UVA spectral regions following irradiation of thin product films on inert substrates. Model formulations containing 3% avobenzone or 5% ZnO provided superior attenuation of UVA wavelengths >360 nm compared with formulas containing 5% TiO(2). Additionally, sunscreen products of similar SPF containing avobenzone or ZnO exhibited significantly higher PFA values than those containing TiO(2). The addition of photostabilized avobenzone or ZnO increased PFA values nearly 3-fold, whereas the addition of

  15. The CD8-derived chemokine XCL1/lymphotactin is a conformation-dependent, broad-spectrum inhibitor of HIV-1.

    Directory of Open Access Journals (Sweden)

    Christina Guzzo

    Full Text Available CD8+ T cells play a key role in the in vivo control of HIV-1 replication via their cytolytic activity as well as their ability to secrete non-lytic soluble suppressive factors. Although the chemokines that naturally bind CCR5 (CCL3/MIP-1α, CCL4/MIP- 1β, CCL5/RANTES are major components of the CD8-derived anti-HIV activity, evidence indicates the existence of additional, still undefined, CD8-derived HIV-suppressive factors. Here, we report the characterization of a novel anti-HIV chemokine, XCL1/lymphotactin, a member of the C-chemokine family that is produced primarily by activated CD8+ T cells and behaves as a metamorphic protein, interconverting between two structurally distinct conformations (classic and alternative. We found that XCL1 inhibits a broad spectrum of HIV-1 isolates, irrespective of their coreceptor-usage phenotype. Experiments with stabilized variants of XCL1 demonstrated that HIV-1 inhibition requires access to the alternative, all-β conformation, which interacts with proteoglycans but does not bind/activate the specific XCR1 receptor, while the classic XCL1 conformation is inactive. HIV-1 inhibition by XCL1 was shown to occur at an early stage of infection, via blockade of viral attachment and entry into host cells. Analogous to the recently described anti-HIV effect of the CXC chemokine CXCL4/PF4, XCL1-mediated inhibition is associated with direct interaction of the chemokine with the HIV-1 envelope. These results may open new perspectives for understanding the mechanisms of HIV-1 control and reveal new molecular targets for the design of effective therapeutic and preventive strategies against HIV-1.

  16. Competition between Phytophthora infestans effectors leads to increased aggressiveness on plants containing broad-spectrum late blight resistance.

    Directory of Open Access Journals (Sweden)

    Dennis A Halterman

    Full Text Available BACKGROUND: The destructive plant disease potato late blight is caused by the oomycete pathogen Phytophthora infestans (Mont. de Bary. This disease has remained particularly problematic despite intensive breeding efforts to integrate resistance into cultivated potato, largely because of the pathogen's ability to quickly evolve to overcome major resistance genes. The RB gene, identified in the wild potato species S. bulbocastanum, encodes a protein that confers broad-spectrum resistance to most P. infestans isolates through its recognition of highly conserved members of the corresponding pathogen effector family IPI-O. IpiO is a multigene family of effectors and while the majority of IPI-O proteins are recognized by RB to elicit host resistance, some variants exist that are able to elude detection (e.g. IPI-O4. METHODS AND FINDINGS: In the present study, analysis of ipiO variants among 40 different P. infestans isolates collected from Guatemala, Thailand, and the United States revealed a high degree of complexity within this gene family. Isolate aggressiveness was correlated with increased ipiO diversity and especially the presence of the ipiO4 variant. Furthermore, isolates expressing IPI-O4 overcame RB-mediated resistance in transgenic potato plants even when the resistance-eliciting IPI-O1 variant was present. In support of this finding, we observed that expression of IPI-O4 via Agrobacterium blocked recognition of IPI-O1, leading to inactivation of RB-mediated programmed cell death in Nicotiana benthamiana. CONCLUSIONS: In this study we definitively demonstrate and provide the first evidence that P. infestans can defeat an R protein through inhibition of recognition of the corresponding effector protein.

  17. 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.

  18. 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)

  19. Inhibition of an aquatic rhabdovirus demonstrates promise of a broad-spectrum antiviral for use in aquaculture

    Science.gov (United States)

    Balmer, Bethany F.; Powers, Rachel L.; Zhang, Ting-Hu; Lee, Jihye; Vigant, Frederic; Lee, Benhur; Jung, Michael E.; Purcell, Maureen K.; Snekvik, Kevin; Aguilar, Hector C.

    2017-01-01

    Many enveloped viruses cause devastating disease in aquaculture, resulting in significant economic impact. LJ001 is a broad-spectrum antiviral compound that inhibits enveloped virus infections by specifically targeting phospholipids in the lipid bilayer via the production of singlet oxygen (1O2). This stabilizes positive curvature and decreases membrane fluidity, which inhibits virus-cell membrane fusion during viral entry. Based on data from previous mammalian studies and the requirement of light for the activation of LJ001, we hypothesized that LJ001 may be useful as a preventative and/or therapeutic agent for infections by enveloped viruses in aquaculture. Here, we report that LJ001 was more stable with a prolonged inhibitory half-life at relevant aquaculture temperatures (15°C), than in mammalian studies at 37°C. When LJ001 was preincubated with our model virus, infectious hematopoietic necrosis virus (IHNV), infectivity was significantly inhibited in vitro (using the epithelioma papulosum cyprini [EPC] fish cell line) and in vivo (using rainbow trout fry) in a dose-dependent and time-dependent manner. While horizontal transmission of IHNV in a static cohabitation challenge model was reduced by LJ001, transmission was not completely blocked at established antiviral doses. Therefore, LJ001 may be best suited as a therapeutic for aquaculture settings that include viral infections with lower virus-shedding rates than IHNV or where higher viral titers are required to initiate infection of naive fish. Importantly, our data also suggest that LJ001-inactivated IHNV elicited an innate immune response in the rainbow trout host, making LJ001 potentially useful for future vaccination approaches.

  20. 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

    2016-04-06

    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 TiO(2-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. TiO(2-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.

  1. Broad spectrum infrared thermal desorption of wipe-based explosive and narcotic samples for trace mass spectrometric detection.

    Science.gov (United States)

    Forbes, Thomas P; Staymates, Matthew; Sisco, Edward

    2017-08-07

    Wipe collected analytes were thermally desorbed using broad spectrum near infrared heating for mass spectrometric detection. Employing a twin tube filament-based infrared emitter, rapid and efficiently powered thermal desorption and detection of nanogram levels of explosives and narcotics was demonstrated. The infrared thermal desorption (IRTD) platform developed here used multi-mode heating (direct radiation and secondary conduction from substrate and subsequent convection from air) and a temperature ramp to efficiently desorb analytes with vapor pressures across eight orders of magnitude. The wipe substrate experienced heating rates up to (85 ± 2) °C s(-1) with a time constant of (3.9 ± 0.2) s for 100% power emission. The detection of trace analytes was also demonstrated from complex mixtures, including plastic-bonded explosives and exogenous narcotics, explosives, and metabolites from collected artificial latent fingerprints. Manipulation of the emission power and duration directly controlled the heating rate and maximum temperature, enabling differential thermal desorption and a level of upstream separation for enhanced specificity. Transitioning from 100% power and 5 s emission duration to 25% power and 30 s emission enabled an order of magnitude increase in the temporal separation (single seconds to tens of seconds) of the desorption of volatile and semi-volatile species within a collected fingerprint. This mode of operation reduced local gas-phase concentrations, reducing matrix effects experienced with high concentration mixtures. IRTD provides a unique platform for the desorption of trace analytes from wipe collections, an area of importance to the security sector, transportation agencies, and customs and border protection.

  2. 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

  3. A genetically modified broad-spectrum strain of Bacillus thuringiensis toxic against Holotrichia parallela, Anomala corpulenta and Holotrichia oblita.

    Science.gov (United States)

    Jia, Yanhua; Zhao, Can; Wang, Qinglei; Shu, Changlong; Feng, Xiaojie; Song, Fuping; Zhang, Jie

    2014-02-01

    Cry8Ea1 from Bacillus thuringiensis strain Bt185 has insecticidal activity against Holotrichia parallela. Cry8Ca2 from strain HBF-1 is effective against Anomala corpulenta. Cry8Ga1 from strain HBF-18 is toxic to H. oblita. Given the need to broaden the spectrum of B. thuringiensis, a broad-spectrum coleopteran active strain of B. thuringiensis, BIOT185, engineered to express multiple cry genes, including cry8Ea1, cry8Fa1 and cry8Ca2, was created by homologous recombination introducing the cry8Ca2 into the B. thuringiensis strain Bt185 by Liu et al. (Appl Microbiol Biotechnol 87:243-249, 2010). To further broaden the spectrum, an engineered B. thuringiensis strain BIOT1858G was constructed by introducing the recombinant plasmid pSTK-8G containing cry8Ga1 into the engineered B. thuringiensis strain BIOT185. PCR and Southern blotting demonstrated that the cry8Ga1 gene was transferred to the novel strain BIOT1858G. SDS-PAGE and RT-PCR confirmed the normal expression and transcription of the cry8Ga1 gene in addition to the cry8Ea1, cry8Fa1 and cry8Ca2 genes. Bioassays of BIOT1858G indicated that the recombinant strain broadened the spectrum against not only H. parallela susceptible to the Cry8E protein and A. corpulenta susceptible to the Cry8C protein but also H. oblita susceptible to the Cry8G protein. The pesticide could also decrease the cost of production and field labor.

  4. 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.

    2016-01-01

    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

  5. 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

  6. 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

  7. Antimicrobial activity of cathelicidins BMAP28, SMAP28, SMAP29, and PMAP23 against Pasteurella multocida is more broad-spectrum than host species specific.

    Science.gov (United States)

    Brogden, Kim A; Nordholm, Gwen; Ackermann, Mark

    2007-01-17

    The antimicrobial activity of linear, cationic alpha-helical peptides from cattle (BMAP28), sheep (SMAP28 and SMAP29), and pigs (PMAP23) were assessed to determine if activity was selective for Pasteurella multocida from a particular animal species or broad-spectrum against all P. multocida tested. The antimicrobial activities of synthetic peptides were determined for P. multocida isolated from cattle (10 isolates), sheep (10 isolates), and pigs (10 isolates) in a broth microdilution assay. All thirty isolates of P. multocida were susceptible to BMAP28 (MICs and MBCs, 1.0-1.9 microM); SMAP28 and SMAP29 (MICs and MBCs, 0.2-0.7 microM); and PMAP23 (MICs and MBCs, 4.3 to > or = 6.8 microM). Overall, the results of this study suggest that synthesized cathelicidins from cattle, sheep, and pigs had broad-spectrum antimicrobial activity against all P. multocida.

  8. 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...

  9. 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.

  10. 关于广谱哲学的交叉性学科特点%The Features of Interdiscipline of Broad-spectrum Philosophy

    Institute of Scientific and Technical Information of China (English)

    苏淼

    2016-01-01

    Broad-spectrum philosophy is a new type of philosophy, which inosculates Marxist philosophy, system science and modern mathematics as a whole, with a laterally interdisciplinary characteristic. It has the important theoretical significance to study laterally interdisciplinary mechanism, functions and characteristics of broad-spectrum philosophy, because it can help to understand the broad-spectrum philosophy and understand the nature of common lateral interdiscipline.%广谱哲学是融马克思主义哲学、系统科学和现代数学为一体的新型哲学门派,具有跨领域性、跨学科性的横断交叉学科的特点。研究广谱哲学横断交叉的机制、作用和特点,对于人们了解广谱哲学,了解一般的横断交叉学科的性质,具有重要的理论意义。

  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. 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.

  13. 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.

  14. 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.

  15. Comparison of measured parameters from a 24-keV and a broad spectrum epithermal neutron beam for neutron capture therapy: an identification of consequential parameters.

    Science.gov (United States)

    Fairchild, R G; Saraf, S K; Kalef-Ezra, J; Laster, B H

    1990-01-01

    Epithermal neutron beams are under development in a number of locations in the U.S. and abroad. The increased penetration in tissue provided by these neurons should circumvent problems associated with the rapid attenuation of thermal neutron beams encountered in previous clinical trials of neutron capture therapy (NCT). Physical and radiobiological experiments with two "intermediate energy" or "epithermal" beams have been reported. A comparison is made here between the 24-keV iron-filtered beam at Harwell, England, and the broad-spectrum Al2 O3 moderated beam at the Brookhaven Medical Research Reactor (BMRR). In addition, parameters which are relevant for NCT, and which are best suited for evaluation and comparison of beams, are discussed. Particular attention is paid to the mean neutron energy which can be tolerated without significant reduction of therapeutic gain (TG), where TG is the ratio of tumor dose to maximum normal tissue dose. It is suggested that the simplest and most meaningful parameters for comparison of beam intensity and purity are the epithermal neutron fluence rate, and the fast neutron dose per epithermal neutron (4.2 X 10(-11) rad/neutron for the broad-spectrum beam and 29 X 10(-11) rad/neutron for the 24-keV beam). While the Al2O3 beam is close to optimal, the 24-keV beam produces a significant fast neutron dose which results in a lower TG.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Sucrose-mediated priming of plant defense responses and broad-spectrum disease resistance by overexpression of the maize pathogenesis-related PRms protein in rice plants.

    Science.gov (United States)

    Gómez-Ariza, Jorge; Campo, Sonia; Rufat, Mar; Estopà, Montserrat; Messeguer, Joaquima; San Segundo, Blanca; Coca, María

    2007-07-01

    Expression of pathogenesis-related (PR) genes is part of the plant's natural defense response against pathogen attack. The PRms gene encodes a fungal-inducible PR protein from maize. Here, we demonstrate that expression of PRms in transgenic rice confers broad-spectrum protection against pathogens, including fungal (Magnaporthe oryzae, Fusarium verticillioides, and Helminthosporium oryzae) and bacterial (Erwinia chrysanthemi) pathogens. The PRms-mediated disease resistance in rice plants is associated with an enhanced capacity to express and activate the natural plant defense mechanisms. Thus, PRms rice plants display a basal level of expression of endogenous defense genes in the absence of the pathogen. PRms plants also exhibit stronger and quicker defense responses during pathogen infection. We also have found that sucrose accumulates at higher levels in leaves of PRms plants. Sucrose responsiveness of rice defense genes correlates with the pathogen-responsive priming of their expression in PRms rice plants. Moreover, pretreatment of rice plants with sucrose enhances resistance to M. oryzae infection. Together, these results support a sucrose-mediated priming of defense responses in PRms rice plants which results in broad-spectrum disease resistance.

  17. Current and Voltage Induced on the Cable by Flash of Lightning between Clouds

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Based on the transmission line equations, this paper has developed computing formulas of current and voltage induced on the cable over the ground plane by Flash of Lightning Between Clouds (FBC), and estimated current and voltage on the cable of metal shielded sheath and analyzed the results.

  18. 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.

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

    Science.gov (United States)

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

    2015-07-03

    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 fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics.

  20. A novel antifungal agent with broad spectrum: 1-(4-biphenylyl)-3-(1H-imidazol-1-yl)-1-propanone.

    Science.gov (United States)

    Roman, Gheorghe; Mareş, Mihai; Năstasă, Valentin

    2013-02-01

    A series of (1-substituted aryl)-3-(1H-imidazol-1-yl)-1-propanones was synthesized through the N-alkylation of imidazole with 3-dimethylamino-1-(substituted aryl)-1-propanone hydrochlorides (ketonic Mannich bases). A second series of N(1) -substituted imidazoles was obtained by the reduction of the carbonyl function of the imidazole-ketones in the previous series by means of NaBH(4) . All of the compounds were evaluated for antifungal activity against 16 strains of Candida, and 3-(1H-imidazol-1-yl)-1-(4-biphenylyl)-1-propanone emerged as a broad-spectrum antifungal agent. Several 3-(1H-imidazol-1-yl)-1-(2'-(substituted benzyl)oxyphenyl)-1-propanones were also active towards Candida kefyr. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2009-12-10

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

  2. 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.

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

    Science.gov (United States)

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

    2014-08-01

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

  4. 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

  5. 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

    2016-10-01

    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.

  6. Prevalence of broad-spectrum cephalosporin-resistant Escherichia coli isolates in food samples in Tunisia, and characterization of integrons and antimicrobial resistance mechanisms implicated.

    Science.gov (United States)

    Ben Slama, Karim; Jouini, Ahlem; Ben Sallem, Rym; Somalo, Sergio; Sáenz, Yolanda; Estepa, Vanesa; Boudabous, Abdellatif; Torres, Carmen

    2010-02-28

    The presence of broad-spectrum-cephalosporin-resistant Escherichia coli isolates and the implicated mechanisms of resistance were investigated in 79 food samples of animal origin obtained in different supermarkets and local butcheries in Tunisia. Ten of these samples (12.6%) harbored extended-spectrum beta-lactamase (ESBL) producing E. coli isolates and 13 ESBL-positive isolates were recovered (one or two/sample), which exhibited nine different Pulsed-Field-Gel-Electrophoresis (PFGE) patterns. ESBLs detected were the following: CTX-M-1 (10 strains), CTX-M-1+TEM-1b (2 strains) and CTX-M-1+TEM-20 (1 strain). The orf477 sequence was identified downstream of bla(CTX-M-1) gene in all 13 strains and ISEcp1 upstream in 9 strains. All ESBL-positive strains were included into phylogenetic group A or B1 (4 and 9 strains, respectively). Three of the 79 food samples (3.8%) contained broad-spectrum-cephalosporin-resistant and ESBL-negative E. coli isolates with AmpC phenotype. One isolate per sample was studied, and they showed unrelated PFGE patterns. The CMY-2 type beta-lactamase was identified in one of these 3 strains and specific point mutations in the promoter/attenuator region of ampC gene (at positions -42, -18, -1 and +58) were detected in the remaining two strains. Twelve ESBL-positive and one ESBL-negative E. coli strains contained class 1 integrons with the following gene cassette arrangements: dfrA1+aadA (6 strains) and dfrA17+aadA5 (7 strains). E. coli strains from food samples could represent a reservoir of ESBL-encoding genes and integrons that could be transmitted to humans through the food chain.

  7. The Coefficient of the Voltage Induced Frequency Shift Measurement on a Quartz Tuning Fork

    Directory of Open Access Journals (Sweden)

    Yubin Hou

    2014-11-01

    Full Text Available We have measured the coefficient of the voltage induced frequency shift (VIFS of a 32.768 KHz quartz tuning fork. Three vibration modes were studied: one prong oscillating, two prongs oscillating in the same direction, and two prongs oscillating in opposite directions. They all showed a parabolic dependence of the eigen-frequency shift on the bias voltage applied across the fork, due to the voltage-induced internal stress, which varies as the fork oscillates. The average coefficient of the VIFS effect is as low as several hundred nano-Hz per millivolt, implying that fast-response voltage-controlled oscillators and phase-locked loops with nano-Hz resolution can be built.

  8. Dynamic magnetization switching and spin wave excitations by voltage-induced torque

    Science.gov (United States)

    Shiota, Yoichi

    2013-03-01

    The effect of electric fields on ultrathin ferromagnetic metal layer is one of the promising approaches for manipulating the spin direction with low-energy consumption, localization, and coherent behavior. Several experimental approaches to realize it have been investigated using ferromagnetic semiconductors, magnetostriction together with piezo-electric materials, multiferroic materials, and ultrathin ferromagnetic layer. In this talk, we will present a dynamic control of spins by voltage-induced torque. We used the magnetic tunnel junctions with ultrathin ferromagnetic layer, which shows voltage-induced perpendicular magnetic anisotropy change. By applying the voltage to the junction, the magnetic easy-axis in the ultrathin ferromagnetic layer changes from in-plane to out-of-plane, which causes a precession of the spins. This precession resulted in a two-way toggle switching by determining an appropriate pulse length. On the other hand, an application of rf-voltage causes an excitation of a uniform spin-wave. Since the precession of spin associates with an oscillation in the resistance of the junction, the applied rf-signal is rectified and produces a dc-voltage. From the spectrum of the dc-voltage as a function of frequency, we could estimate the voltage-induced torque. This research was supported by CREST-JST, G-COE program, and JSPS for the fellowship. Collaborators include T. Nozaki, S. Miwa, F. Bonell, N. Mizuochi, T. Shinjo, and Y. Suzuki.

  9. In Situ Measurement of Voltage-Induced Stress in Conducting Polymers with Redox-Active Dopants.

    Science.gov (United States)

    Sen, Sujat; Kim, Sung Yeol; Palmore, Lia R; Jin, Shenghua; Jadhav, Nitin; Chason, Eric; Palmore, G Tayhas R

    2016-09-14

    Minimization of stress-induced mechanical rupture and delamination of conducting polymer (CP) films is desirable to prevent failure of devices based on these materials. Thus, precise in situ measurement of voltage-induced stress within these films should provide insight into the cause of these failure mechanisms. The evolution of stress in films of polypyrrole (pPy), doped with indigo carmine (IC), was measured in different electrochemical environments using the multibeam optical stress sensor (MOSS) technique. The stress in these films gradually increases to a constant value during voltage cycling, revealing an initial break-in period for CP films. The nature of the ions involved in charge compensation of pPy[IC] during voltage cycling was determined from electrochemical quartz crystal microbalance (EQCM) data. The magnitude of the voltage-induced stress within pPy[IC] at neutral pH correlated with the radius of the hydrated mobile ion in the order Li(+) > Na(+) > K(+). At acidic pH, the IC dopant in pPy[IC] undergoes reversible oxidation and reduction within the range of potentials investigated, providing a secondary contribution to the observed voltage-induced stress. We report on the novel stress response of these polymers due to the presence of pH-dependent redox-active dopants and how it can affect material performance.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-04

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

  11. Fungal Root Microbiome from Healthy and Brittle Leaf Diseased Date Palm Trees (Phoenix dactylifera L.) Reveals a Hidden Untapped Arsenal of Antibacterial and Broad Spectrum Antifungal Secondary Metabolites.

    Science.gov (United States)

    Mefteh, Fedia B; Daoud, Amal; Chenari Bouket, Ali; Alenezi, Faizah N; Luptakova, Lenka; Rateb, Mostafa E; Kadri, Adel; Gharsallah, Neji; Belbahri, Lassaad

    2017-01-01

    In this study, we aimed to explore and compare the composition, metabolic diversity and antimicrobial potential of endophytic fungi colonizing internal tissues of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) widely cultivated in arid zones of Tunisia. A total of 52 endophytic fungi were isolated from healthy and BLD roots of date palm trees, identified based on internal transcribed spacer-rDNA sequence analysis and shown to represent 13 species belonging to five genera. About 36.8% of isolates were shared between healthy and diseased root fungal microbiomes, whereas 18.4 and 44.7% of isolates were specific to healthy and BLD root fungal microbiomes, respectively. All isolates were able to produce at least two of the screened enzymes including amylase, cellulase, chitinase, pectinase, protease, laccase and lipase. A preliminary screening of the isolates using disk diffusion method for antibacterial activity against four Gram-positive and three Gram-negative bacteria and antifungal activities against three phytopathogenic fungi indicated that healthy and BLD root fungal microbiomes displayed interesting bioactivities against examined bacteria and broad spectrum bioactivity against fungal pathogens. Some of these endophytic fungi (17 isolates) were fermented and their extracts were evaluated for antimicrobial potential against bacterial and fungal isolates. Results revealed that fungal extracts exhibited antibacterial activities and were responsible for approximately half of antifungal activities against living fungi. These results suggest a strong link between fungal bioactivities and their secondary metabolite arsenal. EtOAc extracts of Geotrichum candidum and Thielaviopsis punctulata originating from BLD microbiome gave best results against Micrococcus luteus and Bacillus subtilis with minimum inhibitory concentration (MIC, 0.78 mg/mL) and minimum bactericidal concentration (6.25 mg/mL). G. candidum gave the best result against

  12. In vitro activity of a novel broad-spectrum antifungal, E1210, tested against Aspergillus spp. determined by CLSI and EUCAST broth microdilution methods.

    Science.gov (United States)

    Pfaller, Michael A; Duncanson, Frederick; Messer, Shawn A; Moet, Gary J; Jones, Ronald N; Castanheira, Mariana

    2011-11-01

    E1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present study, we extend these findings by examining the activity of E1210 and comparator antifungal agents against Aspergillus spp. by using the methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI methods). Seventy-eight clinical isolates of Aspergillus were tested including 20 isolates of Aspergillus flavus species complex (SC), 22 of A. fumigatus SC, 13 of A. niger SC, and 23 of A. terreus SC. The collection included 15 AMB-R (MIC, ≥ 2 μg/ml) isolates of A. terreus SC and 10 itraconazole-R (MIC, ≥ 4 μg/ml) isolates of A. fumigatus SC (7 isolates), A. niger SC (2 isolates), and A. terreus SC (1 isolate). Comparator antifungal agents included anidulafungin, caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The essential agreement (EA; ± 2 log(2) dilution steps) was 100% for all comparisons with the exception of posaconazole versus A. terreus SC (EA = 91.3%). The minimum effective concentration (MEC)/MIC(90) values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole, respectively, were as follows for each species: for A. flavus SC, 0.03, ≤ 0.008, 0.12, 1, 1, and 1; for A. fumigatus SC, 0.06, 0.015, 0.12, >8, 1, and 4; for A. niger SC, 0.015, 0.03, 0.12, 4, 1, and 2; and for A. terreus SC, 0.06, 0.015, 0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains of A. terreus SC (MEC range, 0.015 to 0.06 μg/ml) and itraconazole-R strains of A. fumigatus SC (MEC range, 0.03 to 0.12 μg/ml), A. niger SC (MEC, 0.008 μg/ml), and A. terreus SC (MEC, 0.015

  13. In Vitro Activity of a Novel Broad-Spectrum Antifungal, E1210, Tested against Aspergillus spp. Determined by CLSI and EUCAST Broth Microdilution Methods ▿

    Science.gov (United States)

    Pfaller, Michael A.; Duncanson, Frederick; Messer, Shawn A.; Moet, Gary J.; Jones, Ronald N.; Castanheira, Mariana

    2011-01-01

    E1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present study, we extend these findings by examining the activity of E1210 and comparator antifungal agents against Aspergillus spp. by using the methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI methods). Seventy-eight clinical isolates of Aspergillus were tested including 20 isolates of Aspergillus flavus species complex (SC), 22 of A. fumigatus SC, 13 of A. niger SC, and 23 of A. terreus SC. The collection included 15 AMB-R (MIC, ≥2 μg/ml) isolates of A. terreus SC and 10 itraconazole-R (MIC, ≥4 μg/ml) isolates of A. fumigatus SC (7 isolates), A. niger SC (2 isolates), and A. terreus SC (1 isolate). Comparator antifungal agents included anidulafungin, caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The essential agreement (EA; ±2 log2 dilution steps) was 100% for all comparisons with the exception of posaconazole versus A. terreus SC (EA = 91.3%). The minimum effective concentration (MEC)/MIC90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole, respectively, were as follows for each species: for A. flavus SC, 0.03, ≤0.008, 0.12, 1, 1, and 1; for A. fumigatus SC, 0.06, 0.015, 0.12, >8, 1, and 4; for A. niger SC, 0.015, 0.03, 0.12, 4, 1, and 2; and for A. terreus SC, 0.06, 0.015, 0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains of A. terreus SC (MEC range, 0.015 to 0.06 μg/ml) and itraconazole-R strains of A. fumigatus SC (MEC range, 0.03 to 0.12 μg/ml), A. niger SC (MEC, 0.008 μg/ml), and A. terreus SC (MEC, 0.015

  14. Fungal Root Microbiome from Healthy and Brittle Leaf Diseased Date Palm Trees (Phoenix dactylifera L.) Reveals a Hidden Untapped Arsenal of Antibacterial and Broad Spectrum Antifungal Secondary Metabolites

    Science.gov (United States)

    Mefteh, Fedia B.; Daoud, Amal; Chenari Bouket, Ali; Alenezi, Faizah N.; Luptakova, Lenka; Rateb, Mostafa E.; Kadri, Adel; Gharsallah, Neji; Belbahri, Lassaad

    2017-01-01

    In this study, we aimed to explore and compare the composition, metabolic diversity and antimicrobial potential of endophytic fungi colonizing internal tissues of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) widely cultivated in arid zones of Tunisia. A total of 52 endophytic fungi were isolated from healthy and BLD roots of date palm trees, identified based on internal transcribed spacer-rDNA sequence analysis and shown to represent 13 species belonging to five genera. About 36.8% of isolates were shared between healthy and diseased root fungal microbiomes, whereas 18.4 and 44.7% of isolates were specific to healthy and BLD root fungal microbiomes, respectively. All isolates were able to produce at least two of the screened enzymes including amylase, cellulase, chitinase, pectinase, protease, laccase and lipase. A preliminary screening of the isolates using disk diffusion method for antibacterial activity against four Gram-positive and three Gram-negative bacteria and antifungal activities against three phytopathogenic fungi indicated that healthy and BLD root fungal microbiomes displayed interesting bioactivities against examined bacteria and broad spectrum bioactivity against fungal pathogens. Some of these endophytic fungi (17 isolates) were fermented and their extracts were evaluated for antimicrobial potential against bacterial and fungal isolates. Results revealed that fungal extracts exhibited antibacterial activities and were responsible for approximately half of antifungal activities against living fungi. These results suggest a strong link between fungal bioactivities and their secondary metabolite arsenal. EtOAc extracts of Geotrichum candidum and Thielaviopsis punctulata originating from BLD microbiome gave best results against Micrococcus luteus and Bacillus subtilis with minimum inhibitory concentration (MIC, 0.78 mg/mL) and minimum bactericidal concentration (6.25 mg/mL). G. candidum gave the best result against

  15. Congenital diaphragmatic hernia and microtia in a newborn with mycophenolate mofetil (MMF) exposure: phenocopy for Fryns syndrome or broad spectrum of teratogenic effects?

    Science.gov (United States)

    Parisi, Melissa A; Zayed, Hatem; Slavotinek, Anne M; Rutledge, Joe C

    2009-06-01

    A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day 2 of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data.

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

    Science.gov (United States)

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

    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 fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics. PMID:26139381

  17. Overexpression of MoSM1, encoding for an immunity-inducing protein from Magnaporthe oryzae, in rice confers broad-spectrum resistance against fungal and bacterial diseases

    Science.gov (United States)

    Hong, Yongbo; Yang, Yayun; Zhang, Huijuan; Huang, Lei; Li, Dayong; Song, Fengming

    2017-01-01

    Potential of MoSM1, encoding for a cerato-platanin protein from Magnaporthe oryzae, in improvement of rice disease resistance was examined. Transient expression of MoSM1 in rice leaves initiated hypersensitive response and upregulated expression of defense genes. When transiently expressed in tobacco leaves, MoSM1 targeted to plasma membrane. The MoSM1-overexpressing (MoSM1-OE) transgenic rice lines showed an improved resistance, as revealed by the reduced disease severity and decreased in planta pathogen growth, against 2 strains belonging to two different races of M. oryzae, causing blast disease, and against 2 strains of Xanthomonas oryzae pv. oryzae, causing bacterial leaf blight disease. However, no alteration in resistance to sheath blight disease was observed in MoSM1-OE lines. The MoSM1-OE plants contained elevated levels of salicylic acid (SA) and jasmonic acid (JA) and constitutively activated the expression of SA and JA signaling-related regulatory and defense genes. Furthermore, the MoSM1-OE plants had no effect on drought and salt stress tolerance and on grain yield. We conclude that MoSM1 confers a broad-spectrum resistance against different pathogens through modulating SA- and JA-mediated signaling pathways without any penalty on abiotic stress tolerance and grain yield, providing a promising potential for application of MoSM1 in improvement of disease resistance in crops. PMID:28106116

  18. RNA-dependent RNA polymerase (NIb) of the potyviruses is an avirulence factor for the broad-spectrum resistance gene Pvr4 in Capsicum annuum cv. CM334.

    Science.gov (United States)

    Kim, Saet-Byul; Lee, Hye-Young; Seo, Seungyeon; Lee, Joo Hyun; Choi, Doil

    2015-01-01

    Potyviruses are one of the most destructive viral pathogens of Solanaceae plants. In Capsicum annuum landrace CM334, a broad-spectrum gene, Pvr4 is known to be involved in resistance against multiple potyviruses, including Pepper mottle virus (PepMoV), Pepper severe mosaic virus (PepSMV), and Potato virus Y (PVY). However, a potyvirus avirulence factor against Pvr4 has not been identified. To identify the avirulence factor corresponding to Pvr4 in potyviruses, we performed Agrobacterium-mediated transient expressions of potyvirus protein coding regions in potyvirus-resistant (Pvr4) and -susceptible (pvr4) pepper plants. Hypersensitive response (HR) was observed only when a RNA-dependent RNA polymerase (NIb) of PepMoV, PepSMV, or PVY was expressed in Pvr4-bearing pepper leaves in a genotype-specific manner. In contrast, HR was not observed when the NIb of Tobacco etch virus (TEV), a virulent potyvirus, was expressed in Pvr4-bearing pepper leaves. Our results clearly demonstrate that NIbs of PepMoV, PepSMV, and PVY serve as avirulence factors for Pvr4 in pepper plants.

  19. Alfalfa benefits from Medicago truncatula: the RCT1 gene from M. truncatula confers broad-spectrum resistance to anthracnose in alfalfa.

    Science.gov (United States)

    Yang, Shengming; Gao, Muqiang; Xu, Chenwu; Gao, Jianchang; Deshpande, Shweta; Lin, Shaoping; Roe, Bruce A; Zhu, Hongyan

    2008-08-26

    Alfalfa is economically the most important forage legume worldwide. A recurrent challenge to alfalfa production is the significant yield loss caused by disease. Although knowledge of molecular mechanisms underlying host resistance should facilitate the genetic improvement of alfalfa, the acquisition of such knowledge is hampered by alfalfa's tetrasomic inheritance and outcrossing nature. However, alfalfa is congeneric with the reference legume Medicago truncatula, providing an opportunity to use M. truncatula as a surrogate to clone the counterparts of many agronomically important genes in alfalfa. In particular, the high degree of sequence identity and remarkably conserved genome structure and function between the two species enables M. truncatula genes to be used directly in alfalfa improvement. Here we report the map-based cloning of RCT1, a host resistance (R) gene in M. truncatula that confers resistance to multiple races of Colletotrichum trifolii, a hemibiotrophic fungal pathogen that causes anthracnose disease of alfalfa. RCT1 is a member of the Toll-interleukin-1 receptor/nucleotide-binding site/leucine-rich repeat (TIR-NBS-LRR) class of plant R genes and confers broad-spectrum anthracnose resistance when transferred into susceptible alfalfa plants. Thus, RCT1 provides a novel resource to develop anthracnose-resistant alfalfa cultivars and contributes to our understanding of host resistance against the fungal genus Colletotrichum. This work demonstrates the potential of using M. truncatula genes for genetic improvement of alfalfa.

  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. 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.

  2. GhMPK7, a novel multiple stress-responsive cotton group C MAPK gene, has a role in broad spectrum disease resistance and plant development.

    Science.gov (United States)

    Shi, Jing; An, Hai-Long; Zhang, Liang; Gao, Zheng; Guo, Xing-Qi

    2010-09-01

    Mitogen-activated protein kinase (MAPK) cascades play a pivotal role in environmental responses and developmental processes in plants. Previous researches mainly focus on the MAPKs in groups A and B, and little is known on group C. In this study, we isolated and characterized GhMPK7, which is a novel gene from cotton belonging to the group C MAPK. RNA blot analysis indicated that GhMPK7 transcript was induced by pathogen infection and multiple defense-related signal molecules. Transgenic Nicotina benthamiana overexpressing GhMPK7 displayed significant resistance to fungus Colletotrichum nicotianae and virus PVY, and the transcript levels of SA pathway genes were more rapidly and strongly induced. Furthermore, the transgenic N. benthamiana showed reduced ROS-mediated injuries by upregulating expression of oxidative stress-related genes. Interestingly, the transgenic plants germinated earlier and grew faster in comparison to wild-type plants. beta-glucuronidase activity driven by the GhMPK7 promoter was detected in the apical meristem at the vegetative stage, and it was enhanced by treatments with signal molecules and phytohormones. These results suggest that GhMPK7 might play an important role in SA-regulated broad-spectrum resistance to pathogen infection, and that it is also involved in regulation of plant growth and development.

  3. A novel broad-spectrum cephalosporin ceftobiprole%新型广谱头孢菌素类抗菌药物头孢吡普

    Institute of Scientific and Technical Information of China (English)

    熊礼玲; 游莉; 刘家健; 李栋宏

    2011-01-01

    Antimicrobial resistance has become a significant problem over the past decade with marked increases in the incidence of MRSA, intermediate- and high level resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci. Ceftobiprole was the first of a new class of broad-spectrum cephalosporin antibiotics that had potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA). This review detailed its mechanism of action, synthesis methods, antibacterial activities in vivo, pharmacokinetic profie and clinical trials.%随着耐甲氧西林金葡萄球菌、耐药金黄色葡萄球菌、耐青霉素肺炎链球菌和耐万古霉素肠球菌显著增加,细菌耐药性成为近年来一个重大难题.Ceftobiprole是第一个对耐甲氧西林金葡萄球菌(MRSA)和万古霉素耐药金黄色葡葡球菌(VRSA)有效的广谱头孢菌素类抗生素.现对其作用机制、合成路线、体外抗菌活性、药动学特性、临床试验等方面作一综述.

  4. Inheritance studies of apple scab resistance and identification of Rvi14, a new major gene that acts together with other broad-spectrum QTL.

    Science.gov (United States)

    Soufflet-Freslon, V; Gianfranceschi, L; Patocchi, A; Durel, C-E

    2008-08-01

    Scab, caused by the fungal pathogen Venturia inaequalis, is the most common disease of cultivated apple (Malus xdomestica). The fungal races 6 and 7 have now overcome the major resistance gene Vf, which is widely used in apple breeding programmes. New breeding strategies to achieve durable resistance are thus necessary. The aim of this study was to determine the genetic basis of quantitative resistance of the apple cultivar 'Dülmener Rosenapfel', known to be scab resistant under different environmental conditions. An F1 progeny derived from the cross between the susceptible cultivar 'Gala' and 'Dülmener Rosenapfel' was tested in a greenhouse with a multi-isolate inoculum of V. inaequalis. Rvi14, a new major gene that conditions a chlorotic-type reaction, was mapped on linkage group (LG) 6 in a genomic region not known to be involved in disease resistance. A further three quantitative trait loci (QTL) for resistance were identified. One co-localized with Rvi14 on LG6, whereas the remaining two were detected on LG11 and LG17, in genomic regions already reported to carry broad-spectrum QTL in other genetic backgrounds. Since a selective genotyping approach was used to detect QTL, an expectation-maximization (EM) computation was used to estimate the corrected QTL contributions to phenotypic variation and was validated by entire progeny genotyping.

  5. 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.

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

    Science.gov (United States)

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

    2009-01-16

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

  7. Activity of broad-spectrum and reduced-risk insecticides on various life stages of cranberry fruitworm (Lepidoptera: Pyralidae) in highbush blueberry.

    Science.gov (United States)

    Wise, John C; Jenkins, Paul E; Poppen, Ryan Vander; Isaacs, Rufus

    2010-10-01

    Laboratory and semifield bioassays were conducted to determine the life-stage activity of insecticides for controlling cranberry fruitworm, Acrobasis vaccinii Riley (Lepidoptera: Pyralidae), a key lepidopteran pest of highbush blueberry, Vaccinium corymbosum L. The organophosphates azinphosmethyl and phosmet, the pyrethroid esfenvalerate, and the carbamate methomyl were lethal to all life stages. The neonicotinoids thiacloprid and acetamiprid demonstrated strong larvicidal and ovicidal activity but were somewhat weaker adulticides than the conventional broad-spectrum compounds. Bacillus thuringiensis, indoxacarb, and emamectin benzoate were shown to control A. vacinii primarily through their larvicidal activity. Spinosad was toxic to all life stages, including eggs laid on top of residues and those that were treated topically, but larvicidal activity was short lived. The growth regulators pyriproxyfen and novaluron had strong ovicidal activity when eggs were laid on top of residues but had limited larvicidal activity. Tebufenozide was not directly toxic to eggs, but demonstrated larvicidal activity, and ovilarvicidal activity when topically applied to eggs. Azinphosmethyl, phosmet, indoxacarb, thiacloprid, and acetamiprid were all toxic to the egg parasitoid Trichogramma minutum Riley. In contrast pyriproxyfen, emamectin benzoate, methomyl, novaluron, and spinosad did not negatively affect the survival of T. minutum within Acrobasis vacinii eggs. These results help inform the ongoing development of integrated strategies for insect management in blueberry.

  8. 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

  9. 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

    2016-02-02

    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.

  10. Transplastomic Nicotiana benthamiana plants expressing multiple defence genes encoding protease inhibitors and chitinase display broad-spectrum resistance against insects, pathogens and abiotic stresses.

    Science.gov (United States)

    Chen, Peng-Jen; Senthilkumar, Rajendran; Jane, Wann-Neng; He, Yong; Tian, Zhihong; Yeh, Kai-Wun

    2014-05-01

    Plastid engineering provides several advantages for the next generation of transgenic technology, including the convenient use of transgene stacking and the generation of high expression levels of foreign proteins. With the goal of generating transplastomic plants with multiresistance against both phytopathogens and insects, a construct containing a monocistronic patterned gene stack was transformed into Nicotiana benthamiana plastids harbouring sweet potato sporamin, taro cystatin and chitinase from Paecilomyces javanicus. Transplastomic lines were screened and characterized by Southern/Northern/Western blot analysis for the confirmation of transgene integration and respective expression level. Immunogold localization analyses confirmed the high level of accumulation proteins that were specifically expressed in leaf and root plastids. Subsequent functional bioassays confirmed that the gene stacks conferred a high level of resistance against both insects and phytopathogens. Specifically, larva of Spodoptera litura and Spodoptera exigua either died or exhibited growth retardation after ingesting transplastomic plant leaves. In addition, the inhibitory effects on both leaf spot diseases caused by Alternaria alternata and soft rot disease caused by Pectobacterium carotovorum subsp. carotovorum were markedly observed. Moreover, tolerance to abiotic stresses such as salt/osmotic stress was highly enhanced. The results confirmed that the simultaneous expression of sporamin, cystatin and chitinase conferred a broad spectrum of resistance. Conversely, the expression of single transgenes was not capable of conferring such resistance. To the best of our knowledge, this is the first study to demonstrate an efficacious stacked combination of plastid-expressed defence genes which resulted in an engineered tolerance to various abiotic and biotic stresses.

  11. Broad spectrum β-lactam resistance in faecal Escherichia coli isolated from severely malnourished and nourished children attending Mbagathi district hospital, Nairobi: A case-control study

    Directory of Open Access Journals (Sweden)

    Samuel Mwangi Njoroge

    2014-01-01

    Full Text Available Context: Severely malnourished children have increased risk of being put on antibiotics due to co-morbidities. Aim: The study′s objective was to characterize the Escherichia coli β-lactamase mediated resistance to the broad spectrum β-lactam antimicrobials among this population and compare them with nourished children as controls. Settings and Design: In this case-control, hospital-based setup, 109 E. coli isolates were obtained from each group, one isolate per subject. Materials and Methods: Stool or anal swabs were collected, enriched in buffered peptone water and cultured on MacConkey and eosin methylene blue agars. Biochemical test were used to identify E. coli. antibiograms to determine phenotypic resistance were determined using a panel of 14 drugs. Only the isolates showing synergy between ampicillin-calvulanic acid and one or more third generation cephalosporins were picked as extended spectrum β-lactamase (ESBL producers. Statistical Analysis: Differences in ESBL rates and susceptibility percentages between cases and controls were evaluated for significance using 2-tailed Fisher′s exact test. Results: Prevalence of ESBL phenotype was higher in severely malnourished children (39% as compared to the controls (7%. The plasmid-encoded AmpC′s (pAmpC-like phenotype was observed in 11% isolates. Conclusions: Isolation of ESBL-E. coli among severely malnourished children is high. Surveillance of ESBL producers, both in the community and hospital settings needs to be stepped up in Kenya.

  12. The effect of heating temperature and nitric acid treatments on the performance of Cu- and Zn-based broad spectrum respirator carbons.

    Science.gov (United States)

    Smith, J W H; Romero, J V; Dahn, T R; Dunphy, K; Sullivan, B; Mallay, M; Croll, L M; Reynolds, J H; Andress, C; Dahn, J R

    2011-12-01

    Impregnated activated carbons (IACs) that are used in broad spectrum gas mask applications have historically contained copper and/or zinc impregnants. The addition of an oxidizing agent, such as nitric acid (HNO(3)) can be useful in distributing the metallic impregnants uniformly on the activated carbon substrate. In this work, we study IACs prepared from copper nitrate (Cu(NO(3))(2)) and zinc nitrate (Zn(NO(3))(2)) precursors as a function of HNO(3) content present in the impregnating solution and as a function of heating temperature. The gas adsorption capacity of the IACs was determined by dynamic flow testing using sulfur dioxide (SO(2)), ammonia (NH(3)), hydrogen cyanide (HCN) and cyclohexane (C(6)H(12)) challenge gases under dry and humid conditions. The thermal decomposition and distribution of the impregnant on the activated carbon substrate is studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermal analysis techniques. Relationships between gas adsorption capacity, impregnant distribution and the species of surface impregnants are discussed.

  13. Discovery and development of kibdelomycin, a new class of broad-spectrum antibiotics targeting the clinically proven bacterial type II topoisomerase.

    Science.gov (United States)

    Singh, Sheo B

    2016-12-15

    Kibdelomycin is a complex novel antibiotic, discovered by applying a highly sophisticated chemical-genetic Staphylococcus aureus Fitness Test (SaFT) approach, that inhibits the clinically established bacterial targets, gyrase and topoisomerase IV. It exhibits broad-spectrum antibacterial activity against aerobic bacteria including MRSA and Acinetobacter baumannii. It is slowly bactericidal and has a low frequency of resistance. In an anaerobic environment, it exhibits narrow-spectrum activity and inhibits the growth of gut bacteria Clostridium difficile (MIC 0.125μg/mL) without affecting the growth of commensal Gram-negative organisms particularly, Bacteroides sp. It is highly efficacious in the hamster model of C. difficile infection providing 100% protection at >6mg/kg and 80% protection at 1.56mg/kg by oral dosing without systemic exposure. X-ray co-crystal structures of kibdelomycin bound to GyrB and ParE showed a unique dual arm 'U shaped' multisite binding never encountered with any other gyrase inhibitors. Kibdelomycin is poised for preclinical development for C. difficile treatment, and most importantly, the co-crystal structures of kibdelomycin provide unique insight for structure-guided structure modification, which could lead to better broader-spectrum systemic antibiotic potentially covering many ESKAPE pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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

    2016-08-25

    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.

  16. 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.

  17. 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.

  18. Graphene transistors via in situ voltage-induced reduction of graphene-oxide under ambient conditions.

    Science.gov (United States)

    Mativetsky, Jeffrey M; Liscio, Andrea; Treossi, Emanuele; Orgiu, Emanuele; Zanelli, Alberto; Samorì, Paolo; Palermo, Vincenzo

    2011-09-14

    Here, we describe a simple approach to fabricate graphene-based field-effect-transistors (FETs), starting from aqueous solutions of graphene-oxide (GO), processed entirely under ambient conditions. The process relies on the site-selective reduction of GO sheets deposited in between or on the surface of micro/nanoelectrodes. The same electrodes are first used for voltage-induced electrochemical GO reduction, and then as the source and drain contacts of FETs, allowing for the straightforward production and characterization of ambipolar graphene devices. With the use of nanoelectrodes, we could reduce different selected areas belonging to one single sheet as well.

  19. Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats

    Science.gov (United States)

    Deng, Yuanyuan; Long, Long; Wang, Keke; Zhou, Jiayin; Zeng, Lingrong; He, Lianzi; Gong, Qihai

    2017-01-01

    Beta-amyloid (Aβ) deposition, associated neuronal apoptosis and neuroinflammation are considered as the important factors which lead to cognitive deficits in Alzheimer’s disease (AD). Icariside II (ICS II), an active flavonoid compound derived from Epimedium brevicornum Maxim, has been extensively used to treat erectile dysfunction, osteoporosis and dementia in traditional Chinese medicine. Recently, ICS II attracts great interest due to its broad-spectrum anti-cancer property. ICS II shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion. It is not yet clear whether the anti-inflammatory effect of ICS II could delay progression of AD. Therefore, the current study aimed to investigate the effects of ICS II on the behavioral deficits, Aβ levels, neuroinflammatory responses and apoptosis in Aβ25-35-treated rats. We found that bilateral hippocampal injection of Aβ25-35 induced cognitive impairment, neuronal damage, along with increase of Aβ, inflammation and apoptosis in hippocampus of rats. However, treatment with ICS II 20 mg/kg could improve the cognitive deficits, ameliorate neuronal death, and reduce the levels of Aβ in the hippocampus. Furthermore, ICS II could suppress microglial and astrocytic activation, inhibit expression of IL-1β, TNF-α, COX-2, and iNOS mRNA and protein, and attenuate the Aβ induced Bax/Bcl-2 ratio elevation and caspase-3 activation. In conclusion, these results showed that ICS II could reverse Aβ-induced cognitive deficits, possibly via the inhibition of neuroinflammation and apoptosis, which suggested a potential protective effect of ICS II on AD. PMID:28210222

  20. 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.

  1. 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.

  2. A broad spectrum, one-step reverse-transcription PCR amplification of the neuraminidase gene from multiple subtypes of influenza A virus

    Directory of Open Access Journals (Sweden)

    Chen Wenbin

    2008-07-01

    Full Text Available Abstract Background The emergence of high pathogenicity strains of Influenza A virus in a variety of human and animal hosts, with wide geographic distribution, has highlighted the importance of rapid identification and subtyping of the virus for outbreak management and treatment. Type A virus can be classified into subtypes according to the viral envelope glycoproteins, hemagglutinin and neuraminidase. Here we review the existing specificity and amplification of published primers to subtype neuraminidase genes and describe a new broad spectrum primer pair that can detect all 9 neuraminidase subtypes. Results Bioinformatic analysis of 3,337 full-length influenza A neuraminidase segments in the NCBI database revealed semi-conserved regions not previously targeted by primers. Two degenerate primers with M13 tags, NA8F-M13 and NA10R-M13 were designed from these regions and used to generate a 253 bp cDNA product. One-step RT-PCR testing was successful in 31/32 (97% cases using a touchdown protocol with RNA from over 32 different cultured influenza A virus strains representing the 9 neuraminidase subtypes. Frozen blinded clinical nasopharyngeal aspirates were also assayed and were mostly of subtype N2. The region amplified was direct sequenced and then used in database searches to confirm the identity of the template RNA. The RT-PCR fragment generated includes one of the mutation sites related to oseltamivir resistance, H274Y. Conclusion Our one-step RT-PCR assay followed by sequencing is a rapid, accurate, and specific method for detection and subtyping of different neuraminidase subtypes from a range of host species and from different geographical locations.

  3. 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

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Structure activity relationship of pyridoxazinone substituted RHS analogs of oxabicyclooctane-linked 1,5-naphthyridinyl novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-6).

    Science.gov (United States)

    Singh, Sheo B; Kaelin, David E; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Meinke, Peter T; Olsen, David B; Lagrutta, Armando; Wei, Changqing; Liao, Yonggang; Peng, Xuanjia; Wang, Xiu; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Yajima, Masanobu; Shibue, Taku; Shibata, Takeshi; Ohata, Kohei; Nishimura, Akinori; Fukuda, Yasumichi

    2015-09-01

    Oxabicyclooctane linked 1,5-naphthyridinyl-pyridoxazinones are novel broad-spectrum bacterial topoisomerase inhibitors (NBTIs) targeting bacterial DNA gyrase and topoisomerase IV at a site different than quinolones. Due to lack of cross-resistance to known antibiotics they present excellent opportunity to combat drug-resistant bacteria. A structure activity relationship of the pyridoxazinone moiety is described in this Letter. Chemical synthesis and activities of NBTIs with substitutions at C-3, C-4 and C-7 of the pyridoxazinone moiety with halogens, alkyl groups and methoxy group has been described. In addition, substitutions of the linker NH proton and its transformation into amide analogs of AM-8085 and AM-8191 have been reported. Fluoro, chloro, and methyl groups at C-3 of the pyridoxazinone moiety retained the potency and spectrum. In addition, a C-3 fluoro analog showed 4-fold better oral efficacy (ED50 3.9 mg/kg) as compared to the parent AM-8085 in a murine bacteremia model of infection of Staphylococcus aureus. Even modest polarity (e.g., methoxy) is not tolerated at C-3 of the pyridoxazinone unit. The basicity and NH group of the linker is important for the activity when CH2 is at the linker position-8. However, amides (with linker position-8 ketone) with a position-7 NH or N-methyl group retained potency and spectrum suggesting that neither basicity nor hydrogen-donor properties of the linker amide NH is essential for the activity. This would suggest likely an altered binding mode of the linker position-7,8 amide containing compounds. The amides showed highly improved hERG (functional IC50 >30 μM) profile.

  6. 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.

  7. In vitro and clinical evaluation of SIG1273: a cosmetic functional ingredient with a broad spectrum of anti-aging and antioxidant activities.

    Science.gov (United States)

    Fernández, José R; Rouzard, Karl; Voronkov, Michael; Huber, Kristen L; Webb, Corey; Stock, Jeffry B; Stock, Maxwell; Gordon, Joel S; Pérez, Eduardo

    2016-06-01

    Isoprenylcysteine (IPC) small molecules were identified as a new class of anti-inflammatory compounds over 20 years ago. Since then, they have been developed as novel cosmetic functional ingredients (CFI) and topical drug candidates. SIG1273 is a second generation CFI that has previously been shown to provide a broad spectrum of benefits for the skin through its anti-inflammatory and antimicrobial properties. To determine whether SIG1273 possesses anti-aging properties in vitro and evaluate the tolerability and activity of SIG1273 when applied topically to human subjects. To model photoaging in vitro, human dermal fibroblasts (HDFs) were exposed in culture to UVA to induce collagenase (MMP-1) production. An in vitro wound-healing model was based on the activation of HDF migration into cell-free tissue culture surface. Hydrogen peroxide-induced oxidative stress was performed using HDFs to measure intracellular ROS activity. Radical scavenging capacity was determined using a colorimetric antioxidant assay kit (ABTS method). Lastly, a 4-week, 29-subject study was performed in which SIG1273 was applied topically as a cream to assess its tolerance and activity in reducing the appearance of aging. In vitro studies demonstrate SIG1273 inhibits UVA-induced MMP-1 production, hydrogen peroxide-induced oxidative stress and promotes wound healing. Moreover, SIG1273 was shown to be a radical scavenging antioxidant. Clinical assessment of SIG1273 cream (0.25%) showed it was well tolerated with significant improvement in the appearance of fine lines, coarse wrinkles, radiance/luminosity, pore size, texture/smoothness, hydration and increased firmness. SIG1273 represents a novel CFI with antioxidant, anti-aging, and anti-inflammatory properties that when applied topically is well tolerated and provides benefits to individuals with aging skin. © 2016 Wiley Periodicals, Inc.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2011-01-01

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

  10. Upregulated expression of La ribonucleoprotein domain family member 6 and collagen type I gene following water-filtered broad-spectrum near-infrared irradiation in a 3-dimensional human epidermal tissue culture model as revealed by microarray analysis.

    Science.gov (United States)

    Tanaka, Yohei; Nakayama, Jun

    2017-02-27

    Water-filtered broad-spectrum near-infrared irradiation can induce various biological effects, as our previous clinical, histological, and biochemical investigations have shown. However, few studies that examined the changes thus induced in gene expression. The aim was to investigate the changes in gene expression in a 3-dimensional reconstructed epidermal tissue culture exposed to water-filtered broad-spectrum near-infrared irradiation. DNA microarray and quantitative real-time polymerase chain reaction (PCR) analysis was used to assess gene expression levels in a 3-dimensional reconstructed epidermal model composed of normal human epidermal cells exposed to water-filtered broad-spectrum near-infrared irradiation. The water filter allowed 1000-1800 nm wavelengths and excluded 1400-1500 nm wavelengths, and cells were exposed to 5 or 10 rounds of near-infrared irradiation at 10 J/cm(2) . A DNA microarray with over 50 000 different probes showed 18 genes that were upregulated or downregulated by at least twofold after irradiation. Quantitative real-time PCR revealed that, relative to control cells, the gene encoding La ribonucleoprotein domain family member 6 (LARP6), which regulates collagen expression, was significantly and dose-dependently upregulated (P < 0.05) by water-filtered broad-spectrum near-infrared exposure. Gene encoding transcripts of collagen type I were significantly upregulated compared with controls (P < 0.05). This study demonstrates the ability of water-filtered broad-spectrum near-infrared irradiation to stimulate the production of type I collagen. © 2017 The Australasian College of Dermatologists.

  11. Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways.

    Science.gov (United States)

    Bitner, Robert S; Bunnelle, William H; Anderson, David J; Briggs, Clark A; Buccafusco, Jerry; Curzon, Peter; Decker, Michael W; Frost, Jennifer M; Gronlien, Jens Halvard; Gubbins, Earl; Li, Jinhe; Malysz, John; Markosyan, Stella; Marsh, Kennan; Meyer, Michael D; Nikkel, Arthur L; Radek, Richard J; Robb, Holly M; Timmermann, Daniel; Sullivan, James P; Gopalakrishnan, Murali

    2007-09-26

    The alpha7 nicotinic acetylcholine receptor (nAChR) plays an important role in cognitive processes and may represent a drug target for treating cognitive deficits in neurodegenerative and psychiatric disorders. In the present study, we used a novel alpha7 nAChR-selective agonist, 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941) to interrogate cognitive efficacy, as well as examine potential cellular mechanisms of cognition. Exhibiting high affinity to native rat (Ki = 10.8 nM) and human (Ki = 16.7 nM) alpha7 nAChRs, A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. In addition, A-582941 normalized sensory gating deficits induced by the alpha7 nAChR antagonist methyllycaconitine in rats, and in DBA/2 mice that exhibit a natural sensory gating deficit. Examination of signaling pathways known to be involved in cognitive function revealed that alpha7 nAChR agonism increased extracellular-signal regulated kinase 1/2 (ERK1/2) phosphorylation in PC12 cells. Furthermore, increases in ERK1/2 and cAMP response element-binding protein (CREB) phosphorylation were observed in mouse cingulate cortex and/or hippocampus after acute A-582941 administration producing plasma concentrations in the range of alpha7 binding affinities and behavioral efficacious doses. The MEK inhibitor SL327 completely blocked alpha7 agonist-evoked ERK1/2 phosphorylation. Our results demonstrate that alpha7 nAChR agonism can lead to broad-spectrum efficacy in animal models at doses that enhance ERK1/2 and CREB phosphorylation/activation and may represent a mechanism that offers potential to improve cognitive deficits associated with neurodegenerative and psychiatric diseases, such as Alzheimer's disease and schizophrenia.

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

    Science.gov (United States)

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

    2015-03-01

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

  13. Effects of a broad-spectrum caspase inhibitor, Z-VAD(OMe)-FMK, on viral hemorrhagic septicemia virus (VHSV) infection-mediated apoptosis and viral replication.

    Science.gov (United States)

    Kim, Min Sun; Lee, Ji Ae; Kim, Ki Hong

    2016-04-01

    In the development of inactivated or attenuated viral vaccines for cultured fish, viral titers harvested from the cultured cells would be the most important factor for the determination of vaccine's cost effectiveness. In this study, we hypothesized that the lengthening of cell survival time by the inhibition of apoptosis can lead to an increase of the final titer of viral hemorrhagic septicemia virus (VHSV). To test the hypothesis, we investigated the effects of a broad-spectrum caspase inhibitor, Z-VAD(OMe)-FMK, on VHSV infection-mediated apoptosis in Epithelioma papulosum cyprini (EPC) cells and on the VHSV titers. VHSV infection induced the DNA laddering in EPC cells, and the progression of DNA fragmentation was in proportion to the CPE extension. The progression of DNA fragmentation in EPC cells infected with VHSV was clearly inhibited by exposure to Z-VAD(OMe)-FMK, and the inhibition was intensified according to the increase of the inhibitor concentration. These results confirmed the previous reports that the death of host cells by VHSV infection is through apoptosis. Cells infected with a recombinant VHSV, rVHSV-ΔNV-eGFP, that was generated from our previous study by replacement of the NV gene ORF with the enhanced green fluorescent protein (eGFP) gene ORF, showed earlier and more distinct DNA fragmentations compared to the cells infected with wild-type VHSV, suggesting the inhibitory role of the NV protein in VHSV-mediated apoptosis that was previously reported. The final viral titers in the supernatant isolated from Z-VAD(OMe)-FMK treated cells after showing an extensive CPE were significantly higher than the viral titers from cells infected with virus alone, indicating that the delay of apoptosis by Z-VAD(OMe)-FMK extended the survival time of EPC cells, which lengthen the time for VHSV replication in the cells. In conclusion, Z-VAD(OMe)-FMK-mediated inhibition of apoptosis significantly increased the final titers of both wild-type VHSV and r

  14. 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.

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

    Science.gov (United States)

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

    2013-01-01

    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. 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 coli and the drug Simvastatin for

  16. 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

  17. Voltage-induced material removal mechanism of copper for electrochemical-mechanical polishing applications

    Institute of Scientific and Technical Information of China (English)

    Sang-Jun HAN; Yong-Jin SEO

    2009-01-01

    The current-voltage (Ⅰ-Ⅴ) curves, such as linear sweep voltammetry (LSV) and cyclic voltammetry (CV), were employed to evaluate the effect of electrolyte concentration on the electrochemical reaction trend. From the Ⅰ-Ⅴ curve, the electrochemical states of active, passive, transient and trans-passive region could be characterized. And then, the mechanism of the process of voltage-induced material removal in electrochemical mechanical polishing (ECMP) of copper was investigated. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analyses were used to observe the surface profile. Finally, the oxidation and reduction processes of the Cu surface were monitored by the repetition of anodic and cathodic potential from cyclic voltammetry (CV) method in acid- and alkali-based electrolyte.

  18. Alternating voltage induced ordered anatase TiO2 nanopores: An electrochemical investigation of sodium storage

    Science.gov (United States)

    Li, Simin; Xie, Lingling; Hou, Hongshuai; Liao, Hanxiao; Huang, Zhaodong; Qiu, Xiaoqing; Ji, Xiaobo

    2016-12-01

    Anatase TiO2 nanopores are successfully prepared through alternating voltage induced electrochemical synthesis (AVIES) approach at room temperature. When utilizing TiO2 nanoporous materials as an anode for Na-ion battery, it delivers a reversible charge-discharge capacity of around 180 mA h g-1 at 0.2 C (67 mA g-1) after 200 cycles. Meanwhile, it also shows a good cycling performance and a high rate capability due to unique nanoporous structures, which promote electrolyte wetting and facilitate diffusion of Na+. Additionally, cyclic voltammetry demonstrate that the sodium-ion storage of as-prepared TiO2 is a cooperative control behavior of diffusion and capacitance, but mainly controlled by capacitive behavior, which further facilitates a rapid (de-)intercalation of Na+.

  19. 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

  20. Analysis of Possibilities to Reduce the Voltages Induced in Multi-circuit and Multi-voltage Overhead Lines

    Directory of Open Access Journals (Sweden)

    Rafał Tarko

    2015-09-01

    Full Text Available This paper presents the issues of electromagnetic interactions in a four-circuit and dual-voltage power line. Such solutions are increasingly used in practice due to difficulties in land acquisition for the construction of new power lines. Lines of this type, however, have some disadvantages, incl. the electromagnetic interactions between the circuits and voltages induced as their consequence. These issues are considered in relation to an existing four-circuit, 110 kV and 15 kV line. Results of the studies of the interaction effects in a real system, and an analysis of selected ways to reduce the voltage induced in 15 kV line circuits are presented.

  1. Behavior of deep level defects on voltage-induced stress of Cu(In,Ga)Se{sub 2} solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D.W.; Cho, S.E. [Department of Physics and Semiconductor Science, Dongguk University, Seoul (Korea, Republic of); Jeong, J.H. [Solar Cell Center, Korea Institute of Science and Technology, Seoul (Korea, Republic of); Cho, H.Y., E-mail: hycho@dongguk.edu [Department of Physics and Semiconductor Science, Dongguk University, Seoul (Korea, Republic of)

    2015-05-01

    The behavior of deep level defects by a voltage-induced stress for CuInGaSe{sub 2} (CIGS) solar cells has been investigated. CIGS solar cells were used with standard structures which are Al-doped ZnO/i-ZnO/CdS/CIGSe{sub 2}/Mo on soda lime glass, and that resulted in conversion efficiencies as high as 16%. The samples with the same structure were isothermally stressed at 100 °C under the reverse voltages. The voltage-induced stressing in CIGS samples causes a decrease in the carrier density and conversion efficiency. To investigate the behavior of deep level defects in the stressed CIGS cells, photo-induced current transient spectroscopy was utilized, and normally 3 deep level defects (including 2 hole traps and 1 electron trap) were found to be located at 0.18 eV and 0.29 eV above the valence band maximum (and 0.36 eV below the conduction band). In voltage-induced cells, especially, it was found that the decrease of the hole carrier density could be responsible for the increase of the 0.29 eV defect, which is known to be observed in less efficient CIGS solar cells. And the carrier density and the defects are reversible at least to a large extent by resting at room-temperature without the bias voltage. From optical capture kinetics in photo-induced current transient spectroscopy measurement, the types of defects could be distinguished into the isolated point defect and the extended defect. In this work, it is suggested that the increase of the 0.29 eV defect by voltage-induced stress could be due to electrical activation accompanied by a loss of positive ion species and the activated defect gives rise to reduction of the carrier density. - Highlights: • We investigated behavior of deep level defects by voltage-induced stress. • Defect generation could affect the decrease of the conversion efficiency of cells. • Defect generation could be electrically activated by a loss of positive ion species. • Type of defects could be studied with models of point defects

  2. 3-(3,4,5-Trimethoxybenzylidene)-2,4-pentanedione: Design of a novel photostabilizer with in vivo SPF boosting properties and its use in developing broad-spectrum sunscreen formulations.

    Science.gov (United States)

    Chaudhuri, R K; Ollengo, M A; Singh, P; Martincigh, B S

    2017-02-01

    The study concerned the synthesis of a novel photostabilizer based on benzylidenepentanedione chemistry and the evaluation of its potential in developing a broad-spectrum sunscreen formulation containing avobenzone. 3-(3,4,5-Trimethoxybenzylidene)-2-4-pentanedione (TMBP) was synthesized through a condensation reaction and incorporated into a sunscreen formulation containing, inter alia, avobenzone. The SPF, critical wavelength and in vitro photostability of the product were measured. The photostability was compared with that afforded by current avobenzone photostabilizers, namely octocrylene, ethylhexylmethoxycrylene and diethylhexylsyringylidenemalonate. The photostability of TMBP either alone or in the presence of avobenzone in a methanolic solution was also evaluated by UV spectrophotometric and HPLC analyses. The optical properties of TMBP were estimated experimentally and supported by time-dependent density functional theory (TD-DFT) calculations. The ability of TMBP to stabilize avobenzone under ultraviolet (UV) light exposure was shown both in formulated products and in solution. A comparative stability study incorporating various combinations of avobenzone, TMBP (vs. three commercial photostabilizers) and UVB sunscreens clearly showed TMBP to be a very effective stabilizer. The photostabilizing effect of TMBP arises from triplet-state energy transfer from avobenzone to TMBP and through light-induced reactions that preserve the main chromophores. Interestingly, a 50% in vivo SPF boosting was observed when TMBP was used with organic and inorganic sunscreens when alone it has no contribution to SPF. TMBP-containing sunscreen formulations clearly showed a critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens. We were able to design a very effective photostabilizer, trimethoxybenzylidene pentanedione (INCI name), based on benzylidenepentanedione chemistry. TMBP is very efficient in stabilizing avobenzone in formulated

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

    Science.gov (United States)

    van der Vaart, Rosalie; Drossaert, Constance

    2017-01-24

    satisfactory overall (total scale intraclass correlation coefficient=.77; subscale intraclass correlation coefficient range .49-.81). The performance-based items did not together form a single construct (alpha=.47) and should be interpreted individually. Results showed that more complex skills were reflected in a lower number of correct responses. Principal component analysis confirmed the theoretical structure of the self-report scale (76% explained variance). Correlations were as expected, showing significant relations with age (ρ=-.41, Pskills but should be studied and adapted further. Future research should examine the acceptability of this instrument in other languages and among different populations.

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

    Science.gov (United States)

    van der Vaart, Rosalie

    2017-01-01

    distribution. Test-retest analysis was satisfactory overall (total scale intraclass correlation coefficient=.77; subscale intraclass correlation coefficient range .49-.81). The performance-based items did not together form a single construct (alpha=.47) and should be interpreted individually. Results showed that more complex skills were reflected in a lower number of correct responses. Principal component analysis confirmed the theoretical structure of the self-report scale (76% explained variance). Correlations were as expected, showing significant relations with age (ρ=–.41, P<.001), education (ρ=.14, P=.047), Internet use (ρ=.39, P<.001), health-related Internet use (ρ=.27, P<.001), health status (ρ range .17-.27, P<.001), health literacy (ρ=.31, P<.001), and the eHEALS (ρ=.51, P<.001). Conclusions This instrument can be accepted as a new self-report measure to assess digital health literacy, using multiple subscales. Its performance-based items provide an indication of actual skills but should be studied and adapted further. Future research should examine the acceptability of this instrument in other languages and among different populations. PMID:28119275

  5. Two phase multiferroics for voltage-induced entropy change with application in near-room-temperature refrigeration

    Science.gov (United States)

    Giri, Prakash; Kumar, Dhananjay; Binek, Christian

    The demand for environmental friendly, cost-effective and energy efficient cooling drives the emerging technology of magnetic refrigeration at room temperature. We fabricate a two phase mutiferroic La0.7Sr0.3MnO3/Pb(Mg1/3Nb2/3) O3-PbTiO3(001) via pulsed laser deposition for application in advanced near room-temperature refrigeration and miniature cooling devices. The key innovation rests on utilizing the magnetocaloric effect in zero applied magnetic fields. The magnetocaloric effect of the composite is activated purely by electric field. We utilize strain originating from stress which is voltage-induced via the inverse piezoelectric effect of PMN-PT. The strain is carried over into the adjacent LSMO thin film thus changing its magnetic order. The voltage-induced variation in magnetization leads to change in isothermal entropy when the experiment is carried out in contact with a thermostat and gives correspondingly rise to an adiabatic temperature change when heat exchange is suppressed. This project is supported by NSF through Nebraska MRSEC DMR-1420645.

  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 passivation, ligands must be used to prevent nanocrystal fusion that leads to introduction of band tail states. The most efficient solution-processed infrared solar cells yet reported are achieved through this approach, opening a path towards low-cost photovoltaics with high spectral usage.

  7. A Fluorescent Broad-Spectrum Proteasome Inhibitor

    NARCIS (Netherlands)

    Verdoes, Martijn; Florea, Bogdan I.; Menendez-Benito, Victoria; Maynard, Christa J.; Witte, Martin D.; Linden, Wouter A. van der; Nieuwendijk, Adrianus M.C.H. van den; Hofmann, Tanja; Berkers, Celia R.; Leeuwen, Fijs W.B. van; Groothuis, Tom A.; Leeuwenburgh, Michiel A.; Ovaa, Huib; Neefjes, Jacques J.; Filippov, Dmitri V.; Marel, Gijs A. van der; Dantuma, Nico P.; Overkleeft, Herman S.

    2006-01-01

    The proteasome is an essential evolutionary conserved protease involved in many regulatory systems. Here, we describe the synthesis and characterization of the activity-based, fluorescent, and cell-permeable inhibitor Bodipy TMR-Ahx3L3VS (MV151), which specifically targets all active subunits of the

  8. Ceftobiprole: a new broad spectrum cephalosporin.

    Science.gov (United States)

    El Solh, Ali

    2009-07-01

    Ceftobiprole, formerly designated BAL9141/Ro 63-9141, is a pyrrolidinone-3-ylidene-methyl cephalosporin with demonstrated in vitro activity against MRSA, Enterococcus faecalis, Enterobacteriaceae and Pseudomonas aeruginosa. Ceftobiprole has a low potential for inducing chromosomal AmpC beta-lactamases but it is hydrolyzed by most extended spectrum beta-lactamases and metallo-beta-lactamases. Glomerular filtration is predominantly responsible for removal of the free drug from the systemic circulation. The efficacy of ceftobiprole in the treatment of complicated skin and ski-structure infections has been recently demonstrated in two Phase III randomized clinical trials involving 1600 patients. Two other Phase III clinical trials to assess ceftobiprole's efficacy in community-acquired pneumonia and nosocomial pneumonia have also concluded. While the drug met the noninferiority criteria for community-acquired pneumonia and nosocomial pneumonia involving non-ventilator associated pneumonia, ceftobiprole was less effective than the comparator in ventilator associated pneumonia subjects. Ceftobiprole was well tolerated with a safety profile consistent with the cephalosporin class of antibiotic. The most frequent drug-related adverse event was dysgeusia. Ceftobiprole is intended for use in the hospital for the treatment of infections that frequently involve beta-lactam-resistant Gram-negative and Gram-positive organisms.

  9. 3C和3CL蛋白酶及广谱抑制剂的研究进展%Broad spectrum inhibitors of 3C and 3CL proteases:research advances

    Institute of Scientific and Technical Information of China (English)

    张启燕; 张文会; 肖军海; 李松

    2016-01-01

    Picornaviruses(PV)and coronaviruses(CoV) are positive-stranded RNA viruses. Pathogens in the family can cause hand,foot and mouth disease,myocarditis, common cold ,severe respiratory and intestinal diseases. 3C and 3CL proteases, belonging to cysteine proteases,are required to process polyproteins into mature proteins for viral replication,which plays an impor⁃tant role in viral replication because substrate binding sites are highly conservative and have similar catalytic mechanism. 3C and 3CL proteases are different from protease in the human body ,which represents a promising anti-viral drug target. Using 3C and 3CL pro⁃teinase structural similarities,broad spectrum protease inhibitors have been found successfully. This review describes recent develop⁃ments of broad spectrum protease inhibitors targeting on 3C and 3CL proteases,and briefly illustrates the mechanism of the inhibitors, which may benefit to the development of virus therapy.%小RNA病毒和冠状病毒属于单正链RNA病毒,其家族中的病原体易导致手足口病、心肌炎、普通感冒以及严重的呼吸道和肠道疾病。3C和3CL蛋白酶都属于半胱氨酸蛋白酶,底物结合位点高度保守且具有相似的催化机制,是催化单正链RNA病毒前体蛋白裂解的关键蛋白酶,对病毒的复制有重要作用。人体中没有与其相似的蛋白酶,是目前广谱抗单正链RNA病毒研究的重要靶点。利用3C和3CL蛋白酶结构的相同点,成功发现了具有广谱作用的蛋白酶抑制剂。本文简要概述3C和3CL蛋白酶的结构、功能和广谱抑制剂的研究进展,并简要阐释抑制剂的作用机制,对该类酶的广谱抑制剂研究和相关病毒的治疗具有指导意义。

  10. Improving qPCR methodology for detection of foaming bacteria by analysis of broad-spectrum primers and a highly specific probe for quantification of Nocardia spp. in activated sludge.

    Science.gov (United States)

    Asvapathanagul, P; Olson, B H

    2017-01-01

    To develop qPCR broad-spectrum primers combined with a Nocardia genus-specific probe for the identification of a broad spectrum of Nocardia spp. and to analyse the effects of using this developed primer and probe set on the ability to quantify Nocardia spp. in mixed DNA. The consequences of using a degenerative primer set and species-specific probe for the genus Nocardia on qPCR assays were examined using DNA extracts of pure cultures and activated sludge. The mixed DNA extracts where the target organism Nocardia flavorosea concentration ranged from 5 × 10(2) to 5 × 10(6) copies per reaction, while the background organism's DNA (Mycobacterium bovis) concentration was held at 5 × 10(6) copies per reaction, only produced comparable cycle threshold florescence levels when N. flavorosea concentration was greater than or equal to the background organism concentration. When concentrations of N. flavorosea were lowered in increments of 1 log, while holding M. bovis concentrations constant at 5 × 10(6) copies per reaction, all assays demonstrated delayed cycle threshold values with a maximum 34·6-fold decrease in cycle threshold at a ratio of 10(6) M. bovis: 10(2) N. flavorosea copies per reaction. The data presented in this study indicated that increasing the ability of a primer set to capture a broad group of organisms can affect the accuracy of quantification even when a highly specific probe is used. This study examined several applications of molecular tools in complex communities such as evaluating the effect of mispriming vs interference. It also elucidates the importance of understanding the community genetic make-up on primer design. Degenerative primers are very useful in amplifying bacterial DNA across genera, but reduce the efficiency of qPCR reactions. Therefore, standards that address closely related background species must be used to obtain accurate qPCR results. © 2016 The Society for Applied Microbiology.

  11. Large Voltage-Induced Changes in the Perpendicular Magnetic Anisotropy of an MgO-Based Tunnel Junction with an Ultrathin Fe Layer

    Science.gov (United States)

    Nozaki, Takayuki; Kozioł-Rachwał, Anna; Skowroński, Witold; Zayets, Vadym; Shiota, Yoichi; Tamaru, Shingo; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji; Suzuki, Yoshishige

    2016-04-01

    We study the voltage control of perpendicular magnetic anisotropy in an ultrathin Fe layer sandwiched between the Cr buffer and MgO tunneling barrier layers. A high-interface magnetic anisotropy energy of 2.1 mJ /m2 is achieved in the Cr/ultrathin Fe /MgO structure. A large voltage-induced perpendicular magnetic anisotropy change is observed under the negative-bias voltage applications for the case of the Fe layer thinner than 0.6 nm. The amplitude of the voltage-induced anisotropy energy change exhibits a strong Fe-thickness dependence and it reaches as high as 290 fJ /Vm . The observed high values of the surface anisotropy and voltage-induced anisotropy energy change demonstrate the feasibility of voltage-driven spintronic devices.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  13. 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.

  14. Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5).

    Science.gov (United States)

    Singh, Sheo B; Kaelin, David E; Meinke, Peter T; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Olsen, David B; Lagrutta, Armando; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Takeuchi, Tomoko; Takano, Hisashi; Ohata, Kohei; Kurasaki, Haruaki; Nishimura, Akinori; Shibata, Takeshi; Fukuda, Yasumichi

    2015-09-01

    Oxabicyclooctane linked novel bacterial topoisomerase inhibitors (NBTIs) are new class of recently reported broad-spectrum antibacterial agents. They target bacterial DNA gyrase and topoisomerase IV and bind to a site different than quinolones. They show no cross-resistance to known antibiotics and provide opportunity to combat drug-resistant bacteria. A structure activity relationship of the C-2 substituted ether analogs of 1,5-naphthyridine oxabicyclooctane-linked NBTIs are described. Synthesis and antibacterial activities of a total of 63 analogs have been summarized representing alkyl, cyclo alkyl, fluoro alkyl, hydroxy alkyl, amino alkyl, and carboxyl alkyl ethers. All compounds were tested against three key strains each of Gram-positive and Gram-negative bacteria as well as for hERG binding activities. Many key compounds were also tested for the functional hERG activity. Six compounds were evaluated for efficacy in a murine bacteremia model of Staphylococcus aureus infection. Significant tolerance for the ether substitution (including polar groups such as amino and carboxyl) at C-2 was observed for S. aureus activity however the same was not true for Enterococcus faecium and Gram-negative strains. Reduced clogD generally showed reduced hERG activity and improved in vivo efficacy but was generally associated with decreased overall potency. One of the best compounds was hydroxy propyl ether (16), which mainly retained the potency, spectrum and in vivo efficacy of AM8085 associated with the decreased hERG activity and improved physical property.

  15. Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies.

    Science.gov (United States)

    Singla, Prinka; Luxami, Vijay; Singh, Raja; Tandon, Vibha; Paul, Kamaldeep

    2017-01-27

    A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10 μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50 values of 1.30 μM, 1.43 μM, 2.38 μM and 2.18 μM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).

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

    Science.gov (United States)

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

    2013-11-27

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

  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)

    Božic, Aleksandar K; Anderson, Robin C; Ricke, Steven C; Crandall, Philip G; O'Bryan, Corliss A

    2012-01-01

    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 effective while not leading to unacceptably long antibiotic withdrawal times. The effects of the CH(4)-inhibitors nitroethane (2 mg/mL), 2-nitro-1-propanol (2 mg/mL), lauric acid (5 mg/mL), the commercial product Lauricidin® (5 mg/mL), and a finely ground product of the Hawaiian marine algae, Chaetoceros (10 mg/mL), were compared in pure cultures of Streptococcus agalactia, Enterococcus faecium, Streptococcus bovis, and in a mixed lactic acid rumen bacterial culture. Lauricidin® and lauric acid exhibited the most bactericidal acidity against all bacteria. These results suggest potential animal health benefits from supplementing cattle diets with lauric acid or Lauricidin® to improve the health of the rumen and help prevent shedding of human pathogens.

  18. Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Pharmacological Properties of (S)-N-[(6-Chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112)

    Science.gov (United States)

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

    2014-01-01

    Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such “neurostabilizers” have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4–9, 10a–i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels, and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies. PMID:24205976

  19. 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

  20. 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.

  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. 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.

  3. 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.

    Science.gov (United States)

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    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 Klebsiella pneumoniae(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 < 0.05). Our findings have major

  4. 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.

  5. Growth of perpendicularly magnetized thin films on a polymer buffer and voltage-induced change of magnetic anisotropy at the MgO|CoFeB interface

    Directory of Open Access Journals (Sweden)

    D. D. Lam

    2015-06-01

    Full Text Available We show that perpendicularly magnetized thin films can be grown onto polyimide, a potentially flexible substrate. With polar Kerr magnetometry, we demonstrate that the coercive field of CoFeB thin film can be modulated by applying a back gate voltage. Our proposed multi-layered structure is suitable for surface-sensitive measurements of the voltage-induced change in anisotropy, and could be used to realize flexible spintronics devices.

  6. The value of in vivo reflectance confocal microscopy in the diagnosis and monitoring of inflammatory and infectious skin diseases: a systematic review

    NARCIS (Netherlands)

    Hoogedoorn, L.; Peppelman, M.; Kerkhof, P.C.M. van de; Erp, P.E.J. van; Gerritsen, M.J.P.

    2015-01-01

    In vivo examination of the skin by reflectance confocal microscopy (RCM) has been performed for about 20 years, leading to a broad spectrum of imaged infectious and inflammatory skin diseases (ISD) with many described RCM features. We systematically reviewed all available literature concerning ISD e

  7. Carbon-dot-decorated TiO2 nanotube arrays used for photo/voltage-induced organic pollutant degradation and the inactivation of bacteria

    Science.gov (United States)

    Feng, Lingyan; Sun, Hanjun; Ren, Jinsong; Qu, Xiaogang

    2016-03-01

    Photoluminescent carbon dots (c-dots) have recently attracted growing interest as a new member of the carbon-nanomaterial family. Here, we report for the first time that c-dot-decorated TiO2 nanotube arrays (c-dot/TiNTs) exhibit highly enhanced abilities regarding photo/voltage-induced organic pollutant degradation and bacterial inactivation. By applying UV irradiation (365 nm) or an electrochemical potential over 3 V (versus Ag/AgCl), an organic dye and a herbicide were efficiently degraded. Moreover, the inactivation of Gram-positive S. aureus and Gram-negative E. coli bacteria was realized on a c-dot/TiNT film. The c-dots were able to absorb light efficiently resulting in multiple exciton generation and also a reduction in the recombination of the e-/h+ pair produced in c-dot/TiNT film during photo/voltage-induced degradation. It was also possible to readily regenerate the surface using ultraviolet light irradiation, leaving the whole film structure undamaged and with high reproducibility and stability.

  8. Carbon-dot-decorated TiO₂ nanotube arrays used for photo/voltage-induced organic pollutant degradation and the inactivation of bacteria.

    Science.gov (United States)

    Feng, Lingyan; Sun, Hanjun; Ren, Jinsong; Qu, Xiaogang

    2016-03-18

    Photoluminescent carbon dots (c-dots) have recently attracted growing interest as a new member of the carbon-nanomaterial family. Here, we report for the first time that c-dot-decorated TiO2 nanotube arrays (c-dot/TiNTs) exhibit highly enhanced abilities regarding photo/voltage-induced organic pollutant degradation and bacterial inactivation. By applying UV irradiation (365 nm) or an electrochemical potential over 3 V (versus Ag/AgCl), an organic dye and a herbicide were efficiently degraded. Moreover, the inactivation of Gram-positive S. aureus and Gram-negative E. coli bacteria was realized on a c-dot/TiNT film. The c-dots were able to absorb light efficiently resulting in multiple exciton generation and also a reduction in the recombination of the e(-)/h(+) pair produced in c-dot/TiNT film during photo/voltage-induced degradation. It was also possible to readily regenerate the surface using ultraviolet light irradiation, leaving the whole film structure undamaged and with high reproducibility and stability.

  9. 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

  10. Using rf voltage induced ferromagnetic resonance to study the spin-wave density of states and the Gilbert damping in perpendicularly magnetized disks

    Science.gov (United States)

    Devolder, Thibaut

    2017-09-01

    We study how the shape of the spin-wave resonance lines in rf voltage induced FMR can be used to extract the spin-wave density of states and the Gilbert damping within the precessing layer in nanoscale magnetic tunnel junctions that possess perpendicular magnetic anisotropy. We work with a field applied along the easy axis to preserve the cylindrical symmetry of the uniaxial perpendicularly magnetized systems. We first describe the experimental setup to study the susceptibility contributions of the spin waves in the field-frequency space. We then identify experimentally the maximum device size above which the spin waves confined in the free layer can no longer be studied in isolation as the linewidths of their discrete responses make them overlap into a continuous density of states. The rf voltage induced signal is the sum of two voltages that have comparable magnitudes: a first voltage that originates from the linear transverse susceptibility and rectification by magnetoresistance and a second voltage that arises from the nonlinear longitudinal susceptibility and the resultant time-averaged change of the exact micromagnetic configuration of the precessing layer. The transverse and longitudinal susceptibility signals have different dc bias dependencies such that they can be separated by measuring how the device rectifies the rf voltage at different dc bias voltages. The transverse and longitudinal susceptibility signals have different line shapes; their joint studies in both fixed field-variable frequency, or fixed frequency-variable field configurations can yield the Gilbert damping of the free layer of the device with a degree of confidence that compares well with standard ferromagnetic resonance. Our method is illustrated on FeCoB-based free layers in which the individual spin waves can be sufficiently resolved only for disk diameters below 200 nm. The resonance line shapes on devices with 90-nm diameters are consistent with a Gilbert damping of 0.011 . A single

  11. Cholesterol favors the emergence of a long-range autocorrelated fluctuation pattern in voltage-induced ionic currents through lipid bilayers.

    Science.gov (United States)

    Corvalán, Natalia A; Kembro, Jackelyn M; Clop, Pedro D; Perillo, María A

    2013-08-01

    The present paper was aimed at evaluating the effect of cholesterol (CHO) on the voltage-induced lipid pore formation in bilayer membranes through a global characterization of the temporal dynamics of the fluctuation pattern of ion currents. The bilayer model used was black lipid membranes (BLMs) of palmitoyloleoylphosphatidylethanolamine and palmitoyloleoylphosphatidylcholine (POPE:POPC) at a 7:3 molar ratio in the absence (BLM0) or in the presence of 30 (BLM30), 40 (BLM40) or 50(BLM50)mol% of cholesterol with respect to total phospholipids. Electrical current intensities (I) were measured in voltage (ΔV) clamped conditions at ΔV ranging between 0 and ±200mV. The autocorrelation parameter α derived from detrended fluctuation analysis (DFA) on temporal fluctuation patterns of electrical currents allowed discriminating between non-correlated (α=0.5, white noise) and long-range correlated (0.5number of conductance states, the magnitude of conductance level, the capacitance of the bilayers and increased the tendency towards the development of long-range autocorrelated (fractal) processes (0.5<α<1) in lipid channel generation. Experiments were performed above the phase transition temperature of the lipid mixtures, but compositions used predicted a superlattice-like organization. This leads to the conclusion that structural defects other than phase coexistence may promote lipid channel formation under voltage clamped conditions. Furthermore, cholesterol controls the voltage threshold that allows the percolation of channel behavior where isolated channels become an interconnected network.

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

    National Research Council Canada - National Science Library

    Lara, Humberto H; Garza-Treviño, Elsa N; Ixtepan-Turrent, Liliana; Singh, Dinesh K

    2011-01-01

    .... 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...

  13. Rufinamide: A Novel Broad-Spectrum Antiepileptic Drug

    OpenAIRE

    Wheless, James W.; Vazquez, Blanca

    2010-01-01

    The last 20 years have witnessed a tremendous explosion in the number of antiepileptic drugs (AEDs) as well as the introduction of AEDS developed for specific epilepsy syndromes. The study of the efficacy and side effect profile of AEDs for unique epilepsy syndromes has allowed neurologists to utilize evidence-based medicine when treating patients. In late 2008, the Food and Drug Administration approved rufinamide for adjunctive use in the treatment of seizures associated with Lennox–Gastaut ...

  14. Rufinamide: a novel broad-spectrum antiepileptic drug

    National Research Council Canada - National Science Library

    Wheless, James W; Vazquez, Blanca

    2010-01-01

    ... has allowed neurologists to utilize evidence-based medicine when treating patients. In late 2008, the Food and Drug Administration approved rufinamide for adjunctive use in the treatment of seizures associated with Lennox-Gastaut syndrome...

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2005-05-01

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

  18. A Lead Compound for the Development of Broad-spectrum ...

    African Journals Online (AJOL)

    NJD

    1. Introduction. The development of untreatable resistant strains of pathogenic ..... rapid screening of antibacterial agents.28 A loopful of culture was taken from the .... Microplate Spectrophotometer, Bio-Rad Laboratories, Hemel. Hempstead ...

  19. 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

  20. 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

  1. Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent.

    Science.gov (United States)

    Miceli, Marisa H; Kauffman, Carol A

    2015-11-15

    Isavuconazole is a new extended-spectrum triazole with activity against yeasts, molds, and dimorphic fungi. It is approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. A randomized, double-blind comparison clinical trial for treatment of invasive aspergillosis found that the efficacy of isavuconazole was noninferior to that of voriconazole. An open-label trial that studied primary as well as salvage therapy of invasive mucormycosis showed efficacy with isavuconazole that was similar to that reported for amphotericin B and posaconazole. In patients in these studies, as well as in normal volunteers, isavuconazole was well tolerated, appeared to have few serious adverse effects, and had fewer drug-drug interactions than those noted with voriconazole. As clinical experience increases, the role of this new triazole in the treatment of invasive fungal infections will be better defined.

  2. 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.

  3. Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin.

    Science.gov (United States)

    Bogdanovich, Tatiana; Ednie, Lois M; Shapiro, Stuart; Appelbaum, Peter C

    2005-10-01

    Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC(50) and MIC(90) values for ceftobiprole were each 0.5 microg/ml against methicillin-susceptible strains and 2 mug/ml against methicillin-resistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC(50) and MIC(90) values were, respectively, 0.125 microg/ml and 1 microg/ml against methicillin-susceptible and 1 microg/ml and 2 microg/ml against methicillin-resistant strains. Teicoplanin was less active than vancomycin against coagulase-negative strains. Linezolid, quinupristin-dalfopristin, and daptomycin were active against all strains, whereas increased MICs for amoxicillin-clavulanate, cefazolin, minocycline, gentamicin, trimethoprim-sulfamethoxazole, levofloxacin, rifampin, mupirocin, fusidic acid, and fosfomycin were sometimes observed. At 2x MIC, ceftobiprole was bactericidal against 11 of 12 test strains by 24 h. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to select for clones with MICs >4 times those of the parents; the maximum MIC achieved for ceftobiprole after 50 passages (in 1 of 10 strains) was 8 mug/ml. Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 mug/ml.

  4. Antianaerobe activity of ceftobiprole, a new broad-spectrum cephalosporin.

    Science.gov (United States)

    Ednie, Lois; Shapiro, Stuart; Appelbaum, Peter C

    2007-05-01

    Agar dilution testing of 463 anaerobes showed most Gram-positive beta-lactamase-negative strains (other than some Clostridium difficile and Peptostreptococcus anaerobius), as well as both beta-lactamase-positive and beta-lactamase-negative strains of Fusobacterium nucleatum, to have ceftobiprole MIC values of Ceftobiprole was less active against beta-lactamase-positive Gram-negative bacilli, especially the members of the Bacteroides fragilis group. Like ceftobiprole, piperacillin was active mainly against beta-lactamase-negative strains, though MIC values for piperacillin were often 1 to 2 dilutions higher than for ceftobiprole. Carbapenems had MIC values < or =4 microg/L against all except some C. difficile and 2 strains of B. fragilis. All strains were susceptible to metronidazole, and all bacteria, except C. difficile and a single Bacteroides distasonis strain, were susceptible to chloramphenicol. Clindamycin resistance was seen in most anaerobe groups, whereas high moxifloxacin MICs were found mainly among the B. fragilis and Prevotella groups, and a few C. difficile and F. nucleatum strains.

  5. Predictive compound accumulation rules yield a broad-spectrum antibiotic

    Science.gov (United States)

    Richter, Michelle F.; Drown, Bryon S.; Riley, Andrew P.; Garcia, Alfredo; Shirai, Tomohiro; Svec, Riley L.; Hergenrother, Paul J.

    2017-05-01

    Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria.

  6. 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.

  7. Development of a Broad-Spectrum Antiviral Agent with Activity ...

    African Journals Online (AJOL)

    Activity Against Herpesvirus Replication and Gene. Expression ... Method: Antiviral activity against Herpes simplex virus type 1 (HSV-1) was determined using thiazolyl ..... Marker; 1 = Vero cells; 2 = HSV-1; 3 = ACV; 4 = H9);. (D) effect of H9 on ...

  8. Wheat-related disorders: A broad spectrum of 'evolving' diseases.

    Science.gov (United States)

    Gasbarrini, Gb; Mangiola, F

    2014-08-01

    Throughout the world, cereals have always been recognized as a fundamental food. Human evolution, through the development of cooking, led to the production of food rich in gluten, in order to take full advantage of the nutritional properties of this food. The result has been that gluten intolerance has arisen only in those populations that developed the art of cooking wheat. It is also recognized that wheat, one of the central elements of the Mediterranean diet, cannot be tolerated in some individuals. Among the wheat-related pathologies, coeliac disease is the best known: it is a chronic inflammatory condition affecting the gastrointestinal tract, which develops in genetically predisposed individuals. The most common manifestation is the malabsorption of nutrients. Recently, another wheat-related disease has appeared: non-coeliac gluten sensitivity, defined as the onset of a variety of manifestations related to wheat, rye and barley ingestion, in patients in whom coeliac disease and wheat allergy have been excluded. In this paper we will explore the damaging power of wheat, analysing the harmful process by which it realizes the onset of clinical manifestations associated with wheat-related disorders.

  9. 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.

  10. Reflecting reflection in supervision

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    Reflection has moved from the margins to the mainstream in supervision. Notions of reflection have become well established since the late 1980s. These notions have provided useful framing devices to help conceptualize some important processes in guidance and counseling. However, some applications...

  11. Construction and Identification of Antibodies 2F5 and 4E10 Target Gene Vectors with the Neutralization of Anti-HIV Broad Spectrum%含抗HIV广谱中和抗体2F5、4E10靶基因载体的构建及鉴定

    Institute of Scientific and Technical Information of China (English)

    王晶妍; 张煜; 王珂; 王建英

    2012-01-01

    目的:构建含HIV gp120,gp41序列中广谱中和抗体2F5,4E10作用靶基因的载体并进行鉴定,为后期重组载体表达产物诱导产生中和抗体及抗HIV亚单位疫苗的研究奠定基础.方法:根据NCBI中HIV gp120,gp41基因序列中可与2F5、4E10结合的区域设计引物并进行PCR反应,将PCR得到的目的片段插入到载体pET28a中,对重组载体进行PCR鉴定、酶切鉴定及DNA测序.结果:PCR鉴定、酶切鉴定及DNA测序结果证实重组载体构建成功.结论:成功构建了含HIV gp120,gp41序列中广谱中和抗体2F5,4E10作用靶基因的载体.%Objective Antibodies 2F5 and 4E10 target gene vectors with the neutralization of anti-HIV broad spectrum were constructed and identified. This will certainly lay the foundation for future research of neutralizing antibodies from recom-binanl vector products in expression and induction and anti-HIV subunit vaccine. Method Primers were designed and PCR was conducted according to the binding region of the HIV gp120, gp41 gene sequences in NCBI and the 2F5 , 4E10. Then the target fragments from PCR were inserted into the vector pET28a. In the end. PCR, restriction enzyme digestion and DNA sequencing were performed for the recombinant vectors. The results; PCR, restriction enzyme digestion and DNA sequencing confirmed that the recombinant vector were successfully constructed. The conclusion; The construction of vectors of broad-spectrum neutralizing antibodies 2F5, 4E10 target genes containing HIV gp120. gp41 gene sequences was successfully conducted in this paper.

  12. Classification of influenza A virus and its value for research of universal influenza vaccine and broad-spectrum neutralization antibody%甲型流感病毒分类与通用流感疫苗及广谱中和活性抗体的研究

    Institute of Scientific and Technical Information of China (English)

    蒋露芳; 居丽雯; 姜庆五

    2011-01-01

    Influenza is a great harm contagious disease for human. Vaccination is considered to be the most effective means to prevent influenza. For the problems of existing vaccine on timeliness and effectiveness,universal influenza vaccine,which can preclude all the influenza virus and induce duration protective immunity, has been a hot research. Meanwhile, the broad-spectrum neutralization antibody against all influenza A viruses is also the current focus. All these have made the request to explore applicable classification of influenza A virus.%流感是对人类危害极大的传染病,疫苗接种被认为是预防流感的最有效手段.为解决流感病毒变异导致现有疫卣时效性与有效性的问题,研制能够预防所有流感病毒毒株、可诱导持久保护性免疫的通用流感疫苗一直是流感研究的热点,同时,能中和所有甲型流感病毒的广谱中和活性抗体的研究也已成为目前关注的重点,因此对甲型流感病毒分类研究也提出了相应的要求.

  13. Reflective Teaching

    Science.gov (United States)

    Farrell, Thomas S. C.

    2013-01-01

    Thomas Farrell's "Reflective Teaching" outlines four principles that take teachers from just doing reflection to making it a way of being. Using the four principles, Reflective Practice Is Evidence Based, Reflective Practice Involves Dialogue, Reflective Practice Links Beliefs and Practices, and Reflective Practice Is a Way of Life,…

  14. 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

  15. Application of broad-spectrum humanized neutralizing monoclonal antibodies to influenza A virus in prevention and treatment of influenza%广谱全人源化甲型流感病毒中和抗体在流感预防与治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    高灵茜; 杨利

    2013-01-01

    针对多个亚型甲型流感病毒的广谱中和性单克隆抗体(monoclonalantibody,mAb)是极具潜力的新型而有效的流感防治手段.抗流感病毒血凝素(hemagglutinin,HA)的保护性mAb,无论通过主动免疫还是被动免疫,均具有很好的效果.迄今,已有不少甲型流感病毒广谱中和性mAb被开发出来.尽管这些mAb具备临床应用潜能以及作为研制新型疫苗(抗独特型抗体疫苗)的可能,但仅有几种HA mAb对人类流感防治真正有效.此文主要对能高效识别多个亚型HA的人源化甲型流感病毒mAb做一综述.%Broad-spectrum neutralizing monoclonal antibodies (mAbs) against different subtypes of influenza A viruses are potential tools to prevent and treat influenza.Protective mAbs to influenza hemagglutinin (HA) have good results by passive and active immunization.So far,a number of mAbs against influenza HA have been developed.But only few of them are effective for influenza prevention and treatment.In this article,the human mAbs which can recognize divergent influenza isolates are reviewed.

  16. 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。

  17. Reflective Writing

    DEFF Research Database (Denmark)

    Ahrenkiel Jørgensen, Andriette

    2016-01-01

    Høeg etetera. The dialogues work as a tool of reflection in terms of providing opportunity to examine his own beliefs, to explore the possible reasons for engaging in a particular activity. On the basis of Sven-Ingvar Andersson’s book a teaching program at the Aarhus School of Architecture provides...... a contribution to the discussions about the role of reflection in design work and in learning situations at large. By engaging with the dialogic reflection, which is one of the four essential types of reflection, (the three others being descriptive writing, descriptive reflection and critical reflection...

  18. 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.

  19. Preservative Effect of Broad-Spectrum Enterocin LM-2 on Cold Sliced Ham%广谱乳酸菌细菌素enterocin LM-2对低温切片火腿的防腐保鲜效果(英文)

    Institute of Scientific and Technical Information of China (English)

    刘国荣; 王成涛; 王洋; 张宝; 李平兰

    2012-01-01

    为考察广谱乳酸菌细菌素enterocin LM-2对低温切片火腿的防腐保鲜效果,并探讨其在低温肉制品防腐保鲜中的应用可行性。本研究在不添加任何化学防腐剂的前提下,分别添加80、320、1280AU/g enterocin LM-2处理低温切片火腿,分析不同浓度细菌素处理前后样品中微生物数量、理化指标以及感官特性的变化。结果发现:细菌素enterocin LM-2的添加可明显延长低温切片火腿的货架期,有效减少贮藏过程中挥发性盐基氮的生成及脂肪氧化程度,并保持产品原有色泽、气味、质构等感官特性。综合微生物和理化特性分析结果,确定添加1280AU/g enterocin LM-2的处理组防腐效果最好,可将低温切片火腿的货架期延长至49d。这些结果都显示出乳酸菌细菌素enterocin LM-2有作为天然生物防腐剂应用于低温肉制品防腐保鲜中的巨大应用潜力。%Enterocin LM-2,a broad-spectrum bacteriocin isolated from Chinese traditional cheese,was produced by Enterococcus faecium LM-2.In order to examine the potential of enterocin LM-2 as a biopreservative in sliced cooked ham,the effect of enterocin LM-2 at different concentrations(80,320,1280 AU/g) on microbiological,physicochemical and sensory quality properties of sliced cooked ham during the refrigerated storage at 4 ℃ was explored in this paper.The addition of enterocin LM-2 could substantially suppress the growth of microflora,especially Listeria monocytogenes and Salmonella enteritidis,and decrease the accumulation of TVB-N and lipid oxidation during refrigerated storage of sliced cooked ham.Overall,the most effective treatment was achieved by adding 1280 AU/g enterocin LM-2,which could extend the shelf life up to 49 days and produce a better sensory profile during the whole storage period.These results clearly indicate that enterocin LM-2 has a great potential as a biopreservative for enhancing the safety and quality of refrigerated sliced cooked

  20. 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 .

  1. 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

  2. Non-fusion soluble expression of broad-spectrum antivirus protein in Escherichia coli by translational-coupling with SUMO%利用翻译偶联实现广谱抗病毒蛋白在大肠杆菌中的可溶性表达

    Institute of Scientific and Technical Information of China (English)

    邢伶越; 谢德健; 叶丙雨; 张章; 李平; 沈文龙; 师明磊; 张彦; 赵志虎

    2015-01-01

    目的:以具有广泛助溶活性的小泛素相关修饰蛋白( small ubiquitin-related modifier,SUMO)为辅助蛋白,利用翻译偶联,构建一种新型非融合可溶原核表达载体,实现广谱抗病毒蛋白RA在大肠杆菌中的非融合可溶表达。方法以PCR方法从酵母基因组中克隆SUMO蛋白基因smt3并进行定点突变,去除其中的EcoRⅠ酶切位点,获得同义突变体mSUMO。通过翻译偶联Linker序列的设计、合成,构建以mSUMO蛋白为辅助蛋白的翻译偶联表达载体pTIG-mSUMO。 PCR扩增获得带有相应酶切位点的广谱抗病毒蛋白 RA 的基因,将其克隆至 pTIG-mSUMO中,获得表达载体pTIG-mSUMO/RA,实现RA在大肠杆菌中的非融合可溶性表达。结果 IPTG诱导蛋白表达以后,SDS-PAGE和Western印迹检测证实,目的蛋白RA的表达量明显增加,且可溶比例约占50%。结论以优化后的SUMO为辅助蛋白,成功构建了一种非融合的可溶原核表达载体pTIG-mSUMO,实现了RA蛋白在大肠杆菌中的高效非融合可溶表达,既提高了表达水平,也提高了可溶性。 pTIG-mSUMO作为一种可溶的非融合表达载体,在实现外源蛋白的高效可溶表达方面,很可能具有一定的普遍性。%Objective To design and construct a new non-fusion soluble expression vector pTIG-mSUMO(small ubiq-uitin-related modifier) using the widely used solubility promoting protein SUMO and based on the translational coupling phenomenon in order to enable the non-fusion soluble expression of the broad-spectrum antiviral protein RA in Escherichia coli by pTIG-mSUMO.Methods The smt3 gene coding for SUMO protein was cloned from yeast genome DNA by PCR. After directed-site silent mutation to eliminate the EcoRⅠsite, the mutant mSUMO was inserted into pET-22b to obtain the translational coupling expression vector pTIG-mSUMO.The RA was subject to PCR amplification and cloned into the pTIG-mSUMO to

  3. Quantifying Reflection

    DEFF Research Database (Denmark)

    Alcock, Gordon Lindsay

    2013-01-01

    This paper documents 1st semester student reflections on “learning to learn” in a team-based PBL environment with quantitative and qualitative student reflective feedback on the learning gains of 60 Architectural Technology and Construction Management students at VIA University College, Denmark....... It contrasts the students’ self-assessment in a range of ‘product’ skills such as Revit, Structural Design, Mathematics of construction, Technical Installations; as well as ‘process’ competencies such as ‘Working in a team’, Sharing knowledge, Maintaining a portfolio and Reflecting ON learning and FOR learning......´ These are all based on Blooms taxonomy and levels of competence and form a major part of individual student and group learning portfolios. Key Words :Project-Based learning, Reflective Portfolios, Self assessment, Defining learning gains, Developing learning strategies , Reflections on and for learning...

  4. Reflection ciphers

    DEFF Research Database (Denmark)

    Boura, Christina; Canteaut, Anne; Knudsen, Lars Ramkilde

    2017-01-01

    study the necessary properties for this coupling permutation. Special care has to be taken of some related-key distinguishers since, in the context of reflection ciphers, they may provide attacks in the single-key setting.We then derive some criteria for constructing secure reflection ciphers...... and analyze the security properties of different families of coupling permutations. Finally, we concentrate on the case of reflection block ciphers and, as an illustration, we provide concrete examples of key schedules corresponding to several coupling permutations, which lead to new variants of the block...

  5. 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

  6. Reflective optics

    CERN Document Server

    Korsch, Dietrich

    1991-01-01

    This is the first book dedicated exclusively to all-reflective imaging systems. It is a teaching tool as well as a practical design tool for anyone who specializes in optics, particularly for those interested in telescopes, infrared, and grazing-incidence systems. The first part of the book describes a unified geometric optical theory of all-reflective imaging systems (from near-normal to grazing incidence) developed from basic principles. The second part discusses correction methods and a multitude of closed-form solutions of well-corrected systems, supplemented with many conventional and unc

  7. Reflective equilibrium

    NARCIS (Netherlands)

    van der Burg, W.; van Willigenburg, T.

    1998-01-01

    The basic idea of reflective equilibrium, as a method for theory construction and decision making in ethics, is that we should bring together a broad variety of moral and non-moral beliefs and, through a process of critical scrutiny and mutual adjustment, combine these into one coherent belief syste

  8. Reflective equilibrium

    NARCIS (Netherlands)

    van der Burg, W.; van Willigenburg, T.

    1998-01-01

    The basic idea of reflective equilibrium, as a method for theory construction and decision making in ethics, is that we should bring together a broad variety of moral and non-moral beliefs and, through a process of critical scrutiny and mutual adjustment, combine these into one coherent belief syste

  9. On Reflection

    DEFF Research Database (Denmark)

    Blasco, Maribel

    2012-01-01

    This article explores how the concept of reflexivity is used in intercultural education. Reflexivity is often presented as a key learning goal in acquiring intercultural competence (ICC). Yet, reflexivity can be defined in different ways, and take different forms across time and space, depending...... on the concepts of selfhood that prevail and how notions of difference are constructed. First, I discuss how the dominant usages of reflexivity in intercultural education reflect and reproduce a Cartesian view of the self that shapes how ICC is conceptualized and taught. I discuss three assumptions that this view...... in designing learning objectives in intercultural education and in devising ways to attain them. Greater attention is also needed in intercultural education to the ways in which selfhood, and hence also reflexivity and constructions of difference, differ across space and time....

  10. Inspiring Reflections

    DEFF Research Database (Denmark)

    Muchie, Mammo

    2011-01-01

    contributions have been put together. There are a number of ways to continue Chris Freeman's legacy on innovation research. The first is to build in a critical tradition in the economics of innovation research by introducing fearlessly emancipatory epistemology. Second the economic system that dominates social......A numberof Chris Freeman's colleagues were asked to reflect on what they thought describes his life and work in a few words. Some of the colleagues replied including former SPRU students that were taught or supervised by Chris Freeman. Their views on what they thought were Chris Freeman's defining...... life is not free from fluctuations, cycles, disruptions, crises and destructions both human and ecological. Innovation research ought to position itself to address environmental, financial and economic crises. The third is innovation research for development by addressing not only poverty erdaication...

  11. Reflected Glory

    Science.gov (United States)

    2011-02-01

    The nebula Messier 78 takes centre stage in this image taken with the Wide Field Imager on the MPG/ESO 2.2-metre telescope at the La Silla Observatory in Chile, while the stars powering the bright display take a backseat. The brilliant starlight ricochets off dust particles in the nebula, illuminating it with scattered blue light. Igor Chekalin was the overall winner of ESO's Hidden Treasures 2010 astrophotography competition with his image of this stunning object. Messier 78 is a fine example of a reflection nebula. The ultraviolet radiation from the stars that illuminate it is not intense enough to ionise the gas to make it glow - its dust particles simply reflect the starlight that falls on them. Despite this, Messier 78 can easily be observed with a small telescope, being one of the brightest reflection nebulae in the sky. It lies about 1350 light-years away in the constellation of Orion (The Hunter) and can be found northeast of the easternmost star of Orion's belt. This new image of Messier 78 from the MPG/ESO 2.2-metre telescope at the La Silla Observatory is based on data selected by Igor Chekalin in his winning entry to the Hidden Treasures competition [1]. The pale blue tint seen in the nebula in this picture is an accurate representation of its dominant colour. Blue hues are commonly seen in reflection nebulae because of the way the starlight is scattered by the tiny dust particles that they contain: the shorter wavelength of blue light is scattered more efficiently than the longer wavelength red light. This image contains many other striking features apart from the glowing nebula. A thick band of obscuring dust stretches across the image from the upper left to the lower right, blocking the light from background stars. In the bottom right corner, many curious pink structures are also visible, which are created by jets of material being ejected from stars that have recently formed and are still buried deep in dust clouds. Two bright stars, HD 38563A and

  12. 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.

  13. 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…

  14. Broad-spectrum bactericidal activity of Ag(2)O-doped bioactive glass.

    Science.gov (United States)

    Bellantone, Maria; Williams, Huw D; Hench, Larry L

    2002-06-01

    Bioactive glass has found extensive application as an orthopedic and dental graft material and most recently also as a tissue engineering scaffold. Here we report an initial investigation of the in vitro antibacterial properties of AgBG, a novel bioactive glass composition doped with Ag(2)O. The bacteriostatic and bactericidal properties of this new material and of two other bioactive glass compositions, 45S5 Bioglass and BG, have been studied by using Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus as test microorganisms. Concentrations of AgBG in the range of 0.05 to 0.20 mg of AgBG per ml of culture medium were found to inhibit the growth of these bacteria. Not only was AgBG bacteriostatic, but it also elicited a rapid bactericidal action. A complete bactericidal effect was elicited within the first hours of incubation at AgBG concentrations of 10 mg ml(-1). 45S5 Bioglass and BG had no effect on bacterial growth or viability. The antibacterial action of AgBG is attributed exclusively to the leaching of Ag(+) ions from the glass matrix. Analytical measurements rule out any contribution to AgBG-mediated bacterial killing by changes in pH or ionic strength or the dissolution of other ionic species from the biomaterials. Our observations of the dissolution profiles of Ag(+) from AgBG in the presence and absence of bacteria are consistent with silver accumulation by the bacteria.

  15. Broad Spectrum Microbicidal Activity of Photocatalysis by TiO2

    Directory of Open Access Journals (Sweden)

    Yoshinobu Kubota

    2013-03-01

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

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

    NARCIS (Netherlands)

    Von Korff, Michael; Alonso, Jordi; Ormel, Johan; Angermeyer, Matthais; Bruffaerts, Ronny; Fleiz, Clara; de Girolamo, Giovanni; Kessler, Ronald C.; 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

  17. Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin.

    Science.gov (United States)

    Huang, Liyi; Szewczyk, Grzegorz; Sarna, Tadeusz; Hamblin, Michael R

    2017-02-23

    It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or fungi. However, the aPDI activity of PF against Gram-negative bacteria is accepted to be extremely low. Here we report that the nontoxic inorganic salt potassium iodide (KI) at a concentration of 100 mM when added to microbial cells (10(8)/mL) + PF (10 μM hematoporphyrin equivalent) + 415 nm light (10 J/cm(2)) can eradicate (>6 log killing) five different Gram-negative species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii), whereas no killing was obtained without KI. The mechanism of action appears to be the generation of microbicidal molecular iodine (I2/I3(-)) as shown by comparable bacterial killing when cells were added to the mixture after completion of illumination and light-dependent generation of iodine as detected by the formation of the starch complex. Gram-positive methicillin-resistant Staphylococcus aureus is much more sensitive to aPDI (200-500 nM PF), and in this case potentiation by KI may be mediated mainly by short-lived iodine reactive species. The fungal yeast Candida albicans displayed intermediate sensitivity to PF-aPDI, and killing was also potentiated by KI. The reaction mechanism occurs via singlet oxygen ((1)O2). KI quenched (1)O2 luminescence (1270 nm) at a rate constant of 9.2 × 10(5) M(-1) s(-1). Oxygen consumption was increased when PF was illuminated in the presence of KI. Hydrogen peroxide but not superoxide was generated from illuminated PF in the presence of KI. Sodium azide completely inhibited the killing of E. coli with PF/blue light + KI.

  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.

  19. 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.

  20. 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

    Natural resources support all of our social and economic activities, as well as our biological existence. Humans have little control over most of the physical, biological, and sociological conditions dictating the status and capacity of natural resources in any particular area. However, the most rapid and threatening influences on natural resources typically are anthropogenic overuse and degradation. In addition, living natural resources (i.e., organisms) do not respect political boundaries, but are aware of their optimal habitat and environmental conditions. Most organisms have wider spatial ranges than the jurisdictional boundaries of environmental agencies that deal with them; even within those jurisdictions, information is patchy and disconnected. Planning and projecting effects of ecological management are difficult, because many organisms, habitat conditions, and interactions are involved. Conservation and responsible resource use involves wise management and manipulation of the aspects of the environment and biological communities that can be effectively changed. Tools and data sets that provide new insights and analysis capabilities can enhance the ability of resource managers to make wise decisions and plan effective, long-term management strategies. Aquatic gap analysis has been developed to provide those benefits. Gap analysis is more than just the assessment of the match or mis-match (i.e., gaps) between habitats of ecological value and areas with an appropriate level of environmental protection (e.g., refuges, parks, preserves), as the name suggests. Rather, a Gap Analysis project is a process which leads to an organized database of georeferenced information and previously available tools to examine conservation and other ecological issues; it provides a geographic analysis platform that serves as a foundation for aquatic ecological studies. This analytical tool box allows one to conduct assessments of all habitat elements within an area of interest. 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.

  1. 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.

  2. Dissemination and genetic support of broad-spectrum beta-lactam ...

    African Journals Online (AJOL)

    Methods: A total of 113 E.coli isolates obtained during the period 2004 through 2012 showed a significant .... Crude enzyme extract was incubated with clavulanic acid ..... Pulsed-field gel electrophoresis (PFGE) of XbaI-digested genomic DNA.

  3. Marine toxins consist of a broad spectrum of bio- logically active ...

    African Journals Online (AJOL)

    spamer

    M. L. FERNÁNDEZ*. Toxins produced by marine microalgae are harmful to humans and a serious threat to aquaculture and fisheries. .... unit is defined as the amount of toxin required to kill a 20 g mouse ... tumor promoters (Fujiki et al. 1988).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-04-15

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

  5. 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.

  6. Novel Plant-Derived Recombinant Human Interferons with Broad Spectrum Antiviral Activity

    Science.gov (United States)

    2011-10-14

    compared the antiviral activities of more than 1400 plant-derived, hybrid IFNs against three RNA viruses and one DNA virus from four different families...highly pathogenic viruses with varying sensitivities to type I IFN. In particular, the DNA virus , MPXV, was not expected to be as susceptible to the...K.M., Callis, R.T., Stephen, E.L., 1980. Lassa virus infection of rhesus monkeys: pathogenesis and treatment with ribavirin. J. Infect. Dis. 141, 580

  7. 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)

  8. Fungal Glucosylceramide-Specific Camelid Single Domain Antibodies Are Characterized by Broad Spectrum Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Barbara De Coninck

    2017-06-01

    Full Text Available Chemical crop protection is widely used to control plant diseases. However, the adverse effects of pesticide use on human health and environment, resistance development and the impact of regulatory requirements on the crop protection market urges the agrochemical industry to explore innovative and alternative approaches. In that context, we demonstrate here the potential of camelid single domain antibodies (VHHs generated against fungal glucosylceramides (fGlcCer, important pathogenicity factors. To this end, llamas were immunized with purified fGlcCer and a mixture of mycelium and spores of the fungus Botrytis cinerea, one of the most important plant pathogenic fungi. The llama immune repertoire was subsequently cloned in a phage display vector to generate a library with a diversity of at least 108 different clones. This library was incubated with fGlcCer to identify phages that bind to fGlcCer, and VHHs that specifically bound fGlcCer but not mammalian or plant-derived GlcCer were selected. They were shown to inhibit the growth of B. cinerea in vitro, with VHH 41D01 having the highest antifungal activity. Moreover, VHH 41D01 could reduce disease symptoms induced by B. cinerea when sprayed on tomato leaves. Based on all these data, anti-fGlcCer VHHs show the potential to be used as an alternative approach to combat fungal plant diseases.

  9. 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....

  10. Legionella shows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase

    Directory of Open Access Journals (Sweden)

    Nicholas J. Tobias

    2016-11-01

    Full Text Available Several members of the genus Legionella cause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites from Legionella. Following whole genome sequencing, we assembled and annotated the Legionella parisiensis DSM 19216 genome. Together with 14 other members of the Legionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found that Legionella contains a huge variety of biosynthetic gene clusters (BGCs that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in all Legionella strains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis and secondary metabolism (polyketide and non-ribosomal peptide synthesis. Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential of Legionella.

  11. Screening bioactives reveals nanchangmycin as a broad spectrum antiviral active against Zika virus

    Science.gov (United States)

    Rausch, Keiko; Hackett, Brent; Weinbren, Nathan; Reeder, Sophia; Sadovsky, Yoel; Hunter, Christopher; Schultz, David C.; Coyne, Carolyn; Cherry, Sara

    2017-01-01

    Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2000 ‘bioactive’ compounds for their ability to block Zika virus infection in three distinct cell-types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested including physiologically relevant primary cells. Nanchanmycin was also active against other medically relevant viruses including West Nile, dengue, and chikungunya virus that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis. PMID:28099856

  12. Discovery of BMS-955176, a Second Generation HIV-1 Maturation Inhibitor with Broad Spectrum Antiviral Activity.

    Science.gov (United States)

    Regueiro-Ren, Alicia; Liu, Zheng; Chen, Yan; Sin, Ny; Sit, Sing-Yuen; Swidorski, Jacob J; Chen, Jie; Venables, Brian L; Zhu, Juliang; Nowicka-Sans, Beata; Protack, Tricia; Lin, Zeyu; Terry, Brian; Samanta, Himadri; Zhang, Sharon; Li, Zhufang; Beno, Brett R; Huang, Xiaohua S; Rahematpura, Sandhya; Parker, Dawn D; Haskell, Roy; Jenkins, Susan; Santone, Kenneth S; Cockett, Mark I; Krystal, Mark; Meanwell, Nicholas A; Hanumegowda, Umesh; Dicker, Ira B

    2016-06-09

    HIV-1 maturation inhibition (MI) has been clinically validated as an approach to the control of HIV-1 infection. However, identifying an MI with both broad polymorphic spectrum coverage and good oral exposure has been challenging. Herein, we describe the design, synthesis, and preclinical characterization of a potent, orally active, second generation HIV-1 MI, BMS-955176 (2), which is currently in Phase IIb clinical trials as part of a combination antiretroviral regimen.

  13. Light-Driven Contact Hearing Aid for Broad-Spectrum Amplification: Safety and Effectiveness Pivotal Study.

    Science.gov (United States)

    Gantz, Bruce J; Perkins, Rodney; Murray, Michael; Levy, Suzanne Carr; Puria, Sunil

    2017-03-01

    Demonstrate safety and effectiveness of the light-driven contact hearing aid to support FDA clearance. A single-arm, open-label investigational-device clinical trial. Two private-practice and one hospital-based ENT clinics. Forty-three subjects (86 ears) with mild-to-severe bilateral sensorineural hearing impairment. Bilateral amplification delivered via a light-driven contact hearing aid comprising a Tympanic Lens (Lens) with a customized platform to directly drive the umbo and a behind-the-ear sound processor (Processor) that encodes sound into light pulses to wirelessly deliver signal and power to the Lens. The primary safety endpoint was a determination of "no change" (PTA4 hearing at the 120-day measurement interval. The primary efficacy endpoint was improvement in word recognition using NU-6 at the 30-day measurement interval over the baseline unaided case. Secondary efficacy endpoints included functional gain from 2 to 10 kHz and speech-in-noise improvement over the baseline unaided case using both omnidirectional and directional microphones. The results for the 86 ears in the study determined a mean change of -0.40 dB in PTA4, indicating no change in residual hearing (p Hearing in Noise Test was 0.75 dB (p = 0.028) and 3.14 dB (p < 0.0001) for the omnidirectional and directional microphone modes, respectively. The safety and effectiveness data supported a de novo 510(k) submission that received clearance from the FDA.

  14. 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.

  15. Broad spectrum antimicrobial activity of forest-derived soil actinomycete, Nocardia sp. PB-52

    Directory of Open Access Journals (Sweden)

    Priyanka eSharma

    2016-03-01

    Full Text Available A mesophilic actinomycete strain designated as PB-52 was isolated from soil samples of Pobitora Wildlife Sanctuary of Assam, India. Based on phenotypic and molecular characteristics, the strain was identified as Nocardia sp. which shares 99.7% sequence similarity with Nocardia niigatensis IFM 0330 (NR_112195. The strain is a Gram-positive filamentous bacterium with rugose spore surface which exhibited a wide range of antimicrobial activity against Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA, Gram-negative bacteria and yeasts. Optimization for the growth and antimicrobial metabolite production of the strain PB-52 was carried out in batch culture under shaking condition. The optimum growth and the antimicrobial metabolite production by the strain PB-52 was recorded in GLM medium at 28ºC, initial pH 7.4 of the medium and incubation period of eight days. Based on polyketide synthases (PKS and nonribosomal peptide synthetases (NRPS gene-targeted PCR amplification, the occurrence of both of these biosynthetic pathways was detected which might be involved in the production of antimicrobial metabolite in PB-52. Extract of the fermented broth culture of PB-52 was prepared with organic solvent extraction method using ethyl acetate. The ethyl acetate extract of PB-52 (EA-PB-52 showed lowest minimum inhibitory concentration (MIC against Staphylococcus aureus MTCC 96 (0.975 μg/ml whereas highest was recorded against Klebsiella pneumoniae ATCC 13883 (62.5 μg/ml. Scanning electron microscopy (SEM revealed that treatment of the test microorganisms with EA-PB-52 destroyed the targeted cells with prominent loss of cell shape and integrity. In order to determine the constituents responsible for its antimicrobial activity, EA-PB-52 was subjected to chemical analysis using gas chromatography-mass spectrometry (GC-MS. GC-MS analysis showed the presence of twelve different chemical constituents in the extract, some of which are reported to possess diverse biological activity. These results confirmed that the presence of bioactive constituents in EA-PB-52 could be a promising source for the development of potent antimicrobial agents effective against wide range of microbial pathogens including MRSA.

  16. 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

  17. Broad-spectrum β-lactamase in Enterobacteriaceae: detection, prevalence, and source tracking

    NARCIS (Netherlands)

    Voets, G.M.

    2013-01-01

    Enterobacteriaceae can cause a wide variety of infections ranging from gastrointestinal syndromes to urinary tract infections. These infections have significant mortality rates. Many classes of antibiotics are used to treat these infections. In particular, third-generation cephalosporins are used as

  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. Community fecal carriage of broad-spectrum cephalosporin-resistant Escherichia coli in Tunisian children.

    Science.gov (United States)

    Ferjani, Sana; Saidani, Mabrouka; Hamzaoui, Zeineb; Alonso, Carla Andrea; Torres, Carmen; Maamar, Elaa; Slim, Amine Faouzi; Boutiba, Ben Boubaker Ilhem

    2017-02-01

    The spread of extended spectrum β-lactamases (ESBL) and plasmid mediated AmpC β-lactamases (pAmpC) was evaluated in Escherichia coli strains collected from the intestinal microbiota of healthy children in Tunisia. The carriage rate of CTX(R)E. coli was 6.6% (7 of 105 samples) and one strain/sample was further characterized (7 isolates). These isolates harbored blaCTX-M-1 (n = 4), blaCTX-M-15 (n = 2), and blaCMY-2 gene (n = 1), which were usually located on FIB replicon type and carried class 1 integrons. The acc(6')-Ib-cr variant was identified in one isolate that harbored blaCTX-M-15. CTX(R)E. coli isolates were genetically unrelated and belonged to B1 (n = 3/ST155/ST398/ST58), D (n = 2/ST117/ST493), B2 (n = 1/ST127), and A (n = 1/ST746) phylogroups. Strain virulence scores varied from 3 to 12, and frequently harbored the pathogenicity island PAI IV536. The intestinal tract of healthy children constitute an important reservoir of ESBL producing E. coli. Thus, improvement of hygiene measures mainly in the school environment and rational use of antibiotics would be of great help in preventing selection and diffusion of resistant strains from intestinal microbiota.

  20. 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

  1. Repurposing Approach Identifies Auranofin with Broad Spectrum Antifungal Activity That Targets Mia40-Erv1 Pathway

    Science.gov (United States)

    Thangamani, Shankar; Maland, Matthew; Mohammad, Haroon; Pascuzzi, Pete E.; Avramova, Larisa; Koehler, Carla M.; Hazbun, Tony R.; Seleem, Mohamed N.

    2017-01-01

    Current antifungal therapies have limited effectiveness in treating invasive fungal infections. Furthermore, the development of new antifungal is currently unable to keep pace with the urgent demand for safe and effective new drugs. Auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, inhibits growth of a diverse array of clinical isolates of fungi and represents a new antifungal agent with a previously unexploited mechanism of action. In addition to auranofin's potent antifungal activity against planktonic fungi, this drug significantly reduces the metabolic activity of Candida cells encased in a biofilm. Unbiased chemogenomic profiling, using heterozygous S. cerevisiae deletion strains, combined with growth assays revealed three probable targets for auranofin's antifungal activity—mia40, acn9, and coa4. Mia40 is of particular interest given its essential role in oxidation of cysteine rich proteins imported into the mitochondria. Biochemical analysis confirmed auranofin targets the Mia40-Erv1 pathway as the drug inhibited Mia40 from interacting with its substrate, Cmc1, in a dose-dependent manner similar to the control, MB-7. Furthermore, yeast mitochondria overexpressing Erv1 were shown to exhibit resistance to auranofin as an increase in Cmc1 import was observed compared to wild-type yeast. Further in vivo antifungal activity of auranofin was examined in a Caenorhabditis elegans animal model of Cryptococcus neoformans infection. Auranofin significantly reduced the fungal load in infected C. elegans. Collectively, the present study provides valuable evidence that auranofin has significant promise to be repurposed as a novel antifungal agent and may offer a safe, effective, and quick supplement to current approaches for treating fungal infections. PMID:28149831

  2. 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.

  3. 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.

  4. Medical and Aesthetic Treatment Across the Broad Spectrum of Ethnicities, Introduction.

    Science.gov (United States)

    Khetarpal, Shilpi; Velez, Mara Weinstein

    2016-12-01

    The ethnic and racial composition of the US population is changing rapidly. There is a continuous rise of individuals with mixed ethnic backgrounds comprising skin of color. It is important for physicians to be comfortable addressing and treating the needs of this population, as it differs significantly from the white population. ©2016 Frontline Medical Communications.

  5. Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review.

    Science.gov (United States)

    Fox, C H; Eberl, M

    2002-12-01

    Phytic acid or IP6 has been extensively studied in animals and is being promoted as an anti-cancer agent in health food stores. It is naturally found in legumes, wheat bran, and soy foods. It is believed to be the active ingredient that gives these substances their cancer fighting abilities. Proposed mechanisms of action include gene alteration, enhanced immunity, and anti-oxidant properties. A Medline search from 1966 to May 2002 using the keywords phytic acid and cancer, and limiting the search to the subheadings of therapeutic uses, prevention, and adverse effects revealed 28 studies. These studies were included in the review. A great majority of the studies were done in animals and showed that phytic acid had anti-neoplastic properties in breast, colon, liver, leukemia, prostate, sarcomas, and skin cancer. There were no human studies. Side effects included chelation of multivalent cations, and an increase in bladder and renal papillomas. This increase in papilloma formation only occurred with the sodium salt of phytic acid. It did not occur with either the potassium or magnesium salts. There is a large body of animal evidence to show that phytic acid may have a role in both the prevention and treatment of many forms of cancer. There is clearly enough evidence to justify the initiation of Phase I and Phase II clinical trials in humans.

  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. Symbionts commonly provide broad spectrum resistance to viruses in insects: a comparative analysis of Wolbachia strains.

    Science.gov (United States)

    Martinez, Julien; Longdon, Ben; Bauer, Simone; Chan, Yuk-Sang; Miller, Wolfgang J; Bourtzis, Kostas; Teixeira, Luis; Jiggins, Francis M

    2014-09-01

    In the last decade, bacterial symbionts have been shown to play an important role in protecting hosts against pathogens. Wolbachia, a widespread symbiont in arthropods, can protect Drosophila and mosquito species against viral infections. We have investigated antiviral protection in 19 Wolbachia strains originating from 16 Drosophila species after transfer into the same genotype of Drosophila simulans. We found that approximately half of the strains protected against two RNA viruses. Given that 40% of terrestrial arthropod species are estimated to harbour Wolbachia, as many as a fifth of all arthropods species may benefit from Wolbachia-mediated protection. The level of protection against two distantly related RNA viruses--DCV and FHV--was strongly genetically correlated, which suggests that there is a single mechanism of protection with broad specificity. Furthermore, Wolbachia is making flies resistant to viruses, as increases in survival can be largely explained by reductions in viral titer. Variation in the level of antiviral protection provided by different Wolbachia strains is strongly genetically correlated to the density of the bacteria strains in host tissues. We found no support for two previously proposed mechanisms of Wolbachia-mediated protection--activation of the immune system and upregulation of the methyltransferase Dnmt2. The large variation in Wolbachia's antiviral properties highlights the need to carefully select Wolbachia strains introduced into mosquito populations to prevent the transmission of arboviruses.

  8. Broad-spectrum resistance to Bacillus thuringiensis toxins in Heliothis virescens.

    OpenAIRE

    1992-01-01

    Evolution of pest resistance to insecticidal proteins produced by Bacillus thuringiensis (Bt) would decrease our ability to control agricultural pests with genetically engineered crops designed to express genes coding for these proteins. Previous genetic and biochemical analyses of insect strains with resistance to Bt toxins indicate that (i) resistance is restricted to single groups of related Bt toxins, (ii) decreased toxin sensitivity is associated with changes in Bt-toxin binding to sites...

  9. Broad Spectrum Chemotherapy: A Novel Approach Using Beta-Galactosidase Activated Pro-Drugs

    Science.gov (United States)

    2007-03-01

    significantly faster than WT. We tried to synthesize a conjugate of 5FU with galactose, although parts of the synthesis were successful, inseparable...100ug 1000ug Re la tiv e vi ab le c el l ( % o f c on tro l) 5-Fu-G / PC3-WT 5-FU/ PC3-WT 5-FU-G/PC3-lacZ 5-FU/PC3-lacZ 13 5FU has a notoriously...narrow window of efficacy. High concentrations cause systemic toxicity. We tested whether lacZ/β-gal could be used to activate and release 5FU in

  10. 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.

  11. 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 triphenylphosphine moiety that show remarkable activity in a panel of cancer cell lines as well as in a mouse model of human breast cancer. The mechanism of action includes mitochondrial localization causing decreased oxygen consumption, increased superoxide production and attenuated growth factor signaling.

  12. 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 light resulted in no lethal effects on L. innocua. Overwhelmingly, the portions of the PL spectrum responsible for bacterial death are the UV-B and UV-C spectral ranges (X light (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.

  13. Broad-spectrum antifungal-producing lactic acid bacteria and their application in fruit models

    National Research Council Canada - National Science Library

    Crowley, Sarah; Mahony, Jennifer; van Sinderen, Douwe

    2013-01-01

    A large-scale screen of some 7,000 presumptive lactic acid bacteria (LAB), isolated from animal, human, or plant origin, identified 1,149 isolates with inhibitory activity against the food-spoilage mould Penicillium expansum...

  14. Interfamily transfer of a plant pattern-recognition receptor confers broad-spectrum bacterial resistance

    NARCIS (Netherlands)

    Lacombe, S.; Rougon-Cardoso, A.; Sherwood, E.; Peeters, N.; Dahlbeck, D.; Esse, van H.P.; Smoker, M.; Rallapalli, G.; Thomma, B.P.H.J.; Staskawicz, B.; Jones, J.D.G.; Zipfel, C.

    2010-01-01

    Plant diseases cause massive losses in agriculture. Increasing the natural defenses of plants may reduce the impact of phytopathogens on agricultural productivity. Pattern-recognition receptors (PRRs) detect microbes by recognizing conserved pathogen-associated molecular patterns (PAMPs)1, 2, 3. Alt

  15. 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 antianaerobic agent) therapy. However, in patients with serious pseudomonal infections (e.g., pneumonia), isolates may rapidly acquire resistance to imipenem or be replaced by resistant strains of Ps. aeruginosa when imipenem is used alone. Therefore, when the recovery of Ps. aeruginosa is anticipated or documented, treatment with imipenem-cilastatin should include an aminoglycoside to reduce the likelihood of the emergency of resistant organisms during therapy.

  16. Symbionts commonly provide broad spectrum resistance to viruses in insects: a comparative analysis of Wolbachia strains.

    Directory of Open Access Journals (Sweden)

    Julien Martinez

    2014-09-01

    Full Text Available In the last decade, bacterial symbionts have been shown to play an important role in protecting hosts against pathogens. Wolbachia, a widespread symbiont in arthropods, can protect Drosophila and mosquito species against viral infections. We have investigated antiviral protection in 19 Wolbachia strains originating from 16 Drosophila species after transfer into the same genotype of Drosophila simulans. We found that approximately half of the strains protected against two RNA viruses. Given that 40% of terrestrial arthropod species are estimated to harbour Wolbachia, as many as a fifth of all arthropods species may benefit from Wolbachia-mediated protection. The level of protection against two distantly related RNA viruses--DCV and FHV--was strongly genetically correlated, which suggests that there is a single mechanism of protection with broad specificity. Furthermore, Wolbachia is making flies resistant to viruses, as increases in survival can be largely explained by reductions in viral titer. Variation in the level of antiviral protection provided by different Wolbachia strains is strongly genetically correlated to the density of the bacteria strains in host tissues. We found no support for two previously proposed mechanisms of Wolbachia-mediated protection--activation of the immune system and upregulation of the methyltransferase Dnmt2. The large variation in Wolbachia's antiviral properties highlights the need to carefully select Wolbachia strains introduced into mosquito populations to prevent the transmission of arboviruses.

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

    OpenAIRE

    2015-01-01

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that a...

  18. 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.

  19. 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.

  20. Recent research on 3-phenyllactic acid, a broad-spectrum antimicrobial compound.

    Science.gov (United States)

    Mu, Wanmeng; Yu, Shuhuai; Zhu, Lanjun; Zhang, Tao; Jiang, Bo

    2012-09-01

    3-Phenyllactic acid (PLA), which is an organic acid widely existing in honey and lactic acid bacteria fermented food, can be produced by many microorganisms, especially lactic acid bacteria. It was proved as an ideal antimicrobial compound with broad and effective antimicrobial activity against both bacteria and fungi. In addition, it could be used as feed additives to replace antibiotics in livestock feeds. This article presented a review of recent studies on the existing resource, antimicrobial activity, and measurement of PLA. In addition, microorganism strains and dehydrogenases producing PLA were reviewed in detail, the metabolic pathway and regulation of PLA synthesis in LAB strains were discussed, and high-level bioproduction of PLA by microorganism fermentation was also summarized.

  1. 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

  2. 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.

  3. Further characerization of the broad-spectrum anthraconse resistance in Andea common bean Amendoim Cavalo

    Science.gov (United States)

    Anthracnose is one of the most significant diseases of common bean (Phaseolus vulgaris) in temperate and subtropical bean production areas of the world. This disease is caused by Colletotrichum lindemuthianum, known for its extensive virulence diversity. Dozens of races of this pathogen have been ch...

  4. Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses

    OpenAIRE

    Sui, Jianhua; Hwang, William C; Perez, Sandra; Wei, Ge; Aird, Daniel; Chen, Li-Mei; Santelli, Eugenio; Stec, Boguslaw; Cadwell, Greg; Ali, Maryam; Wan, Hongquan; Murakami, Akikazu; Yammanuru, Anuradha; Han, Thomas; Cox, Nancy J

    2009-01-01

    Influenza virus remains a constant public health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Monoclonal antibody (mAb)-based immunotherapy is a promising strategy for disease control. Here we use a human Ab phage display library and H5 hemagglutinin (HA) ectodomain to select ten neutralizing mAbs (nAbs) with a remarkably broad range among Group 1 influenza viruses, including the H5N1 “bird flu” and the H1N1 “Spanish flu” strains. Not...

  5. Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance

    NARCIS (Netherlands)

    Pavan, S.N.C.; Jacobsen, E.; Visser, R.G.F.; Bai, Y.

    2010-01-01

    Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant defe

  6. The highly synergistic, broad spectrum, antibacterial activity of organic acids and transition metals

    Science.gov (United States)

    Zhitnitsky, Daniel; Rose, Jessica; Lewinson, Oded

    2017-01-01

    For millennia, transition metals have been exploited to inhibit bacterial growth. We report here the potentiation of the anti-bacterial activity of transition metals by organic acids. Strong synergy between low, non-toxic concentrations of transition metals and organic acids was observed with up to ~1000-fold higher inhibitory effect on bacterial growth. We show that organic acids shuttle transition metals through the permeability barrier of the bacterial membrane, leading to increased influx of transition metals into bacterial cells. We demonstrate that this synergy can be effectively used to inhibit the growth of a broad range of plant and human bacterial pathogens, and suggest that a revision of food preservation and crop protection strategies may be in order. These findings bear significant biomedical, agricultural, financial and environmental opportunities. PMID:28294164

  7. 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.

  8. Reflectable bases for affine reflection systems

    CERN Document Server

    Azam, Saeid; Yousofzadeh, Malihe

    2011-01-01

    The notion of a "root base" together with its geometry plays a crucial role in the theory of finite and affine Lie theory. However, it is known that such a notion does not exist for the recent generalizations of finite and affine root systems such as extended affine root systems and affine reflection systems. As an alternative, we introduce the notion of a "reflectable base", a minimal subset $\\Pi$ of roots such that the non-isotropic part of the root system can be recovered by reflecting roots of $\\Pi$ relative to the hyperplanes determined by $\\Pi$. We give a full characterization of reflectable bases for tame irreducible affine reflection systems of reduced types, excluding types $E_{6,7,8}$. As a byproduct of our results, we show that if the root system under consideration is locally finite then any reflectable base is an integral base.

  9. Shock wave reflection phenomena

    CERN Document Server

    Ben-dor, Gabi

    2007-01-01

    This book provides a comprehensive state-of-the-knowledge description of the shock wave reflection phenomena from a phenomenological point of view. The first part is a thorough introduction to oblique shock wave reflections, presenting the two major well-known reflection wave configurations, namely, regular (RR) and Mach (MR) reflections, the corresponding two- and three-shock theories, their analytical and graphical solution and the proposed transition boundaries between these two reflection-wave configurations. The second, third and fourth parts describe the reflection phenomena in steady, pseudo-steady and unsteady flows, respectively. Here, the possible specific types of reflection wave configurations are described, criteria for their formation and termination are presented and their governing equations are solved analytically and graphically and compared with experimental results. The resolution of the well-known von Neumann paradox and a detailed description of two new reflection-wave configurations - t...

  10. Liberating Moral Reflection

    Science.gov (United States)

    Horell, Harold D.

    2013-01-01

    The author argues that if we are to foster life-giving and liberating moral reflection, we must first liberate moral reflection from distortions; specifically, from the distorting effects of moral insensitivity, destructive moral relativism, and confusions resulting from a failure to understand the dynamics of moral reflection. The author proposes…

  11. Knowledge-Level Reflection

    NARCIS (Netherlands)

    Harmelen, van F.A.H.; Wielinga, B.J.; Bredeweg, Bert; Schreiber, G.; Karbach, Werner; Reinders, Martin; Voss, A.; Akkermans, H.; Bartsch-Spoerl, Brigitte; Vinkhuyzen, Erik

    This paper presents an overview of the REFLECT project. It defines the notion of knowledge level reflection that has been central to the project, it compares this notion with existing approaches to reflection in related fields, and investigates some of the consequences of the concept of knowledge le

  12. Liberating Moral Reflection

    Science.gov (United States)

    Horell, Harold D.

    2013-01-01

    The author argues that if we are to foster life-giving and liberating moral reflection, we must first liberate moral reflection from distortions; specifically, from the distorting effects of moral insensitivity, destructive moral relativism, and confusions resulting from a failure to understand the dynamics of moral reflection. The author proposes…

  13. Imaging seismic reflections

    NARCIS (Netherlands)

    Op 't Root, Timotheus Johannes Petrus Maria

    2011-01-01

    The goal of reflection seismic imaging is making images of the Earth subsurface using surface measurements of reflected seismic waves. Besides the position and orientation of subsurface reflecting interfaces it is a challenge to recover the size or amplitude of the discontinuities. We investigate tw

  14. Reflective Learning in Practice.

    Science.gov (United States)

    Brockbank, Anne, Ed.; McGill, Ian, Ed.; Beech, Nic, Ed.

    This book contains 22 papers on reflective learning in practice. The following papers are included: "Our Purpose" (Ann Brockbank, Ian McGill, Nic Beech); "The Nature and Context of Learning" (Ann Brockbank, Ian McGill, Nic Beech); "Reflective Learning and Organizations" (Ann Brockbank, Ian McGill, Nic Beech); "Reflective Learning in Practice" (Ann…

  15. Reflection Positive Doubles

    CERN Document Server

    Jaffe, Arthur

    2016-01-01

    Here we introduce reflection positive doubles, a general framework for reflection positivity, covering a wide variety of systems in statistical physics and quantum field theory. These systems may be bosonic, fermionic, or parafermionic in nature. Within the framework of reflection positive doubles, we give necessary and sufficient conditions for reflection positivity. We use a reflection-invariant cone to implement our construction. Our characterization allows for a direct interpretation in terms of coupling constants, making it easy to check in concrete situations. We illustrate our methods with numerous examples.

  16. Wave Reflection Coefficient Spectrum

    Institute of Scientific and Technical Information of China (English)

    俞聿修; 邵利民; 柳淑学

    2003-01-01

    The wave reflection coefficient frequency spectrum and directional spectrum for concrete face slope breakwaters and rubble mound breakwaters are investigated through physical model tests in the present study. The reflection coefficients of oblique irregular waves are analyzed by the Modified Two-Point Method (MTPM) proposed by the authors. The results show that the wave reflection coefficient decreases with increasing wave frequency and incident angle or decreasing structure slope. The reflection coefficient frequency spectrum and its variation with Iribarren number are given in this paper. The paper also suggests an empirical 3-dimensional reflection coefficient spectrum, i.e. reflection coefficient directional spectrum, which can be used to illustrate quantitatively the variation of reflection coefficient with the incident angle and the Iribarren number for oblique irregular waves.

  17. Performance of "Moth Eye" Anti-Reflective Coatings for Solar Cell Applications

    Energy Technology Data Exchange (ETDEWEB)

    Clark, E.; Kane, M.; Jiang, P.

    2011-03-14

    An inexpensive, effective anti-reflective coating (ARC) has been developed at the University of Florida to significantly enhance the absorption of light by silicon in solar cells. This coating has nano-scale features, and its microstructure mimics that of various night active insects (e.g. a moth's eye). It is a square array of pillars, each about 700 nm high and having a diameter of about 300 nm. Samples of silicon having this coating were exposed either to various combinations of either elevated temperature and humidity or to gamma irradiation ({sup 60}Co) at the Savannah River National Laboratory, or to a broad spectrum ultraviolet light and to a 532 nm laser light at the University of Florida. The anti-reflective properties of the coatings were unaffected by any of these environmental stresses, and the microstructure of the coating was also unaffected. In fact, the reflectivity of the gamma irradiated ARC became lower (advantageous for solar cell applications) at wavelengths between 400 and 1000 nm. These results show that this coating is robust and should be tested in actual systems exposed to either weather or a space environment. Structural details of the ARCs were studied to optimize their performance. Square arrays performed better than hexagonal arrays - the natural moth-eye coating is indeed a square array. The optimal depth of the templated nanopillars in the ARC was investigated. A wet etching technology for ARC formation was developed that would be less expensive and much faster than dry etching. Theoretical modeling revealed that dimple arrays should perform better than nipple arrays. A method of fabricating both dimple and nipple arrays having the same length was developed, and the dimple arrays performed better than the nipple arrays, in agreement with the modeling. The commercial viability of the technology is quite feasible, since the technology is scalable and inexpensive. This technology is also compatible with current industrial

  18. Media for Reflection

    DEFF Research Database (Denmark)

    Knudsen, Morten

    2016-01-01

    This article develops the concept media for reflection in the interest of conceptualizing the interpretative frames that enable and limit reflection in management and leadership education. The concept ‘media for reflection’ allows us to conceptualize the social and cultural mediation of reflection...... without reducing reflection to an effect of the social structures and cultural norms in which it is embedded. Based on the developed theoretical framework, this article analyses how a renaissance ‘mirror for princes’ and contemporary research-based management education mediate reflection. The content...... of the mediations is analysed as well as the societal and organizational background. Furthermore, the means by which the two media enable and limit reflection in different ways is compared. Finally, the article discusses possible implications of the analysis in terms of management and leadership education....

  19. Reflection in professional practice

    OpenAIRE

    Hetzner, Stefanie Bianca

    2014-01-01

    The purpose of this thesis is to contribute to the research on professional learning through reflective practice. The main goal is to examine—against the backdrop of workplace changes and errors—individual and contextual factors that are theoretically assumed to influence reflection in the context of professional work. Reflective practice is defined as a retrospective but future- and goal-oriented cognitive-affective process that basically involves (a) the awareness and review of incident...

  20. Unanticipated Partial Behavioral Reflection

    OpenAIRE

    Roethlisberger, David; Denker, Marcus; Tanter, Éric

    2006-01-01

    International audience; Dynamic, unanticipated adaptation of running systems is of interest in a variety of situations, ranging from functional upgrades to on-the-fly debugging or monitoring of critical applications. In this paper we study a particular form of computational reflection, called unanticipated partial behavioral reflection, which is particularly well-suited for unanticipated adaptation of real-world systems. Our proposal combines the dynamicity of unanticipated reflection, i.e., ...

  1. X-ray Reflection

    Science.gov (United States)

    Fabian, A. C.; Ross, R. R.

    2010-12-01

    Material irradiated by X-rays produces backscattered radiation which is commonly known as the Reflection Spectrum. It consists of a structured continuum, due at high energies to the competition between photoelectric absorption and electron scattering enhanced at low energies by emission from the material itself, together with a complex line spectrum. We briefly review the history of X-ray reflection in astronomy and discuss various methods for computing the reflection spectrum from cold and ionized gas, illustrated with results from our own work reflionx. We discuss how the reflection spectrum can be used to obtain the geometry of the accretion flow, particularly the inner regions around black holes and neutron stars.

  2. Transparencies and Reflections.

    Science.gov (United States)

    Hubbard, Guy

    1999-01-01

    Discusses the use of perspective, or showing things as the human eye sees them, when creating reflections and transparencies in works of art. Provides examples of artwork using transparency, reflection, and refraction by M. C. Escher, Richard Estes, and Janet Fish to give students an opportunity to learn about these three art techniques. (CMK)

  3. Reflective Practitioner Account

    Institute of Scientific and Technical Information of China (English)

    干青

    2009-01-01

    This article focus on the reflective account of an English teacher learning and teaching in higher education with the British post-graduate certificate program of the Yunnan Agdculture University.As n practitioner for smny years in English learning and teaching for many years,it reflects in four fields.

  4. Reflective Learning in Practice.

    Science.gov (United States)

    Brockbank, Anne, Ed.; McGill, Ian, Ed.; Beech, Nic, Ed.

    This book contains 22 papers on reflective learning in practice. The following papers are included: "Our Purpose" (Ann Brockbank, Ian McGill, Nic Beech); "The Nature and Context of Learning" (Ann Brockbank, Ian McGill, Nic Beech); "Reflective Learning and Organizations" (Ann Brockbank, Ian McGill, Nic Beech);…

  5. Dissenting in Reflective Conversations

    DEFF Research Database (Denmark)

    Bjørn, Pernille; Boulus, Nina

    2011-01-01

    a methodological reflective approach that provides space for taking seriously uncertainties experienced in the field as these can be a catalyst for learning and sharpening our theoretical and empirical skills as action researchers. Through first-person inquiry, we investigate how our reflective conversations...

  6. Reflection and teaching: a taxonomy

    OpenAIRE

    Vos, Henk; Cowan, John

    2009-01-01

    A major problem in teaching reflection is that educational objectives for reflection in terms of student behaviour are lacking. Therefore a taxonomy of reflection has been developed based on Bloom’s taxonomy. Reflective assignments can then be better focused on any chosen educational objectives. The act of reflection has been analysed and abstracted from goal, content, context, means, and moment of reflecting. Reflection was operationalised as answering reflective questions. Bloom’s taxonomy ...

  7. Reflectivity in Research Practice

    Directory of Open Access Journals (Sweden)

    Luigina Mortari

    2015-11-01

    Full Text Available The article grounds on the assumption that researchers, in order to be not mere technicians but competent practitioners of research, should be able to reflect in a deep way. That means they should reflect not only on the practical acts of research but also on the mental experience which constructs the meaning about practice. Reflection is a very important mental activity, both in private and professional life. Learning the practice of reflection is fundamental because it allows people to engage into a thoughtful relationship with the world-life and thus gain an awake stance about one’s lived experience. Reflection is a crucial cognitive practice in the research field. Reflexivity is largely practiced in qualitative research, where it is used to legitimate and validate research procedures. This study introduces different perspectives of analysis by focusing the discourse on the main philosophical approaches to reflection: pragmatistic, critical, hermeneutic, and finally phenomenological. The thesis of this study is that the phenomenological theory makes possible to analyze in depth the reflective activity and just by that to support an adequate process of training of the researcher.

  8. Review of Teacher's Teaching Reflection

    Institute of Scientific and Technical Information of China (English)

    王爽爽

    2015-01-01

    Teacher's teaching reflection has become the core focus in school.However,there are different understandings of the concept of teacher's teaching reflection.The paper introduces and compares different understandings of the concept of teachers' teaching reflection.Based on the summarizing of the concept on reflection and teaching reflection,this paper tries to provide reference for the teacher's teaching reflection.

  9. Self-Reflection

    DEFF Research Database (Denmark)

    Fausing, Bent

    2016-01-01

    will take a look at the establishing of the modern self and possibilities of self-reflection, too. My examples will be from the so-called dark-selfies and from a new selfie form, which merge the present with the previous progressing into the future. I will discuss the media reflections as loos and/or gain....... As another but short viewpoint telepresence, Skype, will be discussed, where new screen types, presence and reflections are established. In a perspective, I debate my term sore-society in relation to my topic and especially the dark selfies....

  10. Encouraging Counsellor Reflection.

    Science.gov (United States)

    Upton, David; Asch, Rachel

    1999-01-01

    Describes the evolution and testing of an "attributes checklist" tool for assisting counselor development. These attributes relate to characteristics of case notes that indicate evidence of counselor reflection and consideration of the counseling process. (Author/GCP)

  11. Thoughts on Reflection (Editorial

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2010-06-01

    Full Text Available There has been some acknowledgement in the published literature that reflection is a crucial element of the evidence based library and information practice (EBLIP model we have adopted (Booth 2004, 2006; Grant 2007; Helliwell 2007. As we work through a problem and try to incorporate the best available evidence into our decision making, reflection is required at several stages, including the very identification of the problem through to our assessment of the process itself and what we have learned in order to inform future practice. However, reflection and reflective writing have not fully been integrated into the process we espouse, and very little has been done to look more closely at this element of the model and how it can be integrated into professional learning.In a recently published research article, Sen (2010 confirms the relationship between reflection and several aspects of professional practice. These include critical review and decision making, two aspects that are tied closely to the evidence based process. Sen notes: Students were more likely to show evidence of learning, self‐development, the ability to review issues crucially, awareness of their own mental functions, ability to make decision [sic] and being empowered when they had mastered the art of reflective practice and the more deeply analytical reflective writing. (p.84 EBLIP (the journal tries to incorporate elements of reflection within the articles we publish. While we clearly believe in the need for our profession to do quality research and publish that research so that it can be accessible to practitioners, we also know that research cannot be looked at in isolation. Our evidence summaries are one way of reflecting critically on previously published research, and in the same vein, our classics bring older research studies back to the foreground. This work needs to continue to be discussed and looked at for its impact on our profession.More directly, the Using

  12. Creation, Identity and Reflection

    Directory of Open Access Journals (Sweden)

    Alina Beatrice Cheşcă

    2015-05-01

    Full Text Available The paper “Creation, Identity and Reflection” approaches the identification in the “mirror” of reality with creation, in other words seeking the authors’ identity in the reflected images. Reflection means attempting to find oneself, the mirror being the main principle of creation. Many characters become interesting only when they step into the world beyond the mirror, when their faces are doubled by the other self or when their selves are returned by other characters. The narcissistic concept of the mirror, i.e. the reflection in the mirror and the representation of the mirror itself, is a recurrent one in literature, but the reflection of the self which is not the self (as it is a reflection does not necessarily appear in a mirror or in a photograph or portrait. Sometimes, the not-self is returned to the self by another person or character. As far as Oscar Wilde’s theories are concerned, the main idea is that people are interesting for their masks, not for their inner nature. What Wilde calls “inner nature” is the characters’ un-reflected self and the mask is the reflection, the self in the mirror. Some characters’ relationships develop within a fiction that they dramatically try to preserve and protect with the risk of suffering. They refuse to take off the masks which define them in the others’ minds and hearts; the narcissistic individuals (both artists and characters seek and love their own image which they project upon facts, thus creating a fictive realm.

  13. First observations of mesospheric dynamics with a partial reflection radar in Hawaii (22 deg N, 160 deg W)

    Science.gov (United States)

    Fritts, David C.; Isler, Joseph R.

    1992-01-01

    A partial-reflection MF radar was installed at the Pacific Missile Range Facility on Kanai, Hawaii in September 1990. The wind measurements obtained with this radar system in Hawaii during the first year of operation are reviewed. The data reveal a broad spectrum of motions ranging from a mix of the equatorial mesopause semiannual oscillation (MSAO) and the annual mean cycle at middle and high latitudes in the zonal mean structure to low-frequency, tidal, and gravity wave motions at higher frequencies. The zonal mean wind structure is characterized by a downward progression of strong eastward and westward phases of the MSAO from approximately January to July. An eastward maximum of about 60/ms near 80 km during January and February is found, which descends rapidly, and a westward maximum of about 50 ms near 85 km during March and April is found, which descends much more slowly. The second MSAO cycle is greatly suppressed relative to the first due to the reversal of the correlation between this and the annual cycle at higher latitudes from July to December.

  14. Invisibility via reflecting coating

    CERN Document Server

    Burdzy, Krzysztof

    2012-01-01

    We construct a subset $A$ of the unit disc with the following properties. (i) The set $A$ is the finite union of disjoint line segments. (ii) The shadow of $A$ is arbitrarily close to the shadow of the unit disc in "most" directions. (iii) If the line segments are considered to be mirrors reflecting light according to the classical law of specular reflection then most light rays hitting the set emerge on the other side of the disc moving along a parallel line and shifted by an arbitrarily small amount. We also construct a set which reflects almost all light rays coming from one direction to another direction but its shadow is arbitrarily small in other directions, except for an arbitrarily small family of directions.

  15. Biology Reflective Assessment Curriculum

    Science.gov (United States)

    Bayley, Cheryl Ann

    Often students and educators view assessments as an obligation and finality for a unit. In the current climate of high-stakes testing and accountability, the balance of time, resources and emphasis on students' scores related to assessment have been slanted considerably toward the summative side. This tension between assessment for accountability and assessment to inform teaching strains instruction and educators' ability to use that information to design learning opportunities that help students develop deeper conceptual understanding. A substantive body of research indicates that formative and reflective assessment can significantly improve student learning. Biology Reflective Assessment Curriculum (BRAC) examines support provided for high school science students through assessment practices. This investigation incorporates the usage of reflective assessments as a guiding practice for differentiated instruction and student choice. Reflective assessment is a metacognitive strategy that promotes self-monitoring and evaluation. The goals of the curriculum are to promote self-efficacy and conceptual understanding in students learning biology through developing their metacognitive awareness. BRAC was implemented in a high school biology classroom. Data from assessments, metacognitive surveys, self-efficacy surveys, reflective journals, student work, a culminating task and field notes were used to evaluate the effectiveness of the curriculum. The results suggest that students who develop their metacognitive skills developed a deeper conceptual understanding and improved feelings of self-efficacy when they were engaged in a reflective assessment unit embedded with student choice. BRAC is a tool for teachers to use assessments to assist students in becoming metacognitive and to guide student choice in learning opportunities.

  16. Reflecting telescope optics

    CERN Document Server

    Wilson, Raymond N

    2004-01-01

    R.N. Wilson's two-volume treatise on reflecting telescope optics has become a classic in its own right. It is intended to give a complete treatment of the subject, addressing professionals in research and industry as well as students of astronomy and amateur astronomers. This first volume, Basic Design Theory and its Historical Development, is devoted to the theory of reflecting telescope optics and systematically recounts the historical progress. The author's approach is morphological, with strong emphasis on the historical development. The book is richly illustrated including spot-diagrams a

  17. Acoustic Bottom Reflectivity

    Science.gov (United States)

    1986-12-01

    Calculates the reflection loss as function of frequency. ---PLOTV/ PLOTF ---Plots loss and phase as function of angle or frequency. ---QUIT--- ENTER YOUR...34Y" if you want to leave PLOTV or PLOTF and return to the HELP MENU. A similar procedure to plot results as a function of frequency is contained in... PLOTF and works in the same way. Figures A-1 and A-2 show the results for an 18-layer sample input file, FLOOR18.DAT, giving the reflection loss as a

  18. Experimental observation of direct current voltage-induced phase synchronization

    Indian Academy of Sciences (India)

    Haihong Li; Weiqing Liu; Qiongling Dai; Jinghua Xiao

    2006-09-01

    The dynamics of two uncoupled distinct Chua circuits driven by a common direct current voltage is explored experimentally. It was found that, with increasing current intensity, the dominant frequencies of these two Chua circuits will first vary at different speeds, approach an identical value for a certain current intensity and then separate. Techniques such as synchronization index and phase difference distribution were employed to analyze the phase coherence between these two Chua circuits.

  19. Reflecting on a room of one reflectance.

    Science.gov (United States)

    Ruppertsberg, Alexa I; Bloj, Marina

    2007-10-30

    We present a numerical analysis of rendered pairs of rooms, in which the spectral power distribution of the illuminant in one room matched the surface reflectance function in the other room, and vice versa. We ask whether distinction between the rooms is possible and on what cues this discrimination is based. Using accurately rendered three-dimensional (3D) scenes, we found that room pairs can be distinguished based on indirect illumination, as suggested by A. L. Gilchrist and A. Jacobsen (1984). In a simulated color constancy scenario, we show that indirect illumination plays a pivotal role as areas of indirect illumination undergo a smaller appearance change than areas of direct illumination. Our study confirms that indirect illumination can play a critical role in surface color recovery and shows how computer rendering programs, which model the light-object interaction according to the laws of physics, are valuable tools that can be used to analyze and explore what image information is available to the visual system from 3D scenes.

  20. Integral representation of Skorokhod reflection

    CERN Document Server

    Anantharam, Venkat

    2010-01-01

    We show that a certain integral representation of the one-sided Skorokhod reflection of a continuous bounded variation function characterizes the reflection in that it possesses a unique maximal solution which solves the Skorokhod reflection problem.

  1. Reflection in learning at work

    DEFF Research Database (Denmark)

    Pedersen, Steen Høyrup

    2006-01-01

    Three domains and approaches of learning - adult learning, problem-solving and cirtical reflection theory are used as different lenses through which the question: what is reflection and how is reflection related to learning, - are interpreted....

  2. Lights, Camera, Reflection!

    Science.gov (United States)

    Mourlam, Daniel

    2013-01-01

    There are many ways to critique teaching, but few are more effective than video. Personal reflection through the use of video allows one to see what really happens in the classrooms--good and bad--and provides a visual path forward for improvement, whether it be in one's teaching, work with a particular student, or learning environment. This…

  3. Value reflected health education

    DEFF Research Database (Denmark)

    Wistoft, Karen; Nordentoft, Helle Merete

    2011-01-01

    This article examines the impact of a value-reflected approach in health education by demonstrating the nature of professional competence development connected to this approach. It is based on findings from two three-year health educational development projects carried out by school health nurses...... develop pedagogical competences in health education improving school childrens’ health....

  4. Self-Reflection

    DEFF Research Database (Denmark)

    Fausing, Bent

    Reflecting has a double meaning, mirroring and thinking. The seminar will investigate how these two meanings intervene in each other. As we perceive we are already in pre-refectory state, and thinking involves a lot of not only thoughts, but also of senses and sensing, wherefrom our thoughts star...

  5. Wave Reflection Model Tests

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Larsen, Brian Juul

    The investigation concerns the design of a new internal breakwater in the main port of Ibiza. The objective of the model tests was in the first hand to optimize the cross section to make the wave reflection low enough to ensure that unacceptable wave agitation will not occur in the port. Secondly...

  6. Changes Brought by Reflection

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Feng: A number of changes have taken place in Europe after reflection, such as specific anti-terrorist measures, progress in the construction of integration, changes in the structure of political forces and adjustments in the EU foreign policy. Would you make some comments first, Dr. Sun?

  7. Self-Reflection

    DEFF Research Database (Denmark)

    Fausing, Bent

    2016-01-01

    Reflecting has a double meaning, mirroring and thinking. The seminar will investigate how these two meanings intervene in each other. As we perceive we are already in pre-refectory state, and thinking involves a lot of not only thoughts, but also of senses and sensing, wherefrom our thoughts star...

  8. Clinical Linguistics: Conversational Reflections

    Science.gov (United States)

    Crystal, David

    2013-01-01

    This is a report of the main points I made in an informal "conversation" with Paul Fletcher and the audience at the 14th ICPLA conference in Cork. The observations arose randomly, as part of an unstructured 1-h Q&A, so they do not provide a systematic account of the subject, but simply reflect the issues which were raised by the conference…

  9. Reflections: Children and Literature.

    Science.gov (United States)

    And Others; Cianciolo, Patricia J.

    1980-01-01

    Six educational leaders--Patricia J. Cianciolo, Lee Bennett Hopkins, Nancy Larrick, Alan C. Purves, Morton Schindel, and James R. Squire--offer reflections on signficiant developments in children's literature during the 1970s, their hopes for the 1980s, and references that constitute required reading for elementary language arts teachers. (ET)

  10. Reflection by Porro Prisms

    Science.gov (United States)

    Greenslade, Thomas B.

    2010-04-01

    Students all know that reflection from a plane mirror produces an image that is reversed right to left and so cannot be read by anyone but Leonardo da Vinci, who kept his notes in mirror writing. A useful counter-example is the Porro prism, which produces an image that is not reversed.

  11. Reflecting on Data

    Science.gov (United States)

    Kraus, Rudolf V.

    2014-01-01

    This article describes a two-day optics laboratory activity that investigates the scientific phenomenon of reflection, which students are generally familiar with but usually have not studied in depth. This investigation can be used on its own or as part of a larger unit on optics. This lesson encourages students to think critically and…

  12. An Evolutionarily Conserved Synthetic Lethal Interaction Network Identifies FEN1 as a Broad-Spectrum Target for Anticancer Therapeutic Development

    OpenAIRE

    Derek M. van Pel; Barrett, Irene J.; Yoko Shimizu; Sajesh, Babu V.; Brent J Guppy; Tom Pfeifer; McManus, Kirk J.; Philip Hieter

    2013-01-01

    Harnessing genetic differences between cancerous and noncancerous cells offers a strategy for the development of new therapies. Extrapolating from yeast genetic interaction data, we used cultured human cells and siRNA to construct and evaluate a synthetic lethal interaction network comprised of chromosome instability (CIN) genes that are frequently mutated in colorectal cancer. A small number of genes in this network were found to have synthetic lethal interactions with a large number of canc...

  13. Demonstration and Verification of a Broad Spectrum Anomalous Dispersion Effects Tool for Index of Refraction and Optical Turbulence Calculations

    Science.gov (United States)

    2009-03-01

    exchange function for heat diffusion , and ε is the energy dissipation rate. Similarity theory (Rachele et al., 1995) can be used to determine surface...frozen purified water (water that had been through a reverse osmosis process) and ensuring they read 0°C. Figure 32 is created using Type K, while

  14. The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

    OpenAIRE

    David Safronetz; Kyle Rosenke; Westover, Jonna B.; Cynthia Martellaro; Atsushi Okumura; Yousuke Furuta; Joan Geisbert; Greg Saturday; Takashi Komeno; Geisbert, Thomas W.; Heinz Feldmann; Gowen, Brian B.

    2015-01-01

    With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this,...

  15. Formulation of a Broad-Spectrum, All-Weather, Solid-Based, Peracetate - "Solvent" Dry Decontaminant Concentrate

    Science.gov (United States)

    2010-04-01

    PAB is peracetic acid , CHjQOJOOH, not hydrogen peroxide, HOOH, but the AO content is still reported on the basis of the latter. 11 y -o c C3 a...to demonstrate the impressive bio efficacy afforded by quite low levels of peracetic acid (derived from PAB) compared to H2O2. Additional studies...stirred. 2.5 Formulation Experiments 2.5.1 PAB Alone 2.5.1.1 Chem Agent Testing of PAB PAB liberates peracetic acid , a powerful oxidant, when

  16. Broad-Spectrum Antiviral Activity of Small Interfering RNA Targeting the Conserved RNA Termini of Lassa Virus▿

    OpenAIRE

    Müller, Stefanie; Günther, Stephan

    2007-01-01

    Small interfering RNAs targeting the conserved RNA termini upstream of NP and L gene were found to reduce reporter gene expression from Lassa virus replicon and Lassa virus mRNA expression construct and to inhibit replication of different Lassa virus strains, lymphocytic choriomeningitis virus, and Mopeia virus in cell culture.

  17. Leveraging the attributes of Mucor hiemalis-derived silver nanoparticles for a synergistic broad-spectrum antimicrobial platform

    Directory of Open Access Journals (Sweden)

    Nafe Aziz

    2016-12-01

    Full Text Available Driven by the need to engineer robust surface coatings for medical devices to prevent infection and sepsis, incorporation of nanoparticles has surfaced as a promising avenue to enhance non-fouling efficacy. Microbial synthesis of such nanoscale metallic structures is of substantive interest as this can offer an eco-friendly, cost-effective and sustainable route for further development. Here we present a Mucor hiemalis-derived fungal route for synthesis of silver nanoparticles, which display significant antimicrobial properties when tested against six pathological bacterial strains (Klebsiella pneumonia, Pseudomonas brassicacearum, Aeromonas hydrophila, Escherichia coli, Bacillus cereus and Staphylococcus aureus and three pathological fungal strains (Candida albicans, oxysporum, and Aspergillus flavus. These antimicrobial attributes were comparable to those of established antibiotics (streptomycin, tetracycline, kanamycin and rifampicin and fungicides (amphotericin B, fluconazole and ketoconazole, respectively. Importantly, these nanoparticles show significant synergistic characteristics when combined with the antibiotics and fungicides to offer substantially greater resistance to microbial growth. The blend of antibacterial and antifungal properties, coupled with their intrinsic green and facile synthesis, makes these biogenic nanoparticles particularly attractive for future applications in nanomedicine ranging from topical ointments and bandages for wound healing to coated stents.

  18. Nuflor, the New Generation Broad Spectrum Bacteriophage%新一代广谱抗菌素--纽弗罗

    Institute of Scientific and Technical Information of China (English)

    娄高明; 荣强

    2006-01-01

    @@ 1背景介绍 氟甲砜霉素(Thiamphenicol)是一种新型氯霉素类广谱抗生素,属于美国FDA认证通过的4种抗菌剂之一.氟甲砜霉素作为1种相对成熟的药物,以其高效、安全、无残留等特点在美洲、欧洲等国家被广泛应用,并在全球动物保健市场享有较高声誉.在中国,氟甲砜霉素又叫氟苯尼考(Florfenicol),是农业部新兽药审评委员会赋予的中文标准命名.

  19. The freshwater sponge Ephydatia fluviatilis harbours diverse Pseudomonas species (Gammaproteobacteria, Pseudomonadales) with broad-spectrum antimicrobial activity

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    Keller-Costa, T.; Jousset, A.; Overbeek, van L.S.; Elsas, J.D.; Costa, R.

    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

  1. 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 with the resi......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...... 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...

  2. Highly and Broad-Spectrum In Vitro Antitumor Active cis-Dichloridoplatinum(II Complexes with 7-Azaindoles.

    Directory of Open Access Journals (Sweden)

    Pavel Štarha

    Full Text Available The cis-[PtCl2(naza2] complexes (1-3 containing monosubstituted 7-azaindole halogeno-derivatives (naza, showed significantly higher activity than cisplatin towards ovarian carcinoma A2780, its cisplatin-resistant variant A2780R, osteosarcoma HOS, breast carcinoma MCF7 and cervix carcinoma HeLa cell lines, with the IC50 values of 3.8, 3.5, 4.5, 2.7, and 9.2 μM, respectively, obtained for the most active complex 3. As for 4 and 5 having disubstituted 7-azaindoles in their molecule, the significant cytotoxicity was detected only for 4 against A2780 (IC50 = 4.8 μM, A2780R (IC50 = 3.8 μM and HOS (IC50 = 4.3 μM, while 5 was evaluated as having only moderate antiproliferative effect against the mentioned cancer cell lines with IC50 = 33.4, 24.7 and 46.7 μM, respectively. All the studied complexes 1-5 effectively avoided the acquired resistance of ovarian carcinoma cell line. On the other hand, the complexes did not reveal any inhibition activity on the purified 20S proteasome from the A2780 cells. The representative complexes 3 and 5 showed low ability to be hydrolysed, but their stability was markedly lowered in the presence of physiological sulphur-containing biomolecule glutathione (GSH, as proved by the 1H NMR spectroscopy and mass spectrometry studies. A rate of interaction of the studied complexes with GSH was affected by an addition of another mechanistically relevant biomolecule guanosine monophosphate. The differences in interactions of 3 and 5 with GSH correlate well with their different cytotoxicity profiles.

  3. Covalent immobilization of lysozyme onto woven and knitted crimped polyethylene terephthalate grafts to minimize the adhesion of broad spectrum pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Al Meslmani, Bassam M., E-mail: almeslmanib@yahoo.com [Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg (Germany); Mahmoud, Gihan F., E-mail: mahmoudg@staff.uni-marburg.de [Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg (Germany); Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Ain Helwan, 11795 Cairo (Egypt); Leichtweiß, Thomas, E-mail: Thomas.Leichtweiss@phys.Chemie.uni-giessen.de [Institute of Physical Chemistry, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 58, 35392 Giessen (Germany); Strehlow, Boris, E-mail: strehlo4@staff.uni-marburg.de [Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg (Germany); Sommer, Frank O., E-mail: sommerf@med.uni-marburg.de [Institute for Medical Microbiology and Hospital Hygiene, Marburg University, Hans Meerwein Str 2, 35032 Marburg (Germany); Lohoff, Michael D., E-mail: lohoff@med.uni-marburg.de [Institute for Medical Microbiology and Hospital Hygiene, Marburg University, Hans Meerwein Str 2, 35032 Marburg (Germany); Bakowsky, Udo, E-mail: ubakowsky@aol.com [Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg (Germany)

    2016-01-01

    Graft-associated infections entirely determine the short-term patency of polyethylene terephthalate PET cardiovascular graft. We attempted to enzymatically inhibit the initial bacterial adhesion to PET grafts using lysozyme. Lysozyme was covalently immobilized onto woven and knitted forms of crimped PET grafts by the end-point method. Our figures of merit revealed lysozyme immobilization yield of 15.7 μg/cm{sup 2}, as determined by the Bradford assay. The activity of immobilized lysozyme on woven and knitted PET manifested 58.4% and 55.87% using Micrococcus lysodeikticus cells, respectively. Noteworthy, the adhesion of vein catheter-isolated Staphylococcus epidermidis decreased by 6- to 8-folds and of Staphylococcus aureus by 11- to 12-folds, while the Gram-negative Escherichia coli showed only a decrease by 3- to 4-folds. The anti-adhesion efficiency was specific for bacterial cells and no significant effect was observed on adhesion and growth of L929 cells. In conclusion, immobilization of lysozyme onto PET grafts can inhibit the graft-associated infection. - Highlights: • Lysozyme was covalently immobilized on crimped polyethylene terephthalate (PET). • The activity of immobilized lysozyme was meaningfully reduced. • The maintained activity significantly declined the adhesion of Gram-positive stains. • The enzymatic anti-adhesion efficiency reported lesser extent against Gram-negative. • The anti-bacterial activity displayed no significant effect on cells compatibility.

  4. MgO Nanoparticle-Catalyzed Synthesis and Broad-Spectrum Antibacterial Activity of Imidazolidine- and Tetrahydropyrimidine-2-Thione Derivatives.

    Science.gov (United States)

    Beyzaei, Hamid; Kooshki, Somaye; Aryan, Reza; Zahedi, Mohammad Mehdi; Samzadeh-Kermani, Alireza; Ghasemi, Behzad; Moghaddam-Manesh, Mohammadreza

    2017-07-05

    The biological properties of imidazolidine- and tetrahydropyrimidine-2-thione derivatives such as antiviral, antitumor, anti-inflammatory, and analgesic activities increase the demand for mild and efficient synthetic routes. In this regard, methods such as reaction of diaminoalkanes with carbon disulfide have been developed. However, this method usually suffers from relatively long reaction times, using excess reagents, vigorous reaction conditions, and emission of pernicious hydrogen sulfide gas. In this project, MgO nanoparticle was used as an efficient, non-toxic, recyclable, and economic catalyst to synthesize cyclic five- or six-membered thioureas 3a-h via reaction of 1:1 molar ratios of 1,2- or 1,3-diaminoalkanes 1a-h and carbon disulfide in ethanol at ambient temperature. More interestingly, no hydrogen sulfide emission was detected during the reaction progress. The in vitro antimicrobial properties of synthesized compounds were investigated against 14 different Gram-positive and Gram-negative pathogenic bacteria according to CLSI (Clinical and Laboratory Standards Institute) broth microdilution and disk diffusion methods. The results were compared to those of penicillin, gentamicin, and ceftriaxone, and reported as inhibition zone diameter (IZD), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC) values. The best inhibitory effects were observed with imidazolidine-2-thiones 3c and 3d. They were effective against 14 and 11 pathogens, respectively. The structure-activity relationships of the prepared heterocyclic compounds were also studied.

  5. Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines.

    Directory of Open Access Journals (Sweden)

    Rahul Subramanian

    2016-12-01

    Full Text Available Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging 'universal' vaccines-targeting more conserved components of the influenza virus-offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in vaccination strategies against influenza: in this context, our results suggest important characteristics to monitor during the clinical development of emerging vaccine technologies.

  6. 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

    and electrophysiologic status of the ischemic penumbra and to reduce lesion size on magnetic resonance images in the acute phase following middle cerebral artery occlusion in rats. The purpose of the present study was to investigate whether these beneficial effects of pinokalant are translated into permanent...... neuroprotection in terms of a reduction in infarct size one week after middle cerebral artery occlusion in rats. Halothane-anaesthetized male Wistar rats subjected to permanent distal middle cerebral artery occlusion were randomly assigned to one of two treatment groups: 1) Control (vehicle intravenous loading...... this period and the spontaneous temperature after course in control rats established in other experiments was imitated. Seven days later histological brain sections were prepared and the infarct volumes measured. Body temperature did not differ between the groups. Mean arterial blood pressure was slightly...

  7. Antimicrobial activity of selected Iranian medicinal plants against a broad spectrum of pathogenic and drug multiresistant micro-organisms.

    Science.gov (United States)

    Abedini, A; Roumy, V; Mahieux, S; Gohari, A; Farimani, M M; Rivière, C; Samaillie, J; Sahpaz, S; Bailleul, F; Neut, C; Hennebelle, T

    2014-10-01

    The antimicrobial activities of 44 methanolic extracts from different parts of Iranian indigenous plant species used in traditional medicines of Iran were tested against a panel of 35 pathogenic and multiresistant bacteria and 1 yeast. The antimicrobial efficacy was determined using Müller-Hinton agar in Petri dishes seeded by a multiple inoculator and minimal inhibition concentration (MIC) method. The 21 most active extracts (MIC micro-organisms) were submitted to a more refined measurement. The best antibacterial activity was obtained by 10 plants. Microdilution assays allowed to determinate the MIC and MBC of the 21 most active extracts. The lowest achieved MIC value was 78 μg ml(-1), with 4 extracts. This work confirms the antimicrobial activity of assayed plants and suggests further examination to identify the chemical structure of their antimicrobial compounds. Significance and impact of the study: This study describes the antimicrobial screening of Iranian plant extracts chosen according to traditional practice against 36 microbial strains, from reference culture collections or recent clinical isolates, and enables to select 4 candidates for further chemical characterization and biological assessment: Dorema ammoniacum, Ferula assa-foetida, Ferulago contracta (seeds) and Perovskia abrotanoides (aerial parts). This may be useful in the development of potential antimicrobial agents, from easily harvested and highly sustainable plant parts. Moreover, the weak extent of cross-resistance between plant extracts and antibiotics warrants further research and may promote a strategy based on less potent but time-trained products.

  8. Development and preliminary validation of a brief broad-spectrum measure of trauma exposure: the Traumatic Life Events Questionnaire.

    Science.gov (United States)

    Kubany, E S; Haynes, S N; Leisen, M B; Owens, J A; Kaplan, A S; Watson, S B; Burns, K

    2000-06-01

    This article describes the development and preliminary validation of a brief questionnaire that assesses exposure to a broad range of potentially traumatic events. Items were generated from multiple sources of information. Events were described in behaviorally descriptive terms, consistent with Diagnostic and Statistical Manual of Mental Disorders IV posttraumatic stress disorder stressor criterion A1. When events were endorsed, respondents were asked if they experienced intense fear, helplessness, or horror (stressor criterion A2). In separate studies with college students, Vietnam veterans, battered women, and residents of a substance abuse program, most items possessed adequate to excellent temporal stability. In a study comparing questionnaire and structured-interview inquiries of trauma history, the 2 formats yielded similar rates of disclosure. Preliminary data on positive predictive power are also presented.

  9. Broad Spectrum Respiratory Pathogen Analysis of Throat Swabs from Military Recruits Reveals Interference Between Rhinoviruses and Adenoviruses

    Science.gov (United States)

    2010-03-09

    components of the respiratory microflora . The technology has been success- fully demonstrated to identify a broad range of pathogens (including bacteria...available, approximately 20 recruits meeting the FRI case definition ( oral temperature of >=38°C and cough or a sore throat, or provider-diagnosed pneumonia

  10. Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk

    Science.gov (United States)

    Fouda, Genevieve G.; Jaeger, Frederick H.; Amos, Joshua D.; Ho, Carrie; Kunz, Erika L.; Anasti, Kara; Stamper, Lisa W.; Liebl, Brooke E.; Barbas, Kimberly H.; Ohashi, Tomoo; Moseley, Martin Arthur; Liao, Hua-Xin; Erickson, Harold P.; Alam, S. Munir; Permar, Sallie R.

    2013-01-01

    Achieving an AIDS-free generation will require elimination of postnatal transmission of HIV-1 while maintaining the nutritional and immunologic benefits of breastfeeding for infants in developing regions. Maternal/infant antiretroviral prophylaxis can reduce postnatal HIV-1 transmission, yet toxicities and the development of drug-resistant viral strains may limit the effectiveness of this strategy. Interestingly, in the absence of antiretroviral prophylaxis, greater than 90% of infants exposed to HIV-1 via breastfeeding remain uninfected, despite daily mucosal exposure to the virus for up to 2 y. Moreover, milk of uninfected women inherently neutralizes HIV-1 and prevents virus transmission in animal models, yet the factor(s) responsible for this anti-HIV activity is not well-defined. In this report, we identify a primary HIV-1–neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing, yet its antimicrobial properties have not previously been established. Purified TNC captured and neutralized multiclade chronic and transmitted/founder HIV-1 variants, and depletion of TNC abolished the HIV-1–neutralizing activity of milk. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by V3 loop- (19B and F39F) and chemokine coreceptor binding site-directed (17B) monoclonal antibodies. Our results demonstrate the ability of an innate mucosal host protein found in milk to neutralize HIV-1 via binding to the chemokine coreceptor site, potentially explaining why the majority of HIV-1–exposed breastfed infants are protected against mucosal HIV-1 transmission. PMID:24145401

  11. Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity.

    Science.gov (United States)

    Grande, Fedora; Aiello, Francesca; Garofalo, Antonio; Neamati, Nouri

    2016-01-01

    Design and discovery of new classes of anticancer agents with unique mechanisms of action is an urgent medical need. During the past several years, a series of salicylhydrazide class of compounds were reported to possess remarkable potency in a large panel of cancer cell lines from different tumor origins. In particular, the optimized lead compound, SC144, was further investigated and selected as a valuable drug candidate endowed with favorable pharmacokinetic and antiproliferative properties in various in vitro and in vivo xenograft models. This lead compound is active in cells resistant to conventional chemotherapies, synergistic with several standard-of-care drugs, and possesses an unique mechanism acting through the inhibition of the gp130-STAT3-survivin axis. Because of this novel mechanism, clinical development of SC144 will provide new therapeutic options for diverse cancers.

  12. Neomycin-phenolic conjugates: polycationic amphiphiles with broad-spectrum antibacterial activity, low hemolytic activity and weak serum protein binding.

    Science.gov (United States)

    Findlay, Brandon; Zhanel, George G; Schweizer, Frank

    2012-02-15

    Here we present a proof-of-concept study, combining two known antimicrobial agents into a hybrid structure in order to develop an emergent cationic detergent-like interaction with the bacterial membrane. Six amphiphilic conjugates were prepared by copper (I)-catalyzed 1,3-dipolar cycloaddition between a neomycin B-derived azide and three alkyne-modified phenolic disinfectants. Three conjugates displayed good activity against a variety of clinically relevant Gram positive and Gram negative bacteria, including MRSA, without the high level of hemolysis or strong binding to serum proteins commonly observed with other cationic antimicrobial peptides and detergents.

  13. Biogenic nanoparticles bearing antibacterial activity and their synergistic effect with broad spectrum antibiotics: Emerging strategy to combat drug

    Directory of Open Access Journals (Sweden)

    Syed Baker

    2017-01-01

    Full Text Available The present study emphasizes on synthesis of bimetallic silver–gold nanoparticles from cell free supernatant of Pseudomonas veronii strain AS41G inhabiting Annona squamosa L. The synthesized nanoparticles were characterized using hyphenated techniques with UV–Visible spectra ascertained absorbance peak between 400 and 800 nm. Possible interaction of biomolecules in mediating and stabilization of nanoparticles was depicted with Fourier transform infrared spectroscopy (FTIR. X-ray diffraction (XRD displayed Bragg’s peak conferring the 100, 111, 200, and 220 facets of the face centered cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. Size and shape of the nanoparticles were determined using Transmission electron microscopy (TEM microgram with size ranging from 5 to 50 nm forming myriad shapes. Antibacterial activity of nanoparticles against significant human pathogens was conferred with well diffusion assay and its synergistic effect with standard antibiotics revealed 87.5% fold increased activity with antibiotic “bacitracin” against bacitracin resistant strains Bacillus subtilis, Escherichia coli and Klebsiella pneumoniae followed by kanamycin with 18.5%, gentamicin with 11.15%, streptomycin with 10%, erythromycin with 9.7% and chloramphenicol with 9.4%. Thus the study concludes with biogenic and ecofriendly route for synthesizing nanoparticles with antibacterial activity against drug resistant pathogens and attributes growing interest on endophytes as an emerging source for synthesis of nanoparticles.

  14. 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. © 2013 Institute of Food Technologists®

  15. Multi-strain co-cultures surpass blends for broad spectrum biological control of maladies of potatoes in storage

    Science.gov (United States)

    Pseudomonas fluorescens strains S11:P:12, P22:Y:05, and S22:T:04 have been documented to suppress four important problems in potato storages — dry rot, late blight, pink rot, and sprouting. This research investigates the efficacy and consistency of strain mixtures produced by co-culturing strains t...

  16. High prevalence of gut microbiota colonization with broad-spectrum cephalosporin resistant Enterobacteriaceae in a Tunisian intensive care unit

    Directory of Open Access Journals (Sweden)

    Elaa Maamar

    2016-11-01

    Full Text Available Healthcare-associated infections due to cefotaxime-resistant Enterobacteriaceae (CRE have become a major public health threat, especially in intensive care units (ICUs. Often acquired nosocomially, CRE can be introduced initially by patients at admission. This study aimed to determine the prevalence and genetic characteristics of CRE-intestinal carriage in ICU patients, to evaluate the rate of acquisition of these organisms during hospitalization, and to explore some of the associated risk factors for both carriage and acquisition.Between December 2014 and February 2015, the 63 patients admitted in the ICU of Charles Nicolle hospital were screened for rectal CRE colonization at admission and once weekly thereafter to identify acquisition. CRE fecal carriage rate was 20.63% (13/63 at admission and the acquisition rate was 42.85% (15/35. Overall, 35 CRE isolates were collected from 28 patients (25 Klebsiella pneumoniae, 7 Escherichia coli and 3 Enterobacter cloacae strains. Seven patients were simultaneously colonized with 2 CRE isolates. CTX-M-15 was detected in most of the CRE isolates (30/35, 88.23%.Three strains co-produced CMY-4 and 22 strains were carbapenem-resistant and co-produced a carbapenemase OXA-48 (n=13 or NDM-1 (n=6. All isolates were multidrug resistant. Molecular typing of K. pneumoniae strains, revealed 8 Pulsed field gel electrophoresis (PFGE patterns and 4 sequence types (ST ST101, ST147, ST429 and ST336. However, E. coli isolates were genetically unrelated and belonged to A (n=2, B1 (n=2 and B2 (n=3 phylogenetic groups and to ST131 (2 strains, ST572 (2 strains, ST615 (one strain and ST617 (one strain. Five colonized patients were infected by CRE (4 with the same strain identified from their rectal swab and 1 with a different strain. Whether imported or acquired during the stay in the ICU, colonization by CRE is a major risk factor for the occurrence of serious nosocomial infections. Their systematic screening in fecal carriage is mandatory to prevent the spread of these multidrug resistant bacteria.

  17. The Non-Lantibiotic Bacteriocin Garvicin Q Targets Man-PTS in a Broad Spectrum of Sensitive Bacterial Genera.

    Science.gov (United States)

    Tymoszewska, Aleksandra; Diep, Dzung B; Wirtek, Paulina; Aleksandrzak-Piekarczyk, Tamara

    2017-08-21

    Mannose phosphotransferase system (Man-PTS) is the main mannose permease in bacteria but it is also a known receptor for subclass IIa bacteriocins (pediocin-like group) as well as subclass IId lactococcin A (LcnA) and lactococcin B (LcnB) (LcnA-like group). Subclass IIa bacteriocins exhibit a strong activity against Listeria spp. but they are not against Lactococcus spp. In contrast, the LcnA-like bacteriocins act only against Lactococcus lactis strains. Garvicin Q (GarQ) is a subclass IId bacteriocin with minor similarity to LcnA-like bacteriocins and a relatively broad antimicrobial spectrum including, among others, Listeria and Lactococcus spp. To identify the GarQ receptor, we obtained GarQ-resistant mutants of Lactococcus garvieae IBB3403 and L. lactis IL1403 and sequenced their genomes that revealed mutations in genes encoding the membrane-bound Man-PTS IIC or IID subunits encoded by ptnCD in L. lactis and manCD in L. garvieae. This is the first time that a bacteriocin outside the pediocin- and LcnA-like groups is shown to target Man-PTS. The interaction between GarQ and Man-PTS may occur through a new binding pattern involving specific amino acids highly conserved among the GarQ-sensitive bacterial species located in the N-terminal part and extracellular loops of subunit IID and in transmembrane region of IIC.

  18. A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIβ

    NARCIS (Netherlands)

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

    2013-01-01

    Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidaz

  19. Broad-spectrum in vitro antibacterial activities of clay minerals against antibiotic-susceptible and antibiotic-resistant bacterial pathogens

    National Research Council Canada - National Science Library

    Haydel, Shelley E; Remenih, Christine M; Williams, Lynda B

    .... The use of geological nanomaterials to heal skin infections has been evident since the earliest recorded history, and specific clay minerals may prove valuable in the treatment of bacterial diseases...

  20. An accurate homogenized tissue phantom for broad spectrum autofluorescence studies: a tool for optimizing quantum dot-based contrast agents

    Science.gov (United States)

    Roy, Mathieu; Wilson, Brian C.

    2008-02-01

    We are investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). The present studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. These contrast optimization studies require optical phantoms that simulate tissue autofluorescence, absorption and scattering over the entire visible spectrum, while allowing us to control the optical thickness. We present an optical phantom made of fresh homogenized tissue diluted in water. The homogenized tissue is poured into a clear polymer tank designed to hold a QD-loaded silica capillary in its center. Because of the non-linear effects of absorption and scattering on measured autofluorescence, direct comparison between results obtained using tissue phantoms of different concentration is not possible. We introduce mathematical models that make it possible to perform measurements on diluted tissue homogenates and subsequently extrapolate the results to intact (non-diluted) tissue. Finally, we present preliminary QD contrast data showing that the 380-420 nm spectral window is optimal for surface QD imaging.

  1. 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.

  2. Development of FGI-106 as a broad-spectrum therapeutic with activity against members of the family Bunyaviridae

    Directory of Open Access Journals (Sweden)

    Darci R Smith

    2010-02-01

    Full Text Available Darci R Smith1, Monica Ogg1, Aura Garrison1, Abdul Yunus2, Anna Honko1, Josh Johnson1, Gene Olinger1, Lisa E Hensley1, Michael S Kinch1United States Army Medical Research Institute of Infectious Diseases (USAMRII D, Fort Detrick, MD, USA; 2Functional Genetics, Inc., Gaithersburg, MD, USAAbstract: The family Bunyaviridae is a diverse group of negative-strand RNA viruses that infect a wide range of arthropod vectors and animal hosts. Based on the continuing need for new therapeutics to treat bunyavirus infections, we evaluated the potential efficacy of FGI-106, a small-molecular compound that previously demonstrated activity against different RNA viruses. FGI-106 displayed substantial antiviral activity in cell-based assays of different bunyavirus family members, including Asian and South American hantaviruses (Hantaan virus and Andes virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, and Rift Valley fever virus. The pharmacokinetic profile of FGI-106 revealed sufficient exposure of the drug to critical target organs (lung, liver, kidney, and spleen, which are frequently the sites of bunyavirus replication. Consistent with these findings, FGI-106 treatment delivered via intraperitoneal injection prior to virus exposure was sufficient to delay the onset of Rift Valley fever virus infection in mouse-based models and to enhance survival in the face of an otherwise lethal infection. Altogether, these results suggest a potential opportunity for the use of FGI-106 to treat infections by members of the family Bunyaviridae.Keywords: Rift Valley fever virus, bunyavirus, hantavirus, antiviral, therapeutic

  3. Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses.

    Science.gov (United States)

    Li, Junwei; Arévalo, Maria T; Chen, Yanping; Posadas, Olivia; Smith, Jacob A; Zeng, Mingtao

    2014-01-01

    Frequent mutation of influenza viruses keep vaccinated and non-vaccinated populations vulnerable to new infections, causing serious burdens to public health and the economy. Vaccination with universal influenza vaccines would be the best way to effectively protect people from infection caused by mismatched or unforeseen influenza viruses. Presently, there is no FDA approved universal influenza vaccine. In this study, we expressed and purified a fusion protein comprising of influenza matrix 2 protein ectodomain peptides, a centralized influenza hemagglutinin stem region, and cholera toxin subunit B. Vaccination of BALB/c mice with this novel artificial antigen resulted in potent humoral immune responses, including induction of specific IgA and IgG, and broad protection against infection by multiple influenza viruses. Furthermore, our results demonstrated that when used as a mucosal antigen, cholera toxin subunit B improved antigen-stimulated T cell and memory B cell responses.

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

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

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

  5. 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

    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

  6. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans.

    Science.gov (United States)

    Sivapirabu, G; Yiasemides, E; Halliday, G M; Park, J; Damian, D L

    2009-12-01

    Ultraviolet (UV) radiation can profoundly suppress the cutaneous immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness against different UV wavebands and mechanism of action is as yet unknown. To determine the effects and mechanisms of topical nicotinamide on UV-induced suppression of delayed type hypersensitivity (DTH) responses in humans. Healthy Mantoux-positive volunteers in four randomised, double-blinded studies were irradiated with solar-simulated (ss)UV (UVB + UVA) or narrowband UVB (300 nm) or UVA (385 nm). Topical nicotinamide (0.2% or 5%) or its vehicle were applied immediately after each irradiation. Mantoux testing was performed at irradiated sites and adjacent unirradiated control sites 48 h after the first irradiation and measured 72 h later. Immunosuppression was calculated as the difference in Mantoux-induced erythema and induration at test sites compared to control sites. Human keratinocyte cell cultures, with and without ssUV and nicotinamide, were used for quantitative real-time reverse transcriptase-polymerase chain reaction assessment of TP53 and enzymes that regulate oxidative phosphorylation. Nicotinamide cooperated with ssUV to increase enzymes involved in cellular energy metabolism and p53, and significantly protected against immunosuppression caused by UVB, longwave UVA and single and repeated ssUV exposures. Longwave UVA, which is poorly filtered by most sunscreens, was highly immune suppressive even at doses equivalent to 20 min of sun exposure. Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.

  7. Antimicrobial resistance in the Bacteroides fragilis group in faecal samples from patients receiving broad-spectrum antibiotics

    DEFF Research Database (Denmark)

    Møller Hansen, Kia Cirkeline; Ferløv-Schwensen, Simon Andreas; Henriksen, Daniel Pilsgaard

    2017-01-01

    Members of the Bacteroides fragilis group are opportunistic pathogens and cause severe infections including bacteraemia. As increased levels of antimicrobial resistance in B. fragilis group bacteria can be detected years after administration of specific antibiotics, monitoring antimicrobial...... susceptibility in the gut microbiota could be important. The objectives of this study were to 1) investigate the distribution of species and the occurrence of reduced antimicrobial susceptibility in the B. fragilis group from patients treated at departments with a high level of antibiotic use, 2) to determine...... susceptibility. Of these 28%, 5%, Bacteroides spp. were isolated. The proportion of B. fragilis belonging to division II (cfiA+) was 5...

  8. Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide.

    Science.gov (United States)

    Huang, Ying-Ying; Choi, Hwanjun; Kushida, Yu; Bhayana, Brijesh; Wang, Yuguang; Hamblin, Michael R

    2016-09-01

    Photocatalysis describes the excitation of titanium dioxide nanoparticles (a wide-band gap semiconductor) by UVA light to produce reactive oxygen species (ROS) that can destroy many organic molecules. This photocatalysis process is used for environmental remediation, while antimicrobial photocatalysis can kill many classes of microorganisms and can be used to sterilize water and surfaces and possibly to treat infections. Here we show that addition of the nontoxic inorganic salt potassium iodide to TiO2 (P25) excited by UVA potentiated the killing of Gram-positive bacteria, Gram-negative bacteria, and fungi by up to 6 logs. The microbial killing depended on the concentration of TiO2, the fluence of UVA light, and the concentration of KI (the best effect was at 100 mM). There was formation of long-lived antimicrobial species (probably hypoiodite and iodine) in the reaction mixture (detected by adding bacteria after light), but short-lived antibacterial reactive species (bacteria present during light) produced more killing. Fluorescent probes for ROS (hydroxyl radical and singlet oxygen) were quenched by iodide. Tri-iodide (which has a peak at 350 nm and a blue product with starch) was produced by TiO2-UVA-KI but was much reduced when methicillin-resistant Staphylococcus aureus (MRSA) cells were also present. The model tyrosine substrate N-acetyl tyrosine ethyl ester was iodinated in a light dose-dependent manner. We conclude that UVA-excited TiO2 in the presence of iodide produces reactive iodine intermediates during illumination that kill microbial cells and long-lived oxidized iodine products that kill after light has ended.

  9. 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

  10. Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity.

    Science.gov (United States)

    Abdel-Mageed, Wael M; Bayoumi, Soad A H; Chen, Caixia; Vavricka, Christopher J; Li, Li; Malik, Ajamaluddin; Dai, Huanqin; Song, Fuhang; Wang, Luoqiang; Zhang, Jingyu; Gao, George F; Lv, Yali; Liu, Lihong; Liu, Xueting; Sayed, Hanaa M; Zhang, Lixin

    2014-04-01

    The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.

  11. Novel Broad-Spectrum Antimicrobial Photoinactivation of In Situ Oral Biofilms by Visible Light plus Water-Filtered Infrared A.

    Science.gov (United States)

    Karygianni, L; Ruf, S; Follo, M; Hellwig, E; Bucher, M; Anderson, A C; Vach, K; Al-Ahmad, A

    2014-12-01

    Antimicrobial photodynamic therapy (APDT) has gained increased attention as an alternative treatment approach in various medical fields. However, the effect of APDT using visible light plus water-filtered infrared A (VIS + wIRA) on oral biofilms remains unexplored. For this purpose, initial and mature oral biofilms were obtained in situ; six healthy subjects wore individual upper jaw acrylic devices with bovine enamel slabs attached to their proximal sites for 2 h or 3 days. The biofilms were incubated with 100 μg ml(-1) toluidine blue O (TB) or chlorin e6 (Ce6) and irradiated with VIS + wIRA with an energy density of 200 mW cm(-2) for 5 min. After cultivation, the CFU of half of the treated biofilm samples were quantified, whereas following live/dead staining, the other half of the samples were monitored by confocal laser scanning microscopy (CLSM). TB- and Ce6-mediated APDT yielded a significant decrease of up to 3.8 and 5.7 log10 CFU for initial and mature oral biofilms, respectively. Quantification of the stained photoinactivated microorganisms confirmed these results. Overall, CLSM revealed the diffusion of the tested photosensitizers into the deepest biofilm layers after exposure to APDT. In particular, Ce6-aided APDT presented elevated permeability and higher effectiveness in eradicating 89.62% of biofilm bacteria compared to TB-aided APDT (82.25%) after 3 days. In conclusion, antimicrobial photoinactivation using VIS + wIRA proved highly potent in eradicating oral biofilms. Since APDT excludes the development of microbial resistance, it could supplement the pharmaceutical treatment of periodontitis or peri-implantitis.

  12. A Broad Spectrum Catalytic System for Removal of Toxic Organics from Water by Deep Oxidation - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Ayusman

    2000-12-01

    A most pressing need for the DOE environmental management program is the removal of toxic organic compounds present in groundwater and soil at specific DOE sites. While several remediation procedures have been proposed, they suffer from one or more drawbacks. The objective of the present research was to develop new catalytic procedures for the removal of toxic organic compounds from the environment through their deep oxidation to harmless products. In water, metallic palladium was found to catalyze the deep oxidation of a wide variety of toxic organic compounds by dioxygen at 80-90 C in the presence of carbon monoxide or dihydrogen. Several classes of organic compounds were examined: benzene, phenol and substituted phenols, nitro and halo organics, organophosphorus, and organosulfur compounds. In every case, deep oxidation to carbon monoxide, carbon dioxide, and water occurred in high yields, resulting in up to several hundred turnovers over a 24 hour period. For substrates susceptible to hydrogenation, the conversions were generally high with dihydrogen than with carbon monoxide. It is clear from the results obtained that we have discovered an exceptionally versatile catalytic system for the deep oxidation of toxic organic compounds in water. This system possesses several attractive features not found simultaneously in other reported systems. These are (a) the ability to directly utilize dioxygen as the oxidant, (b) the ability to carry out the deep oxidation of a particularly wide range of functional organics, and (c) the ease of recovery of the catalyst by simple filtration.

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

    Science.gov (United States)

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

    2014-12-01

    The HIV Rev protein mediates the transport of partially and unspliced HIV mRNA from the nucleus to the cytoplasm. Rev multimerizes on a secondary stem-loop structure present in the viral intron-containing mRNA species and recruits the cellular karyopherin CRM1 to export viral mRNAs from the nucleus to the cytoplasm. Previously we have identified a single-domain intrabody (Nb(190)), derived from a llama heavy-chain antibody, which efficiently inhibits Rev multimerization and suppresses the production of infectious virus. We recently mapped the epitope of this nanobody and demonstrated that Rev residues K20 and Y23 are crucial for interaction while residues V16, H53 and L60 are important to a lesser extent. Here, we generated cell lines stably expressing Nb(190) and assessed the capacity of these cell lines to suppress the replication of different HIV-1 subtypes. These cells stably expressing the single-domain antibody are protected from virus-induced cytopathogenic effect even in the context of high multiplicity of infection. In addition, the replication of different subtypes of group M and one strain of group O is significantly suppressed in these cell lines. Next, we analysed the natural variations of Rev amino acids in sequence samples from HIV-1 infected patients worldwide and assessed the effect of Nb(190) on the most prevalent polymorphisms occurring at the key epitope positions (K20 and Y23) in Rev. We found that Nb(190) was able to suppress the function of these Rev variants except for the K20N mutant, which was present in only 0.7% of HIV-1 sequence populations (n = 4632). Cells stably expressing the single-domain intrabody Nb(190) are protected against virus-induced cytopathogenic effect and display a selective survival advantage upon infection. In addition, Nb(190) suppresses the replication of a wide range of different HIV-1 subtypes. Large-scale sequence analysis reveals that the Nb(190) epitope positions in Rev are well conserved across major HIV-1 subtypes and groups. Altogether, our results indicate that Nb(190) may have broad potential as a gene therapeutic agent against HIV-1.

  14. Krüppeling erythropoiesis: An unexpected broad spectrum of human red blood cell disorders due to KLF1 variants

    NARCIS (Netherlands)

    A. Perkins (Andrew); X. Xu (Xiangmin); D. Higgs (Doug); G.P. Patrinos (George P.); L. Arnaud (Lionel); J.J. Bieker (James J.); J.N.J. Philipsen (Sjaak)

    2016-01-01

    textabstractUntil recently our approach to analyzing human genetic diseases has been to accurately phenotype patients and sequence the genes known to be associated with those phenotypes; for example, in thalassemia, the globin loci are analyzed. Sequencing has become increasingly accessible, and thu

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

    DEFF Research Database (Denmark)

    Krustrup, P; Skoradal, M-B; Randers, M B

    2017-01-01

    to CON (1.1±1.9 kg, P=.09). Over one year, change scores in whole-body bone mineral density (0.004±0.032 vs -0.019±0.026 g·cm(2) ) as well as bone mineral content (30±70 vs -39±113 g) were positive in SOC compared to CON (P2±0.......2 mmol·L(-1) ) and HDL cholesterol increased more (0.2±0.7 vs -0.2±0.2 mmol·L(-1) ) in SOC than in CON (P

  16. Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants.

    Science.gov (United States)

    Perkins, Andrew; Xu, Xiangmin; Higgs, Douglas R; Patrinos, George P; Arnaud, Lionel; Bieker, James J; Philipsen, Sjaak

    2016-04-14

    Until recently our approach to analyzing human genetic diseases has been to accurately phenotype patients and sequence the genes known to be associated with those phenotypes; for example, in thalassemia, the globin loci are analyzed. Sequencing has become increasingly accessible, and thus a larger panel of genes can be analyzed and whole exome and/or whole genome sequencing can be used when no variants are found in the candidate genes. By using such approaches in patients with unexplained anemias, we have discovered that a broad range of hitherto unrelated human red cell disorders are caused by variants in KLF1, a master regulator of erythropoiesis, which were previously considered to be extremely rare causes of human genetic disease.

  17. Chirped InAs/InP quantum-dash laser with enhanced broad spectrum of stimulated emission

    KAUST Repository

    Khan, Mohammed Zahed Mustafa

    2013-03-01

    We report on the demonstration of 50 nm (full-width at half-maximum) broadband stimulated emission from a chirped AlGaInAs barrier thickness multi-stack InAs/InP quantum dash (Qdash) laser. The 2 ?m wide uncoated Fabry-Perot (FP) ridge-waveguide laser exhibits a total power of 0.18 W, corresponding to an average spectral power density of 3.5 mW/nm, under pulsed current conditions. Intentional extended inhomogeneity across the Qdash stacks have been attributed to the enhancement of broadband emission. © 2013 American Institute of Physics.

  18. Fate of a broad spectrum of perfluorinated compounds in soils and biota from Tierra del Fuego and Antarctica.

    Science.gov (United States)

    Llorca, Marta; Farré, Marinella; Tavano, Máximo Sebastián; Alonso, Bruno; Koremblit, Gabriel; Barceló, Damià

    2012-04-01

    In this study, the presence of 18 perfluorinated compounds was investigated in biota and environmental samples from the Antarctica and Tierra de Fuego, which were collected during a sampling campaign carried out along February and March 2010. 61 samples were analysed including fish, superficial soils, guano, algae, dung and tissues of Papua penguin by liquid chromatography coupled to tandem mass spectrometry. The concentrations of PFCs were ranging from 0.10 to 240 ng/g for most of the samples except for penguin dung, which presented levels between 95 and 603 ng/g for perfluorooctane sulfonate, and guano samples from Ushuaia, with concentration levels of 1190-2480 ng/g of perfluorohexanoic acid. PFCs acids presented, in general, the highest levels of concentration and perfluorooctanesulfonate was the most frequently found compound. The present study provides a significant amount of results, which globally supports the previous studies, related to the transport, deposition, biodegradation and bioaccumulation patterns of PFCs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Competitive Between Phytophthora Infestans Effectors Leads to Increased Aggressiveness on Plants Containing Broad-Spectrum Late Blight Resistance

    Science.gov (United States)

    Potato late blight is a particularly destructive plant disease caused by the oomycete pathogen Phytophthora infestans (Mont.) de Bary. Late blight has remained particularly problematic despite intensive breeding efforts to integrate resistance into cultivated potato. This is due to the pathogen’s ab...

  20. 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

  1. Use of sensitive, broad-spectrum molecular assays and human airway epithelium cultures for detection of respiratory pathogens.

    Directory of Open Access Journals (Sweden)

    Krzysztof Pyrc

    Full Text Available Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ~30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1-10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ~76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.

  2. Use of Sensitive, Broad-Spectrum Molecular Assays and Human Airway Epithelium Cultures for Detection of Respiratory Pathogens

    Science.gov (United States)

    Wojcik, Krzysztof; Gawron, Katarzyna; Zeglen, Slawomir; Karolak, Wojciech; Wojarski, Jacek; Ochman, Marek; Hubalewska-Mazgaj, Magdalena; Bochenek, Grazyna; Sanak, Marek; Zembala, Marian; Szczeklik, Andrzej; Potempa, Jan

    2012-01-01

    Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ∼30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1–10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ∼76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used. PMID:22403676

  3. 75 FR 62112 - Notice of Availability of a Broad Spectrum of Patents for Exclusive, Partially Exclusive, or Non...

    Science.gov (United States)

    2010-10-07

    ... force magnetometer. Kecskes 7,645,350 High-density metallic glass alloys. Hoffman 7,646,797 Use of... enhancing the wear resistance of ferrous articles. Redman 7,675,610 Photon counting, chirped AM LADAR system...

  4. Engineering of Paraoxonases for Pre- and Post-treatment of Intoxication by a Broad Spectrum of Nerve Agents and Pesticides

    Science.gov (United States)

    2014-08-01

    inhalation and skin absorption. Commercial OP pesticides such as parathion, chlopyrifos, phorate, and malathion, are also considered as threat...human paraoxonase gene cluster as a target in the treatment of atherosclerosis. Antioxidants & redox signaling 16: 597-632 van den Berg B, Tessari M

  5. "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 for introductory geoscience courses are similar among all higher-education institution types. However, faculty at 4YCs may expect students to acquire and apply multiple quantitative skills in the same class/lab, whereas 2YC faculty may structure assignments to introduce and apply only one quantitative technique at a time.

  6. Leveraging the Attributes of Mucor hiemalis-Derived Silver Nanoparticles for a Synergistic Broad-Spectrum Antimicrobial Platform

    Science.gov (United States)

    Aziz, Nafe; Pandey, Rishikesh; Barman, Ishan; Prasad, Ram

    2016-01-01

    Driven by the need to engineer robust surface coatings for medical devices to prevent infection and sepsis, incorporation of nanoparticles has surfaced as a promising avenue to enhance non-fouling efficacy. Microbial synthesis of such nanoscale metallic structures is of substantive interest as this can offer an eco-friendly, cost-effective, and sustainable route for further development. Here we present a Mucor hiemalis-derived fungal route for synthesis of silver nanoparticles, which display significant antimicrobial properties when tested against six pathological bacterial strains (Klebsiella pneumoniae, Pseudomonas brassicacearum, Aeromonas hydrophila, Escherichia coli, Bacillus cereus, and Staphylococcus aureus) and three pathological fungal strains (Candida albicans, Fusarium oxysporum, and Aspergillus flavus). These antimicrobial attributes were comparable to those of established antibiotics (streptomycin, tetracycline, kanamycin, and rifampicin) and fungicides (amphotericin B, fluconazole, and ketoconazole), respectively. Importantly, these nanoparticles show significant synergistic characteristics when combined with the antibiotics and fungicides to offer substantially greater resistance to microbial growth. The blend of antibacterial and antifungal properties, coupled with their intrinsic “green” and facile synthesis, makes these biogenic nanoparticles particularly attractive for future applications in nanomedicine ranging from topical ointments and bandages for wound healing to coated stents. PMID:28018316

  7. Being a reflective teacher——reflection on group management

    Institute of Scientific and Technical Information of China (English)

    Pan; Lehui

    2015-01-01

    <正>Introduction According to Pollard and Triggs(1997),reflective teaching is a process through which the capacity to make such professional judgments can be developed and maintained.Then what is a reflective teacher?Reflective teacher is someone who reflects systematically on her practice in a constant attempt to improve

  8. Ethical reflection and psychotherapy.

    Science.gov (United States)

    Vyskocilová, Jana; Prasko, Jan

    2013-01-01

    Theories of ethics and ethical reflection may be applied to both theory and practice in psychotherapy. There is a natural affinity between ethics and psychotherapy. Psychotherapy practice is concerned with human problems, dilemmas and emotions related to both one's own and other people's values. Ethics is also concerned with dilemmas in human thinking and with how these dilemmas reflect other individuals' values. Philosophical reflection itself is not a sufficient basis for the ethics of psychotherapy but it may aid in exploring attitudes related to psychotherapy, psychiatry and health care. PubMed, Web of Science and Scopus databases were searched for articles containing the keywords "psychotherapy", "ethics", "therapeutic relationship" and "supervision". The search was conducted by repeating the terms in various combinations without language or time restrictions. Also included were data from monographs cited in reviews. The resulting text is a review with conclusions concerning ethical aspects of psychotherapy. The ability to behave altruistically, sense for justice and reciprocity and mutual help are likely to be genetically determined as dispositions to be later developed by upbringing or to be formed or deformed by upbringing. Early experiences lead to formation of ethical attitudes which are internalized and then applied to both one's own and other people's behavior. Altruistic behavior has a strong impact on an individual's health and its acceptance may positively influence the pathophysiological mechanisms underlying numerous diseases. Ethical theory and reflection, however, may be applied to both theory and practice of psychotherapy in a conscious, targeted and thoughtful manner. In everyday practice, psychotherapists and organizations must necessarily deal with conscious conflicts between therapeutic possibilities, clients' wishes, their own as well as clients' ideas and the real world. Understanding one's own motives in therapy is one of the aims of a

  9. Reflective Inverse Diffusion

    Directory of Open Access Journals (Sweden)

    Kenneth Burgi

    2016-11-01

    Full Text Available Phase front modulation was previously used to refocus light after transmission through scattering media. This process has been adapted here to work in reflection. A liquid crystal spatial light modulator is used to conjugate the phase scattering properties of diffuse reflectors to produce a converging phase front just after reflection. The resultant focused spot had intensity enhancement values between 13 and 122 depending on the type of reflector. The intensity enhancement of more specular materials was greater in the specular region, while diffuse reflector materials achieved a greater enhancement in non-specular regions, facilitating non-mechanical steering of the focused spot. Scalar wave optics modeling corroborates the experimental results.

  10. Clinical linguistics: conversational reflections.

    Science.gov (United States)

    Crystal, David

    2013-04-01

    This is a report of the main points I made in an informal "conversation" with Paul Fletcher and the audience at the 14th ICPLA conference in Cork. The observations arose randomly, as part of an unstructured 1-h Q&A, so they do not provide a systematic account of the subject, but simply reflect the issues which were raised by the conference participants during that time.

  11. Ubuntu feminism: Tentative reflections

    OpenAIRE

    Drucilla Cornell; Karin van Marle

    2015-01-01

    The starting-point for the article is to provide a brief background on the Ubuntu Project that Prof. Drucilla Cornell convened in 2003; most notably the interviews conducted in Khayamandi, the support of a sewing collective, and the continued search to launch an Ubuntu Women�s Centre. The article will reflect on some of the philosophical underpinnings of ubuntu, whereafter debates in Western feminism will be revisited. Ubuntu feminism is suggested as a possible response to these types of femi...

  12. Reflections and Interpretations

    DEFF Research Database (Denmark)

    Reflections and Interpretations is an anthology on The Freedom Writers’ methodology. It is an anthology for all those with a professional need for texts explaining, not only how The Freedom Writers’ tools are being used, but also why they work so convincingly well. It is not an anthology of guide...... of guidelines; it is an anthology of explanations based on theory. And it is an anthology written by Freedom Writer Teachers – who else could do it?...

  13. Reflection and teaching: a taxonomy

    NARCIS (Netherlands)

    Vos, Henk; Cowan, John

    2009-01-01

    A major problem in teaching reflection is that educational objectives for reflection in terms of student behaviour are lacking. Therefore a taxonomy of reflection has been developed based on Bloom’s taxonomy. Reflective assignments can then be better focused on any chosen educational objectives. The

  14. Reflections on preventive medicine.

    Science.gov (United States)

    Miettinen, Olli S

    2014-10-01

    Having thought much about medicine in my career-long effort to understand it and the research for its advancement, I have come to views rather different form the now-prevailing ones in respect to what preventive medicine is about; what epidemiology is in relation to preventive medicine; what distinguishes preventive medicine in preventive healthcare at large; the relation of preventive medicine to public health; the concept of health promotion; and also the core principles of preventive medicine. All of these views I set forth in this article, for the readers' critical reflection.

  15. Reflective writing in medical education.

    Science.gov (United States)

    Song, Philip; Stewart, Rosalyn

    2012-01-01

    The teaching of reflection and the use of reflective writing assignments is commonplace in medical school education. There is a preponderance of research in medical education, which appraises and discusses new ways of teaching reflection. Students often complain about having to write about their experience with that patient. This work explores some of the reasoning between the variability of student acceptance of reflection in medical education. The method is based on available literature as well as a personal perspective regarding reflective writing in medical education. Reflection is a skill that requires teaching and practice. It is within the explicit process of teaching reflection in medical education that reflective learners can be developed. Reflection includes the take-home lesson from patient encounters. Its use can help learners become better physicians in terms of medical and humanistic effectiveness and support personal growth.

  16. Fostering and evaluating reflective capacity in medical education: developing the REFLECT rubric for assessing reflective writing.

    Science.gov (United States)

    Wald, Hedy S; Borkan, Jeffrey M; Taylor, Julie Scott; Anthony, David; Reis, Shmuel P

    2012-01-01

    Reflective writing (RW) curriculum initiatives to promote reflective capacity are proliferating within medical education. The authors developed a new evaluative tool that can be effectively applied to assess students' reflective levels and assist with the process of providing individualized written feedback to guide reflective capacity promotion. Following a comprehensive search and analysis of the literature, the authors developed an analytic rubric through repeated iterative cycles of development, including empiric testing and determination of interrater reliability, reevaluation and refinement, and redesign. Rubric iterations were applied in successive development phases to Warren Alpert Medical School of Brown University students' 2009 and 2010 RW narratives with determination of intraclass correlations (ICCs). The final rubric, the Reflection Evaluation for Learners' Enhanced Competencies Tool (REFLECT), consisted of four reflective capacity levels ranging from habitual action to critical reflection, with focused criteria for each level. The rubric also evaluated RW for transformative reflection and learning and confirmatory learning. ICC ranged from 0.376 to 0.748 for datasets and rater combinations and was 0.632 for the final REFLECT iteration analysis. The REFLECT is a rigorously developed, theory-informed analytic rubric, demonstrating adequate interrater reliability, face validity, feasibility, and acceptability. The REFLECT rubric is a reflective analysis innovation supporting development of a reflective clinician via formative assessment and enhanced crafting of faculty feedback to reflective narratives.

  17. Reflection and Non-Reflection of Particle Wavepackets

    Science.gov (United States)

    Cox, Timothy; Lekner, John

    2008-01-01

    Exact closed-form solutions of the time-dependent Schrodinger equation are obtained, describing the propagation of wavepackets in the neighbourhood of a potential. Examples given include zero reflection, total reflection and partial reflection of the wavepacket, for the sech[superscript 2]x/a, 1/x[superscript 2] and delta(x) potentials,…

  18. Reflections on Conformal Spectra

    CERN Document Server

    Kim, Hyungrok; Ooguri, Hirosi

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions $\\Delta_0$ of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite $\\Delta_0$ as well as for large $\\Delta_0$. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function.

  19. Teachers’ way of reflecting

    DEFF Research Database (Denmark)

    Lund, Lea

    2016-01-01

    of the Danish study was to investigate and understand teachers’ classroom experiences using Fenstermacher’s approach to develop a practical argument, as these classroom experiences are regarded as a potential source of learning for teachers. A three-level scale model from the study describes the teach-ers......’ reflections on practice. Based on this model, the paper provides a proposal regarding how to work with teachers’ professional development and learning processes. Educational implications and future research directions are discussed.......This paper contributes to insights on teachers’ thinking and practice by building partly on the large amount of prior research in the field of continuing professional development (in line with ISATT), and partly on examples from an empirical small-scale study executed in Denmark. The purpose...

  20. Reflections on love's spirals.

    Science.gov (United States)

    Kenny, Gerard

    2011-06-01

    This article seeks to explore how the experience of love and its expression might inform and guide reflection and inquiry into love. Despite the importance of love in our personal and professional lives, it remains a topic that has further scope for inquiry within nursing circles. The article takes as its catalyst an encounter that emerged out of a piece of research that was exploring individuals' experiences of becoming healers and the journey they undertook. One participant spoke deeply and profoundly of his experience of love, which generated for me a personal, experiential, and intellectual process of inquiry. The article seeks to try and create a synthesis between rational inquiry and subjective experience. It explores W. B. Yeats's notion of a gyre, a spiral, as an image and metaphor for integrating different conceptions and understandings of love. It seeks to illustrate how a more integrated understanding of love may open up spaces of inquiry that are more flexible, creative, and spontaneous.

  1. Reflections on Conformal Spectra

    CERN Document Server

    CERN. Geneva

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions Δ0 of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite Δ0 as well as for large Δ0. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function. (based on 1510.08772 with Kim & Ooguri). This seminar will be given via videolink

  2. Quantitative Hyperspectral Reflectance Imaging

    Directory of Open Access Journals (Sweden)

    Ted A.G. Steemers

    2008-09-01

    Full Text Available Hyperspectral imaging is a non-destructive optical analysis technique that can for instance be used to obtain information from cultural heritage objects unavailable with conventional colour or multi-spectral photography. This technique can be used to distinguish and recognize materials, to enhance the visibility of faint or obscured features, to detect signs of degradation and study the effect of environmental conditions on the object. We describe the basic concept, working principles, construction and performance of a laboratory instrument specifically developed for the analysis of historical documents. The instrument measures calibrated spectral reflectance images at 70 wavelengths ranging from 365 to 1100 nm (near-ultraviolet, visible and near-infrared. By using a wavelength tunable narrow-bandwidth light-source, the light energy used to illuminate the measured object is minimal, so that any light-induced degradation can be excluded. Basic analysis of the hyperspectral data includes a qualitative comparison of the spectral images and the extraction of quantitative data such as mean spectral reflectance curves and statistical information from user-defined regions-of-interest. More sophisticated mathematical feature extraction and classification techniques can be used to map areas on the document, where different types of ink had been applied or where one ink shows various degrees of degradation. The developed quantitative hyperspectral imager is currently in use by the Nationaal Archief (National Archives of The Netherlands to study degradation effects of artificial samples and original documents, exposed in their permanent exhibition area or stored in their deposit rooms.

  3. Action Research and Reflective Teaching

    Institute of Scientific and Technical Information of China (English)

    刘阿莉

    2008-01-01

    Reflection is an impontant core of professional development and action research in which the teachers reflect through the Systematic collection and analym of data is a form of srrucured reflection.The teachers can be provided with powerful means of professional development.

  4. Reflective writing and nursing education.

    Science.gov (United States)

    Craft, Melissa

    2005-02-01

    Reflective writing is a valued tool for teaching nursing students and for documentation, support, and generation of nursing knowledge among experienced nurses. Expressive or reflective writing is becoming widely accepted in both professional and lay publications as a mechanism for coping with critical incidents. This article explores reflective writing as a tool for nursing education.

  5. Teacher Reflection: A Phenomenological Study

    Science.gov (United States)

    Wilson, Rebecca E.

    2013-01-01

    This study is concerned with the reflective practices of middle school teachers. Based on Dewey's theory of reflective practice and Schon's types of reflection, this experience is one of student learning, relationships, curriculum planning, and lesson delivery. This is a qualitative study using the research method of phenomenology through…

  6. Reflection in Russian Educational Psychology.

    Science.gov (United States)

    Nelissen, Jo M. C.; Tomic, Welko

    This paper discusses the cultural-historical school founded by Vygotsky, Luria, and Leontiev as the theoretical background of Russian educational psychologists who have been studying how children learn to reflect. Two approaches to reflection are examined within the cultural-historical tradition: first, reflection--like other higher psychological…

  7. Bidirectional reflectance of zinc oxide

    Science.gov (United States)

    Scott, R.

    1973-01-01

    This investigation was undertaken to determine original and useful information about the bidirection reflectance of zinc oxide. The bidirectional reflectance will be studied for the spectra between .25-2.5 microns and the hemisphere above the specimen. The following factors will be considered: (1) surface conditions; (2) specimen preparation; (3) specimen substrate, (4) polarization; (5) depolarization; (6) wavelength; and (7) angles of incident and reflection. The bidirectional reflectance will be checked by experimentally determined angular hemispherical measurements or hemispherical measurements will be used to obtain absolute bidirectional reflectance.

  8. Reflective Fourier ptychography.

    Science.gov (United States)

    Pacheco, Shaun; Zheng, Guoan; Liang, Rongguang

    2016-02-01

    The Fourier ptychography technique in reflection mode has great potential applications in tissue imaging and optical inspection, but the current configuration either has a limitation on cut-off frequency or is not practical. By placing the imaging aperture stop outside the illumination path, the illumination numerical aperture (NA) can be greater than the imaging NA of the objective lens. Thus, the cut-off frequency achieved in the proposed optical system is greater than twice the objective's NA divided by the wavelength (2NAobj/λ ), which is the diffraction limit for the cut-off frequency in an incoherent epi-illumination configuration. We experimentally demonstrated that the synthesized NA is increased by a factor of 4.5 using the proposed optical concept. The key advantage of the proposed system is that it can achieve high-resolution imaging over a large field of view with a simple objective. It will have a great potential for applications in endoscopy, biomedical imaging, surface metrology, and industrial inspection.

  9. Organizations & development: epistemological reflections

    Directory of Open Access Journals (Sweden)

    Fernando Batista Bandeira Fontoura

    2016-01-01

    Full Text Available This theoretical test consists of an epistemic study on the nature and limits of relations between subject and society, from a historical context considering the pre-industrial and industrial macroperíodos and expanding post-industrial contexts. It emphasizes the conceptual and theoretical aspects of these macroperíodos highlighting the year 1970 as a symbol of the Taylor system crisis / Fordist contextualized by the automotive industry, which migrated from one-dimensional industrialization processes for multidimensional processes and customized beyond the advent of globalization and dispossession within a multimarket vision. Conclusively, the development models are still characterized by periods whose social concepts are linked to forms of perception of reality by man and their accumulation processes are entitled to this epistemic reflection on organizations and development and its social impacts, as well as the thesis crisis in still homogenizing mentality in economic and organizational terms in terms of environmental uncertainties macro and micro economic historically impacted the society and organizations.

  10. Venus Highland Anomalous Reflectivity

    Science.gov (United States)

    Simpson, Richard A.; Tyler, G. L.; Häusler, B.; Mattei, R.; Patzold, M.

    2009-09-01

    Maxwell Montes was one of several unusually bright areas identified from early Venus radar backscatter observations. Pioneer Venus' orbiting radar associated low emissivity with the bright areas and established a correlation between reflectivity and altitude. Magellan, using an oblique bistatic geometry, showed that the bright surface dielectric constant was not only large but also imaginary -- i.e., the material was conducting, at least near Cleopatra Patera (Pettengill et al., Science, 272, 1996). Venus Express (VEX) repeated Magellan's bistatic observations over Maxwell, using the more conventional circular polarization carried by most spacecraft. Although VEX signal-to-noise ratio was lower than Magellan's, echoes were sufficiently strong to verify the Magellan conclusions near Cleopatra (see J. Geophys. Res., 114, E00B41, doi:10.1029/2008JE003156). Only about 40% of the surface at Cleopatra scatters specularly, opening the Fresnel (specular) interpretation model to question. Elsewhere in Maxwell, the specular percentage may be even lower. Nonetheless, the echo polarization is reversed throughout Maxwell, a result that is consistent with large dielectric constants and difficult to explain without resorting qualitatively (if not quantitatively) to specular models. VEX was scheduled to explore other high altitude regions when its S-Band (13-cm wavelength) radio system failed in late 2006, so further probing of high altitude targets awaits arrival of a new spacecraft.

  11. Radial Reflection Diffraction Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, S K; Norton, S J

    2003-10-10

    We develop a wave-based tomographic imaging algorithm based upon a single rotating radially outward oriented transducer. At successive angular locations at a fixed radius, the transducer launches a primary field and collects the backscattered field in a ''pitch/catch'' operation. The hardware configuration, operating mode, and data collection method is identical to that of most medical intravascular ultrasound (IVUS) systems. IVUS systems form images of the medium surrounding the probe based upon ultrasonic B-scans, using a straight-ray model of sound propagation. Our goal is to develop a wave-based imaging algorithm using diffraction tomography techniques. Given the hardware configuration and the imaging method, we refer to this system as ''radial reflection diffraction tomography.'' We consider two hardware configurations: a multimonostatic mode using a single transducer as described above, and a multistatic mode consisting of a single transmitter and an aperture formed by multiple receivers. In this latter case, the entire source/receiver aperture rotates about the fixed radius. Practically, such a probe is mounted at the end of a catheter or snaking tube that can be inserted into a part or medium with the goal of forming images of the plane perpendicular to the axis of rotation. We derive an analytic expression for the multimonostatic inverse but ultimately use the new Hilbert space inverse wave (HSIW) algorithm to construct images using both operating modes. Applications include improved IVUS imaging, bore hole tomography, and non-destructive evaluation (NDE) of parts with existing access holes.

  12. Nonlocal reflection by photonic barriers

    OpenAIRE

    Vetter, R. -M.; A. Haibel; Nimtz, G.

    2001-01-01

    The time behaviour of microwaves undergoing partial reflection by photonic barriers was measured in the time and in the frequency domain. It was observed that unlike the duration of partial reflection by dielectric layers, the measured reflection duration of barriers is independent of their length. The experimental results point to a nonlocal behaviour of evanescent modes at least over a distance of some ten wavelengths. Evanescent modes correspond to photonic tunnelling in quantum mechanics.

  13. Polarimetric Control of Reflective Metasurfaces

    CERN Document Server

    Artiga, Xavier; Legay, Hervé; Perruisseau-Carrier, Julien

    2012-01-01

    This letter addresses the synthesis of reflective cells approaching a given desired Floquet's scattering matrix. This work is motivated by the need to obtain much finer control of reflective metasurfaces by controlling not only their co-polarized reflection but also their cross-coupling behavior. The demonstrated capability will enable more powerful design approaches -involving all field components in phase and magnitude- and consequently better performance in applications involving reflective metasurfaces. We first expose some fundamental theoretical constraints on the cell scattering parameters. Then, a successful procedure for controlling all four scattering parameters by applying parallelogram and trapezoid transformations to square patches is presented, considering both normal and oblique incidence.

  14. Students’ Learning through Reflective Journaling

    Directory of Open Access Journals (Sweden)

    Alvyda Liuolienė

    2011-04-01

    Full Text Available The aim of the article is to get acquainted with the types of journals used in education to help students to learn. The paper presents some ways of fostering student’s learning through reflective journaling. It also describes the key aspects of a new method ARRIVE cycle in connection with teachers preparation to use reflective journals in a classroom. The article also presents self-assessment in reflective journaling and students’ need to self-evaluate their learning process. Reflective journaling as central to students’ self-evaluation is described as a means of fostering metacognition.

  15. Studies of the Reflection, Refraction and Internal Reflection of Light

    Science.gov (United States)

    Lanchester, P. C.

    2014-01-01

    An inexpensive apparatus and associated experiments are described for studying the basic laws of reflection and refraction of light at an air-glass interface, and multiple internal reflections within a glass block. In order to motivate students and encourage their active participation, a novel technique is described for determining the refractive…

  16. Postgraduate Education to Support Organisation Change: A Reflection on Reflection

    Science.gov (United States)

    Stewart, Jim; Keegan, Anne; Stevens, Pam

    2008-01-01

    Purpose: This paper aims to explore how teaching and assessing reflective learning skills can support postgraduate practitioners studying organisational change and explores the challenges for tutors in assessing these journals. Design/methodology/approach: Assessment criteria were developed from the literature on reflective practice and…

  17. Audible reflection density for different late reflection criteria in rooms

    DEFF Research Database (Denmark)

    Krueger, Donata; Jeong, Cheol-Ho; Brunskog, Jonas

    2012-01-01

    only specular reflections. Therefore in this study, the upper threshold for audible reflection density is investigated for four different transition times of 25, 50, 75, and 100 ms through a headphone listening test. Binaural impulse responses and speech signals simulated in three rooms with different...

  18. Reflecting on the History, Ethics, and Application of Teacher Reflection.

    Science.gov (United States)

    Hankes, Judith Elaine

    Three social factors are related to the evolution of the discourse on teacher reflection: the role of educational researchers and teacher educators; the social and economic crisis and its impact on education; and the shift from behaviorism to cognitivism. By relating the discourse of teacher change through reflection to these social factors, it…

  19. Ubuntu feminism: Tentative reflections

    Directory of Open Access Journals (Sweden)

    Drucilla Cornell

    2015-06-01

    Full Text Available The starting-point for the article is to provide a brief background on the Ubuntu Project that Prof. Drucilla Cornell convened in 2003; most notably the interviews conducted in Khayamandi, the support of a sewing collective, and the continued search to launch an Ubuntu Women�s Centre. The article will reflect on some of the philosophical underpinnings of ubuntu, whereafter debates in Western feminism will be revisited. Ubuntu feminism is suggested as a possible response to these types of feminisms. The authors support an understanding of ubuntu as critique and ubuntu feminism accordingly as a critical intervention that recalls a politics of refusal. The article ends by raising the importance of thinking about spatiality through ubuntu, and vice versa. It may seem strange to title an article Ubuntu feminism when feminism itself has often been identified as a European or Western idea. But, this article will argue that ubuntu offers conceptions of transindividuality and ways of social belonging that could respond in a meaningful way to some of European feminism�s own dilemmas and contradictions. Famously, one of the most intense debates in feminism was between those who defended an ethic of care in a relational view of the self, on one side, and those feminists who held on to more traditional conceptions of justice, placing an emphasis on individuality and autonomy, on the other side. The authors will suggest that ubuntu could address this tension in feminism. Thus, in this article the focus will not simply be on ubuntu, in order to recognise that there are other intellectual heritages worthy of consideration, other than those in Europe and the United States. It will also take a next step in arguing that ubuntu may be a better standpoint entirely from which to continue thinking about what it means to be a human being, as well as how to conceive of the integral interconnection human beings all have with one another. This connection through

  20. Ethical Reflections on Becoming Teachers

    Science.gov (United States)

    Joseph, Pamela Bolotin

    2016-01-01

    This study analyzes narratives written in a culminating graduate seminar on reflective practice by 36 new secondary teachers who were asked to consider their moral beliefs, moral values and system of ethics as they reflected on their recent student teaching experiences. The findings explore how the participants depicted their constructed moral…

  1. Flexible Bistable Cholesteric Reflective Displays

    Science.gov (United States)

    Yang, Deng-Ke

    2006-03-01

    Cholesteric liquid crystals (ChLCs) exhibit two stable states at zero field condition-the reflecting planar state and the nonreflecting focal conic state. ChLCs are an excellent candidate for inexpensive and rugged electronic books and papers. This paper will review the display cell structure,materials and drive schemes for flexible bistable cholesteric (Ch) reflective displays.

  2. Reflection algebra and functional equations

    NARCIS (Netherlands)

    Galleas, W.; Lamers, J.

    2014-01-01

    In this work we investigate the possibility of using the reflection algebra as a source of functional equations. More precisely, we obtain functional relations determining the partition function of the six-vertex model with domain-wall boundary conditions and one reflecting end. The model's partitio

  3. A Review of Reflective Learning

    Institute of Scientific and Technical Information of China (English)

    刘屹

    2013-01-01

      This thesis aims at exploring theoretical basis of reflective learning in learning experience and providing the learners from all walks of life with an effective way of learning by observing and explaining how the learning as well as practice is promoted effectively and consciously through reflective activities.

  4. Why Reflection in Teacher Education?

    Science.gov (United States)

    LaBoskey, Vicki Kubler

    1993-01-01

    Focuses on preservice teacher education by considering teacher reflectivity as an end rather than a means. The article provides a rationale for reflective teacher education in arguing the need to have teachers who are thoughtful, passionate, and principled educational decision makers. (GLR)

  5. A reflection polarizations zoom metasurfaces

    Science.gov (United States)

    Yang, Fulong; Wang, Xiaoyan

    2017-02-01

    Based on generalized Snell's law, we propose a dual-polarity zoom metasurfaces operating electromagnetic wave in the reflection geometry. The metasurfaces is constructed by two identical ultrathin metal-backed dielectric slabs with metallic Jerusalem cross patterns on the other sides to form a triangular region. The normally incident waves are totally reflected, but the reflection phases of both x- and y-polarized waves are controlled independently. According to the classical theory of optical imaging, the reflection electromagnetic wave phases were obtained in the different polarizations and focus. Each subwavelength units size were determined with the reflection coefficient of the basic unit, the polarizations zoom metasurfaces was designed in the way. The full-wave simulations are in good agreement with theoretical analysis in microwave lengths.

  6. Non-specular Reflective Optics

    CERN Document Server

    Datta, Timir; Wang, Yunjin; Wescott, Michael; Foster, Richard; Bowers, Rebecca

    2009-01-01

    Geometrically decorated two-dimensional (2D) discrete surfaces can be more effective than conventional smooth reflectors in managing wave radiation. Constructive non-specular wave scattering permits the scattering angle to be other than twice that of incidence and can result in gross violations of the law of reflection. Hence significant fraction of the phase space becomes accessible. A wide range of novel reflective behaviors ensues; including the phenomenon of negative reflection were energy transport remains on the same side of the normal. Also, at a critical incidence coherent superposition can force both the transmitted and reflected waves to graze the scattering surface thus synergistically reinforcing the diffractive process in a behavior reminiscent of critical internal reflection of ray optics. We experimentally demonstrate the concept with measurements on a one-dimensionally periodic system (grating) where the scattering angle is shown to be an inverse circular function of a function that depends on...

  7. Intergenerational transmission of reflective functioning

    Directory of Open Access Journals (Sweden)

    Anna Maria Rosso

    2016-12-01

    Full Text Available The present study investigated whether, and to what extent, reflective functioning (RF during preadolescence is associated with maternal attachment security and reflective functioning, and with the child’s attachment security. Thirty-nine mother-preadolescent child dyads from a non clinical population participated in the study. Maternal and child RF were assessed by applying the Reflective Functioning Scale (RFS to the Adult Attachment Interview (AAI and to the Child Attachment Interview (CAI transcripts. Children of mothers who showed a secure attachment model regarding the relationship with their parents during childhood reported higher levels of RF than the children of mothers who were classified as insecure on the AAI. Child RF was positively associated with maternal Coherence of the Mind on the AAI and negatively associated with maternal derogation of attachment.A strong, significant association was also found between child attachment security and child reflective functioning. Children who were rated as being more emotionally open, more able to balance positive and negative descriptions of their parents, more prone to support their assertions through examples, and more able to positively resolve conflicts with their parents showed higher reflective functioning. On the contrary, children who resorted to a higher extent to idealization and dismissal towards their parents showed a lesser degree of reflective functioning. Notably, a very strong association was found between the score on the Overall coherence subscale and the child’s ability to mentalise mixed-ambivalent mental states in the context of their family relationships.As expected, child and maternal reflective functioning resulted significantly positively correlated with each other. In particular, only maternal reflective functioning (and not maternal attachment security predicted child reflective functioning, and only maternal ability to mentalise mixed-ambivalent mental states

  8. Terahertz wide aperture reflection tomography

    Science.gov (United States)

    Pearce, Jeremy; Choi, Hyeokho; Mittleman, Daniel M.; White, Jeff; Zimdars, David

    2005-07-01

    We describe a powerful imaging modality for terahertz (THz) radiation, THz wide aperture reflection tomography (WART). Edge maps of an object's cross section are reconstructed from a series of time-domain reflection measurements at different viewing angles. Each measurement corresponds to a parallel line projection of the object's cross section. The filtered backprojection algorithm is applied to recover the image from the projection data. To our knowledge, this is the first demonstration of a reflection computed tomography technique using electromagnetic waves. We demonstrate the capabilities of THz WART by imaging the cross sections of two test objects.

  9. LEARNER REFLECTION IN PORTFOLIO ASSESSMENT

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The traditional English teaching method makes students feeltoo serious,nervous and formal.Learner reflection in portfolioassessment can increase opportunities for dialogues betweenteachers and students about curriculum goals and learnerprogress,which is very important to provide a healthy,harmonious and democratic situation in English teaching forstudents.This paper analyses some benefits of learner reflectionin portfolios and focuses on how to design reflective tasks for theportfolio.It is obvious that learner reflection is good for bothteachers and students to improve their teaching and studyingmethods as well as to enhance the teaching quality.

  10. Stress and reproductive hormones reflect inter-specific social and nutritional conditions mediated by resource availability in a bear–salmon system

    Science.gov (United States)

    Bryan, Heather M.; Darimont, Chris T.; Paquet, Paul C.; Wynne-Edwards, Katherine E.; Smits, Judit E. G.

    2014-01-01

    for evaluating the responses of a broad spectrum of wildlife to changes in food availability or other environmental conditions. PMID:27293631

  11. Methodological Reflections: Inter- ethnic Research

    DEFF Research Database (Denmark)

    Singla, Rashmi

    2010-01-01

    This article reflects on the methodological and epistemological aspects of the ethical issues involved in encounters between researcher and research participants with ethnic minority background in contexts with diversity. Specific challenges involved in longitudinal research (10 - 15 years) are a...

  12. Exports reflect "safety of products"

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Most of the made-in-China products are absolutely safe, and the steady increase in exports despite the recent widespread criticism reflects their safety standards, a Ministry of Commerce official said Thursday.

  13. Specular Andreev reflection in graphene.

    Science.gov (United States)

    Beenakker, C W J

    2006-08-11

    By combining the Dirac equation of relativistic quantum mechanics with the Bogoliubov-de Gennes equation of superconductivity we investigate the electron-hole conversion at a normal-metal-superconductor interface in graphene. We find that the Andreev reflection of Dirac fermions has several unusual features: (1) the electron and hole occupy different valleys of the band structure; (2) at normal incidence the electron-hole conversion happens with unit efficiency in spite of the large mismatch in Fermi wavelengths at the two sides of the interface; and, most fundamentally: (3) away from normal incidence the reflection angle may be the same as the angle of incidence (retroreflection) or it may be inverted (specular reflection). Specular Andreev reflection dominates in weakly doped graphene, when the Fermi wavelength in the normal region is large compared to the superconducting coherence length.

  14. Worldwide Marine Seismic Reflection Profiles

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NGDC maintains a large volume of both Analog and Digital seismic reflection data. Currently only a limited number of lines are available online. Digital data include...

  15. Reflections on intuition and expertise.

    Science.gov (United States)

    Perry, M A

    2000-01-01

    Reflective practice now appears firmly established in the English speaking world of professional nursing practice and development. Outside this linguistic context, however, the concept seems less well-known. This paper describes an experience drawn from clinical practice and education in French-speaking Switzerland followed by explicit reflection grounded in questions generated by Johns' model for structured reflection. Thus, a concept well-described in the English-language literature underpins an innovative approach to a French-language clinical teaching situation. The professional implications of this situation are explored through meaningful reflection providing new insight into familiar circumstances as they relate to the nurse tutor's role. This exploration is followed by a critical approach to the experience and the subsequent structured reflection in order to address relationships between intuition and expertise and self-awareness through reflection. A hermeneutic perspective provides additional insight into the nurse-patient relationship where both come to the situation with their own 'pre-understandings'. Individual horizons thus endorse a new understanding going beyond taken-for-granted meanings.

  16. Reflections

    OpenAIRE

    Kennedy, Mary B

    2008-01-01

    In the two decades after the founding of Neuron, we witnessed the unfolding of the “molecular biology revolution” and its culmination in the sequencing of individual genomes. Cloning of cDNAs and rapid nucleotide sequencing were invented in the early 1970s. By the mid-1980s, “cDNA-cloning” was all the rage. A new breed of “molecular neuroscientists” began cloning and sequencing transcripts encoding neuronal receptors, ion channels, and signaling enzymes. The wealth of molecular data they gene...

  17. Reflections

    DEFF Research Database (Denmark)

    du Gay, Paul; Vikkelsø, Signe

    2012-01-01

    -readings of two classic, but partially forgotten contributions within organization theory – the work of Wilfred R. Bion on group assumptions and the work of Elliott Jaques on ‘requisite organisation’ – we suggest that contemporary discussion of organizational change could benefit considerably from regaining...

  18. Reflections

    Science.gov (United States)

    Greiner, Walter

    2012-01-01

    This symposium was very special. It was topical: Some of the most outstanding problems in Nuclear Physics were discussed: Superheavy elements; extremely neutron rich elements, as well as nuclei with strangeness and their possible creation in the cosmos and on earth; the nuclear equation of state has to be identified within strongly compressed and hot nuclear matter as it appears in nucleus-nucleus encounters; giant nuclear systems which are short lived (˜ 10-19 - 10-20 seconds) and extremely important for identifying the vacuum decay in overcritical electric fields (this is a very fundamental process - the most fundamental one in Quantum Electrodynamics!); astrophysical centers of extreme high density around which magnificent sun-like objects are Kepler-orbiting are discovered in our Galaxy by R. Genzel and colleagues (these centers are no black holes those don't exist at all because repulsive gravitational forces may play an important role - the pseudocomplex general relativity eliminates the Schwarzschild singularity); network physics for distributing energy (nuclear, wind, sun, tides,...) all over Europe (and over the world) is basic for energy consumption now and even more so in future. We heard wonderful talks and I am grateful to all the friends and speakers (from Russia, America, Europe and India) for coming to Goa. It was a great symposium! Particular thanks go to Professor Bikash Sinha and especially to Professor Debades Bandyopadhyay from Calcutta who had the idea for and organized this Goa-symposium....

  19. Reflectance spectra of subarctic lichens

    Science.gov (United States)

    Petzold, Donald E.; Goward, Samuel N.

    1988-01-01

    Lichens constitute a major portion of the ground cover of high latitude environments, but little has been reported concerning their in situ solar spectral reflectance properties. Knowledge of these properties is important for the interpretation of remotely sensed observations from high latitude regions, as well as in studies of high latitude ecology and energy balance climatology. The spectral reflectance of common boreal vascular plants is similar to that of vascular plants of the midlatitudes. The dominant lichens, in contrast, display variable reflectance patterns in visible wavelengths. The relative reflectance peak at 0.55 microns, common to green vegetation, is absent or indistinct in spectra of pervasive boreal forest and tundra lichens, despite the presence of chlorophyll in the inner algal cells. Lichens of the dominant genus, Cladina, display strong absorption of ultraviolet energy and short-wavelength blue light relative to their absorption in other visible wavelengths. Since the Cladinae dominate both the surface vegetation in open woodlands of the boreal forest and the low arctic tundra, their unusual spectral reflectance patterns will enable accurate monitoring of the boreal forest-tundra ecotone and detection of its vigor and movement in the future.

  20. External observer reflections on QBism

    CERN Document Server

    Khrennikov, Andrei

    2015-01-01

    In this short review I present my personal reflections on QBism. I have no intrinsic sympathy neither to QBism nor to subjective interpretation of probability in general. However, I have been following development of QBism from its very beginning, observing its evolution and success, sometimes with big surprise. Therefore my reflections on QBism can be treated as "external observer" reflections. I hope that my representation of this interpretation of quantum mechanics (QM) has some degree of objectivity. It may be useful for researchers who are interested in quantum foundations, but do not belong to the QBism-community, because I tried to analyze essentials of QBism critically (i.e., not just emphasizing its advantages, as in a typical publication of QBists). QBists may be interested as well - in comments of an external observer who monitored development of this approach to QM during last 16 years. The second part of the paper is devoted to interpretations of probability, objective versus subjective, and view...