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Sample records for broad-spectrum therapeutics discovering

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

    Directory of Open Access Journals (Sweden)

    de Rochefort Anna

    2009-10-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-09-20

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

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

    Science.gov (United States)

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

    2016-06-01

    Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. PMID:26959835

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

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    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

  6. 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.

  7. 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.

  8. 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...

  9. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

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

  10. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  14. Genetically Engineered Broad-Spectrum Disease Resistance in Tomato

    Science.gov (United States)

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

    1998-08-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2016-03-01

    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. PMID:26551316

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Frey Jürg E

    2010-02-01

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

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

    Science.gov (United States)

    Pletzer, Daniel; Hancock, Robert E W

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Francisco Alvarez-Lerma

    2009-05-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

    Fünfgeld, E W

    1989-01-01

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

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

    Science.gov (United States)

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

    2016-05-10

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

  5. 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.

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

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    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.

  7. 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.

  8. 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.

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

    OpenAIRE

    Iyer, Rupa; Damania, Ashish

    2016-01-01

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

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

    OpenAIRE

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hadi Sardarabadi

    2014-08-01

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

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

    Science.gov (United States)

    Iyer, Rupa; Damania, Ashish

    2016-01-01

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

  13. 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...

  14. 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

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

    Science.gov (United States)

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

    2015-08-01

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

  16. 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...

  17. 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.

  18. 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.

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

    OpenAIRE

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

    2006-01-01

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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Amy L Caroline

    2014-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Carine Huard-Chauveau

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

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

    OpenAIRE

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

    2010-01-01

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

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

    Science.gov (United States)

    Rucklidge, Julia J; Kaplan, Bonnie J

    2014-09-01

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

  5. 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.

  6. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Combination therapy with several antibiotics is one strategy that has been applied in order to limit the spread of antimicrobial resistance. We compared the de novo evolution of resistance during combination therapy with the β-lactam ceftazidime and the fluoroquinolone ciprofloxacin...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  8. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  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. 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

  12. 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

  13. 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

  14. 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.

  15. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics

    OpenAIRE

    Si-Yuan Pan; Shu-Feng Zhou; Si-Hua Gao; Zhi-Ling Yu; Shuo-Feng Zhang; Min-Ke Tang; Jian-Ning Sun; Dik-Lung Ma; Yi-Fan Han; Wang-Fun Fong; Kam-Ming Ko

    2013-01-01

    With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, ...

  16. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics

    Science.gov (United States)

    Pan, Si-Yuan; Zhou, Shu-Feng; Gao, Si-Hua; Yu, Zhi-Ling; Zhang, Shuo-Feng; Tang, Min-Ke; Sun, Jian-Ning; Han, Yi-Fan; Fong, Wang-Fun; Ko, Kam-Ming

    2013-01-01

    With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is “experience driven,” the search for a therapeutically useful synthetic drug, like “looking for a needle in a haystack,” is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development. PMID:23634172

  17. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics

    Directory of Open Access Journals (Sweden)

    Si-Yuan Pan

    2013-01-01

    Full Text Available With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is “experience driven,” the search for a therapeutically useful synthetic drug, like “looking for a needle in a haystack,” is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.

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

    Directory of Open Access Journals (Sweden)

    Masters KP

    2009-09-01

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

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

    OpenAIRE

    Hawkins, Denise; Abrahamse, Heidi

    2007-01-01

    Objective. This study aimed to establish if broad-spectrum or infrared (IR) light in combination with laser therapy can assist phototherapy to improve the cell function of wounded cells. Background. The effect of laser light may be partly or completely reduced by broad-spectrum light. Methods. Wounded human skin fibroblasts were irradiated with 5 J/cm2 using a helium-neon laser, a diode laser, or an Nd:YAG laser in the dark, in the light, or in IR. Changes in cell viability were evaluated by ...

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

    OpenAIRE

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Wai-Leung Ng

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

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

    Science.gov (United States)

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

    2009-05-01

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

  4. 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.

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

    Science.gov (United States)

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

    1998-06-18

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

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

    Directory of Open Access Journals (Sweden)

    Saurabh Bhatia

    2010-01-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

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

    2012-01-01

    Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives. PMID:22761573

  9. 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

  10. 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.

  11. 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

  12. 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...

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

    OpenAIRE

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-01-20

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

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

    Directory of Open Access Journals (Sweden)

    Shallu eThakur

    2015-05-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  18. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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.

  2. 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.

  3. 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

  4. 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.

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

    Science.gov (United States)

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

    2016-06-01

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

  6. 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.

  7. 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

  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. 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.

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

    International Nuclear Information System (INIS)

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO3)2/0.04 M H3PO4.12MoO3/4 M HNO3 solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

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

    International Nuclear Information System (INIS)

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

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-08-15

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

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2016-05-13

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

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

    Science.gov (United States)

    Zeder, Melinda A.; Spitzer, Megan D.

    2016-11-01

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

  18. 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.

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

    Science.gov (United States)

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

    2010-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. PMID:26850850

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  5. 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.

  6. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-06

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-02-15

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

  10. 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.

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

    Science.gov (United States)

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

    2014-01-29

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  15. 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

  16. Conjugation of a nonspecific antiviral sapogenin with a specific HIV fusion inhibitor: a promising strategy for discovering new antiviral therapeutics.

    Science.gov (United States)

    Wang, Chao; Lu, Lu; Na, Heya; Li, Xiangpeng; Wang, Qian; Jiang, Xifeng; Xu, Xiaoyu; Yu, Fei; Zhang, Tianhong; Li, Jinglai; Zhang, Zhenqing; Zheng, Baohua; Liang, Guodong; Cai, Lifeng; Jiang, Shibo; Liu, Keliang

    2014-09-11

    Triterpene saponins are a major group of active components in natural products with nonspecific antiviral activities, while T20 peptide (enfuvirtide), which contains a helix zone-binding domain (HBD), is a gp41-specific HIV-1 fusion inhibitor. In this paper, we report the design, synthesis, and structure-activity relationship (SAR) of a group of hybrid molecules in which bioactive triterpene sapogenins were covalently attached to the HBD-containing peptides via click chemistry. We found that either the triterpenes or peptide part alone showed weak activity against HIV-1 Env-mediated cell-cell fusion, while the hybrids generated a strong cooperative effect. Among them, P26-BApc exhibited anti-HIV-1 activity against both T20-sensitive and -resistant HIV-1 strains and improved pharmacokinetic properties. These results suggest that this scaffold design is a promising strategy for developing new HIV-1 fusion inhibitors and possibly novel antiviral therapeutics against other viruses with class I fusion proteins. PMID:25156906

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

    Directory of Open Access Journals (Sweden)

    Vincent E de Meijer

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

  18. 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

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

    OpenAIRE

    Khedr MA

    2015-01-01

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

  20. 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...

  1. 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.

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

    OpenAIRE

    Kaier, Klaus

    2010-01-01

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

  3. Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins

    OpenAIRE

    Sinha, Sharmistha; Lopes, Dahabada H. J.; Du, Zhenming; Pang, Eric S.; Shanmugam, Akila; Lomakin, Aleksey; Talbiersky, Peter; Tennstaedt, Annette; McDaniel, Kirsten; Bakshi, Reena; Kuo, Pei-Yi; Ehrmann, Michael; Benedek, George B.; Loo, Joseph A.; Klärner, Frank-Gerrit

    2011-01-01

    Amyloidoses are diseases characterized by abnormal protein folding and self-assembly, for which no cure is available. Inhibition or modulation of abnormal protein self-assembly therefore is an attractive strategy for prevention and treatment of amyloidoses. We examined Lys-specific molecular tweezers and discovered a lead compound termed CLR01, which is capable of inhibiting the aggregation and toxicity of multiple amyloidogenic proteins by binding to Lys residues and disrupting hydrophobic a...

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

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

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

  5. Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Sabrina Lusvarghi

    2016-10-01

    Full Text Available Griffithsin (GRFT, an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.

  6. 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.

  7. 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.

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

    Science.gov (United States)

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

    2014-07-01

    Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process. PMID:24777097

  9. Discover Earth

    Science.gov (United States)

    Steele, Colleen

    1998-01-01

    Discover Earth is a NASA-sponsored project for teachers of grades 5-12, designed to: (1) enhance understanding of the Earth as an integrated system; (2) enhance the interdisciplinary approach to science instruction; and (3) provide classroom materials that focus on those goals. Discover Earth is conducted by the Institute for Global Environmental Strategies in collaboration with Dr. Eric Barron, Director, Earth System Science Center, The Pennsylvania State University; and Dr. Robert Hudson, Chair, the Department of Meteorology, University of Maryland at College Park. The enclosed materials: (1) represent only part of the Discover Earth materials; (2) were developed by classroom teachers who are participating in the Discover Earth project; (3) utilize an investigative approach and on-line data; and (4) can be effectively adjusted to classrooms with greater/without technology access. The Discover Earth classroom materials focus on the Earth system and key issues of global climate change including topics such as the greenhouse effect, clouds and Earth's radiation balance, surface hydrology and land cover, and volcanoes and climate change. All the materials developed to date are available on line at (http://www.strategies.org) You are encouraged to submit comments and recommendations about these materials to the Discover Earth project manager, contact information is listed below. You are welcome to duplicate all these materials.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Chi-Chieh Huang

    2014-06-01

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

  12. 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

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

    Science.gov (United States)

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

    2016-01-01

    Clostridium difficile (C. difficile) infection (CDI) is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA), and cytotoxin, toxin B (TcdB), which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4) and anti-TcdB (CANmAbB4 and CANmAbB1) antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail) provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively) in a hamster gastrointestinal infection (GI) model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI. PMID:27336843

  14. 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.

  15. 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.

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

    Science.gov (United States)

    Jagota, S C

    1986-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  18. 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.

  19. 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.

  20. 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.

  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. 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.

  3. Discovering Technicolor

    DEFF Research Database (Denmark)

    R. Andersen, J.; Antipin, O.; Azuelos, G.;

    2011-01-01

    We provide a pedagogical introduction to extensions of the Standard Model in which the Higgs is composite. These extensions are known as models of dynamical electroweak symmetry breaking or, in brief, Technicolor. Material covered includes: motivations for Technicolor, the construction of underly...... the relevant experimental benchmarks for Vanilla, Running, Walking, and Custodial Technicolor, and a natural fourth family of leptons, by laying out the framework to discover these models at the Large Hadron Collider....... of underlying gauge theories leading to minimal models of Technicolor, the comparison with electroweak precision data, the low energy effective theory, the spectrum of the states common to most of the Technicolor models, the decays of the composite particles and the experimental signals at the Large Hadron...... Collider. The level of the presentation is aimed at readers familiar with the Standard Model but who have little or no prior exposure to Technicolor. Several extensions of the Standard Model featuring a composite Higgs can be reduced to the effective Lagrangian introduced in the text. We establish...

  4. 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.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

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

  7. 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.

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

    Science.gov (United States)

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

    2013-08-15

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

  9. 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.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2003-08-01

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

  12. 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.

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

    Science.gov (United States)

    Mamy, Laure; Barriuso, Enrique; Gabrielle, Benoît

    2005-09-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  16. Therapeutic drug monitoring of amoxicillin and cloxacillin

    Institute of Scientific and Technical Information of China (English)

    OTRIBUT; PTATTEVIN; MVERDIER; YLETULZO; CMICELET; HALLAIN; DBENTURE-FERRER

    2004-01-01

    AIM: Beta-lactams (BL) are broad-spectrum antibiotics currently used in number of infectious diseases and some infections need high dose of antibiotics. BL studied here are eliminated rather quickly by the kidney. A renal insufficiency involves an increase in BL concentrations. Therapeutic drug monitoring could help in adapting the target concentration. METHODS: We developed a rapid (less than 20 min), sensitive, and specific HPLC method

  17. 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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Background Host defense peptides (HDPs), or antimicrobial peptides (AMPs), are important components of the innate immune system that bacterial pathogens must overcome to establish an infection and HDPs have been suggested as novel antimicrobial therapeutics in treatment of infectious diseases......-type, and phenotypic behavior. Strains within each species were equally sensitive to HDPs and oxidative stress representing important components of the innate immune defense system. Four non-human peptides (protamine, plectasin, novicidin, and novispirin G10) were similar in activity profile (MIC value spectrum...

  19. Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications.

    Science.gov (United States)

    Gudiña, Eduardo J; Teixeira, José A; Rodrigues, Lígia R

    2016-02-18

    Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens), and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics) constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments.

  20. Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    Eduardo J. Gudiña

    2016-02-01

    Full Text Available Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens, and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments.

  1. Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications.

    Science.gov (United States)

    Gudiña, Eduardo J; Teixeira, José A; Rodrigues, Lígia R

    2016-02-01

    Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens), and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics) constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments. PMID:26901207

  2. The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes.

    Science.gov (United States)

    Xu, Weisi; Zhao, Jianxiong; Sun, Jianping; Yin, Qianqian; Wang, Yan; Jiao, Yang; Liu, Junyi; Jiang, Shibo; Shao, Yiming; Wang, Xiaowei; Ma, Liying

    2015-08-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of the highly active antiretroviral therapy (HAART) used to treat human immunodeficiency type 1 virus (HIV-1). However, because of the emergence of drug resistance and the adverse effects of current anti-HIV drugs, it is essential to develop novel NNRTIs with an excellent safety profile, improved activity against NNRTI-resistant viruses, and enhanced activity against clinical isolates of different subtypes. Here, we have identified 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dione (WPR-6), a novel NNRTI with a 50% effective concentration (EC50) of 2 to 4 nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391 with a therapeutic index of >1 × 10(4). A panel of five representative clinical virus isolates of different subtypes circulating predominantly in China was highly sensitive to WPR-6, with EC50s ranging from 1 to 6 nM. In addition, WPR-6 showed excellent antiviral potency against the most prevalent NNRTI-resistant viruses containing the K103N and Y181C mutations. To determine whether WPR-6 selects for novel resistant mutants, in vitro resistance selection was conducted with laboratory-adapted HIV-1 strain SF33 on MT-4 cells. The results demonstrated that V106I and Y188L were the two dominant NNRTI-associated resistance mutations detected in the breakthrough viruses. Taken together, these in vitro data indicate that WPR-6 has greater efficacy than the reference HEPT analogue TNK651 and the marketed drug nevirapine against HIV-1. However, to develop it as a new NNRTI, further improvement of its pharmacological properties is warranted. PMID:26055365

  3. Broad-spectrum pollination of Plectranthus neochilus

    Directory of Open Access Journals (Sweden)

    C. H. Stirton

    1977-12-01

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

  4. 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.

  5. 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.

  6. Wnt/β-catenin signaling in melanoma: Preclinical rationale and novel therapeutic insights.

    Science.gov (United States)

    Xue, Gongda; Romano, Emanuela; Massi, Daniela; Mandalà, Mario

    2016-09-01

    WNT signaling regulates embryonic development and tissue homeostasis in the adult stage. Evolutionarily, activation of the WNT pathway is triggered by a large family of cytokines and activates a broad spectrum of downstream targets through two independent branches mediated by β-catenin (defined as canonical pathway) or PLC and small GTPase (defined as non-canonical pathway), respectively. Recent studies revealed the crucial role of WNT in the maintenance of cell metabolism and stemness as well as its deregulation in tumourigenesis and malignant transformation through oncogenic reprogramming, which contributes to cancer cell proliferation and differentiation, survival, stress response and resistance. In addition, multiple functional mutations discovered in human tumours have been reported to cause malignancy, indicating this pathway as a novel therapeutic target in oncology. Notably, emerging data highlights its involvement in the crosstalk between immune and cancer cells. However, contradictory effects have been also observed in different pre-clinical models when strategic(???) inhibitors are tested. In this review, we address the multifaceted regulatory mechanisms of WNT signaling in cancer, with a particular focus on current melanoma therapy, which has witnessed dramatic improvement in the last five years. PMID:27395773

  7. 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

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

    Institute of Scientific and Technical Information of China (English)

    宗光全; 张茂红; 章冠东; 杜庆安

    2001-01-01

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

  9. 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.

  10. 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.

  11. New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

    Directory of Open Access Journals (Sweden)

    Robert H E Friesen

    Full Text Available BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach

  12. Discovering the Solar System

    Science.gov (United States)

    Jones, Barrie W.

    1999-04-01

    Discovering the Solar System Barrie W. Jones The Open University, Milton Keynes, UK Discovering the Solar System is a comprehensive, up-to-date account of the Solar System and of the ways in which the various bodies have been investigated and modelled. The approach is thematic, with sequences of chapters on the interiors of planetary bodies, on their surfaces, and on their atmospheres. Within each sequence there is a chapter on general principles and processes followed by one or two chapters on specific bodies. There is also an introductory chapter, a chapter on the origin of the Solar System, and a chapter on asteroids, comets and meteorites. Liberally illustrated with diagrams, black and white photographs and colour plates, Discovering the Solar System also features: * tables of essential data * question and answers within the text * end of section review questions with answers and comments Discovering the Solar System is essential reading for all undergraduate students for whom astronomy or planetary science are components of their degrees, and for those at a more advanced level approaching the subject for the first time. It will also be of great interest to non-specialists with a keen interest in astronomy. A small amount of scientific knowledge is assumed plus familiarity with basic algebra and graphs. There is no calculus. Praise for this book includes: ".certainly qualifies as an authoritative text. The author clearly has an encyclopedic knowledge of the subject." Meteorics and Planetary Science ".liberally doused with relevant graphs, tables, and black and white figures of good quality." EOS, Transactions of the American Geophysical Union ".one of the best books on the Solar System I have seen. The general accuracy and quality of the content is excellent." Journal of the British Astronomical Association

  13. 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.

  14. Students Discover Unique Planet

    Science.gov (United States)

    2008-12-01

    Three undergraduate students, from Leiden University in the Netherlands, have discovered an extrasolar planet. The extraordinary find, which turned up during their research project, is about five times as massive as Jupiter. This is also the first planet discovered orbiting a fast-rotating hot star. Omega Centauri ESO PR Photo 45a/08 A planet around a hot star The students were testing a method of investigating the light fluctuations of thousands of stars in the OGLE database in an automated way. The brightness of one of the stars was found to decrease for two hours every 2.5 days by about one percent. Follow-up observations, taken with ESO's Very Large Telescope in Chile, confirmed that this phenomenon is caused by a planet passing in front of the star, blocking part of the starlight at regular intervals. According to Ignas Snellen, supervisor of the research project, the discovery was a complete surprise. "The project was actually meant to teach the students how to develop search algorithms. But they did so well that there was time to test their algorithm on a so far unexplored database. At some point they came into my office and showed me this light curve. I was completely taken aback!" The students, Meta de Hoon, Remco van der Burg, and Francis Vuijsje, are very enthusiastic. "It is exciting not just to find a planet, but to find one as unusual as this one; it turns out to be the first planet discovered around a fast rotating star, and it's also the hottest star found with a planet," says Meta. "The computer needed more than a thousand hours to do all the calculations," continues Remco. The planet is given the prosaic name OGLE2-TR-L9b. "But amongst ourselves we call it ReMeFra-1, after Remco, Meta, and myself," says Francis. The planet was discovered by looking at the brightness variations of about 15 700 stars, which had been observed by the OGLE survey once or twice per night for about four years between 1997 and 2000. Because the data had been made public

  15. Discovering system requirements

    Energy Technology Data Exchange (ETDEWEB)

    Bahill, A.T.; Bentz, B. [Univ. of Arizona, Tucson, AZ (United States). Systems and Industrial Engineering; Dean, F.F. [Sandia National Labs., Albuquerque, NM (United States)

    1996-07-01

    Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirements process. This report provides a high-level overview of the system requirements process, explaining types, sources, and characteristics of good requirements. System requirements, however, are seldom stated by the customer. Therefore, this report shows ways to help you work with your customer to discover the system requirements. It also explains terminology commonly used in the requirements development field, such as verification, validation, technical performance measures, and the various design reviews.

  16. Discovering Phonemes of Bidayuh

    Directory of Open Access Journals (Sweden)

    Jecky Misieng

    2012-07-01

    Full Text Available There are generally three views of the notion of a phoneme. The structuralist view of the phoneme focuses on this language phenomenon as a phonetic reality. In discovering phonemes of a language, phonologists who hold this view will look for minimal contrasting pairs as a way to determine contrasting sounds of that language. They will also look for allophones or two sounds of the same phoneme which may appear in complementary distribution. This paper will discuss the possible application of the structuralist approach to analyzing the phonemes of a dialect of Bidayuh, one of the Malayo-Polynesian languages spoken in the northern region of Borneo.

  17. Student Discovers New Pulsar

    Science.gov (United States)

    2010-01-01

    A West Virginia high-school student has discovered a new pulsar, using data from the giant Robert C. Byrd Green Bank Telescope (GBT). Shay Bloxton, 15, a participant in a project in which students analyze data from the radio telescope, spotted evidence of the pulsar on October 15. Bloxton, along with NRAO astronomers observed the object again one month later. The new observation confirmed that the object is a pulsar, a rotating, superdense neutron star. Bloxton is a sophomore at Nicholas County High School in Summersville, West Virginia. "I was very excited when I found out I had actually made a discovery," Bloxton said. She went to Green Bank in November to participate in the follow-up observation. She termed that visit "a great experience." "It also helped me learn a lot about how observations with the GBT are actually done," she added. The project in which she participated, called the Pulsar Search Collaboratory (PSC), is a joint project of the National Radio Astronomy Observatory (NRAO) and West Virginia University, funded by a grant from the National Science Foundation. Pulsars are known for their lighthouse-like beams of radio waves that sweep through space as the neutron star rotates, creating a pulse as the beam sweeps by the Earth. First discovered in 1967, pulsars serve as valuable natural "laboratories" for physicists studying exotic states of matter, quantum mechanics and General Relativity. The GBT, dedicated in 2000, has become one of the world's leading tools for discovering and studying pulsars. The PSC, led by NRAO Education Officer Sue Ann Heatherly and Project Director Rachel Rosen, includes training for teachers and student leaders, and provides parcels of data from the GBT to student teams. The project involves teachers and students in helping astronomers analyze data from 1500 hours of observing with the GBT. The 120 terabytes of data were produced by 70,000 individual pointings of the giant, 17-million-pound telescope. Some 300 hours of the

  18. Discovering the Envionment

    Directory of Open Access Journals (Sweden)

    Albert Bergesen

    2015-08-01

    Full Text Available This special issue of JWSR presents new research on the environment from a distinctly world-system perspective. World-system studies have recently discovered the environment. The turn toward the environment in any number of disciplines has resulted in the greening of this and that area of study. Now it is world-system studies turn. It is a little late; but better late than never. Actually, environmental and world-system studies have a great deal to offer each other. For environmental studies the focus upon the world economy as a whole makes a great deal of sense. Industrial plants in one country, or one region of the world may generate acid rain, but it can fall on other countries. The environment knows no political borders, hence a focus upon the world economy rather than the French, American or Brazilian economy, makes more sense. It is also the case that looking for systemic effects of different types of economics and political systems on the environment should follow the general direction of political/economic theory, which has been ratcheting its level of analysis ever upward to include more and more parts of the world as components of a singular world system. In effect, if we now believe that the most primal locus of economic and political process resides at the level of global interactions then to study the effects of political/economic processes upon the environment means studying the dynamics of the world-system. It is somewhat inevitable.

  19. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  20. Discovering genes underlying QTL

    International Nuclear Information System (INIS)

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  1. Lightest exoplanet yet discovered

    Science.gov (United States)

    2009-04-01

    Well-known exoplanet researcher Michel Mayor today announced the discovery of the lightest exoplanet found so far. The planet, "e", in the famous system Gliese 581, is only about twice the mass of our Earth. The team also refined the orbit of the planet Gliese 581 d, first discovered in 2007, placing it well within the habitable zone, where liquid water oceans could exist. These amazing discoveries are the outcome of more than four years of observations using the most successful low-mass-exoplanet hunter in the world, the HARPS spectrograph attached to the 3.6-metre ESO telescope at La Silla, Chile. ESO PR Photo 15a/09 Artist's impression of Gliese 581 e ESO PR Photo 15b/09 A planet in the habitable zone ESO PR Video 15a/09 ESOcast 6 ESO PR Video 15b/09 VNR A-roll ESO PR Video 15c/09 Zoom-in on Gliese 581 e ESO PR Video 15d/09 Artist's impression of Gliese 581 e ESO PR Video 15e/09 Artist's impression of Gliese 581 d ESO PR Video 15f/09 Artist's impression of Gliese 581 system ESO PR Video 15g/09 The radial velocity method ESO PR Video 15h/09 Statement in English ESO PR Video 15i/09 Statement in French ESO PR Video 15j/09 La Silla Observatory "The holy grail of current exoplanet research is the detection of a rocky, Earth-like planet in the ‘habitable zone' -- a region around the host star with the right conditions for water to be liquid on a planet's surface", says Michel Mayor from the Geneva Observatory, who led the European team to this stunning breakthrough. Planet Gliese 581 e orbits its host star - located only 20.5 light-years away in the constellation Libra ("the Scales") -- in just 3.15 days. "With only 1.9 Earth-masses, it is the least massive exoplanet ever detected and is, very likely, a rocky planet", says co-author Xavier Bonfils from Grenoble Observatory. Being so close to its host star, the planet is not in the habitable zone. But another planet in this system appears to be. From previous observations -- also obtained with the HARPS spectrograph

  2. Flupirtine, a re-discovered drug, revisited.

    Science.gov (United States)

    Szelenyi, Istvan

    2013-03-01

    Flupirtine was developed long before K(V)7 (KCNQ) channels were known. However, it was clear from the beginning that flupirtine is neither an opioid nor a nonsteroidal anti-inflammatory analgesic. Its unique muscle relaxing activity was discovered by serendipity. In the meantime, broad and intensive research has resulted in a partial clarification of its mode of action. Flupirtine is the first therapeutically used K(V)7 channel activator with additional GABA(A)ergic mechanisms and thus the first representative of a novel class of analgesics. The presently accepted main mode of its action, potassium K(V)7 (KCNQ) channel activation, opens a series of further therapeutic possibilities. One of them has now been realized: its back-up compound, the bioisostere retigabine, has been approved for the treatment of epilepsy. PMID:23322112

  3. Therapeutic anticancer efficacy of a synthetic diazonamide analog in the absence of overt toxicity.

    Science.gov (United States)

    Williams, Noelle S; Burgett, Anthony W G; Atkins, Ashley S; Wang, Xiaodong; Harran, Patrick G; McKnight, Steven L

    2007-02-13

    Blocking cell division through the inhibition of mitosis is one of the most successful clinical strategies for the treatment of cancer. Taxanes and vinca alkaloids are in widespread use and have demonstrated substantive therapeutic efficacy. Both classes of compounds bind directly to tubulin, a structural component of the mitotic spindle. The ubiquitous utilization of tubulin in cell division in both cancerous and normal cells, however, tempers the broad spectrum of activity of currently used antimitotics by significant toxicities in normal dividing tissue. Moreover, peripheral nerve cells that rely on microtubules to shuttle cargo along axonal processes are also damaged by tubulin-binding drugs. Thus, neutropenia and peripheral neuropathy are the most frequently cited dose-limiting toxicities of this class of chemotherapeutics. Here we report the preclinical assessment of AB-5, a structural and functional analog of the natural product diazonamide A. AB-5, like taxanes and vinca alkaloids, blocks cell division during mitosis. However, AB-5 works not by binding tubulin but rather through inhibition of a newly discovered role for ornithine-delta-aminotransferase in mitosis. We hereby report that, unlike other antimitotics, AB-5 is extremely well tolerated by mice when administered under conditions where the drug cures xenografted tumors as effectively as taxanes and vinca alkaloids. AB-5-treated mice show no weight loss, no change in overall physical appearance, and no evidence of neutropenia. These observations raise the possibility that AB-5 may have clinical utility for cancer therapy under conditions largely devoid of chemotherapeutic toxicity and suggest that further preclinical evaluation of AB-5 is warranted. PMID:17287337

  4. Two Transients discovered by PSST

    Science.gov (United States)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-08-01

    Two transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  5. Bright Transients discovered by PSST

    Science.gov (United States)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-08-01

    Six bright transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  6. 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

  7. Discovering Natural Laws by Reduction

    Institute of Scientific and Technical Information of China (English)

    吴轶华

    1989-01-01

    A polynomial algorithm.called Reduction,is presented to discover natural laws by analysing a set of experimental data.instead of a heuristic exploration which,when adopted in BACON,can only lead to rediscovering simple laws.A complex law with multiple variables involved can be discovered by reducing it to a search.This search is so efficient that it does not need any backtracking and is able to cover most of possible laws.A reduction-based discovery system,called DISCOVER 2.0,was developed with a flexible knowledge base and an ability of dealing with imperfect data.The system has been verified to be valid computationally,practically,and theoretically,by discovering a great number o complex laws,and can be also viewed as a leaming engine embodied in any intelligent systems to improve their performance by obtaining a general rule from the accumulated data.

  8. An overview of leech and its therapeutic applications

    Directory of Open Access Journals (Sweden)

    Parimannan Sivachandran

    2015-05-01

    Full Text Available Hirudotherapy has a broad spectrum of therapeutic application in the medical field ranging from cardiology, gynaecology, ophthalmology, plastic and reconstructive surgeries. In medieval and early modern medicine, leeches were used to remove blood from patients in an attempt to balance the biological humours. Leeches are widely used to treat venous congestion in microvascular replantation, free and conventional flap surgery and traumatology. Recently, Food and Drug Administration has approved the usage of live leeches as medical device for therapeutic applications. Presently, some of the leech species have declined dramatically in its population due to the over utilization of leech for medicinal purposes and also due to pollution in several parts of the world particularly in European and Asian countries. This review presents an overview of leech including the history, biology, classification, and its application as medical device. Further, it also covers the controversies and misconception related to leech species identification and complications of post hirudotherapy.

  9. An overview of leech and its therapeutic applications

    Institute of Scientific and Technical Information of China (English)

    Parimannan Sivachandran; Rajandas Heera; Pattabhiraman Lalitha; Manickam Ravichandran; Shalini Sivadasan; Kasi Marimuthu

    2015-01-01

    Hirudotherapy has a broad spectrum of therapeutic application in the medical field ranging from cardiology, gynaecology, ophthalmology, plastic and reconstructive surgeries. In medieval and early modern medicine, leeches were used to remove blood from patients in an attempt to balance the biological humours. Leeches are widely used to treat venous congestion in microvascular replantation, free and conventional flap surgery and traumatology. Recently, Food and Drug Administration has approved the usage of live leeches as medical device for therapeutic applications. Presently, some of the leech species have declined dramatically in its population due to the over utilization of leech for medicinal purposes and also due to pollution in several parts of the world particularly in European and Asian countries. This review presents an overview of leech including the history, biology, classification, and its application as medical device. Further, it also covers the controversies and misconception related to leech species identification and complications of post hirudotherapy.

  10. New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2011-01-01

    Full Text Available MMP intervention strategies have met with limited clinical success due to severe toxicities. In particular, treatment with broad-spectrum MMP-inhibitors (MMPIs caused musculoskeletal pain and inflammation. Selectivity may be essential for realizing the clinical potential of MMPIs. Here we review discoveries pinpointing membrane-bound MMPs as mediators of mechanisms underlying cancer and inflammation and as possible therapeutic targets for prevention/treatment of these diseases. We discuss strategies to target these therapeutic proteases using highly selective inhibitory agents (i.e., human blocking antibodies against individual membrane-bound MMPs.

  11. Discovering fuzzy spatial association rules

    Science.gov (United States)

    Kacar, Esen; Cicekli, Nihan K.

    2002-03-01

    Discovering interesting, implicit knowledge and general relationships in geographic information databases is very important to understand and use these spatial data. One of the methods for discovering this implicit knowledge is mining spatial association rules. A spatial association rule is a rule indicating certain association relationships among a set of spatial and possibly non-spatial predicates. In the mining process, data is organized in a hierarchical manner. However, in real-world applications it may not be possible to construct a crisp structure for this data, instead some fuzzy structures should be used. Fuzziness, i.e. partial belonging of an item to more than one sub-item in the hierarchy, could be applied to the data itself, and also to the hierarchy of spatial relations. This paper shows that, strong association rules can be mined from large spatial databases using fuzzy concept and spatial relation hierarchies.

  12. Discovering Diversity in Introductory Economics

    OpenAIRE

    Robin L. Bartlett

    1996-01-01

    Instructors can begin the process of integrating race and gender issues into introductory economics by reexamining their courses with a new lens of diversity. The content of introductory economics can be expanded by 'adding and stirring' race and gender data from standard statistical sources or from the students themselves. This paper offers some 'add-and-stir' macro- and microeconomic examples. To discover the appropriate mix of these examples and how to present them, this paper also offers ...

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

    OpenAIRE

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

    1997-01-01

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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Sameer Dixit

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

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

    Science.gov (United States)

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

    2016-07-19

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

  17. 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

  18. 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.

  19. 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.

  20. Who discovered the magnetocaloric effect?

    DEFF Research Database (Denmark)

    Smith, Anders

    2013-01-01

    A magnetic body changes its thermal state when subjected to a changing magnetic field. In particular, if done under adiabatic conditions, its temperature changes. For the past 15 years the magnetocaloric effect has been the focus of significant research due to its possible application for efficient...... refrigeration near room temperature. At the same time, it has become common knowledge within the magnetic refrigeration research community that the magnetocaloric effect was discovered by the German physicist E. Warburg in 1881. We re-examine the original literature and show that this is a misleading reading...

  1. Discovering evolution equations with applications

    CERN Document Server

    McKibben, Mark

    2011-01-01

    Most existing books on evolution equations tend either to cover a particular class of equations in too much depth for beginners or focus on a very specific research direction. Thus, the field can be daunting for newcomers to the field who need access to preliminary material and behind-the-scenes detail. Taking an applications-oriented, conversational approach, Discovering Evolution Equations with Applications: Volume 2-Stochastic Equations provides an introductory understanding of stochastic evolution equations. The text begins with hands-on introductions to the essentials of real and stochast

  2. Bacteriophage Procurement for Therapeutic Purposes.

    Science.gov (United States)

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  3. Who discovered the expanding universe?

    CERN Document Server

    Nussbaumer, Harry

    2011-01-01

    Who discovered the expanding universe? Was it Hubble, or Lemaitre, or was it just the end result of a long series of investigations? In this article we summarise the main steps and contributions that led to one of the most exciting discoveries ever made, of which Lemaitre was the principal architect. In 1927 he combined his dynamical solutions of the Einstein equations with astronomical observations to conclude that the universe is expanding. He derived the linear velocity-distance relationship and calculated the first numerical value of what later was called the "Hubble constant". His discovery paper of 1927 was written in French and in 1931 it was translated into English and published in Monthly Notices. However, the translation omits the section where Lemaitre computed the "Hubble constant". Why was that done, and who was responsible? We do not speculate on this question, but present in a very condensed way the facts along the path of discovery. The documented details from primary sources can be found in o...

  4. 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

  5. Discovering Mobile Social Networks by Semantic Technologies

    Science.gov (United States)

    Jung, Jason J.; Choi, Kwang Sun; Park, Sung Hyuk

    It has been important for telecommunication companies to discover social networks from mobile subscribers. They have attempted to provide a number of recommendation services, but they realized that the services were not successful. In this chapter, we present semantic technologies for discovering social networks. The process is mainly composed of two steps; (1) profile identification and (2) context understanding. Through developing a Next generation Contents dElivery (NICE) platform, we were able to generate various services based on the discovered social networks.

  6. The arsenal of pathogens and antivirulence therapeutic strategies for disarming them

    Science.gov (United States)

    Brannon, John R; Hadjifrangiskou, Maria

    2016-01-01

    Pathogens deploy an arsenal of virulence factors (VFs) to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their development into therapeutics has made a monumental impact on human and microbial populations. Although humans have used antimicrobials for medicinal and agricultural purposes, microorganism populations have developed and shared resistance mechanisms to persevere in the face of classical antimicrobials. However, a positive substitute is antivirulence therapy; antivirulence therapeutics prevent or interrupt an infection by counteracting a pathogen’s VFs. Their application can reduce the use of broad-spectrum antimicrobials and dampen the frequency with which resistant strains emerge. Here, we summarize the contribution of VFs to various acute and chronic infections. In correspondence with this, we provide an overview of the research and development of antivirulence strategies. PMID:27313446

  7. Scientists Discover Sugar in Space

    Science.gov (United States)

    2000-06-01

    . Glycolaldehyde is a simpler molecular cousin to table sugar, the scientists say. The sugar molecule was detected in a large cloud of gas and dust some 26,000 light-years away, near the center of our Galaxy. Such clouds, often many light-years across, are the material from which new stars are formed. Though very rarified by Earth standards, these interstellar clouds are the sites of complex chemical reactions that occur over hundreds of thousands or millions of years. So far, about 120 different molecules have been discovered in these clouds. Most of these molecules contain a small number of atoms, and only a few molecules with eight or more atoms have been found in interstellar clouds. The 12 Meter Telescope "Finding glycolaldehyde in one of these interstellar clouds means that such molecules can be formed even in very rarified conditions," said Hollis. "We don't yet understand how it could be formed there," he added. "A combination of more astronomical observations and theoretical chemistry work will be required to resolve the mystery of how this molecule is formed in space." "We hope this discovery inspires renewed efforts to find even more kinds of molecules, so that, with a better idea of the total picture, we may be able to deduce the details of the prebiotic chemistry taking place in interstellar clouds," Hollis said. The discovery was made by detecting faint radio emission from the sugar molecules in the interstellar cloud. Molecules rotate end-for-end, and as they change from one rotational energy state to another, they emit radio waves at precise frequencies. The "family" of radio frequencies emitted by a particular molecule forms a unique "fingerprint" that scientists can use to identify that molecule. The scientists identified glycolaldehyde by detecting six frequencies of radio emission in what is termed the millimeter-wavelength region of the electromagnetic spectrum -- a region between more-familiar microwaves and infrared radiation. The NRAO 12 Meter Telescope

  8. Probable Bright Supernova discovered by PSST

    Science.gov (United States)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-09-01

    A bright transient, which is a probable supernova, has been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  9. 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。

  10. A novel method to discover fluoroquinolone antibiotic resistance (qnr genes in fragmented nucleotide sequences

    Directory of Open Access Journals (Sweden)

    Boulund Fredrik

    2012-12-01

    Full Text Available Abstract Background Broad-spectrum fluoroquinolone antibiotics are central in modern health care and are used to treat and prevent a wide range of bacterial infections. The recently discovered qnr genes provide a mechanism of resistance with the potential to rapidly spread between bacteria using horizontal gene transfer. As for many antibiotic resistance genes present in pathogens today, qnr genes are hypothesized to originate from environmental bacteria. The vast amount of data generated by shotgun metagenomics can therefore be used to explore the diversity of qnr genes in more detail. Results In this paper we describe a new method to identify qnr genes in nucleotide sequence data. We show, using cross-validation, that the method has a high statistical power of correctly classifying sequences from novel classes of qnr genes, even for fragments as short as 100 nucleotides. Based on sequences from public repositories, the method was able to identify all previously reported plasmid-mediated qnr genes. In addition, several fragments from novel putative qnr genes were identified in metagenomes. The method was also able to annotate 39 chromosomal variants of which 11 have previously not been reported in literature. Conclusions The method described in this paper significantly improves the sensitivity and specificity of identification and annotation of qnr genes in nucleotide sequence data. The predicted novel putative qnr genes in the metagenomic data support the hypothesis of a large and uncharacterized diversity within this family of resistance genes in environmental bacterial communities. An implementation of the method is freely available at http://bioinformatics.math.chalmers.se/qnr/.

  11. Did the ancient egyptians discover Algol?

    Science.gov (United States)

    Jetsu, L.; Porceddu, S.; Porceddu, S.; Lyytinen, J.; Kajatkari, P.; Markkanen, T.; Toivari-Viitala, J.

    2013-02-01

    Fabritius discovered the first variable star, Mira, in 1596. Holwarda determined the 11 months period of Mira in 1638. Montanari discovered the next variable star, Algol, in 1669. Its period, 2.867 days, was determined by Goodricke (178). Algol was associated with demon-like creatures, "Gorgon" in ancient Greek and "ghoul" in ancient Arab mythology. This indicates that its variability was discovered much before 1669 (Wilk 1996), but this mythological evidence is ambiguous (Davis 1975). For thousands of years, the Ancient Egyptian Scribes (AES) observed stars for timekeeping in a region, where there are nearly 300 clear nights a year. We discovered a significant periodicity of 2.850 days in their calendar for lucky and unlucky days dated to 1224 BC, "the Cairo Calendar". Several astrophysical and astronomical tests supported our conclusion that this was the period of Algol three millennia ago. The "ghoulish habits" of Algol could explain this 0.017 days period increase (Battersby 2012).

  12. Discover Effective Pattern for Text Mining

    OpenAIRE

    Khade, A. D.; A. B. Karche

    2014-01-01

    Many data mining techniques have been discovered for finding useful patterns in documents like text document. However, how to use effective and bring to up to date discovered patterns is still an open research task, especially in the domain of text mining. Text mining is the finding of very interesting knowledge (or features) in the text documents. It is a challenging task to find appropriate knowledge (or features) in text documents to help users to find what they exactly want...

  13. Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention.

    Directory of Open Access Journals (Sweden)

    Ziying Han

    2015-10-01

    Full Text Available Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg and arenaviruses (Lassa and Junín viruses, are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1 and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.

  14. Therapeutic ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Crum, Lawrence A [Center for Industrial and Medical Ultrasound, 1013 NE 40th Street, University of Washington, Seattle, WA 98105 (United States)

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  15. Therapeutic alliance.

    Science.gov (United States)

    Fox, Valerie

    2002-01-01

    I have been very fortunate in my journey of mental illness. I respond well to medication, but I don't think that is the complete answer to living successfully with serious, persistent mental illness. I believe a person's environment is also of utmost importance, enabling the person suffering with mental illness to continually grow in life. I found early in my struggle with mental illness a psychiatrist with whom I have always had a very good rapport. Until recently I didn't know that what I have with this psychiatrist is professionally known as a therapeutic alliance. Over the years, when I need someone to talk over anything that is troubling to me, I seek my psychiatrist. A therapeutic alliance is non-judgmental; it is nourishing; and finally it is a relationship of complete trust. Perhaps persons reading this article who have never experienced this alliance will seek it. I believe it can make an insecure person secure; a frightened person less frightened; and allow a person to continue the journey of mental health with a sense of belief in oneself. PMID:12433224

  16. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  17. 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

  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. 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 .

  20. Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

    Directory of Open Access Journals (Sweden)

    Shih-Chang Chien

    2015-01-01

    Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

  1. Endogenous angiogenesis inhibitors and their therapeutic implications.

    Science.gov (United States)

    Cao, Y

    2001-04-01

    A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and

  2. A Bayesian Model for Discovering Typological Implications

    CERN Document Server

    Daumé, Hal

    2009-01-01

    A standard form of analysis for linguistic typology is the universal implication. These implications state facts about the range of extant languages, such as ``if objects come after verbs, then adjectives come after nouns.'' Such implications are typically discovered by painstaking hand analysis over a small sample of languages. We propose a computational model for assisting at this process. Our model is able to discover both well-known implications as well as some novel implications that deserve further study. Moreover, through a careful application of hierarchical analysis, we are able to cope with the well-known sampling problem: languages are not independent.

  3. Bioengineering lantibiotics for therapeutic success

    Directory of Open Access Journals (Sweden)

    Des eField

    2015-11-01

    Full Text Available Several examples of highly modified antimicrobial peptides have been described. While many such peptides are non-ribosomally synthesized, ribosomally synthesised equivalents are being discovered with increased frequency. Of the latter group, the lantibiotics continue to attract most attention. In the present review, we discuss the implementation of in vivo and in vitro engineering systems to alter, and even enhance, the antimicrobial activity, antibacterial spectrum and physico-chemical properties, including heat stability, solubility, diffusion and protease resistance, of these compounds. Additionally, we discuss the potential applications of these lantibiotics for use as therapeutics.

  4. How to discover and express subtext

    Institute of Scientific and Technical Information of China (English)

    刘晓冰

    2016-01-01

    Subtext is the spirit of actor's lines, and it is a must in performance. As a consequence, subtext is important in both performance and actor's lines. This paper will give subtext a comprehensive analysis and discussion in four sections, say, what subtext is, the significance and function of subtext, how to discover subtext and how to express subtext.

  5. Discovering the Sequential Structure of Thought

    Science.gov (United States)

    Anderson, John R.; Fincham, Jon M.

    2014-01-01

    Multi-voxel pattern recognition techniques combined with Hidden Markov models can be used to discover the mental states that people go through in performing a task. The combined method identifies both the mental states and how their durations vary with experimental conditions. We apply this method to a task where participants solve novel…

  6. Did Viking discover life on Mars?

    Science.gov (United States)

    Klein, H. P.

    1999-01-01

    A major argument in the claim that life had been discovered during the Viking mission to Mars is that the results obtained in the Labeled Release (LR) experiment are analogous to those observed with terrestrial microorganisms. This assertion is critically examined and found to be implausible.

  7. Digging Deeper: Looking Beyond Behavior to Discover Meaning

    Medline Plus

    Full Text Available ... Behavior to Discover Meaning A Unit of Four Online Lessons Digging Deeper: Looking Beyond Behavior to Discover ... Behavior to Discover Meaning. A Unit of Four Online Lessons. HHS/ACF/OHS/EHSNRC. 2006. English. Last ...

  8. Psychodrama: Discovering New Meaning in Personal Drama.

    Science.gov (United States)

    Pearlman, William D.

    1990-01-01

    Psychodrama as a therapeutic exercise and a format for understanding emotional and cognitive development is a form of experiential learning that can help adults practice inner reflection and imagine change. (SK)

  9. Discovering Resume Information using linked data

    Directory of Open Access Journals (Sweden)

    Ujjal Marjit

    2012-05-01

    Full Text Available In spite of having different web applications to create and collect resumes, these web applications suffer mainly from a common standard data model, data sharing, and data reusing. Though, different web applications provide same quality of resume information, but internally there are many differences in terms of data structure and storage which makes computer difficult to process and analyse the information from different sources. The concept of Linked Data has enabled the web to share data among different data sources and to discover any kind of information while resolving the issues like heterogeneity, interoperability, and data reusing between different data sources and allowing machine process-able data on the web. In this paper we present Linked Data approach to discover resume information enabling the task aggregation, sharing and reusing the information among different resume information providers and organizations. We also demonstrate experimental results on semantically rich resume information.

  10. Discovering Recurrent Image Semantics from Class Discrimination

    Directory of Open Access Journals (Sweden)

    Jin Jesse S

    2006-01-01

    Full Text Available Supervised statistical learning has become a critical means to design and learn visual concepts (e.g., faces, foliage, buildings, etc. in content-based indexing systems. The drawback of this approach is the need of manual labeling of regions. While several automatic image annotation methods proposed recently are very promising, they usually rely on the availability and analysis of associated text descriptions. In this paper, we propose a hybrid learning framework to discover local semantic regions and generate their samples for training of local detectors with minimal human intervention. A multiscale segmentation-free framework is proposed to embed the soft presence of discovered semantic regions and local class patterns in an image independently for indexing and matching. Based on 2400 heterogeneous consumer images with 16 semantic queries, both similarity matching based on individual index and integrated similarity matching have outperformed a feature fusion approach by 26% and 37% in average precisions, respectively.

  11. 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

  12. Transpleural central venous catheter discovered during thoracotomy

    Directory of Open Access Journals (Sweden)

    Ashima Malhotra

    2014-01-01

    Full Text Available We report an uncommon complication of subclavian central venous catheterization, discovered at thoracotomy. The central venous catheter (CVC was placed by left infraclavicular route after induction of general anesthesia. CVC was secured after aspiration of blood and satisfactory central venous tracing. On thoracotomy, CVC was noticed to traverse the pleural cavity while the tracing was normal. CVC was thus removed consequent to which bleeding from each puncture site was noticed, that were secured surgically.

  13. Discovering Multidimensional Structure in Relational Data

    DEFF Research Database (Denmark)

    Jensen, Mikael Rune; Holmgren, Thomas; Pedersen, Torben Bach

    2004-01-01

    On-Line Analytical Processing (OLAP) systems based on multidimensional databases are essential elements of decision support. However, most existing data is stored in “ordinary” relational OLTP databases, i.e., data has to be (re-) modeled as multidimensional cubes before the advantages of OLAP to...... algorithms for discovering multidimensional schemas from relational databases. The algorithms take a wide range of available metadata into account in the discovery process, including functional and inclusion dependencies, and key and cardinality information....

  14. Discovering beautiful attributes for aesthetic image analysis

    OpenAIRE

    Marchesotti, Luca; Murray, Naila; Perronnin, Florent

    2014-01-01

    Aesthetic image analysis is the study and assessment of the aesthetic properties of images. Current computational approaches to aesthetic image analysis either provide accurate or interpretable results. To obtain both accuracy and interpretability by humans, we advocate the use of learned and nameable visual attributes as mid-level features. For this purpose, we propose to discover and learn the visual appearance of attributes automatically, using a recently introduced database, called AVA, w...

  15. How to discover and develop leadership potencial

    OpenAIRE

    Javorská, Anna

    2012-01-01

    This paper focuses on leadership development in the corporate environment. It aims to discover the most important competencies, skills and personal qualities necessary for a successful leader and the best ways to develop these. The theoretical part introduces the key issues of the topic and defines leadership and leadership development. The practical part investigates approach to the leadership development in three different companies and compares them based on a qualitative research using qu...

  16. What if Fleming had not discovered penicillin?

    Science.gov (United States)

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

    2014-09-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents.

  17. Discovering Attack Path Oriented-IP Traceback

    Institute of Scientific and Technical Information of China (English)

    Fu Jianming(傅建明); Zhu Fuxi; Peng Guojun

    2003-01-01

    The technique of IP traceback may effectively block DOS (Denial Of Service) and meet the requirement of the computer forensic, but its accuracy depends upon that condition that each node in the Internet must support IP packet marking or detected agents. So far, this requirement is not satisfied. On the basis of traditional traceroute,this paper investigates the efficiency of discovering path methods from aspects of the size and order of detecting packets, and the length of paths.It points out that the size of padding in probed packets has a slight effect on discovering latency, and the latency with the method of bulk sending-receiving is much smaller than one with the traditional traceroute. Moreover, the loss rate of packets with the technique of TTL (Time To Live) which increases monotonously is less than that with the technique of TTL which decreases monotonously. Lastly,OS (Operating System) passive fingerprint is used as heuristic to predict the length of the discovered path so as to reduce disturbance in network traffic.

  18. Discovering Typed Communities in Mobile Social Networks

    Institute of Scientific and Technical Information of China (English)

    Huai-Yu Wan; You-Fang Lin; Zhi-Hao Wu; Hou-Kuan Huang

    2012-01-01

    Mobile social networks,which consist of mobile users who communicate with each other using cell phones,are reflections of people's interactions in social lives.Discovering typed communities (e.g.,family communities or corporate communities) in mobile social networks is a very promising problem.For example,it can help mobile operators to determine the target users for precision marketing.In this paper we propose discovering typed communities in mobile social networks by utilizing the labels of relationships between users.We use the user logs stored by mobile operators,including communication and user movement records,to collectively label all the relationships in a network,by employing an undirected probabilistic graphical model,i.e.,conditional random fields.Then we use two methods to discover typed communities based on the results of relationship labeling:one is simply retaining or cutting relationships according to their labels,and the other is using sophisticated weighted community detection algorithms.The experimental results show that our proposed framework performs well in terms of the accuracy of typed community detection in mobile social networks.

  19. Therapeutic advancements in multiple myeloma.

    Science.gov (United States)

    Gozzetti, Alessandro; Candi, Veronica; Papini, Giulia; Bocchia, Monica

    2014-01-01

    Multiple myeloma survival has significantly improved in the latest years due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib, and lenalidomide together with autologous stem-cell transplantation has considerably increased complete remission rate and progression-free survival resulting ultimately in prolonged survival in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to further implement responses. Finally, a number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, making the future of myeloma patients brighter. PMID:25237651

  20. Ivermectin: pharmacology and therapeutic applications

    Directory of Open Access Journals (Sweden)

    Sunita B. Chhaiya

    2012-06-01

    Full Text Available Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. It belongs to the family of avermectins. It binds to glutamate-gated chloride iron channels, which are present in invertebrate nerve and muscle cells, and causes the paralysis and death of the parasite. Ivermectin is approved by the US Food and Drug Administration, and used worldwide to treat patients with onchocerciasis and strongyloidiasis. It is also used against a wide range of endoparasites (nematodes and ectoparasites (insects, acarine of animals and humans. [Int J Basic Clin Pharmacol 2012; 1(3.000: 132-139

  1. Therapeutic advancements in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Alessandro eGozzetti

    2014-09-01

    Full Text Available Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

  2. Dinosaur Footprint Fossils Discovered in Xinjiang

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Recently,a Chinese-German science fieldwork investigation team,composed of staff from the SinoGerman Paleontology and Geography Joint Lab and the Xinjiang Geological Work Station,announced that they discovered a batch of dinosaur footprint fossils in the dessert 20 kilometers to the east of Shanshan County in the Turpan Basin,Xinjiang Uyghur Autonomous Region.These fossils spread around an area of 100 square meters and scientists believed that these footprints were left behind by carnivore dinosaurs.This major discovery has been published in Global Geology,an English journal published by the NorthEast Asia Geology Center.

  3. The discovered preference hypothesis - an empirical test

    DEFF Research Database (Denmark)

    Lundhede, Thomas; Ladenburg, Jacob; Olsen, Søren Bøye

    Using stated preference methods for valuation of non-market goods is known to be vulnerable to a range of biases. Some authors claim that these so-called anomalies in effect render the methods useless for the purpose. However, the Discovered Preference Hypothesis, as put forth by Plott [31], offers...... an nterpretation and explanation of biases which entails that the stated preference methods need not to be completely written off. In this paper we conduct a test for the validity and relevance of the DPH interpretation of biases. In a choice experiment concerning preferences for protection of Danish nature areas...

  4. Recently discovered pulsars and unidentified EGRET sources

    CERN Document Server

    Torres, D F; Camilo, F M; Torres, Diego F.; Butt, Yousaf M.; Camilo, Fernando

    2001-01-01

    We present a correlative study between all unidentified EGRET sources at low Galactic latitudes and the newly discovered pulsars in the released portion of the Parkes multibeam radio survey. We note 14 positional coincidences: eight of these are ``Vela-like'' pulsars, with relatively small periods, small characteristic ages, and high spin-down luminosities. Three of these coincidences have been investigated by D'Amico et al. (2001) and Camilo et al. (2001). Among the others, we argue that PSR J1015-5719 may plausibly generate part of the high energy radiation observed from 3EG J1014-5705. Three additional interesting cases are: 3EG J1410-6147 and either of PSRs J1412-6145 or J1413-6141, if the pulsars are at the estimated distance of the coincident SNR G312.4-0.4; and 3EG J1639-4702/PSR J1637-4642. The remaining positional coincidences between the EGRET sources and the newly discovered pulsars are almost certainly spurious.

  5. The Universe for all to discover

    Science.gov (United States)

    Ortiz-Gil, A.; Ballesteros, F.; Espinós, H.; Fernández-Soto, A.; Lanzara, M.; Moya, M. J.; Navarro, J.

    2015-05-01

    In the title of this paper, we have changed the slogan of the International Year of Astronomy, ``The Universe yours to discover" to ``The Universe for all to discover" in order to emphasize the need to think about broader audiences when we plan astronomical activities at school or during outreach events. The strategy we propose follows what is known as the Universal Design for Learning (UDL). UDL allows to reach to the general public as well as to audiences which might be regarded as ``special" because they have some disability. It has been shown that everybody has a preferred style of learning (some remember better what they see, others what they hear or what they touch) and therefore, everybody is more or less able under the different styles of learning. Through this talk I am going to outline some of the principles of the UDL that can be applied in the teaching and communication of Astronomy, along with an example of its implementation in the project ``A Touch of the Universe".

  6. Therapeutic Benefits of Cannabis: A Patient Survey

    OpenAIRE

    Webb, Charles W; Webb, Sandra M

    2014-01-01

    Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai‘i.

  7. expression, physiological actions and therapeutic potential

    OpenAIRE

    Steckelings, Ulrike

    2012-01-01

    Angiotensin II mediates its action via 2 receptor subtypes: the AT1- and AT2-receptor. The existence of more than one receptor for angiotensin II has been discovered not earlier than 1989. This "Habilitationsschrift" is based on six publications which represent mosaic stones within the growing picture of AT2-receptor expression, regulation of expression, physiological and patho-physiological function as well as potential therapeutic use. The first part is dealing with tissue specific ex...

  8. Discovering, Indexing and Interlinking Information Resources

    Science.gov (United States)

    Celli, Fabrizio; Keizer, Johannes; Jaques, Yves; Konstantopoulos, Stasinos; Vudragović, Dušan

    2015-01-01

    The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS. PMID:26834982

  9. Discovering User Profiles for Web Personalized Recommendation

    Institute of Scientific and Technical Information of China (English)

    Ai-Bo Song; Mao-Xian Zhao; Zuo-Peng Liang; Yi-Sheng Dong; Jun-Zhou Luo

    2004-01-01

    With the growing popularity of the World Wide Web, large volume of user access data has been gathered automatically by Web servers and stored in Web logs. Discovering and understanding user behavior patterns from log files can provide Web personalized recommendation services. In this paper, a novel clustering method is presented for log files called Clustering large Weblog based on Key Path Model (CWKPM), which is based on user browsing key path model, to get user behavior profiles. Compared with the previous Boolean model,key path model onsiders the major features of users' accessing to the Web: ordinal, contiguous and duplicate.Moreover, for clustering, it has fewer dimensions. The analysis and experiments show that CWKPM is an efficient and effective approach for clustering large and high-dimension Web logs.

  10. Discovering User Profiles for Web Personalized Recommendation

    Institute of Scientific and Technical Information of China (English)

    Ai-BoSong; Mao-XianZhao; Zuo-PengLiang; Yi-ShengDong; Jun-ZhouLuo

    2004-01-01

    With the growing popularity of the World Wide Web, large volume of user access data has been gathered automatically by Web servers and stored in Web logs. Discovering and understanding user behavior patterns from log files can provide Web personalized recommendation services. In this paper, a novel clustering method is presented for log files called Clustering large Weblog based on Key Path Model (CWKPM), which is based on user browsing key path model, to get user behavior profiles. Compared with the previous Boolean model, key path model considers the major features of users' accessing to the Web: ordinal, contiguous and duplicate. Moreover, for clustering, it has fewer dimensions. The analysis and experiments show that CWKPM is an efficient and effective approach for clustering large and high-dimension Web logs.

  11. Michael Maier--nine newly discovered letters.

    Science.gov (United States)

    Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

    2014-02-01

    The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony. PMID:25241502

  12. Discovering general partial orders in event streams

    CERN Document Server

    Achar, Avinash; Raajay, V; Sastry, P S

    2009-01-01

    Sequence of time-ordered events arise in a variety of applications like customer transaction databases, alarm sequences in telecommunication networks, fault logs in manufacturing plant data, web interaction logs, etc. A popular framework for temporal pattern extraction from such data is the frequent episode discovery paradigm. An episode is a set of nodes with a partial order prescribed on it, with each node associated with an event type. Efficient algorithms exist for episode discovery when the associated partial order is total(serial episode) or trivial(parallel episode). In this paper, we propose efficient algorithms for discovering frequent episodes with general partial orders. The algorithms generalize the existing apriori-based discovery algorithms for serial and parallel episodes. There is an inherent combinatorial explosion in frequent partial order mining. We point out that frequency alone is not a sufficient measure of interestingness for general episodes. We present post-processing techniques to pr...

  13. Discovering New Drugs on the Cellular Level

    Science.gov (United States)

    2005-01-01

    With the Vision for Space Exploration calling for a sustained human presence in space, astronauts will need to grow plants, while in orbit, for nourishment that they will not receive from only consuming dehydrated foods. As a potential source of food for long-duration missions, space-grown plants could also give astronauts an important psychological boost, as fresh vegetables could serve as a welcomed change from monotonous meals consisting of reconstituted foods in plastic bags. Even more, these plants could likely aid in the recycling of air and wastewater on spacecraft. With a helping hand from a company by the name of Biolog, Inc., NASA is studying the impacts of decreased gravity and spaceborne bacteria on the plants being grown for food in space. With a helping hand from NASA, this very same company is creating powerful new cell- and bacteria-analysis tools for use in discovering and developing new drugs on Earth.

  14. Discovering, Indexing and Interlinking Information Resources.

    Science.gov (United States)

    Celli, Fabrizio; Keizer, Johannes; Jaques, Yves; Konstantopoulos, Stasinos; Vudragović, Dušan

    2015-01-01

    The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS. PMID:26834982

  15. Automatically Discovering Hidden Transformation Chaining Constraints

    CERN Document Server

    Chenouard, Raphael; 10.1007/978-3-642-04425-0_8

    2010-01-01

    Model transformations operate on models conforming to precisely defined metamodels. Consequently, it often seems relatively easy to chain them: the output of a transformation may be given as input to a second one if metamodels match. However, this simple rule has some obvious limitations. For instance, a transformation may only use a subset of a metamodel. Therefore, chaining transformations appropriately requires more information. We present here an approach that automatically discovers more detailed information about actual chaining constraints by statically analyzing transformations. The objective is to provide developers who decide to chain transformations with more data on which to base their choices. This approach has been successfully applied to the case of a library of endogenous transformations. They all have the same source and target metamodel but have some hidden chaining constraints. In such a case, the simple metamodel matching rule given above does not provide any useful information.

  16. Discovering and Mining Links for Protein Databases

    Directory of Open Access Journals (Sweden)

    A.Immaculate Mercy

    2014-01-01

    Full Text Available This work introduces a link analysis procedure for discovering relationships in a protein database or a relational database generalizing simple correspondence analysis. It is based on extracting the links to the rela ted protein database and malfunctioned protein database. The datasets are trained in order to find out missing interactions and the sequences related to them. Further the analysis of links proceeds by performing a random walk defining a Markov chain. The e lements of interest are analysed through stochastic complementation which gives a reduced Markov chain. This reduced map is then analysed by projecting the elements of interest through Principal component analysis. Several Protein datasets are analysed using the proposed methodology, showing the usefulness of the technique for extracting relationships in relational databases or graphs.

  17. Discovering and Mining Links for Protein Databases

    Directory of Open Access Journals (Sweden)

    A. Immaculate Mercy

    2015-10-01

    Full Text Available discovering relationships in a protein database or a relational database generalizing simple correspondence analysis. It is based on extracting the links to the related protein database and malfunctioned protein database. The datasets are trained in order to find out missing interactions and the sequences related to them. Further the analysis of links proceeds by performing a random walk defining a Markov chain. The elements of interest are analysed through stochastic complementation which gives a reduced Markov chain. This reduced map is then analysed by projecting the elements of interest through Principal component analysis. Several Protein datasets are analysed using the proposed methodology, showing the usefulness of the technique for extracting relationships in relational databases or graphs.

  18. Michael Maier--nine newly discovered letters.

    Science.gov (United States)

    Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

    2014-02-01

    The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony.

  19. Digging Deeper: Looking Beyond Behavior to Discover Meaning

    Medline Plus

    Full Text Available ... Email Client Print Español Digging Deeper: Looking Beyond Behavior to Discover Meaning A Unit of Four Online Lessons Digging Deeper: Looking Beyond Behavior to Discover Meaning is a unit of four ...

  20. Digging Deeper: Looking Beyond Behavior to Discover Meaning

    Medline Plus

    Full Text Available ... Digging Deeper: Looking Beyond Behavior to Discover Meaning A Unit of Four Online Lessons Digging Deeper: Looking Beyond Behavior to Discover Meaning is a unit of four lessons that explore and apply ...

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

    Institute of Scientific and Technical Information of China (English)

    张晓; 曾晓燕; 刘哲; 金秋; 徐言; 冯振卿; 焦永军

    2011-01-01

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

  2. Imminent science what remains to be discovered

    CERN Document Server

    Bignami, Giovanni F

    2014-01-01

    This is not science fiction. It’s a voyage on the arrow of time to the coming fifty years. The legendary palindromic character Mr. Qfwfq from Italo Calvino’s collection of short stories, The Cosmicomics, will go with us – he who knows all the answers but will give out no hints. He will help us to discover the innovations that will have changed our lives by 2062, when, riding astride Halley’s Comet, our omniscient extraterrestrial will return to visit us.In this book, we shall learn how astronomers will devote themselves to the study of the mysterious force of dark energy, which makes up some three-quarters of the Universe. We shall also delve deeply into the study of our Earth, to exploit the immense thermal energy that lies beneath our feet. We shall solve another enigma in today’s science: the origin of life. We shall come to understand how to develop direct contacts between our brains and the rest of the world. We shall learn about the future of genetics, the reason for the longevity of Methusela...

  3. Discovering the Ancient Maya from Space

    Science.gov (United States)

    Sever, T. L.

    2008-01-01

    The Pet6n region of northern Guatemala contains some of the most significant Mayan archeological sites in Latin America. It was in this region that the Maya civilization began, flourished, and abruptly disappeared. Remote sensing technology is helping to locate and map ancient Maya sites that are threatened today by accelerating deforestation and looting. Thematic Mapper, IKONOS, and QuickBird satellite, and airborne STAR-3i and AIRSAR radar data, combined with Global Positioning System (GPS) technology, are successfully detecting ancient Maya features such as sites, roadways, canals, and water reservoirs. Satellite imagery is also being used to map the bajos, which are seasonally flooded swamps that cover over 40% of the land surface. Through the use of various airborne and satellite sensor systems we have been able to detect and map ancient causeways, temples, reservoirs, and land forms, and locate these features on the ground through GPS technology. Recently, we have discovered that there is a strong relationship between a tropical forest vegetation signature in satellite imagery and the location of archeological sites. We believe that the use of limestone and lime plasters in ancient Maya construction affects the moisture, nutrition, and plant species of the surface vegetation. We have mapped these vegetation signatures in the imagery and verified through field survey that they are indicative of archeological sites. Through the use of remote sensing and GIS technology it is possible to identify unrecorded archeological features in a dense tropical forest environment and monitor these cultural features for their protection.

  4. How the antihypertensive losartan was discovered.

    Science.gov (United States)

    Bhardwaj, Gaurab

    2006-11-01

    Based on interviews and publications, this case study is a history of how DuPont scientists discovered losartan, the first angiotensin II receptor antagonist. Essential aspects of the story include: i) the discovery occurred at a young and inexperienced pharmaceutical business; ii) three bench scientists had recently graduated from PhD programmes and only the fourth had any industrial research experience; iii) pivotal to its success was the support and risk-taking of the highly experienced and recently hired head of pharmaceutical research; iv) a timely patent issued to Takeda Chemical Industries suggested a new line of research; v) a mistake made by an inexperienced pharmacologist yielded pivotal information; vi) the bench scientists were given the freedom to explore while being supported by research managers; vii) luck favoured the scientists in losartan's subreceptor-binding and metabolite; and viii) the marketing group insisted that losartan not be developed until Merck expressed an interest in the drug candidate. Today, losartan is a multibillion dollar drug. PMID:23506070

  5. The Most Luminous Galaxies Discovered by WISE

    CERN Document Server

    Tsai, Chao-Wei; Wu, Jingwen; Stern, Daniel; Assef, Roberto; Blain, Andrew; Bridge, Carrie; Benford, Dominic; Cutri, Roc; Griffith, Roger; Jarrett, Thomas; Lonsdale, Carol; Masci, Frank; Moustakas, Leonidas; Petty, Sara; Sayers, Jack; Stanford, S Adam; Wright, Edward; Yan, Lin; Leisawitz, David; Liu, Fengchuan; Mainzer, Amy; McLean, Ian; Padgett, Deborah; Skrutskie, Michael; Gelino, Christopher; Beichman, Charles; Juneau, Stéphanie

    2014-01-01

    We present 20 WISE-selected galaxies with bolometric luminosities L_bol > 10^14 L_sun, including five with infrared luminosities L_IR = L(rest 8-1000 micron) > 10^14 L_sun. These "extremely luminous infrared galaxies," or ELIRGs, were discovered using the "W1W2-dropout" selection criteria (Eisenhardt et al. 2012) which requires marginal or non-detections at 3.4 and 4.6 micron (W1 and W2, respectively) but strong detections at 12 and 22 micron in the WISE survey. Their spectral energy distributions are dominated by emission at rest-frame 4-10 micron, suggesting that hot dust with T_d ~ 450K is responsible for the high luminosities. These galaxies are likely powered by highly obscured AGNs, and there is no evidence suggesting these systems are beamed or lensed. We compare this WISE-selected sample with 116 optically selected quasars that reach the same L_bol level, corresponding to the most luminous unobscured quasars in the literature. We find that the rest-frame 5.8 and 7.8 micron luminosities of the WISE-sel...

  6. Discover Space: an IYA program for libraries

    Science.gov (United States)

    Dusenbery, P.

    2009-12-01

    Across the country, there is a growing concern regarding the number of students entering science and technology careers. While the focus for education reform is on school improvement, there is considerable research that supports the role that out-of-school experiences can play in student achievement. This is particularly true when family interactions are factored in. Libraries provide an untapped resource for engaging underserved youth and their families in fostering an appreciation and deeper understanding of science and technology topics. The nation’s more than 17,000 public libraries attract diverse audiences in almost every community. Science exhibits in libraries could potentially reach many adults and upper elementary and middle school students with STEM content. The Space Science Institute (SSI) is partnering with the American Library Association (ALA) to develop a pilot exhibit called Discover Space. The exhibit includes two areas: Space Storms and Star Quest and is currently on tour in Colorado. It is a featured IYA outreach project from SSI. This presentation will focus on the results of a national survey of libraries that SSI and ALA conducted in 2008 about interest in STEM exhibits as well as the development process that was used to design and fabricate the exhibit. Preliminary evaluation results will also be shared. The presentation will conclude with an examination of how this program could benefit underserved communities around the country.

  7. Astronomers Discover Fastest-Spinning Pulsar

    Science.gov (United States)

    2006-01-01

    Astronomers using the National Science Foundation's Robert C. Byrd Green Bank Telescope have discovered the fastest-spinning neutron star ever found, a 20-mile-diameter superdense pulsar whirling faster than the blades of a kitchen blender. Their work yields important new information about the nature of one of the most exotic forms of matter known in the Universe. Pulsar Graphic Pulsars Are Spinning Neutron Stars CREDIT: Bill Saxton, NRAO/AUI/NSF (Click on image for larger version) "We believe that the matter in neutron stars is denser than an atomic nucleus, but it is unclear by how much. Our observations of such a rapidly rotating star set a hard upper limit on its size, and hence on how dense the star can be.," said Jason Hessels, a graduate student at McGill University in Montreal. Hessels and his colleagues presented their findings to the American Astronomical Society's meeting in Washington, DC. Pulsars are spinning neutron stars that sling "lighthouse beams" of radio waves or light around as they spin. A neutron star is what is left after a massive star explodes at the end of its "normal" life. With no nuclear fuel left to produce energy to offset the stellar remnant's weight, its material is compressed to extreme densities. The pressure squeezes together most of its protons and electrons to form neutrons; hence, the name "neutron star." "Neutron stars are incredible laboratories for learning about the physics of the fundamental particles of nature, and this pulsar has given us an important new limit," explained Scott Ransom, an astronomer at the National Radio Astronomy Observatory and one of Hessels' collaborators on this work. The scientists discovered the pulsar, named PSR J1748-2446ad, in a globular cluster of stars called Terzan 5, located some 28,000 light-years from Earth in the constellation Sagittarius. The newly-discovered pulsar is spinning 716 times per second, or at 716 Hertz (Hz), readily beating the previous record of 642 Hz from a pulsar

  8. Discovering New R Coronae Borealis Stars

    Science.gov (United States)

    Clayton, Geoffrey C.; Tisserand, Patrick; Welch, Douglas L.; LeBleu, Amy

    2016-01-01

    The R Coronae Borealis (RCB) stars are rare hydrogen-deficient, carbon-rich supergiants. Two evolutionary scenarios have been suggested, a double degenerate merger of two white dwarfs, or a final helium shell flash in a PN central star. The evidence pointing toward a white-dwarf merger or a final-flash origin for RCB stars is contradictory. The distribution on the sky and radial velocities of the RCB stars tend toward those of the bulge population but a much larger sample of stars is needed to determine the true population. We need to discover RCB stars much more efficiently. In order to do this, we have used a series of IR color-color cuts, using the recent release of the WISE All-Sky Catalog, to produce a sample of 2200 candidates that may yield over 200 new RCB star identifications. Most of these candidates do not have lightcurves, the traditional technique of identifying RCB stars from their characteristic large and irregular light variations. We have obtained optical spectra of several hundred candidates and have confirmed over 40 new RCB stars in the Galaxy. We are attempting to develop a quantitative spectral classification system for the RCB stars so that they can be identified without an accompanying light curve. The cooler RCB stars look like carbon stars with strong C2 bands, but they can be differentiated from carbon stars by their extreme hydrogen deficiency and very low 13C/12C ratio. Also, the red CN bands are much weaker in RCB stars than in carbon stars. The number of RCB stars in the Galaxy may be consistent with the predicted number of He/CO white-dwarf mergers. Solving the mystery of how the RCB stars evolve would be a watershed event in the study of stellar evolution that will lead to a better understanding of other important types of stellar merger events such as Type Ia SNe.

  9. ROSAT Discovers Unique, Distant Cluster of Galaxies

    Science.gov (United States)

    1995-06-01

    Brightest X-ray Cluster Acts as Strong Gravitational Lens Based on exciting new data obtained with the ROSAT X-ray satellite and a ground-based telescope at the ESO La Silla Observatory, a team of European astronomers [2] has just discovered a very distant cluster of galaxies with unique properties. It emits the strongest X-ray emission of any cluster ever observed by ROSAT and is accompanied by two extraordinarily luminous arcs that represent the gravitationally deflected images of even more distant objects. The combination of these unusual characteristics makes this cluster, now known as RXJ1347.5-1145, a most interesting object for further cosmological studies. DISCOVERY AND FOLLOW-UP OBSERVATIONS This strange cluster of galaxies was discovered during the All Sky Survey with the ROSAT X-ray satellite as a moderately intense X-ray source in the constellation of Virgo. It could not be identified with any already known object and additional ground-based observations were therefore soon after performed with the Max-Planck-Society/ESO 2.2-metre telescope at the La Silla observatory in Chile. These observations took place within a large--scale redshift survey of X-ray clusters of galaxies detected by the ROSAT All Sky Survey, a so-called ``ESO Key Programme'' led by astronomers from the Max-Planck-Institut fur Extraterrestrische Physik and the Osservatorio Astronomico di Brera. The main aim of this programme is to identify cluster X-ray sources, to determine the distance to the X-ray emitting clusters and to investigate their overall properties. These observations permitted to measure the redshift of the RXJ1347.5-1145 cluster as z = 0.45, i.e. it moves away from us with a velocity (about 106,000 km/sec) equal to about one-third of the velocity of light. This is an effect of the general expansion of the universe and it allows to determine the distance as about 5,000 million light-years (assuming a Hubble constant of 75 km/sec/Mpc). In other words, we see these

  10. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

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

  11. THE MOST LUMINOUS GALAXIES DISCOVERED BY WISE

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Chao-Wei; Eisenhardt, Peter R. M.; Stern, Daniel; Moustakas, Leonidas A. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Dr., Pasadena, CA 91109 (United States); Wu, Jingwen; Wright, Edward L. [Department of Physics and Astronomy, UCLA, Los Angeles, CA 90095-1547 (United States); Assef, Roberto J. [Núcleo de Astronomía de la Facultad deIngeniería, Universidad Diego Portales, Av. Ejército Libertador 441, Santiago (Chile); Blain, Andrew W. [Department of Physics and Astronomy, University of Leicester, 1 University Road, Leicester, LE1 7RH (United Kingdom); Bridge, Carrie R.; Sayers, Jack [Division of Physics, Math, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Benford, Dominic J.; Leisawitz, David T. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Cutri, Roc M.; Masci, Frank J.; Yan, Lin [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Griffith, Roger L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Jarrett, Thomas H. [Astronomy Department, University of Cape Town, Private Bag X3, Rondebosch 7701 (South Africa); Lonsdale, Carol J. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Petty, Sara M. [Department of Physics, Virginia Tech, Blacksburg, VA 24061 (United States); Stanford, S. Adam, E-mail: Chao-Wei.Tsai@jpl.nasa.gov [Department of Physics, University of California Davis, One Shields Avenue, Davis, CA 95616 (United States); and others

    2015-06-01

    We present 20 Wide-field Infrared Survey Explorer (WISE)-selected galaxies with bolometric luminosities L{sub bol} > 10{sup 14} L{sub ☉}, including five with infrared luminosities L{sub IR} ≡ L{sub (rest} {sub 8–1000} {sub μm)} > 10{sup 14} L{sub ☉}. These “extremely luminous infrared galaxies,” or ELIRGs, were discovered using the “W1W2-dropout” selection criteria which requires marginal or non-detections at 3.4 and 4.6 μm (W1 and W2, respectively) but strong detections at 12 and 22 μm in the WISE survey. Their spectral energy distributions are dominated by emission at rest-frame 4–10 μm, suggesting that hot dust with T{sub d} ∼ 450 K is responsible for the high luminosities. These galaxies are likely powered by highly obscured active galactic nuclei (AGNs), and there is no evidence suggesting these systems are beamed or lensed. We compare this WISE-selected sample with 116 optically selected quasars that reach the same L{sub bol} level, corresponding to the most luminous unobscured quasars in the literature. We find that the rest-frame 5.8 and 7.8 μm luminosities of the WISE-selected ELIRGs can be 30%–80% higher than that of the unobscured quasars. The existence of AGNs with L{sub bol} > 10{sup 14} L{sub ☉} at z > 3 suggests that these supermassive black holes are born with large mass, or have very rapid mass assembly. For black hole seed masses ∼10{sup 3} M{sub ☉}, either sustained super-Eddington accretion is needed, or the radiative efficiency must be <15%, implying a black hole with slow spin, possibly due to chaotic accretion.

  12. VLA Discovers Giant Rings Around Galaxy Cluster

    Science.gov (United States)

    2006-11-01

    Astronomers using the National Science Foundation's Very Large Array (VLA) radio telescope have discovered giant, ring-like structures around a cluster of galaxies. The discovery provides tantalizing new information about how such galaxy clusters are assembled, about magnetic fields in the vast spaces between galaxy clusters, and possibly about the origin of cosmic rays. Radio-Optical Image of Cluster Galaxy Cluster Abell 3376 (Radio/Optical) CREDIT: Joydeep Bagchi, IUCAA, NRAO/AUI/NSF Above, a combined radio/optical image shows the galaxy cluster Abell 3376 in visible light (blue) and radio (red) images. The giant radio arcs surrounding the cluster were discovered using the Very Large Array. The visible-light image is from the Digitized Sky survey. Below, an X-ray image of Abell 3376 made using the European Space Agency's XMM-Newton telescope shows a spectacular, bullet-shaped region of X-rays coming from gas heated to 60 million degrees Kelvin. The bullet shape results from the supersonic collision of a smaller smaller galaxy subcluster with the main body of the larger cluster. Click on images for larger version. X-Ray Image of Cluster Galaxy Cluster Abell 3376 (X-Ray) CREDIT: Joydeep Bagchi, IUCAA, ESA "These giant, radio-emitting rings probably are the result of shock waves caused by violent collisions of smaller groups of galaxies within the cluster," said Joydeep Bagchi, of the Inter-University Centre for Astronomy and Astrophysics in Pune, India, who led an international research team. The scientists reported their findings in the November 3 edition of the journal Science. The newly-discovered ring segments, some 6 million light-years across, surround a galaxy cluster called Abell 3376, more than 600 million light-years from Earth. They were revealed because fast-moving electrons emitted radio waves as they spiraled around magnetic field lines in intergalactic space. "Even from this large distance, the feeble radio waves were easily picked up by the VLA

  13. The Impact of Discovering Life beyond Earth

    Science.gov (United States)

    Dick, Steven J.

    2015-10-01

    Introduction: astrobiology and society Steven J. Dick; Part I. Motivations and Approaches. How Do We Frame the Problems of Discovery and Impact?: Introduction; 1. Current approaches to finding life beyond earth, and what happens if we do Seth Shostak; 2. The philosophy of astrobiology: the Copernican and Darwinian presuppositions Iris Fry; 3. History, discovery, analogy: three approaches to the impact of discovering life beyond earth Steven J. Dick; 4. Silent impact: why the discovery of extraterrestrial life should be silent Clément Vidal; Part II. Transcending Anthropocentrism. How Do We Move beyond our Own Preconceptions of Life, Intelligence and Culture?: Introduction; 5. The landscape of life Dirk Schulze-Makuch; 6. The landscape of intelligence Lori Marino; 7. Universal biology: assessing universality from a single example Carlos Mariscal; 8. Equating culture, civilization, and moral development in imagining extraterrestrial intelligence: anthropocentric assumptions? John Traphagan; 9. Communicating with the other: infinity, geometry, and universal math and science Douglas Vakoch; Part III. Philosophical, Theological, and Moral Impact. How Do We Comprehend the Cultural Challenges Raised by Discovery?: Introduction; 10. Life, intelligence and the pursuit of value in cosmic evolution Mark Lupisella; 11. 'Klaatu barada nikto' - or, do they really think like us? Michael Ruse; 12. Alien minds Susan Schneider; 13. The moral subject of astrobiology: guideposts for exploring our ethical and political responsibilities towards extraterrestrial life Elspeth Wilson and Carol Cleland; 14. Astrobiology and theology Robin Lovin; 15. Would you baptize an extraterrestrial? Guy Consolmagno, SJ; Part IV. Practical Considerations: How Should Society Prepare for Discovery - and Non-Discovery?: Introduction; 16. Is there anything new about astrobiology and society? Jane Maienschein; 17. Evaluating preparedness for the discovery of extraterrestrial life: considering potential

  14. Discovering Extrasolar Planets with Microlensing Surveys

    Science.gov (United States)

    Wambsganss, J.

    2016-06-01

    An astronomical survey is commonly understood as a mapping of a large region of the sky, either photometrically (possibly in various filters/wavelength ranges) or spectroscopically. Often, catalogs of objects are produced/provided as the main product or a by-product. However, with the advent of large CCD cameras and dedicated telescopes with wide-field imaging capabilities, it became possible in the early 1990s, to map the same region of the sky over and over again. In principle, such data sets could be combined to get very deep stacked images of the regions of interest. However, I will report on a completely different use of such repeated maps: Exploring the time domain for particular kinds of stellar variability, namely microlens-induced magnifications in search of exoplanets. Such a time-domain microlensing survey was originally proposed by Bohdan Paczynski in 1986 in order to search for dark matter objects in the Galactic halo. Only a few years later three teams started this endeavour. I will report on the history and current state of gravitational microlensing surveys. By now, routinely 100 million stars in the Galactic Bulge are monitored a few times per week by so-called survey teams. All stars with constant apparent brightness and those following known variability patterns are filtered out in order to detect the roughly 2000 microlensing events per year which are produced by stellar lenses. These microlensing events are identified "online" while still in their early phases and then monitored with much higher cadence by so-called follow-up teams. The most interesting of such events are those produced by a star-plus-planet lens. By now of order 30 exoplanets have been discovered by these combined microlensing surveys. Microlensing searches for extrasolar planets are complementary to other exoplanet search techniques. There are two particular advantages: The microlensing method is sensitive down to Earth-mass planets even with ground-based telecopes, and it

  15. New Galactic supernova remnants discovered with IPHAS

    Science.gov (United States)

    Sabin, L.; Parker, Q. A.; Contreras, M. E.; Olguín, L.; Frew, D. J.; Stupar, M.; Vázquez, R.; Wright, N. J.; Corradi, R. L. M.; Morris, R. A. H.

    2013-05-01

    As part of a systematic search programme of a 10° wide strip of the northern Galactic plane, we present preliminary evidence for the discovery of four (and possibly five) new supernova remnants (SNRs). The pilot search area covered the 19-20 h right ascension zone sampling from +20° to +55° in declination using binned mosaic images from the Isaac Newton Telescope Photometric Hα Survey (IPHAS). The optical identification of the candidate SNRs was based mainly on their filamentary and arc-like emission morphologies, their apparently coherent, even if fractured, structure and clear disconnection from any diffuse neighbouring H II region type nebulosity. Follow-up optical spectroscopy was undertaken, sampling carefully across prominent features of these faint sources. The resulting spectra revealed typical emission-line ratios for shock-excited nebulae which are characteristic of SNRs, which, along with the latest diagnostic diagrams, strongly support the likely SNR nature of these sources: G038.7-1.3 (IPHASX J190640.5+042819), G067.6+0.9 (IPHASX J195744.9+305306), G066.0-0.0 (IPHASX J195749.2+290259) and G065.8-0.5 (IPHASX J195920.4+283740). A fifth possible younger, higher density nebula SNR candidate, G067.8+0.5 (IPHASX J200002.4+305035), was discovered ˜5 arcmin to the west of IPHASX J195744.9+305306, and it warrants further study. A multiwavelength cross-check from available archived data in the regions of these candidates was also performed with a focus on possible radio counterparts. A close positional match between previously unrecognized radio structures at several frequencies and across various components of the Hα optical image data was found for all SNR candidates. This lends further direct support for the SNR nature of these objects. Evolved SNRs may have very weak and/or highly fragmented radio emission which could explain why they had not been previously recognized, but the association becomes clear in combination with the optical emission.

  16. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.

    Science.gov (United States)

    Hancock, Robert E W; Sahl, Hans-Georg

    2006-12-01

    Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.

  17. Strategies for the discovery of therapeutic Aptamers

    Science.gov (United States)

    Yang, Xianbin; Li, Na; Gorenstein, David G.

    2010-01-01

    Importance of the field Therapeutic aptamers are synthetic, structured oligonucleotides that bind to a very broad range of targets with high affinity and specificity. They are an emerging class of targeting ligand that show great promise for treating a number of diseases. A series of aptamers currently in various stages of clinical development highlights the potential of aptamers for therapeutic applications. Area covered in this review This review will cover in vitro selection of oligonucleotide ligands, called aptamers, from a combinatorial library using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process as well as the other known strategies for finding aptamers against various targets. What the reader will gain Readers will gain an understanding of the highly useful strategies for successful aptamer discovery. They may also be able combine two or more of the presented strategies for their aptamer discovery projects. Take home message Although many processes are available for discovering aptamers, it is not trivial to discover an aptamer candidate that is ready to move toward pharmaceutical drug development. It is also apparent that there have been relatively few therapeutic advances and clinical trials undertaken due to the small number of companies that participate in aptamer development. PMID:21359096

  18. PSLQ: An Algorithm to Discover Integer Relations

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, J. M.

    2009-04-03

    Let x = (x{sub 1}, x{sub 2} {hor_ellipsis}, x{sub n}) be a vector of real or complex numbers. x is said to possess an integer relation if there exist integers a{sub i}, not all zero, such that a{sub 1}x{sub 1} + a{sub 2}x{sub 2} + {hor_ellipsis} + a{sub n}x{sub n} = 0. By an integer relation algorithm, we mean a practical computational scheme that can recover the vector of integers ai, if it exists, or can produce bounds within which no integer relation exists. As we will see in the examples below, an integer relation algorithm can be used to recognize a computed constant in terms of a formula involving known constants, or to discover an underlying relation between quantities that can be computed to high precision. At the present time, the most effective algorithm for integer relation detection is the 'PSLQ' algorithm of mathematician-sculptor Helaman Ferguson [10, 4]. Some efficient 'multi-level' implementations of PSLQ, as well as a variant of PSLQ that is well-suited for highly parallel computer systems, are given in [4]. PSLQ constructs a sequence of integer-valued matrices B{sub n} that reduces the vector y = xB{sub n}, until either the relation is found (as one of the columns of B{sub n}), or else precision is exhausted. At the same time, PSLQ generates a steadily growing bound on the size of any possible relation. When a relation is found, the size of smallest entry of the vector y abruptly drops to roughly 'epsilon' (i.e. 10{sup -p}, where p is the number of digits of precision). The size of this drop can be viewed as a 'confidence level' that the relation is real and not merely a numerical artifact - a drop of 20 or more orders of magnitude almost always indicates a real relation. Very high precision arithmetic must be used in PSLQ. If one wishes to recover a relation of length n, with coefficients of maximum size d digits, then the input vector x must be specified to at least nd digits, and one must employ nd

  19. Ultrasound: A Revenant Therapeutic Modality in Dentistry.

    Science.gov (United States)

    Karumuri, Sunil Kumar; Rastogi, Trisha; Beeraka, Kartheeki; Penumatcha, Mohan Raju; Olepu, Sanjeeva Rao

    2016-07-01

    An ultrasound (US) gives a visible image of the organs that are present inside the body. In medicine it serves for diagnosing and also its therapeutic benefits are well established for bone healing, osteointegration and soft tissue healing. In dentistry it is widely used for diagnostic purposes. When it was discovered it was introduced for therapeutic purposes, but due to lack of clinical studies its use as therapy was remittent in dentistry. The aim of the present paper was to establish the efficiency of therapeutic US in maxillofacial region for alleviating the pain and to see the other applications. Our search included the English terms like ultrasonography, applications, dentistry in Google search engine, PubMed and Medline from 1980 to 2015. We found very few articles showing the effects of therapeutic Ultrasound (US) in treatment of pain and healing in dentistry. We concluded that clinical benefits of in vivo studies were very little and demands further rigorous research to strive for the therapeutic success of US. PMID:27630969

  20. Pathogenic inflammation and its therapeutic targeting in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Timothy Andrew Gottschalk

    2015-10-01

    Full Text Available Systemic Lupus Erythematosus (SLE, lupus is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues including skin, kidneys and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B and T lymphocyte activation, and, with the single exception of an agent known as Belimumab which targets the B cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immuno-suppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and

  1. 76 FR 4393 - Discover Financial Services Negotiated Service Agreement

    Science.gov (United States)

    2011-01-25

    ... Financial Services negotiated service agreement to the market dominant product list. This notice addresses... 3020, et seq., to add a Discover Financial Services (DFS) negotiated service agreement to the market... Data and Request to Add Discover Financial Services Negotiated Service Agreement to the...

  2. Therapeutic Recreation Practicum Manual.

    Science.gov (United States)

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  3. Cytokines and therapeutic oligonucleotides.

    Science.gov (United States)

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  4. 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.

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

    OpenAIRE

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-07-24

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

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

    Science.gov (United States)

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

  8. 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.

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

    OpenAIRE

    Yang, Ying; 楊穎

    2014-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

  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 400 nm). This work provides additional supporting evidence that cell death in PL treatment is due to exposure to UV light. Additionally, it was shown that even a minor modification of the light path or the UV light spectrum in PL treatments can have a significant negative impact on the treatment intensity and effectiveness. PMID:17477260

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. 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.

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

    OpenAIRE

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

    1999-01-01

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

  19. 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.

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  3. 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....

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

    Science.gov (United States)

    Stone, Judy

    2010-01-01

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

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

    Science.gov (United States)

    Stone, Judy

    2010-01-01

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

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

    Science.gov (United States)

    Ebrahimi, Pouria

    2010-01-01

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

  7. 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.

  8. 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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    International Nuclear Information System (INIS)

    The excretion and metabolism of 14C-warfarin in rats was examined in a crossover experiment, the first phase consisting of treatment with normal saline, the second phase using the same animals given neomycin, bacitracin, and tetracycline orally. Urine and feces were collected every 24 hours for 72 hours and examined for warfarin and its metabolites, both unconjugated and conjugated. Significantly more radioactivity was eliminated in th feces of antibiotic-treated rats. The feces of antibiotic-treated rats contained only trace amounts of beta-glucuronidase activity. Urine contained a similar ratio of unconjugated to conjugated radioactivity in both treatment groups, but the antibiotic-treated animals had significantly larger amount of conjugates in their feces. Examination of metabolic profiles of conjugated and unconjugated fractions revealed significantly fewer hydroxylated metabolites in antibiotic-treated rats, especially in the feces. The lower amount of hydroxylative metabolism in attributed to a reduction in gut flora-medicated interohepatic recycling caused by the antibiotics

  11. Broad-spectrum antibacterial properties of metal-ion doped borate bioactive glasses for clinical applications

    Science.gov (United States)

    Ottomeyer, Megan

    Bioactive glasses with antimicrobial properties can be implemented as coatings on medical devices and implants, as well as a treatment for tissue repair and prevention of common hospital-acquired infections such as MRSA. A borate-containing glass, B3, is also undergoing clinical trials to assess wound-healing properties. The sensitivities of various bacteria to B3, B3-Ag, B3-Ga, and B3-I bioactive glasses were tested. In addition, the mechanism of action for the glasses was studied by spectroscopic enzyme kinetics experiments, Live-Dead staining fluorescence microscopy, and luminescence assays using two gene fusion strains of Escherichia coli. It was found that gram-positive bacteria were more sensitive to all four glasses than gram negative bacteria, and that a single mechanism of action for the glasses is unlikely, as the rates of catalysis for metabolic enzymes as well as membrane permeability were altered after glass exposure.

  12. 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

  13. 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.

  14. 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.

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

    DEFF Research Database (Denmark)

    Faurschou, A.; Wulf, Hans Chr.

    2008-01-01

    . Observations: Three patients with idiopathic solar urticaria underwent phototesting with UV-B and UV-A radiation. The minimal urticarial dose (MUD) was determined 15 minutes after irradiation. The patients were subsequently tested with 5 times the MUD, and the reaction was graded every minute for 15 minutes......Background: It can be difficult to provide patients with idiopathic solar urticaria adequate protection from sunlight. In a nonrandomized controlled trial, we used a standardized phototest procedure to determine the effects of using sunscreen and antihistamine to control idiopathic solar urticaria......). Antihistamine use did not increase the patients' MUD but did suppress wheal formation and itch, and only immediate erythema sharply located in the irradiated areas occurred. The combination of sunscreen and antihistamine acted synergistically and increased the tolerance to UV radiation markedly (80-267 times...

  16. 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.

  17. 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.

  18. The broad spectrum of Trichinella hosts: from cold- to warm-blooded animals.

    Science.gov (United States)

    Pozio, E

    2005-09-01

    In recent years, studies on Trichinella have shown that the host range is wider than previously believed and new Trichinella species and genotypes have been described. Three classes of vertebrates are known to act as hosts, mammals, birds and reptiles, and infected vertebrates have been detected on all continents but Antarctica. Mammals represent the most important hosts and all Trichinella species are able to develop in this vertebrate class. Natural infections with Trichinella have been described in more than 150 mammalian species belonging to 12 orders (i.e., Marsupialia, Insectivora, Edentata, Chiroptera, Lagomorpha, Rodentia, Cetacea, Carnivora, Perissodactyla, Artiodactyla, Tylopoda and Primates). The epidemiology of the infection greatly varies by species relative to characteristics, such as diet, life span, distribution, behaviour, and relationships with humans. The non-encapsulated species Trichinella pseudospiralis, detected in both mammals (14 species) and birds (13 species), shows a cosmopolitan distribution with three distinguishable populations in the Palearctic, Nearctic and Australian regions. Two additional non-encapsulated species, Trichinella papuae, detected in wild pigs and saltwater crocodiles of Papua New Guinea, and Trichinella zimbabwensis, detected in farmed Nile crocodiles of Zimbabwe, can complete their life cycle in both mammals and reptiles. To the best of our knowledge, T. papuae and T. zimbabwensis are the only two parasites known to complete their entire life cycle independently of whether the host is warm-blooded or cold-blooded. This suggests that these two Trichinella species are capable of activating different physiological mechanisms, according to the specific vertebrate class hosting them. PMID:15970384

  19. 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)

  20. Broad Spectrum Activity of a Lectin-Like Bacterial Serine Protease Family on Human Leukocytes

    Science.gov (United States)

    Ayala-Lujan, Jorge Luis; Vijayakumar, Vidhya; Gong, Mei; Smith, Rachel; Santiago, Araceli E.; Ruiz-Perez, Fernando

    2014-01-01

    The serine protease autotransporter from Enterobacteriaceae (SPATE) family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system. PMID:25251283

  1. Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs.

    Science.gov (United States)

    McTier, Tom L; Chubb, Nathan; Curtis, Michael P; Hedges, Laura; Inskeep, Gregory A; Knauer, Christopher S; Menon, Sanjay; Mills, Brian; Pullins, Aleah; Zinser, Erich; Woods, Debra J; Meeus, Patrick

    2016-05-30

    The novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties. The flea and tick activity resides in the chirally pure S-enantiomer, which was purified to alleviate potential off-target effects from the inactive enantiomer. The mechanism of action was established in electrophysiology assays using CHO-K1 cell lines stably expressing cat flea (Ctenocephalides felis) RDL (resistance-to-dieldrin) genes for assessment of GABA-gated chloride channel (GABACls) pharmacology. As expected, sarolaner inhibited GABA-elicited currents at both susceptible (CfRDL-A285) and resistant (CfRDL-S285) flea GABACls with similar potency. Initial whole organism screening was conducted in vitro using a blood feeding assay against C. felis. Compounds which demonstrated robust activity in the flea feed assay were subsequently tested in an in vitro ingestion assay against the soft tick, Ornithodoros turicata. Efficacious compounds which were confirmed safe in rodents at doses up to 30mg/kg were progressed to safety, PK and efficacy studies in dogs. In vitro sarolaner demonstrated an LC80 of 0.3μg/mL against C. felis and an LC100 of 0.003μg/mL against O. turicata. In a head-to-head comparative in vitro assay with both afoxolaner and fluralaner, sarolaner demonstrated superior flea and tick potency. In exploratory safety studies in dogs, sarolaner demonstrated safety in dogs≥8 weeks of age upon repeated monthly dosing at up to 20mg/kg. Sarolaner was rapidly and well absorbed following oral dosing. Time to maximum plasma concentration occurred within the first day post-dose. Bioavailability for sarolaner was calculated at >85% and the compound was highly protein bound (>99.9%). The half-life for sarolaner was calculated at 11-12 days. Sarolaner plasma concentrations indicated dose proportionality over the range 1.25-5mg/kg, and these same doses provided robust efficacy (>99%) for ≥35days against both fleas (C. felis) and multiple species of ticks (Rhipicephalus sanguineus, Ixodes ricinus and Dermacentor reticulatus) after oral administration to dogs. As a result of these exploratory investigations, sarolaner was progressed for development as an oral monthly dose for treatment and control of fleas and ticks on dogs. PMID:26961590

  2. 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.

  3. 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.

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

    OpenAIRE

    Ragioto DA; Carrasco LD; Carmona-Ribeiro AM

    2014-01-01

    Danielle AMT Ragioto, Letícia DM Carrasco, Ana M Carmona-Ribeiro Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil Abstract: Dioctadecyldimethylammonium bromide (DODAB) is an antimicrobial lipid that can be dispersed as large closed bilayers (LV) or bilayer disks (BF). Gramicidin (Gr) is an antimicrobial peptide assembling as channels in membranes and increasing their permeability towards ca...

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

    Directory of Open Access Journals (Sweden)

    Ragioto DA

    2014-06-01

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

  6. Laboratory simulation of interplanetary ultraviolet radiation (broad spectrum) and its effects on Deinococcus radiodurans

    Science.gov (United States)

    Paulino-Lima, Ivan Gláucio; Pilling, Sérgio; Janot-Pacheco, Eduardo; de Brito, Arnaldo Naves; Barbosa, João Alexandre Ribeiro Gonçalves; Leitão, Alvaro Costa; Lage, Claudia de Alencar Santos

    2010-08-01

    The radiation-resistant bacterium Deinococcus radiodurans was exposed to a simulated interplanetary UV radiation at the Brazilian Synchrotron Light Laboratory (LNLS). Bacterial samples were irradiated on different substrates to investigate the influence of surface relief on cell survival. The effects of cell multi-layers were also investigated. The ratio of viable microorganisms remained virtually the same (average 2%) for integrated doses from 1.2 to 12 kJ m -2, corresponding to 16 h of irradiation at most. The asymptotic profiles of the curves, clearly connected to a shielding effect provided by multi-layering cells on a cavitary substrate (carbon tape), means that the inactivation rate may not change significantly along extended periods of exposure to radiation. Such high survival rates reinforce the possibility of an interplanetary transfer of viable microbes.

  7. 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.

  8. 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

  9. Synthesis and antimicrobial evaluation of nitazoxanide-based analogues: identification of selective and broad spectrum activity.

    Science.gov (United States)

    Ballard, T Eric; Wang, Xia; Olekhnovich, Igor; Koerner, Taylor; Seymour, Craig; Salamoun, Joseph; Warthan, Michelle; Hoffman, Paul S; Macdonald, Timothy L

    2011-02-01

    A library composed of nitazoxanide-based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate-ferredoxin oxidoreductase (PFOR) using microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt the PFOR enzyme directly. The library was also screened for activity against staphylococci and resulted in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations with low toxicity to human foreskin cells. PMID:21275058

  10. 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.

  11. Discovering Aptamers by Cell-SELEX against Human Soluble Growth Factors Ectopically Expressed on Yeast Cell Surface

    OpenAIRE

    Hsien-Wei Meng; Pagano, John M.; White, Brian S.; Yoshiko Toyoda; Min, Irene M.; Craighead, Harold G; David Shalloway; Lis, John T.; Kai Xiao; Moonsoo M Jin

    2014-01-01

    SELEX, the process of selecting aptamers, is often hampered by the difficulty of preparing target molecules in their native forms and by a lack of a simple yet quantitative assay for monitoring enrichment and affinity of reactive aptamers. In this study, we sought to discover DNA aptamers against human serum markers for potential therapeutic and diagnostic applications. To circumvent soluble expression and immobilization for performing SELEX, we ectopically expressed soluble growth factors on...

  12. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  13. Digging Deeper: Looking Beyond Behavior to Discover Meaning

    Medline Plus

    Full Text Available ... Email Client Print Español Digging Deeper: Looking Beyond Behavior to Discover Meaning A Unit of Four Online ... started ZIP Code Search Department of Health and Human Services Administration for Children and Families Office of ...

  14. Strontium-90 Error Discovered in Subcontract Laboratory Spreadsheet. Topical Report

    International Nuclear Information System (INIS)

    West Valley Demonstration Project health physicists and environment scientists discovered a series of errors in a subcontractor's spreadsheet being used to reduce data as part of their strontium-90 analytical process

  15. Discovering Patterns in Biological Sequences by Optimal Segmentation

    OpenAIRE

    Bockhorst, Joseph; Jojic, Nebojsa

    2012-01-01

    Computational methods for discovering patterns of local correlations in sequences are important in computational biology. Here we show how to determine the optimal partitioning of aligned sequences into non-overlapping segments such that positions in the same segment are strongly correlated while positions in different segments are not. Our approach involves discovering the hidden variables of a Bayesian network that interact with observed sequences so as to form a set of independent mixture ...

  16. HIV capsid is a tractable target for small molecule therapeutic intervention.

    Directory of Open Access Journals (Sweden)

    Wade S Blair

    Full Text Available Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA via a novel mechanism of action. The compounds exhibit potent antiviral activity against HIV-1 laboratory strains, clinical isolates, and HIV-2, and inhibit both early and late events in the viral replication cycle. We present mechanistic studies indicating that these early and late activities result from the compound affecting viral uncoating and assembly, respectively. We show that amino acid substitutions in the N-terminal domain of HIV-1 CA are sufficient to confer resistance to this class of compounds, identifying CA as the target in infected cells. A high-resolution co-crystal structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the N-terminal domain of the protein. Our data demonstrate that broad-spectrum antiviral activity can be achieved by targeting this new binding site and reveal HIV CA as a tractable drug target for HIV therapy.

  17. G protein-coupled receptors as therapeutic targets for multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Changsheng Du; Xin Xie

    2012-01-01

    G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones,neurotransmitters and environmental stimulants.They are considered as the most successful therapeutic targets for a broad spectrum of diseases.Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS).It is the leading cause of non-traumatic disability in young adults.Great progress has been made over the past few decades in understanding the pathogenesis of MS.Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis,including antigen presentation,cytokine production,T-cell differentiation,T-cell proliferation,T-cell invasion,etc.In this review,we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models,and the influences of GPCRs on disease severity upon genetic or pharmacological manipulations.Hopefully some of these findings will lead to the development of novel therapies for MS in the near future.

  18. Therapeutic potential of stem cells in skin repair and regeneration

    Institute of Scientific and Technical Information of China (English)

    ZHANG Cui-ping; FU Xiao-bing

    2008-01-01

    @@ Stem cells are defined by their capacity of self-renewal and multilineage differentiation, which make them uniquely situated to treat a broad spectrum of human diseases. Based on a series of remarkable studies in several fields of regen-erative medicine, their application is not too far from the clinical practice.

  19. Maintaining Discovered Frequent Itemsets: Cases for Changeable Database and Support

    Institute of Scientific and Technical Information of China (English)

    DU XiaoPing(杜孝平); TANG ShiWei(唐世渭); Akifumi Makinouchi(牧之内顕文)

    2003-01-01

    Mining frequent itemsets from large databases has played an essential role inmany data mining tasks. It is also important to maintain the discovered frequent itemsets forthese data mining tasks when the database is updated. All algorithms proposed so far for the maintenance of discovered frequent itemsets are only performed with a fixed minimum support,which is the same as that used to obtain the discovered frequent itemsets. That is, users cannot change the minimum support even if the new results are unsatisfactory to the users. In thispaper two new complementary algorithms, FMP (First Maintaining Process) and RMP (Repeated Maintaining Process), are proposed to maintain discovered frequent itemsets in the case that new transaction data are added to a transaction database. Both algorithms allow users to change theminimum support for the maintenance processes. FMP is used for the first maintaining process, andwhen the result derived from the FMP is unsatisfactory, RMP will be performed repeatedly untilsatisfactory results are obtained. The proposed algorithms re-use the previous results to cut downthe cost of maintenance. Extensive experiments have been conducted to assess the performance of the algorithms. The experimental results show that the proposed algorithms are very resultful compared with the previous mining and maintenance algorithms for maintenance of discovered frequent itemsets.

  20. Lymphedema and Therapeutic Lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Yukihiro Saito

    2013-01-01

    Full Text Available Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor.

  1. Pluristem Therapeutics, Inc.

    Science.gov (United States)

    Prather, William

    2008-01-01

    Pluristem Therapeutics, Inc., based in Haifa, Israel, is a regenerative, biotherapeutics Company dedicated to the commercialization of nonpersonalized (allogeneic) cell therapy products. The Company is expanding noncontroversial placental-derived mesenchymal stem cells via a proprietary 3D process, named PluriX, into therapeutics for a variety of degenerative, malignant and autoimmune disorders. Pluristem will be conducting Phase I trials in the USA with its first product, PLX-I, which addresses the global shortfall of matched tissue for bone marrow transplantation by improving the engraftment of hematopoietic stem cells contained in umbilical cord blood. PMID:18154467

  2. The Magic of Mathematics Discovering the Spell of Mathematics

    CERN Document Server

    Pappas, Theoni

    2011-01-01

    Delves into the world of ideas, explores the spell mathematics casts on our lives, and helps you discover mathematics where you least expect it. Be spellbound by the mathematical designs found in nature. Learn how knots may untie the mysteries of life. Be mesmerized by the computer revolution. Discover how the hidden forces of mathematics hold architectural structures together connect your telephone calls help airplanes get off the ground solve the mysteries of the living cell. See how some artists use a mathematical palette in their works and how many writers draw upon the wealth of its ideas

  3. Swift Follow-up Observations of MAXI Discovered Galactic Transients

    OpenAIRE

    Kennea, J. A.; Romano, P; Mangano, V.; Beardmore, A. P.; Evans, P A; Curran, P. A.; Krimm, H.A.; Yamaoka, K.

    2011-01-01

    We describe the results of the first year of a program to localize new Galactic Transient sources discovered by MAXI with NASA's Swift mission. Swift is ideally suited for follow-up of MAXI discovered transients as its X-ray Telescope (XRT) field of view (~0.2 degrees radius) is closely matched to the typical MAXI error circle. The XRT is capable of localizing new sources to an accuracy of up to 1.5 arc-seconds radius (90% confidence), and the Swift Optical/UV Telescope also provides optical ...

  4. Ontology Building Using Classification Rules and Discovered Concepts

    Directory of Open Access Journals (Sweden)

    Gorskis Henrihs

    2015-12-01

    Full Text Available Building an ontology is a difficult and time-consuming task. In order to make this task easier and faster, some automatic methods can be employed. This paper examines the feasibility of using rules and concepts discovered during the classification tree building process in the C4.5 algorithm, in a completely automated way, for the purposes of building an ontology from data. By building the ontology directly from continuous data, concepts and relations can be discovered without specific knowledge about the domain. This paper also examines how this method reproduces the classification capabilities of the classification three within an ontology using concepts and class expression axioms.

  5. A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA.

    Directory of Open Access Journals (Sweden)

    Christoph Coch

    Full Text Available Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR or RIG-I like helicases (RLH are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4 was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.

  6. Discovering Fuzzy Censored Classification Rules (Fccrs: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Renu Bala

    2012-08-01

    Full Text Available Classification Rules (CRs are often discovered in the form of ‘If-Then’ Production Rules (PRs. PRs, beinghigh level symbolic rules, are comprehensible and easy to implement. However, they are not capable ofdealing with cognitive uncertainties like vagueness and ambiguity imperative to real word decision makingsituations. Fuzzy Classification Rules (FCRs based on fuzzy logic provide a framework for a flexiblehuman like reasoning involving linguistic variables. Moreover, a classification system consisting of simple‘If-Then’ rules is not competent in handling exceptional circumstances. In this paper, we propose aGenetic Algorithm approach to discover Fuzzy Censored Classification Rules (FCCRs. A FCCR is aFuzzy Classification Rule (FCRs augmented with censors. Here, censors are exceptional conditions inwhich the behaviour of a rule gets modified. The proposed algorithm works in two phases. In the firstphase, the Genetic Algorithm discovers Fuzzy Classification Rules. Subsequently, these FuzzyClassification Rules are mutated to produce FCCRs in the second phase. The appropriate encodingscheme, fitness function and genetic operators are designed for the discovery of FCCRs. The proposedapproach for discovering FCCRs is then illustrated on a synthetic dataset.

  7. Discovering Site-Specific Qualities in Venice and Marseille

    DEFF Research Database (Denmark)

    Reeh, Henrik

    2015-01-01

    When “site-specificity” becomes a central value in city and harbor transfor-mation, it soon proves necessary to address the ways in which scholars and professionals actually come to determine site-specific qualities in urban fab-rics and social life. How are certain traits and habits discovered...

  8. US NSF: scientists discover planetary system similar to our own

    CERN Multimedia

    2003-01-01

    An international team of scientists has discovered a planet and star that may share the same relationship as Jupiter and our Sun, the closest comparison that researchers have found since they began their search for extra-solar planets nearly a decade ago (1 page).

  9. Scientists discover planetary system similar to our own

    CERN Multimedia

    2003-01-01

    'An international team of scientists has discovered a planet and star that may share the same relationship as Jupiter and our Sun, the closest comparison that researchers have found since they began their search for extra-solar planets nearly a decade ago' (1 page).

  10. The Spy VI child : A newly discovered Neandertal infant

    NARCIS (Netherlands)

    Crevecoeur, Isabelle; Bayle, Priscilla; Rougier, Helene; Maureille, Bruno; Higham, Thomas; van der Plicht, Johannes; De Clerck, Nora; Semal, Patrick

    2010-01-01

    Spy cave (Jemeppe-sur-Sambre Belgium) is reputed for the two adult Neandertal individuals discovered in situ in 1886 Recent reassessment of the Spy collections has allowed direct radiocarbon dating of these individuals The sorting of all of the faunal collections has also led to the discovery of the

  11. Therapeutic and cosmetic applications of Evodiamine and its derivatives--A patent review.

    Science.gov (United States)

    Gavaraskar, Kirti; Dhulap, Sivakami; Hirwani, R R

    2015-10-01

    Evodiamine, ((+)-(S)-8,13,13b,14-tetrahydro-14-methylindolo[2',3':3,4]pyrido[2,1-b]quinazolin-5(7H)-one) indoloquinazoline alkaloid, is the major component isolated from the fruits of Evodia rutaecarpa, family Rutaceae. Broad spectrum of pharmacological activities of Evodiamine suggests its imperative role in treating a variety of diseases influencing the function of diverse targets. A comprehensive search was carried out to collect patent information regarding Evodiamine and its derivatives using different patent databases covering priority years to till date. The patents claiming therapeutic as well as cosmetic applications of Evodiamine and its derivatives were analyzed in detail and were classified technically based on the its application such as treatment of metabolic disorders, cancer, neurological disorders, and cardiovascular disorders, etc. The analysis revealed that the use and the mode of actions of Evodiamine and its derivatives in weight management treatments are currently well established. For example the fat reducing property of this alkaloid is primarily due to its mode of actions such as prevention of muscle protein catabolism, enhancement of thermogenesis and lipid oxidation. Apart from its use for treating obesity, Evodiamine and its derivatives are also experimentally explored for their anti-cancer, anti-diabetic and anti-inflammatory properties. The possible mechanisms related to its anti-cancer activity as illustrated by different experimental studies include its potential action as modulator of specific receptors such as topoisomerase I, NF-kappa B and B-cell lymphoma 2 (Bcl2). The analysis hence highlights that, clinical studies pertaining to the anti-cancer, anti-diabetes as well as anti-inflammatory activities of the Evodiamine and its derivatives would possess important market potential for the development of Evodiamine based therapeutics. PMID:26255828

  12. Multistage vector (MSV) therapeutics.

    Science.gov (United States)

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  13. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity......Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... and hence adjuvants are included to enhance and direct the immune response. Although the vaccine has been tested in ART naïve individuals, we recommend future testing of the vaccine during (early started) ART that improves immune function and to select individuals likely to benefit. Peptides representing...

  14. Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

    Directory of Open Access Journals (Sweden)

    Gao CH

    2014-03-01

    Full Text Available Chu-Han Gao,1 Lu-Shan Yu,2 Su Zeng,2 Yu-Wen Huang,1 Quan Zhou11Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of ChinaBackground: Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities, socioeconomic, and cultural factors. Levofloxacin (LVX is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.Methods: Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.Results: In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX

  15. Corneal neovascularization and contemporary antiangiogenic therapeutics.

    Science.gov (United States)

    Hsu, Chih-Chien; Chang, Hua-Ming; Lin, Tai-Chi; Hung, Kuo-Hsuan; Chien, Ke-Hung; Chen, Szu-Yu; Chen, San-Ni; Chen, Yan-Ting

    2015-06-01

    Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research-the alkali-induced model and the suture-induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet-derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

  16. Lymphedema and Therapeutic Lymphangiogenesis

    OpenAIRE

    Yukihiro Saito; Hironori Nakagami; Yasufumi Kaneda; Ryuichi Morishita

    2013-01-01

    Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The r...

  17. Polycyclic peptide therapeutics.

    Science.gov (United States)

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

  18. A drug from poison: how the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered.

    Science.gov (United States)

    Rao, Yi; Li, Runhong; Zhang, Daqing

    2013-06-01

    It is surprising that, while arsenic trioxide (ATO) is now considered as "the single most active agent in patients with acute promyelocytic leukemia (APL)", the most important discoverer remains obscure and his original papers have not been cited by a single English paper. The discovery was made during the Cultural Revolution when most Chinese scientists and doctors struggled to survive. Beginning with recipes from a countryside practitioner that were vague in applicable diseases, Zhang TingDong and colleagues proposed in the 1970s that a single chemical in the recipe is most effective and that its target is APL. More than 20 years of work by Zhang and colleagues eliminated the confusions about whether and how ATO can be used effectively. Other researchers, first in China and then in the West, followed his lead. Retrospective analysis of data from his own group proved that APL was indeed the most sensitive target. Removal of a trace amount of mercury chloride from the recipe by another group in his hospital proved that only ATO was required. Publication of Western replication in 1998 made the therapy widely accepted, though neither Western, nor Chinese authors of English papers on ATO cited Zhang's papers in the 1970s. This article focuses on the early papers of Zhang, but also suggests it worth further work to validate Chinese reports of ATO treatment of other cancers, and infers that some findings published in Chinese journals are of considerable value to patients and that doctors from other countries can benefit from the clinical experience of Chinese doctors with the largest population of patients. PMID:23645104

  19. 77 FR 27785 - Request for Information Regarding the NIH-Industry Program To Discover New Therapeutic Uses for...

    Science.gov (United States)

    2012-05-11

    ... from the pharmaceutical industry, government, academia, and the non-profit sector ( http://www.ncats... biomedical researchers and the pharmaceutical industry as well as your experiences with drug rescue or... HUMAN SERVICES National Institutes of Health Request for Information Regarding the NIH-Industry...

  20. Fundamental Parameters of Some New Discovered Open star Clusters

    CERN Document Server

    El-Bendary, R

    2010-01-01

    We present here the fundamental properties of some newly discovered open star clusters (Teutsch 144, Alessi 53, Riddle 4 and Juchrt 12) using the JHK Near-IR photometry (2MASS survey) of Cutri et al. (2003). These clusters have been selected from Kronberger et al. (2006) who presented some new discovered stellar groups on the basis of 2MASS photometry and the DSS visual images. The astrometry and photometric parameters are determined using the stellar density distributions and color-magnitude diagrams fittings. Center, radius, membership, distances, reddening, age, luminosity function, mass function, total mass, and the dynamical relaxation time have been estimated for the first time. This paper is a part of Reda's PhD project.

  1. Newly discovered angiogenesis inhibitors and their mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Ze-hong MIAO; Jian-ming FENG; Jian DING

    2012-01-01

    In the past decade,the success of angiogenesis inhibitors in clinical contexts has established the antiangiogenic strategy as an important part of cancer therapy,During that time period,we have discovered and reported 17 compounds that exert potent inhibition on angiogenesis.These compounds exhibit tremendous diversity in their sources,structures,targets and mechanisms.These studies have generated new models for further modification and optimization of inhibitory compounds,new information for mechanistic studies and a new drug candidate for clinical development.In particular,through studies on the antiangiogenic mechanism of pseudolaric acid B,we discovered a novel mechanism by which the stability of hypoxia-irducible factor 1α is regulated by the transcription factor c-Jun.We also completed a preclinical study of AL3810,a compound with the potential to circumvent tumor drug resistance to a certain extent.All of these findings will be briefly reviewed in this article.

  2. Discovering Glaser: My Experience of Doing Grounded Theory

    Directory of Open Access Journals (Sweden)

    Lesley Margaret Piko

    2014-12-01

    Full Text Available For my investigation into how general practitioners (GPs experience their medical careers, I used a grounded theory methodology based on the early work of Glaser and Strauss (1967 and Glaser’s subsequent work (Glaser, 1978, 1998. Glaser (1998 suggested you need to do grounded theory in order to understand the methodology. I found as I engaged in the process I began to understand the meaning of Glaser’s teachings and to discover Glaser. In this article, I share my experience of discovering my theory of optimising professional life. This theory explains how GPs develop their professional life in response to their need for sustainment—a need that encapsulates self-care to sustain wellbeing, work interest to sustain motivation and income to sustain lifestyle.

  3. Line drawing of anomaly discovered in redesigned shuttle motor nozzle

    Science.gov (United States)

    1987-01-01

    Line drawing titled 'DM-9 Case-to-Nozzle Joint' shows anomaly discovered in redesigned shuttle motor nozzle. The second full-duration test firing of NASA's redesigned Space Shuttle solid rocket motor (SRM), designated DM-9, was conducted 12-23-87 at Morton Thiokol's Wasatch facility in Utah. A post-test examination of the motor has revealed an anomaly in one nozzle component. Material was discovered missing from the nozzle outer boot ring, a large carbon phenolic composite ring used to anchor one end of the flexible boot that allows the nozzle to move and 'steer' the vehicle. About one-third of the missing 160 degrees of missing ring material was found adjacent to the forward nozzle section inside the motor. This diagram shows the location of the nozzle joint on an assembled SRM, and points out the shaded location of the outer boot ring that circles the motor within the nozzle joint.

  4. Discovering simple DNA sequences by the algorithmic significance method.

    Science.gov (United States)

    Milosavljević, A; Jurka, J

    1993-08-01

    A new method, 'algorithmic significance', is proposed as a tool for discovery of patterns in DNA sequences. The main idea is that patterns can be discovered by finding ways to encode the observed data concisely. In this sense, the method can be viewed as a formal version of the Occam's Razor principle. In this paper the method is applied to discover significantly simple DNA sequences. We define DNA sequences to be simple if they contain repeated occurrences of certain 'words' and thus can be encoded in a small number of bits. Such definition includes minisatellites and microsatellites. A standard dynamic programming algorithm for data compression is applied to compute the minimal encoding lengths of sequences in linear time. An electronic mail server for identification of simple sequences based on the proposed method has been installed at the Internet address pythia/anl.gov. PMID:8402207

  5. Metagenomic approach for discovering new pathogens in infection disease outbreaks

    Directory of Open Access Journals (Sweden)

    Emanuela Giombini

    2011-09-01

    Full Text Available Viruses represent the most abundant biological components on earth.They can be found in every environment, from deep layers of oceans to animal bodies.Although several viruses have been isolated and sequenced, in each environment there are millions of different types of viruses that have not been identified yet.The advent of nextgeneration sequencing technologies with their high throughput capabilities make possible to study in a single experiment all the community of microorganisms present in a particular sample “microbioma”.They made more feasible the application of the metagenomic approach, by which it is also possible to discover and identify new pathogens, that may pose a threat to public health.This paper summarizes the most recent applications of nextgeneration sequencing to discover new viral pathogens during the occurrence of infection disease outbreaks.

  6. Discovering and Promoting Commodity Health Attributes: Programs and Issues

    OpenAIRE

    Carman, Hoy F.

    2007-01-01

    There is a growing consumer segment demanding healthy foods and diets, health and nutrition messages can expand food demand, and governments in the U.S. and EU, faced with increasing obesity and associated health outcomes, want consumers to have reliable information to choose healthy diets. California commodity organizations, charged with expanding the demand for almonds, avocados, strawberries and walnuts, are funding health and nutrition research as a means to discover a unique selling prop...

  7. A Precious Fern Species Discovered in Jiulong, Sichuan

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Supported by the US National Science Foundation and the National Natural Science Foundation of China, a rare and endangered fern, Isoetes hypsophila, was discovered by a Sino-US research team headed by Prof. SUN Hang from the CAS Kunming Institute of Botany (KIB) and Dr. David E. Boufford from Harvard University in a recent trip to Jiulong, Sichuan, during its botanical survey in the Hengduan Mountains in south China. Scientists say the plant is found for the first time in the region.

  8. MASTER: OT discovered during inspection of HESE 58537957 trigger

    Science.gov (United States)

    Tyurina, N.; Lipunov, V.; Buckley, D.; Gorbovskoy, E.; Balanutsa, P.; Kuznetsov, A.; Kornilov, V.; Kuvshinov, D.; Vlasenko, D.; Gress, O.; Ivanov, K.; Shumkov, V.; Potter, S.

    2016-08-01

    MASTER-SAAO auto-detection system ( Lipunov et al., "MASTER Global Robotic Net", Advances in Astronomy, 2010, 349171 ) discovered OT source at (RA, Dec) = 13h 08m 45.02s -32d 32m 54.9s on 2016-08-24.73811 UT during inspection of HESE alert ( 58537957 trigger number ) http://gcn.gsfc.nasa.gov/notices_amon/58537957_128340.amon . The OT unfiltered magnitude is 19.6m (limit 20.5m).

  9. Discovering Light Pseudoscalar Bosons in Double-Pulsar Observations

    OpenAIRE

    Dupays, Arnaud; Roncadelli, Marco

    2006-01-01

    The axion is just one from a general class of new particles -- called Light Pseudoscalar Bosons (LPBs) -- predicted by many realistic extensions of the Standard Model. We offer a somewhat pedagogical review of their main properties, with particular emphasis on the effects they induce in a light beam travelling in an external magnetic field, like photon-LPB oscillations, birefringence and dichroism. Moreover, we discuss a new strategy whereby LPBs can be discovered by high-precision observatio...

  10. Classifying transcription factor targets and discovering relevant biological features

    OpenAIRE

    DeLisi Charles; Kon Mark; Holloway Dustin T

    2008-01-01

    Abstract Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved r...

  11. A new hard X-ray transient discovered by INTEGRAL

    DEFF Research Database (Denmark)

    Gibaud, L.; Bazzano, A.; Bozzo, E.;

    2011-01-01

    INTEGRAL discovered a new hard X-ray transient, IGR J17498-2921, during the observations performed from 2011-08-11 22:45 to 2011-08-12 05:54 UTC. The source is detected in the IBIS/ISGRI mosaic at a preliminary significance level of 11 and 9 sigma in the 20-40 keV and 40-80 keV energy bands...

  12. VITAMIN D: Newly Discovered Actions Require Reconsideration of Physiologic Requirements

    OpenAIRE

    Bikle, Daniel D.

    2010-01-01

    Vitamin D is not just for preventing rickets and osteomalacia. Recent findings in animal experiments, epidemiologic studies and clinical trials, indicate that adequate vitamin D levels are important for cancer prevention, controlling hormone levels, and regulating the immune response. Although 25 Hydroxyvitamin D (25OHD) levels above 10ng/ml may prevent rickets and osteomalacia, these levels are not sufficient to provide these more recently discovered clinical benefits. Rather, levels of 25OH...

  13. Therapeutic cloning in the mouse

    OpenAIRE

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of d...

  14. Discovering health topics in social media using topic models.

    Directory of Open Access Journals (Sweden)

    Michael J Paul

    Full Text Available By aggregating self-reported health statuses across millions of users, we seek to characterize the variety of health information discussed in Twitter. We describe a topic modeling framework for discovering health topics in Twitter, a social media website. This is an exploratory approach with the goal of understanding what health topics are commonly discussed in social media. This paper describes in detail a statistical topic model created for this purpose, the Ailment Topic Aspect Model (ATAM, as well as our system for filtering general Twitter data based on health keywords and supervised classification. We show how ATAM and other topic models can automatically infer health topics in 144 million Twitter messages from 2011 to 2013. ATAM discovered 13 coherent clusters of Twitter messages, some of which correlate with seasonal influenza (r = 0.689 and allergies (r = 0.810 temporal surveillance data, as well as exercise (r =  .534 and obesity (r =  -.631 related geographic survey data in the United States. These results demonstrate that it is possible to automatically discover topics that attain statistically significant correlations with ground truth data, despite using minimal human supervision and no historical data to train the model, in contrast to prior work. Additionally, these results demonstrate that a single general-purpose model can identify many different health topics in social media.

  15. Chaperones as potential therapeutics for Krabbe disease.

    Science.gov (United States)

    Graziano, Adriana Carol Eleonora; Pannuzzo, Giovanna; Avola, Rosanna; Cardile, Venera

    2016-11-01

    Krabbe's disease (KD) is an autosomal recessive, neurodegenerative disorder. It is classified among the lysosomal storage diseases (LSDs). It was first described in , but the genetic defect for the galactocerebrosidase (GALC) gene was not discovered until the beginning of the 1970s, 20 years before the GALC cloning. Recently, in 2011, the crystal structures of the GALC enzyme and the GALC-product complex were obtained. For this, compared with other LSDs, the research on possible therapeutic interventions is much more recent. Thus, it is not surprising that some treatment options are still under preclinical investigation, whereas their relevance for other pathologies of the same group has already been tested in clinical studies. This is specifically the case for pharmacological chaperone therapy (PCT), a promising strategy for selectively correcting defective protein folding and trafficking and for enhancing enzyme activity by small molecules. These compounds bind directly to a partially folded biosynthetic intermediate, stabilize the protein, and allow completion of the folding process to yield a functional protein. Here, we review the chaperones that have demonstrated potential therapeutics during preclinical studies for KD, underscoring the requirement to invigorate research for KD-addressed PCT that will benefit from recent insights into the molecular understanding of GALC structure, drug design, and development in cellular models. © 2016 Wiley Periodicals, Inc. PMID:27638605

  16. Therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  17. Pneumothorax following therapeutic thoracentesis

    International Nuclear Information System (INIS)

    The authors retrospectively studied 319 patients undergoing therapeutic thoracentesis. Of these, 223 patients had malignant pleural effusions and 96 had nonmalignant and noninfected collections. The effusions ranged from 100 to 4,000 mL in size. All patients presented with pain and/or respiratory compromise prompting the need for drainage. Overall there was a t% (22 of 319) incidence of pneumothorax. In six patients (3%) chest tube placement was necessary. Four of these six patients were successfully managed with 7 - 16-French catheters and a Heimlich valve. Persistent pneumothorax in two cases required placement of large, 28-F chest tubes supplemented with Pleura-vac drainage and hospital admission. There was a subset of nine patients with malignant effusions and lymphangitic spread who developed large but asymptomatic pneumothoraces. All but 5% of these patients required no therapy for pneumothorax. The authors' results suggest that pneumothoraces following therapeutic thoracentesis can be managed within the radiology department. The prevalence, mechanism, and management of pneumothoraces in these patients is discussed

  18. Therapeutic nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Baum, Richard P. (ed.) [ENETS Center of Excellence, Bad Berka (Germany). THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging

    2014-07-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  19. Engineering therapeutic protein disaggregases

    Science.gov (United States)

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  20. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  1. The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics.

    Science.gov (United States)

    Krawczyk-Balska, A; Markiewicz, Z

    2016-02-01

    Intrinsic resistance to antibiotics is a serious therapeutic problem in the case of many bacterial species. The Gram-positive human pathogen Listeria monocytogenes is intrinsically resistant to broad spectrum cephalosporin antibiotics, which are commonly used in therapy of bacterial infections. Besides three penicillin-binding proteins the intrinsic cephalosporin resistome of L. monocytogenes includes multidrug resistance transporter transporters, proteins involved in peptidoglycan biosynthesis and modification, cell envelope proteins with structural or general detoxification function, cytoplasmic proteins with unknown function and regulatory proteins. Analysis of the regulation of the expression of genes involved in the intrinsic resistance of L. monocytogenes to cephalosporins highlights the high complexity of control of the intrinsic resistance phenotype. The regulation of the transcription of the intrinsic resistome determinants involves the activity of eight regulators, namely LisR, CesR, LiaR, VirR, σ(B) , σ(H) , σ(L) and PrfA, of which the most prominent role play LisR, CesR and σ(B) . Furthermore, the vast majority of the intrinsic resistome determinants contribute to the tolerance of different stress conditions and virulence. A study indicates that O-acetyltransferase OatA is the most promising candidate for co-drug development since an agent targeting OatA should sensitize L. monocytogenes to certain antibiotics, therefore improving the efficacy of listeriosis treatment as well as food preservation measures. PMID:26509460

  2. DNA methylome and the complexity of discovering prostate cancer biomarkers

    Institute of Scientific and Technical Information of China (English)

    Shahriar Koochekpour

    2011-01-01

    @@ Prostate cancer (PCa) remains the most common malignancy and a leading cause of cancer-related deaths in men.Molecular discrimination at an early stage between indolent and aggressive primary tumors in pathologically confirmed PCa is required to develop personalized therapeutic interventions.

  3. Discovering the first microRNA-targeted drug

    DEFF Research Database (Denmark)

    Lindow, Morten; Kauppinen, Sakari

    2012-01-01

    MicroRNAs (miRNAs) are important post-transcriptional regulators of nearly every biological process in the cell and play key roles in the pathogenesis of human disease. As a result, there are many drug discovery programs that focus on developing miRNA-based therapeutics. The most advanced...

  4. [Therapeutic education didactic techniques].

    Science.gov (United States)

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  5. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    and the drug which increased the potency of the conjugates significantly. A different approach to drug delivery is that of surface mediated drug delivery. Hydrogels of poly(vinyl alcohol) has shown great promise in this regard. The chemical opportunities of this polymer are explored through the virtues...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein......The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...

  6. Homocystinuria: Therapeutic approach.

    Science.gov (United States)

    Kumar, Tarun; Sharma, Gurumayum Suraj; Singh, Laishram Rajendrakumar

    2016-07-01

    Homocystinuria is a disorder of sulfur metabolism pathway caused by deficiency of cystathionine β-synthase (CBS). It is characterized by increased accumulation of homocysteine (Hcy) in the cells and plasma. Increased homocysteine results in various vascular and neurological complications. Present strategies to lower cellular and plasma homocysteine levels include vitamin B6 intake, dietary methionine restriction, betaine supplementation, folate and vitamin B12 administration. However, these strategies are inefficient for treatment of homocystinuria. In recent years, advances have been made towards developing new strategies to treat homocystinuria. These mainly include functional restoration to mutant CBS, enhanced clearance of Hcy from the body, prevention of N-homocysteinylation-induced toxicity and inhibition of homocysteine-induced oxidative stress. In this review, we have exclusively discussed the recent advances that have been achieved towards the treatment of homocystinuria. The review is an attempt to help clinicians in developing effective therapeutic strategies and designing novel drugs against homocystinuria. PMID:27059523

  7. On being therapeutic.

    Science.gov (United States)

    Greben, S E

    1977-11-01

    Psychotherapy is both an art and a science. The art deserves as careful study as does the science. In this paper the author puts forward the view that the effectiveness of psychotherapy is dependent to a marked degree upon certain innate characteristics of the therapist: these include his character structure, his personal values, and his spontaneous personality style. In order to explore this thesis, the author examines what has been written about some successful and well-known psychotherapists, by their patients, their colleagues, and their friends. He concludes that these therapists strongly evidenced the following characteristics: empathy and concern, caring and protectiveness, warmth, therapeutic forcefulness, expectation of improvement, freedom from despair, reliability, friendliness and respectfulness. It is felt that such factors in the therapist must be taken into account in order to achieve a view of psychotherapy which is not reductionistic. PMID:589551

  8. Targeting Glycogen Synthase Kinase-3β for Therapeutic Benefit against Oxidative Stress in Alzheimer's Disease: Involvement of the Nrf2-ARE Pathway

    Directory of Open Access Journals (Sweden)

    Katja Kanninen

    2011-01-01

    Full Text Available Specific regions of the Alzheimer's disease (AD brain are burdened with extracellular protein deposits, the accumulation of which is concomitant with a complex cascade of overlapping events. Many of these pathological processes produce oxidative stress. Under normal conditions, oxidative stress leads to the activation of defensive gene expression that promotes cell survival. At the forefront of defence is the nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor that regulates a broad spectrum of protective genes. Glycogen synthase kinase-3β (GSK-3β regulates Nrf2, thus making this kinase a potential target for therapeutic intervention aiming to boost the protective activation of Nrf2. This paper aims to review the neuroprotective role of Nrf2 in AD, with special emphasis on the role of GSK-3β in the regulation of the Nrf2 pathway. We also examine the potential of inducing GSK-3β by small-molecule activators, dithiocarbamates, which potentially exert their beneficial therapeutic effects via the activation of the Nrf2 pathway.

  9. Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy.

    Science.gov (United States)

    Schrand, Brett; Berezhnoy, Alexey; Brenneman, Randall; Williams, Anthony; Levay, Agata; Kong, Ling-Yuan; Rao, Ganesh; Zhou, Shouhao; Heimberger, Amy B; Gilboa, Eli

    2014-09-01

    Despite the recent successes of using immune modulatory Abs in patients with cancer, autoimmune pathologies resulting from the activation of self-reactive T cells preclude the dose escalations necessary to fully exploit their therapeutic potential. To reduce the observed and expected toxicities associated with immune modulation, here we describe a clinically feasible and broadly applicable approach to limit immune costimulation to the disseminated tumor lesions of the patient, whereby an agonistic 4-1BB oligonucleotide aptamer is targeted to the tumor stroma by conjugation to an aptamer that binds to a broadly expressed stromal product, VEGF. This approach was predicated on the premise that by targeting the costimulatory ligands to products secreted into the tumor stroma, the T cells will be costimulated before their engagement of the MHC-peptide complex on the tumor cell, thereby obviating the need to target the costimulatory ligands to noninternalizing cell surface products expressed on the tumor cells. Underscoring the potency of stroma-targeted costimulation and the broad spectrum of tumors secreting VEGF, in preclinical murine tumor models, systemic administration of the VEGF-targeted 4-1BB aptamer conjugates engendered potent antitumor immunity against multiple unrelated tumors in subcutaneous, postsurgical lung metastasis, methylcholantrene-induced fibrosarcoma, and oncogene-induced autochthonous glioma models, and exhibited a superior therapeutic index compared with nontargeted administration of an agonistic 4-1BB Ab or 4-1BB aptamer.

  10. Discovering Astronomy: An Astro 101 e-book

    Science.gov (United States)

    Shawl, Stephen J.; Byrd, Gene; Deustua, Susana E.; LoPresto, Michael C.

    2016-01-01

    Discovering Astronomy, now available in its 6th edition as an eText, has many advantages and features for your students. We have partnered with etextink.com and WebAssign.net to produce an affordable set of cost-saving options for your students. Also available is the Discovering Astronomy Activity Manual, which provides students with an active-learning experience.Our etext is device independent and thus accessible through any web browser. Americans with Disabilities Act compatibility provides access for all students. Hotlinks to outside sites provide further information for interested students. Lecture demonstration videos of important concepts, made specifically for this new edition, are embedded within the text as appropriate. Students can highlight text, take notes, and bookmark locations within the text. Important terms are linked to the glossary. Search capabilities allow students to easily find what they want.Instructors can interact with their students directly through the etext once the class roster has been provided. For example, instructors can embed assignments into their students' etext and add their own notes and updates, which are immediately visible to their students.Updates can be quickly made by us as new findings become available. For example, updates from New Horizons were added at the time of the closest approach to Pluto, and an update on the recent announcement of current water on Mars was added the day of the announcement.We will present results of our own experience with college and high school students' use of Discovering Astronomy in online courses.Details of the book, a sample chapter, and other information are available at discoveringastronomy.weebly.com.

  11. Discovering sequence motifs with arbitrary insertions and deletions.

    Directory of Open Access Journals (Sweden)

    Martin C Frith

    2008-04-01

    Full Text Available BIOLOGY IS ENCODED IN MOLECULAR SEQUENCES: deciphering this encoding remains a grand scientific challenge. Functional regions of DNA, RNA, and protein sequences often exhibit characteristic but subtle motifs; thus, computational discovery of motifs in sequences is a fundamental and much-studied problem. However, most current algorithms do not allow for insertions or deletions (indels within motifs, and the few that do have other limitations. We present a method, GLAM2 (Gapped Local Alignment of Motifs, for discovering motifs allowing indels in a fully general manner, and a companion method GLAM2SCAN for searching sequence databases using such motifs. glam2 is a generalization of the gapless Gibbs sampling algorithm. It re-discovers variable-width protein motifs from the PROSITE database significantly more accurately than the alternative methods PRATT and SAM-T2K. Furthermore, it usefully refines protein motifs from the ELM database: in some cases, the refined motifs make orders of magnitude fewer overpredictions than the original ELM regular expressions. GLAM2 performs respectably on the BAliBASE multiple alignment benchmark, and may be superior to leading multiple alignment methods for "motif-like" alignments with N- and C-terminal extensions. Finally, we demonstrate the use of GLAM2 to discover protein kinase substrate motifs and a gapped DNA motif for the LIM-only transcriptional regulatory complex: using GLAM2SCAN, we identify promising targets for the latter. GLAM2 is especially promising for short protein motifs, and it should improve our ability to identify the protein cleavage sites, interaction sites, post-translational modification attachment sites, etc., that underlie much of biology. It may be equally useful for arbitrarily gapped motifs in DNA and RNA, although fewer examples of such motifs are known at present. GLAM2 is public domain software, available for download at http://bioinformatics.org.au/glam2.

  12. Macrophage Metalloelastase: Stretching Therapeutic Opportunities

    Institute of Scientific and Technical Information of China (English)

    Jeannie Q. He; Menno van Lookeren Campagne

    2009-01-01

    While tissue macrophages are at the first line of microbial host defense, they are also convenient hideouts for pathogens escaping immune attack. Houghton et al. discovered that alveolar macrophage mobilizes macrophage metalloelastase to destroy bacteria present inside the cell.

  13. Growing Self-Estemm and Discovering Intelligences through Oral Production

    Directory of Open Access Journals (Sweden)

    Ochoa Dora Liliana

    2002-08-01

    Full Text Available After having applied a needs analysis in an eleventh grade course of English, I could notice that there was a big lack of security and self-confidence in the students. They expressed in different data-gathering instruments their fear when speaking in front of the class. Also, they talked about their insecurity when pronouncing English and the need for more opportunities for developing speaking. Therefore, the implementation of an innovation in class was carried out in order to respond to the students¿ needs and make them discover their talents. The implementation was successful and students improved some areas of their communicative competence.

  14. Astrophysical parameters of ten new discovered open star clusters

    CERN Document Server

    Tadross, A L; Osman, A; Ismail, N; Bakry, A

    2011-01-01

    We present here the fundamental parameters of ten open star clusters, nominated from Kronberger et al. (2006) who presented some new discovered stellar groups on the basis of 2MASS photometry and DSS visual images. Star counts and photometric parameters (radius, membership, distances, color excess, age, luminosity function, mass function, total mass, and the dynamical relaxation time) have been determined for these ten clusters for the first time. In order to calibrate our procedures, the main parameters (distance, age, and color excesses) have been re-estimated for another five clusters, which are studied by Kronberger et al. (2006) as well.

  15. Insights into newly discovered marks and readers of epigenetic information.

    Science.gov (United States)

    Andrews, Forest H; Strahl, Brian D; Kutateladze, Tatiana G

    2016-08-18

    The field of chromatin biology has been advancing at an accelerated pace. Recent discoveries of previously uncharacterized sites and types of post-translational modifications (PTMs) and the identification of new sets of proteins responsible for the deposition, removal, and reading of these marks continue raising the complexity of an already exceedingly complicated biological phenomenon. In this Perspective article we examine the biological importance of new types and sites of histone PTMs and summarize the molecular mechanisms of chromatin engagement by newly discovered epigenetic readers. We also highlight the imperative role of structural insights in understanding PTM-reader interactions and discuss future directions to enhance the knowledge of PTM readout. PMID:27538025

  16. Discovering New Oilfield within 18 Months Using Integrated Geophysical Technology

    Institute of Scientific and Technical Information of China (English)

    JiLiansheng; KongFanshu; SunJianchen

    2003-01-01

    The Yanqi basin is small and located at the northeastern corner of the Tarim basin. Before April 1993, the Yanqi basin was only surveyed with surface geology and seldom known among the explorers. After that, the gravitational, magnetic and MT prospecting were carried out and found some interesting local structures, which might be oil-and-gas-bearing. A few seismic lines were utilized to confirm them. An exploratory well was drilled in the summer of 1994 and discovered oil flow with industrial value in Oct., the same year. The petroleum exploration obtained breakthrough in the Yanqi basin in only 18 months.

  17. Sir Alexander Fleming: Scottish researcher who discovered penicillin.

    Science.gov (United States)

    Ligon, B Lee

    2004-01-01

    The discovery and development of penicillin changed the entire direction of approaches to treating infectious diseases and saved the lives of millions of people. Indeed, the development of penicillin was a watershed event in the battle against infectious diseases, and the individual who discovered it, Sir Alexander Fleming, remains a prominent individual in the annals of medical history. This article focuses primarily on the personal life of Alexander Fleming, an individual who had a remarkable diversity of interests and who made many contributions to science and medicine.

  18. An approach for discovering keywords from Spanish tweets using Wikipedia

    Directory of Open Access Journals (Sweden)

    Daniel AYALA

    2016-05-01

    Full Text Available Most approaches to keywords discovery when analyzing microblogging messages (among them those from Twitter are based on statistical and lexical information about the words that compose the text. The lack of context in the short messages can be problematic due to the low co-occurrence of words. In this paper, we present a new approach for keywords discovering from Spanish tweets based on the addition of context information using Wikipedia as a knowledge base. We present four different ways to use Wikipedia and two ways to rank the new keywords. We have tested these strategies using more than 60000 Spanish tweets, measuring performance and analyzing particularities of each strategy.

  19. Three low surface brightness dwarfs discovered around NGC 4631

    OpenAIRE

    Karachentsev, Igor D.; Bautzmann, Dirk; Neyer, Fabian; Polzl, Robert; Riepe, Peter; Zilch, Thorsten; Mattern, Bruno

    2014-01-01

    We report the discovery of three low surface brightness companions to the spiral galaxy NGC 4631, made with small amateur telescopes. Assuming their distances to be 7.4 Mpc, the same as that of NGC 4631, the absolute magnitudes and linear diameters of the dwarfs are ranged within [-12.5, -9.6] mag and [4.7 - 1.3] kpc, respectively. These new three dwarfs, together with the discovered by us diffuse structure called "bridge", look like parts of a tidal filament directed towards NGC 4656 at tota...

  20. High throughput techniques for discovering new glycine receptor modulators and their binding sites

    Directory of Open Access Journals (Sweden)

    Daniel F Gilbert

    2009-10-01

    Full Text Available The inhibitory glycine receptor (GlyR is a member of the Cys-loop receptor family that mediates inhibitory neurotransmission in the central nervous system. These receptors are emerging as potential drug targets for inflammatory pain, immunomodulation, spasticity and epilepsy. Antagonists that specifically inhibit particular GlyR isoforms are also required as pharmacological probes for elucidating the roles of particular GlyR isoforms in health and disease. Although a substantial number of both positive and negative GlyR modulators have been identified, very few of these are specific for the GlyR over other receptor types. Thus, the potential of known compounds as either therapeutic leads or pharmacological probes is limited. It is therefore surprising that there have been few published studies describing attempts to discover novel GlyR isoform-specific compounds. The first aim of this review is to consider various methods for efficiently screening compounds against these receptors. We conclude that an anion sensitive yellow fluorescent protein is optimal for primary screening and that automated electrophysiology of cells stably expressing GlyRs is useful for confirming hits and quantitating the actions of identified compounds. The second aim of this review is to demonstrate how these techniques are used in our laboratory for the purpose of both discovering novel GlyR-active compounds and characterizing their binding sites. We also describe a reliable, cost effective method for transfecting HEK293 cells in single wells of a 384 well plate using nanogram quantities of cDNA.

  1. Adenosine can thwart antitumor immune responses elicited by radiotherapy. Therapeutic strategies alleviating protumor ADO activities

    International Nuclear Information System (INIS)

    By studying the bioenergetic status we could show that the development of tumor hypoxia is accompanied, apart from myriad other biologically relevant effects, by a substantial accumulation of adenosine (ADO). ADO has been shown to act as a strong immunosuppressive agent in tumors by modulating the innate and adaptive immune system. In contrast to ADO, standard radiotherapy (RT) can either stimulate or abrogate antitumor immune responses. Herein, we present ADO-mediated mechanisms that may thwart antitumor immune responses elicited by RT. An overview of the generation, accumulation, and ADO-related multifaceted inhibition of immune functions, contrasted with the antitumor immune effects of RT, is provided. Upon hypoxic stress, cancer cells release ATP into the extracellular space where nucleotides are converted into ADO by hypoxia-sensitive, membrane-bound ectoenzymes (CD39/CD73). ADO actions are mediated upon binding to surface receptors, mainly A2A receptors on tumor and immune cells. Receptor activation leads to a broad spectrum of strong immunosuppressive properties facilitating tumor escape from immune control. Mechanisms include (1) impaired activity of CD4 + T and CD8 + T, NK cells and dendritic cells (DC), decreased production of immuno-stimulatory lymphokines, and (2) activation of Treg cells, expansion of MDSCs, promotion of M2 macrophages, and increased activity of major immunosuppressive cytokines. In addition, ADO can directly stimulate tumor proliferation and angiogenesis. ADO mechanisms described can thwart antitumor immune responses elicited by RT. Therapeutic strategies alleviating tumor-promoting activities of ADO include respiratory hyperoxia or mild hyperthermia, inhibition of CD39/CD73 ectoenzymes or blockade of A2A receptors, and inhibition of ATP-release channels or ADO transporters. (orig.)

  2. A multifunctional drug combination shows highly potent therapeutic efficacy against human cancer xenografts in athymic mice.

    Directory of Open Access Journals (Sweden)

    Xiu-Jun Liu

    Full Text Available The tumor microenvironment plays a crucial role during tumor development. Integrated combination of drugs that target tumor microenvironment is a promising approach to anticancer therapy. Here, we report a multifunctional combination of low-cytotoxic drugs composed of dipyridamole, bestatin and dexamethasone (DBDx which mainly acts on the tumor microenvironment shows highly potent antitumor efficacy in vivo. In mouse hepatoma H22 model, the triple drug combination showed synergistic and highly potent antitumor efficacy. The combination indices of various combinations of the triple drugs were between 0.2 and 0.5. DBDx inhibited the growth of a panel of human tumor xenografts and showed no obvious systemic toxicity. At tolerated doses, DBDx suppressed the growth of human hepatocellular carcinoma BEL-7402, HepG2, and lung adenocarcinoma A549 xenografts by 94.5%, 93.7% and 96.9%, respectively. Clonogenic assay demonstrated that DBDx showed weak cytotoxicity. Western blot showed that Flk1 and Nos3 were down-regulated in the DBDx-treated group. Proteomic analysis showed that DBDx mainly affected the metabolic process and immune system process; in addition, the angiogenesis and VEGF signaling pathway were also affected. Conclusively, DBDx, a multifunctional drug combination of three low-cytotoxic drugs, shows synergistic and highly potent antitumor efficacy evidently mediated by the modulation of tumor microenvironment. Based on its low-cytotoxic attributes and its broad-spectrum antitumor therapeutic efficacy, this multifunctional combination might be useful in the treatment of cancers, especially those refractory to conventional chemotherapeutics.

  3. NEOKepler: Discovering Near-Earth Objects Using the Kepler Spacecraft

    CERN Document Server

    Stevenson, Kevin B; Jedicke, Robert; Bottke, William; Denneau, Larry

    2013-01-01

    We propose a new Kepler mission, called NEOKepler, that would survey near Earth's orbit to identify potentially hazardous objects (PHOs). To understand its surveying power, Kepler's large field of view produces an 'etendue' (A*Omega) that is 4.5 times larger than the best survey telescope currently in operation. In this paper, we investigate the feasibility of NEOKepler using a double "fence post" survey pattern that efficiently detects PHOs. In a simulated 12-month survey, we estimate that NEOKepler would detect ~150 new NEOs with absolute magnitudes of less than 21.5, ~50 of which would be new PHOs. This would increase the annual PHO discovery rate by at least 50% and improve upon our goal of discovering 90% of PHOs by the end of 2020. Due to its heliocentric orbit, Kepler would also be sensitive to objects inside Earth's orbit, discovering more objects in its first year than are currently known to exist. Understanding this undersampled sub-population of NEOs will reveal new insights into the actual PHO dis...

  4. Discovering link communities in complex networks by exploiting link dynamics

    International Nuclear Information System (INIS)

    Discovery of communities in complex networks is a fundamental data analysis problem with applications in various domains. Most of the existing approaches have focused on discovering communities of nodes, while recent studies have shown great advantages and utilities of the knowledge of communities of links in networks. From this new perspective, we propose a link dynamics based algorithm, called UELC, for identifying link communities of networks. In UELC, the stochastic process of a link–node–link random walk is employed to unfold an embedded bipartition structure of links in a network. The local mixing properties of the Markov chain underlying the random walk are then utilized to extract two emerging link communities. Further, the random walk and the bipartitioning processes are wrapped in an iterative subdivision strategy to recursively identify link partitions that segregate the network links into multiple subdivisions. We evaluate the performance of the new method on synthetic benchmarks and demonstrate its utility on real-world networks. Our experimental results show that our method is highly effective for discovering link communities in complex networks. As a comparison, we also extend UELC to extracting communities of nodes, and show that it is effective for node community identification. (paper)

  5. Novel virophages discovered in a freshwater lake in China

    Directory of Open Access Journals (Sweden)

    Chaowen eGong

    2016-01-01

    Full Text Available Virophages are small double-stranded DNA viruses that are parasites of giant DNA viruses that infect unicellular eukaryotes. Here we identify a novel group of virophages, named Dishui Lake virophages (DSLVs that were discovered in Dishui Lake (DSL: an artificial freshwater lake in Shanghai, China. Based on PCR and metagenomic analysis, the complete genome of DSLV1 was found to be circular and 28,788 base pairs in length, with a G+C content 43.2%, and 28 predicted open reading frames (ORFs. Fifteen of the DSLV1 ORFs have sequence similarity to known virophages. Two DSLV1 ORFs exhibited sequence similarity to that of prasinoviruses (Phycodnaviridae and chloroviruses (Phycodnaviridae, respectively, suggesting horizontal gene transfer occurred between these large algal DNA viruses and DSLV1. 46 other virophages-related contigs were also obtained, including six homologous major capsid protein (MCP gene. Phylogenetic analysis of these MCPs showed that DSLVs are closely related to OLV (Organic Lake virophage and YSLVs (Yellowstone Lake virophages, especially to YSLV3, except for YSLV7. These results indicate that freshwater ecotopes are the hotbed for discovering novel virophages as well as understanding their diversity and properties.

  6. Discover protein sequence signatures from protein-protein interaction data

    Directory of Open Access Journals (Sweden)

    Haasl Ryan J

    2005-11-01

    Full Text Available Abstract Background The development of high-throughput technologies such as yeast two-hybrid systems and mass spectrometry technologies has made it possible to generate large protein-protein interaction (PPI datasets. Mining these datasets for underlying biological knowledge has, however, remained a challenge. Results A total of 3108 sequence signatures were found, each of which was shared by a set of guest proteins interacting with one of 944 host proteins in Saccharomyces cerevisiae genome. Approximately 94% of these sequence signatures matched entries in InterPro member databases. We identified 84 distinct sequence signatures from the remaining 172 unknown signatures. The signature sharing information was then applied in predicting sub-cellular localization of yeast proteins and the novel signatures were used in identifying possible interacting sites. Conclusion We reported a method of PPI data mining that facilitated the discovery of novel sequence signatures using a large PPI dataset from S. cerevisiae genome as input. The fact that 94% of discovered signatures were known validated the ability of the approach to identify large numbers of signatures from PPI data. The significance of these discovered signatures was demonstrated by their application in predicting sub-cellular localizations and identifying potential interaction binding sites of yeast proteins.

  7. Learning Faster by Discovering and Exploiting Object Similarities

    Directory of Open Access Journals (Sweden)

    Tadej Janež

    2013-03-01

    Full Text Available In this paper we explore the question: “Is it possible to speed up the learning process of an autonomous agent by performing experiments in a more complex environment (i.e., an environment with a greater number of different objects?” To this end, we use a simple robotic domain, where the robot has to learn a qualitative model predicting the change in the robot’s distance to an object. To quantify the environment’s complexity, we defined cardinal complexity as the number of objects in the robot’s world, and behavioural complexity as the number of objects’ distinct behaviours. We propose Error reduction merging (ERM, a new learning method that automatically discovers similarities in the structure of the agent’s environment. ERM identifies different types of objects solely from the data measured and merges the observations of objects that behave in the same or similar way in order to speed up the agent’s learning. We performed a series of experiments in worlds of increasing complexity. The results in our simple domain indicate that ERM was capable of discovering structural similarities in the data which indeed made the learning faster, clearly superior to conventional learning. This observed trend occurred with various machine learning algorithms used inside the ERM method.

  8. Novel Virophages Discovered in a Freshwater Lake in China

    Science.gov (United States)

    Gong, Chaowen; Zhang, Weijia; Zhou, Xuewen; Wang, Hongming; Sun, Guowei; Xiao, Jinzhou; Pan, Yingjie; Yan, Shuling; Wang, Yongjie

    2016-01-01

    Virophages are small double-stranded DNA viruses that are parasites of giant DNA viruses that infect unicellular eukaryotes. Here we identify a novel group of virophages, named Dishui Lake virophages (DSLVs) that were discovered in Dishui Lake (DSL): an artificial freshwater lake in Shanghai, China. Based on PCR and metagenomic analysis, the complete genome of DSLV1 was found to be circular and 28,788 base pairs in length, with a G+C content 43.2%, and 28 predicted open reading frames (ORFs). Fifteen of the DSLV1 ORFs have sequence similarity to known virophages. Two DSLV1 ORFs exhibited sequence similarity to that of prasinoviruses (Phycodnaviridae) and chloroviruses (Phycodnaviridae), respectively, suggesting horizontal gene transfer occurred between these large algal DNA viruses and DSLV1. 46 other virophages-related contigs were also obtained, including six homologous major capsid protein (MCP) gene. Phylogenetic analysis of these MCPs showed that DSLVs are closely related to OLV (Organic Lake virophage) and YSLVs (Yellowstone Lake virophages), especially to YSLV3, except for YSLV7. These results indicate that freshwater ecotopes are the hotbed for discovering novel virophages as well as understanding their diversity and properties. PMID:26834726

  9. Discovering Color Styles from Fine Art Images of Impressionism

    Directory of Open Access Journals (Sweden)

    Man-Kwan Shan

    2009-10-01

    Full Text Available Content-based image retrieval (CBIR has attracted much interest since the last decade. Finding painting styles from fine art images is useful for CBIR. However, little research has been done on the painting style mining. In this paper, we investigated the color style mining technique for fine art of Impressionism. Three design issues for the color style mining are the feature extraction, the feature representation, and the style mining algorithm. For the feature extraction and presentation, dominate colors, adjacent color combinations and some MPEG-7 color descriptors, are utilized to represent the color features. Above all, we utilize the spatial data structure, 2D string, to represent color layout descriptor. For the style mining algorithms, we proposed a two-stage color style mining scheme. The first stage discovers the common properties of paintings of the same style. The second stage discovers the discriminative properties among styles. The experiment on the art work of European Impressionist was conducted. The performance of effectiveness is measure by the classification accuracy of the proposed style mining scheme. The classification accuracy ranges from 70% to 90%.

  10. FAQ about Recreational Therapy/Therapeutic Recreation

    Science.gov (United States)

    ... is the relationship between recreational therapy and therapeutic recreation? Therapeutic Recreation is the field ​​Recreational ... for individuals with disabilities." About the American Therapeutic Recreation Association: The American Therapeutic Recreation Association (ATRA) is ...

  11. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  12. Clinical applications of therapeutic phlebotomy

    Science.gov (United States)

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. PMID:27486346

  13. Clinical applications of therapeutic phlebotomy.

    Science.gov (United States)

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program.

  14. Plasmids encoding therapeutic agents

    Science.gov (United States)

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  15. [Liver metastasis: therapeutic strategy].

    Science.gov (United States)

    Gennari, L; Doci, R; Bignami, P

    1996-01-01

    The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed. PMID:9214269

  16. A systematic approach to discover and characterize natural plant biostimulants

    Directory of Open Access Journals (Sweden)

    Giovanni ePovero

    2016-04-01

    Full Text Available The use of natural plant biostimulants is proposed as an innovative solution to address the challenges to sustainable agriculture, to ensure optimal nutrient uptake, crop yield, quality, and tolerance to abiotic stress. However, the process of selection and characterization of plant biostimulant matrices is complex and involves a series of rigorous evaluations customized to the needs of the plant.Here, we propose a highly differentiated plant biostimulant development and production platform, which involves a combination of technology, processes, and know-how. Chemistry, biology and omic concepts are combined/integrated to investigate and understand the specific mode(s of action of bioactive ingredients. The proposed approach allows to predict and characterize the function of natural compounds as biostimulants. By managing and analyzing massive amounts of complex data, it is therefore possible to discover, evaluate and validate new product candidates, thus expanding the uses of existing products to meet the emerging needs of agriculture.

  17. Drifting sub-pulses in two newly discovered pulsars

    Science.gov (United States)

    Ord, S. M.; Edwards, R.; Bailes, M.

    2001-12-01

    We have detected the rare phenomenon of stable, drifting sub-pulse behaviour in two pulsars discovered in the recent Swinburne intermediate latitude pulsar survey. The pulsars, PSR J1231-47 and PSR J1919+0134, have approximate periods (P) of 1.873 and 1.6039s respectively. Both pulsars have multicomponent profiles, and distinct drifting is observed across them. We have identified a single drift mode in both pulsars: the drift rate for PSR J1231-47 being 5.4(1) ms P-1 and 5.8(2) ms P-1 for PSR 1919+0134. The drifting is linear across the profile with no departure from linearity at the edges within the sensitivity of our observations.

  18. Communication Boot Camp: Discover the Speaker in You!

    Directory of Open Access Journals (Sweden)

    Zuraidah Binti Ali

    2013-07-01

    Full Text Available Learning can take place almost anywhere, and this is especially true for our undergraduates who wish to become public speakers. Besides university course and public speaking workshops on campus grounds, undergraduates are now looking for a different learning environment – communication boot camps!! This study presents a compilation of learners’ experience, fun-filled activities, insightful feedback and memorable boot camp moments as captured in camp photos and feedback surveys. It involves a total of thirty seven undergraduates who enrolled in a Communication Boot Camp at Janda Baik, Pahang. Results show that Communication Boot Camp is a successful strategy to groom public speakers with a positive correlation between camp success and camp objectives, particularly in reducing shyness, motivating participants to become public speakers and discovering their talent and skills. In short, the study adds to the promise of zest and delight in public speaking.

  19. Discovered DNAs of Protein with Using Parallel Prefixspan Method

    Directory of Open Access Journals (Sweden)

    Mehdi Sobhkhiz Talouki

    2012-07-01

    Full Text Available Discovery of Sequential pattern mining is an important data mining mission with wide applications. There is no model that used multi coring techniques for parallel mining of closed sequential patterns. The parallelization of a prefixspan method to discover DNAs is proposed in this study. The prefixspan method is used to extract the frequent pattern from a sequence database. This system requires the use of multiple computers connected in local area network. This algorithm includes multi-coring to achieve communication between a master process and multiple slave processes. This algorithm applies dynamic scheduling to avoid tasks idling. Moreover we employ a technique, called selective sampling. We implement this algorithm with using a 4G memory and AMD phenomX4. Our experimental results show that this algorithm attains good efficiencies on motifs extraction.

  20. David Levy's Guide to Observing and Discovering Comets

    Science.gov (United States)

    Levy, David H.

    2003-05-01

    Preface; Part I. Why Observe Comets?: 1. Of history, superstition, magic, and science; 2. Comet science progresses; Part II. Discovering Comets: 3. Comet searching begins; 4. Tails and trails; 5. Comet searching in the twentieth century; 6. How I search for comets; 7. Searching for comets photographically; 8. Searching for comets with CCDs; 9. Comet hunting by reading; 10. Hunting for sungrazers over the Internet; 11. What to do when you think you've found a comet; Part III. A New Way of Looking at Comets: 12. When comets hit planets; 13. The future of visual comet hunting; Part IV. How to Observe Comets: 14. An introduction to comet hunting; 15. Visual observing of comets; 16. Estimating the magnitude of a comet; 17. Taking a picture of a comet; 18. Measuring where a comet is in the sky; Part V. Closing Notes: 19. My passion for comets.

  1. Gastrointestinal parasitoses discovered in agricultural workers in South Bohemia, Czechoslovakia.

    Science.gov (United States)

    Stĕrba, J; Ditrich, O; Prokopic, J; Kadlcík, K

    1988-01-01

    In the years from 1975 to 1982 1,750 persons, mostly employed by agricultural enterprises in the South Bohemian Region in Czechoslovakia, were examined. We discovered seven species of parasites: Taenia saginata in 0.3%, Enterobius vermicularis in 10.1%, Giardia lamblia in 1.0%, Endolimax nana in 0.8%, Entamoeba coli in 0.7%, Entamoeba hartmanni in 0.2%, and Chilomastix mesnili in 0.5%. The greatest number of parasites was found in students of the Secondary agricultural and technical school. Only two species of parasites were diagnosed in children of the employees. The incidence of E. vermicularis was 75% in children, in adult employees of agricultural enterprises, however, only 9.8%. PMID:3169645

  2. [Recently discovered hormones with a role in energy homeostasis].

    Science.gov (United States)

    Krykorková, I; Nedvídková, J

    2003-02-01

    Adipocytal hormones resistin and adiponectin and gastric peptide ghrelin are recently discovered hormones, which are considered to take part in energy metabolism regulation. Resistin is expressed in adipose tissue only and its increased levels could cause insulin resistance and thus link obesity with type 2 diabetes. Adiponectin, as well as resistin, are products of genes, expressed in adipose tissue. Adiponectin could prevent development of aterosclerosis and it could play a role in anti-inflammatory reactions. Ghrelin is produced mainly in the stomach. Beside its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. Main roles of resistin, adiponectin and ghrelin are summarised in the presented overview.

  3. Discovering shared and individual latent structure in multiple time series

    CERN Document Server

    Saria, Suchi; Penn, Anna

    2010-01-01

    This paper proposes a nonparametric Bayesian method for exploratory data analysis and feature construction in continuous time series. Our method focuses on understanding shared features in a set of time series that exhibit significant individual variability. Our method builds on the framework of latent Diricihlet allocation (LDA) and its extension to hierarchical Dirichlet processes, which allows us to characterize each series as switching between latent ``topics'', where each topic is characterized as a distribution over ``words'' that specify the series dynamics. However, unlike standard applications of LDA, we discover the words as we learn the model. We apply this model to the task of tracking the physiological signals of premature infants; our model obtains clinically significant insights as well as useful features for supervised learning tasks.

  4. Therapeutics in Huntington's Disease.

    Science.gov (United States)

    Killoran, Annie; Biglan, Kevin M

    2012-02-01

    OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there

  5. Discovering opinion leaders for medical topics using news articles

    Directory of Open Access Journals (Sweden)

    Jonnalagadda Siddhartha

    2012-03-01

    Full Text Available Abstract Background Rapid identification of subject experts for medical topics helps in improving the implementation of discoveries by speeding the time to market drugs and aiding in clinical trial recruitment, etc. Identifying such people who influence opinion through social network analysis is gaining prominence. In this work, we explore how to combine named entity recognition from unstructured news articles with social network analysis to discover opinion leaders for a given medical topic. Methods We employed a Conditional Random Field algorithm to extract three categories of entities from health-related new articles: Person, Organization and Location. We used the latter two to disambiguate polysemy and synonymy for the person names, used simple rules to identify the subject experts, and then applied social network analysis techniques to discover the opinion leaders among them based on their media presence. A network was created by linking each pair of subject experts who are mentioned together in an article. The social network analysis metrics (including centrality metrics such as Betweenness, Closeness, Degree and Eigenvector are used for ranking the subject experts based on their power in information flow. Results We extracted 734,204 person mentions from 147,528 news articles related to obesity from January 1, 2007 through July 22, 2010. Of these, 147,879 mentions have been marked as subject experts. The F-score of extracting person names is 88.5%. More than 80% of the subject experts who rank among top 20 in at least one of the metrics could be considered as opinion leaders in obesity. Conclusion The analysis of the network of subject experts with media presence revealed that an opinion leader might have fewer mentions in the news articles, but a high network centrality measure and vice-versa. Betweenness, Closeness and Degree centrality measures were shown to supplement frequency counts in the task of finding subject experts. Further

  6. Discovering Tradeoffs, Vulnerabilities, and Dependencies within Water Resources Systems

    Science.gov (United States)

    Reed, P. M.

    2015-12-01

    There is a growing recognition and interest in using emerging computational tools for discovering the tradeoffs that emerge across complex combinations infrastructure options, adaptive operations, and sign posts. As a field concerned with "deep uncertainties", it is logically consistent to include a more direct acknowledgement that our choices for dealing with computationally demanding simulations, advanced search algorithms, and sensitivity analysis tools are themselves subject to failures that could adversely bias our understanding of how systems' vulnerabilities change with proposed actions. Balancing simplicity versus complexity in our computational frameworks is nontrivial given that we are often exploring high impact irreversible decisions. It is not always clear that accepted models even encompass important failure modes. Moreover as they become more complex and computationally demanding the benefits and consequences of simplifications are often untested. This presentation discusses our efforts to address these challenges through our "many-objective robust decision making" (MORDM) framework for the design and management water resources systems. The MORDM framework has four core components: (1) elicited problem conception and formulation, (2) parallel many-objective search, (3) interactive visual analytics, and (4) negotiated selection of robust alternatives. Problem conception and formulation is the process of abstracting a practical design problem into a mathematical representation. We build on the emerging work in visual analytics to exploit interactive visualization of both the design space and the objective space in multiple heterogeneous linked views that permit exploration and discovery. Many-objective search produces tradeoff solutions from potentially competing problem formulations that can each consider up to ten conflicting objectives based on current computational search capabilities. Negotiated design selection uses interactive visualization

  7. Discovering multiple realistic TFBS motifs based on a generalized model

    Directory of Open Access Journals (Sweden)

    Leung Kwong-Sak

    2009-10-01

    Full Text Available Abstract Background Identification of transcription factor binding sites (TFBSs is a central problem in Bioinformatics on gene regulation. de novo motif discovery serves as a promising way to predict and better understand TFBSs for biological verifications. Real TFBSs of a motif may vary in their widths and their conservation degrees within a certain range. Deciding a single motif width by existing models may be biased and misleading. Additionally, multiple, possibly overlapping, candidate motifs are desired and necessary for biological verification in practice. However, current techniques either prohibit overlapping TFBSs or lack explicit control of different motifs. Results We propose a new generalized model to tackle the motif widths by considering and evaluating a width range of interest simultaneously, which should better address the width uncertainty. Moreover, a meta-convergence framework for genetic algorithms (GAs, is proposed to provide multiple overlapping optimal motifs simultaneously in an effective and flexible way. Users can easily specify the difference amongst expected motif kinds via similarity test. Incorporating Genetic Algorithm with Local Filtering (GALF for searching, the new GALF-G (G for generalized algorithm is proposed based on the generalized model and meta-convergence framework. Conclusion GALF-G was tested extensively on over 970 synthetic, real and benchmark datasets, and is usually better than the state-of-the-art methods. The range model shows an increase in sensitivity compared with the single-width ones, while providing competitive precisions on the E. coli benchmark. Effectiveness can be maintained even using a very small population, exhibiting very competitive efficiency. In discovering multiple overlapping motifs in a real liver-specific dataset, GALF-G outperforms MEME by up to 73% in overall F-scores. GALF-G also helps to discover an additional motif which has probably not been annotated in the dataset

  8. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  9. Differential impact of cysteine cathepsins on genetic mouse models of de novo carcinogenesis: cathepsin B as emerging therapeutic target

    Directory of Open Access Journals (Sweden)

    Thomas eReinheckel

    2012-07-01

    Full Text Available Lysosomal cysteine cathepsins belong to a family of 11 human proteolytic enzymes. Some of them correlate with progression in a variety of cancers and therefore are considered as potential therapeutic targets. Until recently, the contribution of individual cathepsins to tumorigenesis and tumor progression remained unknown. By crossing various types of mouse cancer models with mice where specific cathepsins have been ablated, we contributed to this gap of knowledge and will summarize the results in this report. The employed models are the Rip1-Tag2 model for pancreatic neuroendocrine tumors, the K14-HPV16 model for squamous skin and cervical cancers, and the MMTV-PyMT model for metastasizing breast cancer, the KPC model for pancreatic ductal adenocarcinoma, and the APCmin mice developing early stages of intestinal neoplasia. All models harbor mutations in relevant tumor suppressors and/or cell-type specific expression of potent oncogenes, which initiate de novo carcinogenesis in the targeted tissues. In all these models deletion of cathepsin B led to suppression of the aggressiveness of the respective cancer phenotype. Cathepsin B may network with other proteases as it was shown for cathepsin X/Z. In contrast, deletion of cathepsin L was beneficial in the RiP1-Tag2 model, but enhanced tumorigenesis in the APCmin, and the K14-HPV16 mice. A logical consequence of these results would be to further pursue selective inhibition of cathepsin B. Moreover, it became clear that cathepsins B and S derived from cells of the tumor microenvironment support cancer growth. Strikingly, delivery of broad spectrum cysteine cathepsin inhibitors in the tumor microenvironment disrupts the permissive ecosystem of the cancer and results in impaired growth or even in regression of the tumor. In addition, combination of cysteine cathepsin inhibition and standard chemotherapy improves the therapeutic response of the latter.

  10. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  11. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  12. Clinical applications of therapeutic phlebotomy

    Directory of Open Access Journals (Sweden)

    Kim KH

    2016-07-01

    Full Text Available Kyung Hee Kim,1 Ki Young Oh,2 1Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, 2Department of Physical Medicine and Rehabilitation, Soonchunhyang University, Cheonan Hospital, Cheonan, South Korea Abstract: Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. Keywords: therapeutic phlebotomy, hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, nonalcoholic fatty liver disease

  13. siRNA Genome Screening Approaches to Therapeutic Drug Repositioning

    Directory of Open Access Journals (Sweden)

    Ralph A. Tripp

    2013-01-01

    Full Text Available Bridging high-throughput screening (HTS with RNA interference (RNAi has allowed for rapid discovery of the molecular basis of many diseases, and identification of potential pathways for developing safe and effective treatments. These features have identified new host gene targets for existing drugs paving the pathway for therapeutic drug repositioning. Using RNAi to discover and help validate new drug targets has also provided a means to filter and prioritize promising therapeutics. This review summarizes these approaches across a spectrum of methods and targets in the host response to pathogens. Particular attention is given to the utility of drug repurposing utilizing the promiscuous nature of some drugs that affect multiple molecules or pathways, and how these biological pathways can be targeted to regulate disease outcome.

  14. Therapeutic postprostatectomy irradiation.

    Science.gov (United States)

    Youssef, Emad; Forman, Jeffrey D; Tekyi-Mensah, Samuel; Bolton, Susan; Hart, Kim

    2002-06-01

    factors. The results of therapeutic radiation for patients with elevated postprostatectomy PSA levels are sufficiently poor; other strategies should be explored as alternatives, including early adjuvant postprostatectomy irradiation or the use of combined hormonal and radiation therapy in the salvage situation. PMID:15046710

  15. Colloidal supramolecular aggregates for therapeutic application in neuromedicine.

    Science.gov (United States)

    Cosco, Donato; Di Marzio, Luisa; Marianecci, Carlotta; Trapasso, Elena; Paolino, Donatella; Celia, Christian; Carafa, Maria; Fresta, Massimo

    2014-01-01

    Neuromedicine has recently been emerging on the research scene and presents interesting challenges in therapeutics. The range of therapies generally used to treat neurological disorders are limited in their efficacy and degree of patient compliance because of the necessity of multiple drug dosages, low drug concentration in the central nervous system and side effects. Moreover, therapeutics require standard drug dosages which cannot be personalized. The limiting obstacle in neuromedicine is still the blood-brain barrier, which prevents the accumulation of endogenous and exogenous compounds inside the brain. Various transporters located on the blood-brain barrier modulate the crossing of endogenous compounds. It has been discovered that these transporters can be used as pathways for the transport of therapeutic agents and macromolecules that pass the blood-brain barrier allowing the uptake of bioactive compounds into the central nervous system. Several attempts have recently been made to develop forms of nanomedicine capable of overcoming the limitations of conventional therapy, above all the crossing of the blood-brain barrier. An outstandingly promising option could be the use of colloidal supramolecular aggregates. These nanodrugs are safe, biodegradable, and biocompatible and can combine biomaterials useful for diagnostic and therapeutical applications. They can be modified using monoclonal antibodies, proteins, peptides and macromolecules, thus providing personalized neuromedicine, which can be used in the treatment of various neurological disorders. In this review, recent advancements of supramolecular colloidal devices as neuromedicines are discussed, with particular focus on the latest developments. PMID:25174931

  16. Therapeutic interaction with an older personality disordered patient.

    Science.gov (United States)

    Josephs, Lawrence; Sanders, Avihay; Gorman, Bernard S

    2014-06-01

    This study reflects an assessment of the relationship between change in defensive functioning and change in the therapeutic interaction during an eight-year treatment episode of an older personality disordered woman. The patient, Ms. Q, possessed schizoid, avoidant, and depressive personality disorders as well as major depression as assessed by the Millon Clinical Multiaxial Inventory-III (MCMI-III). At the end of the treatment episode, Ms. Q still possessed an avoidant personality disorder and significant depressive personality traits but no longer possessed clinically significant schizoid traits or major depression. Ms. Q made significant positive change in her adaptive defensive functioning as assessed by the Defense Mechanism Rating Scale (DMRS). Through time-series analysis it was discovered that positive change in adaptive defenses was predicted by increases in a specific type of therapeutic interaction as assessed by the Psychotherapy Q Sort (PQS). In this therapeutic interaction the therapist in a didactic and advice-giving manner highlighted the patient's role in a problem in a clear and coherent way that could be perceived as tactless. Time-series analysis revealed a reciprocal relationship in which positive changes in adaptive defenses predicted further increases in that particular quality of therapeutic interaction.

  17. Neutrophils: potential therapeutic targets in tularemia?

    Directory of Open Access Journals (Sweden)

    Lee-Ann H Allen

    2013-12-01

    Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

  18. Therapeutic benefits of cannabis: a patient survey.

    Science.gov (United States)

    Webb, Charles W; Webb, Sandra M

    2014-04-01

    Clinical research regarding the therapeutic benefits of cannabis ("marijuana") has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai'i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai'i. No serious adverse effects were reported. These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety. Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.

  19. Adenosine and adenosine receptors: Newer therapeutic perspective

    Directory of Open Access Journals (Sweden)

    Manjunath S

    2009-01-01

    Full Text Available Adenosine, a purine nucleoside has been described as a ′retaliatory metabolite′ by virtue of its ability to function in an autocrine manner and to modify the activity of a range of cell types, following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by binding of adenosine to any of the four adenosine receptor subtypes namely A1, A2a, A2b, A3, which have been cloned in humans, and are expressed in most of the organs. Each is encoded by a separate gene and has different functions, although overlapping. For instance, both A1 and A2a receptors play a role in regulating myocardial oxygen consumption and coronary blood flow. It is a proven fact that adenosine plays pivotal role in different physiological functions, such as induction of sleep, neuroprotection and protection against oxidative stress. Until now adenosine was used for certain conditions like paroxysmal supraventricular tachycardia (PSVT and Wolff Parkinson White (WPW syndrome. Now there is a growing evidence that adenosine receptors could be promising therapeutic targets in a wide range of conditions including cardiac, pulmonary, immunological and inflammatory disorders. After more than three decades of research in medicinal chemistry, a number of selective agonists and antagonists of adenosine receptors have been discovered and some have been clinically evaluated, although none has yet received regulatory approval. So this review focuses mainly on the newer potential role of adenosine and its receptors in different clinical conditions.

  20. Therapeutically Active Biomolecules from Marine Actinomycetes

    Directory of Open Access Journals (Sweden)

    Mani Jayaprakashvel

    2012-09-01

    Full Text Available For the past few centuries, the biological sources of terrestrial origin have been explored and exploited for bioactive metabolites. This has resulted in the stagnancy of discovering either novel compounds or compounds with novel bioactivities. Thus, researchers across the globe have started exploring our big Oceans, for the search of bioactive metabolites. During the past few decades, the research on bioactive metabolites from marine biological resources has geared up and among the sources marine actinomycetes are proved to be best. Marine actinomycetes, the filamentous bacteria from marine environment have been intensively studied for bioactive metabolites. The biological diversity of marine actinomycetes was found to be enormous, thanks to culture dependent and culture independent biodiversity approaches. This great diversity of marine actinomycetes has offered greater chemical diversity. The diverse chemical compounds of marine actinomycetes have been found to have various biological activities such as antimicrobial, anti-tumor, anti-malarial, anti-algal, antioxidant, anti-inflammatory etc. These various bioactive metabolites of marine actinomycetes are having scope for developing as potent therapeutic agents. The potential of marine actinomycetes is rightly realized though the current biological wealth of these organisms isrelatively unexplored.

  1. Discovering Patterns in Brain Signals Using Decision Trees

    Directory of Open Access Journals (Sweden)

    Narusci S. Bastos

    2016-01-01

    Full Text Available Even with emerging technologies, such as Brain-Computer Interfaces (BCI systems, understanding how our brains work is a very difficult challenge. So we propose to use a data mining technique to help us in this task. As a case of study, we analyzed the brain’s behaviour of blind people and sighted people in a spatial activity. There is a common belief that blind people compensate their lack of vision using the other senses. If an object is given to sighted people and we asked them to identify this object, probably the sense of vision will be the most determinant one. If the same experiment was repeated with blind people, they will have to use other senses to identify the object. In this work, we propose a methodology that uses decision trees (DT to investigate the difference of how the brains of blind people and people with vision react against a spatial problem. We choose the DT algorithm because it can discover patterns in the brain signal, and its presentation is human interpretable. Our results show that using DT to analyze brain signals can help us to understand the brain’s behaviour.

  2. Can we discover multi-component WIMP dark matter?

    CERN Document Server

    Profumo, Stefano; Ubaldi, Lorenzo

    2009-01-01

    We address the question of whether the upcoming generation of dark matter search experiments and colliders will be able to discover if the dark matter in the Universe has more than one weakly interacting massive particle (WIMP) component. We outline a model-independent approach, and we study the specific cases of (1) indirect detection of dark matter via the discovery of gamma-ray lines corresponding to direct dark matter annihilation into monochromatic gamma rays, (2) direct detection with low-background 0.1 and 1 ton noble-gas detectors and (3) a 0.5 TeV center of mass energy electron-positron linear collider. For each search "channel", we outline a few assumptions to relate the very small set of parameters we consider (defining the masses of the two WIMPs and their relative abundance in the overall dark matter density) with the relevant detection rates. We then draw general conclusions on which corners of a generic multi-partite dark matter scenario can be explored with current and next generation experime...

  3. Oxygen and carbon discovered in exoplanet atmosphere `blow-off'

    Science.gov (United States)

    2004-02-01

    Oxygen and carbon discovered in exoplanet atmosphere ‘blow-off’ hi-res Size hi-res: 1096 kb Credits: ESA/Alfred Vidal-Madjar (Institut d’Astrophysique de Paris, CNRS, France) Oxygen and carbon discovered in exoplanet atmosphere ‘blow-off’ This artist’s impression shows an extended ellipsoidal envelope - the shape of a rugby-ball - of oxygen and carbon discovered around the well-known extrasolar planet HD 209458b. An international team of astronomers led by Alfred Vidal-Madjar (Institut d’Astrophysique de Paris, CNRS, France) observed the first signs of oxygen and carbon in the atmosphere of a planet beyond our Solar System for the first time using the NASA/ESA Hubble Space Telescope. The atoms of carbon and oxygen are swept up from the lower atmosphere with the flow of escaping atmospheric atomic hydrogen - like dust in a supersonic whirlwind - in a process called atmospheric ‘blow off’. Oxygen and carbon have been detected in the atmosphere of a planet beyond our Solar System for the first time. Scientists using the NASA/ESA Hubble Space Telescope have observed the famous extrasolar planet HD 209458b passing in front of its parent star, and found oxygen and carbon surrounding the planet in an extended ellipsoidal envelope - the shape of a rugby-ball. These atoms are swept up from the lower atmosphere with the flow of the escaping atmospheric atomic hydrogen, like dust in a supersonic whirlwind. The team led by Alfred Vidal-Madjar (Institut d’Astrophysique de Paris, CNRS, France) reports this discovery in a forthcoming issue of Astrophysical Journal Letters. The planet, called HD 209458b, may sound familiar. It is already an extrasolar planet with an astounding list of firsts: the first extrasolar planet discovered transiting its sun, the first with an atmosphere, the first observed to have an evaporating hydrogen atmosphere (in 2003 by the same team of scientists) and now the first to have an atmosphere containing oxygen and carbon. Furthermore

  4. Inner solar system material discovered in the Oort cloud.

    Science.gov (United States)

    Meech, Karen J; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R; Berdyugina, Svetlana; Keane, Jacqueline V; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J

    2016-04-01

    We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud.

  5. Unified Photo Enhancement by Discovering Aesthetic Communities From Flickr.

    Science.gov (United States)

    Hong, Richang; Zhang, Luming; Tao, Dacheng

    2016-03-01

    Photo enhancement refers to the process of increasing the aesthetic appeal of a photo, such as changing the photo aspect ratio and spatial recomposition. It is a widely used technique in the printing industry, graphic design, and cinematography. In this paper, we propose a unified and socially aware photo enhancement framework which can leverage the experience of photographers with various aesthetic topics (e.g., portrait and landscape). We focus on photos from the image hosting site Flickr, which has 87 million users and to which more than 3.5 million photos are uploaded daily. First, a tagwise regularized topic model is proposed to describe the aesthetic topic of each Flickr user, and coherent and interpretable topics are discovered by leveraging both the visual features and tags of photos. Next, a graph is constructed to describe the similarities in aesthetic topics between the users. Noticeably, densely connected users have similar aesthetic topics, which are categorized into different communities by a dense subgraph mining algorithm. Finally, a probabilistic model is exploited to enhance the aesthetic attractiveness of a test photo by leveraging the photographic experiences of Flickr users from the corresponding communities of that photo. Paired-comparison-based user studies show that our method performs competitively on photo retargeting and recomposition. Moreover, our approach accurately detects aesthetic communities in a photo set crawled from nearly 100000 Flickr users. PMID:26742134

  6. AN EFFICIENT WEB PERSONALIZATION APPROACH TO DISCOVER USER INTERESTED DIRECTORIES

    Directory of Open Access Journals (Sweden)

    M. Robinson Joel

    2014-04-01

    Full Text Available Web Usage Mining is the application of data mining technique used to retrieve the web usage from web proxy log file. Web Usage Mining consists of three major stages: preprocessing, clustering and pattern analysis. This paper explains each of these stages in detail. In this proposed approach, the web directories are discovered based on the user’s interestingness. The web proxy log file undergoes a preprocessing phase to improve the quality of data. Fuzzy Clustering Algorithm is used to cluster the user and session into disjoint clusters. In this paper, an effective approach is presented for Web personalization based on an Advanced Apriori algorithm. It is used to select the user interested web directories. The proposed method is compared with the existing web personalization methods like Objective Probabilistic Directory Miner (OPDM, Objective Community Directory Miner (OCDM and Objective Clustering and Probabilistic Directory Miner (OCPDM. The result shows that the proposed approach provides better results than the aforementioned existing approaches. At last, an application is developed with the user interested directories and web usage details.

  7. Inner solar system material discovered in the Oort cloud.

    Science.gov (United States)

    Meech, Karen J; Yang, Bin; Kleyna, Jan; Hainaut, Olivier R; Berdyugina, Svetlana; Keane, Jacqueline V; Micheli, Marco; Morbidelli, Alessandro; Wainscoat, Richard J

    2016-04-01

    We have observed C/2014 S3 (PANSTARRS), a recently discovered object on a cometary orbit coming from the Oort cloud that is physically similar to an inner main belt rocky S-type asteroid. Recent dynamical models successfully reproduce the key characteristics of our current solar system; some of these models require significant migration of the giant planets, whereas others do not. These models provide different predictions on the presence of rocky material expelled from the inner solar system in the Oort cloud. C/2014 S3 could be the key to verifying these predictions of the migration-based dynamical models. Furthermore, this object displays a very faint, weak level of comet-like activity, five to six orders of magnitude less than that of typical ice-rich comets on similar Orbits coming from the Oort cloud. For the nearly tailless appearance, we are calling C/2014 S3 a Manx object. Various arguments convince us that this activity is produced by sublimation of volatile ice, that is, normal cometary activity. The activity implies that C/2014 S3 has retained a tiny fraction of the water that is expected to be present at its formation distance in the inner solar system. We may be looking at fresh inner solar system Earth-forming material that was ejected from the inner solar system and preserved for billions of years in the Oort cloud. PMID:27386512

  8. SUBic: A Scalable Unsupervised Framework for Discovering High Quality Biclusters

    Institute of Scientific and Technical Information of China (English)

    Jooil Lee; Yanhua Jin; Won Suk Lee

    2013-01-01

    A biclustering algorithm extends conventional clustering techniques to extract all of the meaningful subgroups of genes and conditions in the expression matrix of a microarray dataset.However,such algorithms are very sensitive to input parameters and show poor scalability.This paper proposes a scalable unsupervised biclustering framework,SUBic,to find high quality constant-row biclusters in an expression matrix effectively.A one-dimensional clustering algorithm is proposed to partition the attributes,that is,columns of an expression matrix into disjoint groups based on the similarity of expression values.These groups form a set of short transactions and are used to discover a set of frequent itemsets each of which corresponds to a bicluster.However,a bicluster may include any attribute whose expression value is not similar enough to others,so a bicluster refinement is used to enhance the quality of a bicluster by removing those attributes based on its distribution of expression values.The performance of the proposed method is comparatively analyzed through a series of experiments on synthetic and real datasets.

  9. Timing of Five PALFA-Discovered Millisecond Pulsars

    CERN Document Server

    Stovall, K; Bogdanov, S; Brazier, A; Camilo, F; Cardoso, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J S; Ferdman, R; Freire, P C C; Hessels, J W T; Jenet, F; Kaplan, D L; Karako-Argaman, C; Kaspi, V M; Knispel, B; Kotulla, R; Lazarus, P; Lee, K J; van Leeuwen, J; Lynch, R; Lyne, A G; Madsen, E; McLaughlin, M A; Patel, C; Ransom, S M; Scholz, P; Siemens, X; Stairs, I H; Stappers, B W; Swiggum, J; Zhu, W W; Venkataraman, A

    2016-01-01

    We report the discovery and timing results for five millisecond pulsars (MSPs) from the Arecibo PALFA survey: PSRs J1906+0055, J1914+0659, J1933+1726, J1938+2516, and J1957+2516. Timing observations of the 5 pulsars were conducted with the Arecibo and Lovell telescopes for time spans ranging from 1.5 to 3.3 yr. All of the MSPs except one (PSR J1914+0659) are in binary systems with low eccentricities. PSR J1957+2516 is likely a redback pulsar, with a ~0.1 $M_\\odot$ companion and possible eclipses that last ~10% of the orbit. The position of PSR J1957+2516 is also coincident with a NIR source. All 5 MSPs are distant (>3.1 kpc) as determined from their dispersion measures, and none of them show evidence of $\\gamma$-ray pulsations in a search of Fermi Gamma-Ray Space Telescope data. These 5 MSPs bring the total number of MSPs discovered by the PALFA survey to 26 and further demonstrate the power of this survey in finding distant, highly dispersed MSPs deep in the Galactic plane.

  10. Timing of 29 Pulsars Discovered in the PALFA Survey

    CERN Document Server

    Lyne, A G; Bogdanov, S; Ferdman, R; Freire, P C C; Kaspi, V M; Knispel, B; Lynch, R; Allen, B; Brazier, A; Camilo, F; Cardoso, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J S; Hessels, J W T; Jenet, F A; Lazarus, P; van Leeuwen, J; Lorimer, D R; Madsen, E; McKee, J; McLaughlin, M A; Parent, E; Patel, C; Ransom, S M; Scholz, P; Seymour, A; Siemens, X; Spitler, L G; Stairs, I H; Stovall, K; Swiggum, J; Wharton, R S; Zhu, W W

    2016-01-01

    We report on the discovery and timing observations of 29 distant long-period pulsars discovered in the ongoing Arecibo PALFA pulsar survey. Following discovery with the Arecibo Telescope, confirmation and timing observations of these pulsars over several years at Jodrell Bank Observatory have yielded high-precision positions and measurements of rotation and radiation properties. We have used multi-frequency data to measure the interstellar scattering properties of some of these pulsars. Most of the pulsars have properties that mirror those of the previously known pulsar population, although four show some notable characteristics. PSRs J1907+0631 and J1925+1720 are young and are associated with supernova remnants or plerionic nebulae: J1907+0631 lies close to the center of SNR G40.5-0.5, while J1925+1720 is coincident with a high-energy Fermi gamma-ray source. One pulsar, J1932+1500, is in a surprisingly eccentric, 199-day binary orbit with a companion having a minimum mass of 0.33 solar masses. Several of the...

  11. Two Radio Supernova Remnants Discovered in the Outer Galaxy

    CERN Document Server

    Foster, Tyler; Reich, Wolfgang; Kothes, Roland; West, Jennifer; 10.1051/0004-6361/201220362

    2013-01-01

    We report on the discovery of two supernova remnants (SNRs) designated G152.4-2.1 and G190.9-2.2, using Canadian Galactic Plane Survey data. The aims of this paper are, first, to present evidence that favours the classification of both sources as SNRs, and, second, to describe basic parameters (integrated flux density, spectrum, and polarization) as well as properties (morphology, line-of-sight velocity, distance and physical size) to facilitate and motivate future observations. Spectral and polarization parameters are derived from multiwavelength data from existing radio surveys carried out at wavelengths between 6 and 92cm. In particular for the source G152.4-2.1 we also use new observations at 11cm done with the Effelsberg 100m telescope. The interstellar medium around the discovered sources is analyzed using 1-arcminute line data from neutral hydrogen (HI) and 45-arcsecond 12CO(J=1-0). G152.4-2.1 is a barrel shaped SNR with two opposed radio-bright polarized flanks on the North and South. The remnant, whi...

  12. Discovering Topology of MultiSubnet LAN using MIB

    Directory of Open Access Journals (Sweden)

    Sapna Harishankar

    2012-08-01

    Full Text Available Today, Ethernet is the dominant local area network(LAN technology. These networks, typically, comprise large number of elements from different vendors. This raises considerable difficulties in performing network management tasks, such as resource management and root cause analysis, which are practically impossible without an up-to-date knowledge of the physical network topology. Given the dynamic nature of today's LANs, keeping track of topology information manually is a daunting (if not impossible task. Therefore, it is essential to develop practical schemes for automatic inference of the physical topology of Ethernet networks. In this paper, we propose a simple and efficient algorithmic solution for discovering the physical topology of large, heterogeneous Ethernet LANs that may include multiple subnets as well as uncooperative network elements, like hubs. Our scheme utilizes only generic MIB information and does not required any hardware or software modification of the underlying network elements. By rigorous analysis, we prove that our method correctly infers the network topology and has low communication and computational overheads.

  13. Discovering High-Quality Threaded Discussions in Online Forums

    Institute of Scientific and Technical Information of China (English)

    Jung-Tae Lee; Min-Chul Yang; Hae-Chang Rim

    2014-01-01

    Archives of threaded discussions generated by users in online forums and discussion boards contain valuable knowledge on various topics. However, not all threads are useful because of deliberate abuses, such as trolling and flaming, that are commonly observed in online conversations. The existence of various users with different levels of expertise also makes it difficult to assume that every discussion thread stored online contains high-quality contents. Although finding high-quality threads automatically can help both users and search engines sift through a huge amount of thread archives and make use of these potentially useful resources effectively, no previous work to our knowledge has performed a study on such task. In this paper, we propose an automatic method for distinguishing high-quality threads from low-quality ones in online discussion sites. We first suggest four different artificial measures for inducing overall quality of a thread based on ratings of its posts. We then propose two tasks involving prediction of thread quality without using post rating information. We adopt a popular machine learning framework to solve the two prediction tasks. Experimental results on a real world forum archive demonstrate that our method can significantly improve the prediction performance across all four measures of thread quality on both tasks. We also compare how different types of features derived from various aspects of threads contribute to the overall performance and investigate key features that play a crucial role in discovering high-quality threads in online discussion sites.

  14. Chandra Observations of Eight Sources Discovered by INTEGRAL

    CERN Document Server

    Tomsick, John A; Wang, Qinan; Bodaghee, Arash; Chaty, Sylvain; Rahoui, Farid; Rodriguez, Jerome; Fornasini, Francesca M

    2015-01-01

    We report on 0.3-10 keV observations with the Chandra X-ray Observatory of eight hard X-ray sources discovered within 8 degrees of the Galactic plane by the INTEGRAL satellite. The short (5 ks) Chandra observations of the IGR source fields have yielded very likely identifications of X-ray counterparts for three of the IGR sources: IGR J14091-6108, IGR J18088-2741, and IGR J18381-0924. The first two have very hard spectra in the Chandra band that can be described by a power-law with photon indices of Gamma = 0.6+/-0.4 and -0.7(+0.4)(-0.3), respectively (90% confidence errors are given), and both have a unique near-IR counterpart consistent with the Chandra position. IGR J14091-6108 also displays a strong iron line and a relatively low X-ray luminosity, and we argue that the most likely source type is a Cataclysmic Variable (CV), although we do not completely rule out the possibility of a High Mass X-ray Binary. IGR J18088-2741 has an optical counterpart with a previously measured 6.84 hr periodicity, which may...

  15. Discovering Light Pseudoscalar Bosons in Double-Pulsar Observations

    CERN Document Server

    Dupays, A; Dupays, Arnaud; Roncadelli, Marco

    2006-01-01

    The axion is just one from a general class of new particles -- called Light Pseudoscalar Bosons (LPBs) -- predicted by many realistic extensions of the Standard Model. We offer a somewhat pedagogical review of their main properties, with particular emphasis on the effects they induce in a light beam travelling in an external magnetic field, like photon-LPB oscillations, birefringence and dichroism. Moreover, we discuss a new strategy whereby LPBs can be discovered by high-precision observations of certain binary neutron-star systems. Basically, in a double pulsar seen almost edge-on, photon-LPB oscillations can give rise to a characteristic attenuation pattern of the light beam emitted by one of the pulsars when it goes through the magnetosphere of the companion. Depending on the actual values of the LPB mass and its two-photon coupling constant, the effect can be seen in the $\\gamma$-ray band with the upcoming GLAST mission. We also shown that this method provides a remarkable cross-check for the recent clai...

  16. Unified Photo Enhancement by Discovering Aesthetic Communities From Flickr.

    Science.gov (United States)

    Hong, Richang; Zhang, Luming; Tao, Dacheng

    2016-03-01

    Photo enhancement refers to the process of increasing the aesthetic appeal of a photo, such as changing the photo aspect ratio and spatial recomposition. It is a widely used technique in the printing industry, graphic design, and cinematography. In this paper, we propose a unified and socially aware photo enhancement framework which can leverage the experience of photographers with various aesthetic topics (e.g., portrait and landscape). We focus on photos from the image hosting site Flickr, which has 87 million users and to which more than 3.5 million photos are uploaded daily. First, a tagwise regularized topic model is proposed to describe the aesthetic topic of each Flickr user, and coherent and interpretable topics are discovered by leveraging both the visual features and tags of photos. Next, a graph is constructed to describe the similarities in aesthetic topics between the users. Noticeably, densely connected users have similar aesthetic topics, which are categorized into different communities by a dense subgraph mining algorithm. Finally, a probabilistic model is exploited to enhance the aesthetic attractiveness of a test photo by leveraging the photographic experiences of Flickr users from the corresponding communities of that photo. Paired-comparison-based user studies show that our method performs competitively on photo retargeting and recomposition. Moreover, our approach accurately detects aesthetic communities in a photo set crawled from nearly 100000 Flickr users.

  17. Decision Tree Approach to Discovering Fraud in Leasing Agreements

    Directory of Open Access Journals (Sweden)

    Horvat Ivan

    2014-09-01

    Full Text Available Background: Fraud attempts create large losses for financing subjects in modern economies. At the same time, leasing agreements have become more and more popular as a means of financing objects such as machinery and vehicles, but are more vulnerable to fraud attempts. Objectives: The goal of the paper is to estimate the usability of the data mining approach in discovering fraud in leasing agreements. Methods/Approach: Real-world data from one Croatian leasing firm was used for creating tow models for fraud detection in leasing. The decision tree method was used for creating a classification model, and the CHAID algorithm was deployed. Results: The decision tree model has indicated that the object of the leasing agreement had the strongest impact on the probability of fraud. Conclusions: In order to enhance the probability of the developed model, it would be necessary to develop software that would enable automated, quick and transparent retrieval of data from the system, processing according to the rules and displaying the results in multiple categories.

  18. Chandra Identification of Two AGN Discovered by INTEGRAL

    CERN Document Server

    Tomsick, John A; Rahoui, Farid; Ajello, Marco; Rodriguez, Jerome; Barriere, Nicolas; Bodaghee, Arash; Chaty, Sylvain

    2015-01-01

    Here, we report on observations of two hard X-ray sources that were originally discovered with the INTEGRAL satellite: IGR J04059+5416 and IGR J08297-4250. We use the Chandra X-ray Observatory to localize the sources and then archival near-IR images to identify the counterparts. Both sources have counterparts in the catalog of extended 2 Micron All-Sky Survey sources, and the counterpart to IGR J04059+5416 has been previously identified as a galaxy. Thus, we place IGR J04059+5416 in the class of Active Galactic Nuclei (AGN), and we suggest that IGR J08297-4250 is also an AGN. If this identification is correct, the near-IR images suggest that the host galaxy of IGR J08297-4250 may be merging with a smaller nearby galaxy. For IGR J04059+5416, the 0.3-86 keV spectrum from Chandra and INTEGRAL is consistent with an absorbed power-law with a column density of N_H = 3.1(+2.0)(-1.5)e22 cm-2 and a photon index of Gamma = 1.4+/-0.7, and we suggest that it is a Seyfert galaxy. For IGR J08297-4250, the photon index is s...

  19. Discovering English tense-backshift parameters through discourse

    Directory of Open Access Journals (Sweden)

    Silvana Orel Kos

    2014-12-01

    Full Text Available English grammars and teaching materials often fail to include references to specific discoursal and communicative functions. This facilitates the foreign language acquisition process during which learners acquire basic linguistic skills. The teaching of indirect discourse or so-called reported speech is no exception in this respect: easy-to-learn grammatical rules governing tense-backshift are combined with rather open-ended communicative functions. The CEFR 2011, however, aims at developing the user’s communicative competence, which at its most naturally-occurring level includes the pragmatic-discursive components. The article presents a discourse-oriented approach to indirect discourse teaching and learning, in which the role of the communication mediator, i.e. the indirect discourse producer, is presented as one of the most significant parameters that have been analytically disregarded, yet it provides an identification model for the learner as an active language user. Our approach focuses on further important parameters of indirect discourse, i.e. the discoursal macrotextual type, the focus on the original communicator or the message, the communication mediator’s attitude or involvement, semantic, stylistic and syntactic restrictions. The suggested discourse-oriented approach encourages students to discover “grammatical rules” on their own, which should enable them to develop more internalized and confident language production skills.

  20. Discovering Psychological Principles by Mining Naturally Occurring Data Sets.

    Science.gov (United States)

    Goldstone, Robert L; Lupyan, Gary

    2016-07-01

    The very expertise with which psychologists wield their tools for achieving laboratory control may have had the unwelcome effect of blinding psychologists to the possibilities of discovering principles of behavior without conducting experiments. When creatively interrogated, a diverse range of large, real-world data sets provides powerful diagnostic tools for revealing principles of human judgment, perception, categorization, decision-making, language use, inference, problem solving, and representation. Examples of these data sets include patterns of website links, dictionaries, logs of group interactions, collections of images and image tags, text corpora, history of financial transactions, trends in twitter tag usage and propagation, patents, consumer product sales, performance in high-stakes sporting events, dialect maps, and scientific citations. The goal of this issue is to present some exemplary case studies of mining naturally existing data sets to reveal important principles and phenomena in cognitive science, and to discuss some of the underlying issues involved with conducting traditional experiments, analyses of naturally occurring data, computational modeling, and the synthesis of all three methods. PMID:27404718

  1. Discovering Tau and Muon Solar Neutrino Flares above backgrounds

    CERN Document Server

    Fargion, D

    2004-01-01

    Solar neutrino flares astronomy is at the edge of its discover. High energy flare particles (protons, alpha) whose self scattering within the solar corona is source of a rich prompt charged pions are also source of sharp solar neutrino "burst" (at tens-hundred MeV) produced by their pion-muon primary decay in flight. This brief (minute) solar neutrino "burst" at largest peak overcome by four-five order of magnitude the steady atmospheric neutrino noise at the Earth. Later on, solar flare particles hitting the terrestrial atmosphere may marginally increase the atmospheric neutrino flux without relevant consequences. Largest prompt "burst" solar neutrino flare may be detected in present or better in future largest neutrino underground neutrino detectors. Our estimate for the recent and exceptional October - November 2003 solar flares gives a number of events above or just near unity for Super-Kamiokande. The neutrino spectra may reflect in a subtle way the neutrino flavour mixing in flight. A surprising tau app...

  2. Fast Algorithms for Discovering Sequential Patterns in Massive Datasets

    Directory of Open Access Journals (Sweden)

    S. Dharani

    2011-01-01

    Full Text Available Problem statement: Sequential pattern mining is one of the specific data mining tasks, particularly from retail data. The task is to discover all sequential patterns with a user-specified minimum support, where support of a pattern is the number of data-sequences that contain the pattern. Approach: To find a sequence patterns variety of algorithm like AprioriAll and Generalized Sequential Patterns (GSP were there. We present fast and efficient algorithms called AprioriAllSID and GSPSID for mining sequential patterns that were fundamentally different from known algorithms. Results: The proposed algorithm had been implemented and compared with AprioriAll and Generalized Sequential Patterns (GSP. Its performance was studied on an experimental basis. We combined the AprioriAllSID algorithm with AprioriAll algorithm into a Hybrid algorithm, called AprioriAll Hybrid. Conclusion: Implementation shows that the execution time of the algorithm to find sequential pattern depends on total no of candidates generated at each level and the time taken to scan the database. Our performance study shows that the proposed algorithms have an excellent performance over the best existing algorithms.

  3. Prediction of Human Activity by Discovering Temporal Sequence Patterns.

    Science.gov (United States)

    Li, Kang; Fu, Yun

    2014-08-01

    Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units. PMID:26353344

  4. Prasinoxanthin-constaining Prasinophyceae Discovered in Jiaozhou Bay, China

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Yu; Chun-Mei Deng; Peng Yao; Yu Zhen; Shu-Ben Qian

    2007-01-01

    The class Prasinophyceae (Chlorophyta) contains some photosynthetic eukaryotlc ultraplankton species characterized by containing prasinoxanthin. The existence and abundance of these organisms can be estimated by the diagnostic pigment. We detected the unique pigments of prasinoxanthin-contalning Prasinophyceae in Jlaozhou Bay, China using high performance liquid chromatography (HPLC). This was the first finding of this kind in Chinese seas. Using the ratio of prasinoxanthin to chlorophyll a, the abundance of prasinoxanthin-containing Prasinophyceae has been calculated. The average contribution of prasinoxanthin-contalning Prasinophyceae to the chlorophyll a pool was 8.5% and 17.0% in May and August 2004 in Jiaozhou Bay, and the maximums were 25.9% and 36.3%. Size fractionated pigment analysis suggested that more than 80% of prasinoxanthin were in the fraction of 2-20 μm.According to the results of pigment and morphological analysis, the possible genera of prasinoxanthin-containing Prasinophyceae and the reasons for causing this high abundant phytoplankton in Jiaozhou Bay were discussed.This kind of phytoplankton can not be discovered in traditional biological investigation, but its contribution to the coastal ecosystem is significant enough to be studied further.

  5. Nitric oxide: a newly discovered function on wound healing

    Institute of Scientific and Technical Information of China (English)

    Jian-dong LUO; Alex F CHEN

    2005-01-01

    Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in this process, emerging evidence from both animal and human studies indicates that nitric oxide (NO) plays a key role in wound repair. The beneficial effects of NO on wound repair may be attributed to its functional influences on angiogenesis,inflammation, cell proliferation, matrix deposition, and remodeling. Recent findings from in vitro and in vivo studies of NO on wound repair are summarized in this review. The unveiled novel mechanisms support the use of NO-containing agents and/or NO synthase gene therapy as new therapeutic regimens for impaired wound healing.

  6. How to Use Equipment Therapeutically.

    Science.gov (United States)

    Bowne, Douglas

    1986-01-01

    Shares therapeutic and economic practices surrounding equipment used in New York's Higher Horizons adventure program of therapy for troubled youth. Encourages educators, therapists, and administrators to explore relationship between equipment selection, program goals, and clients. (NEC)

  7. Novel chinmedomics strategy for discovering effective constituents from ShenQiWan acting on ShenYangXu syndrome.

    Science.gov (United States)

    Zhou, Xiao-Hang; Zhang, Ai-Hua; Wang, Liang; Tan, Yun-Long; Guan, Yu; Han, Ying; Sun, Hui; Wang, Xi-Jun

    2016-08-01

    Elucidation of the efficacy of traditional Chinese medicine (TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background?Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of ShenQiWan (SQW) acting on ShenYangXu (kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae. PMID:27608946

  8. Attachment theory and therapeutic relationships

    OpenAIRE

    Boysan, Zehra

    2015-01-01

    The aims of this study were to examine the associations between current self-reported attachment styles, retrospective reports of childhood experiences, and the development of the therapeutic alliance. It was hypothesised that anxious and avoidant attachment would be correlated with negative childhood experiences and that both attachment anxiety and avoidance would be inversely correlated with the therapeutic alliance. The third hypothesis stated that negative childhood recollections would co...

  9. [Therapeutic touch and anorexia nervosa].

    Science.gov (United States)

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. PMID:27615696

  10. Metrics for antibody therapeutics development

    OpenAIRE

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  11. Therapeutic cloning: promises and issues

    OpenAIRE

    Kfoury, Charlotte

    2007-01-01

    Advances in biotechnology necessitate both an understanding of scientific principles and ethical implications to be clinically applicable in medicine. In this regard, therapeutic cloning offers significant potential in regenerative medicine by circumventing immunorejection, and in the cure of genetic disorders when used in conjunction with gene therapy. Therapeutic cloning in the context of cell replacement therapy holds a huge potential for de novo organogenesis and the permanent treatment o...

  12. Therapeutic Vaccines for Chronic Infections

    Science.gov (United States)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  13. Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties.

    Science.gov (United States)

    Gamal El-Din, Mahmoud M; El-Gamal, Mohammed I; Abdel-Maksoud, Mohammed S; Yoo, Kyung Ho; Oh, Chang-Hyun

    2016-08-25

    A novel series of 1,3,4-triarylpyrazole derivatives possessing terminal arylamide or arylurea terminal moieties has been designed and synthesized. Their in vitro antiproliferative activities were investigated against a panel of 58 cell lines of nine different cancer types at the NCI, USA. The urea analogues 2b, 2c, and 2f as well as the amide derivatives 3e and 3f exerted the highest mean % inhibition values over the 58 cell line panel at 10 μM, and thus were further tested in 5-dose testing mode to determine their GI50, TGI, and LC50 values. The above mentioned compounds have shown stronger antiproliferative activities in terms of potency and efficacy upon comparing their results with Sorafenib as a reference compound. Among them, compounds 2c and 2f possessing 3,4-dichlorophenylurea terminal moiety showed the highest mean %inhibition value of about 99.85 and 104.15% respectively over the 58-cell line panel at 10 μM concentration. Also compounds 2b, 3e, and 3f exhibited mean % inhibition over 80% at 10 μM concentration. The GI50 value of compound 3e over K-562 cancer cell line was 0.75 μM. Accordingly, compound 2f was screened over seven kinases at a single-dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly inhibitory activities (90.44% and 87.71%) against BRAF (V600E) and RAF1 kinases, respectively. Its IC50 value against BRAF (V600E) was 0.77 μM. Compounds 2b, 2c, 2f, 3e, and 3f exerted high selectivity towards cancer cell lines than L132 normal lung cells. PMID:27155467

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

    Science.gov (United States)

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

    2014-01-01

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

  15. HIV-1 Nef and Vpu Are Functionally Redundant Broad-Spectrum Modulators of Cell Surface Receptors, Including Tetraspanins

    Science.gov (United States)

    Haller, Claudia; Müller, Birthe; Fritz, Joëlle V.; Lamas-Murua, Miguel; Stolp, Bettina; Pujol, François M.; Keppler, Oliver T.

    2014-01-01

    ABSTRACT HIV-1 Nef and Vpu are thought to optimize virus replication in the infected host, at least in part via their ability to interfere with vesicular host cell trafficking. Despite the use of distinct molecular mechanisms, Nef and Vpu share specificity for some molecules such as CD4 and major histocompatibility complex class I (MHC-I), while disruption of intracellular transport of the host cell restriction factor CD317/tetherin represents a specialized activity of Vpu not exerted by HIV-1 Nef. To establish a profile of host cell receptors whose intracellular transport is affected by Nef, Vpu, or both, we comprehensively analyzed the effect of these accessory viral proteins on cell surface receptor levels on A3.01 T lymphocytes. Thirty-six out of 105 detectable receptors were significantly downregulated by HIV-1 Nef, revealing a previously unappreciated scope with which HIV-1 Nef remodels the cell surface of infected cells. Remarkably, the effects of HIV-1 Vpu on host cell receptor exposure largely matched those of HIV-1 Nef in breadth and specificity (32 of 105, all also targeted by Nef), even though the magnitude was generally less pronounced. Of particular note, cell surface exposure of all members of the tetraspanin (TSPAN) protein family analyzed was reduced by both Nef and Vpu, and the viral proteins triggered the enrichment of TSPANs in a perinuclear area of the cell. While Vpu displayed significant colocalization and physical association with TSPANs, interactions of Nef with TSPANs were less robust. TSPANs thus emerge as a major target of deregulation in host cell vesicular transport by HIV-1 Nef and Vpu. The conservation of this activity in two independent accessory proteins suggests its importance for the spread of HIV-1 in the infected host. IMPORTANCE In this paper, we define that HIV-1 Nef and Vpu display a surprising functional overlap and affect the cell surface exposure of a previously unexpected breadth of cellular receptors. Our analyses furthermore identify the tetraspanin protein family as a previously unrecognized target of Nef and Vpu activity. These findings have implications for the interpretation of effects detected for these accessory gene products on individual host cell receptors and illustrate the coevolution of Nef and Vpu function. PMID:25275127

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

    Science.gov (United States)

    Netíková, Ladislava; Bogusch, Petr; Heneberg, Petr

    2013-09-01

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

  17. 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.

  18. 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.

  19. Gamma radiation-induced mutant of NSIC RC144 with broad-spectrum resistance to bacterial blight

    International Nuclear Information System (INIS)

    Mutant lines derived from gamma radiation-treated commercial variety NSIC RC144 were produced and screened for novel resistance to bacterial blight, one of the most serious diseases of rice. Preliminary screening of a bulk M2 population through induced method using race 3 of the pathogen Xanthomonas oryzae pv. oryzae (Xoo) resulted in the selection of 89 resistant plants. Subsequent repeated bacterial blight screenings and generation advance for five seasons resulted in the selection of two highly resistant M7 sister lines whose origin can be traced to a single M2 plant. DNA fingerprinting using 63 genome-wide simple sequence repeat (SSR) markers revealed an identical pattern in these lines. Using the same set of markers, they also exhibited 98% similarity to wild type NSIC RC144 indicating that the resistance is due to mutation and not due to genetic admixture or seed impurity. Two seasons of bacterial blight screening using 14 local isolates representing ten races of Xoo revealed an identical reaction pattern in these lines. The reaction pattern was observed to be unique compared to known patterns in four IRBB isolines (IRBB 4, 5, 7 and 21) with strong resistant reaction to bacterial blight suggesting possible novel resistance. The susceptible reaction in F1 testcrosses using Xoo race 6 and the segregation patterns in two F2 populations that fit with the expected 3 susceptible: 1 resistant ratio (P = 0.4, ns) suggest a single-gene recessive mutation in these lines. These mutants are now being used as resistance donor in the breeding program while further molecular characterization to map and characterize the mutated gene is being pursued

  20. 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.

  1. 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. PMID:22325444

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

    International Nuclear Information System (INIS)

    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. - Highlights: ► 61 samples from the Antarctica and Tierra de Fuego analysed for the presence of 18 perfluorinated compounds. ► Acid compounds presented the highest levels of concentration and perfluorooctane sulfonate was the most frequently found. ► Concentrations in algae much higher than those in soils. ► Data supporting existing models for the transport, deposition, biodegradation and bioaccumulation patterns are presented. - 18 perfluorinated compounds assessed in biota and environmental samples from Tierra del Fuego and the Antarctica. Concentrations related to Compounds properties.

  3. 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

  4. "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.

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

    Science.gov (United States)

    Stone, Judy

    2016-01-01

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

  6. Mice with a naturally occurring DISC1 mutation display a broad spectrum of behaviors associated to psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Raquel eGomez-Sintes

    2014-07-01

    Full Text Available DISC1 (disrupted in schizophrenia-1 gene is associated with several neuropsychiatric disorders as it is disrupted by a balanced translocation involving chromosomes 1 and 11 in a large Scottish pedigree with high prevalence of schizophrenia, bipolar disorder and major depression. Since its identification, several mouse models with DISC1 genetic modifications have been generated using different approaches. Interestingly, a natural deletion of 25bp in the 129 mouse alters the DISC1 gene reading frame leading to a premature stop codon very close to the gene breakpoint in the mutant allele of the Scottish family. In the present study we confirmed that the 129DISC1Del mutation results in reduced level of full length DISC1 in hippocampus of heterozygous mice and we have characterized the behavioral consequences of heterozygous 129DISC1Del mutation in a mixed B6129 genetic background. We found alterations in spontaneous locomotor activity (hyperactivity in males and hypoactivity in females, deficits in pre-pulse inhibition and also increased despair behavior in heterozygous 129DISC1Del mice, thus reproducing typical behaviors associated to psychiatric disorders. Since this mouse strain is widely and commercially available, we propose it as an amenable tool to study DISC1-related biochemical alterations and psychiatric behaviors.

  7. 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.

  8. Novel Indole-2-Carboxamide Compounds Are Potent Broad-Spectrum Antivirals Active against Western Equine Encephalitis Virus In Vivo

    OpenAIRE

    Delekta, Phillip C.; Dobry, Craig J.; Sindac, Janice A.; Barraza, Scott J.; Blakely, Pennelope K.; Xiang, Jianming; Kirchhoff, Paul D.; Keep, Richard F; Irani, David N; Larsen, Scott D.; Miller, David J.

    2014-01-01

    Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950–957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequent...

  9. 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.

  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. 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

  12. Graphene oxide exhibits broad-spectrum antimicrobial activity against bacterial phytopathogens and fungal conidia by intertwining and membrane perturbation

    Science.gov (United States)

    Chen, Juanni; Peng, Hui; Wang, Xiuping; Shao, Feng; Yuan, Zhaodong; Han, Heyou

    2014-01-01

    To understand the interaction mechanism between graphene oxide (GO) and typical phytopathogens, a particular investigation was conducted about the antimicrobial activity of GO against two bacterial pathogens (P. syringae and X. campestris pv. undulosa) and two fungal pathogens (F. graminearum and F. oxysporum). The results showed that GO had a powerful effect on the reproduction of all four pathogens (killed nearly 90% of the bacteria and repressed 80% macroconidia germination along with partial cell swelling and lysis at 500 μg mL-1). A mutual mechanism is proposed in this work that GO intertwinds the bacteria and fungal spores with a wide range of aggregated graphene oxide sheets, resulting in the local perturbation of their cell membrane and inducing the decrease of the bacterial membrane potential and the leakage of electrolytes of fungal spores. It is likely that GO interacts with the pathogens by mechanically wrapping and locally damaging the cell membrane and finally causing cell lysis, which may be one of the major toxicity actions of GO against phytopathogens. The antibacterial mode proposed in this study suggests that the GO may possess antibacterial activity against more multi-resistant bacterial and fungal phytopathogens, and provides useful information about the application of GO in resisting crop diseases.To understand the interaction mechanism between graphene oxide (GO) and typical phytopathogens, a particular investigation was conducted about the antimicrobial activity of GO against two bacterial pathogens (P. syringae and X. campestris pv. undulosa) and two fungal pathogens (F. graminearum and F. oxysporum). The results showed that GO had a powerful effect on the reproduction of all four pathogens (killed nearly 90% of the bacteria and repressed 80% macroconidia germination along with partial cell swelling and lysis at 500 μg mL-1). A mutual mechanism is proposed in this work that GO intertwinds the bacteria and fungal spores with a wide range of aggregated graphene oxide sheets, resulting in the local perturbation of their cell membrane and inducing the decrease of the bacterial membrane potential and the leakage of electrolytes of fungal spores. It is likely that GO interacts with the pathogens by mechanically wrapping and locally damaging the cell membrane and finally causing cell lysis, which may be one of the major toxicity actions of GO against phytopathogens. The antibacterial mode proposed in this study suggests that the GO may possess antibacterial activity against more multi-resistant bacterial and fungal phytopathogens, and provides useful information about the application of GO in resisting crop diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr04941h

  13. 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...

  14. Baulamycins A and B, Broad-Spectrum Antibiotics Identified as Inhibitors of Siderophore Biosynthesis in Staphylococcus aureus and Bacillus anthracis

    OpenAIRE

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

    2014-01-01

    Siderophores are high-affinity iron chelators produced by microorganisms and frequently contribute to the virulence of human pathogens. Targeted inhibition of the biosynthesis of siderophores staphyloferrin B of Staphylococcus aureus and petrobactin of Bacillus anthracis hold considerable potential as a single or combined treatment for methicillin-resistant S. aureus (MRSA) and anthrax infection, respectively. The biosynthetic pathways for both siderophores involve a nonribosomal peptide synt...

  15. 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

    ... antenna. Allen 7,629,080 Electrode materials for electrochemical cells. Hill 7,631,567 Systems and methods... Methods for detecting and classifying loads on AC lines. Jiang 7,695,601 Electrochemical test apparatus... reduced noise. Meyers 7,805,079 Free-space quantum communications process operative absent line-of-...

  16. Swarming of Pseudomonas aeruginosa Is Controlled by a Broad Spectrum of Transcriptional Regulators, Including MetR ▿ †

    OpenAIRE

    Yeung, Amy T. Y.; Torfs, Ellen C. W.; Jamshidi, Farzad; Bains, Manjeet; Wiegand, Irith; Hancock, Robert E. W.; Overhage, Joerg

    2009-01-01

    Pseudomonas aeruginosa exhibits swarming motility on semisolid surfaces (0.5 to 0.7% agar). Swarming is a more than just a form of locomotion and represents a complex adaptation resulting in changes in virulence gene expression and antibiotic resistance. In this study, we used a comprehensive P. aeruginosa PA14 transposon mutant library to investigate how the complex swarming adaptation process is regulated. A total of 233 P. aeruginosa PA14 transposon mutants were verified to have alteration...

  17. 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.

  18. 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. PMID:27381399

  19. 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.

  20. Vaccination with embryonic stem cells protects against lung cancer: is a broad-spectrum prophylactic vaccine against cancer possible?

    Directory of Open Access Journals (Sweden)

    Kavitha Yaddanapudi

    Full Text Available The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC. Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF in order to provide immunostimulatory adjuvant activity. Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC. ESC-induced anti-tumor immunity was not due to a non-specific "allo-response" as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8(+ T effector responses, Th1 cytokine response, higher intratumoral CD8(+ T effector/CD4(+CD25(+Foxp3(+ T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL response because in vivo depletion of CD8(+ T lymphocytes completely abrogated the protective effect of vaccination. Importantly, this vaccination strategy also suppressed the development of lung cancer induced by the combination of carcinogen administration and chronic pulmonary inflammation. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, perhaps more importantly, could represent a first step toward the development of prophylactic cancer vaccines.