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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

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

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    Marjanovic, Goran

    2017-01-01

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

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

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

    2016-06-01

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

  4. 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

  5. Broad spectrum bioactive sunscreens.

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

    2008-11-03

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

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

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  8. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

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    Ofra Benny

    2010-09-01

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

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

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

    2009-09-01

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

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

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    Luca Ruiu

    2013-09-01

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

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

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

    2016-03-02

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

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

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

    2015-01-01

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

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

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

    2017-09-07

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

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

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

    2010-09-01

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

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

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

    2010-01-01

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

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

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    Frey Jürg E

    2010-02-01

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

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

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    Avi Raveh

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

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

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

    2004-06-29

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

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

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

    2001-01-01

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

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

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

    2018-02-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  2. Probing Gallic Acid for Its Broad Spectrum Applications.

    Science.gov (United States)

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

    2018-03-29

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

  3. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  8. 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. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Ira Ekmekciu

    2017-05-01

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

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

    OpenAIRE

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

    2015-01-01

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

  12. 77 FR 27785 - Request for Information Regarding the NIH-Industry Program To Discover New Therapeutic Uses for...

    Science.gov (United States)

    2012-05-11

    ...: Discovering New Therapeutic Uses for Existing Molecules are sufficient for biotechnology and pharmaceutical... discovery program might be defined. 6. Comments on the resources that a biotechnology or pharmaceutical... Molecules is designed to be carried out through collaborations between pharmaceutical companies and the...

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

    Mukherjee, Jagriti

    2018-01-01

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

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

    International Nuclear Information System (INIS)

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

    1979-01-01

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

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

    Science.gov (United States)

    Zeun, Ronald; Scalliet, Gabriel; Oostendorp, Michael

    2013-04-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  18. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  20. 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.

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

    Science.gov (United States)

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

    2017-06-28

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Yunjeong Kim

    2016-03-01

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

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

    Science.gov (United States)

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

    2010-03-01

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

  7. Using Big Data to Discover Diagnostics and Therapeutics for Gastrointestinal and Liver Diseases

    Science.gov (United States)

    Wooden, Benjamin; Goossens, Nicolas; Hoshida, Yujin; Friedman, Scott L.

    2016-01-01

    Technologies such as genome sequencing, gene expression profiling, proteomic and metabolomic analyses, electronic medical records, and patient-reported health information have produced large amounts of data, from various populations, cell types, and disorders (big data). However, these data must be integrated and analyzed if they are to produce models or concepts about physiologic function or mechanisms of pathogenesis. Many of these data are available to the public, allowing researchers anywhere to search for markers of specific biologic processes or therapeutic targets for specific diseases or patient types. We review recent advances in the fields of computational and systems biology, and highlight opportunities for researchers to use big data sets in the fields of gastroenterology and hepatology, to complement traditional means of diagnostic and therapeutic discovery. PMID:27773806

  8. 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.

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

    Science.gov (United States)

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

    2017-09-01

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

  10. 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.

  11. 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; Ma, Dik-Lung; 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.

  12. Therapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks.

    Science.gov (United States)

    Mallikarjun, Venkatesh; Swift, Joe

    2016-12-01

    Ageing is a leading risk factor for many debilitating diseases. While age-related diseases have been the subject of over a century of intense investigation, until recently, physiological ageing was considered unavoidable. Pharmacological and genetic studies have since shown that ageing is a malleable process and that its abrogation can prevent its associated diseases. This review summarises a sample of the most promising efforts to deliver the products of ageing research to the clinic. Current efforts include the use of clinically approved drugs that have since been repurposed, as well as the development of novel therapeutics, to target ageing. Furthermore, ongoing research has sought reliable biomarkers of ageing that will accelerate the development of such therapeutics. Development of these technologies will improve quality of late-life and help relieve the enormous stress placed on state healthcare systems by a rapidly ageing global population. Thus, for both medical and socioeconomic reasons, it is imperative that ageing is made to yield to intervention. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. 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

  14. Discovering and Developing Successful Cardiovascular Therapeutics: A Conversation With James N. Topper, MD, PhD.

    Science.gov (United States)

    Topper, James N; Rutherford, John D

    2016-11-15

    Dr James (also known as Jamie) N. Topper, MD, PhD, serves as Managing General Partner at Frazier Healthcare Partners, where he leads the Life Science Venture practice. In 2011, and 2016, he was named to the Midas List of leading venture capitalists, and, in 2013, he was recognized by Forbes as one of the top 10 healthcare investors. He has >25 years of experience working with entrepreneurs to found and build successful therapeutics-focused companies. Dr Topper holds a BS from the University of Michigan. He received an MD and PhD (in biophysics) from Stanford University School of Medicine. He completed postgraduate training in internal medicine and cardiovascular disease at the Brigham and Women's Hospital in Boston and is board certified in both disciplines. © 2016 American Heart Association, Inc.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

    Levine, Joseph; Toker, Lilach; Agam, Galila

    2018-01-01

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

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

    Science.gov (United States)

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

    2014-11-09

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

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

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

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

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

    Science.gov (United States)

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

    1987-07-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Paolo Grieco

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Pan Kyeom Kim

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

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

  7. 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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Sajad Ali

    2017-10-01

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

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

    Science.gov (United States)

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

    2013-01-07

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

  12. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-08-14

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

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

    Science.gov (United States)

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

    2013-10-07

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

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

    Science.gov (United States)

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-12-13

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2018-03-12

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    李承辉; 王锴; 郑玮; 王致祥; 刘建; 游效曾

    2012-01-01

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

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

    Science.gov (United States)

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

    2018-01-25

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

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

    Science.gov (United States)

    Anantharaman, Aparna; Sahal, Dinkar

    2010-08-26

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

  5. 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.

  6. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

    OpenAIRE

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

    2017-01-01

    Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from in...

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

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  9. Identification of an antioxidant small-molecule with broad-spectrum antiviral activity.

    Science.gov (United States)

    Panchal, Rekha G; Reid, St Patrick; Tran, Julie P; Bergeron, Alison A; Wells, Jay; Kota, Krishna P; Aman, Javad; Bavari, Sina

    2012-01-01

    The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets. Published by Elsevier B.V.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2014-08-15

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

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

    International Nuclear Information System (INIS)

    Hawkins, D.; Abrahamse, H.

    2007-01-01

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

  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. Novel Naja atra cardiotoxin 1 (CTX-1 derived antimicrobial peptides with broad spectrum activity.

    Directory of Open Access Journals (Sweden)

    Andrea Sala

    new way for discovering a large number of novel and promising antimicrobial peptides families.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-04

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

  19. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

    Directory of Open Access Journals (Sweden)

    Keiko Rausch

    2017-01-01

    Full Text Available Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested, including physiologically relevant primary cells. Nanchangmycin also was active against other medically relevant viruses, including West Nile, dengue, and chikungunya viruses that use a similar route of entry. This study provides a resource of small molecules to study Zika virus pathogenesis.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-09-01

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

  2. 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

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

    Science.gov (United States)

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

    2018-03-01

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

  4. 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.

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

    Science.gov (United States)

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

    2011-02-01

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

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

    Science.gov (United States)

    2013-01-01

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

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

    Science.gov (United States)

    Kaminski, Krzysztof

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-06-15

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

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

    Directory of Open Access Journals (Sweden)

    Akira Sakurai

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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    International Nuclear Information System (INIS)

    Bogdanov, A.T.

    1990-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2017-11-30

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-06

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2006-10-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  1. 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.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  4. Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21.

    Science.gov (United States)

    Iglesias, Pedro; Selgas, Rafael; Romero, Sara; Díez, Juan J

    2012-09-01

    renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.

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

    Directory of Open Access Journals (Sweden)

    Zahid Raja

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Hacer Yapicioglu Yildizdas

    2017-03-01

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

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

    Science.gov (United States)

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

    1993-01-01

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

  10. 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.

  11. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Ayusman

    2000-12-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2016-12-05

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

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

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

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

  16. In Vitro and In Vivo Antibacterial Activities of OPC-20011, a Novel Parenteral Broad-Spectrum 2-Oxaisocephem Antibiotic

    Science.gov (United States)

    Matsumoto, Makoto; Tamaoka, Hisashi; Ishikawa, Hiroshi; Kikuchi, Mikio

    1998-01-01

    OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 μg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2′ in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptible S. pneumoniae T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats). PMID:9797230

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2009-12-10

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

  19. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

  1. Discovering Wavelets

    CERN Document Server

    Aboufadel, Edward

    1999-01-01

    An accessible and practical introduction to wavelets. With applications in image processing, audio restoration, seismology, and elsewhere, wavelets have been the subject of growing excitement and interest over the past several years. Unfortunately, most books on wavelets are accessible primarily to research mathematicians. Discovering Wavelets presents basic and advanced concepts of wavelets in a way that is accessible to anyone with only a fundamental knowledge of linear algebra. The basic concepts of wavelet theory are introduced in the context of an explanation of how the FBI uses wavelets

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

    Science.gov (United States)

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

    2014-08-01

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

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Chae Kim

    2011-09-01

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

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

    Science.gov (United States)

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

    2009-01-16

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

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    1996-01-01

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

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

    Science.gov (United States)

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

    2006-07-01

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

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

    Science.gov (United States)

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

    2017-04-03

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    International Nuclear Information System (INIS)

    Krien, P.M.; Moyal, D.

    1994-01-01

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

  16. 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...

  17. A desirability-based multi objective approach for the virtual screening discovery of broad-spectrum anti-gastric cancer agents.

    Directory of Open Access Journals (Sweden)

    Yunierkis Perez-Castillo

    Full Text Available Gastric cancer is the third leading cause of cancer-related mortality worldwide and despite advances in prevention, diagnosis and therapy, it is still regarded as a global health concern. The efficacy of the therapies for gastric cancer is limited by a poor response to currently available therapeutic regimens. One of the reasons that may explain these poor clinical outcomes is the highly heterogeneous nature of this disease. In this sense, it is essential to discover new molecular agents capable of targeting various gastric cancer subtypes simultaneously. Here, we present a multi-objective approach for the ligand-based virtual screening discovery of chemical compounds simultaneously active against the gastric cancer cell lines AGS, NCI-N87 and SNU-1. The proposed approach relays in a novel methodology based on the development of ensemble models for the bioactivity prediction against each individual gastric cancer cell line. The methodology includes the aggregation of one ensemble per cell line using a desirability-based algorithm into virtual screening protocols. Our research leads to the proposal of a multi-targeted virtual screening protocol able to achieve high enrichment of known chemicals with anti-gastric cancer activity. Specifically, our results indicate that, using the proposed protocol, it is possible to retrieve almost 20 more times multi-targeted compounds in the first 1% of the ranked list than what is expected from a uniform distribution of the active ones in the virtual screening database. More importantly, the proposed protocol attains an outstanding initial enrichment of known multi-targeted anti-gastric cancer agents.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

  20. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Samson B. Wayah

    2018-03-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Erkan Kiris

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

  7. 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.

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

    Science.gov (United States)

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

    2015-03-01

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

  9. 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.

  10. 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kristensen Hans-Henrik

    2008-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-01

    ABSTRACT

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  15. Broad-spectrum antiviral properties of andrographolide.

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

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

    2013-11-27

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Robert H E Friesen

    2010-02-01

    Full Text Available 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.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.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 as intervention for both seasonal and pandemic influenza.

  2. 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.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2017-06-09

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

  5. Top quark discovered

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Nine months after a careful announcement of tentative evidence for the long-awaited sixth 'top' quark, physicists from the CDF and DO experiments at Fermilab's Tevatron proton-antiproton collider declared on 2 March that they had finally discovered the top quark. Last year (June 1994, page 1), the CDF experiment at the Tevatron reported a dozen candidate top events. These, said CDF, had all the characteristics expected of top, but the difficulties of extracting the tiny signal from a trillion proton-antiproton collisions made them shy of claiming a discovery. For its part, the companion DO Tevatron experiment reported a few similar events but were even more guarded about their interpretation as top quarks. Just after these hesitant announcements, performance at the Tevatron improved dramatically last summer. After the commissioning of a new linear accelerator and a magnet realignment, the machine reached a new world record proton-antiproton collision luminosity of 1.28 x 10 31 per sq cm per s, ten times that originally planned. Data began to pour in at an unprecedented rate and the data sample grew to six trillion collisions. Luminosity has subsequently climbed to 1.7 x 10 31 . The top quark is the final letter in the alphabet of Standard Model particles. According to this picture, all matter is composed of six stronglyinteracting subnuclear particles, the quarks, and six weakly interacting particles, the leptons. Both sextets are neatly arranged as three pairs in order of increasing mass. The fifth quark, the 'beauty' or 'b' quark, was also discovered at Fermilab, back in 1977. Since then physicists have been eagerly waiting for the top to turn up, but have been frustrated by its heaviness - the top is some 40 times the mass of its 'beautiful' partner. Not only is the top quark the heaviest by far, but it is the only quark which has been actively hunted. After the quarry was glimpsed last year, the net has now been

  6. 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)

  7. Nitric oxide nanoparticles: Pre-clinical utility as a therapeutic for intramuscular abscesses

    OpenAIRE

    Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

    2012-01-01

    Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine absce...

  8. Chandra Discovers Cosmic Cannonball

    Science.gov (United States)

    2007-11-01

    One of the fastest moving stars ever seen has been discovered with NASA's Chandra X-ray Observatory. This cosmic cannonball is challenging theories to explain its blistering speed. Astronomers used Chandra to observe a neutron star, known as RX J0822-4300, over a period of about five years. During that span, three Chandra observations clearly show the neutron star moving away from the center of the Puppis A supernova remnant. This remnant is the stellar debris field created during the same explosion in which the neutron star was created about 3700 years ago. Chandra X-ray Image of RX J0822-4300 in Puppis A Chandra X-ray Image of RX J0822-4300 in Puppis A By combining how far it has moved across the sky with its distance from Earth, astronomers determined the neutron star is moving at over 3 million miles per hour. At this rate, RX J0822-4300 is destined to escape from the Milky Way after millions of years, even though it has only traveled about 20 light years so far. "This star is moving at 3 million miles an hour, but it's so far away that the apparent motion we see in five years is less than the height of the numerals in the date on a penny, seen from the length of a football field," said Frank Winkler of Middlebury College in Vermont. "It's remarkable, and a real testament to the power of Chandra, that such a tiny motion can be measured." Labeled Image of RX J0822-4300 in Puppis A Labeled Image of RX J0822-4300 in Puppis A "Just after it was born, this neutron star got a one-way ticket out of the Galaxy," said co-author Robert Petre of NASA's Goddard Space Flight Center in Greenbelt, Md. "Astronomers have seen other stars being flung out of the Milky Way, but few as fast as this." So-called hypervelocity stars have been previously discovered shooting out of the Milky Way with speeds around one million miles per hour. One key difference between RX J0822-4300 and these other reported galactic escapees is the source of their speed. The hypervelocity stars are

  9. Antimicrobial Peptides for Therapeutic Applications: A Review

    Directory of Open Access Journals (Sweden)

    Tsogbadrakh Mishig-Ochir

    2012-10-01

    Full Text Available Antimicrobial peptides (AMPs have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to conventional antibiotics. Although AMPs possess considerable benefits as new generation antibiotics, their clinical and commercial development still have some limitations, such as potential toxicity, susceptibility to proteases, and high cost of peptide production. In order to overcome those obstacles, extensive efforts have been carried out. For instance, unusual amino acids or peptido-mimetics are introduced to avoid the proteolytic degradation and the design of short peptides retaining antimicrobial activities is proposed as a solution for the cost issue. In this review, we focus on small peptides, especially those with less than twelve amino acids, and provide an overview of the relationships between their three-dimensional structures and antimicrobial activities. The efforts to develop highly active AMPs with shorter sequences are also described.

  10. Discovering Hands - México

    OpenAIRE

    Salamanca Cárdenas, Daniela; Castelblanco Domínguez, Junio Andrés; Aguilar Ardila, Laura Andrea

    2016-01-01

    El modelo de Discovering Hands ha sido reconocido internacionalmente como un proyecto innovador que se ha expandido por diferentes países del mundo, como Austria, y se ha empezado a estudiar la propuesta en países como República Checa, India y Colombia. (Discovering Hands, 2016). Esto se debe a que no solo mejora el tratamiento de cáncer de mama, sino que también reduce los costos totales de tratamiento de la enfermedad y aumenta la fuerza laborar de los países donde esté presente. Al represe...

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

    Science.gov (United States)

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

    2015-03-01

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

  12. Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    HuaLin Cai

    2018-03-01

    Full Text Available Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents.

  13. 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.

  14. Stimuli-responsive nanomaterials for therapeutic protein delivery.

    Science.gov (United States)

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-11-28

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Bacterial Inclusion Bodies: Discovering Their Better Half.

    Science.gov (United States)

    Rinas, Ursula; Garcia-Fruitós, Elena; Corchero, José Luis; Vázquez, Esther; Seras-Franzoso, Joaquin; Villaverde, Antonio

    2017-09-01

    Bacterial inclusion bodies (IBs) are functional, non-toxic amyloids occurring in recombinant bacteria showing analogies with secretory granules of the mammalian endocrine system. The scientific interest in these mesoscale protein aggregates has been historically masked by their status as a hurdle in recombinant protein production. However, progressive understanding of how the cell handles the quality of recombinant polypeptides and the main features of their intriguing molecular organization has stimulated the interest in inclusion bodies and spurred their use in diverse technological fields. The engineering and tailoring of IBs as functional protein particles for materials science and biomedicine is a good example of how formerly undesired bacterial byproducts can be rediscovered as promising functional materials for a broad spectrum of applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Mikhail Petrovich Neustroev

    2011-10-01

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

  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. Synthetic histatin analogues with broad-spectrum antimicrobial activity.

    OpenAIRE

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

    1997-01-01

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

  20. Studies on broad spectrum corrosion resistant oxide coatings

    Indian Academy of Sciences (India)

    Unknown

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

  1. The broad spectrum of preclinical radiobiology: British contributions

    International Nuclear Information System (INIS)

    Denekamp, Juliana

    1996-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2005-05-01

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

  4. Graduated diagnostics required. Broad spectrum of differential diagnoses

    International Nuclear Information System (INIS)

    Auer, I.O.

    1997-01-01

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

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

    Science.gov (United States)

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

    2000-09-01

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

  6. Broad-spectrum physical fitness benefits of recreational football

    DEFF Research Database (Denmark)

    Milanović, Zoran; Pantelić, Saša; Čović, Nedim

    2018-01-01

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

  7. Glowing Hot Transiting Exoplanet Discovered

    Science.gov (United States)

    2003-04-01

    VLT Spectra Indicate Shortest-Known-Period Planet Orbiting OGLE-TR-3 Summary More than 100 exoplanets in orbit around stars other than the Sun have been found so far. But while their orbital periods and distances from their central stars are well known, their true masses cannot be determined with certainty, only lower limits. This fundamental limitation is inherent in the common observational method to discover exoplanets - the measurements of small and regular changes in the central star's velocity, caused by the planet's gravitational pull as it orbits the star. However, in two cases so far, it has been found that the exoplanet's orbit happens to be positioned in such a way that the planet moves in front of the stellar disk, as seen from the Earth. This "transit" event causes a small and temporary dip in the star's brightness, as the planet covers a small part of its surface, which can be observed. The additional knowledge of the spatial orientation of the planetary orbit then permits a direct determination of the planet's true mass. Now, a group of German astronomers [1] have found a third star in which a planet, somewhat larger than Jupiter, but only half as massive, moves in front of the central star every 28.5 hours . The crucial observation of this solar-type star, designated OGLE-TR-3 [2] was made with the high-dispersion UVES spectrograph on the Very Large Telescope (VLT) at the ESO Paranal Observatory (Chile). It is the exoplanet with the shortest period found so far and it is very close to the star, only 3.5 million km away. The hemisphere that faces the star must be extremely hot, about 2000 °C and the planet is obviously losing its atmosphere at high rate . PR Photo 10a/03 : The star OGLE-TR-3 . PR Photo 10b/03 : VLT UVES spectrum of OGLE-TR-3. PR Photo 10c/03 : Relation between stellar brightness and velocity (diagram). PR Photo 10d/03 : Observed velocity variation of OGLE-TR-3. PR Photo 10e/03 : Observed brightness variation of OGLE-TR-3. The search

  8. 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

  9. Discovering workflow nets using integer linear programming

    NARCIS (Netherlands)

    van Zelst, S.J.; van Dongen, B.F.; van der Aalst, W.M.P.; Verbeek, H.M.W.

    Process mining is concerned with the analysis, understanding and improvement of business processes. Process discovery, i.e. discovering a process model based on an event log, is considered the most challenging process mining task. State-of-the-art process discovery algorithms only discover local

  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. Decision Mining Revisited – Discovering Overlapping Rules

    NARCIS (Netherlands)

    Mannhardt, F.; de Leoni, M.; Reijers, H.A.; van der Aalst, W.M.P.

    2016-01-01

    Decision mining enriches process models with rules underlying decisions in processes using historical process execution data. Choices between multiple activities are specified through rules defined over process data. Existing decision mining methods focus on discovering mutually-exclusive rules,

  12. Decision Mining Revisited - Discovering Overlapping Rules

    NARCIS (Netherlands)

    Mannhardt, F.; De Leoni, M.; Reijers, H.A.; van der Aalst, W.M.P.; Nurcan, S.; Soffer, P.; Bajec, M.; Eder, J.

    2016-01-01

    Decision mining enriches process models with rules underlying decisions in processes using historical process execution data. Choices between multiple activities are specified through rules defined over process data. Existing decision mining methods focus on discovering mutually-exclusive rules,

  13. Decision mining revisited - Discovering overlapping rules

    NARCIS (Netherlands)

    Mannhardt, Felix; De Leoni, Massimiliano; Reijers, Hajo A.; Van Der Aalst, Wil M P

    2016-01-01

    Decision mining enriches process models with rules underlying decisions in processes using historical process execution data. Choices between multiple activities are specified through rules defined over process data. Existing decision mining methods focus on discovering mutually-exclusive rules,

  14. 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).

  15. Discovering Diabetes Complications: an Ontology Based Model.

    Science.gov (United States)

    Daghistani, Tahani; Shammari, Riyad Al; Razzak, Muhammad Imran

    2015-12-01

    Diabetes is a serious disease that spread in the world dramatically. The diabetes patient has an average of risk to experience complications. Take advantage of recorded information to build ontology as information technology solution will help to predict patients who have average of risk level with certain complication. It is helpful to search and present patient's history regarding different risk factors. Discovering diabetes complications could be useful to prevent or delay the complications. We designed ontology based model, using adult diabetes patients' data, to discover the rules of diabetes with its complications in disease to disease relationship. Various rules between different risk factors of diabetes Patients and certain complications generated. Furthermore, new complications (diseases) might be discovered as new finding of this study, discovering diabetes complications could be useful to prevent or delay the complications. The system can identify the patients who are suffering from certain risk factors such as high body mass index (obesity) and starting controlling and maintaining plan.

  16. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  18. 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.

  19. Discovering English with the Sketch Engine

    Science.gov (United States)

    Thomas, James

    2014-01-01

    "Discovering English with the Sketch Engine" is the title of a new book (Thomas, 2014) which introduces the use of corpora in language study, teaching, writing and translating. It focuses on using the Sketch Engine to identify patterns of normal usage in many aspects of English ranging from morphology to discourse and pragmatics. This…

  20. Discovering Science through Art-Based Activities

    Science.gov (United States)

    Alberts, Rebecca

    2010-01-01

    Art and science are intrinsically linked; the essence of art and science is discovery. Both artists and scientists work in a systematic but creative way--knowledge and understanding are built up through pieces of art or a series of labs. In the classroom, integrating science and visual art can provide students with the latitude to think, discover,…

  1. Two Newly Discovered Plants in Taiwan

    OpenAIRE

    Tian-Chuan Hsu; Jia-Jung Lin; Shih-Wen Chung

    2009-01-01

    Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst.) Seem. (Scrophulariaceae), native in SE Asia, is recognized from southern lowlands. Anagallis minima (L.) E. H. L. Krause (Primulaceae), native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

  2. 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.

  3. Discovering Alaska's Salmon: A Children's Activity Book.

    Science.gov (United States)

    Devaney, Laurel

    This children's activity book helps students discover Alaska's salmon. Information is provided about salmon and where they live. The salmon life cycle and food chains are also discussed. Different kinds of salmon such as Chum Salmon, Chinook Salmon, Coho Salmon, Sockeye Salmon, and Pink Salmon are introduced, and various activities on salmon are…

  4. Challenges in service mining : record, check, discover

    NARCIS (Netherlands)

    Aalst, van der W.M.P.; Daniel, F.; Dolog, P.; Li, Q.

    2013-01-01

    Process mining aims to discover, monitor and improve real processes by extracting knowledge from event logs abundantly available in today’s information systems. Although process mining has been applied in hundreds of organizations and process mining techniques have been embedded in a variety of

  5. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    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)

  6. 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.

  7. 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)

  8. 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...... as respondents evaluate more and more choice sets. This finding supports the Discovered Preference Hypothesis interpretation and explanation of starting point bias....

  9. Discovering the secrets of the Olifants sediments

    CSIR Research Space (South Africa)

    Petersen, C

    2012-07-01

    Full Text Available is an important component of an aquatic ecosystem in that it provides habitat, feed- ing and spawning areas for aquatic fauna such as fish and benthic Discovering the secrets of THE OLIFANTS SEDIMENTS The polluted Upper Olifants River, in Mpumalanga, has... the distribution of bed material sizes. This allows for the determination ? Top right: The Koffie- spruit, a tributary of the Upper Olifants River. Middle right: Bank erosion was evident throughout the Koffiespruit study reach. This section of river...

  10. Two Newly Discovered Plants in Taiwan

    Directory of Open Access Journals (Sweden)

    Tian-Chuan Hsu

    2009-11-01

    Full Text Available Two herbs are newly discovered in Taiwan. Limnophila fragrans (G. Forst. Seem. (Scrophulariaceae, native in SE Asia, is recognized from southern lowlands. Anagallis minima (L. E. H. L. Krause (Primulaceae, native in N America and Europe, was found from northern mountainous region at low altitudes. In this study, descriptions, line drawings, color photos and a distribution map of the two species are provided.

  11. Discovering More Accurate Frequent Web Usage Patterns

    OpenAIRE

    Bayir, Murat Ali; Toroslu, Ismail Hakki; Cosar, Ahmet; Fidan, Guven

    2008-01-01

    Web usage mining is a type of web mining, which exploits data mining techniques to discover valuable information from navigation behavior of World Wide Web users. As in classical data mining, data preparation and pattern discovery are the main issues in web usage mining. The first phase of web usage mining is the data processing phase, which includes the session reconstruction operation from server logs. Session reconstruction success directly affects the quality of the frequent patterns disc...

  12. 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.

  13. 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".

  14. Discovering context-aware conditional functional dependencies

    Institute of Scientific and Technical Information of China (English)

    Yuefeng DU; Derong SHEN; Tiezheng NIE; Yue KOU; Ge YU

    2017-01-01

    Conditional functional dependencies(CFDs) are important techniques for data consistency.However,CFDs are limited to 1) provide the reasonable values for consistency repairing and 2) detect potential errors.This paper presents context-aware conditional functional dependencies(CCFDs) which contribute to provide reasonable values and detect potential errors.Especially,we focus on automatically discovering minimal CCFDs.In this paper,we present context relativity to measure the relationship of CFDs.The overlap of the related CFDs can provide reasonable values which result in more accuracy consistency repairing,and some related CFDs are combined into CCFDs.Moreover,we prove that discovering minimal CCFDs is NP-complete and we design the precise method and the heuristic method.We also present the dominating value to facilitate the process in both the precise method and the heuristic method.Additionally,the context relativity of the CFDs affects the cleaning results.We will give an approximate threshold of context relativity according to data distribution for suggestion.The repairing results are approved more accuracy,even evidenced by our empirical evaluation.

  15. Chronic candidal osteomyelitis of mid face: A therapeutic dilemma

    OpenAIRE

    Bali, Rishi; Sharma, Parveen; Gupta, Prachi; Gaba, Shivani

    2013-01-01

    Numerous explanations have been proposed for the increase in fungal infections including the use of broad-spectrum antibiotics, antineoplastic agents and prosthetic devices. Also increase in proportion of immunocompromised population predisposed to fungal infection might be a contributory factor.

  16. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  17. Endophytic Fungi as Novel Resources of natural Therapeutics

    Directory of Open Access Journals (Sweden)

    Maheshwari Rajamanikyam

    2017-08-01

    Full Text Available ABSTRACT Fungal endophytes constitute a major part of the unexplored fungal diversity. Endophytic fungi (EF are an important source for novel, potential and active metabolites. Plant-endophyte interaction and endophyte -endophyte interactions study provide insights into mutualism and metabolite production by fungi. Bioactive compounds produced by endophytes main function are helping the host plants to resist external biotic and abiotic stress, which benefit the host survival in return. These organisms mainly consist of members of the Ascomycota, Basidiomycota, Zygomycota and Oomycota. Recently, the genome sequencing technology has emerged as one of the most efficient tools that can provide whole information of a genome in a small period of time. Endophytes are fertile ground for drug discovery. EFare considered as the hidden members of the microbial world and represent an underutilized resource for new therapeutics and compounds. Endophytes are rich source of natural products displaying broad spectrum of biological activities like anticancer, antibacterial, antiviral, immunomodulatory, antidiabetic, antioxidant, anti-arthritis and anti-inflammatory.

  18. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-02-07

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

  19. 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.

  20. 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....... tools are available. In this paper we present an approach for the automatic construction of multidimensional OLAP database schemas from existing relational OLTP databases, enabling easy OLAP design and analysis for most existing data sources. This is achieved through a set of practical and effective...

  1. Discovering new information in bibliographic databases

    Directory of Open Access Journals (Sweden)

    Emil Hudomalj

    2005-01-01

    Full Text Available Databases contain information that can usually not be revealed by standard query systems. For that purpose, the methods for knowledge discovery from databases can be applied, which enable the user to browse aggregated data, discover trends, produce online reports, explore possible new associations within the data etc. Such methods are successfully employed in various fields, such as banking, insurance and telecommunications, while they are seldom used in libraries. The article reviews the development of query systems for bibliographic databases, including some early attempts to apply modern knowledge discovery methods. Analytical databases are described in more detail, since they usually serve as the basis for knowledge discovery. Data mining approaches are presented, since they are a central step in the knowledge discovery process. The key role of librarians who can play a key part in developing systems for finding new information in existing bibliographic databases is stressed.

  2. 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.

  3. Nuclear fission discovered fifty years ago

    International Nuclear Information System (INIS)

    Weis, M.

    1988-01-01

    Fifty years ago, Otto Hahn, Lise Meitner and Fritz Strassmann discovered the process of nuclear fission which, more than other scientific discoveries to date, profoundly has changed the world and continues to influence our life significantly: This discovery made the up to then incontestable physicists' view of the atom as an inseparable whole suddenly shatter to pieces. It has brought about the invaluable advantages of a peaceful utilization of nuclear energy, and at the same time put scientists in the position to build the most terrible weapon ever, threatening mankind and earth with complete destruction. All this certainly is reason enough to recall the scientists, their work and the spirit of the time. (orig.) [de

  4. Discovering network behind infectious disease outbreak

    Science.gov (United States)

    Maeno, Yoshiharu

    2010-11-01

    Stochasticity and spatial heterogeneity are of great interest recently in studying the spread of an infectious disease. The presented method solves an inverse problem to discover the effectively decisive topology of a heterogeneous network and reveal the transmission parameters which govern the stochastic spreads over the network from a dataset on an infectious disease outbreak in the early growth phase. Populations in a combination of epidemiological compartment models and a meta-population network model are described by stochastic differential equations. Probability density functions are derived from the equations and used for the maximal likelihood estimation of the topology and parameters. The method is tested with computationally synthesized datasets and the WHO dataset on the SARS outbreak.

  5. Discovering the Library with Google Earth

    Directory of Open Access Journals (Sweden)

    Michaela Brenner

    2008-06-01

    Full Text Available Libraries need to provide attractive and exciting discovery tools to draw patrons to the valuable resources in their catalogs. The authors conducted a pilot project to explore the free version of Google Earth as such a discover tool for Portland State Library’s digital collection of urban planning documents. They created eye-catching placemarks with links to parts of this collection, as well as to other pertinent materials like books, images, and historical background information. The detailed how-to-do part of this article is preceded by a discussion about discovery of library materials and followed by possible applications of this Google Earth project.

  6. Pancreatic sarcoidosis discovered during Whipple procedure.

    Science.gov (United States)

    Cook, Jonathan; Spees, Tanner; Telefus, Phillip; Ranaudo, Jeffrey M; Carryl, Stephen; Xiao, Philip

    2013-04-04

    Pancreatic sarcoidosis is a rare variant of systemic sarcoidosis, with cases described in literature as recently as January 2010. We present here a case of pancreatic involvement with non-caseating granulomas discovered on laparotomy in a patient with a preoperative diagnosis of pancreatic carcinoma. Computer tomography scan without contrast revealed a well-marginated smooth-shaped tumor in the head of the pancreas morphologically consistent with malignancy. During Whipple procedure, the mass was found to be a large lymph node that contained numerous non-caseating granulomas. Radiologically and clinically, non-caseating granulomas of the pancreas are often misdiagnosed as malignant tumor. Special attention given to this differential diagnosis by surgeons, pathologists and clinicians can avoid misdiagnosis and unnecessary treatment. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.

  7. Discovering Sentinel Rules for Business Intelligence

    Science.gov (United States)

    Middelfart, Morten; Pedersen, Torben Bach

    This paper proposes the concept of sentinel rules for multi-dimensional data that warns users when measure data concerning the external environment changes. For instance, a surge in negative blogging about a company could trigger a sentinel rule warning that revenue will decrease within two months, so a new course of action can be taken. Hereby, we expand the window of opportunity for organizations and facilitate successful navigation even though the world behaves chaotically. Since sentinel rules are at the schema level as opposed to the data level, and operate on data changes as opposed to absolute data values, we are able to discover strong and useful sentinel rules that would otherwise be hidden when using sequential pattern mining or correlation techniques. We present a method for sentinel rule discovery and an implementation of this method that scales linearly on large data volumes.

  8. Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

    Science.gov (United States)

    Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

    2017-08-15

    Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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.

  10. CORNELL: CLEO discovers B meson penguins

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The CLEO collaboration at Cornell's CESR electron-positron storage ring has discovered a rare type of B meson decay in which only a high energy photon and a K* meson are produced. These decays provide the first unambiguous evidence for an alternative route for heavy quark decay that has been given the whimsical name ''penguin diagram''. In the mid-1970s penguin diagrams were proposed to explain the puzzling strangeness quantum number selection rules in the decay of K mesons. At the same time it was realized that penguin diagrams could also be important in the CP violation seen in neutral K meson decay. CP violation, an asymmetry between matter and antimatter, is an essential ingredient in understanding why there is much more matter than antimatter in the universe. CP violation introduces a definite direction to the arrow of time, which could otherwise point equally forwards or backwards. In addition, penguin decays are very sensitive to some extensions of the Standard Model of weak decay. Although penguin diagrams were first proposed to explain an effect in K meson decay, the K system gives no unique signature for them, and verification of penguin processes meant looking elsewhere. In the Standard Model, quarks decay under the influence of the weak force, emitting a W boson. Since the W is charged, the charge of the initial quark differs from that of the final quark, so the charge of the quark changes as well as its flavour

  11. Discovering Alzheimer Genetic Biomarkers Using Bayesian Networks

    Directory of Open Access Journals (Sweden)

    Fayroz F. Sherif

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs contribute most of the genetic variation to the human genome. SNPs associate with many complex and common diseases like Alzheimer’s disease (AD. Discovering SNP biomarkers at different loci can improve early diagnosis and treatment of these diseases. Bayesian network provides a comprehensible and modular framework for representing interactions between genes or single SNPs. Here, different Bayesian network structure learning algorithms have been applied in whole genome sequencing (WGS data for detecting the causal AD SNPs and gene-SNP interactions. We focused on polymorphisms in the top ten genes associated with AD and identified by genome-wide association (GWA studies. New SNP biomarkers were observed to be significantly associated with Alzheimer’s disease. These SNPs are rs7530069, rs113464261, rs114506298, rs73504429, rs7929589, rs76306710, and rs668134. The obtained results demonstrated the effectiveness of using BN for identifying AD causal SNPs with acceptable accuracy. The results guarantee that the SNP set detected by Markov blanket based methods has a strong association with AD disease and achieves better performance than both naïve Bayes and tree augmented naïve Bayes. Minimal augmented Markov blanket reaches accuracy of 66.13% and sensitivity of 88.87% versus 61.58% and 59.43% in naïve Bayes, respectively.

  12. CORNELL: CLEO discovers B meson penguins

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1993-06-15

    The CLEO collaboration at Cornell's CESR electron-positron storage ring has discovered a rare type of B meson decay in which only a high energy photon and a K* meson are produced. These decays provide the first unambiguous evidence for an alternative route for heavy quark decay that has been given the whimsical name ''penguin diagram''. In the mid-1970s penguin diagrams were proposed to explain the puzzling strangeness quantum number selection rules in the decay of K mesons. At the same time it was realized that penguin diagrams could also be important in the CP violation seen in neutral K meson decay. CP violation, an asymmetry between matter and antimatter, is an essential ingredient in understanding why there is much more matter than antimatter in the universe. CP violation introduces a definite direction to the arrow of time, which could otherwise point equally forwards or backwards. In addition, penguin decays are very sensitive to some extensions of the Standard Model of weak decay. Although penguin diagrams were first proposed to explain an effect in K meson decay, the K system gives no unique signature for them, and verification of penguin processes meant looking elsewhere. In the Standard Model, quarks decay under the influence of the weak force, emitting a W boson. Since the W is charged, the charge of the initial quark differs from that of the final quark, so the charge of the quark changes as well as its flavour.

  13. 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

  14. 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

  15. 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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Brannon JR

    2016-05-01

    Full Text Available John R Brannon,1 Maria Hadjifrangiskou1,21Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, 2Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN, USAAbstract: 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.Keywords: virulence factors, antivirulence therapeutics, biofilms, regulation, Escherichia coli, quorum sensing, persister cells

  18. Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

    Science.gov (United States)

    Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

    2017-01-01

    Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries

  19. 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

  20. The Impact of Discovering Life beyond Earth

    Science.gov (United States)

    Dick, Steven J.

    2016-01-01

    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

  1. Scientix in our school- discovering STEM

    Science.gov (United States)

    Melcu, Cornelia

    2017-04-01

    My name is Cornelia Melcu and I am a primary school teacher in Brasov. Additionally, I am a teacher trainer of Preparatory Class Curriculum, Google Application in Education Course and European Projects Course and a mentor to new teachers and students in university. I am an eTwinning, Scientix and ESERO ambassador too. During the last three school years my school was involved in several STEM projects, part of Scientix community. The main goal of those projects was to develop basic STEM skills of our students based on project work integrated into the curriculum. Open the Gates to the Universe (http://gatestotheuniverse.blogspot.ro; https://twinspace.etwinning.net/12520/home) is an eTwinning project for primary school students started on September 2015 and finished on September 2016. Some of our partners were from the Mediterranean area. The students discovered different aspects of space science and astronomy working on international groups. They explored some aspects of Science included in their curriculum using resources from ESERO, ROEDUSEIS and Space Awareness (e.g. Calculate with Rosetta, Writing the travel diary, Build Rosetta, How to become an astronaut, etc.) The project was a great opportunity to apply integrated learning methods for developing competencies which are a part of the primary school curriculum in Romania. In Language and Communication classes the students talked about their partners living places and their traditions and habits. They learnt some basic words in their partners language related to the weather. They created stories- both in Romanian and English; they described life in space and astronomical phenomena. They talked to the other partners during the several online meetings we organized and wrote short stories in English. In Mathematics and Science they found out about the Milky Way, the Solar System, the weather, famous astronauts and astronomers. They calculated, solved problems, made experiments and explained specific natural phenomena

  2. Astronomers Discover Six-Image Gravitational Lens

    Science.gov (United States)

    2001-08-01

    An international team of astronomers has used the National Science Foundation's Very Long Baseline Array (VLBA) radio telescope and NASA's Hubble Space Telescope (HST) to discover the first gravitational lens in which the single image of a very distant galaxy has been split into six different images. The unique configuration is produced by the gravitational effect of three galaxies along the line of sight between the more-distant galaxy and Earth. Optical and Radio Images of Gravitational Lens "This is the first gravitational lens with more than four images of the background object that is produced by a small group of galaxies rather than a large cluster of galaxies," said David Rusin, who just received his Ph.D. from the University of Pennsylvania. "Such systems are expected to be extremely rare, so this discovery is an important stepping stone. Because this is an intermediate case between gravitational lenses produced by single galaxies and lenses produced by large clusters of galaxies, it will give us insights we can't get from other types of lenses," Rusin added. The gravitational lens, called CLASS B1359+154, consists of a galaxy more than 11 billion light-years away in the constellation Bootes, with a trio of galaxies more than 7 billion light-years away along the same line of sight. The more-distant galaxy shows signs that it contains a massive black hole at its core and also has regions in which new stars are forming. The gravitational effect of the intervening galaxies has caused the light and radio waves from the single, more-distant galaxy to be "bent" to form six images as seen from Earth. Four of these images appear outside the triangle formed by the three intermediate galaxies and two appear inside that triangle. "This lens system is a very interesting case to study because it is more complicated than lenses produced by single galaxies, and yet simpler than lenses produced by clusters of numerous galaxies," said Chris Kochanek of the Harvard

  3. Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Bălănescu, Paul; Lădaru, Anca; Bălănescu, Eugenia; Băicuş, Cristian; Dan, Gheorghe Andrei

    2014-08-01

    Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. Medline and Embase databases were searched in February 2014. Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

  4. Most Powerful Eruption in the Universe Discovered

    Science.gov (United States)

    2005-01-01

    emission within the cavities shows that jets from the black hole erupted to create the cavities. Gas is being pushed away from the black hole at supersonic speeds over a distance of about a million light years. The mass of the displaced gas equals about a trillion Suns, more than the mass of all the stars in the Milky Way. LA Radio & Chandra X-ray Composite of MS 0735.6+7421 VLA Radio & Chandra X-ray Composite of MS 0735.6+7421 The rapid growth of supermassive black holes is usually detected by observing very bright radiation from the centers of galaxies in the optical and X-ray wavebands, or luminous radio jets. In MS 0735 no bright central radiation is found and the radio jets are faint. Therefore, the true nature of MS 0735 is only revealed through X-ray observations of the hot cluster gas. "Until now we had no idea that this black hole was gorging itself", said co-author Michael Wise of the Massachusetts Institute of Technology. "The discovery of this eruption shows that X-ray telescopes are necessary to understand some of the most violent events in the Universe." The astronomers estimated how much energy was needed to create the cavities by calculating the density, temperature and pressure of the hot gas. By making a standard assumption, that 10% of the gravitational energy goes into launching the jets, they estimated how much material the black hole swallowed. Size Comparison of MS 0735.6+7421 & Perseus Cluster Size Comparison of MS 0735.6+7421 & Perseus Cluster Besides generating the cavities, some of the energy from this eruption should keep the hot gas around the black hole from cooling, and some of it may also generate large-scale magnetic fields in the galaxy cluster. Chandra observers have discovered other cavities in galaxy clusters, but this one is easily the largest and the most powerful. For example, the energy content here exceeds that of the Perseus cavities by 250 times, and dwarfs the cavities in M87 by a factor of 10,000. NASA's Marshall Space Flight

  5. The potential of the ILC for discovering new particles

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Keisuke [High Energy Accelerator Research Organization (KEK), Ibaraki (Japan); Grojean, Christophe [DESY, Hamburg (Germany); Humboldt-Univ., Berlin (Germany). Inst. fuer Physik; ICREA, Barcelona (Spain); Peskin, Michael E. [Stanford Univ., Menlo Park, CA (United States). SLAC; Collaboration: LCC Physics Working Group; and others

    2017-02-15

    This paper addresses the question of whether the International Linear Collider has the capability of discovering new particles that have not already been discovered at the CERN Large Hadron Collider. We summarize the various paths to discovery offered by the ILC, and discuss them in the context of three different scenarios: 1. LHC does not discover any new particles, 2. LHC discovers some new low mass states and 3. LHC discovers new heavy particles. We will show that in each case, ILC plays a critical role in discovery of new phenomena and in pushing forward the frontiers of high-energy physics as well as our understanding of the universe in a manner which is highly complementary to that of LHC. For the busy reader, a two-page executive summary is provided at the beginning of the document.

  6. The potential of the ILC for discovering new particles

    International Nuclear Information System (INIS)

    Fujii, Keisuke; Grojean, Christophe; Peskin, Michael E.

    2017-02-01

    This paper addresses the question of whether the International Linear Collider has the capability of discovering new particles that have not already been discovered at the CERN Large Hadron Collider. We summarize the various paths to discovery offered by the ILC, and discuss them in the context of three different scenarios: 1. LHC does not discover any new particles, 2. LHC discovers some new low mass states and 3. LHC discovers new heavy particles. We will show that in each case, ILC plays a critical role in discovery of new phenomena and in pushing forward the frontiers of high-energy physics as well as our understanding of the universe in a manner which is highly complementary to that of LHC. For the busy reader, a two-page executive summary is provided at the beginning of the document.

  7. Youngest Stellar Explosion in Our Galaxy Discovered

    Science.gov (United States)

    2008-05-01

    Astronomers have found the remains of the youngest supernova, or exploded star, in our Galaxy. The supernova remnant, hidden behind a thick veil of gas and dust, was revealed by the National Science Foundation's Very Large Array (VLA) and NASA's Chandra X-Ray Observatory, which could see through the murk. The object is the first example of a "missing population" of young supernova remnants. 1985 and 2008 VLA Images Move cursor over image to blink. VLA Images of G1.9+0.3 in 1985 and 2008: Circle for size comparison. CREDIT: Green, et al., NRAO/AUI/NSF From observing supernovae in other galaxies, astronomers have estimated that about three such stellar explosions should occur in our Milky Way every century. However, the most recent one known until now occurred around 1680, creating the remnant called Cassiopeia A. The newly-discovered object is the remnant of an explosion only about 140 years ago. "If the supernova rate estimates are correct, there should be the remnants of about 10 supernova explosions in the Milky Way that are younger than Cassiopeia A," said David Green of the University of Cambridge in the UK, who led the VLA study. "It's great to finally track one of them down." Supernova explosions, which mark the violent death of a star, release tremendous amounts of energy and spew heavy elements such as calcium and iron into interstellar space. They thus seed the clouds of gas and dust from which new stars and planets are formed and, through their blast shocks, can even trigger such formation. The lack of evidence for young supernova remnants in the Milky Way had caused astronomers to wonder if our Galaxy, which appears otherwise normal, differed in some unknown way from others. Alternatively, scientists thought that the "missing" Milky Way supernovae perhaps indicated that their understanding of the relationship between supernovae and other galactic processes was in error. The astronomers made their discovery by measuring the expansion of the debris from

  8. Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

    Directory of Open Access Journals (Sweden)

    Carolina Alves Nicolau

    2018-02-01

    Full Text Available Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7 followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic, and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1 antimicrobial activity; (2 treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy; (3 treatment of cardiovascular diseases, and (4 anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

  9. Colonization, Pathogenicity, Host Susceptibility and Therapeutics for Staphylococcus aureus: What is the Clinical Relevance?1

    Science.gov (United States)

    Tong, Steven Y.C.; Chen, Luke F.; Fowler, Vance G.

    2011-01-01

    Staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. Factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance and host susceptibility. Additionally, infection control measures aimed at the environmental niches of S. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. This review article focuses on the clinical relevance of advances in our understanding of staphylococcal colonization, virulence, host susceptibility and therapeutics. Over the past decade key developments have arisen. First, rates of nosocomial methicillin-resistant S. aureus (MRSA) infections have significantly declined in many countries. Second, we have made great strides in our understanding of the molecular pathogenesis of S. aureus in general and community-associated MRSA in particular. Third, host risk factors for invasive staphylococcal infections, such as advancing age, increasing numbers of invasive medical interventions, and a growing proportion of patients with healthcare contact, remain dynamic. Finally, several new antimicrobial agents active against MRSA have become available for clinical use. Humans and S. aureus co-exist and the dynamic interface between host, pathogen and our attempts to influence these interactions will continue to rapidly change. Although progress has been made in the past decade, we are likely to face further surprises such as the recent waves of community-associated MRSA. PMID:22160374

  10. 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

  11. Preventive and Therapeutic Effects of Propolis in Gamma Irradiated Rats

    International Nuclear Information System (INIS)

    Hamza, R.G.; El-Shahat, A.N.

    2011-01-01

    Ionizing radiation is known to stimulate the generation of oxygen radicals which destabilize organic molecules resulting in a decrease of the system's antioxidant potential. Propolis (bee glue) is a complex mixture of natural substances that exhibits a broad spectrum of biological activities. As the possibility exists that it may exert a radio protections role, the present study aimed to examine the preventive and therapeutic effects of propolis on the gamma irradiation-induced changes in antioxidant status and certain biochemical parameters. HPLC chromatography for analysis of propolis showed that the number of identified phenols was 6 compounds (natural antioxidants). Male albino rats were exposed to 6 Gy of gamma radiation. The efficiency of propolis was evaluated when propolis was administered orally to rats at a dose of 200 mg/kg as follow: non-irradiated rats received orally propolis extract for 6 weeks (positive control) and rats received orally propolis extract for 3 weeks before or after gamma irradiation. The obtained results revealed that propolis given to rats before gamma irradiation protect the hazardous effects of gamma irradiation. In addition, administration of propolis to gamma irradiated rats caused significant enhancement in hepatic antioxidant enzymes (glutathion reductase; GR and catalase; CAT) and total antioxidant capacity associated with a remarkable decrease in the level of lipid peroxidation (TBARS). Also, it significantly reduced the changes induced by gamma irradiation in the serum levels of glucose and liver enzymes; aminotransferases (AST, ALT) and alkaline phosphatase (ALP). In addition, a significant improvement was observed in the serum levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein- cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). In conclusion, the positive results obtained in the gamma irradiated rats given propolis indicated that propolis could be considered as effective

  12. Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

    Science.gov (United States)

    Gottschalk, Timothy A.; Tsantikos, Evelyn; Hibbs, Margaret L.

    2015-01-01

    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 immunosuppression 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 review the known

  13. Medicinal benefits of marine invertebrates: sources for discovering natural drug candidates.

    Science.gov (United States)

    De Zoysa, Mahanama

    2012-01-01

    Marine invertebrates are one of the major groups of organisms, which could be diversified under the major taxonomic groups of Porifera, Cnidaria, Mollusca, Arthropoda, Echinodermata, and many other minor phyla. To date, range of medicinal benefits and a significant number of marine natural products (MNPs) have been discovered from marine invertebrates. Seafood diet from edible marine invertebrates such as mollusks and crustaceans has been linked with various medicinal benefits to improve human health. Among marine invertebrates, spongers from phylum Porifera is the most dominant group responsible for discovering large number of MNPs, which have been used as template to develop therapeutic drugs. MNPs isolated from invertebrates have shown wide range of therapeutic properties including antimicrobial, antioxidant, antihypertensive, anticoagulant, anticancer, anti-inflammatory, wound healing and immune modulator, and other medicinal effects. Therefore, marine invertebrates are rich sources of chemical diversity and health benefits for developing drug candidates, cosmetics, nutritional supplements, and molecular probes that can be supported to increase the healthy life span of human. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. A new screening method for discovering antibacterial agents from ...

    African Journals Online (AJOL)

    A new screening method for discovering antibacterial agents from filamentous fungi. ... African Journal of Biotechnology ... Keywords: Drug-resistant bacterial pathogens, novel antibiotics; screening method, filamentous fungi products ...

  15. On a New Technique for Discovering Variable Stars

    Directory of Open Access Journals (Sweden)

    Mironov A. V.

    2003-12-01

    Full Text Available A technique for discovering variable stars based on the calculation of the correlation coefficients is proposed. Applications of the technique are shown on the results of numerical experiments and on the Hipparcos photometric data.

  16. Scientists discover how deadly fungal microbes enter host cells

    OpenAIRE

    Whyte, Barry James

    2010-01-01

    A research team led by scientists at the Virginia Bioinformatics Institute at Virginia Tech has discovered a fundamental entry mechanism that allows dangerous fungal microbes to infect plants and cause disease.

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

    International Nuclear Information System (INIS)

    Brown, D.D.; Nagel, A.S.

    1999-07-01

    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

  18. Arbidol (Umifenovir): A broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses

    Czech Academy of Sciences Publication Activity Database

    Haviernik, J.; Štefánik, M.; Fojtíková, M.; Kali, S.; Tordo, N.; Rudolf, Ivo; Hubálek, Zdeněk; Eyer, Luděk; Růžek, Daniel

    2018-01-01

    Roč. 10, č. 4 (2018), č. článku 184. ISSN 1999-4915 R&D Projects: GA ČR(CZ) GA16-20054S Institutional support: RVO:68081766 ; RVO:60077344 Keywords : Antiviral activity * Arbidol * Cell-type dependent antiviral effect * Cytotoxicity * Flavivirus * Umifenovir Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 3.465, year: 2016

  19. Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

    International Nuclear Information System (INIS)

    Altmann, S.E.; Jones, J.C.; Schultz-Cherry, S.; Brandt, C.R.

    2009-01-01

    Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC 50 of 15 μM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC 50 > 200 μM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption was unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of β-galactosidase expression from an early viral promoter with an EC 50 of 45 μM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.

  20. Self-esteem in a broad-spectrum approach for mental health promotion

    NARCIS (Netherlands)

    Mann, M.; Hosman, C.M.H.; Schaalma, H.P.; Vries, N.K. de

    2004-01-01

    Self-evaluation is crucial to mental and social well-being. It influences aspirations, personal goals and interaction with others. This paper stresses the importance of self-esteem as a protective factor and a non-specific risk factor in physical and mental health. Evidence is presented illustrating

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

    Science.gov (United States)

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

    2017-12-01

    Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.

  2. 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.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    African Journals Online (AJOL)

    Methods: A total of 113 E.coli isolates obtained during the period 2004 through 2012 showed a ... to the PFGE analysis and characterization of the regions surrounding the blaCTX-M-15 ... 240-Gly which increases its catalytic efficiency against.

  5. A mutagenesis-derived broad-spectrum disease resistance locus in wheat

    Science.gov (United States)

    Wheat leaf rust, stem rust, stripe rust, and powdery mildew caused by the fungal pathogens Puccinia triticina, P. graminis f. sp. tritici, P. striiformis f. sp. tritici, and Blumeria graminis f. sp. tritici, respectively, are destructive diseases of wheat worldwide. The most effective and widely uti...

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

    Directory of Open Access Journals (Sweden)

    Barbara De Coninck

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Huixiang Xiao

    2017-01-01

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

  8. 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.

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

    Science.gov (United States)

    Zenick, Raymond; Kohlhepp, Kimberly; Partch, Russell

    2004-09-01

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

  10. POSACONAZOLE — NEW AZOLE BROAD-SPECTRUM ANTIFUNGAL AGENT FOR PREVENTION AND TREATMENT OF INVASIVE MYCOSES

    Directory of Open Access Journals (Sweden)

    N.N. Klimko

    2008-01-01

    Full Text Available Invasive mycoses are a common complication of various categories of immune depressed patients that are characterized with heavy clinical presentations and high lethal rate. Many causatives of invasive mycoses are resistant to currently applied antifungal medications, and some are polybresistant. Posaconazole (Noksafil is a new triazole antimycotic of second generation that is active both in vitro and in vivo against most causatives of invasive mycoses, including poly resistant microbmycets. Clinical study demonstrate high efficiency and safety of applying this medication. in russia posaconazole is allowed for prevention of invasive mycoses for hematological patients with longbrunning neutropenia resulting from chemical therapy, who are prescribed large doses of immune suppressors, recipients of transplants of hemapoietic stem cells, as well as for treatment of invasive candidoses, aspergillus, zigomicosys, criptococcosis, fuzariosis, chromomycosis and micetoma, as well as cocsidiodosis that are refractory towards other anti fungal medications, or in cases of intolerance.Key words: mycoses, posaconazole, treatment.

  11. 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.

  12. Investigating AAK1-and GAK-Regulated Virus-Host Interactions Uncovers Broad-Spectrum Antivirals

    Science.gov (United States)

    2017-02-16

    AP1) and AP2M1 (AP2) were 527 selected from the Human ORFeome library of cDNA clones (65) (Open Biosystems) and 528 recombined into either pCherry...TSV01 Renilla reporter plasmid was a gift from Pei-Yong Shi (68). 534 Lentiviral constructs used for AP2 overexpression were cloned into the pRRLSIN...681 total of 10 days and observed daily for 28 days for lethality or clinical signs of disease. 682 683 Animal study approval/ Ethics Statement

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-04-15

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

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

    Science.gov (United States)

    Kumar, Manoj; Srivastava, Sheela

    2010-10-01

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

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

    Science.gov (United States)

    Gems, David; McElwee, Joshua J

    2005-03-01

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

  17. Chitosanase purified from bacterial isolate Bacillus licheniformis of ruined vegetables displays broad spectrum biofilm inhibition.

    Science.gov (United States)

    Muslim, Sahira Nsayef; Al-Kadmy, Israa M S; Hussein, Nadheema Hammood; Mohammed Ali, Alaa Naseer; Taha, Buthainah Mohammed; Aziz, Sarah Naji; Kheraif, Abdulaziz Abdullah Al; Divakar, Darshan Devang; Ramakrishnaiah, Ravikumar

    2016-11-01

    A number of bacterial species produces chitosanases which has variety of applications because of its high biodegradability, non-toxicity and antimicrobial assets. In the present study chitosanase is purified from new bacterial species Bacillus licheniformis from spoiled vegetable. This novel strain of Bacillus licheniformis isolated from spoilt cucumber and pepper samples has the ability to produce the chitosanase enzyme when grown on chitosan substrate. Study also examined its antibiofilm properties against diverse bacterial species with biofilm forming ability. The purified chitosanase inhibited the biofilm formation ability for all Gram-negative and Gram-positive biofilm-forming bacteria [biofilm producers] tested in this study in congo red agar and microtiter plate's methods. Highly antibiofilm activity of chitosanase was recorded against Pseudomonas aeruginosa followed by Klebsiella pneumoniae with reduction of biofilm formation upto 22 and 29%, respectively compared with [100] % of control. Biofilm formation has multiple role including ability to enhance resistance and self-protection from external stress. This chitosanase has promising benefit as antibiofilm agent against biofilm forming pathogenic bacteria and has promising application as alternative antibiofilm agents to combat the growing number of multidrug resistant pathogen-associated infections, especially in situation where biofilms are involved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 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.

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

    African Journals Online (AJOL)

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

  20. The broad spectrum of unbearable suffering in end of life cancer studied in dutch primary care

    NARCIS (Netherlands)

    Ruijs, C.D.M.; Kerkhof, A.J.F.M.; van der Wal, G.; Onwuteaka-Philipsen, B.D.

    2012-01-01

    Background: Unbearable suffering most frequently is reported in end-of-life cancer patients in primary care. However, research seldom addresses unbearable suffering. The aim of this study was to comprehensively investigate the various aspects of unbearable suffering in end-of-life cancer patients

  1. 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.

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

    Czech Academy of Sciences Publication Activity Database

    Cagno, V.; Andreozzi, P.; D'Alicarnasso, M.; Silva, P. J.; Mueller, M.; Galloux, M.; Le Goffic, R.; Jones, S. T.; Vallino, M.; Hodek, Jan; Weber, Jan; Sen, S.; Janeček, E. R.; Bekdemir, A.; Sanavio, B.; Martinelli, C.; Donalisio, M.; Welti, M. A. R.; Eleouet, J. F.; Han, Y.; Kaiser, L.; Vukovic, L.; Tapparel, C.; Král, P.; Krol, S.; Lembo, D.; Stellacci, F.

    2018-01-01

    Roč. 17, č. 2 (2018), s. 195-203 ISSN 1476-1122 R&D Projects: GA MŠk(CZ) LK11207 Institutional support: RVO:61388963 Keywords : coli polysaccharide derivatives * multivalent gold nanoparticles * respiratory syncytial virus Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 39.737, year: 2016

  3. Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

    Czech Academy of Sciences Publication Activity Database

    Seydlová, G.; Pohl, Radek; Zborníková, Eva; Ehn, Marcel; Šimák, Ondřej; Panova, Natalya; Kolář, M.; Bogdanová, K.; Večeřová, R.; Fišer, R.; Šanderová, Hana; Vítovská, Dragana; Sudzinová, Petra; Pospíšil, Jiří; Benada, Oldřich; Křížek, T.; Sedlák, David; Bartůněk, Petr; Krásný, Libor; Rejman, Dominik

    2017-01-01

    Roč. 60, č. 14 (2017), s. 6098-6118 ISSN 0022-2623 R&D Projects: GA MŠk LO1220; GA MŠk LM2015063; GA ČR(CZ) GBP305/12/G034; GA MŠk(CZ) LM2015055; GA MZd(CZ) NV17-29680A Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:68378050 Keywords : resistant Staphylococcus aureus * cationic steroid antibiotics * antimicrobial peptides Subject RIV: EE - Microbiology, Virology; EE - Microbiology, Virology (MBU-M) OBOR OECD: Microbiology; Microbiology (MBU-M) Impact factor: 6.259, year: 2016

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Priyanka eSharma

    2016-03-01

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

  6. Colostrum of Healthy Mothers Contains Broad Spectrum of Secretory IgA Autoantibodies

    Czech Academy of Sciences Publication Activity Database

    Přibylová, Jaroslava; Krausová, Klára; Kocourková, I.; Rossmann, Pavel; Klimešová, Klára; Kverka, Miloslav; Tlaskalová-Hogenová, Helena

    2012-01-01

    Roč. 32, č. 6 (2012), s. 1372-1380 ISSN 0271-9142 R&D Projects: GA ČR(CZ) GAP304/11/1252 Institutional support: RVO:61388971 Keywords : Autoantibodies * mucosal immunity * immunoglobulins Subject RIV: EC - Immunology Impact factor: 3.382, year: 2012

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  8. Surface structures for enhancement of quantum yield in broad spectrum emission nanocrystals

    Science.gov (United States)

    Schreuder, Michael A.; McBride, James R.; Rosenthal, Sandra J.

    2014-07-22

    Disclosed are inorganic nanoparticles comprising a body comprising cadmium and/or zinc crystallized with selenium, sulfur, and/or tellurium; a multiplicity of phosphonic acid ligands comprising at least about 20% of the total surface ligand coverage; wherein the nanocrystal is capable of absorbing energy from a first electromagnetic region and capable of emitting light in a second electromagnetic region, wherein the maximum absorbance wavelength of the first electromagnetic region is different from the maximum emission wavelength of the second electromagnetic region, thereby providing a Stokes shift of at least about 20 nm, wherein the second electromagnetic region comprises an at least about 100 nm wide band of wavelengths, and wherein the nanoparticle exhibits has a quantum yield of at least about 10%. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  9. Broad spectrum screening of 463 organic contaminants in rivers in Macedonia.

    Science.gov (United States)

    Stipaničev, Draženka; Dragun, Zrinka; Repec, Siniša; Rebok, Katerina; Jordanova, Maja

    2017-01-01

    Target screening of 463 organic contaminants in surface water using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) with direct injection was performed in spring of 2015 in northern Macedonia, at six sampling sites in four rivers belonging to Vardar basin: Kriva, Zletovska, Bregalnica and Vardar. The aim of the study was to differentiate between various types of organic contamination characteristic for different types of anthropogenic activities, such as mining, agriculture, and urbanization. Depending on the studied river, 9-16% of analyzed compounds were detected. The highest total levels of organic contaminants were recorded in agriculturally impacted Bregalnica River (1839-1962ngL -1 ) and Vardar River downstream from the city of Skopje (1945ngL -1 ), whereas the lowest level was found in the mining impacted Zletovska River (989ngL -1 ). The principal organic contaminants of the Bregalnica River were herbicides (45-55% of all detected compounds; 838-1094ngL -1 ), with the highest concentrations of bentazone (407-530ngL -1 ) and molinate (84-549ngL -1 ), common herbicides in rice cultivation. The main organic contaminants in the other rivers were drugs (70-80% of all detected compounds), with antibiotics as a predominant drug class. The highest drug concentrations were measured in the Vardar River, downstream from Skopje (1544ngL -1 ). Screening of surface water by UHPLC-QTOF-MS was proven as a practical tool for fast collection of comprehensive preliminary information on organic contamination of natural waters, which can present a significant contribution in the monitoring and preservation of good ecological status of freshwater ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nicholas J. Tobias

    2016-11-01

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

  11. Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

    International Nuclear Information System (INIS)

    Dutta, Ranu A.; Sharma, Prashant K.; Tiwari, Vandana; Tiwari, Vivek; Patel, Anant B.; Pandey, Ravindra; Pandey, Avinash C.

    2014-01-01

    The engineering of the Gadolinium based nanostructures have been demonstrated in this paper. Nanostructures of α-Gd 2 S 3 exhibit a unique transition between ferromagnetic state and paramagnetic state of the system. It was demonstrated that their properties could be tuned for a wide range of applications ranging from hyperthermia to Magnetic Resonance Imaging, owing to their magnetic moments and large relaxivities. Metallic Gd nanoparticles obtained by reduction method were employed for cancer imaging in mice. The Gd nanoparticles were coated with Curcumin and their biomedical implications in the field of simultaneous diagnosis and therapy of cancer and related diseases has been discussed

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

    Science.gov (United States)

    Macfadyen, Sarina; Nash, Michael A.

    2017-01-01

    Background Pesticide application is the dominant control method for arthropod pests in broad-acre arable systems. In Australia, organophosphate pesticides are often applied either prophylactically, or reactively, including at higher concentrations, to control crop establishment pests such as false wireworms and earth mite species. Organophosphates are reported to be disruptive to beneficial species, such as natural enemies, but this has not been widely assessed in Australian systems. Neither has the risk that secondary outbreaks may occur if the natural enemy community composition or function is altered. Methods We examine the abundance of ground-dwelling invertebrate communities in an arable field over successive seasons under rotation; barley, two years of wheat, then canola. Two organophosphates (chlorpyrifos and methidathion) were initially applied at recommended rates. After no discernible impact on target pest species, the rate for chlorpyrifos was doubled to elicit a definitive response to a level used at establishment when seedling damage is observed. Invertebrates were sampled using pitfalls and refuge traps throughout the experiments. We applied measures of community diversity, principal response curves and multiple generalised linear modelling techniques to understand the changes in pest and natural enemy communities. Results There was large variability due to seasonality and crop type. Nevertheless, both pest (e.g., mites and aphids) and natural enemy (e.g., predatory beetles) invertebrate communities were significantly affected by application of organophosphates. When the rate of chlorpyrifos was increased there was a reduction in the number of beetles that predate on slug populations. Slugs displayed opposite trends to many of the other target pests, and actually increased in numbers under the higher rates of chlorpyrifos in comparison to the other treatments. Slug numbers in the final rotation of canola resulted in significant yield loss regardless of pesticide application. Discussion Organophosphates are a cost-effective tool to control emergent pests in broad-acre arable systems in Australia. We found risks associated with prophylactic application in fields under rotation between different crop types and significant changes to the community of pests and natural enemy. Disrupting key predators reduced effective suppression of other pests, such as slugs, and may lead to secondary outbreaks when rotating with susceptible crops such as canola. Such non-target impacts are rarely documented when studies focus on single-species, rather than community assessments. This study represents a single demonstration of how pesticide application can lead to secondary outbreaks and reinforces the need for studies that include a longer temporal component to understand this process further. PMID:29302395

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

    Directory of Open Access Journals (Sweden)

    Matthew P. Hill

    2017-12-01

    Full Text Available Background Pesticide application is the dominant control method for arthropod pests in broad-acre arable systems. In Australia, organophosphate pesticides are often applied either prophylactically, or reactively, including at higher concentrations, to control crop establishment pests such as false wireworms and earth mite species. Organophosphates are reported to be disruptive to beneficial species, such as natural enemies, but this has not been widely assessed in Australian systems. Neither has the risk that secondary outbreaks may occur if the natural enemy community composition or function is altered. Methods We examine the abundance of ground-dwelling invertebrate communities in an arable field over successive seasons under rotation; barley, two years of wheat, then canola. Two organophosphates (chlorpyrifos and methidathion were initially applied at recommended rates. After no discernible impact on target pest species, the rate for chlorpyrifos was doubled to elicit a definitive response to a level used at establishment when seedling damage is observed. Invertebrates were sampled using pitfalls and refuge traps throughout the experiments. We applied measures of community diversity, principal response curves and multiple generalised linear modelling techniques to understand the changes in pest and natural enemy communities. Results There was large variability due to seasonality and crop type. Nevertheless, both pest (e.g., mites and aphids and natural enemy (e.g., predatory beetles invertebrate communities were significantly affected by application of organophosphates. When the rate of chlorpyrifos was increased there was a reduction in the number of beetles that predate on slug populations. Slugs displayed opposite trends to many of the other target pests, and actually increased in numbers under the higher rates of chlorpyrifos in comparison to the other treatments. Slug numbers in the final rotation of canola resulted in significant yield loss regardless of pesticide application. Discussion Organophosphates are a cost-effective tool to control emergent pests in broad-acre arable systems in Australia. We found risks associated with prophylactic application in fields under rotation between different crop types and significant changes to the community of pests and natural enemy. Disrupting key predators reduced effective suppression of other pests, such as slugs, and may lead to secondary outbreaks when rotating with susceptible crops such as canola. Such non-target impacts are rarely documented when studies focus on single-species, rather than community assessments. This study represents a single demonstration of how pesticide application can lead to secondary outbreaks and reinforces the need for studies that include a longer temporal component to understand this process further.

  14. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.

    Science.gov (United States)

    Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

    2001-03-31

    Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

  15. 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....

  16. A review on toxicological properties of thymoquinone a natural broad spectrum ingredient

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Nigella sativa is a delicate floral vegetable belonging to Ranunculaceae family. Thymoquinone (TQ is the dominant active component in Nigella sativa seed oil which has a variety of pharmacological properties such as antioxidant, anticancer, anti-inflammatory and analgesic activities. However, TQ is a quinone derivative, which may lead to the generation of reactive oxygen species and resulting intermediate toxicity with various adverse effects in vivo, including acute cytotoxicity, genotoxicity, immunotoxicity, and carcinogenesis. In this review we have mentioned several studies on the toxicity properties of thymoquinone and Nigella sativa. Methods: A literature search was conducted using the Web of Science, PubMed, MEDLINE and Scopus. The search included the following keywords: "thymoquinone", "hydroquinone"," quinone" and "Nigella sativa". Citations within articles were also reviewed to identify the relevant sources. We studied about 170 articles and put aside the articles that were performed on the effect of Nigella sativa and thymoquinone on cancer cell lines. Results:  Since TQ is a quinone derivative, we observed the generation of reactive oxygen species and the toxicity of this substance in some studies. LD50 of Thymoquinone was very higher than Nigella sativa and also LD50 of this substance in oral route was higher than intrapritoneal route of administration. Conclusion: The findings have provided approximate safety information for TQ, which will further help researchers.

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

    International Nuclear Information System (INIS)

    Remmel, R.P.; Elmer, G.W.

    1981-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

    Importance: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. Objectives: To estimate the single-nucleotide

  19. 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...

  20. Broad-Spectrum Behavioral Treatment for Chronic Alcoholics: Effects of Training Controlled Drinking Skills.

    Science.gov (United States)

    Foy, David W.; And Others

    1984-01-01

    Assessed unique treatment effects of training controlled drinking skills in a chronic alcoholic population of veterans (N=62). Results of a six-month posttreatment follow-up revealed that subjects in the drinking skills condition had significantly fewer abstinent days and more abusive drinking days than subjects in the untrained condition. (LLL)

  1. Broad Spectrum Microbicidal Activity of Photocatalysis by TiO2

    Directory of Open Access Journals (Sweden)

    Yoshinobu Kubota

    2013-03-01

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

  2. [Wide-spectrum clinical interventions in mental health: 'care' and 'subject supposed to know' in therapeutic assistance].

    Science.gov (United States)

    Estellita-Lins, Carlos; Oliveira, Verônica Miranda; Coutinho, Maria Fernanda

    2009-01-01

    This paper discusses the theme therapeutic assistance (TA), understood as homecare-based mental health intervention. We emphasize the importance of community interventions for dealing with psychic suffering, either through reading the symptoms based on visibility, or through a psychoanalytic approach mainly concerned with listening. Lacking an independent theoretical background to support this practice, therapeutic assistance makes use of theories coming from other related fields of knowledge. Therefore, we discuss the influence of psychoanalysis and its role among broad spectrum mental health practice through clinical interventions belonging to the field of TA, focusing on two long-range operative concepts: Lacan's subject supposed to know and Winnicott's care (or caring process). Both concepts guide the clinical action and provide answers to theoretical problems within the TA field. We conclude that TA meets some requirements of the classical management of transference by means of a complex care process developed in the daily life and environment of the patient, in which desire and subjectivity are necessarily recognized although no psychotherapic setting is intentionally settled. Therapeutic assistance performs the role of an advanced clinical sentinel in the field of community psychiatry and public health.

  3. Prospects for therapeutic mitochondrial transplantation.

    Science.gov (United States)

    Gollihue, Jenna L; Rabchevsky, Alexander G

    2017-07-01

    Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  4. MICRO-STRUCTURAL INVESTIGATION OF SOME ARTIFACTS DISCOVERED AT POROLISSUM

    Directory of Open Access Journals (Sweden)

    MUNTEANU Mihai

    2014-09-01

    Full Text Available the paper presents the investigation of two fragments of roman bronze artefacts, discovered during archaeological works performed at Porolissum, an important military and economical point on the northern limes of Dacia Province. One of the analyzed fragments (Mi1 was taken from a consistent fragment of a Roman bronze statue, while the second (Mi2 was among a lot of small metal pieces, discovered in the same investigated area. Using highly sophisticated micro-structural analysing techniques – X-Ray diffraction, the paper investigates the possibility that the Mi2 fragment may have belonged to the same statue from which the sample Mi1 was taken

  5. 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

  6. Nitric oxide nanoparticles: pre-clinical utility as a therapeutic for intramuscular abscesses.

    Science.gov (United States)

    Schairer, David; Martinez, Luis R; Blecher, Karin; Chouake, Jason; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M; Nosanchuk, Joshua D; Friedman, Adam

    2012-01-01

    Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections.

  7. Microbiological study of therapeutic soft contact lenses used in the treatment of recurrent corneal erosion syndrome.

    Science.gov (United States)

    Park, Young Min; Kwon, Han Jo; Lee, Jong Soo

    2015-03-01

    To determine the bacteriological spectrum of the removed therapeutic soft contact lenses (TSCLs) and to establish efficacy of prophylactic antibiotics on TSCLs used for 2 weeks for treatment of patients with recurrent corneal erosion syndrome (RCES). This study included idiopathic RCES treated using highly oxygen-permeable silicone hydrogel contact lenses (CLs), and treated 4 times per day with topical tobramycin 3% for 2 weeks. After TSCLs were applied for 2 weeks, the lenses were removed with sterile forceps under which a speculum was inserted, and placed on blood agar with the inner face down. The TSCLs were analyzed for bacterial colonization, and antibiotic susceptibility tests were performed for the isolates, using disk diffusion. Of the 40 lenses analyzed, 9 (22.5%) yielded positive cultures. Staphylococcus epidermidis was the most commonly isolated microorganism; there were five methicillin-sensitive coagulase-negative staphylococci and two methicillin-resistant coagulase-negative staphylococci. Furthermore, we found two lenses that were colonized by Enterobacter gergoviae and Citrobacter freundii. All cultured bacteria showed intermediate or complete sensitivity to ciprofloxacin, tigecycline, and tobramycin. Despite bacterial colonization in 9 CLs, no clinical signs of infectious keratitis were found in any of the patients with prophylactic topical tobramycin 3%. In case of using TSCLs for 2 weeks, tobramycin or ciprofloxacin may be useful as prophylactic topical antibiotics for preventing secondary corneal infections. Considering currently growing incidence of ciprofloxacin-resistant ocular isolates, tobramycin seems to be a reasonable prophylactic topical antibiotic susceptible broad spectrum of bacteria in clinics.

  8. Hematopoietic stem cells transplant in patients with common variable immunodeficiency. Is a therapeutic option?

    Directory of Open Access Journals (Sweden)

    Julio César Cambray-Gutiérrez

    2017-02-01

    Full Text Available Background: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality. Clinical case: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood. At adolescence, she was diagnosed with common variable immunodeficiency; she was prescribed intravenous gamma-globulin, broad-spectrum antimicrobials and macrolides. At 22 years of age, she underwent hematopoietic stem cell transplantation owing to continued severe infections. At 4 months, post-transplantation she was diagnosed with hypothyroidism and ovarian insufficiency. During the following 3 years, she had no infections, but at 25 years of age she had immune thrombocytopenic purpura diagnosed, which persists together with Raynaud’s disease and upper respiratory tract persistent infections. At the moment of this report she is being treated with intravenous gamma-globulin and receiving prophylaxis with clarithromycin, without steroids or danazol. Conclusions: Given the high rate of morbidity and mortality associated and immune reconstitution failure, hematopoietic stem cell transplantation should be carefully evaluated in patients with treatment-unresponsive infections or lymphoproliferative disorders.

  9. Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

    Science.gov (United States)

    Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

    2017-12-01

    Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

  10. Grave’s Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge

    Directory of Open Access Journals (Sweden)

    Ashok Krishna Bhuyan

    2014-01-01

    Full Text Available Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations.

  11. Grave's Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge.

    Science.gov (United States)

    Bhuyan, Ashok Krishna; Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

    2014-01-01

    Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations.

  12. Discover 4-H Clubs: The Essential Resource for 4-H

    Science.gov (United States)

    MacArthur, Stacey; Nelson, Cindy; Brower, Naomi; Memmott, Margie; Peterson, Gaelynn

    2016-01-01

    Obstacles facing new 4-H volunteers include time constraints and difficulty finding project-specific information, resources, and opportunities available for club members. As a solution to these obstacles and an aid for assisting volunteers in becoming confident in delivering information to youth, content experts produced Discover 4-H Clubs, a…

  13. 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).

  14. 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).

  15. Re-discovering indigenous knowledge – Ulwazi Lwemveli for ...

    African Journals Online (AJOL)

    Therefore, the imperative to re-discover and re-store IK cannot be underestimated since building on this knowledge is particularly effective in helping to reach those living in rural communities. This knowledge is often the main asset they control, and certainly one with which they are more familiar. The case studies discussed ...

  16. REVIEW: Discovering Statistics Using SPSS for Windows ANDY FIELD (2000)

    OpenAIRE

    SHARMA, Reviewed By Ashok

    2015-01-01

    The book "Discovering Statistics Using SPSS for Windows" is exactly that! Since it calculates amazingly fast, in the recent years, the computer has become the most useful and helpful tool for the researchers in almost every field of knowledge - be it open and distance education, psychology, sociology, management or else.

  17. 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

  18. How to Discover the Rogers–Ramanujan Identities

    Indian Academy of Sciences (India)

    IAS Admin

    The purpose of this article is to introduce you to the. Rogers–Ramanujan identities, by discussing an approach to discover them. When you see that they appear from a very simple generalization of the simplest possible in- finite continued fraction, that in turn is related to the celebrated Fibonacci sequence, perhaps you may ...

  19. Towards precision medicine: discovering novel gynecological cancer biomarkers and pathways using linked data.

    Science.gov (United States)

    Jha, Alokkumar; Khan, Yasar; Mehdi, Muntazir; Karim, Md Rezaul; Mehmood, Qaiser; Zappa, Achille; Rebholz-Schuhmann, Dietrich; Sahay, Ratnesh

    2017-09-19

    Next Generation Sequencing (NGS) is playing a key role in therapeutic decision making for the cancer prognosis and treatment. The NGS technologies are producing a massive amount of sequencing datasets. Often, these datasets are published from the isolated and different sequencing facilities. Consequently, the process of sharing and aggregating multisite sequencing datasets are thwarted by issues such as the need to discover relevant data from different sources, built scalable repositories, the automation of data linkage, the volume of the data, efficient querying mechanism, and information rich intuitive visualisation. We present an approach to link and query different sequencing datasets (TCGA, COSMIC, REACTOME, KEGG and GO) to indicate risks for four cancer types - Ovarian Serous Cystadenocarcinoma (OV), Uterine Corpus Endometrial Carcinoma (UCEC), Uterine Carcinosarcoma (UCS), Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) - covering the 16 healthy tissue-specific genes from Illumina Human Body Map 2.0. The differentially expressed genes from Illumina Human Body Map 2.0 are analysed together with the gene expressions reported in COSMIC and TCGA repositories leading to the discover of potential biomarkers for a tissue-specific cancer. We analyse the tissue expression of genes, copy number variation (CNV), somatic mutation, and promoter methylation to identify associated pathways and find novel biomarkers. We discovered twenty (20) mutated genes and three (3) potential pathways causing promoter changes in different gynaecological cancer types. We propose a data-interlinked platform called BIOOPENER that glues together heterogeneous cancer and biomedical repositories. The key approach is to find correspondences (or data links) among genetic, cellular and molecular features across isolated cancer datasets giving insight into cancer progression from normal to diseased tissues. The proposed BIOOPENER platform enriches mutations by filling in

  20. The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via fcg receptor-mediated cross-linking

    DEFF Research Database (Denmark)

    Overdijk, Marije B.; Jansen, J. H. Marco; Nederend, Maaike

    2016-01-01

    RIIb as well as activating FcgRs induce DARA cross-linking-mediated PCD. In conclusion, our in vitro and in vivo data show that FcgRmediated cross-linking of DARA induces PCD of CD38-expressing multiple myeloma tumor cells, which potentially contributes to the depth of response observed in DARA......Emerging evidence suggests that FcgR-mediated cross-linking of tumor-bound mAbs may induce signaling in tumor cells that contributes to their therapeutic activity. In this study, we show that daratumumab (DARA), a therapeutic human CD38 mAb with a broad-spectrum killing activity, is able to induce...... programmed cell death (PCD) of CD38+ multiple myeloma tumor cell lines when cross-linked in vitro by secondary Abs or via an FcgR. By comparing DARA efficacy in a syngeneic in vivo tumor model using FcRg-chain knockout or NOTAM mice carrying a signaling-inactive FcRg-chain, we found that the inhibitory Fcg...

  1. A Network Biology Approach to Discover the Molecular Biomarker Associated with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Liwei Zhuang

    2014-01-01

    Full Text Available In recent years, high throughput technologies such as microarray platform have provided a new avenue for hepatocellular carcinoma (HCC investigation. Traditionally, gene sets enrichment analysis of survival related genes is commonly used to reveal the underlying functional mechanisms. However, this approach usually produces too many candidate genes and cannot discover detailed signaling transduction cascades, which greatly limits their clinical application such as biomarker development. In this study, we have proposed a network biology approach to discover novel biomarkers from multidimensional omics data. This approach effectively combines clinical survival data with topological characteristics of human protein interaction networks and patients expression profiling data. It can produce novel network based biomarkers together with biological understanding of molecular mechanism. We have analyzed eighty HCC expression profiling arrays and identified that extracellular matrix and programmed cell death are the main themes related to HCC progression. Compared with traditional enrichment analysis, this approach can provide concrete and testable hypothesis on functional mechanism. Furthermore, the identified subnetworks can potentially be used as suitable targets for therapeutic intervention in HCC.

  2. Radiobiological speculations on therapeutic total body irradiation

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.

    1990-01-01

    Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references

  3. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    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...... 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...

  4. 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.

  5. Possible origin of Saturn's newly discovered outer ring

    International Nuclear Information System (INIS)

    Moehlmann, D.

    1986-01-01

    Within a planetogonic model the self-gravitationally caused formation of pre-planetary and pre-satellite rings from an earlier thin disk is reported. The theoretically derived orbital radii of these rings are compared with the orbital levels in the planetary system and the satellite systems of Jupiter, Saturn and Uranus. From this comparison it is concluded that at the radial position of Saturn's newly discovered outer ring an early pre-satellite ring of more or less evolved satellites could have existed. These satellites should have been disturbed in their evolution by the gravitation of the neighbouring massive satellite Titan. The comparison also may indicate similarities between the asteroidal belt and the newly discovered outer ring of Saturn

  6. UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry.

    Science.gov (United States)

    Zhao, Ying-Yong; Cheng, Xian-Long; Vaziri, Nosratola D; Liu, Shuman; Lin, Rui-Chao

    2014-10-01

    Metabonomics is a powerful and promising analytic tool that allows assessment of global low-molecular-weight metabolites in biological systems. It has a great potential for identifying useful biomarkers for early diagnosis, prognosis and assessment of therapeutic interventions in clinical practice. The aim of this review is to provide a brief summary of the recent advances in UPLC-based metabonomic approach for biomarker discovery in a variety of diseases, and to discuss their significance in clinical chemistry. All the available information on UPLC-based metabonomic applications for discovering biomarkers of diseases were collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Springer, Google Scholar, etc.). Metabonomics has been used in clinical chemistry to identify and evaluate potential biomarkers and therapeutic targets in various diseases affecting the liver (hepatocarcinoma and liver cirrhosis), lung (lung cancer and pneumonia), gastrointestinal tract (colorectal cancer) and urogenital tract (prostate cancer, ovarian cancer and chronic kidney disease), as well as metabolic diseases (diabetes) and neuropsychiatric disorders (Alzheimer's disease and schizophrenia), etc. The information provided highlights the potential value of determination of endogenous low-molecular-weight metabolites and the advantages and potential drawbacks of the application of UPLC-based metabonomics in clinical setting. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Decision Tree Approach to Discovering Fraud in Leasing Agreements

    OpenAIRE

    Horvat Ivan; Pejić Bach Mirjana; Merkač Skok Marjana

    2014-01-01

    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 mo...

  8. 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...

  9. Discovering the quantum universe the role of particle colliders

    CERN Document Server

    2006-01-01

    What does "Quantum Universe" mean? To discover what the universe is made of and how it works is the challenge of particle physics. "Quantum Universe" defines the quest to explain the universe in terms of quantum physics, which governs the behavior of the microscopic, subatomic world. It describes a revolution in particle physics and a quantum leap in our understanding of the mystery and beauty of the universe.

  10. Discovering Social Circles in Ego Networks (Author’s Manuscript)

    Science.gov (United States)

    2013-01-10

    refer to as social cir- cles. Practically all major social networks provide such functionality, for example, ‘circles’ on Google+, and ‘lists’ on Facebook ...Discovering Social Circles in Ego Networks Julian McAuley and Jure Leskovec Stanford jmcauley@cs.stanford.edu, jure@cs.stanford.edu January 11, 2013...Abstract People’s personal social networks are big and cluttered, and currently there is no good way to automatically organize them. Social networking

  11. A systematic framework to discover pattern for web spam classification

    OpenAIRE

    Jelodar, Hamed; Wang, Yongli; Yuan, Chi; Jiang, Xiaohui

    2017-01-01

    Web spam is a big problem for search engine users in World Wide Web. They use deceptive techniques to achieve high rankings. Although many researchers have presented the different approach for classification and web spam detection still it is an open issue in computer science. Analyzing and evaluating these websites can be an effective step for discovering and categorizing the features of these websites. There are several methods and algorithms for detecting those websites, such as decision t...

  12. Discovering Authentication Credentials in Volatile Memory of Android Mobile Devices

    OpenAIRE

    Apostolopoulos , Dimitris; Marinakis , Giannis; Ntantogian , Christoforos; Xenakis , Christos

    2013-01-01

    Part 5: Adoption Issues in e/m-Services; International audience; This paper investigates whether authentication credentials in the volatile memory of Android mobile devices can be discovered using freely available tools. The experiments that we carried out for each application included two different sets: In the first set, our goal was to check if we could recover our own submitted credentials from the memory dump of the mobile device. In the second set of experiments, the goal was to find pa...

  13. Marketing therapeutic recreation services.

    Science.gov (United States)

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  14. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  15. Therapeutic applications of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baker, W.J.; Datz, F.L.; Beightol, R.W.

    1987-01-01

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  16. An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

    Directory of Open Access Journals (Sweden)

    Syed Babar Jamal

    Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

  17. Approaches to Preventative and Therapeutic HIV vaccines

    Science.gov (United States)

    Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

    2016-01-01

    Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

  18. 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

  19. PYTHIOSIS: A THERAPEUTIC APPROACH

    Directory of Open Access Journals (Sweden)

    C. M. C. Falcão

    2015-10-01

    Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

  20. Tools and strategies for discovering novel enzymes and metabolic pathways

    Directory of Open Access Journals (Sweden)

    John A. Gerlt

    2016-12-01

    Full Text Available The number of entries in the sequence databases continues to increase exponentially – the UniProt database is increasing with a doubling time of ∼4 years (2% increase/month. Approximately 50% of the entries have uncertain, unknown, or incorrect function annotations because these are made by automated methods based on sequence homology. If the potential in complete genome sequences is to be realized, strategies and tools must be developed to facilitate experimental assignment of functions to uncharacterized proteins discovered in genome projects. The Enzyme Function Initiative (EFI; previously supported by U54GM093342 from the National Institutes of Health, now supported by P01GM118303 developed web tools for visualizing and analyzing (1 sequence and function space in protein families (EFI-EST and (2 genome neighbourhoods in microbial and fungal genomes (EFI-GNT to assist the design of experimental strategies for discovering the in vitro activities and in vivo metabolic functions of uncharacterized enzymes. The EFI developed an experimental platform for large-scale production of the solute binding proteins (SBPs for ABC, TRAP, and TCT transport systems and their screening with a physical ligand library to identify the identities of the ligands for these transport systems. Because the genes that encode transport systems are often co-located with the genes that encode the catabolic pathways for the transported solutes, the identity of the SBP ligand together with the EFI-EST and EFI-GNT web tools can be used to discover new enzyme functions and new metabolic pathways. This approach is demonstrated with the characterization of a novel pathway for ethanolamine catabolism.

  1. NLRC5: a newly discovered MHC class I transactivator (CITA)

    OpenAIRE

    Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.

    2011-01-01

    Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class II gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NLR protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as “CITA” (MHC class I transactivator)...

  2. Knots and surfaces a guide to discovering mathematics

    CERN Document Server

    Farmer, David W

    1995-01-01

    In most mathematics textbooks, the most exciting part of mathematics-the process of invention and discovery-is completely hidden from the reader. The aim of Knots and Surfaces is to change all that. By means of a series of carefully selected tasks, this book leads readers to discover some real mathematics. There are no formulas to memorize; no procedures to follow. The book is a guide: its job is to start you in the right direction and to bring you back if you stray too far. Discovery is left to you. Suitable for a one-semester course at the beginning undergraduate level, there are no prerequi

  3. 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.

  4. 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.

  5. Discovering Communicable Scientific Knowledge from Spatio-Temporal Data

    Science.gov (United States)

    Schwabacher, Mark; Langley, Pat; Norvig, Peter (Technical Monitor)

    2001-01-01

    This paper describes how we used regression rules to improve upon a result previously published in the Earth science literature. In such a scientific application of machine learning, it is crucially important for the learned models to be understandable and communicable. We recount how we selected a learning algorithm to maximize communicability, and then describe two visualization techniques that we developed to aid in understanding the model by exploiting the spatial nature of the data. We also report how evaluating the learned models across time let us discover an error in the data.

  6. Very Bright CV discovered by MASTER-ICATE (Argentina)

    Science.gov (United States)

    Saffe, C.; Levato, H.; Mallamaci, C.; Lopez, C.; Lipunov, F. Podest V.; Denisenko, D.; Gorbovskoy, E.; Tiurina, N.; Balanutsa, P.; Kornilov, V.; Belinski, A.; Shatskiy, N.; Chazov, V.; Kuznetsov, A.; Yecheistov, V.; Yurkov, V.; Sergienko, Y.; Varda, D.; Sinyakov, E.; Gabovich, A.; Ivanov, K.; Yazev, S.; Budnev, N.; Konstantinov, E.; Chuvalaev, O.; Poleshchuk, V.; Gress, O.; Frolova, A.; Krushinsky, V.; Zalozhnih, I.; Popov, A.; Bourdanov, A.; Parkhomenko, A.; Tlatov, A.; Dormidontov, D.; Senik, V.; Podvorotny, P.; Shumkov, V.; Shurpakov, S.

    2013-06-01

    MASTER-ICATE very wide-field camera (d=72mm f/1.2 lens + 11 Mpix CCD) located near San Juan, Argentina has discovered OT source at (RA, Dec) = 14h 20m 23.5s -48d 55m 40s on the combined image (exposure 275 sec) taken on 2013-06-08.048 UT. The OT unfiltered magnitude is 12.1m (limit 13.1m). There is no minor planet at this place. The OT is seen in more than 10 images starting from 2013-06-02.967 UT (275 sec exposure) when it was first detected at 12.4m.

  7. 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...

  8. 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.

  9. Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool

    OpenAIRE

    Pickett, Andy; Perrow, Karen

    2011-01-01

    The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review ...

  10. Discovering the cosmos with small spacecraft the American explorer program

    CERN Document Server

    Harvey, Brian

    2018-01-01

    Explorer was the original American space program and Explorer 1 its first satellite, launched in 1958. Sixty years later, it is the longest continuously running space program in the world, demonstrating to the world how we can explore the cosmos with small spacecraft. Almost a hundred Explorers have already been launched.  Explorers have made some of the fundamental discoveries of the Space Age.Explorer 1 discovered Earth’s radiation belts. Later Explorers surveyed the Sun, the X-ray and ultraviolet universes, black holes, magnetars and gamma ray bursts. An Explorer found the remnant of the Big Bang. One Explorer chased and was the first to intercept a comet. The program went through a period of few launches during the crisis of funding for space science in the 1980s. However, with the era of ‘faster, cheaper, better,’ the program was reinvented, and new exiting missions began to take shape, like Swift and the asteroid hunter WISE.  Discovering the Cosmos with Small Spacecraft gives an account of ...

  11. Discovering objects in a blood recipient information system.

    Science.gov (United States)

    Qiu, D; Junghans, G; Marquardt, K; Kroll, H; Mueller-Eckhardt, C; Dudeck, J

    1995-01-01

    Application of object-oriented (OO) methodologies has been generally considered as a solution to the problem of improving the software development process and managing the so-called software crisis. Among them, object-oriented analysis (OOA) is the most essential and is a vital prerequisite for the successful use of other OO methodologies. Though there are already a good deal of OOA methods published, the most important aspect common to all these methods: discovering objects classes truly relevant to the given problem domain, has remained a subject to be intensively researched. In this paper, using the successful development of a blood recipient information system as an example, we present our approach which is based on the conceptual framework of responsibility-driven OOA. In the discussion, we also suggest that it may be inadequate to simply attribute the software crisis to the waterfall model of the software development life-cycle. We are convinced that the real causes for the failure of some software and information systems should be sought in the methodologies used in some crucial phases of the software development process. Furthermore, a software system can also fail if object classes essential to the problem domain are not discovered, implemented and visualized, so that the real-world situation cannot be faithfully traced by it.

  12. 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.

  13. Screening individual hybridomas by microengraving to discover monoclonal antibodies

    Science.gov (United States)

    Ogunniyi, Adebola O; Story, Craig M; Papa, Eliseo; Guillen, Eduardo; Love, J Christopher

    2014-01-01

    The demand for monoclonal antibodies (mAbs) in biomedical research is significant, but the current methodologies used to discover them are both lengthy and costly. Consequently, the diversity of antibodies available for any particular antigen remains limited. Microengraving is a soft lithographic technique that provides a rapid and efficient alternative for discovering new mAbs. This protocol describes how to use microengraving to screen mouse hybridomas to establish new cell lines producing unique mAbs. Single cells from a polyclonal population are isolated into an array of microscale wells (~105 cells per screen). The array is then used to print a protein microarray, where each element contains the antibodies captured from individual wells. The antibodies on the microarray are screened with antigens of interest, and mapped to the corresponding cells, which are then recovered from their microwells by micromanipulation. Screening and retrieval require approximately 1–3 d (9–12 d including the steps for preparing arrays of microwells). PMID:19528952

  14. Thymolipoma combined with hyperthyroidism discovered by neurological symptoms.

    Science.gov (United States)

    Takahashi, Hidenobu; Harada, Masahiko; Kimura, Masakazu; Kato, Harubumi

    2007-04-01

    Thymolipomas are rare slow-growing mediastinal thymic neoplasms. Most cases are asymptomatic and are sometimes discovered as a huge mass on chest x-ray films. A few cases have been discovered during examinations for other diseases. We report the second case of thymolipoma combined with hyperthyroidism in the English language literature. Neurological symptoms suddenly appeared in a 45-year-old woman. Central nervous system disorder was suggested but no significant abnormalities were found on brain MR nor were there any neurological signs. Several months later, neurological and systemic examinations on admission revealed hyperthyroidism and an anterior mediastinal tumor, 9.0x5.0x3.0 cm in size on chest CT films. Despite treatment of hyperthyroidism by medication, her neurological symptoms remained. Neurologists recommended resection of the mediastinal tumor. Malignancy could not be ruled out because of the irregularity of the tumor appearance on contrast-enhanced chest CT. Furthermore, the tumor appeared to be attached to the ascending aorta, so cytological and/or pathological diagnosis by CT-guided needle biopsy before operation were contraindicated. Extended thymectomy was performed in May 2005. The pathological diagnosis was benign thymolipoma consisting of mature fatty tissue and thymic tissue structures with Hassall's corpuscles. Her neurological symptoms seemed slightly but not markedly improved. The relationship between thymolipoma and hyperthyroidism is still unknown.

  15. 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. © 2015 The Society for Applied Microbiology.

  16. Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies.

    Science.gov (United States)

    Dichtelmüller, Herbert O; Biesert, Lothar; Fabbrizzi, Fabrizio; Gajardo, Rodrigo; Gröner, Albrecht; von Hoegen, Ilka; Jorquera, Juan I; Kempf, Christoph; Kreil, Thomas R; Pifat, Dominique; Osheroff, Wendy; Poelsler, Gerhard

    2009-09-01

    Solvent/detergent (S/D) treatment is an established virus inactivation technology that has been applied in the manufacture of medicinal products derived from human plasma for more than 20 years. Data on the inactivation of enveloped viruses by S/D treatment collected from seven Plasma Protein Therapeutics Association member companies demonstrate the robustness, reliability, and efficacy of this virus inactivation method. The results from 308 studies reflecting production conditions as well as technical variables significantly beyond the product release specification were evaluated for virus inactivation, comprising different combinations of solvent and detergent (tri(n-butyl) phosphate [TNBP]/Tween 80, TNBP/Triton X-100, TNBP/Na-cholate) and different products (Factor [F]VIII, F IX, and intravenous and intramuscular immunoglobulins). Neither product class, process temperature, protein concentration, nor pH value has a significant impact on virus inactivation. A variable that did appear to be critical was the concentration of solvent and detergent. The data presented here demonstrate the robustness of virus inactivation by S/D treatment for a broad spectrum of enveloped test viruses and process variables. Our data substantiate the fact that no transmission of viruses such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or of other enveloped viruses was reported for licensed plasma derivatives since the introduction of S/D treatment.

  17. Stroke and Therapeutic Hypothermia

    Directory of Open Access Journals (Sweden)

    Ozlem Ozkan Kuscu

    2016-09-01

    Full Text Available Stroke is significant cause of morbidity and mortality caused by disruption of blood flow. Neural injury occurs with two stage; while primary neural injury occurs with disruption of blood flow, after days and hours with metabolic processes secondary injury develops in tissues which is non injured in the first stage. Therefore it is important to prevent and treat the secondary injury as much as preventing and treating the primary neural injury. In this article developing pathophysiological changes after stroke, mechanisms of therapeutic hypothermia, application methods, the factors that determine the effectiveness, side effects and complications were reviewed. [Archives Medical Review Journal 2016; 25(3.000: 351-368

  18. Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Odiba Arome

    2017-09-01

    Full Text Available Science always strives to find an improved way of doing things and nanoscience is one such approach. Nanomaterials are suitable for pharmaceutical applications mostly because of their size which facilitates absorption, distribution, metabolism and excretion of the nanoparticles. Whether labile or insoluble nanoparticles, their cytotoxic effect on malignant cells has moved the use of nanomedicine into focus. Since nanomedicine can be described as the science and technology of diagnosing, treating and preventing diseases towards ultimately improving human health, a lot of nanotechnology options have received approval by various regulatory agencies. Nanodrugs also have been discovered to be more precise in targeting the desired site, hence maximizing the therapeutic effects, while minimizing side-effects on the rest of the body. This unique property and more has made nanomedicine popular in therapeutic medicine employing nanotechnology in genetic therapy, drug encapsulation, enzyme manipulation and control, tissue engineering, target drug delivery, pharmacogenomics, stem cell and cloning, and even virus-based hybrids. This review highlights nanoproducts that are in development and have gained approval through one clinical trial stage or the other.

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

    Science.gov (United States)

    Gao, Chu-Han; Yu, Lu-Shan; Zeng, Su; Huang, Yu-Wen; Zhou, Quan

    2014-01-01

    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. 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. 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 more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of calcium formulations and oral LVX was insufficient to prevent a chelation interaction in cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be

  20. Discovering regulatory motifs in the Plasmodium genome using comparative genomics

    OpenAIRE

    Wu, Jie; Sieglaff, Douglas H.; Gervin, Joshua; Xie, Xiaohui S.

    2008-01-01

    Motivation: Understanding gene regulation in Plasmodium, the causative agent of malaria, is an important step in deciphering its complex life cycle as well as leading to possible new targets for therapeutic applications. Very little is known about gene regulation in Plasmodium, and in particular, few regulatory elements have been identified. Such discovery has been significantly hampered by the high A-T content of some of the genomes of Plasmodium species, as well as the challenge in associat...

  1. Simultaneously Discovering and Localizing Common Objects in Wild Images.

    Science.gov (United States)

    Wang, Zhenzhen; Yuan, Junsong

    2018-09-01

    Motivated by the recent success of supervised and weakly supervised common object discovery, in this paper, we move forward one step further to tackle common object discovery in a fully unsupervised way. Generally, object co-localization aims at simultaneously localizing objects of the same class across a group of images. Traditional object localization/detection usually trains specific object detectors which require bounding box annotations of object instances, or at least image-level labels to indicate the presence/absence of objects in an image. Given a collection of images without any annotations, our proposed fully unsupervised method is to simultaneously discover images that contain common objects and also localize common objects in corresponding images. Without requiring to know the total number of common objects, we formulate this unsupervised object discovery as a sub-graph mining problem from a weighted graph of object proposals, where nodes correspond to object proposals, and edges represent the similarities between neighbouring proposals. The positive images and common objects are jointly discovered by finding sub-graphs of strongly connected nodes, with each sub-graph capturing one object pattern. The optimization problem can be efficiently solved by our proposed maximal-flow-based algorithm. Instead of assuming that each image contains only one common object, our proposed solution can better address wild images where each image may contain multiple common objects or even no common object. Moreover, our proposed method can be easily tailored to the task of image retrieval in which the nodes correspond to the similarity between query and reference images. Extensive experiments on PASCAL VOC 2007 and Object Discovery data sets demonstrate that even without any supervision, our approach can discover/localize common objects of various classes in the presence of scale, view point, appearance variation, and partial occlusions. We also conduct broad

  2. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  3. Therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Baum, Richard P.

    2014-01-01

    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.

  4. 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.

  5. 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.

  6. 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......, respectively. The corresponding fluxes are 19+/-2 and 23+/-3 mCrab (68% c.l., only statistical). The best determined source position is at RA=17:49:49; DEC=-29:21:14 (J2000) with a 90% confinement radius of 2.3 arcmin. The IBIS/ISGRI spectrum (exposure time 15.9 ks) can be well described by a a power...

  7. Discovering Mira Ceti: Celestial Change and Cosmic Continuity

    Science.gov (United States)

    Hatch, Robert Alan

    In the short narrative that follows I introduce two new heroes. Although we begin with Fabricius's first sighting in 1596, the new pivot point in the drama is the collaboration between Hevelius and Boulliau that began around 1660. As it happens, Learned Europe paid little attention to Mira in the generation after the first scattered sightings of 1596, indeed, nearly 70 years passed before the New Star was given a working identity. Like Columbus discovering America, Fabricius and Holwarda saw different things - for convenience, I call them Fabricius's Star and Holwarda's Star. Hevelius's Historiola (Danzig, 1662) and Boulliau's Ad astronomos (Paris, 1667) presented a different vision. It made Mira famous. As I shall argue, if Hevelius gave Mira a history, Boulliau gave Mira a future.5 In the end, the New Star not only challenged the ancient cosmos, it became an enduring icon for the New Science, a returning reminder of celestial continuity and cosmic order.

  8. SOLAR SYSTEM ANALOGS AROUND IRAS-DISCOVERED DEBRIS DISKS

    International Nuclear Information System (INIS)

    Chen, Christine H.; Sheehan, Patrick; Watson, Dan M.; Manoj, P.; Najita, Joan R.

    2009-01-01

    We have rereduced Spitzer IRS spectra and reanalyzed the spectral energy distributions (SEDs) of three nearby debris disks: λ Boo, HD 139664, and HR 8799. We find that the thermal emission from these objects is well modeled using two single temperature black body components. For HR 8799 - with no silicate emission features despite a relatively hot inner dust component (T gr = 150 K) - we infer the presence of an asteroid belt interior to and a Kuiper Belt exterior to the recently discovered orbiting planets. For HD 139664, which has been imaged in scattered light, we infer the presence of strongly forward scattering grains, consistent with porous grains, if the cold, outer disk component generates both the observed scattered light and thermal emission. Finally, careful analysis of the λ Boo SED suggests that this system possesses a central clearing, indicating that selective accretion of solids onto the central star does not occur from a dusty disk.

  9. Discovering Related Clinical Concepts Using Large Amounts of Clinical Notes.

    Science.gov (United States)

    Ganesan, Kavita; Lloyd, Shane; Sarkar, Vikren

    2016-01-01

    The ability to find highly related clinical concepts is essential for many applications such as for hypothesis generation, query expansion for medical literature search, search results filtering, ICD-10 code filtering and many other applications. While manually constructed medical terminologies such as SNOMED CT can surface certain related concepts, these terminologies are inadequate as they depend on expertise of several subject matter experts making the terminology curation process open to geographic and language bias. In addition, these terminologies also provide no quantifiable evidence on how related the concepts are. In this work, we explore an unsupervised graphical approach to mine related concepts by leveraging the volume within large amounts of clinical notes. Our evaluation shows that we are able to use a data driven approach to discovering highly related concepts for various search terms including medications, symptoms and diseases.

  10. Discovering Related Clinical Concepts Using Large Amounts of Clinical Notes

    Directory of Open Access Journals (Sweden)

    Kavita Ganesan

    2016-01-01

    Full Text Available The ability to find highly related clinical concepts is essential for many applications such as for hypothesis generation, query expansion for medical literature search, search results filtering, ICD-10 code filtering and many other applications. While manually constructed medical terminologies such as SNOMED CT can surface certain related concepts, these terminologies are inadequate as they depend on expertise of several subject matter experts making the terminology curation process open to geographic and language bias. In addition, these terminologies also provide no quantifiable evidence on how related the concepts are. In this work, we explore an unsupervised graphical approach to mine related concepts by leveraging the volume within large amounts of clinical notes. Our evaluation shows that we are able to use a data driven approach to discovering highly related concepts for various search terms including medications, symptoms and diseases.

  11. Occult carcinoma discovered after simple hysterectomy treated with postoperative radiotherapy

    International Nuclear Information System (INIS)

    Crane, Christopher H.; Schneider, Bernard F.

    1999-01-01

    Purpose: Treatment of patients with occult carcinoma of the cervix discovered after simple hysterectomy is controversial. The purpose of this review is to examine our results with postoperative radiotherapy and to compare them to similar reports and to reports of treatment with radical parametrectomy. Methods and Materials: Between November 1979 and April:, 18 patients were treated with radiotherapy at the University of Virginia for invasive carcinoma of the cervix discovered after simple hysterectomy. Simple hysterectomy was performed in all 18 patients for a variety of indications. After surgery gross residual carcinoma remained in four patients; and microscopic disease was present at the surgical margins in two patients. The remaining patients had no evidence of residual disease. All 18 patients had postoperative radiotherapy with or without brachytherapy. The endpoints for this study were local control, survival, and treatment-related toxicity. Actuarial rates were calculated using the Life method. Results: Median follow-up for all 18 patients was 42 months (range 2-202 months). Both the 5 and the 10-year actuarial local control rates were 88%. Five and 10-year actuarial overall survival rates were both 93%. Two patients had both local and distant cancer recurrences. There were no recurrences among the six patients treated with external beam alone. The remaining patients are all alive without evidence of disease, including two patients who had gross residual disease after surgery, and one patient with both microscopic positive margin and a positive lymph node (the only patient to undergo lymph node sampling). There was no severe acute morbidity and only one patient had severe late morbidity. Conclusions: Invasive carcinoma found after simple hysterectomy may be treated safely and effectively with postoperative radiotherapy. Patients with known residual disease following surgery do poorly with either radiotherapy or reoperation, but treatment with radiotherapy

  12. Risk of appendicitis in patients with incidentally discovered appendicoliths.

    Science.gov (United States)

    Khan, Muhammad Sohaib; Chaudhry, Mustafa Belal Hafeez; Shahzad, Noman; Tariq, Marvi; Memon, Wasim Ahmed; Alvi, Abdul Rehman

    2018-01-01

    An appendicolith-related appendiceal obstruction leading to appendicitis is a commonly encountered surgical emergency that has clear evidence-based management plans. However, there is no consensus on management of asymptomatic patients when appendicoliths are found incidentally. The objective of this study was to determine the risk of appendicitis in patients with an incidental finding of the appendicolith. A retrospective matched cohort study of patients with appendicolith discovered incidentally on computed tomographic scan from January 2008 to December 2014 at our institution was completed. The size and position of the appendicolith were ascertained. The study group was matched by age and gender to a control group. Both groups were contacted and interviewed regarding development of appendicitis. In total, 111 patients with appendicolith were successfully contacted and included in the study. Mean age was found to be 38 ± 15 y with 36 (32%) of the study population being females. Mean length of appendix was 66 ± 16 mm, and mean width was 5.8 ± 0.9 mm. Mean size of the appendicolith was 3.6 ± 1.1 mm (1.4-7.8 mm). Fifty-eight percent of appendicoliths was located at the proximal end or whole of appendix, 31% at mid area, and 11% at the distal end of appendix. All patients of the study and control groups were contacted, and at a mean follow-up of 4.0 ± 1.7 y, there was no occurrence of acute appendicitis in either group. Patients with incidentally discovered appendicolith on radiological imaging did not develop appendicitis. Hence, the risk of developing acute appendicitis for these patients does not seem higher than the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Prophylactic and therapeutic management of acute radiation related morbidity of the skin and mucosa. Part I. Results of a German multicenter questionnaire

    International Nuclear Information System (INIS)

    Zimmermann, J.S.; Wilhelm, R.; Niehoff, P.; Schneider, R.; Kovacs, G.; Kimmig, B.

    1998-01-01

    In this work, it was to evaluate the remedies, which are used for prevention and therapeutic management of acute radiation related morbidity of the skin and mucosa (mouth, pharynx, esophagus, small and large bowel, rectum and vagina). A questionnaire was sent to 130 radiotherapeutic departments in Germany in Juli 1995. The questionnaire had been designed with 22 open questions concerning the preventive and therapeutic management of acute radiation related morbidity of skin and mucosal sites. From 130 questionnaires, 89 (68.4%) were sent back till August 1995. All of them were evaluable. The recommendations showed a broad spectrum for each site. Especially the oral mucositis was treated in many different ways and combinations. The prevention and therapy of complicating superinfections seem to be the joint principle of most of the recommendations. The management of the acute radiation related morbidity has a wide clinical spectrum among different radiation therapy centers. Systematic prospectively designed investigations are necessary in order to achieve a further reduction in the radiation related acute morbidity. Therefore, a multicenter collaborative working group has been founded. (orig./MG) [de

  14. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  15. Therapeutic and diagnostic nanomaterials

    CERN Document Server

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  16. [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.

  17. Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds

    Science.gov (United States)

    Pfalzgraff, Anja; Brandenburg, Klaus; Weindl, Günther

    2018-01-01

    Alarming data about increasing resistance to conventional antibiotics are reported, while at the same time the development of new antibiotics is stagnating. Skin and soft tissue infections (SSTIs) are mainly caused by the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) which belong to the most recalcitrant bacteria and are resistant to almost all common antibiotics. S. aureus and P. aeruginosa are the most frequent pathogens isolated from chronic wounds and increasing resistance to topical antibiotics has become a major issue. Therefore, new treatment options are urgently needed. In recent years, research focused on the development of synthetic antimicrobial peptides (AMPs) with lower toxicity and improved activity compared to their endogenous counterparts. AMPs appear to be promising therapeutic options for the treatment of SSTIs and wounds as they show a broad spectrum of antimicrobial activity, low resistance rates and display pivotal immunomodulatory as well as wound healing promoting activities such as induction of cell migration and proliferation and angiogenesis. In this review, we evaluate the potential of AMPs for the treatment of bacterial SSTIs and wounds and provide an overview of the mechanisms of actions of AMPs that contribute to combat skin infections and to improve wound healing. Bacteria growing in biofilms are more resistant to conventional antibiotics than their planktonic counterparts due to limited biofilm penetration and distinct metabolic and physiological functions, and often result in chronification of infections and wounds. Thus, we further discuss the feasibility of AMPs as anti-biofilm agents. Finally, we highlight perspectives for future therapies and which issues remain to bring AMPs successfully to the market. PMID:29643807

  18. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

    Science.gov (United States)

    Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

  19. Towards new uses of botulinum toxin as a novel therapeutic tool.

    Science.gov (United States)

    Pickett, Andy; Perrow, Karen

    2011-01-01

    The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

  20. Towards New Uses of Botulinum Toxin as a Novel Therapeutic Tool

    Directory of Open Access Journals (Sweden)

    Karen Perrow

    2011-01-01

    Full Text Available The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

  1. Data Recommender: An Alternative Way to Discover Open Scientific Datasets

    Science.gov (United States)

    Klump, J. F.; Devaraju, A.; Williams, G.; Hogan, D.; Davy, R.; Page, J.; Singh, D.; Peterson, N.

    2017-12-01

    Over the past few years, institutions and government agencies have adopted policies to openly release their data, which has resulted in huge amounts of open data becoming available on the web. When trying to discover the data, users face two challenges: an overload of choice and the limitations of the existing data search tools. On the one hand, there are too many datasets to choose from, and therefore, users need to spend considerable effort to find the datasets most relevant to their research. On the other hand, data portals commonly offer keyword and faceted search, which depend fully on the user queries to search and rank relevant datasets. Consequently, keyword and faceted search may return loosely related or irrelevant results, although the results may contain the same query. They may also return highly specific results that depend more on how well metadata was authored. They do not account well for variance in metadata due to variance in author styles and preferences. The top-ranked results may also come from the same data collection, and users are unlikely to discover new and interesting datasets. These search modes mainly suits users who can express their information needs in terms of the structure and terminology of the data portals, but may pose a challenge otherwise. The above challenges reflect that we need a solution that delivers the most relevant (i.e., similar and serendipitous) datasets to users, beyond the existing search functionalities on the portals. A recommender system is an information filtering system that presents users with relevant and interesting contents based on users' context and preferences. Delivering data recommendations to users can make data discovery easier, and as a result may enhance user engagement with the portal. We developed a hybrid data recommendation approach for the CSIRO Data Access Portal. The approach leverages existing recommendation techniques (e.g., content-based filtering and item co-occurrence) to produce

  2. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  3. Discovering geothermal supercritical fluids: a new frontier for seismic exploration.

    Science.gov (United States)

    Piana Agostinetti, Nicola; Licciardi, Andrea; Piccinini, Davide; Mazzarini, Francesco; Musumeci, Giovanni; Saccorotti, Gilberto; Chiarabba, Claudio

    2017-11-06

    Exploiting supercritical geothermal resources represents a frontier for the next generation of geothermal electrical power plant, as the heat capacity of supercritical fluids (SCF),which directly impacts on energy production, is much higher than that of fluids at subcritical conditions. Reconnaissance and location of intensively permeable and productive horizons at depth is the present limit for the development of SCF geothermal plants. We use, for the first time, teleseismic converted waves (i.e. receiver function) for discovering those horizons in the crust. Thanks to the capability of receiver function to map buried anisotropic materials, the SCF-bearing horizon is seen as the 4km-depth abrupt termination of a shallow, thick, ultra-high (>30%) anisotropic rock volume, in the center of the Larderello geothermal field. The SCF-bearing horizon develops within the granites of the geothermal field, bounding at depth the vapor-filled heavily-fractured rock matrix that hosts the shallow steam-dominated geothermal reservoirs. The sharp termination at depth of the anisotropic behavior of granites, coinciding with a 2 km-thick stripe of seismicity and diffuse fracturing, points out the sudden change in compressibility of the fluid filling the fractures and is a key-evidence of deep fluids that locally traversed the supercritical conditions. The presence of SCF and fracture permeability in nominally ductile granitic rocks open new scenarios for the understanding of magmatic systems and for geothermal exploitation.

  4. Metabolome analysis for discovering biomarkers of gastroenterological cancer.

    Science.gov (United States)

    Suzuki, Makoto; Nishiumi, Shin; Matsubara, Atsuki; Azuma, Takeshi; Yoshida, Masaru

    2014-09-01

    Improvements in analytical technologies have made it possible to rapidly determine the concentrations of thousands of metabolites in any biological sample, which has resulted in metabolome analysis being applied to various types of research, such as clinical, cell biology, and plant/food science studies. The metabolome represents all of the end products and by-products of the numerous complex metabolic pathways operating in a biological system. Thus, metabolome analysis allows one to survey the global changes in an organism's metabolic profile and gain a holistic understanding of the changes that occur in organisms during various biological processes, e.g., during disease development. In clinical metabolomic studies, there is a strong possibility that differences in the metabolic profiles of human specimens reflect disease-specific states. Recently, metabolome analysis of biofluids, e.g., blood, urine, or saliva, has been increasingly used for biomarker discovery and disease diagnosis. Mass spectrometry-based techniques have been extensively used for metabolome analysis because they exhibit high selectivity and sensitivity during the identification and quantification of metabolites. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Furthermore, the findings of studies that attempted to discover biomarkers of gastroenterological cancer are also outlined. Finally, we discuss metabolome analysis-based disease diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 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.

  6. The 3D model of debriefing: defusing, discovering, and deepening.

    Science.gov (United States)

    Zigmont, Jason J; Kappus, Liana J; Sudikoff, Stephanie N

    2011-04-01

    The experiential learning process involves participation in key experiences and analysis of those experiences. In health care, these experiences can occur through high-fidelity simulation or in the actual clinical setting. The most important component of this process is the postexperience analysis or debriefing. During the debriefing, individuals must reflect upon the experience, identify the mental models that led to behaviors or cognitive processes, and then build or enhance new mental models to be used in future experiences. On the basis of adult learning theory, the Kolb Experiential Learning Cycle, and the Learning Outcomes Model, we structured a framework for facilitators of debriefings entitled "the 3D Model of Debriefing: Defusing, Discovering, and Deepening." It incorporates common phases prevalent in the debriefing literature, including description of and reactions to the experience, analysis of behaviors, and application or synthesis of new knowledge into clinical practice. It can be used to enhance learning after real or simulated events. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Can doubly strange dibaryon resonances be discovered at RHIC?

    International Nuclear Information System (INIS)

    Paganis, S. D.; Hoffmann, G. W.; Ray, R. L.; Tang, J.-L.; Udagawa, T.; Longacre, R. S.

    2000-01-01

    The baryon-baryon continuum invariant mass spectrum generated from relativistic nucleus + nucleus collision data may reveal the existence of doubly strange dibaryons not stable against strong decay if they lie within a few MeV of threshold. Furthermore, since the dominant component of these states is a superposition of two color-octet clusters which can be produced intermediately in a color-deconfined quark-gluon plasma (QGP), an enhanced production of dibaryon resonances could be a signal of QGP formation. A total of eight, doubly strange dibaryon states are considered for experimental search using the STAR detector (solenoidal tracker at RHIC) at the new Relativistic Heavy Ion Collider (RHIC). These states may decay to ΛΛ and/or pΞ - , depending on the resonance energy. STAR's large acceptance, precision tracking and vertex reconstruction capabilities, and large data volume capacity, make it an ideal instrument to use for such a search. Detector performance and analysis sensitivity are studied as a function of resonance production rate and width for one particular dibaryon which can directly strong decay to pΞ - , but not ΛΛ. Results indicate that such resonances may be discovered using STAR if the resonance production rates are comparable to coalescence model predictions for dibaryon bound states. (c) 2000 The American Physical Society

  8. 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.

  9. More Far-Side Deep Moonquake Nests Discovered

    Science.gov (United States)

    Nakamura, Y.; Jackson, John A.; Jackson, Katherine G.

    2004-01-01

    As reported last year, we started to reanalyze the seismic data acquired from 1969 to 1977 with a network of stations established on the Moon during the Apollo mission. The reason for the reanalysis was because recent advances in computer technology make it possible to employ much more sophisticated analysis techniques than was possible previously. The primary objective of the reanalysis was to search for deep moonquakes on the far side of the Moon and, if found, to use them to infer the structure of the Moon's deep interior, including a possible central core. The first step was to identify any new deep moonquakes that escaped our earlier search by applying a combination of waveform cross-correlation and single-link cluster analysis, and then to see if any of them are from previously unknown nests of deep moonquakes. We positively identified 7245 deep moonquakes, more than a five-fold increase from the previous 1360. We also found at least 88 previously unknown deep-moonquake nests. The question was whether any of these newly discovered nets were on the far side of the Moon, and we now report that our analysis of the data indicates that some of them are indeed on the far side.

  10. 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.

  11. 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.

  12. Commentary: discovering a different model of medical student education.

    Science.gov (United States)

    Watson, Robert T

    2012-12-01

    Traditional medical schools in modern academic health centers make discoveries, create new knowledge and technology, provide innovative care to the sickest patients, and educate future academic and practicing physicians. Unfortunately, the growth of the research and clinical care missions has sometimes resulted in a loss of emphasis on the general professional education of medical students. The author concludes that it may not be practical for many established medical schools to functionally return to the reason they were created: for the education of medical students.He had the opportunity to discover a different model of medical student education at the first new MD-granting medical school created in the United States in 25 years (in 2000), the Florida State University College of Medicine. He was initially skeptical about how its distributed regional campuses model, using practicing primary care physicians to help medical students learn in mainly ambulatory settings, could be effective. But his experience as a faculty member at the school convinced him that the model works very well.He proposes a better alignment of form and function for many established medical schools and an extension of the regional community-based model to the formation of community-based primary care graduate medical education programs determined by physician workforce needs and available resources.

  13. 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.

  14. Systematic Serendipity: A Method to Discover the Anomalous

    Science.gov (United States)

    Giles, Daniel; Walkowicz, Lucianne

    2018-01-01

    One of the challenges in the era of big data astronomical surveys is identifying anomalous data, data that exhibits as-of-yet unobserved behavior. These data may result from systematic errors, extreme (or rare) forms of known phenomena, or, most interestingly, truly novel phenomena that has historically required a trained eye and often fortuitous circumstance to identify. We describe a method that uses machine clustering techniques to discover anomalous data in Kepler lightcurves, as a step towards systematizing the detection of novel phenomena in the era of LSST. As a proof of concept, we apply our anomaly detection method to Kepler data including Boyajian's Star (KIC 8462852). We examine quarters 4, 8, 11, and 16 of the Kepler data which contain Boyajian’s Star acting normally (quarters 4 and 11) and anomalously (quarters 8 and 16). We demonstrate that our method is capable of identifying Boyajian’s Star’s anomalous behavior in quarters of interest, and we further identify other anomalous light curves that exhibit a range of interesting variability.

  15. 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.

  16. Discovering EEG resting state alterations of semantic dementia.

    Science.gov (United States)

    Grieder, Matthias; Koenig, Thomas; Kinoshita, Toshihiko; Utsunomiya, Keita; Wahlund, Lars-Olof; Dierks, Thomas; Nishida, Keiichiro

    2016-05-01

    Diagnosis of semantic dementia relies on cost-intensive MRI or PET, although resting EEG markers of other dementias have been reported. Yet the view still holds that resting EEG in patients with semantic dementia is normal. However, studies using increasingly sophisticated EEG analysis methods have demonstrated that slightest alterations of functional brain states can be detected. We analyzed the common four resting EEG microstates (A, B, C, and D) of 8 patients with semantic dementia in comparison with 8 healthy controls and 8 patients with Alzheimer's disease. Topographical differences between the groups were found in microstate classes B and C, while microstate classes A and D were comparable. The data showed that the semantic dementia group had a peculiar microstate E, but the commonly found microstate C was lacking. Furthermore, the presence of microstate E was significantly correlated with lower MMSE and language scores. Alterations in resting EEG can be found in semantic dementia. Topographical shifts in microstate C might be related to semantic memory deficits. This is the first study that discovered resting state EEG abnormality in semantic dementia. The notion that resting EEG in this dementia subtype is normal has to be revised. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Saw, M.M.

    2007-01-01

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  18. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  19. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    Whittaker, Peter A.

    2005-01-01

    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

  20. Therapeutic cloning in the mouse

    Science.gov (United States)

    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 derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  1. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  2. Dental therapeutic systems.

    Science.gov (United States)

    Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in

  3. PALFA Discovers Neutron Stars on a Collision Course

    Science.gov (United States)

    Kohler, Susanna

    2018-03-01

    Got any plans in 46 million years? If not, you should keep an eye out for PSR J1946+2052 around that time this upcoming merger of two neutron stars promises to be an exciting show!Survey SuccessAverage profile for PSR J1946+2052 at 1.43 GHz from a 2 hr observation from the Arecibo Observatory. [Stovall et al. 2018]It seems like we just wrote about the dearth of known double-neutron-star systems, and about how new surveys are doing their best to find more of these compact binaries. Observing these systems improves our knowledge of how pairs of evolved stars behave before they eventually spiral in, merge, and emit gravitational waves that detectors like the Laser Interferometer Gravitational-wave Observatory might observe.Todays study, led by Kevin Stovall (National Radio Astronomy Observatory), goes to show that these surveys are doing a great job so far! Yet another double-neutron-star binary, PSR J1946+2052, has now been discovered as part of the Arecibo L-Band Feed Array pulsar (PALFA) survey. This one is especially unique due to the incredible speed with which these neutron stars orbit each other and their correspondingly (relatively!) short timescale for merger.An Extreme ExampleThe PALFA survey, conducted with the enormous 305-meter radio dish at Arecibo, has thus far resulted in the discovery of 180 pulsars including two double-neutron-star systems. The most recent discovery by Stovall and collaborators brings that number up to three, for a grand total of 16 binary-neutron-star systems (confirmed and unconfirmed) known to date.The 305-m Arecibo Radio Telescope, built into the landscape at Arecibo, Puerto Rico. [NOAO/AURA/NSF/H. Schweiker/WIYN]The newest binary in this collection, PSR J1946+2052, exhibits a pulsar with a 17-millisecond spin period thatwhips around its compact companion at a terrifying rate: the binary period is just 1.88 hours. Follow-up observations with the Jansky Very Large Array and other telescopes allowed the team to identify the binarys

  4. 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

  5. Discovering significant evolution patterns from satellite image time series.

    Science.gov (United States)

    Petitjean, François; Masseglia, Florent; Gançarski, Pierre; Forestier, Germain

    2011-12-01

    Satellite Image Time Series (SITS) provide us with precious information on land cover evolution. By studying these series of images we can both understand the changes of specific areas and discover global phenomena that spread over larger areas. Changes that can occur throughout the sensing time can spread over very long periods and may have different start time and end time depending on the location, which complicates the mining and the analysis of series of images. This work focuses on frequent sequential pattern mining (FSPM) methods, since this family of methods fits the above-mentioned issues. This family of methods consists of finding the most frequent evolution behaviors, and is actually able to extract long-term changes as well as short term ones, whenever the change may start and end. However, applying FSPM methods to SITS implies confronting two main challenges, related to the characteristics of SITS and the domain's constraints. First, satellite images associate multiple measures with a single pixel (the radiometric levels of different wavelengths corresponding to infra-red, red, etc.), which makes the search space multi-dimensional and thus requires specific mining algorithms. Furthermore, the non evolving regions, which are the vast majority and overwhelm the evolving ones, challenge the discovery of these patterns. We propose a SITS mining framework that enables discovery of these patterns despite these constraints and characteristics. Our proposal is inspired from FSPM and provides a relevant visualization principle. Experiments carried out on 35 images sensed over 20 years show the proposed approach makes it possible to extract relevant evolution behaviors.

  6. A DISK MIRROR RECENTLY DISCOVERED SOUTH THE LOWER MUREȘ

    Directory of Open Access Journals (Sweden)

    Vitalie Bârcă

    2016-11-01

    Full Text Available The object of this study is the analysis of the disk mirror discovered in 2010 during the rescue archaeological excavations carried out in occasion of the construction of the Arad-Timişoara motorway, respectively the Arad-Seceani sector. The mirror was found at  ca. 1 m north grave 1 in site B0_6, where beside other two cremation graves, poorly preserved, other 129 archaeological features were also investigated.Though not exhaustively, we attempt herein to present the origin, distribution of this mirror type in the Sarmatian world and the chronological interval of their use within said environment.The author notes that these disk mirror types from the funerary Sarmatian features of the Great Hungarian Plain count amongst the most numerous, being found within funerary contexts on the entire duration of the Sarmatian inhabitancy of this geographical area. Further, the author notes that mirrors of the type are widely spread on broad geographical areas, hence the establishment of any production centres is highly difficult, but also that very likely, they were produced in various cultural environments over several centuries. Their high numbers in the Sarmatian world proves it is possible they made them, although there is no certain substantiating evidence. The author does not exclude either the possibility of the presence of travelling artisans in the Sarmatian environment making certain item categories upon order, mirrors of the type included.In terms of the dating of G 1 at Arad (site B_06, where the mirror most definitely originates, the author concludes that together with the other two graves (G 2 and G 3 are contemporary and date sometime to the end of the 2nd century – early decades of the 3rd century AD.

  7. Discovering Higgs Bosons of the MSSM using Jet Substructure

    International Nuclear Information System (INIS)

    Kribs, Graham D.; Martin, Adam; Roy, Tuhin S.; Spannowsky, Michael

    2010-01-01

    We present a qualitatively new approach to discover Higgs bosons of the MSSM at the LHC using jet substructure techniques applied to boosted Higgs decays. These techniques are ideally suited to the MSSM, since the lightest Higgs boson overwhelmingly decays to b(bar b) throughout the entire parameter space, while the heavier neutral Higgs bosons, if light enough to be produced in a cascade, also predominantly decay to b(bar b). The Higgs production we consider arises from superpartner production where superpartners cascade decay into Higgs bosons. We study this mode of Higgs production for several superpartner hierarchies: m # tilde q#,m # tilde g# > m # tilde W#, # tilde B# > m h + μ; m(tilde q);m # tilde q#,m # tilde g# > m # tilde W#, # tilde B# > m h,H,A + μ; and m # tilde q#,m # tilde g# > m # tilde W# > m h + μ with m # tilde B# ∼ μ. In these cascades, the Higgs bosons are boosted, with pT > 200 GeV a large fraction of the time. Since Higgs bosons appear in cascades originating from squarks and/or gluinos, the cross section for events with at least one Higgs boson can be the same order as squark/gluino production. Given 10 fb -1 of 14 TeV LHC data, with m # tilde q# ∼< 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S√ B of the Higgs signal is sufficiently high that the b(bar b) mode can become the discovery mode of the lightest Higgs boson of the MSSM.

  8. Discovering Higgs bosons of the MSSM using jet substructure

    International Nuclear Information System (INIS)

    Kribs, Graham D.; Roy, Tuhin S.; Spannowsky, Michael; Martin, Adam

    2010-01-01

    We present a qualitatively new approach to discover Higgs bosons of the minimal supersymmetric standard model (MSSM) at the LHC using jet substructure techniques applied to boosted Higgs decays. These techniques are ideally suited to the MSSM, since the lightest Higgs boson overwhelmingly decays to bb throughout the entire parameter space, while the heavier neutral Higgs bosons, if light enough to be produced in a cascade, also predominantly decay to bb. The Higgs production we consider arises from superpartner production where superpartners cascade decay into Higgs bosons. We study this mode of Higgs production for several superpartner hierarchies: m q -tilde, m g -tilde>m W -tilde ,B -tilde>m h +μ; m q -tilde, m g -tilde>m W -tilde ,B -tilde>m h,H,A +μ; and m q -tilde, m g -tilde>m W -tilde>m h +μ with m B -tilde≅μ. In these cascades, the Higgs bosons are boosted, with p T >200 GeV a large fraction of the time. Since Higgses appear in cascades originating from squarks and/or gluinos, the cross section for events with at least one Higgs can be the same order as squark/gluino production. Given 10 fb -1 of 14 TeV LHC data, with m q -tilde < or approx. 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S/√(B) of the Higgs signal is sufficiently high that the bb mode can become the discovery mode of the lightest Higgs boson of the MSSM.

  9. Feature-based morphometry: discovering group-related anatomical patterns.

    Science.gov (United States)

    Toews, Matthew; Wells, William; Collins, D Louis; Arbel, Tal

    2010-02-01

    This paper presents feature-based morphometry (FBM), a new fully data-driven technique for discovering patterns of group-related anatomical structure in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between subjects, FBM explicitly aims to identify distinctive anatomical patterns that may only be present in subsets of subjects, due to disease or anatomical variability. The image is modeled as a collage of generic, localized image features that need not be present in all subjects. Scale-space theory is applied to analyze image features at the characteristic scale of underlying anatomical structures, instead of at arbitrary scales such as global or voxel-level. A probabilistic model describes features in terms of their appearance, geometry, and relationship to subject groups, and is automatically learned from a set of subject images and group labels. Features resulting from learning correspond to group-related anatomical structures that can potentially be used as image biomarkers of disease or as a basis for computer-aided diagnosis. The relationship between features and groups is quantified by the likelihood of feature occurrence within a specific group vs. the rest of the population, and feature significance is quantified in terms of the false discovery rate. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer's (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and an equal error classification rate of 0.80 is achieved for subjects aged 60-80 years exhibiting mild AD (CDR=1). Copyright (c) 2009 Elsevier Inc. All rights reserved.

  10. Therapeutic Inertia and Treatment Intensification.

    Science.gov (United States)

    Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

    2018-01-29

    This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

  11. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  12. Homology modeling and virtual screening to discover potent inhibitors targeting the imidazole glycerophosphate dehydratase protein in Staphylococcus xylosus

    Science.gov (United States)

    Chen, Xing-Ru; Wang, Xiao-Ting; Hao, Mei-Qi; Zhou, Yong-Hui; Cui, Wen-Qiang; Xing, Xiao-Xu; Xu, Chang-Geng; Bai, Jing-Wen; Li, Yan-Hua

    2017-11-01

    The imidazole glycerophosphate dehydratase (IGPD) protein is a therapeutic target for herbicide discovery. It is also regarded as a possible target in Staphylococcus xylosus (S. xylosus) for solving mastitis in the dairy cow. The 3D structure of IGPD protein is essential for discovering novel inhibitors during high-throughput virtual screening. However, to date, the 3D structure of IGPD protein of S. xylosus has not been solved. In this study, a series of computational techniques including homology modeling, Ramachandran Plots, and Verify 3D were performed in order to construct an appropriate 3D model of IGPD protein of S. xylosus. Nine hits were identified from 2500 compounds by docking studies. Then, these 9 compounds were first tested in vitro in S. xylosus biofilm formation using crystal violet staining. One of the potential compounds, baicalin was shown to significantly inhibit S. xylosus biofilm formation. Finally, the baicalin was further evaluated, which showed better inhibition of biofilm formation capability in S. xylosus by scanning electron microscopy. Hence, we have predicted the structure of IGPD protein of S. xylosus using computational techniques. We further discovered the IGPD protein was targeted by baicalin compound which inhibited the biofilm formation in S. xylosus. Our findings here would provide implications for the further development of novel IGPD inhibitors for the treatment of dairy mastitis.

  13. Targeting hepatocellular carcinoma: what did we discover so far?

    Directory of Open Access Journals (Sweden)

    Ana Filipa Brito

    2016-10-01

    Full Text Available Hepatocellular carcinoma (HCC is increasingly considered an issue of global importance. Its rates of incidence and mortality have been markedly increasing over the last decades. Among risk factors, some should be highlighted, namely the infections by hepatitis B and C virus, as well as clinical cases of cirrhosis. HCC is characterized as asymptomatic disease in the initial stages which most often leads to a late diagnosis. At molecular and genetic level HCC represents a highly complex tumor entity, including a wide variety of mutations, thus accounting for different mechanisms of resistance towards therapeutic approaches. In particular, mutations of the TP53 gene, as well as a deregulation between the expression of pro- and anti-apoptotic proteins of the BCL-2 family are observed. Regarding treatment modalities, surgical procedures offer the best chance of cure, however, due to a late diagnosis, most of concerned patients cannot be subjected to them. Chemotherapy and radiotherapy are also ineffective, and currently, the treatment with sorafenib is the most commonly used systemic therapy although it can only increase the patient survival for some months. In this sense, a quick and accurate investigation is of utmost importance in order to develop ways of early diagnosis as well as new therapies for HCC.

  14. 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.

  15. The therapeutic potential of cannabis and cannabinoids.

    Science.gov (United States)

    Grotenhermen, Franjo; Müller-Vahl, Kirsten

    2012-07-01

    Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany. Selective literature review. Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.

  16. 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.

  17. Data-driven analysis of biomedical literature suggests broad-spectrum benevolence of culinary herbs and spices

    OpenAIRE

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

    2018-01-01

    Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empiri...

  18. Aleutian Array of Arrays (A-cubed) to probe a broad spectrum of fault slip under the Aleutian Islands

    Science.gov (United States)

    Ghosh, A.; LI, B.

    2016-12-01

    Alaska-Aleutian subduction zone is one of the most seismically active subduction zones in this planet. It is characterized by remarkable along-strike variations in seismic behavior, more than 50 active volcanoes, and presents a unique opportunity to serve as a natural laboratory to study subduction zone processes including fault dynamics. Yet details of the seismicity pattern, spatiotemporal distribution of slow earthquakes, nature of interaction between slow and fast earthquakes and their implication on the tectonic behavior remain unknown. We use a hybrid seismic network approach and install 3 mini seismic arrays and 5 stand-alone stations to simultaneously image subduction fault and nearby volcanic system (Makushin). The arrays and stations are strategically located in the Unalaska Island, where prolific tremor activity is detected and located by a solo pilot array in summer 2012. The hybrid network is operational between summer 2015 and 2016 in continuous mode. One of the three arrays starts in summer 2014 and provides additional data covering a longer time span. The pilot array in the Akutan Island recorded continuous seismic data for 2 months. An automatic beam-backprojection analysis detects almost daily tremor activity, with an average of more than an hour per day. We imaged two active sources separated by a tremor gap. The western source, right under the Unalaska Island shows the most prolific activity with a hint of steady migration. In addition, we are able to identify more than 10 families of low frequency earthquakes (LFEs) in this area. They are located within the tremor source area as imaged by the bean-backprojection technique. Application of a match filter technique reveals that intervals between LFE activities are shorter during tremor activity and longer during quiet time period. We expect to present new results from freshly obtained data. The experiment A-cubed is illuminating subduction zone processes under Unalaska Island in unprecedented detail.

  19. Genetically pyramiding protease-inhibitor genes for dual broad-spectrum resistance against insect and phytopathogens in transgenic tobacco.

    Science.gov (United States)

    Senthilkumar, Rajendran; Cheng, Chiu-Ping; Yeh, Kai-Wun

    2010-01-01

    Protease inhibitors provide a promising means of engineering plant resistance against attack by insects and pathogens. Sporamin (trypsin inhibitor) from sweet potato and CeCPI (phytocystatin) from taro were stacked in a binary vector, using pMSPOA (a modified sporamin promoter) to drive both genes. Transgenic tobacco lines of T0 and T1 generation with varied inhibitory activity against trypsin and papain showed resistance to both insects and phytopathogens. Larvae of Helicoverpa armigera that ingested tobacco leaves either died or showed delayed growth and development relative to control larvae. Transgenic tobacco-overexpressing the stacked genes also exhibited strong resistance against bacterial soft rot disease caused by Erwinia carotovora and damping-off disease caused by Pythium aphanidermatum. Thus, stacking protease-inhibitor genes, driven by the wound and pathogen responsive pMSPOA promoter, is an effective strategy for engineering crops to resistance against insects and phytopathogens.

  20. TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Hanaki, H; Akagi, H; Masaru, Y; Otani, T; Hyodo, A; Hiramatsu, K

    1995-01-01

    TOC-39, a new parenteral cephalosporin, is a hydroxyimino-type cephem antibiotic with vinylthio-pyridyl moiety at the 3 position. TOC-39 was evaluated for antibacterial activity against various clinically isolated strains. TOC-39 had excellent activity, stronger than that of methicillin, oxacillin, the cephalosporins tested, imipenem, gentamicin, minocycline, tobramycin, ofloxacin, and ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and had an MIC comparable to that of vancomycin (the MICs of TOC-39 and vancomycin for 90% of the strains tested were 3.13 and 1.56 micrograms/ml, respectively). Against Enterococcus faecalis strains, which are resistant to cephalosporins, TOC-39 was twice as active as ampicillin. Against methicillin-susceptible S. aureus, coagulase-negative Staphylococcus spp., and Streptococcus pneumoniae, TOC-39 was twice as active as or more active than cefotiam, ceftazidime, flomoxef, and cefpirome. Against Streptococcus pyogenes, TOC-39 was superior to cefotiam, ceftazidime, and flomoxef and was similar to cefpirome. In addition, the activity of TOC-39 was equal to or greater than that of cefotiam, ceftazidime, flomoxef, and cefpirome against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii. In terms of bactericidal effect against MRSA, TOC-39 was superior to vancomycin. No mutant resistant to TOC-39 or vancomycin was obtained from susceptible MRSA strains. In murine systemic infection models, TOC-39 showed potent activity against S. aureus and E. coli. Against highly MRSA, the activity of TOC-39 was comparable to that of vancomycin. PMID:7625799

  1. 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

  2. 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

    ... Systems and methods for collecting particles from a large volume of gas into a small volume of liquid... semiconductor laser systems and methods. Nguyen 7,796,829 Method and system for forming an image with enhanced...

  3. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint.

  4. A sensitive whole-cell biosensor for the simultaneous detection of a broad-spectrum of toxic heavy metal ions.

    Science.gov (United States)

    Cerminati, S; Soncini, F C; Checa, S K

    2015-04-07

    Bacterial biosensors are simple, cost-effective and efficient analytical tools for detecting bioavailable heavy metals in the environment. This work presents the design, construction and calibration of a novel whole-cell fluorescent biosensory device that, simultaneously and with high sensitivity, reports the presence of toxic mercury, lead, cadmium and/or gold ions in aqueous samples. This bio-reporter can be easily applied as an immediate alerting tool for detecting the presence of harmful pollutants in drinking water.

  5. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.

    Science.gov (United States)

    Taylor, Raymond; Kotian, Pravin; Warren, Travis; Panchal, Rekha; Bavari, Sina; Julander, Justin; Dobo, Sylvia; Rose, Angela; El-Kattan, Yahya; Taubenheim, Brian; Babu, Yarlagadda; Sheridan, William P

    2016-01-01

    The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

  6. Chromosome-Encoded Broad-Spectrum Ambler Class A β-Lactamase RUB-1 from Serratia rubidaea.

    Science.gov (United States)

    Bonnin, Rémy A; Didi, Jennifer; Ergani, Ayla; Lima, Sandra; Naas, Thierry

    2017-02-01

    Whole-genome sequencing of Serratia rubidaea CIP 103234 T revealed a chromosomally located Ambler class A β-lactamase gene. The gene was cloned, and the β-lactamase, RUB-1, was characterized. RUB-1 displayed 74% and 73% amino acid sequence identity with the GIL-1 and TEM-1 penicillinases, respectively, and its substrate profile was similar to that of the latter β-lactamases. Analysis by 5' rapid amplification of cDNA ends revealed promoter sequences highly divergent from the Escherichia coli σ 70 consensus sequence. This work further illustrates the heterogeneity of β-lactamases among Serratia spp. Copyright © 2017 American Society for Microbiology.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    this period and the spontaneous temperature after course in control rats established in other experiments was imitated. Seven days later histological brain sections were prepared and the infarct volumes measured. Body temperature did not differ between the groups. Mean arterial blood pressure was slightly...... higher in the pinokalant group. Pinokalant treatment significantly reduced cortical infarct volume from 33.8+/-15.8 mm3 to 24.5+/-13.1 mm3 (control group versus pinokalant group, P=0.017, t-test). Taking the effective drug plasma concentration established in other experiments into account revealed...... and electrophysiologic status of the ischemic penumbra and to reduce lesion size on magnetic resonance images in the acute phase following middle cerebral artery occlusion in rats. The purpose of the present study was to investigate whether these beneficial effects of pinokalant are translated into permanent...

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

    International Nuclear Information System (INIS)

    Al Meslmani, Bassam M.; Mahmoud, Gihan F.; Leichtweiß, Thomas; Strehlow, Boris; Sommer, Frank O.; Lohoff, Michael D.; Bakowsky, Udo

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-01

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

  11. Transgenic rice expressing a codon-modified synthetic CP4-EPSPS confers tolerance to broad-spectrum herbicide, glyphosate.

    Science.gov (United States)

    Chhapekar, Sushil; Raghavendrarao, Sanagala; Pavan, Gadamchetty; Ramakrishna, Chopperla; Singh, Vivek Kumar; Phanindra, Mullapudi Lakshmi Venkata; Dhandapani, Gurusamy; Sreevathsa, Rohini; Ananda Kumar, Polumetla

    2015-05-01

    Highly tolerant herbicide-resistant transgenic rice was developed by expressing codon-modified synthetic CP4--EPSPS. The transformants could tolerate up to 1% commercial glyphosate and has the potential to be used for DSR (direct-seeded rice). Weed infestation is one of the major biotic stress factors that is responsible for yield loss in direct-seeded rice (DSR). Herbicide-resistant rice has potential to improve the efficiency of weed management under DSR. Hence, the popular indica rice cultivar IR64, was genetically modified using Agrobacterium-mediated transformation with a codon-optimized CP4-EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene, with N-terminal chloroplast targeting peptide from Petunia hybrida. Integration of the transgenes in the selected rice plants was confirmed by Southern hybridization and expression by Northern and herbicide tolerance assays. Transgenic plants showed EPSPS enzyme activity even at high concentrations of glyphosate, compared to untransformed control plants. T0, T1 and T2 lines were tested by herbicide bioassay and it was confirmed that the transgenic rice could tolerate up to 1% of commercial Roundup, which is five times more in dose used to kill weeds under field condition. All together, the transgenic rice plants developed in the present study could be used efficiently to overcome weed menace.

  12. ‪Creating a Team Culture Through the Provision of a Broad Spectrum of Educational Programs at DHS‬ [video

    OpenAIRE

    Tanner, George; Center for Homeland Defense and Security Naval Postgraduate School

    2014-01-01

    [13 Nov 2007]. In this Viewpoints interview Dr. George Tanner talks about the educational mission of the Department of Homeland Security's Office of the Chief Learning Officer and the implementation of a comprehensive, department-wide employee learning program for all DHS employees.

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

    OpenAIRE

    Lin, Liang-Tzung; Chen, Ting-Ying; Lin, Song-Chow; Chung, Chueh-Yao; Lin, Ta-Chen; Wang, Guey-Horng; Anderson, Robert; Lin, Chun-Ching; Richardson, Christopher D

    2013-01-01

    Background We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. Results Extensive analysis of the tannins? mechanism of action was performed on a ...

  14. High Prevalence of Gut Microbiota Colonization with Broad-Spectrum Cephalosporin Resistant Enterobacteriaceae in a Tunisian Intensive Care Unit

    Science.gov (United States)

    Maamar, Elaa; Ferjani, Sana; Jendoubi, Ali; Hammami, Samia; Hamzaoui, Zaineb; Mayonnove-Coulange, Laure; Saidani, Mabrouka; Kammoun, Aouatef; Rehaiem, Amel; Ghedira, Salma; Houissa, Mohamed; Boutiba-Ben Boubaker, Ilhem; Slim, Amine; Dubois, Veronique

    2016-01-01

    Healthcare-associated infections due to cefotaxime-resistant (CTX-R) Enterobacteriaceae have become a major public health threat, especially in intensive care units (ICUs). Often acquired nosocomially, CTX-R Enterobacteriaceae can be introduced initially by patients at admission. This study aimed to determine the prevalence and genetic characteristics of CTX-R Enterobacteriaceae-intestinal carriage in ICU patients, to evaluate the rate of acquisition of these organisms during hospitalization, and to explore some of the associated risk factors for both carriage and acquisition. Between December 2014 and February 2015, the 63 patients admitted in the ICU of Charles Nicolle hospital were screened for rectal CTX-R Enterobacteriaceae colonization at admission and once weekly thereafter to identify acquisition. CTX-R Enterobacteriaceae fecal carriage rate was 20.63% (13/63) at admission. Among the 50 non-carriers, 35 were resampled during their hospitalization and the acquisition rate was 42.85% (15/35). Overall, 35 CTX-R Enterobacteriaceae isolates were collected from 28 patients (25 Klebsiella pneumoniae, seven Escherichia coli, and three Enterobacter cloacae strains). Seven patients were simultaneously colonized with two CTX-R Enterobacteriaceae isolates. CTX-M-15 was detected in most of the CTX-R Enterobacteriaceae isolates (30/35, 88.23%). Three strains co-produced CMY-4 and 22 strains were carbapenem-resistant and co-produced a carbapenemase [OXA-48 (n = 13) or NDM-1 (n = 6)]. Molecular typing of K. pneumoniae strains, revealed eight Pulsed field gel electrophoresis (PFGE) patterns and four sequence types (ST) [ST101, ST147, ST429, and ST336]. However, E. coli isolates were genetically unrelated and belonged to A (n = 2), B1 (n = 2) and B2 (n = 3) phylogenetic groups and to ST131 (two strains), ST572 (two strains), ST615 (one strain) and ST617 (one strain). Five colonized patients were infected by CTX-R Enterobacteriaceae (four with the same strain identified from their rectal swab and one with a different strain). Whether imported or acquired during the stay in the ICU, colonization by CTX-R Enterobacteriaceae is a major risk factor for the occurrence of serious nosocomial infections. Their systematic screening in fecal carriage is mandatory to prevent the spread of these multidrug resistant bacteria. PMID:27965626

  15. A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood

    OpenAIRE

    Cartwright, Mark; Rottman, Martin; Shapiro, Nathan I.; Seiler, Benjamin; Lombardo, Patrick; Gamini, Nazita; Tomolonis, Julie; Watters, Alexander L.; Waterhouse, Anna; Leslie, Dan; Bolgen, Dana; Graveline, Amanda; Kang, Joo H.; Didar, Tohid; Dimitrakakis, Nikolaos

    2016-01-01

    Background: Blood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis. Methods: An Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, contai...

  16. A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood.

    Science.gov (United States)

    Cartwright, Mark; Rottman, Martin; Shapiro, Nathan I; Seiler, Benjamin; Lombardo, Patrick; Gamini, Nazita; Tomolonis, Julie; Watters, Alexander L; Waterhouse, Anna; Leslie, Dan; Bolgen, Dana; Graveline, Amanda; Kang, Joo H; Didar, Tohid; Dimitrakakis, Nikolaos; Cartwright, David; Super, Michael; Ingber, Donald E

    2016-07-01

    Blood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis. An Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries. The FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (animals, even when blood cultures were negative and bacteriocidal antibiotics were administered. In patients with suspected sepsis, the FcMBL ELLecSA detected infection in 55 of 67 patients with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein. The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs in Whole Blood

    Directory of Open Access Journals (Sweden)

    Mark Cartwright

    2016-07-01

    Conclusion: The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    Members of the Bacteroides fragilis group are opportunistic pathogens and cause severe infections including bacteraemia. As increased levels of antimicrobial resistance in B. fragilis group bacteria can be detected years after administration of specific antibiotics, monitoring antimicrobial...... susceptibility in the gut microbiota could be important. The objectives of this study were to 1) investigate the distribution of species and the occurrence of reduced antimicrobial susceptibility in the B. fragilis group from patients treated at departments with a high level of antibiotic use, 2) to determine...... the prevalence of the carbapenem resistance gene cfiA in B. fragilis in this patient group, and 3) to determine the association between previous antibiotic treatment and reduced susceptibility to clindamycin, meropenem, metronidazole, and piperacillin-tazobactam. Consecutive faecal samples (n = 197) were...

  19. Characterization of d-boroAla as a Novel Broad Spectrum Antibacterial Agent Targeting d-Ala-d-Ala Ligase

    OpenAIRE

    Putty, Sandeep; Rai, Aman; Jamindar, Darshan; Pagano, Paul; Quinn, Cheryl L.; Mima, Takehiko; Schweizer, Herbert P.; Gutheil, William G.

    2011-01-01

    d-boroAla was previously characterized as an inhibitor of bacterial alanine racemase and d-Ala-d-Ala ligase enzymes [Duncan, K., et al Biochemistry 1989, 28:3541–9]. In the present study, d-boroAla was identified and characterized as an antibacterial agent. d-boroAla has activity against both Gram-positive and Gram-negative organisms, with MICs down to 8 µg/mL. A structure-function study on the alkyl side chain (NH2-CHR-B(OR’)2) revealed that d-boroAla is the most effective agent in a series ...

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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. - 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.

  1. Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy.

    Science.gov (United States)

    Mason, Katie L; Erb Downward, John R; Mason, Kelly D; Falkowski, Nicole R; Eaton, Kathryn A; Kao, John Y; Young, Vincent B; Huffnagle, Gary B

    2012-10-01

    Candida albicans is a normal member of the gastrointestinal (GI) tract microbiota of healthy humans, but during host immunosuppression or alterations in the bacterial microbiota, C. albicans can disseminate and cause life-threatening illness. The bacterial microbiome of the GI tract, including lactic acid bacteria (LAB), plays a vital role in preventing fungal invasion. However, little is known about the role of C. albicans in shaping the bacterial microbiota during antibiotic recovery. We investigated the fungal burdens in the GI tracts of germfree mice and mice with a disturbed microbiome to demonstrate the role of the microbiota in preventing C. albicans colonization. Histological analysis demonstrated that colonization with C. albicans during antibiotic treatment does not trigger overt inflammation in the murine cecum. Bacterial diversity is reduced long term following cefoperazone treatment, but the presence of C. albicans during antibiotic recovery promoted the recovery of bacterial diversity. Cefoperazone diminishes Bacteroidetes populations long term in the ceca of mice, but the presence of C. albicans during cefoperazone recovery promoted Bacteroidetes population recovery. However, the presence of C. albicans resulted in a long-term reduction in Lactobacillus spp. and promoted Enterococcus faecalis populations. Previous studies have focused on the ability of bacteria to alter C. albicans; this study addresses the ability of C. albicans to alter the bacterial microbiota during nonpathogenic colonization.

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

    Science.gov (United States)

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

    2009-02-01

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

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

    KAUST Repository

    Khan, Mohammed Zahed Mustafa

    2013-03-01

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

  4. PRODUCT NEEM AZAL T/S - BROAD-SPECTRUM PHYPOPESTICIDE FOR CONTROL OF PESTS ON VEGETABLE CROPS

    Directory of Open Access Journals (Sweden)

    Vinelina Yankova

    2016-09-01

    Full Text Available Experiments for determination of the effectiveness of product Neem Azal T/S (a. i. azadirachtin were conducted at a concentration of 0,3% against some major pests in vegetable crops grown in greenhouses at the Maritsa Vegetable Crops research Institute, Plovdiv during the period 2010-2016. It was established very good insecticidal and acaricidal action of phytopesticide against: cotton aphid (Aphis gossypii Glov.; green peach aphid (Myzus persicae Sulz.; western flower trips (Frankliniella occidentalis Perg.; cotton bollworm (Helicoverpa armigera Hubn.; tomato borer (Tuta absoluta Meyrick and two-spotted spider mite (Tetranichus urticae Koch.. This product is a successful alternative to using chemical insecticides and acaricides.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    middle-aged women were separated into a soccer training group (n=19; SOC) and a control group (n=12; CON). SOC performed 128±29 (±SD) one-h small-sided soccer training sessions over one year. Blood pressure, body composition, blood lipid profile, and fitness level were determined pre- and post......The study tested the hypothesis that long-term soccer training has positive impact on cardiovascular profile, body composition, bone health, and physical capacity in inactive, pre-menopausal women with mild hypertension. The study applied a randomized controlled design in which physically inactive.......2±0.2 mmol·L(-1) ) and HDL cholesterol increased more (0.2±0.7 vs -0.2±0.2 mmol·L(-1) ) in SOC than in CON (Ptraining resulted...

  6. Combining carbon footprinting, monitoring, feedback, and rewards for a broad spectrum reduction of household induced greenhouse gas emissions

    Energy Technology Data Exchange (ETDEWEB)

    Perrels, Adriaan (Government Institute for Economic Research VATT (Finland)); Hongisto, Mikko; Kallio, Arto (VTT Technical Research Centre of Finland (Finland)); Hyvoenen, Kaarina (National Consumer Research Centre KTK (Finland)); Katajajuuri, Juha-Matti (MTT Agrifood Research Finland (Finland)); Nissinen, Ari (Finnish Environment Institute SYKE (Finland))

    2009-07-01

    The study reported in this article (named CLIMATE BONUS) concerns the combined use of verified carbon footprints (possibly visualised through labels), personalised monitoring and feedback services to households regarding the greenhouse gas intensities of their purchases, and a reward system (bonuses) for consumers who manage to reduce the embodied emissions. The study assesses the accuracy and verification requirements and the harmonisation needs for the various information systems and their interfaces. This should culminate in a data strategy, in which a data acquisition, generation and co-ordination strategy and a data quality assurance strategy will be developed. Equally important, the study also assesses, via an own pilot, what the response of households (as consumers) can amount to and how the responsiveness to various incentives can be rated. The paper provides an outline of the intended system, including its rationale. Subsequently, the paper focuses on the consumer pilot and the feedback from the participants. It also provides a brief impression of the expected overall economic effectiveness of the system.

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

    International Nuclear Information System (INIS)

    Alfonso, A.A.; Avellanoza, E.S.; Miranda, R.T.; Espejo, E.O.; Garcia, N.S.

    2014-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Syed Baker

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-04-23

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

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

    KAUST Repository

    Khan, Mohammed Zahed Mustafa; Bhattacharya, Pallab K.; Lee, Chi-Sen; Ng, Tien Khee; Ooi, Boon S.

    2013-01-01

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

  11. A broad spectrum catalytic system for removal of toxic organics from water by deep oxidation. 1998 annual progress report

    International Nuclear Information System (INIS)

    Sen, A.

    1998-01-01

    'Toxic organics and polymers pose a serious threat to the environment, especially when they are present in aquatic systems. The objective of the research is the design of practical procedures for the removal and/or recycling of such pollutants by oxidation. This report summarizes the work performed in the first one and half years of a three year project. The authors had earlier described a catalytic system for the deep oxidation of toxic organics, such as benzene, phenol and substituted phenols, aliphatic and aromatic halogenated compounds, organophosphorus, and organosulfur compounds [1]. In this system, metallic palladium was found to catalyze the oxidation of the substrate by dioxygen in aqueous medium at 80--100 C in the presence of carbon monoxide. For all the substrates examined, deep oxidation to carbon monoxide, carbon dioxide, and water occurred in high yields, resulting in up to several hundred turnovers over a 24 h period. Because of a pressing need for new procedures for the destruction of chemical warfare agents, the authors have examined in detail the deep oxidation of appropriate model compounds containing phosphorus-carbon and sulfur-carbon bonds using the same catalytic system. The result is the first observation of the efficient catalytic oxidative cleavage of phosphorus-carbon and sulfur-carbon bonds under mild conditions, using dioxygen as the oxidant [2]. In addition to the achievements described above, they have unpublished results in several other areas. For example, they have investigated the possibility of using dihydrogen rather than carbon monoxide as a coreductant in the catalytic deep oxidation of substrates. Even more attractive from a practical standpoint is the possibility of using a mixture of carbon monoxide and dihydrogen (synthesis gas). Indeed, experiments indicated that it is possible to substitute carbon monoxide by dihydrogen or synthesis gas. Significantly, in the case of nitro compounds, the deep oxidation in fact proceeded faster when dihydrogen rather than carbon monoxide was the coreductant. Finally, they have achieved the oxidative degradation and chemical recycling of a wide range of polymeric materials under relatively mild conditions using nitrogen oxides and dioxygen [3]. With the production of polymeric materials on the rise and landfill space at a premium, it becomes increasingly important to develop new techniques for reducing the amount of material lost to the landfill. While some condensation polymers are chemically recycled, there is very little, if any, recycling of addition polymers which constitute 75% by weight of all polymers manufactured. Using the procedure, a wide variety of addition and condensation polymers can be oxidatively degraded. In the particular cases of polystyrene, high and low density polyethylene and, perhaps, polypropylene useful organics are produced in moderate to good yields.'

  12. Broad-Spectrum Liquid- and Gas-Phase Decontamination of Chemical Warfare Agents by One-Dimensional Heteropolyniobates.

    Science.gov (United States)

    Guo, Weiwei; Lv, Hongjin; Sullivan, Kevin P; Gordon, Wesley O; Balboa, Alex; Wagner, George W; Musaev, Djamaladdin G; Bacsa, John; Hill, Craig L

    2016-06-20

    A wide range of chemical warfare agents and their simulants are catalytically decontaminated by a new one-dimensional polymeric polyniobate (P-PONb), K12 [Ti2 O2 ][GeNb12 O40 ]⋅19 H2 O (KGeNb) under mild conditions and in the dark. Uniquely, KGeNb facilitates hydrolysis of nerve agents Sarin (GB) and Soman (GD) (and their less reactive simulants, dimethyl methylphosphonate (DMMP)) as well as mustard (HD) in both liquid and gas phases at ambient temperature and in the absence of neutralizing bases or illumination. Three lines of evidence establish that KGeNb removes DMMP, and thus likely GB/GD, by general base catalysis: a) the k(H2 O)/k(D2 O) solvent isotope effect is 1.4; b) the rate law (hydrolysis at the same pH depends on the amount of P-PONb present); and c) hydroxide is far less active against the above simulants at the same pH than the P-PONbs themselves, a critical control experiment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes

    DEFF Research Database (Denmark)

    Andreasen, Laura; Ahlberg, Gustav; Tang, Chuyi

    2018-01-01

    Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of st...

  14. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group.

    Science.gov (United States)

    Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

    2001-03-31

    Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue. 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis. Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability. However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis. A follow-up study of childhood development and disability after pPROM is planned.

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

    Directory of Open Access Journals (Sweden)

    Rahul Subramanian

    2016-12-01

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

  16. 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,

  17. Human Factor in Therapeutic Relationship

    Directory of Open Access Journals (Sweden)

    Ramazan Akdogan

    2011-03-01

    Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

  18. Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry

    Science.gov (United States)

    Peng, Fang; Li, Jianglin; Guo, Tianyao; Yang, Haiyan; Li, Maoyu; Sang, Shushan; Li, Xuejun; Desiderio, Dominic M.; Zhan, Xianquan

    2015-12-01

    Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-β-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of β-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the

  19. [End therapeutic nihilism towards COPD].

    Science.gov (United States)

    Juergens, Uwe R

    2007-03-15

    Prevention of COPD requires appropriate patient education, especially of adolescents, as well as the establishment of an effective national health policy. The new GOLD guidelines represent the current standard of knowledge on the management of chronic, progressive, obstructive pulmonary diseases. It points out that COPD is avoidable and treatable,and hence, there is no reason for therapeutic nihilism. Chronic bronchitis preceding a progressive respiratory obstruction cannot be improved with the presently available respiratory therapeutics. For this reason, therapeutic measures concentrate on the avoidance of exacerbations, which are primarily responsible for the severity of the course of COPD.

  20. Frontiers in nano-therapeutics

    CERN Document Server

    Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

    2017-01-01

    This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

  1. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  2. Planetary dreams : the quest to discover life beyond earth

    Science.gov (United States)

    Shapiro, Robert

    1999-03-01

    The Quest To Discover Life Beyond Earth. "The 'dreams' that I write of are not the usual ones, the images that come up in our minds involuntarily during certain stages of sleep, but rather the hopes and expectations that we have lavished upon other worlds around us."-from the Preface. The surprisingly long history of debate over extraterrestrial life is full of marvelous visions of what life "out there" might be like, as well as remarkable stories of alleged sightings and heated disputes about the probability that life might actually have arisen more than once. In Planetary Dreams, acclaimed author Robert Shapiro explores this rich history of dreams and debates in search of the best current answers to the most elusive and compelling of all questions: Are we alone? In his pursuit, he presents three contrasting views regarding how life might have started: through Divine Creation, by a highly unlikely stroke of luck, or by the inevitable process of a natural law that he terms the Life Principle. We are treated to a lively fictional dinner debate among the leading proponents of these schools of thought-with the last named group arguing that life has almost surely formed in many places throughout the universe, and the others that life may well be entirely unique to our own blue planet. To set the stage for a deep exploration of the question, the author then leads us on a fantastic journey through the museum of the cosmos, an imagined building that holds models of the universe at different degrees of magnification. We then journey deep into inner space to view the astonishingly intricate life of a single cell, and learn why the origin of such a complex object from simple chemical mixtures poses one of the most profound enigmas known to science. Writing in a wonderfully entertaining style, Shapiro then reviews the competing theories about the start of life on Earth, and suggests the debate may best be settled by finding signs of life on the other worlds of our solar

  3. Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-γ: Therapeutic Implications for Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Florence Gizard

    2008-01-01

    Full Text Available Proliferation of vascular smooth muscle cells (SMCs is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR γ is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD, used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARγ is prominently upregulated during neointima formation and suppresses the proliferative response to injury of the arterial wall. Among the molecular target genes regulated by PPARγ in SMCs are genes encoding proteins involved in the regulation of cell-cycle progression, cellular senescence, and apoptosis. This inhibition of SMC proliferation is likely to contribute to the prevention of atherosclerosis and postangioplasty restenosis observed in animal models and proof-of-concept clinical studies. This review will summarize the transcriptional target genes regulated by PPARγ in SMCs and outline the therapeutic implications of PPARγ activation for the treatment and prevention of atherosclerosis and its complications.

  4. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection.

    Science.gov (United States)

    Pinto, Amelia K; Brien, James D; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V; Barrett, Alan D; Shresta, Sujan; Diamond, Michael S

    2015-09-15

    With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features

  5. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Science.gov (United States)

    Yadav, Saveg; Pandey, Shrish Kumar; Singh, Vinay Kumar; Goel, Yugal; Kumar, Ajay; Singh, Sukh Mahendra

    2017-01-01

    Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP), with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA) and propionic acid (PA), with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  6. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Directory of Open Access Journals (Sweden)

    Saveg Yadav

    Full Text Available Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP, with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA and propionic acid (PA, with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  7. Design Considerations in Therapeutic Exergaming

    OpenAIRE

    Doyle, Julie; Kelly, Daniel; Caulfield, B.

    2011-01-01

    In this paper we discuss the importance of feedback in therapeutic exergaming. It is widely believed that exergaming benefits the patient in terms of encouraging adherence and boosting the patient’s confidence of correct execution and feedback is essential in achieving these. However, feedback and in particular visual feedback, may also have potential negative effects on the quality of the exercise. We describe in this paper a prototype single-sensor therapeutic exergame that we have develope...

  8. Evaluation of therapeutic patient education

    OpenAIRE

    D'Ivernois , Jean-François; Gagnayre , Rémi; Assal , Jean-Philippe; Golay , Alain; Libion , France; Deccache , Alain

    2006-01-01

    9 pages; These guidelines mainly focus on the principles of evaluating Therapeutic Patient Education; Over the past thirty years, therapeutic patient education (TPE) has become an essential part of the treatment of long-term diseases. Evaluations of this new practice are expected, and are sometimes imposed according to protocols and criteria that do not always reflect the complexity of changes taking place within patients and healthcare providers. Sometimes, expected results are not achieved ...

  9. Profiling Prostate Cancer Therapeutic Resistance

    OpenAIRE

    Cameron A. Wade; Natasha Kyprianou

    2018-01-01

    The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival ...

  10. A knowledge-based integrated approach for discovering and repairing declare maps

    NARCIS (Netherlands)

    Maggi, F.M.; Jagadeesh Chandra Bose, R.P.; Aalst, van der W.M.P.; Salinesi, C.; Norrie, M.C.; Pastor, O.

    2013-01-01

    Process mining techniques can be used to discover process models from event data. Often the resulting models are complex due to the variability of the underlying process. Therefore, we aim at discovering declarative process models that can deal with such variability. However, for real-life event

  11. 32 CFR 644.533 - Contamination discovered after return of land to owner, or sale.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Contamination discovered after return of land to owner, or sale. 644.533 Section 644.533 National Defense Department of Defense (Continued) DEPARTMENT OF... Other Contamination from Proposed Excess Land and Improvements § 644.533 Contamination discovered after...

  12. The Use of a Performance Assessment for Identifying Gifted Lebanese Students: Is DISCOVER Effective?

    Science.gov (United States)

    Sarouphim, Ketty M.

    2009-01-01

    The purpose of this study was to investigate the effectiveness of DISCOVER, a performance- based assessment in identifying gifted Lebanese students. The sample consisted of 248 students (121 boys, 127 girls) from Grades 3-5 at two private schools in Beirut, Lebanon. Students were administered DISCOVER and the Raven Standard Progressive Matrices…

  13. Interactions between Therapeutic Proteins and Acrylic Acid Leachable.

    Science.gov (United States)

    Liu, Dengfeng; Nashed-Samuel, Yasser; Bondarenko, Pavel V; Brems, David N; Ren, Da

    2012-01-01

    Leachables are chemical compounds that migrate from manufacturing equipment, primary containers and closure systems, and packaging components into biopharmaceutical and pharmaceutical products. Acrylic acid (at concentration around 5 μg/mL) was detected as leachable in syringes from one of the potential vendors (X syringes). In order to evaluate the potential impact of acrylic acid on therapeutic proteins, an IgG 2 molecule was filled into a sterilized X syringe and then incubated at 45 °C for 45 days in a pH 5 acetate buffer. We discovered that acrylic acid can interact with proteins at three different sites: (1) the lysine side chain, (2) the N-terminus, and (3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed. Even thought a small amount (from 0.02% to 0.3%) of protein was found to be modified by acrylic acid, the modified protein can potentially be harmful due to the toxicity of acrylic acid. After being modified by acrylic acid, the properties of the therapeutic protein may change due to charge and hydrophobicity variations. Acrylic acid was detected to migrate from syringes (Vendor X) into a therapeutic protein solution (at a concentration around 5 μg/mL). In this study, we discovered that acrylic acid can modify proteins at three different sites: (1) the lysine side chain, 2) the N-terminus, and 3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed.

  14. [Advances in Neurological Therapeutics for Friedreich Ataxia and Machado-Joseph Disease].

    Science.gov (United States)

    Yabe, Ichiro; Sasaki, Hidenao

    2017-08-01

    We reviewed advances in therapeutics for both Friedreich ataxia and Machado-Joseph disease. Various clinical trials have been carried out, mainly for Friedreich ataxia; however, the therapeutic reports from these trials have not provided much evidence for success. Some interesting clinical trials have been reported, and further developments are expected. Regenerative therapy using umbilical cord mesenchymal stem cells and a therapeutic study investigating a new pathomechanism in animal and/or cell culture studies were reported. We expect that these results will translate to therapeutic strategies for patients with these disorders. In addition, biomarkers play an important role when novel treatments are discovered and clinical trials are performed: hence at present, a number of biomarkers such as gait analysis by triaxial accelerometers and prism adaptation of hand-reaching movements, are being examined.

  15. Therapeutic patient education in heart failure: do studies provide sufficient information about the educational programme?

    Science.gov (United States)

    Albano, Maria Grazia; Jourdain, Patrick; De Andrade, Vincent; Domenke, Aukse; Desnos, Michel; d'Ivernois, Jean-François

    2014-05-01

    Therapeutic patient education programmes on heart failure have been widely proposed for many years for heart failure patients, but their efficiency remains questionable, partly because most articles lack a precise programme description, which makes comparative analysis of the studies difficult. To analyse the degree of precision in describing therapeutic patient education programmes in recent randomized controlled trials. Three major recent recommendations on therapeutic patient education in heart failure inspired us to compile a list of 23 relevant items that an 'ideal' description of a therapeutic patient education programme should contain. To discover the extent to which recent studies into therapeutic patient education in heart failure included these items, we analysed 19 randomized controlled trials among 448 articles published in this field from 2005 to 2012. The major elements required to describe a therapeutic patient education programme were present, but some other very important pieces of information were missing in most of the studies we analysed: the patient's educational needs, health literacy, projects, expectations regarding therapeutic patient education and psychosocial status; the educational methodology used; outcomes evaluation; and follow-up strategies. Research into how therapeutic patient education can help heart failure patients will be improved if more precise descriptions of patients, educational methodology and evaluation protocols are given by authors, ideally in a standardized format. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Distant World in Peril Discovered from La Silla

    Science.gov (United States)

    2003-01-01

    Giant Exoplanet Orbits Giant Star Summary When, in a distant future, the Sun begins to expand and evolves into a "giant" star, the surface temperature on the Earth will rise dramatically and our home planet will eventually be incinerated by that central body. Fortunately for us, this dramatic event is several billion years away. However, that sad fate will befall another planet, just discovered in orbit about the giant star HD 47536, already within a few tens of millions of years. At a distance of nearly 400 light-years from us, it is the second-remotest planetary system discovered to date [1]. This is an interesting side-result of a major research project, now carried out by a European-Brazilian team of astronomers [2]. In the course of a three-year spectroscopic survey, they have observed about 80 giant stars in the southern sky with the advanced FEROS spectrograph on the 1.52-m telescope installed at the ESO La Silla Observatory (Chile). It is one of these stars that has just been found to host a giant planet. This is only the fourth such case known and with a diameter of about 33 million km (or 23.5 times that of our Sun), HD 47536 is by far the largest of those giant stars [1]. The distance of the planet from the star is still of the order of 300 million km (or twice the distance of the Earth from the Sun), a safe margin now, but this will not always be so. The orbital period is 712 days, i.e., somewhat less than two Earth years, and the planet's mass is 5 - 10 times that of Jupiter. The presence of exoplanets in orbit around giant stars, some of which will eventually perish into their central star (be "cannibalized"), provides a possible explanation of the anomalous abundance of certain chemical elements that is observed in the atmospheres of some stars, cf. ESO PR 10/01. This interesting discovery bodes well for coming observations of exoplanetary systems with new, more powerful instruments, like HARPS to be installed next year at the ESO 3.6-m telescope on

  17. LIGO Discovers the Merger of Two Black Holes

    Science.gov (United States)

    Kohler, Susanna

    2016-02-01

    is: how do binary black holes form? Two primary mechanisms have been proposed:A binary star system contains two stars that are each massive enough to individually collapse into a black hole. If the binary isnt disrupted during the two collapse events, this forms an isolated black-hole binary.Single black holes form in dense cluster environments and then because they are the most massive objects sink to the center of the cluster. There they form pairs through dynamical interactions.Now that were able to observe black-hole binaries through gravitational-wave detections, one way we could distinguish between the two formation mechanisms is from spin measurements. If we discover a clear preference for the misalignment of the two black holes spins, this would favor formation in clusters, where theres no reason for the original spins to be aligned.The current, single detection is not enough to provide constraints, but if we can compile a large enough sample of events, we can start to present a statistical case favoring one channel over the other.What does GW150914 mean for the future of gravitational-wave detection?The fact that Advanced LIGO detected an event even before the start of its first official observing run is certainly promising! The LIGO team estimates that the volume the detectors can probe will still increase by at least a factor of ~10 as the observing runs become more sensitive and of longer duration.Aerial view of the Virgo interferometer near Pisa, Italy. [Virgo Collaboration]In addition, LIGO is not alone in the gravitational-wave game. LIGOs counterpart in Europe, Virgo, is also undergoing design upgrades to increase its sensitivity. Within this year, Virgo should be able to take data simultaneously with LIGO, allowing for better localization of sources. And the launch of (e)LISA, ESAs planned space-based interferometer, will grant us access to a new frequency range, opening a further window to the gravitational-wave sky.The detection of GW150914 marks

  18. Clinical and therapeutic aspects of osteoporosis

    Energy Technology Data Exchange (ETDEWEB)

    Compston, Juliet [University of Cambridge School of Clinical Medicine, Box 157, Department of Medicine, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ (United Kingdom)], E-mail: jec1001@cam.ac.uk

    2009-09-15

    Osteoporosis is characterized by reduced bone mass and alteration in bone architecture, resulting in increased fracture risk. These fractures are a major cause of morbidity and mortality in the elderly and impose a huge economic burden on health services. Oestrogen deficiency plays a major role in the pathogenesis of bone loss and fracture in both women and men. Other pathogenetic factors include reduced physical activity and vitamin D insufficiency. A range of options is available for the prevention of fractures in high risk postmenopausal women. These include the bisphosphonates, strontium ranelate, raloxifene and parathyroid hormone peptides. Because of their broad spectrum of demonstrated anti-fracture efficacy, alendronate, risedronate, zoledronate and strontium ranelate are generally considered as front-line options for most women. The optimum duration of treatment has not been established but re-evaluation of risk and the need for continued therapy after 5 years of treatment may be appropriate. Compliance and persistence with long-term treatment is poor but may be improved by less frequent dosing regimens.

  19. Clinical and therapeutic aspects of osteoporosis

    International Nuclear Information System (INIS)

    Compston, Juliet

    2009-01-01

    Osteoporosis is characterized by reduced bone mass and alteration in bone architecture, resulting in increased fracture risk. These fractures are a major cause of morbidity and mortality in the elderly and impose a huge economic burden on health services. Oestrogen deficiency plays a major role in the pathogenesis of bone loss and fracture in both women and men. Other pathogenetic factors include reduced physical activity and vitamin D insufficiency. A range of options is available for the prevention of fractures in high risk postmenopausal women. These include the bisphosphonates, strontium ranelate, raloxifene and parathyroid hormone peptides. Because of their broad spectrum of demonstrated anti-fracture efficacy, alendronate, risedronate, zoledronate and strontium ranelate are generally considered as front-line options for most women. The optimum duration of treatment has not been established but re-evaluation of risk and the need for continued therapy after 5 years of treatment may be appropriate. Compliance and persistence with long-term treatment is poor but may be improved by less frequent dosing regimens.

  20. The History of Therapeutic Aerosols: A Chronological Review.

    Science.gov (United States)

    Stein, Stephen W; Thiel, Charles G

    2017-02-01

    In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We