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Sample records for evaluating potency specificity

  1. Botulinum neurotoxin serotype A specific cell-based potency assay to replace the mouse bioassay.

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    Ester Fernández-Salas

    Full Text Available Botulinum neurotoxin serotype A (BoNT/A, a potent therapeutic used to treat various disorders, inhibits vesicular neurotransmitter exocytosis by cleaving SNAP25. Development of cell-based potency assays (CBPAs to assess the biological function of BoNT/A have been challenging because of its potency. CBPAs can evaluate the key steps of BoNT action: receptor binding, internalization-translocation, and catalytic activity; and therefore could replace the current mouse bioassay. Primary neurons possess appropriate sensitivity to develop potential replacement assays but those potency assays are difficult to perform and validate. This report describes a CBPA utilizing differentiated human neuroblastoma SiMa cells and a sandwich ELISA that measures BoNT/A-dependent intracellular increase of cleaved SNAP25. Assay sensitivity is similar to the mouse bioassay and measures neurotoxin biological activity in bulk drug substance and BOTOX® product (onabotulinumtoxinA. Validation of a version of this CBPA in a Quality Control laboratory has led to FDA, Health Canada, and European Union approval for potency testing of BOTOX®, BOTOX® Cosmetic, and Vistabel®. Moreover, we also developed and optimized a BoNT/A CBPA screening assay that can be used for the discovery of novel BoNT/A inhibitors to treat human disease.

  2. Evaluating the antibacterial and anticandidal potency of mangrove, Avicennia marina

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    Aseer Manilal

    2016-02-01

    Full Text Available Objective: To evaluate the antibiotic activity of mangrove plant, Avicennia marina (A. marina against human and shrimp pathogens and to delineate bioactive constituents by gas chromatography-mass spectrometer (GC-MS profiling. Methods: The antimicrobial activity of the different polar and non-polar extracts of A. marina was inspected by well diffusion technique against 16 bacterial pathogens and two fungal pathogens. Results: Of the six organic extracts examined, methanolic extract of A. marina fairly repressed the growth of all bacterial and fungal pathogenic strains tested. In general, mangrove extract was more active against the bacterial pathogens while against yeasts, the activity was lesser. The antibiotic activity was attributed to the presence of diverse bioactive secondary metabolites. The chemical profiling of the methanolic extract was performed by GC combined with mass spectrometry. The results of GC-MS showed that the main phytoconstituents were benzeneethanol,4-hydroxy- (RT = 12.173, followed by benzaldehyde,3-methyl- (RT = 6.811. Finally, the GC-MS data evinced that the antimicrobial activity of A. marina was due to the synergistic effect of all constituents or the activity of major constituents. Conclusions: Considering the urgent need of novel antibiotics, the present study brings out a new insight on the exploration of mangroves for antibiotic production in future.

  3. Evaluating the Effect of Peptoid Lipophilicity on Antimicrobial Potency, Cytotoxicity, and Combinatorial Library Design.

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    Turkett, Jeremy A; Bicker, Kevin L

    2017-04-10

    Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relates to antibacterial potency and mammalian cell toxicity. The information gleaned from this optimization was then applied using the aforementioned screening method to examine the relative potency of peptoid libraries against Staphylococcus aureus, Acinetobacter baumannii, and Enterococcus faecalis prior to and following functionalization with long alkyl tails. The data indicate that overall peptoid hydrophobicity and not simply alkyl tail length is strongly correlated with mammalian cell toxicity. Furthermore, this work demonstrates the utility of the PLAD assay in rapidly evaluating the effect of molecular property changes in similar libraries.

  4. Relative potency as a means of evaluating ELF (Extremely Low Frequency) health risks

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    Easterly, C.E.; Glass, L.R.

    1990-09-01

    In the 1970's, a variety of developments took place to heightened public and scientific interest in electromagnetic fields. During this time, biological studies of nonionizing electromagnetic fields were taking place, but no clear evidence of risks to public health was identified. Then came the surprising epidemiological finding suggesting that 60 Hz magnetic fields may be related to some childhood leukemias. Our particular interest at ORNL was how to interpret the available data with respect to human exposures to the nearly ubiquitous fields. A review of the available data showed that consistent biological effects were difficult to identify. Classical toxicological tests used in chemical risk assessment had not been performed with Extremely Low Frequency (ELF) fields but rather a wide range of mechanistic studies had been pursued. To evaluate the level of anticipated hazard or risk there was neither a mechanistic understanding nor a consistent phenomenological outcome. A risk evaluation normally requires one or the other of these two types of information. Two quite different approaches were pursued: meta-analysis and relative potency. The first of these is a method to combine data from similar experiments to enhance the relative statistical power of a collection of small sample size studies, and will not be discussed further. The second, relative potency, will be the focus of this paper. 20 refs., 2 figs.

  5. Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies.

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    Verma, Swati; Soto, Jackeline; Vasudevan, Anupama; Schmeisser, Falko; Alvarado-Facundo, Esmeralda; Wang, Wei; Weiss, Carol D; Weir, Jerry P

    2017-01-01

    Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA) from the two virus lineages. Monoclonal antibodies (mAbs) specific for the two lineages of influenza B HA were generated and characterized and used to set-up simple identity tests that distinguish the influenza B antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific mAbs bound well to the HA of influenza B strains included in influenza vaccines over a period of more than 10 years, suggesting that identity tests using such lineage-specific mAbs would not necessarily have to be updated with every influenza B vaccine strain change. These lineage-specific mAbs were also used in an antibody capture ELISA format to quantify HA in vaccine samples, including monovalent, trivalent, and quadrivalent vaccine samples from various manufacturers. The results demonstrated correlation with HA values determined by the traditional single radial immunodiffusion (SRID) assay. Further, the antibody-capture ELISA was able to distinguish heat-stressed vaccine from unstressed vaccine, and was similar to the SRID in quantifying the resultant loss of potency. These mAb reagents should be useful for further development of antibody-based alternative influenza B identity and potency assays.

  6. Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies.

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    Swati Verma

    Full Text Available Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA from the two virus lineages. Monoclonal antibodies (mAbs specific for the two lineages of influenza B HA were generated and characterized and used to set-up simple identity tests that distinguish the influenza B antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific mAbs bound well to the HA of influenza B strains included in influenza vaccines over a period of more than 10 years, suggesting that identity tests using such lineage-specific mAbs would not necessarily have to be updated with every influenza B vaccine strain change. These lineage-specific mAbs were also used in an antibody capture ELISA format to quantify HA in vaccine samples, including monovalent, trivalent, and quadrivalent vaccine samples from various manufacturers. The results demonstrated correlation with HA values determined by the traditional single radial immunodiffusion (SRID assay. Further, the antibody-capture ELISA was able to distinguish heat-stressed vaccine from unstressed vaccine, and was similar to the SRID in quantifying the resultant loss of potency. These mAb reagents should be useful for further development of antibody-based alternative influenza B identity and potency assays.

  7. Facile synthesis and stereochemical investigation of Mannich base derivatives: evaluation of antioxidant property and antituberculostic potency.

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    Parthiban, Paramasivam; Subalakshmi, Viswalingam; Balasubramanian, Krishnamurthy; Islam, Md Nurul; Choi, Jae Sue; Jeong, Yeon Tae

    2011-04-15

    A mini-library of diversely substituted 2,4-diaryl-3-azabicyco[3.3.1]nonan-9-one O-methyloximes and their N-methyl analogs were synthesized by a non-laborious, modified and an optimized Mannich condensation in good yields. Both the ring N-methylation and oxime O-methylation were employed by various methods; of them, the usage of (t)BuOK was found to be the superior in terms of good yield in short time. Stereochemistry of all the synthesized compounds was unambiguously established by their NMR spectral ((1)H, (13)C, (1)H-(1)H COSY, (1)H-(13)C one and multiple bond COSY and NOESY) as well as single-crystal XRD studies. Irrespective of the nature and position of the substituents, all the synthesized oxime ethers of the bicyclic Mannich bases as well as their N-methyl analogs adopted the twin-chair conformation with equatorial orientations of all the substituents. All the synthesized oxime ethers were evaluated for their antioxidant property by DPPH radical scavenging method. According to the structure-activity correlations, compound 4y was found to be a lead molecule with the IC(50) of 0.187 mg/mL. Thus, the present study exploits the scope of finding more active analogs by further optimization with the incorporation of more electron enriched alkoxy/amino and/or phenolic groups on the heterocycle as well as oxime ether pharmacophore. Most of the synthesized molecules were screened for their antituberculostic potency against Mycobacterium tuberculosis H(37)Rv by zone of inhibition method. Of them, 4w/5d and 4x showed very promising inhibition zones of 21 and 23 mm, respectively, which leads to the optimization of 4x by introducing various substituents on the O-benzyl moiety to enhance the antituberculostic potency. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Systematic evaluation of the metabolic to mitogenic potency ratio for B10-substituted insulin analogues.

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    Tine Glendorf

    Full Text Available BACKGROUND: Insulin analogues comprising acidic amino acid substitutions at position B10 have previously been shown to display increased mitogenic potencies compared to human insulin and the underlying molecular mechanisms have been subject to much scrutiny and debate. However, B10 is still an attractive position for amino acid substitutions given its important role in hexamer formation. The aim of this study was to investigate the relationships between the receptor binding properties as well as the metabolic and mitogenic potencies of a series of insulin analogues with different amino acid substitutions at position B10 and to identify a B10-substituted insulin analogue without an increased mitogenic to metabolic potency ratio. METHODOLOGY/PRINCIPAL FINDINGS: A panel of ten singly-substituted B10 insulin analogues with different amino acid side chain characteristics were prepared and insulin receptor (both isoforms and IGF-I receptor binding affinities using purified receptors, insulin receptor dissociation rates using BHK cells over-expressing the human insulin receptor, metabolic potencies by lipogenesis in isolated rat adipocytes, and mitogenic potencies using two different cell types predominantly expressing either the insulin or the IGF-I receptor were systematically investigated. Only analogues B10D and B10E with significantly increased insulin and IGF-I receptor affinities as well as decreased insulin receptor dissociation rates displayed enhanced mitogenic potencies in both cell types employed. For the remaining analogues with less pronounced changes in receptor affinities and insulin receptor dissociation rates, no apparent correlation between insulin receptor occupancy time and mitogenicity was observed. CONCLUSIONS/SIGNIFICANCE: Several B10-substituted insulin analogues devoid of disproportionate increases in mitogenic compared to metabolic potencies were identified. In the present study, receptor binding affinity rather than insulin

  9. Progestational potency of oral contraceptives: a polemic.

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    Edgren, R A

    1978-01-01

    Dickey and Stone have attempted an evaluation of progestational potencies of oral contraceptives based upon such uterine criteria as subnuclear vacuolization and delay of menses. Their review, unfortunately, is marred by numerous errors which vitiate the potency estimates. The actions of progestagens in target organs depend upon the specific binding of the compounds to a protein receptor that is produced by estrogen treatment. Potency of hormones depends ultimately upon this binding. Since it seems unlikely that specific binding occurs in such nontarget sites as the blood vessels, direct potency relationships are highly improbable between diverse phenomena. Possible relationships between oral contraceptives and specific side effects must be studied in relationship to individual side effects and particular contraceptive products. Possible coincidental activities, no matter how analyzed, are unlikely to contribute meaningfully to our understanding of these drugs.

  10. First systematic evaluation of the potency of Cannabis sativa plants grown in Albania.

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    Bruci, Zana; Papoutsis, Ioannis; Athanaselis, Sotirios; Nikolaou, Panagiota; Pazari, Ermira; Spiliopoulou, Chara; Vyshka, Gentian

    2012-10-10

    Cannabis products (marijuana, hashish, cannabis oil) are the most frequently abused illegal substances worldwide. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of Cannabis sativa plant, whereas cannabidiol (CBD) and cannabinol (CBN) are other major but no psychoactive constituents. Many studies have already been carried out on these compounds and chemical research was encouraged due to the legal implications concerning the misuse of marijuana. The aim of this study was to determine THC, CBD and CBN in a significant number of cannabis samples of Albanian origin, where cannabis is the most frequently used drug of abuse, in order to evaluate and classify them according to their cannabinoid composition. A GC-MS method was used, in order to assay cannabinoid content of hemp samples harvested at different maturation degree levels during the summer months and grown in different areas of Albania. This method can also be used for the determination of plant phenotype, the evaluation of psychoactive potency and the control of material quality. The highest cannabinoid concentrations were found in the flowers of cannabis. The THC concentrations in different locations of Albania ranged from 1.07 to 12.13%. The influence of environmental conditions on cannabinoid content is discussed. The cannabinoid content of cannabis plants were used for their profiling, and it was used for their classification, according to their geographical origin. The determined concentrations justify the fact that Albania is an area where cannabis is extensively cultivated for illegal purposes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Evaluation of a digital dispenser for direct curve dilutions in a vaccine potency assay.

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    Roselle, Christopher; Whitehouse, Dana; Follmer, Thy; Ansbro, Fran; Bouaraphan, Silikhone; Guan, Liming; Wang, Sha-Ke; Shank-Retzlaff, Mary; Verch, Thorsten

    2017-03-01

    Dilutions are a common source of analytical error, both in terms of accuracy and precision, and a common source of analyst mistakes. When serial dilutions are used, errors compound, even when employing laboratory automation. Direct point dilutions instead of serial dilutions can reduce error but is often impractical as they require either large diluent volumes or very small sample volumes when performed with traditional liquid handling equipment. We evaluated preparation of dilution curves using a picoliter digital dispenser, the HP, Inc. / TECAN D300 which is capable of accurately delivering picoliter volumes directly into sample wells filled with assay diluent. Dilution linearity and variability of the direct dilutions were similar to or less than those generated with a traditional liquid handler as measured using a fluorophore assay and an ELISA used to measure vaccine potency. Minimum concentrations for detergent in the dispensed sample were identified but no correlation with detergent characteristics was observed. The tolerance to protein in the sample was evaluated as well with up to 5% BSA having no impact on dispense linearity and precision. We found the digital dispenser to reduce automation complexity while maintaining or improving assay performance in addition to facilitating complex plate lay-outs. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A CONCEPTUAL MODEL FOR EVALUATING RELATIVE POTENCY DATA FOR USE IN ECOLOGICAL RISK ASSESSMENTS

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    For chemicals with a common mechanism of toxicity, relative potency factors (RPFs) allow dose and exposure measures to be normalized to an equivalent toxicity amount of a model chemical... In ecological risk assessments the large number of possible target species, variety of expo...

  13. Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitation

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    Basketter, David A; Andersen, Klaus E; Liden, Carola

    2005-01-01

    The Technical Committee of Classification and Labelling dealing with harmonized classification of substances and classification criteria under Directive 67/548/EEC on behalf of the European Commission nominated an expert group on skin sensitization in order to investigate further the possibility...... for potency consideration of skin sensitizers for future development of the classification criteria. All substances and preparations should be classified on the basis of their intrinsic properties and should be labelled accordingly with the rules set up in the Directive 67/548/EEC. The classification should...... products, cosmetics, food and feeding stuffs, which are subject to specific community legislation. The main questions that are answered in this report are whether it would be possible to give detailed guidance on how to grade allergen potency based on the existing methods, whether such grading could...

  14. Potency Evaluation of Recombinant Human Erythropoietin in Brazil: Assessment of Reproducibility Using a Practical Approach

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    Michele Cardoso do Nascimento

    2015-08-01

    Full Text Available In this study, we compared the results of potency determination of recombinant human erythropoietin (rhEPO obtained between 2010 and 2012 by the National Institute of Quality Control in Health (INCQS/Fiocruz, i.e., the National Control Laboratory (NCL, and by a manufacturer of rhEPO. In total, 47 different batches of commercially prepared rhEPO (alpha isoform were analyzed. All results, including those of the control and warning limits, remained within the limits recommended by European Pharmacopoeia (Ph. Eur.. All relative error (RE values were less than ± 30%, wh ereas most were approximately ± 20%. Applying the Bland-Altman plot, only two of 47 values remained outside the limits of agreement (LA. In addition, agreement of potency determination between INCQS and the manufacturer coefficient of variation of reproducibility (% CVR was considered satisfactory. Taken together, our results demonstrate (i. the potency assay of rhEPO performed at INCQS, is standardized and controlled, (ii. the comparison of our results with those of the manufacturer, revealed an adequate inter-laboratory variation, and (iii. the critical appraisal proposed here appears to be a feasible tool to assess the reproducibility of biological activity, providing additional information regarding monitoring and production consistency to manufacturers and NCLs.

  15. A retrospective evaluation of the efficacy of intravenous bumetanide and comparison of potency with furosemide

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    Nappi JM

    2013-03-01

    Full Text Available Background: The potency of intravenous bumetanide to furosemide using a ratio of 1:40 has been suggested; however, there are little data supporting this ratio. Recent drug shortages required the use of bumetanide in a large patient population, enabling further characterization of the efficacy of IV bumetanide.Objective: The primary objective of this study was to estimate a dose-response effect of IV bumetanide on urine output (UOP in all patients that received 48 hours of therapy as well as in a subgroup of patients with heart failure (HF. This subgroup was used to compare the potency of bumetanide with furosemide. A secondary safety objective described electrolyte replacement required during therapy. Methods: This was a single-center retrospective study examining the dose-response effect of IV bumetanide in patients receiving at least 48 hours of intermittent (iIV or continuous (cIV dosing, measured by UOP per mg of drug received (mL/mg. The potency of IV bumetanide was compared with furosemide in a subset of patients with HF using pre-existing data. The safety of IV bumetanide was analyzed by quantifying electrolyte replacement received during the study period.Results: The primary outcome was higher in the iIV group (n=93 at 1273 ± 844 mL/mg compared with the cIV group (n=16 at 749 ± 370 mL/mg (P=0.002. Among patients with HF who received furosemide (iIV n=30, cIV n=26 or bumetanide (iIV n=30, cIV n=3, a potency ratio of 41:1 was found for the iIV group and 34:1 for all patients with HF. There was no significant difference in electrolyte replacement between groups.Conclusion: A greater response was seen with intermittent bumetanide compared with continuous infusion bumetanide. This study supports the 40:1 dose equivalence ratio (furosemide:bumetanide in patients with HF receiving at least 48 hours of intravenous intermittent bumetanide.

  16. The potency and specificity of the interaction between the IA3 inhibitor and its target aspartic proteinase from Saccharomyces cerevisiae

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    Phylip, L H; Lees, W E; Brownsey, B G

    2001-01-01

    The yeast IA3 polypeptide consists of only 68 residues, and the free inhibitor has little intrinsic secondary structure. IA3 showed subnanomolar potency toward its target, proteinase A from Saccharomyces cerevisiae, and did not inhibit any of a large number of aspartic proteinases with similar se...

  17. Development and Characterization of an HPV Type-16 Specific Modified DNA Aptamer for the Improvement of Potency Assays.

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    Trausch, Jeremiah J; Shank-Retzlaff, Mary; Verch, Thorsten

    2017-03-21

    Measuring vaccine potency is critical for vaccine release and is often accomplished using antibody-based ELISAs. Antibodies can be associated with significant drawbacks that are often overlooked including lot-to-lot variability, problems with cell-line maintenance, limited stability, high cost, and long discovery lead times. Here, we address many of these issues through the development of an aptamer, known as a slow off-rate modified DNA aptamer (SOMAmer), which targets a vaccine antigen in the human papillomavirus (HPV) vaccine Gardasil. The aptamer, termed HPV-07, was selected to bind the Type 16 virus-like-particle (VLP) formed by the self-assembling capsid protein L1. It is capable of binding with high sensitivity (EC50 of 0.1 to 0.4 μg/mL depending on assay format) while strongly discriminating against other VLP types. The aptamer competes for binding with the neutralizing antibody H16.V5, indicating at least partial recognition of a neutralizing and clinically relevant epitope. This makes it a useful reagent for measuring both potency and stability. When used in an ELISA format, the aptamer displays both high precision (intermediate precision of 6.3%) and a large linear range spanning from 25% to 200% of a typical formulation. To further exploit the advantages of aptamers, a simplified mix and read assay was also developed. This assay format offers significant time and resource reductions compared to a traditional ELISA. These results show aptamers are suitable reagents for biological potency assays, and we expect that their implementation could improve upon current assay formats.

  18. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    movies work to dispel fear by producing potency and bolstering resolve. We can thus understand action movies as participating in the biopolitical effects of contemporary warfare. Affect is globalized and intensified through action movies’ aesthetics, with the aim of producing a kind of drone subject....... Robin James significantly posits a drone atmosphere where our perceptual limit reconfigures through ‘droning’ – the creation of an affective timbre [James, R., 2013. Drones, sound, and super-panoptic surveillance. Cyborgology]. As James argues, ‘[d]roning rivets you to material conditions, affects......, and sensations that compel you to behave in specific ways, and not in others’ (n.p.). So while drones currently work overseas to target morale, action movies work on the home front to target our potency and resolve and so engender a mode of sensation that also functions as action. Affect works as a translator...

  19. A step forward in the quality control testing of inactivated rabies vaccines - extensive evaluation of European vaccines by using alternative methods to the in vivo potency tests.

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    Servat, Alexandre; Kempff, Sébastien; Brogat, Valère; Litaize, Estelle; Schereffer, Jean-Luc; Cliquet, Florence

    2015-03-01

    The mouse challenge test still remains the reference method for the potency determination of human and animal inactivated rabies vaccines, and it is still widely used throughout the world. This test suffers from many disadvantages - it is expensive and time consuming, uses a large number of mice, causes significant animal distress, and suffers from high variability. Recently, the European Pharmacopoeia has recognised the use of a serological potency assay (SPA) as an alternative method to the challenge test. This new test is based on the determination of rabies neutralising antibody titres in vaccinated mice, by using the modified Rapid Fluorescent Focus Inhibition Test (mRFFIT). With the objective of adopting this new method for the batch release of inactivated rabies vaccines, we evaluated its performance on a large collection of rabies vaccines currently assessed in our laboratory. The Fluorescent Antibody Virus Neutralisation test (FAVNt) was used in parallel with the mRFFIT, and the results were compared to the mouse challenge test. Our results demonstrate that the SPA is capable of estimating the potency of vaccines formulated with a potency margin well above the minimum of 1IU/dose. For low potency vaccines, this new method demonstrated some limitations, due to the recurrent invalidation of the assay. We have also demonstrated the superior sensitivity of the FAVNt when compared to the mRFFIT, and the importance of minimising the risk of detecting non-responders in vaccinated mice. 2015 FRAME.

  20. An International Standard for specifying the minimum potency of anti-D blood-grouping reagents: evaluation of a candidate preparation in an international collaborative study

    NARCIS (Netherlands)

    Thorpe, S. J.; Fox, B.; Heath, A. B.; Scott, M.; de Haas, M.; Kochman, S.; Padilla, A.

    2006-01-01

    The aim of this study was to evaluate a lyophilized monoclonal immunoglobulin M (IgM) anti-D preparation for use as an International Standard to specify a recommended minimum acceptable potency of anti-D blood-grouping reagents. The candidate International Standard (99/836) for specifying the

  1. Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

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    Contrera, Joseph F

    2011-02-01

    The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Rhynchophorus ferrugineus midgut cell line to evaluate insecticidal potency of different plant essential oils.

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    Rizwan-ul-Haq, Muhammad; Aljabr, Ahmed Mohammed

    2015-03-01

    Cell cultures can be a potent and strong tool to evaluate the insecticidal efficiency of natural products. Plant essential oils have long been used as the fragrance or curative products around the world which means that they are safer to be used in close proximity of humans and mammals. In this study, a midgut cell line, developed from Rhynchophorus ferrugineus (RPW-1), was used for screening essential oils from nine different plants. Assays revealed that higher cell mortality was observed at 500 ppm which reached to 86, 65, 60, 59, 56, 54, 54, 53, and 53%, whereas lowest cell mortality at 1 ppm remained at 41, 23, 20, 17, 16, 15, 14, 13, and 10%, for Azadirachta indica, Piper nigrum, Mentha spicata, Cammiphora myrrha, Elettaria cardamomum, Zingiber officinale, Curcuma longa, Schinus molle, and Rosmarinus officinalis, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay revealed the percentage of cell growth inhibition was highest at 500 ppm and remained at 48, 45, 42, 37, 34, 29, 24, 22, and 18% against A. indica, P. nigrum, M. spicata, C. myrrha, E. cardamomum, Z. officinale, C. longa, S. molle, and R. officinalis, respectively. Lowest LC50 value (7.98 ppm) was found for A. indica, whereas the highest LC50 (483.11 ppm) was against R. officinalis. Thus, in this study, essential oils of A. indica exhibited the highest levels of toxicity, whereas those from R. officinalis exhibited the lowest levels of toxicity toward RPW-1 cells.

  3. Antidiabetic and antioxidant potency evaluation of different fractions obtained from Cucumis prophetarum fruit.

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    Gawli, Kavishankar; Lakshmidevi, N

    2015-05-01

    Cucumis prophetarum Linn. (Cucurbitaceae) fruit is used for inflammatory-related problems and is proved to be possessing anticancer and hepatoprotective effects. The present investigation was to study the effect of different fractions of C. prophetarum on antidiabetic and antioxidant activity. Aqueous crude extract (CE) of C. prophetarum fruits was fractionated into water soluble fraction 1 (F1), chloroform fraction 2 (F2), basic fraction 3 (F3), and neutral fraction 4 (F4) by acid-base extraction. CE and its fractions at different doses (0.02-0.1 mg/mL) were subjected to antidiabetic (α-amylase and α-glucosidase inhibition assays) and antioxidant (DPPH, superoxide radical scavenging (SO) and metal chelation) evaluation. F1 exhibited effective antidiabetic activity (p F4 > F3 > F2, according to α-amylase assay, which were the same, with the exception of the rank order of F4 and CE, as the α-glucosidase assay. Furthermore, F1 (IC50 = 73 µg/mL) showed better reducing ability than CE >F4 >F2 > F3 (IC50 = 78-272 µg/mL), according to the DPPH assay. In SO and metal chelation assays, F1 showed the highest activity (IC50 = 101 and 147 µg/mL), respectively; the activity decreased in the order of CE >F4 >F3 > F2 (IC50 = 126-469 µg/mL) for SO and 194-944 µg/mL for metal chelation assay. The results indicate that F1 possesses potent in vitro antidiabetic and antioxidant activities.

  4. Exploring quality and its potential effects of multi-components antibiotic: consistency evaluation between matrix components ratio and microbiological potency of teicoplanin.

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    Chang, Yan; Wang, Nan; Yao, Shang-Chen; Hu, Chang-Qin

    2013-11-01

    The production process, such as fermentation and purification etc., can significantly affect the relative ratio of matrix components in a multi-component antibiotic. The ratio of components can be varied in different products. This status causes a difficulty to assure the homogeneity and consistency between reference standards and test samples in potency determination, which hinders the results judgment and accuracy of a routine microbiological assay. In the current study, a multi-component antibiotic, teicoplanin, was selected as a model to explore the relationship between the ratio of matrix component and antibiotics potency. Single-component samples, TA3-1, TA2-1, and mixed-component samples, TA2-2.3, TA2-4.5, of teicoplanin were prepared and purified. Dose-response relationship of each sample has been determined by HPLC and microbiological assay, respectively. The accuracy of the potency result was guaranteed by choosing a test organism with the same sensitivity to each component of teicoplanin when there were differences existing in the ratio of components between the reference standard and the test sample. The experimental methods in current specifications can be replaced with the new potency determination method, which can provide a more realistic reflection of the biological activity of the product.

  5. Evaluation of different extraction methods on antimicrobial potency of Adenium obesum stem against food borne pathogenic bacterial strains in Oman

    Directory of Open Access Journals (Sweden)

    Mohammad Amzad Hossain

    2014-09-01

    Full Text Available Objective: To determine and compare the effect on antimicrobial potency of crude stems extract of Adenium obesum (A. obesum by Soxhlet and maceration extraction methods. Methods: The crude extracts were prepared from the coarse samples of stems with methanol by using Soxhlet and maceration extraction methods. Both the crude extracts from two extraction methods were dissolved in water and successively extracted by different polarities solvents with increasing polarities. In vitro antimicrobial potency of different polarities crude extracts obtained from Soxhlet and maceration methods was determined by agar gel diffusion method against different food borne pathogenic bacterial strains. Results: The results for antimicrobial potency of different crude extracts were almost similar by Soxhlet and maceration and methods. The average range of inhibition potency of different polarities crude extracts was 0%-17% by Soxhlet method and inhibition potency 0%-24% by maceration method. Conclusions: These results obtained from in vitro approach give promising basic information about this plant as well as some potential crude extracts can be used for the treatment of infectious diseases.

  6. A simple and rapid Hepatitis A Virus (HAV titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2008-12-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the

  7. 3.0T MR Diffusion-weighted Imaging: Evaluating Diagnosis Potency 
of Pulmonary Solid Benign Lesions and Malignant Tumors and Optimizing b Value

    Directory of Open Access Journals (Sweden)

    Weidong LI

    2011-11-01

    Full Text Available Background and objective Diffusion is caused by random translational molecular motion, also known as Brownian water motion. Diffusion-weighted imaging (DWI is the only imaging method that can be used to evaluate the diffusion process in vivo. The aim of this study is to evaluate 3.0T magnetic resonance imaging (MRI DWI with phased-array coil and the array spatial sensitivity encoding technique (ASSET of diagnosis potency in the discrimination of pulmonary solid benign lesions and malignant tumors. This study also aims to optimize b value. Methods One hundred and sixteen patients with 120 lesions confirmed by pathology and clinical diagnosis underwent T2 weighted imaging (T2WI, T1 weighted imaging, T2WI fat suppression, and DWI (diffusion factors of 200 s/mm2, 500 s/mm2, 800 s/mm2, 1,000 s/mm2 examinations by ASSET with 3.0T MR. The signal intensity of DWI images and the apparent diffusion coefficient (ADC values of the lesions were measured. Signal-to-noise ratio (SNR, contrast-to-noise ratio (CNR, and ADC were compared among different b values. Receiver operating characteristic (ROC curves were analyzed and the b values were optimized. Results Both the SNR and CNR significantly differed among varied b values (P<0.001, P=0.002. The ADC values of pulmonary solid benign lesions and malignant tumors were gradually reduced with increasing b value, and the differences were statistically significant (P<0.001, P<0.001. ROC analysis shows that the area under curve (AUC values were 0.831, 0.876, 0.813, 0.785 (b=200 s/mm2, 500 s/mm2, 800 s/mm2, 1,000 s/mm2, respectively. The AUC with a b value of 500 s/mm2 was the largest. The optimal threshold of ADC was 1.473×10-3 mm2/s, and the sensitivity and specificity were 80% and 84%, respectively. Conclusion 3.0T MR DWI with phased-array coil and ASSET has moderate diagnosis potency in differentiating pulmonary solid benign lesions and malignant tumors. The optimal b value is 500 s/mm2.

  8. Skin sensitization potency and cross-reactivity of p-phenylenediamine and its derivatives evaluated by non-radioactive murine local lymph node assay and guinea-pig maximization test.

    Science.gov (United States)

    Yamano, Tetsuo; Shimizu, Mitsuru

    2009-04-01

    p-Phenylenediamine (PPD)-related chemicals have been used as antioxidants in rubber products, and many cases of contact dermatitis caused by these chemicals have been reported. The aim of this study was to investigate relative sensitizing potency and cross-reactivity among PPD derivatives. Five PPD derivatives, p-aminodiphenylamine (PADPA), N,N'-diphenyl-p-phenylenediamine (DPPD), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (DMBPPD), N-(1-methylheptyl)-N'-phenyl-p-phenylenediamine (MHPPD), and the core chemical PPD were evaluated for their sensitizing potency and cross-reactivity using the non-radioactive murine local lymph node assay (LLNA) and the guinea-pig maximization test (GPMT). PPD and all the derivatives were identified as primary sensitizers in both tests. The order of potency in the LLNA was as follows: IPPD and PADPA > PPD > DMBPPD and MHPPD > DPPD. In the GPMT, all six groups of animals sensitized with one of these chemicals cross-reacted to four other derivatives. Specifically, the five groups that have a common basic PADPA structure, that is PADPA, DPPD, IPPD, DMBPPD, and MHPPD, all reacted to each other at almost the same scores, while none of them reacted to PPD. The cross-reactivity profile found in the study was to some extent different from that in previous human data, where distinction between cross-reaction and concomitant primary sensitization is not always clear.

  9. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: statistical analysis

    NARCIS (Netherlands)

    Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH

    1993-01-01

    This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual

  10. Induction of Staphylococcus aureus-specific IgA and agglutination potency in milk of cows by mucosal immunization.

    Science.gov (United States)

    Tempelmans Plat-Sinnige, Marjan J; Verkaik, Nelianne J; van Wamel, Willem J B; de Groot, Nanda; Acton, Dennis S; van Belkum, Alex

    2009-06-19

    Lactating cows were immunized with inactivated Staphylococcus aureus strains and concentrated culture supernatants. Application of a repeated mucosal immunization scheme resulted in significant levels of S. aureus-specific IgA in milk of dairy cows. Average IgA titers against whole cell S. aureus increased during the first 10 weeks of immunization after which a plateau level was reached and maintained during lactation. Immune whey agglutinated both bovine and human S. aureus strains including methicillin-resistant S. aureus (MRSA) strains and recognized extracted S. aureus proteins on Western blot. ELISAs to quantify milk IgA reactive with a number of S. aureus virulence proteins (e.g. enterotoxins, microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) and immune modulating proteins) and cell wall components, demonstrated the polyclonality of the IgA. Correlations observed between agglutination and specific IgA titers for whey and for purified IgA suggested functionality of the induced antibodies. Milk from immunized cows may provide a way of producing potentially therapeutic polyclonal antibodies against S. aureus colonization and infection.

  11. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase

    Energy Technology Data Exchange (ETDEWEB)

    Filgueira de Azevedo, W. Jr.; Mueller-Dieckmann, H.J.; Schulze-Gahmen, U. [Lawrence Berkeley National Lab., CA (United States)] [and others

    1996-04-02

    The central role of cyclin-dependent kinases (CDKs) in cell cycle regulation makes them a promising target for studying inhibitory molecules that can modify the degree of cell proliferation. The discovery of specific inhibitors of CDKs such as polyhydroxylated flavones has opened the way to investigation and design of antimitotic compounds. A novel flavone, (-)-cis-5,7-dihydroxyphenyl-8-[4-(3-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one hydrochloride hemihydrate (L868276), is a potent inhibitor of CDKs. A chlorinated form, flavopiridol, is currently in phase I clinical trials as a drug against breast tumors. We determined the crystal structure of a complex between CDK2 and L868276 at 2.33-{Angstrom} resolution and refined to an R{sub factor} of 20.3%. The aromatic portion of the inhibitor binds to the adenine-binding pocket of CDK2, and the position of the phenyl group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP complex structure. The analysis of the position of this phenyl ring not only explains the great differences of kinase inhibition among the flavonoid inhibitors but also explains the specificity of L868276 to inhibit CDK2 and CDC2. 36 refs., 4 figs., 2 tabs.

  12. Impact of pre-existing MSP142-allele specific immunity on potency of an erythrocytic Plasmodium falciparum vaccine

    Directory of Open Access Journals (Sweden)

    Bergmann-Leitner Elke S

    2012-09-01

    Full Text Available Abstract Background MSP1 is the major surface protein on merozoites and a prime candidate for a blood stage malaria vaccine. Preclinical and seroepidemiological studies have implicated antibodies to MSP1 in protection against blood stage parasitaemia and/or reduced parasite densities, respectively. Malaria endemic areas have multiple strains of Plasmodium falciparum circulating at any given time, giving rise to complex immune responses, an issue which is generally not addressed in clinical trials conducted in non-endemic areas. A lack of understanding of the effect of pre-existing immunity to heterologous parasite strains may significantly contribute to vaccine failure in the field. The purpose of this study was to model the effect of pre-existing immunity to MSP142 on the immunogenicity of blood-stage malaria vaccines based on alternative MSP1 alleles. Methods Inbred and outbred mice were immunized with various recombinant P. falciparum MSP142 proteins that represent the two major alleles of MSP142, MAD20 (3D7 and Wellcome (K1, FVO. Humoral immune responses were analysed by ELISA and LuminexTM, and functional activity of induced MSP142-specific antibodies was assessed by growth inhibition assays. T-cell responses were characterized using ex vivo ELISpot assays. Results Analysis of the immune responses induced by various immunization regimens demonstrated a strong allele-specific response at the T cell level in both inbred and outbred mice. The success of heterologous regimens depended on the degree of homology of the N-terminal p33 portion of the MSP142, likely due to the fact that most T cell epitopes reside in this part of the molecule. Analysis of humoral immune responses revealed a marked cross-reactivity between the alleles. Functional analyses showed that some of the heterologous regimens induced antibodies with improved growth inhibitory activities. Conclusion The development of a more broadly efficacious MSP1 based vaccine may be

  13. SHORT COMMUNICATION CARCINOGENIC POTENCY OF ...

    African Journals Online (AJOL)

    ABSTRACT. Carcinogenic potency of polycyclic aromatic hydrocarbons (PAHs) in soils obtained from seven different sampling locations in Effurun metropolis and its environs of Niger Delta Area of Nigeria were evaluated. The 16 US EPA priority PAHs were determined with GC-MS. The concentrations of individual PAHs ...

  14. Development of a flow cytometric bead immunoassay and its assessment as a possible aid to potency evaluation of enterotoxaemia vaccines

    Directory of Open Access Journals (Sweden)

    Angela Buys

    2014-02-01

    Full Text Available Enterotoxaemia, an economically important disease of sheep, goats and calves, is caused by systemic effects of the epsilon toxin produced by the anaerobic bacterium Clostridium perfringens type D. The only practical means of controlling the occurrence of enterotoxaemia is to immunise animals by vaccination. The vaccine is prepared by deriving a toxoid from the bacterial culture filtrate and the potency of the vaccine is tested with the in vivo mouse neutralisation test (MNT. Due to ethical, economic and technical reasons, alternative in vitro assays are needed. In this study an indirect cytometric bead immunoassay (I-CBA was developed for use in vaccine potency testing and the results were compared with those obtained using an indirect enzyme-linked immunosorbent assay (I-ELISA and the MNT. Sera were collected from guinea pigs immunised with three different production batches of enterotoxaemia vaccine and the levels of anti-epsilon toxin antibodies were determined. Although the intra- and inter-assay variability was satisfactory, epsilon antitoxin levels determined by both the I-ELISA and indirect cytometric bead immunoassay (I-CBA tests were higher than those of the MNT assay. In contrast to the MNT, all of the serum samples were identified as having antitoxin levels above the required minimum (not less than 5 U/mL. These results indicate that the respective in vitro tests in their current formats are not yet suitable alternatives to the in vivo MNT. The growing demand for a more humane, cost-effective and efficient method for testing the potency of enterotoxaemia vaccines, however, provides a strong impetus for further optimisation and standardisation of the I-CBA assay but further analytical research is required.

  15. In vitro potency evaluations of various piperacillin/tazobactam generic products compared with the contemporary branded (Zosyn, Wyeth) formulation.

    Science.gov (United States)

    Jones, Ronald N; Fritsche, Thomas R; Moet, Gary J

    2008-05-01

    Twenty-three generic intravenous piperacillin/tazobactam products were compared for in vitro activity to the branded formulation (Zosyn, Wyeth, Philadelphia, PA) by disk diffusion and incremental broth microdilution assay methods. All but 1 lot demonstrated significantly decreased activity (-5 to -35%), necessitating further investigations regarding the chemical purity, potency, and therapeutic equivalence of these products worldwide. The average -16% activity across all generic lots was equivalent to underdosing piperacillin/tazobactam by 2.6 g daily for serious clinical infections (4.5 g Q6 h).

  16. Zinc-Metalloproteinase Inhibitors: Evaluation of the Complex Role Played by the Zinc-Binding Group on Potency and Selectivity.

    Science.gov (United States)

    Rouanet-Mehouas, Cecile; Czarny, Bertrand; Beau, Fabrice; Cassar-Lajeunesse, Evelyne; Stura, Enrico A; Dive, Vincent; Devel, Laurent

    2017-01-12

    The most exploited strategy to develop potent zinc-metalloprotease inhibitors relies on a core zinc chelator and a peptidic or nonpeptidic scaffold that provides supplementary interactions for optimized potency and selectivity. Applied to matrix metalloproteases (MMPs) with highly conserved catalytic domains, this strategy failed to identify inhibitors with the desired selectivity profiles. To question the precise role of the zinc-binding group (ZBG), we have carried out a study on MMP-12 inhibitors with a common peptidic core but different ZBGs. We find that exchanging the ZBG modifies inhibitor positioning and affects its dynamics and selectivity. The binding properties of these compounds were compared through biochemical, structural, and calorimetric studies, showing a complex interplay between cooperative interactions and dynamics dictated by the ZBG. Improving selectivity will require expanding the ZBG repertoire within inhibitor libraries, since relying on a single ZBG significantly decreases our chance to identify effective inhibitors.

  17. An Extended Structure-Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors.

    Science.gov (United States)

    Holland, Erika B; Feng, Wei; Zheng, Jing; Dong, Yao; Li, Xueshu; Lehmler, Hans-Joachim; Pessah, Isaac N

    2017-01-01

    Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca(2+ )channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure-activity relationship and a quantitative structure-activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [(3)H]Ryanodine ([(3)H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta-substitutions to the para-position resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Fluorescence-Based Comparative Evaluation of Bactericidal Potency and Food Application Potential of Anti-listerial Bacteriocin Produced by Lactic Acid Bacteria Isolated from Indigenous Samples.

    Science.gov (United States)

    Singh, Atul Kumar; Mukherjee, Sandipan; Adhikari, Manab Deb; Ramesh, Aiyagari

    2012-06-01

    The aim of the present study was to ascertain the potency of anti-listerial bacteriocin produced by lactic acid bacteria (LAB) isolated from indigenous samples of dahi, dried fish, and salt-fermented cucumber. A total of 231 LAB isolates were obtained from the samples, of which 51 isolates displayed anti-listerial activity. The anti-listerial LAB were identified by PCR as Lactobacillus sp., Pediococcus sp., Enterococcus sp., and Lactococcus sp. PCR also enabled the detection of Class IIa bacteriocin-encoding genes such as enterocin A, pediocin, and plantaricin A in some of the LAB isolates. The culture filtrate from anti-listerial LAB isolates demonstrated bacteriocin-like inhibitory substance (BLIS) against common Gram-positive pathogenic bacteria such as Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus, and partial characterization of BLIS confirmed the production of bacteriocin by the LAB isolates. Sensitive fluorescence-based assays employing specific probes indicated the comparative potencies of the bacteriocin and clearly revealed the membrane-targeted anti-listerial activity of the purified bacteriocin produced by selected LAB isolates. The food application potential of plantaricin A produced by a native isolate Lactobacillus plantarum CRA52 was evidenced as the bacteriocin suppressed the growth of Listeria monocytogenes Scott A inoculated in paneer samples that were stored at 8 °C for 5 days.

  19. Evaluation of the lethal potency of scorpion and snake venoms and comparison between intraperitoneal and intravenous injection routes.

    Science.gov (United States)

    Oukkache, Naoual; El Jaoudi, Rachid; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

    2014-06-12

    Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD₅₀) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD₅₀ values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD₅₀ values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD₅₀ values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the

  20. Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

    Directory of Open Access Journals (Sweden)

    Naoual Oukkache

    2014-06-01

    Full Text Available Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50 of scorpion and snake venoms appears to be an important step to assess (and compare venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP versus intravenous (IV. The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am is intrinsically more toxic than Androctonus australis hector (Aah species, whereas the latter is more toxic than Buthus occitanus (Bo. Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc is more toxic than either Bitis arietans (Ba or Macrovipera lebetina (Ml species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of

  1. Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

    Science.gov (United States)

    Oukkache, Naoual; Jaoudi, Rachid El; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

    2014-01-01

    Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins

  2. Potency of Stem Cells

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Potency of Stem Cells. Totipotent Stem Cells (Zygote + first 2 divisions). -Can form placenta, embryo, and any cell of the body. Pluripotent (Embryonic Stem Cells). -Can form any cell of the body but can not form placenta, hence no embryo. Multipotent (Adult stem cells).

  3. CPDB: Carcinogenic Potency Database.

    Science.gov (United States)

    Fitzpatrick, Roberta Bronson

    2008-01-01

    The Carcinogenic Potency Database reports analyses of animal cancer tests on 1,547 chemicals. These tests are used in support of cancer risk assessments for humans. Results are searchable and are made available via the National Library of Medicine's (NLM) TOXNET system. This column will provide background information on the database, as well as present search basics.

  4. Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency

    Directory of Open Access Journals (Sweden)

    Sebastien Boucle

    2015-01-01

    Full Text Available This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1–11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

  5. Biological Parameters for Evaluating the Toxic Potency of Petroleum Ether Extract of Wattakaka volubilis in Wistar Female Rats

    Directory of Open Access Journals (Sweden)

    Velmani Gopal

    2014-09-01

    Full Text Available Objectives: The present study investigated the toxic properties of petroleum ether extract of Wattakaka (W. volubilis in Wistar female rats. Methods: An in vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the lethality concentrations were assessed for petroleum ether extract of W. volubilis. A water soluble portion of the test extract was used in different concentrations from 100-1000 μg/mL of 1 mg/mL stock solution. A 24-hours incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to calculate the percentage rate of dead nauplii with test extract administration against a potassium-dichromate positive control. The acute and the sub-acute toxicities of petroleum ether extract of W. volubilis were evaluated orally by using gavage in female Wistar rats. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Toxicity or death was evaluated following the administration of petroleum ether extract for 28 consecutive days in the female rats. Serum biochemical parameters, such as alanine aminotransferase (ALT, alkaline phosphatase (ALP, bilirubin, total cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium, potassium and α-amylase levels, were measured in the toxicity evaluations. Pathological changes in isolated organs, such as the liver, kidneys, and pancreas, were also examined using hematoxylin and eosin dye fixation after the end of the test extract’s administration. Results: The results of the brine-shrimp assay indicate that the evaluated concentrations of petroleum ether extract of W. volubilis were found to be non-toxic. In the acute and the sub-acute toxicity evaluations, no significant differences were observed between the control animals and the animals treated with extract of W. volubilis. No abnormal histological changes were observed in any of the animal groups treated with petroleum ether extract of W. volubilis

  6. Quantitative structure - mesothelioma potency model ...

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and comprehensive rat intra-pleural (IP) dose characterization data set with a wide variety of EP size, shape, crystallographic, chemical, and bio-durability properties facilitated extensive statistical analyses of 50 rat IP exposure test results for evaluation of alternative dose pleural mesothelioma response models. Utilizing logistic regression, maximum likelihood evaluations of thousands of alternative dose metrics based on hundreds of individual EP dimensional variations within each test sample, four major findings emerged: (1) data for simulations of short-term EP dose changes in vivo (mild acid leaching) provide superior predictions of tumor incidence compared to non-acid leached data; (2) sum of the EP surface areas (ÓSA) from these mildly acid-leached samples provides the optimum holistic dose response model; (3) progressive removal of dose associated with very short and/or thin EPs significantly degrades resultant ÓEP or ÓSA dose-based predictive model fits, as judged by Akaike’s Information Criterion (AIC); and (4) alternative, biologically plausible model adjustments provide evidence for reduced potency of EPs with length/width (aspect) ratios 80 µm. Regar

  7. Evaluacion de la tecnica de contraimmunoelectroforesis para determinar la potencia antigena de las vacunas antirrabicas Evaluation ot the counterimmunoelectrophoresis technique to determine the antigenic potency of antirrabic vaccines

    Directory of Open Access Journals (Sweden)

    Graciela Miceli

    1993-12-01

    paper presents the results obtained when using a counterimmunoelectrophoresis (CIE techniques to determine the antigens content in samples of 84 and 40 samples of lots of suckling mouse rabies and tissue culture rabies vaccines, respectively. The evaluation of rabies vaccines under, at, near and up to 0.3 UI by the NIH and CIE tests showed that for practical use, a CIE titer of 1:4 would match the minimum of NIH potency test requirement. Low degree of CIE test variability within our laboratory was observed, when two working reference and 7 lots of rabies vaccines from different origin and activity were tested in five independent assays. All titres fell within one double dilution what is an indication of its reproducibility. Good sensitivity to detect antigen deterioration in thermal degradation test was observed when samples of 3 lots of liquid suckling mouse rabies vaccine were held stored at 4ºC or at 37ºC for 4 weeks and assays by CIE and NIH tests. Finally, CIE test could apply by manufactures to follow the concentration procedures to determine the final end point which could match a desired antigenic value in the NIH potency test.

  8. Optimization and validation of ELISA immunoassay for the evaluation of in-vitro relative potency of a four-component human papillomavirus vaccine products.

    Science.gov (United States)

    Mostafa, Moushira M; Al-Ghobashy, Medhat A; Fathalla, Faten A; Salem, Maissa Y

    2016-11-01

    A sandwich-type ELISA was optimized and validated to determine the in-vitro relative potency of the four-component prophylactic Human papillomavirus (HPV) vaccine. The vaccine contains the non-infectious virus like particles (VLP) corresponding to HPV Types 6, 11, 16 and 18. A modification of the desorption step required to release the VLPs from the aluminum adjuvant was carried out. Samples were incubated with citrate buffer for two hours at 37 °C instead of overnight incubation at room temperature. Assay validation was then carried out according to ICH guidelines. The assay was linear over a concentration range of 0.30-2000.00 ng/mL for the four HPV types. The assay was accurate and precise with a LOD of 0.092, 0.081, 0.086 and 0.068 ng/mL for type 6, 11, 16 and 18 respectively. Results were also statistically compared to those obtained using the reported ELISA assay and no significant difference was noted. In contrary to the reported ELISA protocol, this optimized immunoassay was superior with respect to analysis time, without affecting the accuracy and precision (RSD useful for evaluating the efficacy of the quadrivalent HPV vaccine and is applicable for quality control and batch release purposes. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  9. ANTIOXIDANT POTENCY OF WATER KEFIR

    Directory of Open Access Journals (Sweden)

    Muneer Alsayadi M.S.

    2013-06-01

    Full Text Available Reactive oxygen species (ROS have strong relationship with several diseases. Many fermented foods were reported to be important sources for antioxidant compounds. Antioxidant activity of water kefir never reported in the scientific literature. The objective of this study was to detect and investigate the antioxidant potency of water kefir. Water kefir was prepared by fermentation of sugar solution with kefir grains for 24h. Antioxidant activity of fresh water kefir drink and its extract with (0.125–5 mg/ml was evaluated using 2,2,-diphenyl-1-pricrylhydrozyl (DPPH scavenging method, and inhibition of ascorbate autoxidation and the reducing power of water kefir were determined, Butylated hydroxyanisole (BHA and ascorbic acid were used for comparison. Water kefir demonstrated great ability to DPPH scavenging ranged (9.88-63.17%. And inhibit ascorbate oxidation by (6.08-25.57% increased in consequent with concentration raising. These results prime to conclude that water kefir could be promisor source of natural antioxidants with good potency in health developing.

  10. Performance evaluation and specification of trackless tack.

    Science.gov (United States)

    2016-09-01

    Several trackless tack products have come to market in Texas; however, there are currently no specifications to : ensure the products have trackless properties and adequate bond strength. The objectives of this project were to : (1) evaluate the trac...

  11. The evaluation of a physical method for the quantification of inactivated poliovirus particles and its relationship to D-antigenicity and potency testing in rats.

    NARCIS (Netherlands)

    T.R. Doel; A.D.M.E. Osterhaus (Albert); A.L. van Wezel; G. van Steenis (Bert)

    1984-01-01

    textabstractThe use of a density gradient procedure for the quantification of intact, inactivated poliovirus particles in vaccine preparations is described. The procedure is both sensitive and highly reproducible and the results correlate with those of potency tests in rats and with D-antigen

  12. Detection of Virus-Specific CD8+ T Cells With Cross-Reactivity Against Alloantigens: Potency and Flaws of Present Experimental Methods

    OpenAIRE

    van den Heuvel, Heleen; Heutinck, Kirstin M.; van der Meer-Prins, Ellen P.M.W.; Yong, Si La; Claas, Frans H. J; ten Berge, Ineke J. M.

    2015-01-01

    Background Virus-specific T cells have the intrinsic capacity to cross-react against allogeneic HLA antigens, a phenomenon known as heterologous immunity. In transplantation, these cells may contribute to the alloimmune response and negatively impact graft outcome. This study describes the various techniques that can be used to detect heterologous immune responses of virus-specific CD8+ T cells against allogeneic HLA antigens. The strengths and weaknesses of the different approaches are discu...

  13. Opioid analgesics: does potency matter?

    Science.gov (United States)

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  14. SHORT COMMUNICATION CARCINOGENIC POTENCY OF ...

    African Journals Online (AJOL)

    were used to compute the carcinogenic risk potency of the PAHs relative to benzo(a)pyrene (reference carcinogen). .... The health risk assessment methodology provided the basis for estimation of ..... IRIS, Integrated Risk Information System.

  15. Contact sensitivity by diisocyanates: potencies and cross-reactivities.

    Science.gov (United States)

    Thorne, P S; Hillebrand, J A; Lewis, G R; Karol, M H

    1987-01-01

    The dermal sensitizing potencies of four diisocyanates were investigated using the mouse ear-swelling test (MEST) with BALB/cBy mice. Mice were administered topical doses of diisocyanates to the abdomen and were challenged on the ear 4 days later with a nonirritating dose of chemical. The increase in ear thickness at 24 hr postchallenge indicated the extent of contact sensitivity. Ear thickness increase plotted against the log of the dose of diisocyanate indicated three regions of effects: a no-effect region, a dose-response region, and a region of reduced response at highest dosages. The potencies of the diisocyanates expressed as the SD50 (dose required to sensitize 50% of the animals in each group) were hexamethylene diisocyanate, 0.088 mg/kg; diphenylmethane-4,4'-diisocyanate, 0.73 mg/kg; and toluene diisocyanate, 5.3 mg/kg. For dicyclohexylmethane diisocyanate, the steep dose-response curve suggested a threshold-type response occurring at 0.24 mg/kg. The specificity of sensitization was evaluated by challenging sensitized animals with heterologous diisocyanates. The homologous reactions were always the most extensive. However, cross-reactions were noted between aryl and alkyl diisocyanates. Toluene diisocyanate, the weakest sensitizer, elicited the fewest cross-reactions. The MEST proved to be a simple and effective method for assessing delayed-type hypersensitivity without need of adjuvants, occlusive patches, abrasions, or other procedures which fail to mimic industrial exposures. The observation that very high exposures resulted in reduced response indicates that protocols which generate dose-response data must be utilized to accurately assess the sensitizing potencies of industrial chemicals.

  16. An Evaluation of the Antimicrobial Potency of Lasianthera africana (BEAUV and Heinsia crinata (G. Taylor on Escherichia coli, Salmonella typhi, Staphylococcus aureus and Candida albicans

    Directory of Open Access Journals (Sweden)

    Andy, I. E.

    2008-01-01

    Full Text Available Information on the potency of many African medical plants against microorganisms is scanty, and in the current wave of antimicrobial resistance against chemotherapeutic drugs, there is need to search for plants that could be resistance-free and affordable. The objective of this study was to investigate the antimicrobial effects of the extracts of Lasianthera africana (E1 and Heinsia crinata (E2 in combination with chloramphenicol, on Escherichia coli, Salmonella typhi, Staphlococcus aureus and Candida albicans. For this purpose, the dilution sensitivity and disc diffusion techniques were respectively applied in determining minimum inhibitory concentration (MIC of the plant extracts, and the sensitivities of the organisms to the plant extracts and their combinations with chloramphenicol. L. africana and H. crinata showed very high antimicrobial activity against all the test organisms. In combination, the effect of E1 on E. coli and S. typhi was completely antagonized by that of E2, whereas additive effect on S. aureus and C. albicans was observed, indicating that the combination of E1 and E2 might be effective against gram positive pathogenic organisms. The combination of either plant extract with chloramphenicol produced synergistic effect on only C. albicans. The smaller MIC of E2 indicated greater effectivity than E1. It is concluded that the additive effect produced by the combination of the two plant extracts, and the synergic effect from the combination of any of the extracts with chloramphenicol, offer alternative therapy to gram positive bacterial infections and candidiasis respectively.

  17. Evaluation of drug content (potency) for compounded and FDA-approved formulations of doxycycline on receipt and after 21 days of storage.

    Science.gov (United States)

    KuKanich, Kate; KuKanich, Butch; Slead, Tanner; Warner, Matt

    2017-10-01

    OBJECTIVE To determine drug content (potency) of compounded doxycycline formulations for veterinary use and of US FDA-approved doxycycline formulations for human use content was measured in 5 samples of each tablet, chew, or capsule formulation and 5 replicates/bottle of liquid formulation on days 1 and 21 by liquid chromatography and compared with US Pharmacopeia acceptable ranges. RESULTS All FDA-approved formulations had acceptable content on days 1 and 21. On day 1, mean doxycycline content for the 3 compounded tablet formulations was 89%, 98%, and 116% (3/5, 5/5, and 1/5 samples within acceptable ranges); day 21 content range was 86% to 112% (1/5, 5/5, and 4/5 samples within acceptable ranges). Day 1 content of chews was 81%, 78%, and 98% (0/5, 0/5, and 5/5 samples within acceptable ranges), and that of compounded liquids was 50%, 52%, and 85% (no results within acceptable ranges). No chews or compounded liquid formulations met USP standards on day 21. CONCLUSIONS AND CLINICAL RELEVANCE FDA-approved doxycycline should be prescribed when possible. Whole tablets yielded the most consistent doxycycline content for compounded formulations.

  18. The Effects of Medical Marijuana Laws on Potency

    Science.gov (United States)

    Pacula, Rosalie Liccardo; Heaton, Paul

    2014-01-01

    Background Marijuana potency has risen dramatically over the past two decades. In the United States, it is unclear whether state medical marijuana policies have contributed to this increase. Methods Employing a differences-in-differences model within a mediation framework, we analyzed data on n = 39,157 marijuana samples seized by law enforcement in 51 U.S. jurisdictions between 1990-2010, producing estimates of the direct and indirect effects of state medical marijuana laws on potency, as measured by Δ9-tetrahydrocannabinol content. Results We found evidence that potency increased by a half percentage point on average after legalization of medical marijuana, although this result was not significant. When we examined specific medical marijuana supply provisions, results suggest that legal allowances for retail dispensaries had the strongest influence, significantly increasing potency by about one percentage point on average. Our mediation analyses examining the mechanisms through which medical marijuana laws influence potency found no evidence of direct regulatory impact. Rather, the results suggest that the impact of these laws occurs predominantly through a compositional shift in the share of the market captured by high-potency sinsemilla. Conclusion Our findings have important implications for policymakers and those in the scientific community trying to understand the extent to which greater availability of higher potency marijuana increases the risk of negative public health outcomes, such as drugged driving and drug-induced psychoses. Future work should reconsider the impact of medical marijuana laws on health outcomes in light of dramatic and ongoing shifts in both marijuana potency and the medical marijuana policy environment. PMID:24502887

  19. ANTIOXIDANT POTENCY OF WATER KEFIR

    OpenAIRE

    Muneer Alsayadi M.S.; Yaser Al Jawfi; Meriem Belarbi; Fatima Z. Sabri

    2013-01-01

    Reactive oxygen species (ROS) have strong relationship with several diseases. Many fermented foods were reported to be important sources for antioxidant compounds. Antioxidant activity of water kefir never reported in the scientific literature. The objective of this study was to detect and investigate the antioxidant potency of water kefir. Water kefir was prepared by fermentation of sugar solution with kefir grains for 24h. Antioxidant activity of fresh water kefir drink and its extract with...

  20. Direct analysis of prostaglandin-E2 and -D2 produced in an inflammatory cell reaction and its application for activity screening and potency evaluation using turbulent flow chromatography liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Shin, Jeong-Sook; Peng, Lei; Kang, Kyungsu; Choi, Yongsoo

    2016-09-09

    Direct analysis of prostaglandin-E2 (PGE2) and -D2 (PGD2) produced from a RAW264.7 cell-based reaction was performed by liquid chromatography high-resolution mass spectrometry (LC-HRMS), which was online coupled with turbulent flow chromatography (TFC). The capability of this method to accurately measure PG levels in cell reaction medium containing cytokines or proteins as a reaction byproduct was cross-validated by two conventional methods. Two methods, including an LC-HRMS method after liquid-liquid extraction (LLE) of the sample and a commercial PGE2 enzyme-linked immunosorbent assay (ELISA), showed PGE2 and/or PGD2 levels almost similar to those obtained by TFC LC-HRMS over the reaction time after LPS stimulation. After the cross-validation, significant analytical throughputs, allowing simultaneous screening and potency evaluation of 80 natural products including 60 phytochemicals and 20 natural product extracts for the inhibition of the PGD2 produced in the cell-based inflammatory reaction, were achieved using the TFC LC-HRMS method developed. Among the 60 phytochemicals screened, licochalcone A and formononetin inhibited PGD2 production the most with IC50 values of 126 and 151nM, respectively. For a reference activity, indomethacin and diclofenac were used, measuring IC50 values of 0.64 and 0.21nM, respectively. This method also found a butanol extract of Akebia quinata Decne (AQ) stem as a promising natural product for PGD2 inhibition. Direct and accurate analysis of PGs in the inflammatory cell reaction using the TFC LC-HRMS method developed enables the high-throughput screening and potency evaluation of as many as 320 samples in less than 48h without changing a TFC column. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. carcinogenic potency of polycyclic aromatic hydrocarbons in soil

    African Journals Online (AJOL)

    Carcinogenic potency of polycyclic aromatic hydrocarbons (PAHs) in soils obtained from seven different sampling locations in Effurun metropolis and its environs of Niger Delta Area of Nigeria were evaluated. The 16 US EPA priority PAHs were determined with GC-MS. The concentrations of individual PAHs observed were ...

  2. Evaluation of Quantitative Anti-F1 IgG and Anti-V IgG ELISAs for use as an in Vitro-Based Potency Assay of Plague Vaccine in Mice

    National Research Council Canada - National Science Library

    Little, S. F; Webster, W. M; Wilhelm, H; Powell, B; Enama, J; Adamovicz, J. J

    2008-01-01

    .... Experimental results suggested that a potency assay based upon the serological response of female Swiss Webster mice, as measured by quantitative anti-F1 IgG and anti-V IgG ELISAs, might be used...

  3. Evaluation of Antimicrobial Potency and Phytochemical Screening of Persea americana Leaf Extracts against Selected Bacterial and Fungal Isolates of Clinical Importance

    OpenAIRE

    O. E. Ajayi; S. I. Awala; O. T. Olalekan; O. A. Alabi

    2017-01-01

    Aim: The quest for novel bioactive from natural sources informed the evaluation of the antimicrobial alongside the phytochemical composition of leaf extracts of Persea americana obtained from Akure, Ondo State, Nigeria. Study Design: This study assessed the prospective antimicrobial efficacy of Persia americana against selected clinically relevant bacteria and fungi. Place and Duration of Study: The study was conducted between April and September, 2015 at the Microbiology Laboratory o...

  4. Establishment of an in vivo potency assay for the recombinant hepatit is B surface antigen in monovalent and combined vaccines

    Directory of Open Access Journals (Sweden)

    Mabel Izquierdo-López

    2014-12-01

    Full Text Available In this paper the development of potency assay in animals (mice was made, with the objective of demonstrating the immunogenic power of the recombinant Hepatitis B surface antigen in monovalent and combined vaccines, produced at the Center of Genetic Engineering and Biotechnology. The potency test is a parameter in quality control and it is also a tool to demonstrate the consistency of the production process. Parameters such as duration of the test, number of animals in the test, as well as different areas for the maintenance of the animals were evaluated. The results on the applicability of the potency test, to two presentations of the vaccines; monovalent Heberbiovac HB and pentavalent liquid in one vial Heberpenta-L are shown, for which specificity studies, evaluating different vaccine lots, the behavior of linearity, and parallelism, as well as establishing quality specification of the test were performed. This assay led to the obtainment of reliable results for the vaccines evaluated, the consistent evaluation of the immunogenic power and the monitoring of different production processes.

  5. Evaluation of Chromane-Based Bryostatin Analogues Prepared via Hydrogen-Mediated C-C Bond Formation: Potency Does Not Confer Bryostatin-like Biology.

    Science.gov (United States)

    Ketcham, John M; Volchkov, Ivan; Chen, Te-Yu; Blumberg, Peter M; Kedei, Noemi; Lewin, Nancy E; Krische, Michael J

    2016-10-12

    The synthesis and biological evaluation of chromane-containing bryostatin analogues WN-2-WN-7 and the previously reported salicylate-based analogue WN-8 are described. Analogues WN-2-WN-7 are prepared through convergent assembly of the chromane-containing fragment B-I with the "binding domain" fragment A-I or its C26-des-methyl congener, fragment A-II. The synthesis of fragment B-I features enantioselective double C-H allylation of 1,3-propanediol to form the C2-symmetric diol 3 and Heck cyclization of bromo-diene 5 to form the chromane core. The synthesis of salicylate WN-8 is accomplished through the union of fragments A-III and B-II. The highest binding affinities for PKCα are observed for the C26-des-methyl analogues WN-3 (Ki = 63.9 nM) and WN-7 (Ki = 63.1 nM). All analogues, WN-2-WN-8, inhibited growth of Toledo cells, with the most potent analogue being WN-7. This response, however, does not distinguish between phorbol ester-like and bryostatin-like behavior. In contrast, while many of the analogues contain a conserved C-ring in the binding domain and other features common to analogues with bryostatin-like properties, all analogues evaluated in the U937 proliferation and cell attachment assays displayed phorbol ester-like and/or toxic behavior, including WN-8, for which "bryostatin-like PKC modulatory activities" previously was suggested solely on the basis of PKC binding. These results underscore the importance of considering downstream biological effects, as tumor suppression cannot be inferred from potent PKC binding.

  6. Sexual Function and the Use of Medical Devices or Drugs to Optimize Potency After Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Whaley, J. Taylor; Levy, Lawrence B. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Swanson, David A. [Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Pugh, Thomas J. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Kudchadker, Rajat J.; Bruno, Teresa L. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Frank, Steven J., E-mail: sjfrank@mdnaderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-04-01

    Purpose: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Methods and Materials: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. Results: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Conclusions: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

  7. Growth stimulation of dwarf peas (Pisum sativum L.) through homeopathic potencies of plant growth substances.

    Science.gov (United States)

    Baumgartner, S; Thurneysen, A; Heusser, P

    2004-10-01

    Efficacy of higher homeopathic potencies is controversial. Universally accepted specific detection assays for homeopathic dilutions do not exist. Basic research has to develop a spectrum of standardized tools to investigate the mode of action and nature of homeopathic potencies. Can the shoot growth reaction of dwarf peas (gibberellin- deficient mutants) be regarded as evidence of treatment with homeopathic potencies of plant growth substances? Pea seed (Pisum sativum L. cv. Fruher Zwerg) is immersed for 24 hours in homeopathic potency or control solutions for soaking. Plants germinate and grow in a standard cultivation substrate under controlled environmental conditions. Shoot length is measured 14 days after planting. A screening of homeopathic potencies (12x-30x) of four different plant growth substances revealed biological activity of certain potency levels of gibberellin and kinetin (p Growth stimulation through gibberellin 17x (5 x 10(-18 M)) was assessed in six independent replications; results confirmed those of the screening (p effect of gibberellin 17x seemed to weaken during the course of the experiments. The results back the hypothesis that homeopathic potencies of plant growth substances affect pea shoot growth. Dwarf peas might thus be an interesting system model for studying the action of homeopathic potencies. Further work is required to identify all boundary conditions modulating the reactivity of this system.

  8. Prion potency in stem cells biology.

    Science.gov (United States)

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  9. An Evaluation of Usefulness of Prostate Specific Antigen and Digital ...

    African Journals Online (AJOL)

    Objective: To evaluate the usefulness of prostate specific antigen (PSA) and digital rectal examination (DRE) in the diagnosis of cancer of the prostate (CaP) amongst unscreened patients. Patients, Materials ans Methods: A prospective study168 unscreened men who were referred for evaluation for CaP. They all had a ...

  10. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: analysis for consistency in production and testing at the laboratory of the Control of Biological Products of the RIVM

    NARCIS (Netherlands)

    Akkermans AM; Hendriksen CFM; Marsman FR; de Jong WH; van de Donk HJM

    1993-01-01

    A single-dilution assay can be a valid procedure to demonstrate that a product exceeds the minimal requirement given for potency provided that consistency in production and testing has been proven. Information is presented justifying the use of a single dilution assay based upon quantitative

  11. Assessment of the analgesic potency of constant rate infusion of ...

    African Journals Online (AJOL)

    In this study, the analgesic potency of constant rate infusion of tramadol hydrochloride and as adjunct to ketoprofen on laparotomy-induced pain was evaluated. Dogs were randomly assigned to 4 groups (n=5). Groups 1, 2 and 3 received 0.5mg/kg/hr, 1.0mg/kg/hr and 2.0mg/kg/hr IV; CRI of tramadol hydrochloride ...

  12. Assessment of pepper spray product potency in Asian and Caucasian forearm skin using transepidermal water loss, skin temperature and reflectance colorimetry.

    Science.gov (United States)

    Pershing, Lynn K; Reilly, Christopher A; Corlett, Judy L; Crouch, Dennis J

    2006-01-01

    Historically, pepper spray product potency has been established using a taste test evaluation. A taste test is subjective and may not be appropriate for assessing pepper potency in skin. The current study evaluated chemically diverse pepper sprays in human forearm skin using three objective, noninvasive parameters: transepidermal water loss, skin surface temperature and erythema, as a means for assessing dermal pharmacology, toxicology and product potency. Five commercial pepper spray products containing various capsaicinoid analogs at various concentrations were evaluated in duplicate on volar forearms of six Caucasians and six Asians using a 10 min exposure. Mean surface skin temperature, transepidermal water loss results were highly variable and therefore did not demonstrate dose responsive behavior to increasing capsaicinoid concentrations. Erythema, as measured by increases in a* (reflected light in the red-to-green color spectrum) of the L*a*b* uniform color scale, was superior among parameters evaluated in discriminating pepper spray potency and correlated well with the relative and total capsaicinoid concentration in the products. Products containing greater than 16 mg ml(-1) capsaicinoid concentration produced greater erythema responses in Caucasians than Asians. Asians responded greater to the synthetic analog, nonivamide, than to mixtures of capsaicinoids, while Caucasians responded equally to both capsaicinoid analogs. Thus, pepper spray product potency in human skin reflects the total capsaicinoid concentration, the specific capsaicin analog(s) present, and the race of the individual exposed. The finding that the reflectance colorimeter a* scale can differentiate these parameters in skin will have a significant impact on evaluating the use and efficacy of pepper spray products in humans. 2005 John Wiley & Sons, Ltd.

  13. MFEprimer: multiple factor evaluation of the specificity of PCR primers.

    Science.gov (United States)

    Qu, Wubin; Shen, Zhiyong; Zhao, Dongsheng; Yang, Yi; Zhang, Chenggang

    2009-01-15

    We developed a program named MFEprimer for evaluating the specificity of PCR primers based on multiple factors, including sequence similarity, stability at the 3'-end of the primer, melting temperature, GC content and number of binding sites between the primer and DNA templates. MFEprimer can help the user to select more suitable primers before running either standard or multiplex PCR reactions. The cDNA and genomic DNA databases of 10 widely used species, as well as user custom databases, were used as DNA templates for analyzing primers specificity. Furthermore, we maintained a Primer3Plus server with a modified Primer3Manager for one-stop primer design and specificity checking.

  14. Identification of Immunoreactive Peptides of Toxins to Simultaneously Assess the Neutralization Potency of Antivenoms against Neurotoxicity and Cytotoxicity of Naja atra Venom.

    Science.gov (United States)

    Liu, Bin-Sin; Wu, Wen-Guey; Lin, Min-Han; Li, Chi-Han; Jiang, Bo-Rong; Wu, Suh-Chin; Leng, Chih-Hsiang; Sung, Wang-Chou

    2017-12-25

    Assessing the neutralization capability of nonlethal but medically relevant toxins in venom has been a challenging task. Nowadays, neutralization efficacy is evaluated based simply on the survival rates of animals injected with antivenom together with a predefined dose of venom, which can determine potency against neurotoxicity but not validate the capability to neutralize cytotoxin-induced complications. In this study, a high correlation with in-vivo and in-vitro neutralization assays was established using the immunoreactive peptides identified from short-chain neurotoxin and cytotoxin A3. These peptides contain conserved residues associated with toxin activities and a competition assay indicated that these peptides could specifically block the antibody binding to toxin and affect the neutralization potency of antivenom. Moreover, the titers of peptide-specific antibody in antivenoms or mouse antisera were determined by enzyme-linked immunosorbent assay (ELISA) simultaneously, and the results indicated that Taiwanese bivalent antivenom (BAV) and Vietnamese snake antivenom-Naja (SAV-Naja) exhibited superior neutralization potency against the lethal effect of short-chain neurotoxin (sNTX) and cytotoxicity of cardiotoxin/cytotoxin (CTX), respectively. Thus, the reported peptide ELISA shows not only its potential for antivenom prequalification use, but also its capability of justifying the cross-neutralization potency of antivenoms against Naja atra venom toxicity.

  15. Identification of Immunoreactive Peptides of Toxins to Simultaneously Assess the Neutralization Potency of Antivenoms against Neurotoxicity and Cytotoxicity of Naja atra Venom

    Directory of Open Access Journals (Sweden)

    Bing-Sin Liu

    2017-12-01

    Full Text Available Assessing the neutralization capability of nonlethal but medically relevant toxins in venom has been a challenging task. Nowadays, neutralization efficacy is evaluated based simply on the survival rates of animals injected with antivenom together with a predefined dose of venom, which can determine potency against neurotoxicity but not validate the capability to neutralize cytotoxin-induced complications. In this study, a high correlation with in-vivo and in-vitro neutralization assays was established using the immunoreactive peptides identified from short-chain neurotoxin and cytotoxin A3. These peptides contain conserved residues associated with toxin activities and a competition assay indicated that these peptides could specifically block the antibody binding to toxin and affect the neutralization potency of antivenom. Moreover, the titers of peptide-specific antibody in antivenoms or mouse antisera were determined by enzyme-linked immunosorbent assay (ELISA simultaneously, and the results indicated that Taiwanese bivalent antivenom (BAV and Vietnamese snake antivenom-Naja (SAV-Naja exhibited superior neutralization potency against the lethal effect of short-chain neurotoxin (sNTX and cytotoxicity of cardiotoxin/cytotoxin (CTX, respectively. Thus, the reported peptide ELISA shows not only its potential for antivenom prequalification use, but also its capability of justifying the cross-neutralization potency of antivenoms against Naja atra venom toxicity.

  16. Fuzzy-Based Evaluation of a Specific Drive Train

    Directory of Open Access Journals (Sweden)

    Attila Piros

    2012-01-01

    Full Text Available This paper introduces a fuzzy-based evaluation method of a specific portion of the power train. In this case study was evaluated a specific combination of a commercial high-performance tractor engine and power split hydrostatic infinitely variable transmission (IVT. The first part of the study describes the field test of the power train, then the mathematical model of this power train is introduced. The objective of this study was the evaluation of the power train in some specific phases. The tractor is one of the most important machines in the agricultural mechanization and the mostly used tractor speed ranges were generated by different engine speed and transmission ratio combinations. In each case the engine consumption and the transmission efficiency were calculated based on this mathematical model. These results were evaluated with the method of corrected fuzzy mean (CFM. All of these calculations were performed in MATLAB. This study gives a design guide for the future processes of the engine-transmission matching as a result.

  17. Assaying the Potency of Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Philip D. Minor

    2015-02-01

    Full Text Available The potency of vaccines must be determined to ensure that the appropriate dose is given. The manufacture and assessment of influenza vaccines are complicated by the continuously changing nature of the pathogen, which makes efficacy estimates difficult but also confounds attempts to produce a well-validated, consistent potency assay. Single radial diffusion has been used for decades and provides a relatively simple way to measure the amount of biologically active materials present in the vaccine. It requires reagents, which are updated on a regular, frequently yearly, basis and alternative methods continue to be sought.

  18. Screening Diospyros mespiliformis extract for antimalarial potency ...

    African Journals Online (AJOL)

    Diospyros mespiliformis is used in ethnomedical practice for treating malaria attack. The aqueous extract of the plant's stem bark was investigated for in vivo antiplasmodial potency in mice. Curative effect against established infection, suppressive activity against early infection and prophylactic effect in residual infection ...

  19. Anaesthetic potency and physiological effects of refrigerated ...

    African Journals Online (AJOL)

    Several in vitro studies have justified the use of thiopentone solutions beyond the period recommended by the manufacturer. We conducted this in vivo study to investigate the anaesthetic potency and physiological effect of refrigerated thiopentone solution. Rabbits in four groups designated A, B, C and D were ...

  20. Novel speed test for evaluation of badminton-specific movements.

    Science.gov (United States)

    Madsen, Christian M; Karlsen, Anders; Nybo, Lars

    2015-05-01

    In this study, we developed a novel badminton-specific speed test (BST). The test was designed to mimic match play. The test starts in the center of the court and consists of 5 maximal actions to sensors located in each of the 4 corners of the court. The 20 actions are performed in randomized order as dictated by computer screen shots displayed 1 second after completion of the previous action. We assessed day-to-day variation in elite players, and specificity of the test was evaluated by comparing 30-m sprint performance and time to complete the BST in 20 elite players, 21 skilled players, and 20 age-matched physical active subjects (non-badminton players). Sprint performance was similar across groups, whereas the elite players were significantly (p ≤ 0.05) faster in the BST (total test time: 32.3 ± 1.1 seconds; average: 1.6 seconds per action) than the skilled (34.1 ± 2.0 seconds) and non-badminton players (35.7 ± 1.7 seconds). Day-to-day coefficient of variation (CV) of the BST was 0.7% for the elite players, whereas CV for repeated tests on the same day was 1.7% for elite, 2.6% for skilled, and 2.5% for non-badminton players. On this basis, we suggest that the BST may be valuable for evaluation of short-term maximal movement speed in badminton players. Thus, the BST seems to be sport specific, as it may discriminate between groups (elite, less trained players, and non-badminton players) with similar sprinting performance, and the low test-retest variation may allow for using the BST to evaluate longitudinal changes, for example, training effects or seasonal variations.

  1. Identification of sequence features that predict competition potency of siRNAs.

    Science.gov (United States)

    Li, Xin; Yoo, Jae Wook; Lee, June Hyung; Hahn, Yoonsoo; Kim, Soyoun; Lee, Dong-Ki

    2010-07-16

    Small interfering RNAs (siRNAs) specifically knock-down target mRNAs via RNA interference (RNAi) mechanism. During this process, introduction of excess amount of exogenous siRNAs could lead to the saturation of cellular RNAi machinery. One consequence of RNAi machinery saturation is the competition between two simultaneously introduced siRNAs, during which one siRNA loses gene silencing activity. Although competition phenomena have been well characterized, the molecular and sequence features of siRNAs that specify the competition potency remain poorly understood. Here, for the first time, we performed a large-scale siRNA competition potency analysis by measuring the competition potency of 56 different siRNAs and ranking them based on their competition potency. We have also established an algorithm to predict the competition potency of siRNAs based upon the conserved sequence features of strong and weak competitor siRNAs. The present study supports our hypothesis that the competition potency of siRNAs is specified by the 5'-half antisense sequence and provides a useful guideline to design siRNAs with minimal RNAi machinery saturation. Copyright 2010 Elsevier Inc. All rights reserved.

  2. 21 CFR 640.56 - Quality control test for potency.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Quality control test for potency. 640.56 Section...) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Cryoprecipitate § 640.56 Quality control test for potency. (a) Quality control tests for potency of antihemophilic factor shall be conducted...

  3. Evaluation of MAP-specific peptides following vaccination of goats

    DEFF Research Database (Denmark)

    Lybeck, Kari; Sjurseth, Siri K.; Melvang, Heidi Mikkelsen

    peptides. IFN-γ responses in healthy goats after the first vaccination were low, but testing of T cell lines from MAP-infected goats identified peptides inducing strong proliferative responses. Peptides for a second vaccination were selected by combining results from this study with a parallel cattle study......Our aim is to develop a subunit MAP vaccine not interfering with the diagnosis of paratuberculosis or bovine tuberculosis. This study’s objective was to evaluate MAP-specific peptides defined by in silico analysis. Peptides were picked by 1) comparing MAP genomes to that of other mycobacterium...... species or 2) selected based on “experience”. Peptides predicted to bind bovine MHC II by in silico analysis were included in further studies, resulting in two panels 1) genome-based and 2) selected. Initially, two groups of 15 healthy goats were vaccinated with one of the two panels (50 µg/peptide in CAF...

  4. 77 FR 67678 - Content Specifications and Shielding Evaluations for Type B Transportation Packages

    Science.gov (United States)

    2012-11-13

    ... COMMISSION Content Specifications and Shielding Evaluations for Type B Transportation Packages AGENCY... Regulatory Issue Summary (RIS) 2012-XX, ``Content Specifications and Shielding Evaluations for Type B... Plan for Transport Packages for Radioactive Material,'' for the review of content specifications and...

  5. Potency of Animal Models in KANSEI Engineering

    Science.gov (United States)

    Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

    Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

  6. In vitro antigen measurement and potency tests: challenges encountered during method development...and lessons learned.

    Science.gov (United States)

    Kubiak, V

    2012-01-01

    Despite significant investment and technical efforts, veterinary vaccine manufacturers continue to experience challenges with the transition from historic animal-based potency methods to in vitro potency assays. These challenges have a number of contributing factors, including an inadequate understanding of protective antigens and epitopes, a lack of ruggedness and discriminating capabilities in evolving immunologically-based methods, inconsistencies between methods used for in-process antigen measurement and finished product potency, and a lack of clear methods to characterize the finished formulation (including complex adjuvants). A lack of harmonized guidelines and consistent regulatory expectations further complicates these efforts. There is room for optimism, however. There are numerous examples of successful in vitro potency test implementations. Titrations of modified live viral and bacterial vaccines, immune-based quantitative assays, and the recent application of direct physicochemical methods have allowed the transition from animal testing in many applications globally. Specific challenges for assay development and implementation are discussed in the areas of 1) target antigen selection, 2) complexity of finished product formulation, 3) potency discrimination, and 4) stability-indicating relevance.

  7. A novel in vitro potency assay of antisera against Thai Naja kaouthia based on nicotinic acetylcholine receptor binding

    OpenAIRE

    Ratanabanangkoon, Kavi; Simsiriwong, Pavinee; Pruksaphon, Kritsada; Tan, Kae Yi; Eursakun, Sukanya; Tan, Choo Hock; Chantrathonkul, Bunkuea; Wongwadhunyoo, Wongsakorn; Youngchim, Sirida; Tan, Nget Hong

    2017-01-01

    Snake envenomation is an important medical problem. One of the hurdles in antivenom development is the in vivo assay of antivenom potency which is expensive, gives variable results and kills many animals. We report a novel in vitro assay involving the specific binding of the postsynaptic neurotoxins (PSNTs) of elapid snakes with purified Torpedo californica nicotinic acetylcholine receptor (nAChR). The potency of an antivenom is determined by its antibody ability to bind and neutralize the PS...

  8. Establishment of the relative antiinflammatory potency of deflazacort and prednisone in polymyalgia rheumatica

    DEFF Research Database (Denmark)

    Lund, B; Egsmose, C; Jørgensen, S

    1987-01-01

    of the present study was to determine the relative antiinflammatory potency of deflazacort and prednisone. In a randomized, cross-over, double-blind trial, 11 patients, all suffering from polymyalgia rheumatica, and all on a stable maintenance dose of prednisone, were treated with equimolar doses of prednisone...... fibrinogen, and serum alkaline phosphatase following the lowest dose of deflazacort, whereas no changes were seen following the higher doses of deflazacort or prednisone. In conclusion, the relative antiinflammatory potency of deflazacort and prednisone lies between 0.83 and 0.66 on a weight basis (1.......02 and 0.82 on a molar basis) as evaluated by clinical and biochemical parameters reflecting disease activity in polymyalgia. This disease appears to represent a sensitive, reliable and reproducible clinical model for assessment of the relative antiinflammatory potency of glucocorticoids....

  9. Potency control of modified live viral vaccines for veterinary use.

    Science.gov (United States)

    Terpstra, C; Kroese, A H

    1996-04-01

    This paper reviews various aspects of efficacy, and methods for assaying the potency of modified live viral vaccines. The pros and cons of parametric versus non-parametric methods for analysis of potency assays are discussed and critical levels of protection, as determined by the target(s) of vaccination, are exemplified. Recommendations are presented for designing potency assays on master virus seeds and vaccine batches.

  10. Biological potency evaluation and characterization of rhG-CSF in pharmaceutical products Avaliação biológica da potência e caracterização de rhG-CSF em produtos farmacêuticos

    Directory of Open Access Journals (Sweden)

    Cristiane F. Codevilla

    2004-01-01

    Full Text Available The identification of rhG-CSF was carried out in pharmaceutical preparations by non-reducing polyacrylamide gel electrophoresis and western blotting with specific antibodies, showing a single band in the 19 kDa region. The potency was assessed by the neutropenia mouse bioassay giving values between 88.4 and 122.4% of the stated potency. The precision index expressed by weight was between 141 and 432 for the independent assays. Batch-to-batch, the samples met the requirements for the safety test and bacterial endotoxins test. The biological and immunological results showed the quality of the products in clinical use and the specifications established contribute to assuring the safety and efficacy of biological medicines.Realizou-se a identificação do fator estimulador da colônia de granulócitos humanos recombinante em produtos farmacêuticos por eletroforese em gel de poliacrilamida não redutora e imunodetecção com anticorpos específicos, que apresentaram banda única na região de, aproximadamente, 19 kDa. A avaliação de potência baseada na contagem do número de neutrófilos em camundongos com neutropenia forneceu valores entre 88,4 - 122,4 % em relação à potência declarada. A precisão expressa pela ponderação, calculada nos ensaios independentes, forneceu valores entre 141 e 432. As amostras lote-a-lote cumpriram os requisitos dos testes de toxicidade e endotoxinas bacterianas. Os resultados dos ensaios biológicos e imunológicos demonstram a qualidade dos produtos farmacêuticos em uso clínico, e as especificações sugeridas contribuem para assegurar a inocuidade e eficácia terapêutica dos produtos biológicos.

  11. Evaluation of hydorhermal resources of Lithuania, the well specific approach

    Science.gov (United States)

    Sliaupa, Saulius; Sliaupiene, Rasa

    2017-04-01

    Lithuania is located in the eastern part of the Baltic sedimentary basin. The thickness of the sedimentary pile changes from 200 m in the southeast to 2300 m in west Lithuania. Two major geothermal aquifers are defined, referred to as Cambrian (30-70 m thick) and Lower Devonian (up to 120 m thick) dominated by sands and loosely cemented sandstones with subordinate shales and siltstones. The geothermal potential of different layers is different owing to different reservoir properties, thickness, and temperature. The latter parameter is controlled by depth and heat flow intensity which is twice as high in west Lithuania (70-80 mW/m2) as that in east Lithuania (40-50 mW/sq.m) The highest temperature close to 100degC is registered in Middle Cambrian sandstones of southwest Lithuania. The methodology of the heat potential calculation was developed that is based on well specific parameters evaluation. It owes to dense distribution of deep wells in Lithuania that allows rather detailed heat potential mapping. The heat potential (MWth) is calculated for the well duplet (production-injection) for each well site (or well group site). It allows compilation of the heat potential map (MWth) for prospective geothermal aquifers in a country scale. Aquifers of temperature exceeding 35degC were considered as potential formations for district heating application. The Cambrian geothermal aquifer covers the largest (29,800 km2) area in Lithuania. The most prospective area is confined to temperature range 35-65degC. A severe quartz cementation, dramatically reducing reservoir properties of Cambrian sandstones, occurs at higher temperatures, while average porosities are in the range of 22-15% within 35-65degC temperature interval. Assessment of geothermal resources show that 1-2 well doublets cover heating needs of individual towns. The well doublet extracted heat potential is estimated to range from 0.5 to 6.5 MWt. The depth in the potential area varies from 1 km in middle Lithuania to

  12. Simultaneous determination of purity and potency of the components of gentamycin using high-performance liquid chromatography.

    Science.gov (United States)

    Yang, Li-Hong; Chang, Yan; Yao, Shang-Chen; Hu, Chang-Qin

    2012-12-01

    The quality of some earlier developed antibiotics is usually ensured by the combination of HPLC purity and microbiological potency measurement in the pharmacopoeias of various countries because the relationship between their purity and potency is not clearly quantified. Due to potency is assessed using certain units of measurement, it can not be directly traced to the international system of units (SI unit). This has become a hotspot in the study of the quantitative relationship between purity and potency of antibiotics. It would be quite an achievement to simultaneously determine both purity and potency using HPLC methods during quality control. This study evaluated a multicomponent antibiotic product, gentamycin, as a test sample. First, pure samples of the C components of gentamycin: C1a, C2, C2a and C1 were prepared, separately. Second, quantitative relationship (theoretical potency) between the purity and potency of each C component of gentamycin were determined using 1H NMR, HPLC-ELSD and microbiological assay method. One milligram of gentamycin C1a, C2, C2a and C1 was equal to 1 286.98, 1 095.74, 1 079.52 and 739.61 gentamycin units, respectively. Finally, a method for the determination of gentamycin potency was established based on the proportion and content of C components of gentamycin. The unification of purity and potency for gentamycin was achieved using only HPLC-ELSD. It is also demonstrated that C components of gentamycin and micronomicin produce the same responses under ELSD, which means that it is not necessary to prepare separate reference standards for each C component of gentamycin and that quantitative testing can be performed accurately using only one micronomicin reference standard. This study simplified the previous method for the determination of the content of C components of gentamycin using HPLC-ELSD. The developed method is suitable for regular use as a part of quality control and can simplify the rigmarole quality control procedures

  13. [Immune stimulative potency of milk proteins].

    Science.gov (United States)

    Ambroziak, Adam; Cichosz, Grazyna

    2014-02-01

    Milk proteins are characterized by the highest immune stimulative potency from among all the proteins present in human diet. Whey proteins and numerous growth factors that regulate insulin secretion, differentiation of intestine epithelium cells, and also tissue restoration, are priceless in stimulation the immune system. Lactoferrin shows the most comprehensive pro-health properties: antioxidative, anticancer, immune stimulative and even chemopreventive. Also peptides and amino acids formed from casein and whey proteins possess immune stimulative activity. The most valuable proteins, i.e. lactoferrin, immune globulins, lactoperoxidase and lisozyme, together with bioactive peptides, are resistant to pepsin and trypsin activity. This is why they maintain their exceptional biological activity within human organism. Properly high consumption of milk proteins conditions correct function of immune system, especially at children and elderly persons.

  14. Improved patient specific seizure detection during pre-surgical evaluation.

    LENUS (Irish Health Repository)

    Chua, Eric C-P

    2011-04-01

    There is considerable interest in improved off-line automated seizure detection methods that will decrease the workload of EEG monitoring units. Subject-specific approaches have been demonstrated to perform better than subject-independent ones. However, for pre-surgical diagnostics, the traditional method of obtaining a priori data to train subject-specific classifiers is not practical. We present an alternative method that works by adapting the threshold of a subject-independent to a specific subject based on feedback from the user.

  15. Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay.

    Science.gov (United States)

    Shoulars, Kevin; Noldner, Pamela; Troy, Jesse D; Cheatham, Lynn; Parrish, Amanda; Page, Kristin; Gentry, Tracy; Balber, Andrew E; Kurtzberg, Joanne

    2016-05-12

    Banked, unrelated umbilical cord blood provides access to hematopoietic stem cell transplantation for patients lacking matched bone marrow donors, yet 10% to 15% of patients experience graft failure or delayed engraftment. This may be due, at least in part, to inadequate potency of the selected cord blood unit (CBU). CBU potency is typically assessed before cryopreservation, neglecting changes in potency occurring during freezing and thawing. Colony-forming units (CFUs) have been previously shown to predict CBU potency, defined as the ability to engraft in patients by day 42 posttransplant. However, the CFU assay is difficult to standardize and requires 2 weeks to perform. Consequently, we developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDH bright [ALDH(br)]), along with viable CD45(+) or CD34(+) cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with prespecified criteria testing accuracy, specificity, repeatability, intermediate precision, and linearity. We then prospectively examined the correlations among ALDH(br), CD34(+), and CFU content of 3908 segments over a 5-year period. ALDH(br) (r = 0.78; 95% confidence interval [CI], 0.76-0.79), but not CD34(+) (r = 0.25; 95% CI, 0.22-0.28), was strongly correlated with CFU content as well as ALDH(br) content of the CBU. These results suggest that the ALDH(br) segment assay (based on unit characteristics measured before release) is a reliable assessment of potency that allows rapid selection and release of CBUs from the cord blood bank to the transplant center for transplantation. © 2016 by The American Society of Hematology.

  16. Development and validation of a rapid, aldehyde dehydrogenase bright–based cord blood potency assay

    Science.gov (United States)

    Noldner, Pamela; Troy, Jesse D.; Cheatham, Lynn; Parrish, Amanda; Page, Kristin; Gentry, Tracy; Balber, Andrew E.; Kurtzberg, Joanne

    2016-01-01

    Banked, unrelated umbilical cord blood provides access to hematopoietic stem cell transplantation for patients lacking matched bone marrow donors, yet 10% to 15% of patients experience graft failure or delayed engraftment. This may be due, at least in part, to inadequate potency of the selected cord blood unit (CBU). CBU potency is typically assessed before cryopreservation, neglecting changes in potency occurring during freezing and thawing. Colony-forming units (CFUs) have been previously shown to predict CBU potency, defined as the ability to engraft in patients by day 42 posttransplant. However, the CFU assay is difficult to standardize and requires 2 weeks to perform. Consequently, we developed a rapid multiparameter flow cytometric CBU potency assay that enumerates cells expressing high levels of the enzyme aldehyde dehydrogenase (ALDH bright [ALDHbr]), along with viable CD45+ or CD34+ cell content. These measurements are made on a segment that was attached to a cryopreserved CBU. We validated the assay with prespecified criteria testing accuracy, specificity, repeatability, intermediate precision, and linearity. We then prospectively examined the correlations among ALDHbr, CD34+, and CFU content of 3908 segments over a 5-year period. ALDHbr (r = 0.78; 95% confidence interval [CI], 0.76-0.79), but not CD34+ (r = 0.25; 95% CI, 0.22-0.28), was strongly correlated with CFU content as well as ALDHbr content of the CBU. These results suggest that the ALDHbr segment assay (based on unit characteristics measured before release) is a reliable assessment of potency that allows rapid selection and release of CBUs from the cord blood bank to the transplant center for transplantation. PMID:26968535

  17. Quantitative correlation of mutagenic and carcinogenic potencies for heterocyclic amines from cooked foods and additional aromatic amines.

    Science.gov (United States)

    Hatch, F T; Knize, M G; Moore, D H; Felton, J S

    1992-06-01

    Aromatic amines have long been recognized as animal and human carcinogens. Recently heterocyclic aromatic amines (thermic amines) have been found in small amounts in cooked foods, primarily meats, and have proven to be potent mutagens and rodent carcinogens. Availability of quantitative databases for mutagenic potency in Salmonella and for carcinogenic potency in rodents has made possible a study of ten heterocyclic thermic amines and 24 aromatic amines. Potencies on mutagenic and carcinogenic scales were significantly correlated. By multiple linear regression analysis and multivariate analysis of variance, two descriptive structural factors were found to modulate the two modes of biological response. These factors were number of rings and methyl substitution at carbon atoms. The quantitative correlation between mutagenic and carcinogenic potencies and the modulating structural factors suggest a significant similarity of molecular mechanisms and support the utility of the short-term bacterial assay in evaluating hazard levels.

  18. Evaluation of Automatically Assigned Job-Specific Interview Modules

    NARCIS (Netherlands)

    Friesen, Melissa C; Lan, Qing; Ge, Calvin; Locke, Sarah J; Hosgood, Dean; Fritschi, Lin; Sadkowsky, Troy; Chen, Yu-Cheng; Wei, Hu; Xu, Jun; Lam, Tai Hing; Kwong, Yok Lam; Chen, Kexin; Xu, Caigang; Su, Yu-Chieh; Chiu, Brian C H; Ip, Kai Ming Dennis; Purdue, Mark P; Bassig, Bryan A; Rothman, Nat; Vermeulen, Roel

    OBJECTIVE: In community-based epidemiological studies, job- and industry-specific 'modules' are often used to systematically obtain details about the subject's work tasks. The module assignment is often made by the interviewer, who may have insufficient occupational hygiene knowledge to assign the

  19. Evaluation of tumor-specific promoter activities in melanoma

    NARCIS (Netherlands)

    Lu, B; Makhija, SK; Nettelbeck, DM; Rivera, AA; Komarova, S; Zhou, F; Yamamoto, M; Haisma, HJ; Alvarez, RD; Curiel, DT; Zhu, ZB

    Gene therapy is a novel therapy for melanoma. To date, however, there is still no powerful tumor specific promoter (TSP) to restrict the transgene expression in melanoma cells. In order to define a useful TSP for targeting in the context of melanoma gene therapy, four promoters, the cyclooxygenase-2

  20. Formulation, development and evaluation of colon-specific ketorolac ...

    African Journals Online (AJOL)

    The major intention to formulate and develop colon targeted tablets is to improve the therapeutic efficacy by increasing therapeutic drug concentrations in colon. The present study was aimed to develop guar gum compression coated tablets ketorolac tromethamine to achieve the colon-specific drug release. In this study ...

  1. Evaluation of the sensitivity and specificity of latex agglutination and ...

    African Journals Online (AJOL)

    The sensitivity and specificity of latex agglutination test (LAT) and Complement fixation test (CFT) for the field diagnosis of Contagious Bovine Pleuropneumonia were determined using 90 bovine sera from various parts of the country. Of the ninety samples tested, 17 (18.9%) were positive in both tests, 2 (2.2%) were ...

  2. Evaluation of potential water conservation using site-specific irrigation

    Science.gov (United States)

    With the advent of site-specific variable-rate irrigation (VRI) systems, irrigation can be spatially managed within sub-field-sized zones. Spatial irrigation management can optimize spatial water use efficiency and may conserve water. Spatial VRI systems are currently being managed by consultants ...

  3. Disease specific methods for economic evaluations of breast cancer therapies

    NARCIS (Netherlands)

    Frederix, G.W.J.

    2013-01-01

    Cost-effectiveness analyses (CEAs) are widely considered to be helpful tools for making informative decisions in a resource constrained environment. Since the introduction of economic evaluations in reimbursement submissions in Australia as a formal requirement in 1993, CEAs have become widespread

  4. Non-specific Adaptive Reactions of Athletes: Evaluation and Correction

    Directory of Open Access Journals (Sweden)

    K. N. Naumova

    2015-12-01

    Full Text Available This work studies changes in non-specific adaptive reactions (NSAR of athletes who practice Wushu and Qigong and take Kladorod, a biological product made from plant material. The results of our study demonstrate the effectiveness of Kladorod as a remedy to enhance adaptive capacity with the possibility of application for training of athletes without any restrictions within the criteria of doping control.

  5. Establishing usability heuristics for heuristics evaluation in a specific domain: is there a consensus?

    OpenAIRE

    Hermawati, Setia; Lawson, Glyn

    2016-01-01

    Heuristics evaluation is frequently employed to evaluate usability. While general heuristics are suitable to evaluate most user interfaces, there is still a need to establish heuristics for specific domains to ensure that their specific usability issues are identified. This paper presents a comprehensive review of 70 studies related to usability heuristics for specific domains. The aim of this paper is to review the processes that were applied to establish heuristics in specific domains and i...

  6. MATHEMATICAL MODELING FOR ERYTHROMYCIN POTENCY DETERMINATION OF MASTIKER

    Directory of Open Access Journals (Sweden)

    Victorita Burghelea

    2016-12-01

    Full Text Available Mastiker E is an antibacterial suspension for intramammary infusion in cattle mastitis. The active drug is erythromycin, a macrolide antibiotic. The main characteristic of commercial product is erythromycin potency. The potency of erythromycin is estimated by comparing the inhibition of growth of sensitive micro-organisms produced by known concentrations of the antibiotic to be examined and a reference substance. The validation study aims to demonstrate the determination of the potency of erythromycin, it is an appropriate analytical method, reproducible and meets the quality requirements of Mastiker product. The paper establishes the performance characteristics of the method considered and identify the factors that influence these characteristics. The diameters of inhibition zones, directly proportional to the logarithm of the concentration of the antibiotic used for the assay, measured and calculated using statistical methods (Combistats Soft. The assay is designed in such a way that the mathematical model on which the potency equation is based can be proved to be valid. A parallel-line model is chosen. The two log dose response lines of the preparation under examination and the standard preparation are parallel; they are rectilinear over the range of doses used in the calculation. These conditions are verified by validity tests for a given probability (P = 0.05. The test is not valid unless the confidence limits (P = 0.95 are not less than 50% and not more than 200% of the estimated potency. The estimated potency is not less than 95% and not more than 105% of the stated potency. The stated potency is not less than 50.000 IU/g. The validation procedure includes details on protocol working to determine the potency of erythromycin, validation criteria, experimental results, mathematical modeling for determining the potency, inter laboratory comparisons.

  7. Relative embryotoxic potency of p-substituted phenols in the embryonic stem cell test (EST) and comparison to their toxic potency in vivo and in the whole embryo culture (WEC) assay.

    Science.gov (United States)

    Strikwold, Marije; Woutersen, Ruud A; Spenkelink, Bert; Punt, Ans; Rietjens, Ivonne M C M

    2012-09-03

    The applicability of the embryonic stem cell test (EST) as an alternative for in vivo embryotoxicity testing was evaluated for a series of five p-substituted phenols. To this purpose, the potency ranking for this class of compounds derived from the inhibition of cardiomyocyte differentiation in the EST was compared to in vivo embryotoxic potency data obtained from literature and to the potency ranking defined in the in vitro whole embryo culture (WEC) assay. From the results obtained it appears that the EST was able to identify the embryotoxic potential for p-substituted phenols, providing an identical potency ranking compared to the WEC assay. However, the EST was not able to predict an accurate ranking for the phenols compared to their potency observed in vivo. Only phenol, the least potent compound within this series, was correctly ranked. Furthermore, p-mercaptophenol was correctly identified as a relative potent congener of the phenols tested, but its ranking was distorted by p-heptyloxyphenol, of which the toxicity was overestimated in the EST. It is concluded that when attempting to explain the observed disparity in potency rankings between in vitro and in vivo embryotoxicity, the in vitro models should be combined with a kinetic model describing in vivo absorption, distribution, metabolism and excretion processes of the compounds. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Specific aspects of evaluation of control systems similarity

    Science.gov (United States)

    Evtushenko, V. F.; Burkov, V. N.; Myshlyaev, L. P.; Makarov, G. V.

    2017-09-01

    The paper discusses the problem of estimating the similarity of two or more control systems. In accordance with the statements made earlier it is indicated that such management systems should be characterized by a strict or approximate equality of the values of targeted indicators (criteria) of control effectiveness. Two main variants of procedures for estimating the control systems similarity are proposed. The first is based on the direct evaluation of the targeted indicators of control performance, the second - on the use of the so-called similarity relations, describing the conditions the fulfillment of which is valid for such systems. The procedures for evaluating the control systems similarity with the help of special similarity relations are associated with considerably less expenses. However, they are formed for a relatively narrow class of automatic control systems and are basically special cases of similarity, which requires further research in this direction.

  9. Critical evaluation of a badminton-specific endurance test.

    Science.gov (United States)

    Fuchs, Michael; Faude, Oliver; Wegmann, Melissa; Meyer, Tim

    2014-03-01

    To overcome the limitations of traditional 1-dimensional fitness tests in analyzing physiological properties of badminton players, a badminton-specific endurance test (BST) was created. This study aimed at analyzing the influence of various fitness dimensions on BST performance. 18 internationally competing male German badminton players (22.4 ± 3.2 y, 79.2 ± 7.7 kg, 1.84 ± 0.06 m, world-ranking position [WRP] 21-501) completed a straight-sprint test, a change-of-direction speed test, various jump tests (countermovement jump, drop jump, standing long jump), a multistage running test (MST), and the BST. During this on-court field test players have to respond to a computerized sign indicating direction and speed of badminton-specific movements by moving into the corresponding corners. Significant correlations were found between performance in MST and BST (individual anaerobic threshold [IAT], r = .63, P = .005; maximum velocity [Vmax], r = .60, P = .009). A negative correlation (r = -.59, P = .014) was observed between IAT in BST and drop-jump contact time. No further associations between performance indices could be detected. Apart from a small portion explained by MST results (IAT, R2 = .40; Vmax, R2 = .36), the majority of BST performance cannot be explained by the determined physiological correlates. Moreover, it was impossible to predict the WRP of a player on the basis of BST results (r = -.15, P = .55). Neither discipline-specific performance nor basic physiological properties were appropriately reflected by a BST in elite badminton players. This does not substantiate its validity for regular use as a testing tool. However, it may be useful for monitoring on-court training sessions.

  10. Development of Leptospira in vitro potency assays: EU/industry experience and perspectives.

    Science.gov (United States)

    Klaasen, H L B M; van der Veen, M; Molkenboer, M J C H; Bruderer, U

    2013-09-01

    Nobivac® Lepto (MSD Animal Health) is a non-adjuvanted canine leptospirosis vaccine containing inactivated whole cells of Leptospira interrogans serogroup Canicola serovar Portlandvere and L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni. The current standard in vivo potency test is a hamster challenge test associated with major drawbacks such as animal suffering and poor reproducibility. Here, the quantification of antigenic mass by ELISA as a new in vitro potency test is described, supporting the 3Rs concept (replacement, reduction, and refinement of animal tests) and in accordance with European Pharmacopoeia Monograph 0447 (Canine Leptospirosis Vaccine [Inactivated]). The two corresponding sandwich ELISAs are based on monoclonal antibodies specific for immunodominant leptospiral lipopolysaccharide epitopes. Protection in passive immunization experiments demonstrate that these monoclonal antibodies recognize key protective antigens in currently licensed human and veterinary whole cell Leptospira vaccines. The high precision and robustness renders the two ELISAs much more reliable correlates of potency in dogs than the hamster potency test. The recent approval of these assays for a new canine leptospirosis vaccine is an important contribution to the 3Rs in quality control testing of Leptospira vaccines. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  11. Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

    Science.gov (United States)

    Walker, A; Srinivas, G B

    2013-09-01

    Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

  12. Pilot implementation Driven by Effects Specifications and Formative Usability Evaluation

    DEFF Research Database (Denmark)

    Barlach, Anders; Hertzum, Morten; Simonsen, Jesper

    2013-01-01

    This chapter reports on the usability-engineering work performed throughout the pilot implementation of an Electronic Healthcare Record (EHR). The case describes and analyzes the use of pilot implementations to formatively evaluate whether the usability of the EHR meets the effects specified...... for its use. The project was initiated during the autumn of 2010 and concluded in the spring of 2012. The project configured and implemented an EHR at a Maternity ward at one hospital located in a European region and then transferred this system to another ward at another hospital in the same region...

  13. Robotic radical prostatectomy for elderly patients: probability of achieving continence and potency 1 year after surgery.

    Science.gov (United States)

    Shikanov, Sergey; Desai, Vikas; Razmaria, Aria; Zagaja, Gregory P; Shalhav, Arieh L

    2010-05-01

    We assessed the probability of achieving continence and potency after robotic radical prostatectomy in elderly patients. The cohort included 1,436 robotic radical prostatectomy cases performed at our institution between 2003 and 2008. Continence (pad-free) and potency (erection sufficient for intercourse) at baseline and 1 year after surgery were evaluated by the UCLA-PCI questionnaire. Point estimates of the predicted probabilities of continence and potency for age 65, 70 and 75 years were calculated from multivariate logistic regression models adjusting for age, nerve sparing status, baseline International Prostate Symptom Score and baseline Sexual Health Inventory for Men score. Patients who were impotent before surgery or those who received hormones or radiation within 1 year after surgery were censored. Mean patient age was 60 years (range 38 to 85) with 25% older than 65 years and 77 (5%) 70 years old or older. Age (OR 0.97, p = 0.002), baseline I-PSS (OR 0.98, p = 0.02) and Sexual Health Inventory for Men scores (OR 1.02, p = 0.005) were independently associated with being pad-free. Age (OR 0.92, p probability of achieving continence and potency after robotic radical prostatectomy in selected elderly patients. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Identification and evaluation of nextgeneration PTM-specific antibodies

    DEFF Research Database (Denmark)

    Persson, Nina Emilia

    -glycosylation. Incomplete O-glycan synthesis in cancer lead totruncated carbohydrate structures like the Tn-antigen (GalNac-Ser/Thr) or the STn-antigen(Neu5Acα2-6GalNAc-O-Ser/Thr). This type of aberrant glycosylation is very frequently foundin cancers and correlate with metastatic behaviour and bad prognosis......-chain fragment variable (scFv)clones. Two different analyses are performed on the same microarray. There is no need for anypurification or enrichment before screening. In the first analysis, the ability of the individualscFv clone to bind to the soluble form of the antigens is evaluated. Favouring selection...... for scFvwith higher affinity rather than avidity. In the second analysis the binding of scFv to denselypresentedantigens enable the identification of clones with lower affinity, resulting in an overallhigher hit rate. This workflow allows for early selection of high affinity binders againstpredefined...

  15. Novel speed test for evaluation of badminton specific movements

    DEFF Research Database (Denmark)

    Madsen, Christian Møller; Karlsen, Anders; Nybo, Lars

    2015-01-01

    In this study we developed a novel badminton speed test (BST). The test was designed to mimic match play. The test starts in the center of the court and consists of five maximal actions to sensors located in each of the four corners of the court. The 20 actions are performed in randomized order......-matched physical active subjects (non-badminton players). Sprint performance was similar across groups, whereas the elite players were significantly (Pbadminton players (35.7 ± 1.7) s. Day......-to-day coefficient of variation (CV) of the BST Test was 0.7 % for the elite players, while CV for repeated tests on the same day was 1.7 % for elite, 2.6 %, for skilled and 2.5 % for non-badminton players. On this basis we suggest that the BST may be valuable for evaluation of short-term maximal movement speed...

  16. Evaluating and Quantifying the Specific Deterrent Effects of DNA Databases.

    Science.gov (United States)

    Bhati, Avinash; Roman, Caterina G

    2014-02-01

    Today, the ability of deoxyribonucleic acid (DNA) evidence to place persons at crime scenes with near certainty is broadly accepted by criminal investigators, courts, policy makers, and the public. However, the public safety benefits of investments in DNA databases are largely unknown and research attempting to quantify these benefits is only gradually emerging. Given the inherent difficulty in randomly assigning offenders to treatment and comparison groups for the purpose of inferring specific deterrence and probative effects (PREs) of DNA databases, this study developed an alternate strategy for extracting these effects from transactional data. Reoffending patterns of a large cohort of offenders released from the Florida Department of Corrections custody between 1996 and 2004 were analyzed across a range of criminal offense categories. First, an identification strategy using multiple clock models was developed that linked the two simultaneous effects of DNA databases to different clocks measuring the same events. Then, a semiparametric approach was developed for estimating the models. The estimation models yielded mixed results. Small deterrent effects-2-3% reductions in recidivism risk attributable to deterrence-were found only for robbery and burglary. However, strong PREs-20-30% increase in recidivism risk attributable to PREs-were uncovered for most offense categories. The probative and deterrent effects of DNA databases can be elucidated through innovative semiparametric models. © The Author(s) 2014.

  17. Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States.

    Science.gov (United States)

    Seeram, Navindra P; Aviram, Michael; Zhang, Yanjun; Henning, Susanne M; Feng, Lydia; Dreher, Mark; Heber, David

    2008-02-27

    A number of different beverage products claim to have antioxidant potency due to their perceived high content of polyphenols. Basic and applied research indicates that pomegranate juice (PJ), produced from the Wonderful variety of Punica granatum fruits, has strong antioxidant activity and related health benefits. Although consumers are familiar with the concept of free radicals and antioxidants, they are often misled by claims of superior antioxidant activity of different beverages, which are usually based only on testing of a limited spectrum of antioxidant activities. There is no available direct comparison of PJ's antioxidant activity to those of other widely available polyphenol-rich beverage products using a comprehensive variety of antioxidant tests. The present study applied (1) four tests of antioxidant potency [Trolox equivalent antioxidant capacity (TEAC), total oxygen radical absorbance capacity (ORAC), free radical scavenging capacity by 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP)]; (2) a test of antioxidant functionality, that is, inhibition of low-density lipoprotein (LDL) oxidation by peroxides and malondialdehyde methods; and (3) evaluation of the total polyphenol content [by gallic acid equivalents (GAEs)] of polyphenol-rich beverages in the marketplace. The beverages included several different brands as follows: apple juice (3), açaí juice (3), black cherry juice (3), blueberry juice (3), cranberry juice (3), Concord grape juice (3), orange juice (3), red wines (3), iced tea beverages (10) [black tea (3), green tea (4), white tea (3)], and a major PJ available in the U.S. market. An overall antioxidant potency composite index was calculated by assigning each test equal weight. PJ had the greatest antioxidant potency composite index among the beverages tested and was at least 20% greater than any of the other beverages tested. Antioxidant potency, ability to inhibit LDL oxidation, and total polyphenol

  18. Expansion of the in vitro assay for Leptospira potency testing to other Serovars: Case study with Leptospira hardjo

    Science.gov (United States)

    The Code for Federal Regulations (9 CFR 113:101-104) specifies how vaccine potency is evaluated in a hamster model for evaluation of leptospiral vaccines against pomona, icterohaemorrhagiae, canicola, and grippotyphosa serotypes of Leptospira interrogans. There are several issues which complicate th...

  19. Variation in Fourier transform infrared spectra of some homeopathic potencies and their diluent media.

    Science.gov (United States)

    Sukul, N C; Ghosh, Sudeshna; Sukul, A; Sinhababu, S P

    2005-10-01

    The aim of this study was to determine whether potentized homeopathic drugs and their diluent media differ from each other with respect to their Fourier transform infrared (FTIR) spectra. FTIR spectra of Nux vomica 30C, Lycopodium 30C, Santonin 30C, Cina 30C, Cina 206C, Cina 1006C, and their diluent media 90% ethanol and Ethanol 30C were obtained in the wave number range of 2000-1000 cm1 at 20 degrees C. Potassium bromide powder soaked with the potencies, pressed into pellets, and air dried were used to measure the spectra. Because water structures in homeopathic potencies are thought to carry specific information on drug molecules and because O-H bending vibrational band (v2) exclusively belongs to water, the study was restricted to the bands in that wave number region. Alcohol has no absorption in the O-H bending region. The potencies were found to differ from each other and their diluent media in the number of v2 bands, their wave number (cm1), shape, and half-width (cm1) of the bands. The number and other characteristics of the v2 band represent the number of hydrogen-bonded water species and their hydrogen-bonding strength, respectively. The potencies and their diluent media therefore differ from each other in the number of hydrogen-bonded water species and their hydrogen-bonding strength. The observation that KBr pellets soaked with a potentized drug retains its specific spectral absorption properties simply confirms that medicated sucrose globules, used in homeopathic dispensing, are capable of retaining the therapeutic properties of the drug.

  20. Solvatochromic dyes detect the presence of homeopathic potencies.

    Science.gov (United States)

    Cartwright, Steven J

    2016-02-01

    A systematic approach to the design of simple, chemical systems for investigating the nature of homeopathic medicines has led to the development of an experimental protocol in which solvatochromic dyes are used as molecular probes of serially diluted and agitated solutions. Electronic spectroscopy has been used to follow changes in the absorbance of this class of dyes across the visible spectrum in the presence of homeopathic potencies. Evidence is presented using six different solvatochromic dyes in three different solvent systems. In all cases homeopathic potencies produce consistent and reproducible changes in the spectra of the dyes. Results suggest that potencies influence the supramolecular chemistry of solvatochromic dyes, enhancing either dye aggregation or disaggregation, depending upon dye structure. Comparable dyes lacking the intramolecular charge transfer feature of solvatochromic dyes are unaffected by homeopathic potencies, suggesting potencies require the oscillating dipole of solvatochromic dyes for effective interaction. The implications of the results presented, both for an eventual understanding of the nature of homeopathic medicines and their mode of action, together with future directions for research in this area, are discussed. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  1. Relative embryotoxic potency of p-substituted phenols in the embryonic stem cell test (EST) and comparison to their toxic potency in vivo and in the whole embryo culture (WEC) assay

    NARCIS (Netherlands)

    Strikwold, M.; Woutersen, R.A.; Spenkelink, A.; Punt, A.; Rietjens, I.M.C.M.

    2012-01-01

    The applicability of the embryonic stem cell test (EST) as an alternative for in vivo embryotoxicity testing was evaluated for a series of five p-substituted phenols. To this purpose, the potency ranking for this class of compounds derived from the inhibition of cardiomyocyte differentiation in the

  2. Conjugation of a cell-penetrating peptide to parathyroid hormone affects its structure, potency, and transepithelial permeation

    DEFF Research Database (Denmark)

    Kristensen, Mie; de Groot, Anne Marit; Berthelsen, Jens

    2015-01-01

    hormone, i.e. PTH(1-34), and to evaluate the effect with regards to secondary structure, potency in Saos-2 cells, immunogenicity, safety as well as the transepithelial permeation across monolayers by using the Caco-2 cell culture model. Further, co-administration of CPP and PTH(1-34) as an alternative......-34) fusion peptides and their potency was found, albeit a general decrease in permeation was observed for both N- and C-terminally CPP-conjugated PTH(1-34) as compared to native PTH(1-34). However, attachment of CPP to the N-terminus significantly increased permeation across Caco-2 cell monolayers...... with an unacceptable low level of cell viability. In conclusion, covalent conjugation of CPPs to PTH(1-34) influenced both the secondary structure, potency, and transepithelial permeation efficiency of the resulting conjugate, and hence this approach appears not to be favorable as compared to co-administration when...

  3. Evaluation of potency of native Bacillus thuringiensis against maize ...

    African Journals Online (AJOL)

    Bacillus thuringiensis is the most used biological control agent to date. Among major constraints to maize production, safety and hence food sufficiency in Kenya is infestation, damage and contamination by insect pests. Maize grains are adversely damaged by. Prostephanus truncatus which occasionally paves way for the ...

  4. Microbiological evaluation of the potencies of brands of four ...

    African Journals Online (AJOL)

    Ten selected clinical bacterial isolates from patients with recurrent UTI were collected from the Microbiology unit of the University College Hospital, Ibadan and authenticated by standard bacteriological methods. The isolates were subjected to susceptibility test against eight standard antibiotics by disc diffusion method.

  5. Evaluation of buffering potency of oyster ( Crassostrea gasar ) shells ...

    African Journals Online (AJOL)

    ) shells on acidic borehole water for fish farming. Eighteen (18), 100-litre shaded plastic tanks (3/4- filled, pH 4.0) of three replicates per treatment of 270 g buffer agent were used. There were four trials of six treatments (T) namely control (C) ...

  6. Comparative sensitizing potencies of fragrances, preservatives, and hair dyes

    DEFF Research Database (Denmark)

    Lidén, Carola; Yazar, Kerem; Johansen, Jeanne Duus

    2016-01-01

    The local lymph node assay (LLNA) is used for assessing sensitizing potential in hazard identification and risk assessment for regulatory purposes. Sensitizing potency on the basis of the LLNA is categorized into extreme (EC3 value of ≤0.2%), strong (>0.2% to ≤2%), and moderate (>2%). To compare...... the sensitizing potencies of fragrance substances, preservatives, and hair dye substances, which are skin sensitizers that frequently come into contact with the skin of consumers and workers, LLNA results and EC3 values for 72 fragrance substances, 25 preservatives and 107 hair dye substances were obtained from...... and hair dyes are thus strong or extreme sensitizers (EC3 value of ≤2%), and fragrances are mostly moderate sensitizers. Although fragrances are typically moderate sensitizers, they are among the most frequent causes of contact allergy. This indicates that factors other than potency need to be addressed...

  7. Roles of participation and feedback in group potency.

    Science.gov (United States)

    Gamero, Nuria; Peiró, José M; Zornoza, Ana; Picazo, Carmen

    2009-08-01

    The roles of group participation and group performance feedback were examined as antecedents of group potency, i.e., beliefs shared among a work group's members about the general effectiveness of the work group. Also examined were how group participation and the congruence of the feedback received from different sources about performance predicted convergence in members' beliefs about group effectiveness. The sample comprised 61 work groups of professionals involved in Master in Business Administration (MBA) programs (284 participants). Mean group size was 4.6 members (SD = .58). 65% of participants were male, and 51% were between 30 and 40 years of age. Data were gathered at two measurement times. Increases in group participation were positively related to increases in group potency and the convergence in beliefs about group effectiveness among group members over time. Results supported the premise that group performance feedback is an antecedent of changes in group potency over time.

  8. Potency trends of delta9-THC and other cannabinoids in confiscated marijuana from 1980-1997.

    Science.gov (United States)

    ElSohly, M A; Ross, S A; Mehmedic, Z; Arafat, R; Yi, B; Banahan, B F

    2000-01-01

    The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahydrocannabinol (delta9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of delta9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of delta9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

  9. Salivary gland-specific P. berghei reporter lines enable rapid evaluation of tissue-specific sporozoite loads in mosquitoes.

    Directory of Open Access Journals (Sweden)

    Chandra Ramakrishnan

    Full Text Available Malaria is a life-threatening human infectious disease transmitted by mosquitoes. Levels of the salivary gland sporozoites (sgs, the only mosquito stage infectious to a mammalian host, represent an important cumulative index of Plasmodium development within a mosquito. However, current techniques of sgs quantification are laborious and imprecise. Here, transgenic P. berghei reporter lines that produce the green fluorescent protein fused to luciferase (GFP-LUC specifically in sgs were generated, verified and characterised. Fluorescence microscopy confirmed the sgs stage specificity of expression of the reporter gene. The luciferase activity of the reporter lines was then exploited to establish a simple and fast biochemical assay to evaluate sgs loads in whole mosquitoes. Using this assay we successfully identified differences in sgs loads in mosquitoes silenced for genes that display opposing effects on P. berghei ookinete/oocyst development. It offers a new powerful tool to study infectivity of P. berghei to the mosquito, including analysis of vector-parasite interactions and evaluation of transmission-blocking vaccines.

  10. Evaluation of Increasing Antecedent Specificity in Goal Statements on Adherence to Positive Behavior-Management Strategies

    Science.gov (United States)

    Cohrs, Corey M.; Shriver, Mark D.; Burke, Raymond V.; Allen, Keith D.

    2016-01-01

    We evaluated the impact of antecedent specificity in goal statements on adherence to positive behavior-management strategies. Teaching staff were recruited from 2 different school settings where there were routine expectations to use behavior-specific praise in the classroom, but adherence was poor. In a concurrent multiple baseline design, the…

  11. 78 FR 26090 - Content Specifications and Shielding Evaluations for Type B Transportation Packages

    Science.gov (United States)

    2013-05-03

    ... this RIS as a draft for public comment on November 13, 2012 (77 FR 67678), for a 45-day comment period... COMMISSION Content Specifications and Shielding Evaluations for Type B Transportation Packages AGENCY... Regulatory Commission (NRC) is issuing Regulatory Issue Summary (RIS) 2013-04, ``Content Specifications and...

  12. In vitro anti-platelet potency of ticagrelor in blood samples from infants and children.

    Science.gov (United States)

    Söderlund, Fredrik; Asztély, Anna-Karin; Jeppsson, Anders; Nylander, Sven; Berggren, Anders; Nelander, Karin; Castellheim, Albert; Romlin, Birgitta S

    2015-09-01

    Ticagrelor, a novel platelet inhibitor acting on the ADP-dependent P2Y12 receptor, is currently approved for treating adults with acute coronary syndrome. The effect of ticagrelor in children has not been explored. As a first step, we here evaluate if the in vitro anti-platelet potency of ticagrelor in blood samples from children of different age is different as compared with in blood samples from adults. Blood samples from 36 healthy children grouped by age (0-2 months, n=6; 2-6 months, n=6; 6months-2years, n=6; 2-6 years, n=10; 6-12 years, n=8) and 13 adults were collected for in vitro analysis using vasodilator stimulated phosphoprotein phosphorylation (VASP) assay in whole blood and ADP-induced light transmission aggregometry (LTA) in platelet rich plasma. Ticagrelor (0.01 - 10μmol/L) was added in vitro and its potency was assessed by calculating the concentration that provided 50% inhibition of the maximum response (IC50). The in vitro potency of ticagrelor in blood from adults and in blood from children of any age group were comparable, both when analyzed with LTA and with VASP. These in vitro results are consistent with the hypothesis that ticagrelor would achieve a comparable anti-platelet effect in children of different ages as in adults at equal plasma exposure. Copyright © 2015. Published by Elsevier Ltd.

  13. In vitro potency and combination testing of antimicrobial agents against Neisseria gonorrhoeae.

    Science.gov (United States)

    Bharat, Amrita; Martin, Irene; Zhanel, George G; Mulvey, Michael R

    2016-03-01

    Antimicrobial resistant Neisseria gonorrhoeae is a major concern to public health due to decreased susceptibility to frontline antimicrobials. To find agents that are active against N. gonorrhoeae, we tested antimicrobials alone or in combination by Etest gradient strips. The potencies (as assessed by minimum inhibitory concentrations) of twenty-five antimicrobials were evaluated against nine reference strains of N. gonorrhoeae (WHO F, G, K, L, M, N, O, P and ATCC 49226). Potency was greatest for netilmicin, quinupristin-dalfopristin, ceftriaxone, ertapenem and piperacillin-tazobactam. Combinations of azithromycin, moxifloxacin, or gentamicin with ceftriaxone, doripenem, or aztreonam were tested against reference isolates and the fractional inhibitory concentration index (FICI) was calculated. All nine combinations resulted in indifference (>0.5 FICI ≤ 4). Combinations with FICI gonorrhoeae. These data on antimicrobials with higher potency and combinations that did not show antagonism can help to guide larger scale susceptibility studies for antimicrobial resistant N. gonorrhoeae. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. Fish model for assessing the in vivo estrogenic potency of the mycotoxin zearalenone and its metabolites.

    Science.gov (United States)

    Arukwe, A; Grotmol, T; Haugen, T B; Knudsen, F R; Goksøyr, A

    1999-09-15

    The in vivo estrogenic potency of zearalenone (ZEA), a mycotoxin produced by different strains of Fusarium fungi, and its metabolites (alpha- and beta-zearalenol), have been studied in fish. Estrogenicity was evaluated using an in vitro competitive receptor binding assay and in vivo induction of vitellogenesis and zonagenesis, two estrogen receptor (ER)-mediated responses that are integral aspects of fish oogenesis. The ER binding affinities of alpha-zearalenol and ZEA in rainbow trout (Oncorhynchus mykiss) were approximately 1/150 and 1/300 to that of estradiol, respectively. Juvenile salmon (Salmo salar) were exposed to a single intraperitoneal injection of ZEA, alpha-zearalenol and beta-zearalenol (each at 1 and 10 mg/kg) and compared to fish injected with estradiol-17 beta (E2; 5 mg/kg) and controls. Using indirect enzyme-linked immunosorbent assay (ELISA) with homologous antibodies, a dose-dependent induction of vitellogenin (Vtg) and eggshell zona radiata proteins (Zr-proteins) were observed 7 days after exposure to ZEA and alpha-zearalenol. beta-Zearalenol did not elevate plasma Vtg levels, but a non-significant elevation of plasma Zr-proteins levels was observed at the highest dose (10 mg/kg). Generally, alpha-zearalenol and ZEA possess estrogenic potencies that are approximately 50% compared to that of E2, and their order of estrogenic potency (in both in vitro receptor competitive binding and in vivo induction of Vtg and Zr-proteins levels) is: alpha-zearalenol > ZEA > beta-zearalenol. Our results show that blood plasma analysis of Vtg and Zr-proteins levels provides a suitable in vivo fish model for assessing the estrogenic potencies of ZEA and its metabolites.

  15. A Domain Specific Language for Performance Evaluation of Medical Imaging Systems

    NARCIS (Netherlands)

    van den Berg, Freek; Remke, Anne Katharina Ingrid; Haverkort, Boudewijn R.H.M.; Turau, Volker; Kwiatkowska, Marta; Mangharam, Rahul; Weyer, Christoph

    2014-01-01

    We propose iDSL, a domain specific language and toolbox for performance evaluation of Medical Imaging Systems. iDSL provides transformations to MoDeST models, which are in turn converted into UPPAAL and discrete-event MODES models. This enables automated performance evaluation by means of model

  16. Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

    Science.gov (United States)

    Thompson, Chad M; Bichteler, Anne; Rager, Julia E; Suh, Mina; Proctor, Deborah M; Haws, Laurie C; Harris, Mark A

    2016-04-01

    Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment. Copyright © 2016 The Authors. Published by

  17. Project W-314 Specific Test and Evaluation Plan for 200E Waste Transfer System

    Energy Technology Data Exchange (ETDEWEB)

    HAMMERS, J.S.

    2000-02-25

    The purpose of this Specific Test and Evaluation Plan (STEP) is to provide a detailed written plan for the systematic testing of the newly constructed 200E Waste Transfer System in the W-314 Project. The STEP provides the outline for test and evaluation methods that verify the system's performance and compliance to the established Project design criteria. The STEP is a ''lower tier'' document based on the W-314 Test & Evaluation Plan (TEP).

  18. Antibacterial and antifungal activity and Bone healing Potency of ...

    African Journals Online (AJOL)

    EDEMA

    Vol. 17, 2012. Antibacterial and antifungal activity and Bone healing Potency of methanol extract of. Cissus arguta Hook F. 1 ... antimicrobial drugs such as ciprofloxacin-antibacterial and fluconazole -antifungal. This study therefore serves to justify its ... boils, wounds, skin and sexually transmitted infections, body pains as ...

  19. potency of aqueous stem bark extract of khaya senegalensis against ...

    African Journals Online (AJOL)

    DR. AMINU

    the induction of liver damage in the rats using carbon tetrachloride, CCl4. The rats treated with a daily dose of 80mg/kg ... Key words: Khaya senegalensis, potency, liver diseases, carbon tetrachloride. INTRODUCTION. The use of herbal .... gas chromatography with electron capture detection. J. Chromatog. Biomed. Appl.

  20. Determination of Total Potency Equivalent Concentration (Tpec) of ...

    African Journals Online (AJOL)

    Determination of Total Potency Equivalent Concentration (Tpec) of Carcinogenic Polycyclic Aromatic Hydrocarbons (Cpahs) In Soils of Bodo-City. ... the application of Dispersion by Chemical Reaction Technology, should be deployed immediately in this area for total detoxification and decontamination of the area.

  1. Assessment of the insecticidal potency of neem ( Azadirachta Indica ...

    African Journals Online (AJOL)

    The potency of aqueous and methanolic extracts of neem (Azadirachta indica A. Juss) seed kernel, in inhibiting and disrupting development of Anopheles mosquito was assessed in the laboratory. Different concentrations of aqueous and methanolic extracts were tested on eggs, larvae and pupae. Both extracts were found ...

  2. High Potency and Other Alcoholic Beverage Consumption among Adolescents

    Science.gov (United States)

    Jobli, Edessa C.; Dore, Heather S.; Werch, Chudley E.; Moore, Michele J.

    2005-01-01

    This study examined the prevalence of high potency (liquor, malt liquor, fortified wine) and other alcoholic beverage consumption (beer, wine/wine coolers) among adolescents, the impact of gender and ethnicity, and the risk and protective factors that predicted consumption. A confidential survey revealed that, among eighth grade students,…

  3. A laboratory assessment of the potential molluscicidal potency of ...

    African Journals Online (AJOL)

    Preliminary laboratory studies were conducted to determine the molluscicidal potency of Jatropha curcas, the physic nut. Biomphalaria glabrata and Bulinus globosus snails were exposed to varying concentrations of aqueous extracts of crushed J. curcas seeds from unripe, ripe and overripe fruits collected from two ...

  4. Antimicrobial Potency of Pentaclethra Macrophylla Seed Extract on ...

    African Journals Online (AJOL)

    The least inhibitory zone (25.0mm) was best recorded in ethanol extract against A. niger and C. albicans. The minimum inhibitory concentration of the extracts ranges between 62.5-250mg/ml on the test isolates. However, the antimicrobial potency of Pentaclethra macrophylla was more prominent against bacterial isolates ...

  5. Potency of aqueous stem bark extract of Khaya senegalensis ...

    African Journals Online (AJOL)

    In order to assess the potency of aqueous stem bark extract of Khaya senegalensis (KS) against liver diseases, serum aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were assayed in rats treated with two (2) different doses of the extract after the induction of liver damage in the ...

  6. Are High Potency Multivitamin Syrups Toxic | Mendle | Nigerian ...

    African Journals Online (AJOL)

    Background: High potency liquid multivitamin preparations contain many active vitamin ingredients having maximal daily dosage and formulated for prolonged administrations. They are intended to be used as food supplements and in the treatment or prophylaxis of vitamin deficiencies. Multivitamin preparations are highly ...

  7. Comparison Of The Safety, Immunogeni City And Potency Of La ...

    African Journals Online (AJOL)

    Some Poultry vaccines found in Nigeria are imported. Therefore, there is a need to compare the safety, immunogenicity and potency of some of the vaccines used to control Newcastle disease (ND) particularly La Sota ND vaccines and the V4 ND vaccine. A total of 120 day — o Id pullets were obtained from a commercial ...

  8. Ranking of hair dye substances according to predicted sensitization potency

    DEFF Research Database (Denmark)

    Søsted, H; Basketter, D A; Estrada, E

    2004-01-01

    substances registered in Europe and to provide their tonnage data. The sensitization potential of each substance was then estimated by using a quantitative structure-activity relationship (QSAR) model and the substances were ranked according to their predicted potency. A cluster analysis was performed...

  9. Potency of fibrolytic bacteria isolated from Indonesian sheep's colon ...

    African Journals Online (AJOL)

    Three fibrolytic bacteria were isolated from sheep's colon using cellulose (b), xylan (c) and lignin (d) as selective substrates. The potency of fibrolytic was identified by Subbarao methods. These isolates were then used both in pure and mixed culture with cattle cellulolytic bacteria (a) from the previous research. The isolates ...

  10. Mutagenic Potency of Food-Derived Heterocyclic Amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Knize, M G; Wu, R W; Colvin, M E; Hatch, F T; Malfatti, M A

    2006-10-26

    The understanding of mutagenic potency has been primarily approached using ''quantitative structure activity relationships'' (QSAR). Often this method allows the prediction of mutagenic potency of the compound based on its structure. But it does not give the underlying reason why the mutagenic activities differ. We have taken a set of heterocyclic amine structures and used molecular dynamic calculations to dock these molecules into the active site of a computational model of the cytochrome P-450 1A1 enzyme. The calculated binding strength using Boltzman distribution constants was then compared to the QSAR value (HF/6-31G* optimized structures) and the Ames/Salmonella mutagenic potency. Further understanding will only come from knowing the complete set of mutagenic determinants. These include the nitrenium ion half-life, DNA adduct half-life, efficiency of repair of the adduct, and ultimately fixation of the mutation through cellular processes. For two isomers, PhIP and 3-Me-PhIP, we showed that for the 100-fold difference in the mutagenic potency a 5-fold difference can be accounted for by differences in the P450 oxidation. The other factor of 20 is not clearly understood but is downstream from the oxidation step. The application of QSAR (chemical characteristics) to biological principles related to mutagenesis is explored in this report.

  11. The anaesthetic potency of benzocaine-hydrochloride in three ...

    African Journals Online (AJOL)

    The anaesthetic potency of benzocaine-hydrochloride in three freshwater fish species. J.T. Ferreira, H.J. Schoonbee and G.L. Smit. Research Unit for Fish Biology, Rand Afrikaans University, Johannesburg. Anaesthesia was induced in the common carp, Cyprinus carpio, tilapia, Oreochromis mossambicus and rainbow trout, ...

  12. Potency Studies of live- Attenuated Viral Vaccines Administered in ...

    African Journals Online (AJOL)

    We critically carried out a potency study in 1992 and 1997 on measles and poliovirus vaccines administered at five different vaccination centers in the metropolitan Lagos, Nigeria. using WHO guidelines on titration of live- viral vaccines, our results revealed that only 6 (16.7%) of 36 measles vaccine (MV) vials and 11 ...

  13. Establishing usability heuristics for heuristics evaluation in a specific domain: Is there a consensus?

    Science.gov (United States)

    Hermawati, Setia; Lawson, Glyn

    2016-09-01

    Heuristics evaluation is frequently employed to evaluate usability. While general heuristics are suitable to evaluate most user interfaces, there is still a need to establish heuristics for specific domains to ensure that their specific usability issues are identified. This paper presents a comprehensive review of 70 studies related to usability heuristics for specific domains. The aim of this paper is to review the processes that were applied to establish heuristics in specific domains and identify gaps in order to provide recommendations for future research and area of improvements. The most urgent issue found is the deficiency of validation effort following heuristics proposition and the lack of robustness and rigour of validation method adopted. Whether domain specific heuristics perform better or worse than general ones is inconclusive due to lack of validation quality and clarity on how to assess the effectiveness of heuristics for specific domains. The lack of validation quality also affects effort in improving existing heuristics for specific domain as their weaknesses are not addressed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Sanctioning Large-Scale Domestic Cannabis Production - Potency, Yield and Professionalism

    DEFF Research Database (Denmark)

    Møller, Kim; Lindholst, Christian

    2014-01-01

    Domestically cultivated cannabis, referred to as sinsemilla, constitutes a growing share of the illicit drug markets in the Scandinavian countries. In this study we present forensic evidence of THC content in sinsemilla and resin confiscated by the Danish police from 2008 to 2012. The purpose...... that courts do not apply a yield-percentage estimate. The specificities of domestic cannabis cultivation also relate to the sanction criteria „professionalism”. Firstly, the number of plants found can provide for calculation of an aggregate quantum. Secondly, this can be related to the formal quantum......-scale cannabis cases would improve by applying a 1:1 potency level between sinsemilla and resin....

  15. Evaluation of new asphalt concrete density specification. Final report, July 1987-June 1988

    Energy Technology Data Exchange (ETDEWEB)

    Maupin, G.W.

    1988-06-01

    The purpose of the investigation was to evaluate a new asphalt concrete density specification that utilizes a nuclear gauge and a control strip technique. The specification was studied on two field projects, and recommendations were made to improve it. The recommendations were to eliminate the correction factor, increase the number of density determinations, adopt a uniform policy in establishing the Marshall density, and provide instruction concerning roller patterns.

  16. Project W-314 specific test and evaluation plan 241-AN-B valve pit

    Energy Technology Data Exchange (ETDEWEB)

    Hays, W.H.

    1998-04-08

    The purpose of this Specific Test and Evaluation Plan (STEP) is to provide a detailed written plan for the systematic testing of modifications made to the 241-AN-B Valve Pit by the W-314 Project. The STEP develops the outline for test procedures that verify the system`s performance to the established Project design criteria. The STEP is a lower tier document based on the W-314 Test and Evaluation Plan (TEP).

  17. Status of JENDL High Energy File. Evaluation method, tools, specification, release procedure, etc

    Energy Technology Data Exchange (ETDEWEB)

    Fukahori, Tokio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-11-01

    The ENDF-6 format file should be kept as a standard distribution file and it is not difficult to convert into some other form for code`s libraries. From this point of view, status of JENDL High Energy File is introduced in this report as well as evaluation strategy, recommended specification, stored nuclides and quantities, a format structure, evaluation methods and tools, and release plan. (author)

  18. Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified Timothy grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12 in patients undergoing hyposensitization treatment

    Directory of Open Access Journals (Sweden)

    Renato Enzo Rossi

    2002-01-01

    Conclusions: These results indicate that grass pollen immunotherapy elicits an array of antibody specificities that reflect the allergen content and the potency of allergen extracts; this could be of pivotal importance to define optimal allergen extract doses.

  19. A Systematic Mapping Study on Empirical Evaluation of Software Requirements Specifications Techniques

    NARCIS (Netherlands)

    Condori-Fernandez, Nelly; Condori-Fernandez, Nelly; Daneva, Maia; Sikkel, Nicolaas; Wieringa, Roelf J.; Dieste, Oscar; Pastor, Oscar; Williams, L.; Miller, J.; Selby, R.

    2009-01-01

    This paper describes an empirical mapping study, which was designed to identify what aspects of Software Requirement Specifications (SRS) are empirically evaluated, in which context, and by using which research method. On the basis of 46 identified and categorized primary studies, we found that

  20. Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test

    Science.gov (United States)

    Willinger, Ulrike; Schmoeger, Michaela; Deckert, Matthias; Eisenwort, Brigitte; Loader, Benjamin; Hofmair, Annemarie; Auff, Eduard

    2017-01-01

    Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler…

  1. The performance evaluation of novices : The importance of competence in specific work activity clusters

    NARCIS (Netherlands)

    Molleman, Eric; van der Vegt, Gerben S.

    In this study, we examine the relationships between newcomers' competence in specific work activity clusters and the evaluation of their performance. Longitudinal data were gathered on 92 novice nurses from themselves and from the senior staff at three stages: before entering the job, 6 weeks after

  2. Evaluation of Transmission Line Model Structures for Silicide-to-Silicon Specific Contact Resistance Extraction

    NARCIS (Netherlands)

    Stavitski, N.; van Dal, Mark J.H.; Lauwers, Anne; Vrancken, Christa; Kovalgin, Alexeij Y.; Wolters, Robertus A.M.

    2008-01-01

    In order to measure silicide-to-silicon specific contact resistance �?c, transmission line model (TLM) structures were proposed as attractive candidates for embedding in CMOS processes. We optimized TLM structures for nickel silicide and platinum silicide and evaluated them for various doping levels

  3. Can biochemistry drive drug discovery beyond simple potency measurements?

    Science.gov (United States)

    Chène, Patrick

    2012-04-01

    Among the fields of expertise required to develop drugs successfully, biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of biochemistry in drug discovery could facilitate the identification and/or development of new drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Measuring kinetics and potency of hERG block for CiPA.

    Science.gov (United States)

    Windley, Monique J; Abi-Gerges, Najah; Fermini, Bernard; Hancox, Jules C; Vandenberg, Jamie I; Hill, Adam P

    2017-09-01

    The Comprehensive in vitro Proarrhythmic Assay (CiPA) aims to update current cardiac safety testing to better evaluate arrhythmic risk. A central theme of CiPA is the use of in silico approaches to risk prediction incorporating models of drug binding to hERG. To parameterize these models, accurate in vitro measurement of potency and kinetics of block is required. The Ion Channel Working Group was tasked with: i) selecting a protocol that could measure kinetics of block and was easily implementable on automated platforms for future rollout in industry and ii) acquiring a reference dataset using the standardized protocol. Data were acquired using a 'step depolarisation' protocol using manual patch-clamp at ambient temperature. Potency, kinetics and trapping characteristics of hERG block for the CiPA training panel of twelve drugs were measured. Timecourse of block and trapping characteristics could be reliably measured if the time constant for onset of block was between ~500ms and ~15s. Seven drugs, however had time courses of block faster than this cut-off. Here we describe the implementation of the standardized protocol for measurement of kinetics and potency of hERG block for CiPA. The results highlight the challenges in identifying a single protocol to measure hERG block over a range of kinetics. The dataset from this study is being used by the In Silico Working Group to develop models of drug binding for risk prediction and is freely available as a 'gold standard' ambient temperature dataset to evaluate variability across high throughput platforms. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Design and Synthesis of Macrocyclic Peptides with Anti- Cancer Potency /

    OpenAIRE

    Lin, Chun-Chieh

    2013-01-01

    Chapter 1. The background of peptides as therapeutics and anti-cancer agents is discussed in this chapter. The development for peptide synthesis via both solution and solid phase is introduced as well as the macrocyclization strategies. Chapter 2. Sansalvamide A (SanA) exhibits anti -cancer potency in the micromolar range against multiple cancer cell lines. Structure-activity relationship (SAR) and the mechanistic studies of SanA have been investigated in our lab. This chapter focuses on the ...

  6. Progestin potency – Assessment and relevance to choice of oral contraceptives

    Directory of Open Access Journals (Sweden)

    Norman Goldstuck

    2011-12-01

    Conclusions: Newer progestins are more receptor selective and potency is less relevant than it was with older progestins. Epidemiological studies of progestin potency and its role in disease generally use out of date information. There is still confusion about the relationship of dose and potency in some studies. The use of the EPA can help eliminate this.

  7. Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrullinated peptide.

    Science.gov (United States)

    Park, Min; Pyun, Jae-Chul; Akter, Hafeza; Nguyen, Binh Thanh; Kang, Min-Jung

    2015-11-10

    A specific peptide marker for diagnosing rheumatoid arthritis (RA) was found based on cyclic citrullinated peptide (CCP) using the following three steps: (1) analysis of the binding epitope of autoimmune antibodies using ϵ-aminocaproic acid-modified peptides; (2) RA diagnosis using sequence-modified peptides; and (3) evaluation of the peptides' diagnostic performance for RA diagnosis. Ninety-five serum samples were analyzed by ELISA and compared using MedCalc (version 15.2.1). Microplate binding ϵ-aminocaproic acid was added to the N- or C-terminal of the CCP sequence. The N-terminal anchoring peptide assay showed 15% higher specificity compared with the C-terminal anchoring peptide assay. Based on this result, the hydrophilic C-terminal sequence of CCP was substituted with a hydrophobic amino acid. Among the sequence-modified peptides, CCP11A (in which alanine was substituted for the 11th amino acid of CCP) assay showed the highest sensitivity (87%) and specificity (100%) for RA diagnosis. Thus, CCP11A was selected as a possible specific marker peptide for RA diagnosis and further analyzed. The results of this analysis indicated that CCP11A showed better specificity than the CCP assay in both healthy individuals (11% better) and OA cohort (20% better). From these results, CCP11A was evaluated as a specific marker for diagnosing RA with higher diagnostic performance. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Potency-scaled partitioning in descriptor spaces with increasing dimensionality.

    Science.gov (United States)

    Bajorath, Jürgen

    2005-01-01

    Partitioning algorithms are described that operate in chemical reference spaces formed by combinations of binary-transformed molecular descriptors and aim at the identification of potent hits in ligand-based virtual screening. One of these approaches depends on mapping of consensus positions of compound activity sets in descriptor spaces followed by step-wise extension of the dimensionality of these spaces and re-mapping of activity-dependent consensus positions. Dimension extension is carried out to increase the discriminatory power of descriptor combinations and distinguish database compounds from potential hits. This method was originally named Dynamic Mapping of Consensus positions (DMC) and subsequently extended in order to take different potency levels of known active molecules into account and increase the probability of recognizing potent database hits. The extension was accomplished by adding potency scaling to DMC calculations, and the resulting approach was termed POT-DMC. Results of comparisons of DMC and POT-DMC calculations on different classes of active compounds with substantially varying potency levels support the validity of the POT-DMC approach.

  9. Epoxy resin monomers with reduced skin sensitizing potency.

    Science.gov (United States)

    O'Boyle, Niamh M; Niklasson, Ida B; Tehrani-Bagha, Ali R; Delaine, Tamara; Holmberg, Krister; Luthman, Kristina; Karlberg, Ann-Therese

    2014-06-16

    Epoxy resin monomers (ERMs), especially diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to commonly cause skin allergy. This research describes a number of alternative ERMs, designed with the aim of reducing the skin sensitizing potency while maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, and assessed for sensitizing potency using the in vivo murine local lymph node assay (LLNA). All six epoxy resin monomers had decreased sensitizing potencies compared to those of DGEBA and DGEBF. With respect to the LLNA EC3 value, the best of the alternative monomers had a value approximately 2.5 times higher than those of DGEBA and DGEBF. The diepoxides were reacted with triethylenetetramine, and the polymers formed were tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. Four out of the six alternative ERMs gave polymers with a thermal stability comparable to that obtained with DGEBA and DGEBF. The use of improved epoxy resin monomers with less skin sensitizing effects is a direct way to tackle the problem of contact allergy to epoxy resin systems, particularly in occupational settings, resulting in a reduction in the incidence of allergic contact dermatitis.

  10. Process Ontology Specification for Enhancing the Process Compliance of a Measurement and Evaluation Strategy

    Directory of Open Access Journals (Sweden)

    Pablo Becker

    2015-04-01

    Full Text Available In this paper, we specify a generic ontology for the process domain considering the related state-of-the-art research literature. As a result, the recently built process ontology contributes to enrich semantically the terms for the (previously developed measurement and evaluation domain ontology by means of stereotypes. One of the underlying hypothesis in this research is that the generic ontology for process can be seen as a reusable artifact which can be used to enrich semantically not only the measurement and evaluation domain ontology but also to other domains involved in different organizational endeavors. For instance, for the measurement domain, now is explicit that the measurement term has the semantic of task, the measure term has the meaning of outcome, and the metric term has the semantic of method, from the process terminological base standpoint. The augmented conceptual framework, i.e. measurement and evaluation concepts plus process concepts, has also a positive impact on the GOCAME (Goal-Oriented Context-Aware Measurement and Evaluation strategy capabilities since ensures terminological uniformity, consistency and verifiability to its process and method specifications. In order to illustrate how the augmented conceptual framework impacts on the verifiability of GOCAME process and method specifications in addition to the consistency and comparability of results in measurement and evaluation projects, an ICT (Information and Communications Technology security and risk evaluation case study is used.

  11. In vivo potency revisited - Keep the target in sight.

    Science.gov (United States)

    Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

    2017-10-10

    Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl(L)), adding in parallel to the turnover (ksyn, kdeg) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (ke(RL)) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L50, is then derived. L50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L50 is then compared to the dissociation constant Kd (target-ligand binding affinity), the conventional Black & Leff potency estimate EC50, and the derived

  12. Test and evaluation document for DOT Specification 7A Type A Packaging. Revision 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-30

    The US Department of Energy (DOE) has been conducting, through several of its operating contractors, an evaluation and testing program to qualify Type A radioactive material packagings per US Department of Transportation (DOT) Specification 7A (DOT-7A) of the Code of Federal Regulations (CFR), Title 49, Part 178 (49 CFR 178). The program is currently administered by the DOE, Office of Facility Safety Analysis, DOE/EH-32, at DOE-Headquarters (DOE-HQ) in Germantown, Maryland. This document summarizes the evaluation and testing performed for all of the packagings successfully qualified in this program.

  13. Technical Note: Evaluation of individual ultraviolet radiation dosimeter sensitivity and specificity for assessing shade use.

    Science.gov (United States)

    Holcomb, K E; Stull, C L

    2017-09-01

    The effects of solar or UV radiation on livestock are often evaluated in research focused on heat stress, dermatological conditions, and other topics, with radiation measurements recorded by instrumentation at a field or local weather station for a general geographical location. Individual sensors would be valuable for quantifying an individual animal's exposure, especially as they move about in a heterogeneous environment. Individual commercially available UV dosimeters were evaluated for specificity and sensitivity and found to be potentially valuable research tools for assessing and comparing the UV radiation exposure of individual animals.

  14. Evaluation of the Sensitivity and Specificity of Immunohistochemical Markers in the Differential Diagnosis of Effusion Cytology

    Directory of Open Access Journals (Sweden)

    Zahraa Mohammed Yahya

    2013-11-01

    Full Text Available Objective: To evaluate the sensitivity and specificity of Calretinin and Carcinoembryonic antigen as immunocytochemical markers in distinguishing mesothelial cells from metastatic adenocarcinoma cells in effusion cytology.Methods: This study included 50 patients who presented with effusions (26 pleural and 24 peritoneal, at Al-Kadhimya Teaching Hospital who were selected according to their preliminary diagnosis from 1st December 2010 to 30th June 2011. Effusion fluids were aspirated and processed for both conventional cytological methods using Papanicolaou-stain and immunocytochemical staining with anti Calretinin and Carcinoembryonic antigen.Results: The sensitivity of cytology for detection of malignant cells was 77%, with 100% specificity and 86% accuracy. Calretinin was observed to be a specific (100% and sensitive (90% marker for mesothelial cells (of benign etiology. Carcinoembryonic antigen exhibited 70% sensitivity and 100% specificity for adenocarcinoma cells. When the results of both cytology and immunocytochemistry were considered in conjunction, the sensitivity for the detection of malignancy increased to 97%, with 100% specificity and 98% accuracy.Conclusion: Calretinin and Carcinoembryonic antigen were found to be useful markers for differentiating reactive mesothelial cells from metastatic adenocarcinoma cells in smears prepared from body fluids. Also, the combination of both cytology and immunocytochemical studies using the two markers can greatly enhance the diagnostic accuracy, sensitivity and specificity in malignant effusions.

  15. In vitro and in vivo evaluation of cysteine and site specific conjugated herceptin antibody-drug conjugates.

    Directory of Open Access Journals (Sweden)

    Dowdy Jackson

    Full Text Available Antibody drug conjugates (ADCs are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR, can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs.

  16. Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy.

    Science.gov (United States)

    Blank, Simon; Etzold, Stefanie; Darsow, Ulf; Schiener, Maximilian; Eberlein, Bernadette; Russkamp, Dennis; Wolf, Sara; Graessel, Anke; Biedermann, Tilo; Ollert, Markus; Schmidt-Weber, Carsten B

    2017-10-03

    Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.

  17. Approach for an improved experimental evaluation of the specific absorption rate in magnetic fluid hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Iacob, N. [National Institute for Lasers, Plasma and Radiation Physics (Romania); Schinteie, G.; Palade, P.; Kuncser, V., E-mail: kuncser@infim.ro [National Institute of Materials Physics (Romania)

    2015-04-15

    A new methodology for the accurate determination of the specific absorption rate of ferrofluids with magnetite nanoparticles of average size of about 10 nm subjected to alternative current magnetic fields is proposed. A simple numerical compensation of the heating rates by the cooling rates obtained at similar temperatures is employed. Comparisons of the as-obtained adiabatic heating curves with theoretical evaluations are discussed.

  18. Psychometric evaluation of commonly used game-specific skills tests in rugby: A systematic review.

    Science.gov (United States)

    Oorschot, Sander; Chiwaridzo, Matthew; Cm Smits-Engelsman, Bouwien

    2017-01-01

    To (1) give an overview of commonly used game-specific skills tests in rugby and (2) evaluate available psychometric information of these tests. The databases PubMed, MEDLINE CINAHL and Africa Wide information were systematically searched for articles published between January 1995 and March 2017. First, commonly used game-specific skills tests were identified. Second, the available psychometrics of these tests were evaluated and the methodological quality of the studies assessed using the Consensus-based Standards for the selection of health Measurement Instruments checklist. Studies included in the first step had to report detailed information on the construct and testing procedure of at least one game-specific skill, and studies included in the second step had additionally to report at least one psychometric property evaluating reliability, validity or responsiveness. 287 articles were identified in the first step, of which 30 articles met the inclusion criteria and 64 articles were identified in the second step of which 10 articles were included. Reactive agility, tackling and simulated rugby games were the most commonly used tests. All 10 studies reporting psychometrics reported reliability outcomes, revealing mainly strong evidence. However, all studies scored poor or fair on methodological quality. Four studies reported validity outcomes in which mainly moderate evidence was indicated, but all articles had fair methodological quality. Game-specific skills tests indicated mainly high reliability and validity evidence, but the studies lacked methodological quality. Reactive agility seems to be a promising domain, but the specific tests need further development. Future high methodological quality studies are required in order to develop valid and reliable test batteries for rugby talent identification. PROSPERO CRD42015029747.

  19. Technical specification for the Product Evaluation Management Information System (PREMIS) Version 1. 1. 2

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, D.S.; Hall, R.C.; Orman, J.L.; Klamerus, J.

    1990-06-01

    This document contains the technical specifications and implementation details for the Product Evaluation Management Information System (PREMIS) Version 1.1.2. This document does not include the requirements analysis or design information and is not intended as a user's guide. The INGRES Applications-by-Forms (ABF) software development tool was used to specify and define the modules and screens which comprise the PREMIS application. Several external procedures are called by the ABF procedures; these have been written in VAX/VMS DCL (Digital Command Language) and SQL (Standard Query Language). These specifications together with the PREMIS information model and corresponding database definition constitute the PREMIS Version 1.1.2 technical specification and implementation description presented herein.

  20. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, Susan, E-mail: S.Gibbs@VUMC.nl [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Corsini, Emanuela [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Spiekstra, Sander W. [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Galbiati, Valentina [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Fuchs, Horst W. [CellSystems GmbH, Troisdorf (Germany); DeGeorge, George; Troese, Matthew [MB Research Labs, Spinnerstown, PA (United States); Hayden, Patrick; Deng, Wei [MatTek Corporation, Ashland, MA (United States); Roggen, Erwin [3Rs Management and Consultancy (Denmark)

    2013-10-15

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC{sub 50}) with human and animal data showed a superior correlation with human DSA{sub 05} (μg/cm{sup 2}) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA{sub 05} = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA{sub 05} data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency

  1. G-protein based ELISA as a potency test for rabies vaccines.

    Science.gov (United States)

    Chabaud-Riou, Martine; Moreno, Nadège; Guinchard, Fabien; Nicolai, Marie Claire; Niogret-Siohan, Elisabeth; Sève, Nicolas; Manin, Catherine; Guinet-Morlot, Françoise; Riou, Patrice

    2017-03-01

    The NIH test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. This test is based on mice immunization followed by intracerebral viral challenge. As part of global efforts to reduce animal experimentation and in the framework of the development of Sanofi Pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an ELISA as an alternative to the NIH test. This ELISA is based on monoclonal antibodies recognizing specifically the native form of the viral G-protein, the major antigen that induces neutralizing antibody response to rabies virus. We show here that our ELISA is able to distinguish between potent and different types of sub-potent vaccine lots. Satisfactory agreement was observed between the ELISA and the NIH test in the determination of the vaccine titer and their capacity to discern conform from non-conform batches. Our ELISA meets the criteria for a stability-indicating assay and has been successfully used to develop the new generation of rabies vaccine candidates. After an EPAA international pre-collaborative study, this ELISA was selected as the assay of choice for the EDQM collaborative study aimed at replacing the rabies vaccine NIH in vivo potency test. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. The use of a stably expressed FRET biosensor for determining the potency of cancer drugs.

    Directory of Open Access Journals (Sweden)

    William P Bozza

    Full Text Available Many cancer drugs are intended to kill cancer cells by inducing apoptosis. However, the potency assays used for measuring the bioactivity of these products are generally cell viability assays which do not distinguish between cell death and growth inhibition. Here we describe a cell-based fluorescence resonance energy transfer (FRET biosensor designed to measure the bioactivity of apoptosis inducing cancer drugs. The biosensor contains cyan fluorescent protein (CFP linked via caspase 3 and caspase 8 specific cleavage recognition sequences to yellow fluorescent protein (YFP. Upon caspase activation, as in the case of apoptosis induction, the linker is cleaved abolishing the cellular FRET signal. This assay closely reflects the mechanism of action of cancer drugs, in killing cancer cells and therefore can function as a potency test for different cancer drugs. We rigorously demonstrate this through characterization of a class of proteins targeting the death receptors. The one-step assay appears to be superior to other apoptosis-based assays because of its simplicity, convenience, and robustness.

  3. Contrasting biological potency of particulate matter collected at sites impacted by distinct industrial sources.

    Science.gov (United States)

    Thomson, Errol M; Breznan, Dalibor; Karthikeyan, Subramanian; MacKinnon-Roy, Christine; Vuong, Ngoc Q; Dabek-Zlotorzynska, Ewa; Celo, Valbona; Charland, Jean-Pierre; Kumarathasan, Prem; Brook, Jeffrey R; Vincent, Renaud

    2016-12-01

    Industrial sources contribute a significant proportion of anthropogenic particulate matter (PM) emissions, producing particles of varying composition that may differentially impact health. This study investigated the in vitro toxicity of ambient PM collected near industrial sites in relation to particle size and composition. Size-fractionated particles (ultrafine, PM0.1-2.5, PM2.5-10, PM>10) were collected in the vicinity of steel, copper, aluminium, and petrochemical industrial sites. Human lung epithelial-like A549 and murine macrophage-like J774A.1 cells were exposed for 24 h to particle suspensions (0, 30, 100, 300 μg/cm(2)). Particle potency was assessed using cytotoxic (resazurin reduction, lactate dehydrogenase (LDH) release) and inflammatory (cytokine release) assays, and regressed against composition (metals, polycyclic aromatic hydrocarbons (PAHs), endotoxin). Coarse (PM2.5-10, PM>10) particle fractions were composed primarily of iron and aluminium; in contrast, ultrafine and fine (PM0.1-2.5) fractions displayed considerable variability in metal composition (especially water-soluble metals) across collection sites consistent with source contributions. Semi-volatile and PM-associated PAHs were enriched in the fine and coarse fractions collected near metal industry. Cell responses to exposure at equivalent mass concentrations displayed striking differences among sites (SITE x SIZE and SITE x DOSE interactions, p Industrial sources produce particulate emissions with varying chemical composition that differ in their in vitro potency in relation to particle size and the levels of specific constituents.

  4. Development and Evaluation of Event-Specific Quantitative PCR Method for Genetically Modified Soybean MON87701.

    Science.gov (United States)

    Tsukahara, Keita; Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Nishimaki-Mogami, Tomoko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

    2016-01-01

    A real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) soybean event, MON87701. First, a standard plasmid for MON87701 quantification was constructed. The conversion factor (Cf) required to calculate the amount of genetically modified organism (GMO) was experimentally determined for a real-time PCR instrument. The determined Cf for the real-time PCR instrument was 1.24. For the evaluation of the developed method, a blind test was carried out in an inter-laboratory trial. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr), respectively. The determined biases and the RSDr values were less than 30 and 13%, respectively, at all evaluated concentrations. The limit of quantitation of the method was 0.5%, and the developed method would thus be applicable for practical analyses for the detection and quantification of MON87701.

  5. Evaluation of specific absorbed fractions in voxel phantoms using Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kinase, S.; Zankl, M.; Kuwabara, J.; Sato, K.; Noguchi, H.; Funabiki, J.; Saito, K

    2003-07-01

    There is a need to calculate specific absorbed fractions (SAFs) in voxel phantoms for internal dosimetry. For this purpose, an EGS4 user code for calculating SAFs using voxel phantoms was developed on the basis of an existing EGS4 user code for external dosimetry (UCPIXEL). In the developed code, the transport of photons, electrons and positrons in voxel phantoms can be simulated, particularly the transport simulations of secondary electrons in voxel phantoms. The evaluated SAFs for the GSF 'Child' voxel phantom using the developed code were found to be in good agreement with the GSF evaluated data. In addition, SAFs in adult voxel phantoms developed at JAERI were evaluated using the developed code and were compared with several published data. It was found that SAFs for organ self-absorption depend on the organ masses and would be affected by differences in the structure of the human body. (author)

  6. Evaluation of specific absorbed fractions in voxel phantoms using Monte Carlo simulation.

    Science.gov (United States)

    Kinase, S; Zankl, M; Kuwabara, J; Sato, K; Noguchi, H; Funabiki, J; Saito, K

    2003-01-01

    There is a need to calculate specific absorbed fractions (SAFs) in voxel phantoms for internal dosimetry. For this purpose, an EGS4 user code for calculating SAFs using voxel phantoms was developed on the basis of an existing EGS4 user code for external dosimetry (UCPIXEL). In the developed code, the transport of photons, electrons and positrons in voxel phantoms can be simulated, particularly the transport simulations of secondary electrons in voxel phantoms. The evaluated SAFs for the GSF 'Child' voxel phantom using the developed code were found to be in good agreement with the GSF evaluated data. In addition, SAFs in adult voxel phantoms developed at JAERI were evaluated using the developed code and were compared with several published data. It was found that SAFs for organ self-absorption depend on the organ masses and would be affected by differences in the structure of the human body.

  7. Cannabis-induced psychosis associated with high potency "wax dabs".

    Science.gov (United States)

    Pierre, Joseph M; Gandal, Michael; Son, Maya

    2016-04-01

    With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes. Published by Elsevier B.V.

  8. Potency of Microalgae as Biodiesel Source in Indonesia

    Directory of Open Access Journals (Sweden)

    H Hadiyanto

    2012-04-01

    Full Text Available Within 20 years, Indonesia should find another energy alternative to substitutecurrent fossil oil. Current use of renewable energy is only 5% and need to be improved up to 17%of our energy mix program. Even though, most of the area in Indonesia is covered by sea, howeverthe utilization of microalgae as biofuel production is still limited. The biodiesel from currentsources (Jatropha, palm oil, and sorghum is still not able to cover all the needs if the fossil oilcannot be explored anymore. In this paper, the potency of microalgae in Indonesia was analysed asthe new potential of energy (biodiesel sources.

  9. Potency of Microalgae as Biodiesel Source in Indonesia

    Directory of Open Access Journals (Sweden)

    H Hadiyanto

    2012-02-01

    Full Text Available Within 20 years, Indonesia should find another energy alternative to substitute current fossil oil. Current use of renewable energy is only 5% and need to be improved up to 17% of our energy mix program. Even though, most of the area in Indonesia is covered by sea, however the utilization of microalgae as biofuel production is still limited. The biodiesel from current sources (Jatropha, palm oil, and sorghum is still not able to cover all the needs if the fossil oil cannot be explored anymore. In this paper, the potency of microalgae in Indonesia was analysed as the new potential of energy (biodiesel sources.

  10. Experimental evaluation and design of unfilled and concrete-filled FRP composite piles : Task 4A : design specifications.

    Science.gov (United States)

    2015-08-01

    The overall goal of this project is the experimental evaluation and design of unfilled and concrete-filled FRP composite piles for load-bearing in bridges. This report covers Task 4A, Design Specifications. : Structural design specifications are base...

  11. Titer on chip: new analytical tool for influenza vaccine potency determination.

    Directory of Open Access Journals (Sweden)

    Laura R Kuck

    Full Text Available Titer on Chip (Flu-ToC is a new technique for quantification of influenza hemagglutinin (HA concentration. In order to evaluate the potential of this new technique, a comparison of Flu-ToC to more conventional methods was conducted using recombinant HA produced in a baculovirus expression system as a test case. Samples from current vaccine strains were collected from four different steps in the manufacturing process. A total of 19 samples were analysed by Flu-ToC (blinded, single radial immunodiffusion (SRID, an enzyme-linked immunosorbent assay (ELISA, and the purity adjusted bicinchoninic acid assay (paBCA. The results indicated reasonable linear correlation between Flu-ToC and SRID, ELISA, and paBCA, with regression slopes of log-log plots being 0.91, 1.03, and 0.91, respectively. The average ratio for HA content measured by Flu-ToC relative to SRID, ELISA, and paBCA was 83%, 147%, and 81%, respectively; indicating nearly equivalent potency determination for Flu-ToC relative to SRID and paBCA. These results, combined with demonstrated multiplexed analysis of all components within a quadrivalent formulation and robust response to HA strains over a wide time period, support the conclusion that Flu-ToC can be used as a reliable and time-saving alternative potency assay for influenza vaccines.

  12. Carcinogenic and mutagenic potencies for different PAHs sources in coastal sediments of Shandong Peninsula.

    Science.gov (United States)

    Li, Guo-liang; Lang, Yin-hai; Gao, Mao-sheng; Yang, Wei; Peng, Peng; Wang, Xiao-mei

    2014-07-15

    In this study, sources of PAHs in coastal sediments of Shandong Peninsula were apportioned using the chemical mass balance (CMB) model, and source apportionment of carcinogenic and mutagenic potencies was conducted combining CMB with the formula of benzo(a)pyrene carcinogenic equivalent (BaPTEQ) and BaP mutagenic equivalent (BaPMEQ) concentration. Total concentrations of sixteen PAHs in sediment ranged from 181.2 ng g(-1) to 303.6 ng g(-1), and concentrations of eight carcinogenic PAHs (cPAHs) varied from 98.8 ng g(-1) to 141.1 ng g(-1). The BaP played a dominant role for carcinogenic and mutagenic potencies of PAHs, although the IND showed the highest concentration level. The vehicular sources made the highest contribution to BaPTEQ (57.7%) and BaPMEQ (55.5%), while petrogenic source, the highest contributor for PAHs (39.4%), provided the lowest contribution to BaPTEQ (1.1%) and BaPMEQ (1.5%). Besides, the ecotoxicological evaluation, based on Sediment Quality Guidelines (SQGs), showed low ecological risks generally. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Atlas-based segmentation in breast cancer radiotherapy: Evaluation of specific and generic-purpose atlases.

    Science.gov (United States)

    Ciardo, Delia; Gerardi, Marianna Alessandra; Vigorito, Sabrina; Morra, Anna; Dell'acqua, Veronica; Diaz, Federico Javier; Cattani, Federica; Zaffino, Paolo; Ricotti, Rosalinda; Spadea, Maria Francesca; Riboldi, Marco; Orecchia, Roberto; Baroni, Guido; Leonardi, Maria Cristina; Jereczek-Fossa, Barbara Alicja

    2017-04-01

    Atlas-based automatic segmentation (ABAS) addresses the challenges of accuracy and reliability in manual segmentation. We aim to evaluate the contribution of specific-purpose in ABAS of breast cancer (BC) patients with respect to generic-purpose libraries. One generic-purpose and 9 specific-purpose libraries, stratified according to type of surgery and size of thorax circumference, were obtained from the computed tomography of 200 BC patients. Keywords about contralateral breast volume and presence of breast expander/prostheses were recorded. ABAS was validated on 47 independent patients, considering manual segmentation from scratch as reference. Five ABAS datasets were obtained, testing single-ABAS and multi-ABAS with simultaneous truth and performance level estimation (STAPLE). Center of mass distance (CMD), average Hausdorff distance (AHD) and Dice similarity coefficient (DSC) between corresponding ABAS and manual structures were evaluated and statistically significant differences between different surgeries, structures and ABAS strategies were investigated. Statistically significant differences between patients who underwent different surgery were found, with superior results for conservative-surgery group, and between different structures were observed: ABAS of heart, lungs, kidneys and liver was satisfactory (median values: CMDbreast and spinal cord obtained moderate performance (median values: 2 mm ≤ CMDbreast ABAS. The homogeneity in the selection of atlases based on multiple anatomical and clinical features and the use of specific-purpose libraries can improve ABAS performance with respect to generic-purpose libraries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Design, synthesis and biological evaluation of a multifunctional HER2-specific Affibody molecule for molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Thuy A. [Uppsala University, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden); Rosik, Daniel; Abrahmsen, Lars; Sjoeberg, Anna [Affibody AB, Bromma (Sweden); Sandstroem, Mattias [Uppsala University Hospital, Hospital Physics, Department of Oncology, Uppsala (Sweden); Waallberg, Helena [Royal Institute of Technology, School of Biotechnology, Division of Molecular Biotechnology, Stockholm (Sweden); Ahlgren, Sara [Uppsala University, Division of Nuclear Medicine, Department of Medical Sciences, Uppsala (Sweden); Orlova, Anna [Uppsala University, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden); Affibody AB, Bromma (Sweden); Tolmachev, Vladimir [Uppsala University, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden); Affibody AB, Bromma (Sweden); Uppsala University, Division of Nuclear Medicine, Department of Medical Sciences, Uppsala (Sweden)

    2009-11-15

    The purpose of this study was to design and evaluate a novel platform for labelling of Affibody molecules, enabling both recombinant and synthetic production and site-specific labelling with {sup 99m}Tc or trivalent radiometals. The HER2-specific Affibody molecule PEP05352 was made by peptide synthesis. The chelator sequence SECG (serine-glutamic acid-cysteine-glycine) was anchored on the C-terminal to allow {sup 99m}Tc labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium labelling. The resulting {sup 99m}Tc- and {sup 111}In-labelled Affibody molecules were evaluated both in vitro and in vivo. Both conjugates retained their capacity to bind to HER2 receptors in vitro and in vivo. The tumour to blood ratio in LS174T xenografts was 30 at 4 h post-injection for both conjugates. Biodistribution data showed that the {sup 99m}Tc-labelled Affibody molecule had a fourfold lower kidney accumulation compared with the {sup 111}In-labelled Affibody molecule while the accumulation in other organs was similar. Gamma camera imaging of the conjugates could clearly visualise the tumours 4 h after injection. Incorporation of the C-terminal SECG sequence in Affibody molecules provides a general multifunctional platform for site-specific labelling with different nuclides (technetium, indium, gallium, cobalt or yttrium) and for a flexible production (chemical synthesis or recombinant). (orig.)

  15. An evaluation of a recombinant multiepitope based antigen for detection of Toxoplasma gondii specific antibodies.

    Science.gov (United States)

    Hajissa, Khalid; Zakaria, Robaiza; Suppian, Rapeah; Mohamed, Zeehaida

    2017-12-29

    The inefficiency of the current tachyzoite antigen-based serological assays for the serodiagnosis of Toxoplasma gondii infection mandates the need for acquirement of reliable and standard diagnostic reagents. Recently, epitope-based antigens have emerged as an alternative diagnostic marker for the achievement of highly sensitive and specific capture antigens. In this study, the diagnostic utility of a recombinant multiepitope antigen (USM.TOXO1) for the serodiagnosis of human toxoplasmosis was evaluated. An indirect enzyme-linked immunosorbent assay (ELISA) was developed to evaluate the usefulness of USM.TOXO1 antigen for the detection of IgG antibodies against Toxoplasma gondii in human sera. Whereas the reactivity of the developed antigen against IgM antibody was evaluated by western blot and Dot enzyme immunoassay (dot-EIA) analysis. The diagnostic performance of the new antigens in IgG ELISA was achieved at the maximum values of 85.43% and 81.25% for diagnostic sensitivity and specificity respectively. The USM.TOXO1 was also proven to be reactive with anti- T. gondii IgM antibody. This finding makes the USM.TOXO1 antigen an attractive candidate for improving the toxoplasmosis serodiagnosis and demonstrates that multiepitope antigens could be a potential and promising diagnostic marker for the development of high sensitive and accurate assays.

  16. Pharmacological Identification of a Guanidine-Containing β-Alanine Analogue with Low Micromolar Potency and Selectivity for the Betaine/GABA Transporter 1 (BGT1)

    DEFF Research Database (Denmark)

    Al-Khawaja, Anas Mohammad Ali; Petersen, Jette Gellert; Damgaard, Maria

    2014-01-01

    ,4,5,6-tetrahydropyrimidine-5-carboxylic acid hydrochloride) displayed more than 250 times greater potency than the parent compound β-alanine at BGT1 and is thus the most potent inhibitor reported to date for this subtype (IC50 value of 2.5 µM). In addition, compound 9 displayed about 400, 16 and 40 times lower inhibitory...... potency at GAT1, GAT2 and GAT3, respectively. Compound 9 was shown to be a substrate for BGT1 and to have an overall similar pharmacological profile at the mouse orthologue. Compound 9 constitutes an interesting pharmacological tool for specifically investigating the cellular pharmacology of BGT1...

  17. Subject-specific musculoskeletal modeling in the evaluation of shoulder muscle and joint function.

    Science.gov (United States)

    Wu, Wen; Lee, Peter V S; Bryant, Adam L; Galea, Mary; Ackland, David C

    2016-11-07

    Upper limb muscle force estimation using Hill-type muscle models depends on musculotendon parameter values, which cannot be readily measured non-invasively. Generic and scaled-generic parameters may be quickly and easily employed, but these approaches do not account for an individual subject's joint torque capacity. The objective of the present study was to develop a subject-specific experimental testing and modeling framework to evaluate shoulder muscle and joint function during activities of daily living, and to assess the capacity of generic and scaled-generic musculotendon parameters to predict muscle and joint function. Three-dimensional musculoskeletal models of the shoulders of 6 healthy subjects were developed to calculate muscle and glenohumeral joint loading during abduction, flexion, horizontal flexion, nose touching and reaching using subject-specific, scaled-generic and generic musculotendon parameters. Muscle and glenohumeral joint forces calculated using generic and scaled-generic models were significantly different to those of subject-specific models (pMuscles in generic musculoskeletal models operated further from the plateau of their force-length curves than those of scaled-generic and subject-specific models, while muscles in subject-specific models operated over a wider region of their force length curves than those of the generic or scaled-generic models, reflecting diversity of subject shoulder strength. The findings of this study suggest that generic and scaled-generic musculotendon parameters may not provide sufficient accuracy in prediction of shoulder muscle and joint loading when compared to models that employ subject-specific parameter-estimation approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. PROBIOTIC POTENCY OF LACTOBACILLUS SPP. ISOLATED FROM SUMBAWA MARE MILK

    Directory of Open Access Journals (Sweden)

    I Nengah Sujaya

    2008-03-01

    Full Text Available This research was deigned to elucidate the potency of Lactobacillus spp. isolated from sumbawa mare milk to be developed as a probiotic. Sixteen lacobacilli were screened based on their resitancy to a model of gastric juice at pH 2, 3, and 4, then followed by their resistncy to small intestional fluid model containing deoxycholic. Three lactobacilli i.e. Lactobacillus sp. SKA13, Lactobacillus rhamnosus SKG34 and Lactobacillus rhamnosus SKG49 were found to be resistentent to gastric juice at pH 3 and 4. However, there were no lactobacilli resisted to pH 2. Lactobacillus rhamnosus SKG34 and Lactobacillus rhamnosus SKG49 were able to reach the colon even after being expossed to a model of intestinal fluid containing 0,4 mM deoxycholate and pancreatine. Therefore, these isolates have a potency to be developed as probiotic lactobacilli. Nevertherless, these lactobcailli could probably transform cholic acid into secondary bile acids, which were not expected to be found in the probiotic, and this capability is not appropriate for probiotic. This character is worthly to be studied since it has never been reported in lactobacilli.

  19. Geohydrology, geochemistry, geothermal potency of Rianiate Toba Lake North Sumatera

    Science.gov (United States)

    Nainggolan, Juliper; Sitepu, Cristin; Pardede, Sanggam; Diantoro, Markus

    2017-09-01

    This research was performed to determine the potency of Rianiate’s geothermal an alternative of energy source and determine the types of geothermal that was begun with the position’s measurement by using GPS (Global Position System), and then the direct observation of chemical and physical properties such as pH, surface’s temperature, color etc. The following steps were taking sample in four different springs indicated by spring 1, spring 2, spring 3, and spring 4. The chemical nature was measured by titrimetry method by using AAS, XRD, and gas Chromathology. The calculating of temperature of subsurface has done by using geothermometer and sequentially followed by geothermal potency’s calculation. The position of four springs are located about N: 02° 31,852’ and E: 098° 44. 021’ where were average height from sea’s level is 958 m. The highest surface’s temperature is 80 °C and the temperature under soil is about 130.5 °C described the average of geothermal. The calculation of content of chloride, sulfate, bicarbonations revealed that the water can be categorized as chloride type. The trilateral diagram Na/1000 - K/100 - √Mg of hot water is in the regime of immature water. From the calculation of Indonesia’s Standardized Geotherm, it was obtained that the estimated reservoir potency of Rianiate geotherm is 2,68 MWe.

  20. Immunologic and clinical evaluation of a 12-month course of specific immunotherapy.

    Science.gov (United States)

    Scordamaglia, A; Pizzorno, G; Caria, M; Passalacqua, G; Ruffoni, S; Ciprandi, G; Canonica, G W

    1989-07-01

    Allergen specific immunoglobulins (IgE, IgG, IgG1, and IgG4) were evaluated during the course of a 12-month specific immunotherapy (ITS) in 27 allergic subjects: 12 Dermatophagoides pteronyssinus (DP)-, 9 Parietaria officinalis (W19)-, six perennial and timothy rye grass (G5 and G6)-sensitive cases. Further, the modifications of the specific Ig levels were compared with the significant improvement in symptoms and drug consumption observed after 12 months of ITS. IgE levels significantly decreased after 6 and 12 months, while IgG1 significantly increased in the early phases of ITS (3rd month), and IgG4 significantly and progressively increased during the course of ITS. No modification was observed in specific total IgG. Regression analysis test among the various Ig levels revealed a strict correlation only between IgE and IgG4 (high levels of IgE before ITS correlated with high levels of IgG4 after 12 months of ITS). No correlation was observed between total Ig changes and improvement of clinical status or drug consumption.

  1. Evaluating sustainable architectural solutions such as multi-angled facades in specific urban contexts

    DEFF Research Database (Denmark)

    Hannoudi, Loay Akram; Lauring, Gert Michael; Christensen, Jørgen Erik

    specific urban contexts, all in Copenhagen: A dense and traditional part of the city; A dense and modern part; And a less dense area with modern, detached buildings. The aim of the paper is to structure and qualify discussions about and architectural evaluations of the use of multi-angled façades in given......A multi-angled facade system may be defined as the use of two or more different orientations of glazing in each façade. With the appropriate window properties and solar shading control systems such facades may improve the energy efficiency and the indoor climates of buildings. The system...... systems in specific urban contexts and analyses its architectural relations to other surrounding buildings and how this is perceived. A qualitative research/ phenomenological method is applied to provide a deeper understanding of implementing this facade system on an existing building, and to investigate...

  2. Multicentre evaluation of Capture Assay Radim Liquid Allergen for measurement of specific IgE antibodies.

    Science.gov (United States)

    Banfi, G; Ferrara, F; Bonini, P; Colombo, G; Plebani, M; Borghesan, F; Faggian, D; Caputo, M; Andri, L; Senna, G E

    1995-10-01

    A multicentre trial of Capture Assay Radim Liquid Allergen was performed to define the sensitivity, specificity and clinical reliability of the system in diagnostic allergology. The results of the evaluation were compared with clinical data and in vivo testing. Good agreement was obtained for Dermatophagoides pteronyssinus (D1), Cat's epithelium (E1), Betula verrucosa (T3) and Olea europea (T9), Artemisia vulgaris (W6) and Parietaria officinalis (W19). Some spreading of data was observed for Artemisia absinthium (W5), Cynodon dactylon (G2), and Lolium perenne (G5). We found a high number of negative cases for Alternaria alternata (M6). The advantages offered by the system are the automation, the small quantity of serum requested, the supply of quantitative results in international units of specific IgE, the user-friendly software. The data are sufficiently reliable for the diagnostic system to be introduced into the clinical laboratory allergological routine.

  3. Economic evaluation of vaccines: specificities and future challenges illustrated by recent European examples.

    Science.gov (United States)

    Postma, Maarten J; Westra, Tjalke A; Quilici, Sibilia; Largeron, Nathalie

    2013-05-01

    This study reviews the current challenges in the economic evaluation of vaccines with a focus on European countries. In particular, the type of clinical evidence generally available, the impact of discounting for time preference and the use of modeling to derive valid cost-effectiveness assessments are considered. First, the characteristics of evidence for vaccines are discussed, as well as potential difficulties faced when using evidence-based medicine applied to curative drugs to interpret vaccine evidence. Then, discounting is considered and specific examples illustrating issues with different types of discounting are described, taking HPV as the example. Finally, the need for sometimes complex dynamic models for vaccines is explored, and specific types of models are reviewed, keeping into consideration the adage "complex when needed, straightforward if allowed."

  4. Reassessment of MTBE cancer potency considering modes of action for MTBE and its metabolites.

    Science.gov (United States)

    Bogen, Kenneth T; Heilman, Jacqueline M

    2015-01-01

    A 1999 California state agency cancer potency (CP) evaluation of methyl tert-butyl ether (MTBE) assumed linear risk extrapolations from tumor data were plausible because of limited evidence that MTBE or its metabolites could damage DNA, and based such extrapolations on data from rat gavage and rat and mouse inhalation studies indicating elevated tumor rates in male rat kidney, male rat Leydig interstitial cells, and female rat leukemia/lymphomas. More recent data bearing on MTBE cancer potency include a rodent cancer bioassay of MTBE in drinking water; several new studies of MTBE genotoxicity; several similar evaluations of MTBE metabolites, formaldehyde, and tert-butyl alcohol or TBA; and updated evaluations of carcinogenic mode(s) of action (MOAs) of MTBE and MTBE metabolite's. The lymphoma/leukemia data used in the California assessment were recently declared unreliable by the U.S. Environmental Protection Agency (EPA). Updated characterizations of MTBE CP, and its uncertainty, are currently needed to address a variety of decision goals concerning historical and current MTBE contamination. To this end, an extensive review of data sets bearing on MTBE and metabolite genotoxicity, cytotoxicity, and tumorigenicity was applied to reassess MTBE CP and related uncertainty in view of MOA considerations. Adopting the traditional approach that cytotoxicity-driven cancer MOAs are inoperative at very low, non-cytotoxic dose levels, it was determined that MTBE most likely does not increase cancer risk unless chronic exposures induce target-tissue toxicity, including in sensitive individuals. However, the corresponding expected (or plausible upper bound) CP for MTBE conditional on a hypothetical linear (e.g., genotoxic) MOA was estimated to be ∼2 × 10(-5) (or 0.003) per mg MTBE per kg body weight per day for adults exposed chronically over a lifetime. Based on this conservative estimate of CP, if MTBE is carcinogenic to humans, it is among the weakest 10% of chemical

  5. Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    2011-03-01

    Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

  6. After Action Report: Specific Manufacturing Capability 2014 Evaluated Drill October 29, 2014

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, V. Scott [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-12-01

    On October 29, 2014, the Specific Manufacturing Capability (SMC) facility located at the Idaho National Laboratory (INL) conducted its annual evaluated emergency drill. As a result, this after action report is required by DOE O 151.1C, “Comprehensive Emergency Management System.” The SMC facility, in coordination with other onsite organizations, and the Department of Energy Idaho Operations Office (DOE ID) conducted an annual facility emergency drill to demonstrate the ability to implement the requirements of DOE O 151.1C, “Comprehensive Emergency Management System.” The INL contractor, Battelle Energy Alliance, LLC (BEA) in coordination with other onsite organizations, conducted operations and demonstrated proper response measures to mitigate an event and protect the health and safety of onsite personnel, the environment, and property. Report data was collected from multiple sources, including documentation generated during drill response, critiques conducted immediately after terminating the drill, and evaluation critiques.

  7. Collaborative study for establishment of a global standard for the potency assay of human anti-D immunoglobulin.

    Science.gov (United States)

    Thorpe, S J; Sands, D; Fox, B; Schäffner, G; Yu, M W; Behr-Gross, M-E

    2004-01-01

    An international collaborative study aimed at establishing a global standard for the potency assay of anti-D immunoglobulin was started in 2002. 25 laboratories participated in this study run under the common aegis of the World Health Organization, the United States Food and Drug Administration (US-FDA) and the European Directorate for the Quality of Medicines (EDQM). The potencies of three candidate materials and the US-FDA standard (lot 3) included for comparison were evaluated using AutoAnalyzer, competitive enzyme-linked immunoassay (competitive EIA), flow cytometric methods or own "in-house" methods. Critical reagent, standardised procedures and standardised assay design were provided for either method, where appropriate. Central statistical evaluation of the potency data submitted by the participants was performed using a parallel line model. Agreement between laboratories and assay methods for all samples was observed. Intra-laboratory variability was lowest for laboratories performing flow cytometry and highest for laboratories that performed their in-house methods. Inter-laboratory variability was acceptable for all samples when assayed by AutoAnalyzer, competitive (EIA) and flow cytometric methods. It was concluded that sample A is most suitable to serve as a global standard and that sample C could serve as a reserve European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) batch provided that suitable stability is demonstrated. Sample A was adopted by the Ph. Eur. Commission at its 115th session (March 2003) as the first Ph. Eur. BRP (available from the EDQM: catalog number Y0000219) with the assigned potency of 285 IU/ampoule.

  8. The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Hansen, Maria; Kawa, Anna

    2011-01-01

    Valproic acid (VPA) is a known teratogen. In the present study, the effects of VPA and seven VPA derivatives with different teratogenic potencies (isobutyl-, 5-methyl-, ethyl-, propyl-, butyl-, pentyl- and hexyl-4-yn-VPA) were investigated in L929 cells in vitro. Evaluated end-points included...... associated with the teratogenic potencies of the VPA derivatives. However, in contrast to changes in Erk1/2 phosphorylation and H3 acetylation, significant changes in GSK-3ß phosphorylation could only be obtained in response to prolonged incubation at high drug concentration. There was an association between...... changes in H3 acetylation and GSK-3ß-Tyr216 phosphorylation, whereas none of these end-points were associated with changes in Erk1/2 phosphorylation. These results suggest that the teratogenic potencies of VPA and VPA derivatives are related to effects on both Erk1/2 and histone deacetylase activities...

  9. Guidance to risk-informed evaluation of technical specifications using PSA

    Energy Technology Data Exchange (ETDEWEB)

    Baeckstroem, O.; Haeggstroem, A. (Scandpower AB, Stockholm (Sweden)); Maennistoe, I. (VTT, Helsingfors (Finland))

    2010-04-15

    This report presents guidance for evaluation of Technical Specification conditions with PSA. It covers quality in PSA, how to verify that the PSA model is sufficiently robust and sufficiently complete and general requirements on methods. Acceptance criteria for evaluation of changes in the TS conditions are presented. As the probabilistic safety assessment (PSA) has developed over the years, it has demonstrated to constitute a useful tool for evaluating many aspects of the TS from a risk point of view. and in that way making the PSAs as well as the decision tools better. This also means that it will be possible to take credit for safety system overcapacity as well as inherent safety features and strength of non-safety classed systems. However, PSA is only one of the tools that shall be used in an evaluation process of TS changes (strengthening/relaxation). PSA is an excellent tool to be used to verify the importance, and thereby possibly relaxation, of TS requirements. But, since PSA is only one tool in the evaluation, it is not sufficient in itself for defining which equipment that shall or shall not have TS requirements. The purpose of this guidance document is to provide general requirements, requirements on methods and acceptance criteria on risk-informed evaluation of TS changes based on PSA. The purpose is not to provide a single solution. As part of the review of the TS conditions this guidance specify requirements on: - Quality verification of the PSA model; - Verification that the PSA model is sufficiently robust with regard to SSCs for which requirements both are and are not defined by the TS; - Verification that the SSCs, for which TS demands are to be evaluated, are modelled in a sufficient manner; - Methods for performing the evaluation; - Which evaluation criteria that shall be used (and how that is verified to be correct); - Acceptance criteria: This guidance also briefly discusses the documentation of the analysis of the TS changes. This guidance

  10. In vitro evaluation of Moringa oleifera gum for colon-specific drug delivery.

    Science.gov (United States)

    Singhal, Anil Kumar; Jarald, Edwin E; Showkat, Ahmad; Daud, Anwar

    2012-01-01

    Moringa gum obtained from stem of the plant Moringa oleifera Lam. belonging to family Moringaceae. Number of naturally occurring polysaccharides obtained from plant (guar gum, inulin), animal (chitosan, chondrotin sulphate), algal (alginates) or microbial (dextran) origin. The present study was evaluated Moringa oleifera gum as a carrier for colon specific drug delivery using in vitro drug release studies. Six formulations of curcumin were prepared using varying concentration of Moringa oleifera gum containing 50 mg curcumin by wet granulation method. Tablets were subjected for evaluation by studying the parameter like hardness, friability, drug content uniformity and in vitro drug release study. Hardness was found to be in the range of 5.5 to 7.3 kg/cm(2), the percentage friability was in the range of 0.60 to 0.89%, and tablet showed 98.99% to 99.89% of the labeled amount of curcumin indicating uniformity in drug content. In vitro drug release study was performed using simulated stomach, intestinal and colonic fluid. The susceptibility of Moringa gum to colonic bacteria was also assessed using drug release study with rat caecal contents. 30% Moringa gum containing formulation (F-3) was shown better drug released that is 90.46%, at the end of 24 h of dissolution study in the presence of rat caecal contents in comparison to 40% Moringa gum containing formulation (F-4) that was 78.03%. The results illustrate the usefulness of Moringa olefera gum as a potential carrier for colon-specific drug delivery.

  11. Potency of Culled Saanen Crossbred Goat in Supplying Raw Meat for Traditional Thai Butchery

    Directory of Open Access Journals (Sweden)

    A. A. Putra

    2017-08-01

    Full Text Available Potency of culled Saanen crossbred goat meat to replace the supply of yearling Boer crossbred goat meat was evaluated. Selected muscles from leg and shoulder cuts were analysed for their nutritional (proximate composition, collagen, amino acids, fatty acids, physicochemical (pH, myoglobin, drip loss, cook loss, shear force, lightness (L* redness (a* yellowness (b*, microstructure, and sensory (triangle test, hedonic test evaluations. Meat samples from culled Saanen crossbred goat exhibited higher values in protein, collagen, and MUFA (P<0.05 than those from Boer crossbred goat, while lower values in ash, soluble collagen, and SFA were obtained (P<0.05. Meat from culled Saanen crossbred goat revealed higher cook loss, shear force, and redness compared to those from a yearling Boer crossbred goat (P<0.05. In addition, thicker perimysium in meat of Saanen crossbred goat was obtained particularly that could be seen on leg part. In sensory evaluation result, the panels could detect the differences between raw meat characteristics of these goat breeds (P<0.05 within the same muscle. However, the panels could not distinguish the difference between breeds in leg meat after being cooked. Shoulder meat of Saanen crossbred goat had less acceptance level compared to the other samples (P<0.05 particularly on its texture and taste quality. In summary, shoulder cut of culled Saanen crossbred goat exhibited a well-intentioned potency to substitute the supply of meat from yearling Boer crossbred goat. Nevertheless, pre-treatment might be applied to leg cut of Saanen crossbred goat to solve the less acceptance level of its textural and taste characteristics.

  12. Sexual outcomes after organ potency-sparing surgery and glans reconstruction in patients with penile carcinoma

    Directory of Open Access Journals (Sweden)

    Gaetano Gulino

    2013-01-01

    Full Text Available Introduction: Radical surgery is the "gold standard" for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis. Materials and Methods: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2, treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance. Results: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery. Conclusions: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patient′s life including

  13. Discovery and computer aided potency optimization of a novel class of small molecule CXCR4 antagonists.

    Directory of Open Access Journals (Sweden)

    Victoria Vinader

    Full Text Available Amongst the chemokine signalling axes involved in cancer, chemokine CXCL12 acting on chemokine receptor CXCR4 is particularly significant since it orchestrates migration of cancer cells in a tissue-specific metastatic process. High CXCR4 tumour expression is associated with poor prognosis of lung, brain, CNS, blood and breast cancers. We have identified a new class of small molecule CXCR4 antagonists based on the use of computational modelling studies in concert with experimental determination of in vitro activity against CXCL12-induced intracellular calcium mobilisation, proliferation and chemotaxis. Molecular modelling proved to be a useful tool in rationalising our observed potencies, as well as informing the direction of the synthetic efforts aimed at producing more potent compounds.

  14. Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency.

    Science.gov (United States)

    Beresford, Nicola; Baynes, Alice; Kanda, Rakesh; Mills, Matthew R; Arias-Salazar, Karla; Collins, Terrence J; Jobling, Susan

    2016-09-11

    Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters. Much of the estrogenic potency of wastewater treatment plant (WWTP) effluents can be attributed to the discharge of steroid estrogens including estradiol (E2), EE2 and E1 due to incomplete removal of these substances at the treatment plant. An evaluation of the efficacy of wastewater treatment processes requires the quantitative determination of individual substances most often undertaken using chemical analysis methods. Most frequently used methods include Gas Chromatography-Mass Spectrometry (GCMS/MS) or Liquid Chromatography-Mass Spectrometry (LCMS/MS) using multiple reaction monitoring (MRM). Although very useful for regulatory purposes, targeted chemical analysis can only provide data on the compounds (and specific metabolites) monitored. Ecotoxicology methods additionally ensure that any by-products produced or unknown estrogenic compounds present are also assessed via measurement of their biological activity. A number of in vitro bioassays including the Yeast Estrogen Screen (YES) are available to measure the estrogenic activity of wastewater samples. Chemical analysis in conjunction with in vivo and in vitro bioassays provides a useful toolbox for assessment of the efficacy and suitability of wastewater treatment processes with respect to estrogenic endocrine disrupting compounds. This paper utilizes a battery of chemical and ecotoxicology tests to assess conventional, advanced and emerging wastewater treatment processes in laboratory and field studies.

  15. Developing Toxicogenomics as a Research Tool by Applying Benchmark Dose-Response Modeling to inform Chemical Mode of Action and Tumorigenic Potency

    Science.gov (United States)

    ABSTRACT Results of global gene expression profiling after short-term exposures can be used to inform tumorigenic potency and chemical mode of action (MOA) and thus serve as a strategy to prioritize future or data-poor chemicals for further evaluation. This compilation of cas...

  16. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, L; Pejtersen, J; Gunnarsen, L

    2007-01-01

    linear part of the concentration-response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR = 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR = 1.5). No single...... symptoms correlated with the potency of surface dust. The PD was not related to single building factors. The inflammatory PD may be used as an integrated proxy measure of biologically active compounds in dust, reflecting health relevant properties of the dust. PRACTICAL IMPLICATIONS: The potency of surface...

  17. Reduced antimicrobial potencies of Oxytetracycline, tylosin, sulfadiazine, streptomycin, ciprofloxacin and olaquindox due to environmental processes

    DEFF Research Database (Denmark)

    Halling-Sørensen, Bent; Sengeløv, G.; Ingerslev, Flemming

    2003-01-01

    the assessment of whether a loss in antibacterial potency was reflected in a similar reduction of substance concentration. If a potency reduction is not reflected in a decreased substance concentration, the results may indicate the formation of less potent degradation products possessing the same chromophoric...... system (same UV absorbance maximum) as the parent compound. With the exception of ST and CF, the antimicrobial agents generally lost a considerable amount of their antimicrobial potency in aerobic experiments. In the anaerobic experiments having either an experimental duration of 21 or 100 days only OTC...... retained potency. These results correspond well with the fact that several degradation products were encountered in the study for this compound....

  18. State-specific differences in school sports preparticipation physical evaluation policies.

    Science.gov (United States)

    Caswell, Shane V; Cortes, Nelson; Chabolla, Mary; Ambegaonkar, Jatin P; Caswell, Amanda M; Brenner, Joel S

    2015-01-01

    This study evaluated the current preparticipation physical evaluation (PPE) administrative policies and cardiovascular screening content of all 50 states and Washington, DC. PPE policies, documents, and forms from all 50 states and Washington, DC, were compared with the preparticipation physical evaluation-fourth edition (PPE-4) consensus recommendations. All electronic documents were publicly available and obtained from state interscholastic athletic associations. Fifty (98%) states required a PPE before participation. Most states (53%, n = 27) required a specific PPE form, whereas 24% (n = 12) of states recommended a specific form. Twenty-three states (45%) required or recommended use of the PPE-4 form or a modified version of it, and 27 states (53%) required or recommended use of outdated or unidentifiable forms. Ten states (20%) had not revised their PPE forms in >5 years. States permitted 9 different health care providers to administer PPEs. Only 22 states (43%) addressed all 12 of the PPE-4 personal and family history cardiovascular screening items, and 2 states (4%) addressed between 8 and 11 items. For the remaining 26 states, most (29%) addressed ≤3 screening items. Our results show that inconsistencies in PPE policies exist nationwide. Most states have been slow to adopt PPE-4 recommendations and do not adequately address the personal and family cardiovascular history questions. Findings suggest a need for PPE standardization nationwide and adoption of an electronic PPE process. This approach would enable creation of a national database and benefit the public by facilitating a more evidenced PPE. Copyright © 2015 by the American Academy of Pediatrics.

  19. A two-step strategy to enhance activity of low potency peptides.

    Directory of Open Access Journals (Sweden)

    Jamie R Doyle

    Full Text Available Novel strategies are needed to expedite the generation and optimization of peptide probes targeting G protein-coupled receptors (GPCRs. We have previously shown that membrane tethered ligands (MTLs, recombinant proteins comprised of a membrane anchor, an extracellular linker, and a peptide ligand can be used to identify targeted receptor modulators. Although MTLs provide a useful tool to identify and/or modify functionally active peptides, a major limitation of this strategy is the reliance on recombinant protein expression. We now report the generation and pharmacological characterization of prototype peptide-linker-lipid conjugates, synthetic membrane anchored ligands (SMALs, which are designed as mimics of corresponding MTLs. In this study, we systematically compare the activity of selected peptides as MTLs versus SMALs. As prototypes, we focused on the precursor proteins of mature Substance P (SubP and Cholecystokinin 4 (CCK4, specifically non-amidated SubP (SubP-COOH and glycine extended CCK4 (CCK4-Gly-COOH. As low affinity soluble peptides these ligands each presented a challenging test case for assessment of MTL/SMAL technology. For each ligand, MTLs and corresponding SMALs showed agonist activity and comparable subtype selectivity. In addition, our results illustrate that membrane anchoring increases ligand potency. Furthermore, both MTL and SMAL induced signaling can be blocked by specific non-peptide antagonists suggesting that the anchored constructs may be orthosteric agonists. In conclusion, MTLs offer a streamlined approach for identifying low activity peptides which can be readily converted to higher potency SMALs. The ability to recapitulate MTL activity with SMALs extends the utility of anchored peptides as probes of GPCR function.

  20. Formulation and evaluation of bilayered gastroretentable mucoadhesive patch for stomach-specific drug delivery.

    Science.gov (United States)

    Pandey, Suneel; Jirwankar, Prachi; Mehta, Sandip; Pandit, Sachin; Tripathi, Pushpendra; Patil, Arun

    2013-08-01

    The aim of the present work was to develop and evaluate stomach-specific controlled release, gastroretentable mucoadhesive patch of lercanidipine HCl. This drug is essentially soluble in gastric pH range of 1- 4 and have a partition coefficient (log p-value) of 6.1; according to this concept, it has been decided to formulate the gastroretentive bioadhesive patch. The patch system consisted of a drug release rate controlling film, using the combination of Eudragit RSPO and RLPO; mucoadhesive film by using the combination of various hydrophilic polymers. Bilayered patch were made by using the selected batch of two films using the layering method and evaluated for the various parameters like in vitro swelling study, ex vivo mucoadhesive strength. Film was folded into a hard gelatin capsule, evaluated for in vitro drug release in pH 1.2 containing 0.2% (w/v) sodium lauryl sulphate (SLS), and in vivo bioavailability in rabbits. Patches could control the drug release up to 12 h, having mucoadhesion strength in the range of 4.05±0.4 N to 4.52±0.12 N. In vivo bioavailability results indicate that the gastroretentive patch system provides a novel way to retain the drug matrix for the longer period of time in a stomach, enhance drug absorption and thereby offer a promising strategy for gastroretentive mucoadhesive drug delivery for the lercanidipine HCl.

  1. Performance Evaluation of CLIA for Treponema Pallidum Specific Antibodies Detection in Comparison with ELISA.

    Science.gov (United States)

    Li, Lixin; Cai, Bei; Tao, Chuanmin; Wang, Lanlan

    2016-05-01

    In this study we aimed to evaluate the performance effects of chemiluminescence assay (CLIA) for Treponema pallidum specific antibodies detection, and to compare T. pallidum specific antibodies detection accuracy between CLIA and ELISA with TPPA (T. pallidum particle agglutination assay) as a confirmatory test. A total of 865 samples from suspected syphilis patients and preoperative patients were included, in which T. pallidum specific antibodies were simultaneously detected by CLIA and ELISA. Among them, 457 samples were determined by TPPA. All coefficients of variation (CVs) of ELISA in high-, median-, and low-level samples were more than 5% and the maximum CV was 54.39% in the low-level sample. CVs of CLIA in different-level samples were all below 5%. Among the three assays the Spearman correlation and Kappa coefficients were 0.771 (P ≤ 0.001) and 0.854 (P ≤ 0.001, CLIA vs. ELISA), 0.806 (P ≤ 0.001) and 0.897 (P ≤ 0.001, ELISA vs. TPPA), 0.937 (P ≤ 0.001) and 0.967 (P ≤ 0.001, CLIA vs. TPPA), respectively. The area under the receiver operating characteristic curve (AUC) of CLIA was higher than that of ELISA (0.994 vs. 0.989) with TPPA as the confirmatory test. In 18 discrepant samples the consistency rate between CLIA and TPPA was elevated compared with that between ELISA and TPPA (72.22% vs. 27.78%, P = 0.008). In gray zone, the consistency rate of CLIA with TPPA was higher than that of ELISA with TPPA (90.91% vs. 41.67%, P = 0.027). Compared with ELISA, CLIA is more reliable, sensitive and accurate to detect serum T. pallidum specific antibodies. In the future it may be an alternative test with higher sensitivity to ELISA. © 2015 Wiley Periodicals, Inc.

  2. [Appendicitis versus non-specific acute abdominal pain: Paediatric Appendicitis Score evaluation].

    Science.gov (United States)

    Prada Arias, Marcos; Salgado Barreira, Angel; Montero Sánchez, Margarita; Fernández Eire, Pilar; García Saavedra, Silvia; Gómez Veiras, Javier; Fernández Lorenzo, José Ramón

    2018-01-01

    Non-specific acute abdominal pain is the most common process requiring differential diagnosis with appendicitis in clinical practice. The aim of this study was to assess the Paediatric Appendicitis Score in differentiating between these two entities. All patients admitted due to suspicion of appendicitis were prospectively evaluated in our hospital over a two-year period. Cases of non-specific acute abdominal pain and appendicitis were enrolled in the study. Several variables were collected, including Score variables and C-reactive protein levels. Descriptive, univariate and multivariate analyses and diagnostic accuracy studies (ROC curves) were performed. A total of 275 patients were studied, in which there were 143 cases of non-specific acute abdominal pain and 132 cases of appendicitis. Temperature and right iliac fossa tenderness on palpation were the variables without statistically significant differences, and with no discrimination power between groups. Pain on coughing, hopping, and/or percussion tenderness in the right lower quadrant was the variable with greater association with appendicitis. The Score correctly stratified the patients into risk groups. Substitution of temperature for C-reactive protein in the Score increased diagnostic accuracy, although with no statistically significant differences. The Paediatric Appendicitis Score helps in differential diagnosis between appendicitis and non-specific acute abdominal pain. It would be advisable to replace the temperature in the Score, since it has no discrimination power between these groups. C-reactive protein at a cut-off value of 25.5mg/L value could be used instead. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms

    Science.gov (United States)

    Harper, Michael S.; Guo, Kejun; Gibbert, Kathrin; Lee, Eric J.; Dillon, Stephanie M.; Barrett, Bradley S.; McCarter, Martin D.; Hasenkrug, Kim J.; Dittmer, Ulf; Wilson, Cara C.; Santiago, Mario L.

    2015-01-01

    HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs) likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8) and weak (IFNα1) subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies. PMID:26529416

  4. Effect of seed treatment with low-potency laser in peppers plants (Capsicum annuum L.

    Directory of Open Access Journals (Sweden)

    Alexander Álvarez Fonseca,

    2014-01-01

    Full Text Available The influence of seed treatment with low-potency laser radiation on some physiological parameters and yield of peppers plants, California Wonder variety, was studied. The seeds were irradiated with a laser He- Ne, 25 mW powers, at different exposure periods 5, 10, 20, 30 and 60 seconds, using untreated seeds as controls. We evaluated plant height (mm, root length (mm, stem diameter (mm, polar average diameter (mm equatorial mean diameter (mm, mean fruit mass (g and yield per plant (kg.plant-1. The results showed a significant increase (p?0.001 in the indicators of plants height (50 %, root length (13 %, stem diameter (17 %, equatorial mean diameter (7 %, mean fruit mass (13 % and yield per plant (67 %, compared to control.

  5. Glycogen-gold nanohybrid escalates the potency of silymarin.

    Science.gov (United States)

    Kandimalla, Raghuram; Dash, Suvakanta; Bhowal, Ashim Chandra; Kalita, Sanjeeb; Talukdar, Narayan Chandra; Kundu, Sarathi; Kotoky, Jibon

    2017-01-01

    In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl 4 -induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma C max supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.

  6. Glycogen–gold nanohybrid escalates the potency of silymarin

    Science.gov (United States)

    Kandimalla, Raghuram; Dash, Suvakanta; Bhowal, Ashim Chandra; Kalita, Sanjeeb; Talukdar, Narayan Chandra; Kundu, Sarathi; Kotoky, Jibon

    2017-01-01

    In this study, a glycogen–gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV–Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl4-induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma Cmax supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly. PMID

  7. Reactive Agility Performance in Handball; Development and Evaluation of a Sport-Specific Measurement Protocol.

    Science.gov (United States)

    Spasic, Miodrag; Krolo, Ante; Zenic, Natasa; Delextrat, Anne; Sekulic, Damir

    2015-09-01

    There is no current study that examined sport-specific tests of reactive-agility and change-of-direction-speed (CODS) to replicate real-sport environment in handball (team-handball). This investigation evaluated the reliability and validity of two novel tests designed to assess reactive-agility and CODS of handball players. Participants were female (25.14 ± 3.71 years of age; 1.77 ± 0.09 m and 74.1 ± 6.1 kg) and male handball players (26.9 ± 4.1 years of age; 1.90 ± 0.09 m and 93.90±4.6 kg). Variables included body height, body mass, body mass index, broad jump, 5-m sprint, CODS and reactive-agility tests. Results showed satisfactory reliability for reactive-agility-test and CODS-test (ICC of 0.85-0.93, and CV of 2.4-4.8%). The reactive-agility and CODS shared less than 20% of the common variance. The calculated index of perceptual and reactive capacity (P&RC; ratio between reactive-agility- and CODS-performance) is found to be valid measure in defining true-game reactive-agility performance in handball in both genders. Therefore, the handball athletes' P&RC should be used in the evaluation of real-game reactive-agility performance. Future studies should explore other sport-specific reactive-agility tests and factors associated to such performance in sports involving agile maneuvers. Key pointsReactive agility and change-of-direction-speed should be observed as independent qualities, even when tested over the same course and similar movement templateThe reactive-agility-performance of the handball athletes involved in defensive duties is closer to their non-reactive-agility-score than in their peers who are not involved in defensive dutiesThe handball specific "true-game" reactive-agility-performance should be evaluated as the ratio between reactive-agility and corresponding CODS performance.

  8. Dentinogenic Specificity in the Preclinical Evaluation of Vital Pulp Treatment Strategies: A Critical Review

    Directory of Open Access Journals (Sweden)

    Dimitrios Tziafas

    2015-11-01

    Full Text Available Reviews on the clinical performance of vital pulp treatment strategies and capping materials repeatedly showed an insufficient grade of evidence concerning their therapeutic validity. The biological mechanisms underlying the regenerative potential of pulp-dentin complex have attracted much attention during the last two decades, since new pulp treatment modalities have been designed and tested at the preclinical level. It has been recognized that evaluation should be based on the specific ability of therapeutic interventions to signal recruitment and differentiation of odontoblast-like cells forming a matrix in a predentin-like pattern, rather than uncontrolled hard tissue deposition in a scar-like form. The aim of the present article was to critically review data from histological experimental studies on pulp capping, published during the last 7 decades. A comprehensive literature search covering the period from 1949 to 2015 was done using the Medline/Pubmed database. Inclusion of a study was dependent on having sufficient data regarding the type of capping material used and the unit of observation (human permanent tooth in vivo or animal permanent dentition; primary teeth were excluded. The post-operatively deposited matrix was categorized into three types: unspecified, osteotypic, or dentin-like matrix. One hundred fifty-two studies were included in the final evaluation. Data from the present systematic review have shown that only 30.2% of the 152 experimental histological pulp capping studies described the heterogenic nature of the hard tissue bridge formation, including osteotypic and tubular mineralized tissue. Structural characteristics of the new matrix and the associated formative cells were not provided by the remaining 106 studies. Analysis showed that more careful preclinical evaluation with emphasis on the evidence regarding the dentinogenic specificity of pulp therapies is required. It seems that selection of appropriate vital pulp

  9. Scenario-Based Specification and Evaluation of Architectures for Health Monitoring of Aerospace Structures

    Science.gov (United States)

    Mukkamala, Ravi; Sundaram, P.

    2001-01-01

    HUMS systems have been an area of increased research in the recent times due to two main reasons: (a) increase in the occurrences of accidents in the aerospace, and (b) stricter FAA regulations on aircrafts maintenance [2]. There are several problems associated with the maintenance of aircrafts that the HUMS systems can solve through the use of several monitoring technologies.This paper documents our methodology of employing scenarios in the specification and evaluation of architecture for HUMS. Section 2 investigates related works that use scenarios in software development. Section 3 describes how we use scenarios in our work, which is followed by a demonstration of our methods in the development of KUMS in section 4. Conclusion summarizes results.

  10. Evaluation of Functional Correlation of Task-Specific Muscle Synergies with Motor Performance in Patients Poststroke

    Directory of Open Access Journals (Sweden)

    Si Li

    2017-07-01

    Full Text Available The central nervous system produces movements by activating specifically programmed muscle synergies that are also altered with injuries in the brain, such as stroke. In this study, we hypothesize that there exists a positive correlation between task-specific muscle synergy and motor functions at joint and task levels in patients following stroke. The purpose here is to define and evaluate neurophysiological metrics based on task-specific muscle synergy for assessing motor functions in patients. A patient group of 10 subjects suffering from stroke and a control group of nine age-matched healthy subjects were recruited to participate in this study. Electromyography (EMG signals and movement kinematics were recorded in patients and control subjects while performing arm reaching tasks. Muscle synergies of individual patients were extracted off-line from EMG records of each patient, and a baseline pattern of muscle synergy was obtained from the pooled EMG data of all nine control subjects. Peak velocities and movement durations of each reaching movement were computed from measured kinematics. Similarity indices of matching components to those of the baseline synergy were defined by synergy vectors and time profiles, respectively, as well as by a combined similarity of vector and time profile. Results showed that pathological synergies of patients were altered from the characteristics of baseline synergy with missing components, or varied vector patterns and time profiles. The kinematic performance measured by peak velocities and movement durations was significantly poorer for the patient group than the control group. In patients, all three similarity indices were found to correlate significantly to the kinematics of movements for the reaching tasks. The correlation to the Fugl-Meyer score of arm was the highest with the vector index, the lowest with the time profile index, and in between with the combined index. These findings illustrate that the

  11. Evaluation of vision-specific quality-of-life in albinism.

    Science.gov (United States)

    Kutzbach, Beth R; Merrill, Kimberly S; Hogue, Kathy M; Downes, Sara J; Holleschau, Ann M; MacDonald, John T; Summers, C Gail

    2009-04-01

    Human albinism is a genetic condition associated with visual impairment that affects many aspects of daily life. Office measurements of visual acuity do not necessarily reflect daily visual function and health status. This study used the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to determine the effect of albinism-associated ophthalmopathy on quality of life (QOL). We administered the NEI-VFQ, which consists of 25 questions about QOL (VFQ-25) and 14 questions about well-being (VFQ-39), to 44 consenting participants with albinism older than the age of 18 years. Nineteen male and 25 female subjects completed the study. Median age was 30.5 years (range, 18-79 years). Mean best-corrected visual acuity was 20/83 (range, 20/20 to 20/320). Forty-eight percent reported that they were currently able to drive with their condition. Participants perceived midscale problems with their general vision (median subscale score 60.0). Visual acuity correlated moderately with overall NEI-VFQ composite scores (r(s) = 0.40, p = 0.01 for VFQ-25 and r(s) = 0.36, p = 0.02 for VFQ-39). Most notable impairment was recorded for distance acuity, vision-specific mental health, and vision-specific role difficulties (VFQ-39 median subscale scores 66.7, 70.0, and 75.0, respectively). Differences by sex were insignificant. Greater ceiling effects were noted for the VFQ-25 than for the VFQ-39. The NEI-VFQ-39 is a method to evaluate self-reported effects of vision-related QOL in albinism and may be used as a baseline for evaluating outcomes in interventional studies in these patients.

  12. StreamQRE: Modular Specification and Efficient Evaluation of Quantitative Queries over Streaming Data.

    Science.gov (United States)

    Mamouras, Konstantinos; Raghothaman, Mukund; Alur, Rajeev; Ives, Zachary G; Khanna, Sanjeev

    2017-06-01

    Real-time decision making in emerging IoT applications typically relies on computing quantitative summaries of large data streams in an efficient and incremental manner. To simplify the task of programming the desired logic, we propose StreamQRE, which provides natural and high-level constructs for processing streaming data. Our language has a novel integration of linguistic constructs from two distinct programming paradigms: streaming extensions of relational query languages and quantitative extensions of regular expressions. The former allows the programmer to employ relational constructs to partition the input data by keys and to integrate data streams from different sources, while the latter can be used to exploit the logical hierarchy in the input stream for modular specifications. We first present the core language with a small set of combinators, formal semantics, and a decidable type system. We then show how to express a number of common patterns with illustrative examples. Our compilation algorithm translates the high-level query into a streaming algorithm with precise complexity bounds on per-item processing time and total memory footprint. We also show how to integrate approximation algorithms into our framework. We report on an implementation in Java, and evaluate it with respect to existing high-performance engines for processing streaming data. Our experimental evaluation shows that (1) StreamQRE allows more natural and succinct specification of queries compared to existing frameworks, (2) the throughput of our implementation is higher than comparable systems (for example, two-to-four times greater than RxJava), and (3) the approximation algorithms supported by our implementation can lead to substantial memory savings.

  13. Clinical evaluation of a new quantitative method for specific IgE antibodies.

    Science.gov (United States)

    Plebani, M; Borghesan, F; Bernardi, D; Faggian, D

    1996-07-01

    We studied the analytical and clinical efficiency of a "second generation" technique for the in vitro determination of specific IgE, the so-called CARLA system (Capture Assay Radim Liquid Allergen). Reproducibility studies demonstrated satisfactory intra- and inter-assay analytical imprecision. The linearity test gave good results, and no significant interference by non-specific total IgE was found. The diagnostic efficiency of the system for the five most representative aeroallergens (D1, Dermatophagoides pteronyssinus; E1, Cat's epithelium; G5, Lolium perenne; W19, Parietaria officinalis and W5, Arthemisia absinthium) was evaluated using the Receiver Operating Characteristic (ROC) analysis in eighty-nine patients with suspected inhalant allergies. For each aeroallergen the area under the ROC curve and the most efficient threshold were calculated. Satisfactory areas under the ROC curve were found for D1, G5, E1 and W19, while a lower diagnostic efficiency was observed for W5. The most efficient thresholds differed from one allergen to another, although the differences were not great.

  14. In vivo evaluation of candidate allele-specific mutant huntingtin gene silencing antisense oligonucleotides.

    Science.gov (United States)

    Southwell, Amber L; Skotte, Niels H; Kordasiewicz, Holly B; Østergaard, Michael E; Watt, Andrew T; Carroll, Jeffrey B; Doty, Crystal N; Villanueva, Erika B; Petoukhov, Eugenia; Vaid, Kuljeet; Xie, Yuanyun; Freier, Susan M; Swayze, Eric E; Seth, Punit P; Bennett, Clarence Frank; Hayden, Michael R

    2014-12-01

    Huntington disease (HD) is a dominant, genetic neurodegenerative disease characterized by progressive loss of voluntary motor control, psychiatric disturbance, and cognitive decline, for which there is currently no disease-modifying therapy. HD is caused by the expansion of a CAG tract in the huntingtin (HTT) gene. The mutant HTT protein (muHTT) acquires toxic functions, and there is significant evidence that muHTT lowering would be therapeutically efficacious. However, the wild-type HTT protein (wtHTT) serves vital functions, making allele-specific muHTT lowering strategies potentially safer than nonselective strategies. CAG tract expansion is associated with single nucleotide polymorphisms (SNPs) that can be targeted by gene silencing reagents such as antisense oligonucleotides (ASOs) to accomplish allele-specific muHTT lowering. Here we evaluate ASOs targeted to HD-associated SNPs in acute in vivo studies including screening, distribution, duration of action and dosing, using a humanized mouse model of HD, Hu97/18, that is heterozygous for the targeted SNPs. We have identified four well-tolerated lead ASOs that potently and selectively silence muHTT at a broad range of doses throughout the central nervous system for 16 weeks or more after a single intracerebroventricular (ICV) injection. With further validation, these ASOs could provide a therapeutic option for individuals afflicted with HD.

  15. Evaluation of functional groups responsible for chloroform formation during water chlorination using compound specific isotope analysis.

    Science.gov (United States)

    Arnold, William A; Bolotin, Jakov; Von Gunten, Urs; Hofstetter, Thomas B

    2008-11-01

    Compound-specific isotope analysis was used to monitor the delta(13)C signature of chloroform produced upon the chlorination of model compounds representing natural organic matter functional groups (resorcinol, acetylacetone, acetophenone, phenol, and 2,4,6-trichlorophenol) and a natural water sample. For each model compound, a different apparent kinetic isotope effect was found for chloroform formation. Normal isotope effects were found for resorcinol, acetylacetone, and acetophenone, and ranged from 1.009 +/- 0.002 to 1.024 +/- 0.004. For the two phenols, an inverse effect was found (0.980 +/- 0.004). Lake Zürich water also had a inverse effect (0.997 +/- NOM, but that other functional groups may also participate. The apparent 13C kinetic isotope effect for the addition/ elimination reaction of 1,1,1-trichloropropanone mediated by OH- to yield chloroform is 1.014 +/- 0.002. A comparison of this value to those found for the chlorination of the model precursors and an evaluation of the differences in chloroform production kinetics for the different model precursors argue against a mechanism in which all NOM precursors react via a common intermediate. Compound specific isotope analysis may give additional insights into chloroform formation mechanisms beyond those allowed by current techniques.

  16. Design and Evaluation of Peptide Nucleic Acid Probes for Specific Identification of Candida albicans

    Science.gov (United States)

    Kim, Hyun-Joong

    2014-01-01

    Candida albicans is an important cause of systemic fungal infections, and rapid diagnostics for identifying and differentiating C. albicans from other Candida species are critical for the timely application of appropriate antimicrobial therapy, improved patient outcomes, and pharmaceutical cost savings. In this work, two 28S rRNA-directed peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) probes, P-Ca726 (targeting a novel region of the ribosome) and P-CalB2208 (targeting a previously reported region), were evaluated. Hybridization conditions were optimized by using both fluorescence microscopy (FM) and flow cytometry (FCM), and probes were screened for specificity and discriminative ability against a panel of C. albicans and various nontarget Candida spp. The performance of these PNA probes was compared quantitatively against that of DNA probes or DNA probe/helper combinations directed against the same target regions. Ratiometric analyses of FCM results indicated that both the hybridization quality and yield of the PNA probes were higher than those of the DNA probes. In FCM-based comparisons of the PNA probes, P-Ca726 was found to be highly specific, showing 2.5- to 5.5-fold-higher discriminatory power for C. albicans than P-CalB2208. The use of formamide further improved the performance of the new probe. Our results reinforce the significant practical and diagnostic advantages of PNA probes over their DNA counterparts for FISH and indicate that P-Ca726 may be used advantageously for the rapid and specific identification of C. albicans in clinical and related applications, especially when combined with FCM. PMID:25428160

  17. Design and evaluation of peptide nucleic acid probes for specific identification of Candida albicans.

    Science.gov (United States)

    Kim, Hyun-Joong; Brehm-Stecher, Byron F

    2015-02-01

    Candida albicans is an important cause of systemic fungal infections, and rapid diagnostics for identifying and differentiating C. albicans from other Candida species are critical for the timely application of appropriate antimicrobial therapy, improved patient outcomes, and pharmaceutical cost savings. In this work, two 28S rRNA-directed peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) probes, P-Ca726 (targeting a novel region of the ribosome) and P-CalB2208 (targeting a previously reported region), were evaluated. Hybridization conditions were optimized by using both fluorescence microscopy (FM) and flow cytometry (FCM), and probes were screened for specificity and discriminative ability against a panel of C. albicans and various nontarget Candida spp. The performance of these PNA probes was compared quantitatively against that of DNA probes or DNA probe/helper combinations directed against the same target regions. Ratiometric analyses of FCM results indicated that both the hybridization quality and yield of the PNA probes were higher than those of the DNA probes. In FCM-based comparisons of the PNA probes, P-Ca726 was found to be highly specific, showing 2.5- to 5.5-fold-higher discriminatory power for C. albicans than P-CalB2208. The use of formamide further improved the performance of the new probe. Our results reinforce the significant practical and diagnostic advantages of PNA probes over their DNA counterparts for FISH and indicate that P-Ca726 may be used advantageously for the rapid and specific identification of C. albicans in clinical and related applications, especially when combined with FCM. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Quality specifications of routine clinical chemistry methods based on sigma metrics in performance evaluation.

    Science.gov (United States)

    Xia, Jun; Chen, Su-Feng; Xu, Fei; Zhou, Yong-Lie

    2017-06-23

    Sigma metrics were applied to evaluate the performance of 20 routine chemistry assays, and individual quality control criteria were established based on the sigma values of different assays. Precisions were expressed as the average coefficient variations (CVs) of long-term two-level chemistry controls. The biases of the 20 assays were obtained from the results of trueness programs organized by National Center for Clinical Laboratories (NCCL, China) in 2016. Four different allowable total error (TEa) targets were chosen from biological variation (minimum, desirable, optimal), Clinical Laboratory Improvements Amendments (CLIA, US), Analytical Quality Specification for Routine Analytes in Clinical Chemistry (WS/T 403-2012, China) and the National Cholesterol Education Program (NECP). The sigma values from different TEa targets varied. The TEa targets for ALT, AMY, Ca, CHOL, CK, Crea, GGT, K, LDH, Mg, Na, TG, TP, UA and Urea were chosen from WS/T 403-2012; the targets for ALP, AST and GLU were chosen from CLIA; the target for K was chosen from desirable biological variation; and the targets for HDL and LDL were chosen from the NECP. Individual quality criteria were established based on different sigma values. Sigma metrics are an optimal tool to evaluate the performance of different assays. An assay with a high value could use a simple internal quality control rule, while an assay with a low value should be monitored strictly. © 2017 Wiley Periodicals, Inc.

  19. Evaluation of Dosimetry Check software for IMRT patient-specific quality assurance.

    Science.gov (United States)

    Narayanasamy, Ganesh; Zalman, Travis; Ha, Chul S; Papanikolaou, Niko; Stathakis, Sotirios

    2015-05-08

    The purpose of this study is to evaluate the use of the Dosimetry Check system for patient-specific IMRT QA. Typical QA methods measure the dose in an array dosimeter surrounded by homogenous medium for which the treatment plan has been recomputed. With the Dosimetry Check system, fluence measurements acquired on a portal dosimeter is applied to the patient's CT scans. Instead of making dose comparisons in a plane, Dosimetry Check system produces isodose lines and dose-volume histograms based on the planning CT images. By exporting the dose distribution from the treatment planning system into the Dosimetry Check system, one is able to make a direct comparison between the calculated dose and the planned dose. The versatility of the software is evaluated with respect to the two IMRT techniques - step and shoot and volumetric arc therapy. The system analyzed measurements made using EPID, PTW seven29, and IBA MatriXX, and an intercomparison study was performed. Plans from patients previously treated at our institution with treated anatomical site on brain, head & neck, liver, lung, and prostate were analyzed using Dosimetry Check system for any anatomical site dependence. We have recommendations and possible precautions that may be necessary to ensure proper QA with the Dosimetry Check system.

  20. Population-based evaluation of type-specific HPV prevalence among women in British Columbia, Canada.

    Science.gov (United States)

    Ogilvie, G S; Cook, D A; Taylor, D L; Rank, C; Kan, L; Yu, A; Mei, W; van Niekerk, D J; Coldman, A J; Krajden, M

    2013-02-04

    British Columbia (BC) introduced a school-based HPV vaccine program in September 2008. As part of the HPV vaccine program evaluation, we determined the type-specific HPV prevalence in a population-based sample of women presenting for routine cervical cancer screening in the province. From June 2010 to February 2011, a total of 1100 physicians from all health regions in BC were invited to return ten sequential cytobrushes used during routine office-based Pap screening to the Provincial Health Services Authority Laboratories for HPV type-specific testing. Client age was the only identifier provided. Specimens were screened by the Digene Hybrid Capture(®) 2 High-Risk (hr) HPV DNA Test (HC2). HC2 positive specimens were then genotyped using the Roche cobas(®) 4800 HPV Test, the Roche Linear Array (LA) HPV Genotyping Test and the Digene(®) HPV Genotyping LQ Test. Overall, 12.2% of the 4330 specimens with valid HC2 results were hrHPV positive. Age range was 15-69 (median 39.0). By age group, the proportion HC2 hrHPV positive was: 15-19, 25.7%; 20-24, 33.2%; 25-29, 21.9%; 30-34, 12.6%; 35-39, 9.5%; 40-44, 8.4%; ≥45, 3.4%. Overall hrHPV prevalence was 10.1% by Roche cobas(®) 4800, 10.5% by Roche LA and 10.3% by Digene LQ. For HPV 16/18, rates by age group by Roche LA were: 15-19, 5.1%/2.8%; 20-24, 9.5%/3.9%; 25-29, 6.2%/1.0%; 30-34, 2.4%/1.7%; 35-39, 1.2%/1.0%; 40-44, 1.6%/0.2%; ≥45, 0.3%/0.2%. Similar HPV 16/18 rates were obtained with the Digene LQ and Roche cobas(®) 4800 methods. Agreement between the three genotyping methods for HPV 16 and 18 was high. Comparable to other evaluations, hrHPV positivity was highest among younger women and HPV 16 was the most frequent genotype detected. These baseline estimates will be useful for monitoring the effectiveness of the HPV vaccine in BC. Type-specific analyses repeated at regular intervals over time may determine whether the use of HPV vaccine results in hrHPV genotype replacement in the province. Copyright © 2012

  1. NPSAG/NKS: Interpretation and evaluation of the technical specification criteria

    Energy Technology Data Exchange (ETDEWEB)

    Baeckstroem, O.; Haeggstroem, A. (Relcon Scandpower AB, Sundbyberg (Sweden)); Simola, K. (VTT (Finland))

    2008-07-15

    The use of risk-informed methods has been discussed since the late 1980s. in the Nordic countries. However, at that time the industry and authorities were not ready for the use of these methods and the use of them have been limited. The common understanding right now is that the industry and authorities are ready for adoption of risk-informed strategies, and the use of risk informed methods in daily operation at the nuclear power plants (NPPs) as well as for long term evaluation and definition of rules and regulations is increasing. The authorities are strengthening the rules and regulations with regard to redundancy and diversification in the safety systems. There are several ongoing projects at the NPPs, such as modernization, power upgrade etc. These projects will require modification of the Technical Specifications (TS). The requirements on a risk analysis to verify exceptions will be a natural part of the TS update. To summarize; there are both activities and trends at the plants that will result in TS changes (modernizations, increase of electrical power, risk informed strategies). At the same time, authorities are increasing the requirements on risk informed evaluation of the TS. TS evaluation from a risk point of view raises several questions: 1) How shall the TS conditions be evaluated? 2) What aspects shall be taken into consideration? 3) Can a prolonged/shortened surveillance test interval (STI) or allowed outage time (AOT) affect the experienced importance of the equipment? 4) What do the conditions in the TS with regard to AOT really represent? Are they conditions that shall be used when spare part storage and/or maintenance strategies are developed or do they represent how a real situation (unavailable component) shall be managed? To form an idea of the opinion on these questions phase 1 of the project is based on a literature study and interviews with persons at the Swedish and Finnish utilities and authorities. A short background to the current TS

  2. Evaluation of exposure-specific risks from two independent samples: a simulation study.

    Science.gov (United States)

    Reichmann, William M; Gagnon, David; Horsburgh, C Robert; Losina, Elena

    2011-01-05

    Previous studies have proposed a simple product-based estimator for calculating exposure-specific risks (ESR), but the methodology has not been rigorously evaluated. The goal of our study was to evaluate the existing methodology for calculating the ESR, propose an improved point estimator, and propose variance estimates that will allow the calculation of confidence intervals (CIs). We conducted a simulation study to test the performance of two estimators and their associated confidence intervals: 1) current (simple product-based estimator) and 2) proposed revision (revised product-based estimator). The first method for ESR estimation was based on multiplying a relative risk (RR) of disease given a certain exposure by an overall risk of disease. The second method, which is proposed in this paper, was based on estimates of the risk of disease in the unexposed. We then multiply the updated risk by the RR to get the revised product-based estimator. A log-based variance was calculated for both estimators. Also, a binomial-based variance was calculated for the revised product-based estimator. 95% CIs were calculated based on these variance estimates. Accuracy of point estimators was evaluated by comparing observed relative bias (percent deviation from the true estimate). Interval estimators were evaluated by coverage probabilities and expected length of the 95% CI, given coverage. We evaluated these estimators across a wide range of exposure probabilities, disease probabilities, relative risks, and sample sizes. We observed more bias and lower coverage probability when using the existing methodology. The revised product-based point estimator exhibited little observed relative bias (max: 4.0%) compared to the simple product-based estimator (max: 93.9%). Because the simple product-based estimator was biased, 95% CIs around this estimate exhibited small coverage probabilities. The 95% CI around the revised product-based estimator from the log-based variance provided better

  3. Evaluation of exposure-specific risks from two independent samples: A simulation study

    Directory of Open Access Journals (Sweden)

    Gagnon David

    2011-01-01

    Full Text Available Abstract Background Previous studies have proposed a simple product-based estimator for calculating exposure-specific risks (ESR, but the methodology has not been rigorously evaluated. The goal of our study was to evaluate the existing methodology for calculating the ESR, propose an improved point estimator, and propose variance estimates that will allow the calculation of confidence intervals (CIs. Methods We conducted a simulation study to test the performance of two estimators and their associated confidence intervals: 1 current (simple product-based estimator and 2 proposed revision (revised product-based estimator. The first method for ESR estimation was based on multiplying a relative risk (RR of disease given a certain exposure by an overall risk of disease. The second method, which is proposed in this paper, was based on estimates of the risk of disease in the unexposed. We then multiply the updated risk by the RR to get the revised product-based estimator. A log-based variance was calculated for both estimators. Also, a binomial-based variance was calculated for the revised product-based estimator. 95% CIs were calculated based on these variance estimates. Accuracy of point estimators was evaluated by comparing observed relative bias (percent deviation from the true estimate. Interval estimators were evaluated by coverage probabilities and expected length of the 95% CI, given coverage. We evaluated these estimators across a wide range of exposure probabilities, disease probabilities, relative risks, and sample sizes. Results We observed more bias and lower coverage probability when using the existing methodology. The revised product-based point estimator exhibited little observed relative bias (max: 4.0% compared to the simple product-based estimator (max: 93.9%. Because the simple product-based estimator was biased, 95% CIs around this estimate exhibited small coverage probabilities. The 95% CI around the revised product

  4. Importance of baseline specification in evaluating conservation interventions and achieving no net loss of biodiversity.

    Science.gov (United States)

    Bull, J W; Gordon, A; Law, E A; Suttle, K B; Milner-Gulland, E J

    2014-06-01

    There is an urgent need to improve the evaluation of conservation interventions. This requires specifying an objective and a frame of reference from which to measure performance. Reference frames can be baselines (i.e., known biodiversity at a fixed point in history) or counterfactuals (i.e., a scenario that would have occurred without the intervention). Biodiversity offsets are interventions with the objective of no net loss of biodiversity (NNL). We used biodiversity offsets to analyze the effects of the choice of reference frame on whether interventions met stated objectives. We developed 2 models to investigate the implications of setting different frames of reference in regions subject to various biodiversity trends and anthropogenic impacts. First, a general analytic model evaluated offsets against a range of baseline and counterfactual specifications. Second, a simulation model then replicated these results with a complex real world case study: native grassland offsets in Melbourne, Australia. Both models showed that achieving NNL depended upon the interaction between reference frame and background biodiversity trends. With a baseline, offsets were less likely to achieve NNL where biodiversity was decreasing than where biodiversity was stable or increasing. With a no-development counterfactual, however, NNL was achievable only where biodiversity was declining. Otherwise, preventing development was better for biodiversity. Uncertainty about compliance was a stronger determinant of success than uncertainty in underlying biodiversity trends. When only development and offset locations were considered, offsets sometimes resulted in NNL, but not across an entire region. Choice of reference frame determined feasibility and effort required to attain objectives when designing and evaluating biodiversity offset schemes. We argue the choice is thus of fundamental importance for conservation policy. Our results shed light on situations in which biodiversity offsets may

  5. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    DEFF Research Database (Denmark)

    Hansen, Martin; Krogh, Kristine A; Brandt, Asbjørn

    2009-01-01

    )). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC(50)-values. The influence of pH, temperature, oxygen concentration and light...

  6. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

    Directory of Open Access Journals (Sweden)

    Hui-Jin Sung

    2012-01-01

    Full Text Available Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50 of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50 of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2=0.9563; P<0.001. The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

  7. 75 FR 8937 - Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH...

    Science.gov (United States)

    2010-02-26

    ... AGENCY Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH...) Approach for Polycyclic Aromatic Hydrocarbon (PAH) Mixtures'' (EPA/635/R-08/012A). The draft document was... of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH) Mixtures'' is...

  8. Potency and control of modified live viral vaccines for veterinary use

    NARCIS (Netherlands)

    Terpstra, C.; Kroese, A.H.

    1996-01-01

    This paper reviews various aspects of efficacy, and methods for assaying the potency of modified live viral vaccines. The pros and cons of parametric versus non-parametric methods for analysis of potency assays are discussed and critical levels of protection, as determined by the target(s) of

  9. International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive-capacity

    NARCIS (Netherlands)

    Teunis, M.A.T.; Spiekstra, S.W.; Smits, M.; Adriaens, E.; Eltze, T.; Galbiati, V.; Krul, C.A.M.; Landsiedel, R.; Pieters, R.; Reinders, J.; Roggen, E.; Corsini, E.; Gibbs, S.

    2014-01-01

    This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50%

  10. International ring trial of the epidermal equivalent sensitizer potency assay : reproducibility and predictive-capacity

    NARCIS (Netherlands)

    Teunis, Marc A T; Spiekstra, Sander W; Smits, Mieke; Adriaens, Els; Eltze, Tobias; Galbiati, Valentina; Krul, Cyrille; Landsiedel, Robert; Pieters, Raymond; Reinders, Judith; Roggen, Erwin; Corsini, Emanuela; Gibbs, Susan

    2014-01-01

    This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50%

  11. Studies on the potency of oral polio vaccine using RD cell line and ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... The potency of vaccines was tested using the Karber's Formula. Key words: Oral polio vaccine, rhabdomyosarcoma, thermostability, potency. INTRODUCTION. Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the faecal-oral ...

  12. 76 FR 9028 - Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability

    Science.gov (United States)

    2011-02-16

    ... Industry: Potency Tests for Cellular and Gene Therapy Products'' dated January 2011. The guidance document provides manufacturers of cellular and gene therapy (CGT) products with recommendations for developing... document entitled ``Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products'' dated...

  13. Potency of veterinary rabies vaccines in The Netherlands: A case for continued vigilance.

    NARCIS (Netherlands)

    E.J.M. Rooijakkers; J.H.M. Nieuwenhuijs; A.A. Vermeulen; A.D.M.E. Osterhaus (Albert); G. van Steenis (Bert)

    1996-01-01

    textabstractCommercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and

  14. Early biochemical recurrence, urinary continence and potency outcomes following robot-assisted radical prostatectomy

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Thomsen, Frederik Birkebæk; Hvarness, Helle

    2014-01-01

    OBJECTIVE: The aim of this study was to describe recovery of urinary continence and potency and report oncological and functional outcomes using the survival, continence and potency (SCP) system for patients undergoing robot-assisted radical prostatectomy (RARP). MATERIAL AND METHODS: From 2009...

  15. Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

    Science.gov (United States)

    Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

    2011-07-26

    The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Development and Rainfed Paddy Soils Potency Derived from Lacustrine Material in Paguyaman, Gorontalo

    Directory of Open Access Journals (Sweden)

    Nurdin

    2011-09-01

    Full Text Available Rainfed paddy soils that are derived from lacustrine and include of E4 agroclimatic zone have many unique properties and potentially for paddy and corn plantations. This sreseach was aimed to: (1 study the soil development of rainfed paddy soils derived from lacustrine and (2 evaluate rainfed paddy soils potency for paddy and corn in Paguyaman. Soil samples were taken from three profiles according to toposequent, and they were analyzed in laboratory. Data were analyzed with descriptive-quantitative analysis. Furthermore, assessment on rainfed paddy soils potency was conducted with land suitability analysis using parametric approach. Results indicate that all pedon had evolved with B horizons structurization. However, pedon located on the summit slope was more developed and intensely weathered than those of the shoulder and foot slopes.The main pedogenesis in all pedons were through elluviation, illuviation, lessivage, pedoturbation, and gleization processes. The main factors of pedogenesis were climate, age (time and topography factors. Therefore, P1 pedons are classified as Ustic Endoaquerts, fine, smectitic, isohypertermic; P2 as Vertic Endoaquepts, fine, smectitic, isohypertermic; and P3 as Vertic Epiaquepts, fine, smectitic, isohypertermic. Based on the potentials of the land, the highest of land suitability class (LSC of land utilization type (LUT local paddy was highly suitable (S1, while the lowest one was not suitable with nutrient availability as the limiting factor (Nna. The highest LCS of paddy-corn LUT was marginally suitable with water availability as the limiting factor (S3wa, while the lower LSC was not suitable with nutrient availabily as the limiting factor (Nna.

  17. Evaluation of biofilm-specific antimicrobial resistance genes in Pseudomonas aeruginosa isolates in Farabi Hospital.

    Science.gov (United States)

    Saffari, Mahmood; Karami, Shabnam; Firoozeh, Farzaneh; Sehat, Mojtaba

    2017-07-01

    Biofilm produced from Pseudomonas aeruginosa is the cause of infection induced by contact lenses, trauma and post-surgery infection. The aim of this study was to evaluate biofilm formation and the presence of the genes ndvB and tssC1 in ocular infection isolates of P. aeruginosa. A total of 92 P. aeruginosa strains were collected from patients with ocular infection referred to Farabi Hospital between March 2014 and July 2015. Antibiotic susceptibility patterns were evaluated by the agar disc-diffusion method according to CLSI guidelines. PCR assays were used to detect ndvB and tssC1, genes associated with resistance in biofilm-producing P. aeruginosa isolates. Biofilm formation ability was examined by crystal violet microtitre plate assay. During the period of study, 92 P. aeruginosa were isolated from ocular infections including keratitis (n=84) and endophthalmitis (n=8). The highest resistance rates were seen against colistin (57.6 %) and gentamicin (50 %) and the lowest resistance rates were seen against imipenem (3.3 %), aztreonam (4.3 %), piperacillin-tazobactam (4.3 %), ceftazidime (4.3 %) and ciprofloxacin (5.4 %). Biofilm production ability was found in 100 % of the isolates. PCR assays showed that of the 92 P. aeruginosa isolates, 96.7 and 90.2 % harboured the genes ndvB and tssC1, respectively. Our results showed a considerable ability of biofilm production, as well as the occurrence of biofilm-specific antimicrobial resistance genes (ndvB and tssC1), in P. aeruginosa isolates from ocular infections in Farabi Hospital.

  18. Evaluation of specific absorption rate as a dosimetric quantity for electromagnetic fields bioeffects.

    Directory of Open Access Journals (Sweden)

    Dimitris J Panagopoulos

    Full Text Available PURPOSE: To evaluate SAR as a dosimetric quantity for EMF bioeffects, and identify ways for increasing the precision in EMF dosimetry and bioactivity assessment. METHODS: We discuss the interaction of man-made electromagnetic waves with biological matter and calculate the energy transferred to a single free ion within a cell. We analyze the physics and biology of SAR and evaluate the methods of its estimation. We discuss the experimentally observed non-linearity between electromagnetic exposure and biological effect. RESULTS: WE FIND THAT: a The energy absorbed by living matter during exposure to environmentally accounted EMFs is normally well below the thermal level. b All existing methods for SAR estimation, especially those based upon tissue conductivity and internal electric field, have serious deficiencies. c The only method to estimate SAR without large error is by measuring temperature increases within biological tissue, which normally are negligible for environmental EMF intensities, and thus cannot be measured. CONCLUSIONS: SAR actually refers to thermal effects, while the vast majority of the recorded biological effects from man-made non-ionizing environmental radiation are non-thermal. Even if SAR could be accurately estimated for a whole tissue, organ, or body, the biological/health effect is determined by tiny amounts of energy/power absorbed by specific biomolecules, which cannot be calculated. Moreover, it depends upon field parameters not taken into account in SAR calculation. Thus, SAR should not be used as the primary dosimetric quantity, but used only as a complementary measure, always reporting the estimating method and the corresponding error. Radiation/field intensity along with additional physical parameters (such as frequency, modulation etc which can be directly and in any case more accurately measured on the surface of biological tissues, should constitute the primary measure for EMF exposures, in spite of similar

  19. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals I. Alternative toxicity measures as an estimator of carcinogenic potency.

    Science.gov (United States)

    Venkatapathy, Raghuraman; Wang, Ching Yi; Bruce, Robert Mark; Moudgal, Chandrika

    2009-01-15

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD(50)]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD(50)) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD(50) and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD(50)s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD(50) for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction.

  20. A method for building and evaluating formal specifications of object-oriented conceptual models of database systems

    NARCIS (Netherlands)

    Wieringa, Roelf J.

    1993-01-01

    This report describes a method called MCM (Method for Conceptual Modeling) for building and evaluating formal specifications of object-oriented models of database system behavior. An important aim of MCM is to bridge the gap between formal specification and informal understanding. Building a MCM

  1. Potency Of Bacteriocin For Animal Health And Food Safety

    Directory of Open Access Journals (Sweden)

    Siti Chotiah

    2013-06-01

    Full Text Available The emergence of antibiotic resistance in many bacteria related to animal and public health stresses the importance of decreasing the use of antibiotics in animal production. The reduction of antibiotic application in livestock can only be achieved if alternative antimicrobial strategies are available. A number of strategies have been explored to control microbial pathogens and to improve growth and feed efficiency in livestock without the use of antibiotics. Bacteriocins have been more extensively studied and proposed as potential alternatives to conventional antibiotics in animal husbandry. Bacteriocins are antimicrobial peptides ribosomally synthesized by many species of Bacteria and some strains of Archaea. In general, bacteriocins just exhibited bactericidal or bacteriostatic activity against other bacteria that are closely related to the producing strain. The main mechanisms of bacteriocin activity vary from pore formation in cytoplasmic membranes to the inhibition of cell wall biosynthesis and enzyme activities (RNAse or DNAse in target cells. The use of bacteriocins in probiotic applications, as preservatives, and most excitingly as alternatives to conventional antibiotics is being broadly explored and studied. This review will describe the bacteriocins potency for animal health and food safety, as well as the results of bacteriocin study that had been conducted in Indonesia.

  2. Importance of Baseline Specification in Evaluating Conservation Interventions and Achieving No Net Loss of Biodiversity

    Science.gov (United States)

    Bull, J W; Gordon, A; Law, E A; Suttle, K B; Milner-Gulland, E J

    2014-01-01

    There is an urgent need to improve the evaluation of conservation interventions. This requires specifying an objective and a frame of reference from which to measure performance. Reference frames can be baselines (i.e., known biodiversity at a fixed point in history) or counterfactuals (i.e., a scenario that would have occurred without the intervention). Biodiversity offsets are interventions with the objective of no net loss of biodiversity (NNL). We used biodiversity offsets to analyze the effects of the choice of reference frame on whether interventions met stated objectives. We developed 2 models to investigate the implications of setting different frames of reference in regions subject to various biodiversity trends and anthropogenic impacts. First, a general analytic model evaluated offsets against a range of baseline and counterfactual specifications. Second, a simulation model then replicated these results with a complex real world case study: native grassland offsets in Melbourne, Australia. Both models showed that achieving NNL depended upon the interaction between reference frame and background biodiversity trends. With a baseline, offsets were less likely to achieve NNL where biodiversity was decreasing than where biodiversity was stable or increasing. With a no-development counterfactual, however, NNL was achievable only where biodiversity was declining. Otherwise, preventing development was better for biodiversity. Uncertainty about compliance was a stronger determinant of success than uncertainty in underlying biodiversity trends. When only development and offset locations were considered, offsets sometimes resulted in NNL, but not across an entire region. Choice of reference frame determined feasibility and effort required to attain objectives when designing and evaluating biodiversity offset schemes. We argue the choice is thus of fundamental importance for conservation policy. Our results shed light on situations in which biodiversity offsets may

  3. Specific Consideration on Superior Performance and Evaluation Methods of Polymer-housed Surge Arresters

    Science.gov (United States)

    Ishizaki, Yoshihiro; Kobayashi, Misao; Suzuki, Hironori; Futagami, Koichi

    It is very suitable to select the polymer materials for the housings of surge arresters (SAs), because the polymer materials are generally soft and light weight. Therefore, many kinds of polymer-housed SAs using various polymer materials have been developed, and expanding into many countries. Considering these backgrounds, the JEC technical report (JEC-TR) 23002-2008; polymer-housed surge arrester(1) has been established based on the existent relevant standards of arresters, such as JEC-2371-2003; Insulator-housed surge arresters(2) and IEC 60099-4 Edition 2.2, Metal-oxide surge arresters (MOSAs) without gaps for a.c. systems(3) in order to introduce the technology and provide a common guide for testing of polymer-housed SAs. According as the JEC-TR, the various new applications of the polymer-housed SAs, which are caused by superior advantages such as compact, light weight, safe failure mode, anti-seismic performance, anti-pollution performance and cost efficiency design, have been realized recently in Japan. Therefore, this paper gives specific consideration on the superior performance of the polymer-housed SAs and the evaluation methods of the polymer-housed SAs, because there are some issues in the existent standards to be solved.

  4. Measurement of confidence: the development and psychometric evaluation of a stroke-specific, measure of confidence.

    Science.gov (United States)

    Horne, Jane C; Lincoln, Nadina B; Logan, Pip A

    2017-11-01

    To design, develop and psychometrically evaluate a stroke-specific measure of confidence, the Confidence after Stroke Measure (CaSM). Cross-sectional. Adults in the community. Stroke survivors and healthy elderly participants. Questionnaire items were generated based on the literature and qualitative interviews and piloted with expert groups to establish face validity. A 53-item CaSM was administered to stroke survivors and healthy elderly participants in the community. A second copy was posted four weeks later. Completed questionnaires were analysed for extreme responses, missing values, construct validity (factor analysis), convergent validity, divergent validity, reliability (internal consistency and temporal stability) and comparing responses according to age and gender. Stroke ( n = 101) and healthy elderly participants ( n = 101) returned questionnaires. Eight items were removed that had extreme responses and large numbers of missing values. Six items had item total correlations Confidence, Positive Attitude and Social Confidence, which explained 52% of variance. Cronbach's alpha coefficient demonstrated good internal consistency ( α = 0.94). A test re-test on the 27 items indicated good temporal stability ( r = 0.85, P = 0.001). The 27-item CaSM was a valid and reliable measure for assessing confidence in stroke survivors.

  5. Evaluation of strain-specific primers for identification of Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Endo, Akihito; Aakko, Juhani; Salminen, Seppo

    2012-12-01

    Lactobacillus rhamnosus strain GG (ATCC 53103) is one of the most widely studied and commercialized probiotic strains, and thus strain-specific identification for the strain is highly valuable. In this study, two published PCR-based identification methods for strain GG, a transposase gene-targeting system and a phage-related gene-targeting system, were evaluated. The former produced amplicons from eight of the 41 strains tested and the phage-related system from five of the tested strains, including the strain GG. Fingerprinting analysis indicated that the strains LMG 18025, LMG 18030, and LMG 18038, which had an amplicon by the former system but none by the latter, were genetically distinguishable from L. rhamnosus GG at strain level. Strains LMG 23320, LMG 23325, LMG 23534, and LMG 25859 showed profiles very similar to that of the strain GG, suggesting that these strains might be identical to GG or derivative strains of it. The results here indicated that the phage-related gene-targeting system is a good tool for accurate identification of L. rhamnosus GG. This system would be able to detect both the original L. rhamnosus GG and its derivative strains. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  6. D-WISE: Diabetes Web-Centric Information and Support Environment: conceptual specification and proposed evaluation.

    Science.gov (United States)

    Abidi, Samina; Vallis, Michael; Raza Abidi, Syed Sibte; Piccinini-Vallis, Helena; Imran, Syed Ali

    2014-06-01

    To develop and evaluate Diabetes Web-Centric Information and Support Environment (D-WISE) that offers 1) a computerized decision-support system to assist physicians to A) use the Canadian Diabetes Association clinical practice guidelines (CDA CPGs) to recommend evidence-informed interventions; B) offer a computerized readiness assessment strategy to help physicians administer behaviour-change strategies to help patients adhere to disease self-management programs; and 2) a patient-specific diabetes self-management application, accessible through smart mobile devices, that offers behaviour-change interventions to engage patients in self-management. The above-mentioned objectives were pursued through a knowledge management approach that involved 1) Translation of paper-based CDA CPGs and behaviour-change models as computerized decision-support tools that will assist physicians to offer evidence-informed and personalized diabetes management and behaviour-change strategies; 2) Engagement of patients in their diabetes care by generating a diabetes self-management program that takes into account their preferences, challenges and needs; 3) Empowering patients to self-manage their condition by providing them with personalized educational and motivational messages through a mobile self-management application. The theoretical foundation of our research is grounded in behaviour-change models and healthcare knowledge management. We used 1) knowledge modelling to computerize the paper-based CDA CPGs and behaviour-change models, in particular, the behaviour-change strategy elements of A) readiness-to-change assessments; B) motivation-enhancement interventions categorized along the lines of patients' being ready, ambivalent or not ready; and C) self-efficacy enhancement. The CDA CPGs and the behaviour-change models are modelled and computerized in terms of A) a diabetes management ontology that serves as the knowledge resource for all the services offered by D-WISE; B) decision

  7. Evaluation of molecular markers for Phytophthora ramorum detection and identification: Testing for specificity using a standardized library of isolates

    Science.gov (United States)

    F.N. Martin; M.D. Coffey; K. Zeller; R.C. Hamelin; P. Tooley; M. Garbelotto; K.J.D. Hughes; T. Kubisiak; G.J. Bilodeau; L. Levy; C. Blomquist; P.H. Berger

    2009-01-01

    Given the importance of Phytophthora ramorum from a regulatory standpoint, it is imperative that molecular markers for pathogen detection are fully tested to evaluate their specificity in detection of the pathogen. In an effort to evaluate 11 reported diagnostic techniques, we assembled a standardized DNA library using accessions from the World...

  8. Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

    Directory of Open Access Journals (Sweden)

    Gareth R. Willis

    2017-10-01

    Full Text Available Exosomes are defined as submicron (30–150 nm, lipid bilayer-enclosed extracellular vesicles (EVs, specifically generated by the late endosomal compartment through fusion of multivesicular bodies with the plasma membrane. Produced by almost all cells, exosomes were originally considered to represent just a mechanism for jettisoning unwanted cellular moieties. Although this may be a major function in most cells, evolution has recruited the endosomal membrane-sorting pathway to duties beyond mere garbage disposal, one of the most notable examples being its cooption by retroviruses for the generation of Trojan virions. It is, therefore, tempting to speculate that certain cell types have evolved an exosome subclass active in intracellular communication. We term this EV subclass “signalosomes” and define them as exosomes that are produced by the “signaling” cells upon specific physiological or environmental cues and harbor cargo capable of modulating the programming of recipient cells. Our recent studies have established that signalosomes released by mesenchymal stem/stromal cells (MSCs represent the main vector of MSC immunomodulation and therapeutic action in animal models of lung disease. The efficacy of MSC-exosome treatments in a number of preclinical models of cardiovascular and pulmonary disease supports the promise of application of exosome-based therapeutics across a wide range of pathologies within the near future. However, the full realization of exosome therapeutic potential has been hampered by the absence of standardization in EV isolation, and procedures for purification of signalosomes from the main exosome population. This is mainly due to immature methodologies for exosome isolation and characterization and our incomplete understanding of the specific characteristics and molecular composition of signalosomes. In addition, difficulties in defining metrics for potency of exosome preparations and the challenges of industrial

  9. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

    Science.gov (United States)

    Sung, Hui-Jin; Ok, Seong-Ho; Sohn, Jin-Young; Son, Yong Hyeok; Kim, Jun Kyu; Lee, Soo Hee; Han, Jeong Yeol; Lim, Dong Hoon; Shin, Il-Woo; Lee, Heon-Keun; Chung, Young-Kyun; Choi, Mun-Jeoung; Sohn, Ju-Tae

    2012-01-01

    Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2 = 0.9563; P local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa. PMID:22778542

  10. In-human subject-specific evaluation of a control-theoretic plasma volume regulation model.

    Science.gov (United States)

    Bighamian, Ramin; Kinsky, Michael; Kramer, George; Hahn, Jin-Oh

    2017-12-01

    The goal of this study was to conduct a subject-specific evaluation of a control-theoretic plasma volume regulation model in humans. We employed a set of clinical data collected from nine human subjects receiving fluid bolus with and without co-administration of an inotrope agent, including fluid infusion rate, plasma volume, and urine output. Once fitted to the data associated with each subject, the model accurately reproduced the fractional plasma volume change responses in all subjects: the error between actual versus model-reproduced fractional plasma volume change responses was only 1.4 ± 1.6% and 1.2 ± 0.3% of the average fractional plasma volume change responses in the absence and presence of inotrope co-administration. In addition, the model parameters determined by the subject-specific fitting assumed physiologically plausible values: (i) initial plasma volume was estimated to be 36 ± 11 mL/kg and 37 ± 10 mL/kg in the absence and presence of inotrope infusion, respectively, which was comparable to its actual counterpart of 37 ± 4 mL/kg and 43 ± 6 mL/kg; (ii) volume distribution ratio, specifying the ratio with which the inputted fluid is distributed in the intra- and extra-vascular spaces, was estimated to be 3.5 ± 2.4 and 1.9 ± 0.5 in the absence and presence of inotrope infusion, respectively, which accorded with the experimental observation that inotrope could enhance plasma volume expansion in response to fluid infusion. We concluded that the model was equipped with the ability to reproduce plasma volume response to fluid infusion in humans with physiologically plausible model parameters, and its validity may persist even under co-administration of inotropic agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Evaluation of effectiveness of specific subcutaneous immunotherapy for patients with allergic rhinitis and asthma

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zandkarimi

    2013-06-01

    Full Text Available Background: Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. This study evaluated the clinical efficacy of immunotherapy with extracts of common aeroallergens North-East of Iran in asthma and allergic rhinitis. Material and Methods: In this prospective study 156 cases were chosen randomley. The mean age of patients was 37 years (range 5-65 years. The patients with mild to moderate asthma and allergic rhinitis and history of atopy were selected for immunotherapy when they showed no effective response to medical treatment.Immunotherapy materials were made from common aeroallergens in north-eastern region of Iran by Dome Hollister US company. Immunotherapy schedule for injection of the extract with vial dilution of 1:10000pg was one injection every week for ten weeks and one injection with dilution of 1:1000pg every other week for the other ten weeks and one injection monthly from dilution of 1:100pg for two years. Results: One hundred twenty (77% of cases had allergic rhinitis 29(18.5% cases had allergic asthma and 7(4.5% cases were mixed. Mean age of patients were 37 years old. 48(30.8% cases were male. Analysis of efficacy of treatment showed that immunotherapy significantlyimproved the signs and symptoms of all the groups. In allergic rhinitis group 84(70% cases completely improved, 22(18.4% patients moderately responded and no response to immunotherapy was observed in 14(11.6% patients. In allergic asthma group, 22(75% cases completely improved 4(13.6% cases moderately responded and no response to immunotherapy was detected in 3(11.4% cases. In mixed group, 3(42.8% cases completely improved, 3(42.8% cases moderately responded and no response was observed in 1(14.4% case. Conclusion: Specific allergen immunotherapy for patients with allergic persistent

  12. Geospatial evaluation of lead bioaccessibility and distribution for site specific prediction of threshold limits.

    Science.gov (United States)

    Bower, Jennifer A; Lister, Sydney; Hazebrouck, Garrett; Perdrial, Nicolas

    2017-10-01

    Recent work identified the need for site-specific Pb bioaccessibility evaluation and scaled contaminant modeling. Pb heterogeneity has made bioaccessibility characterization difficult, and complicated distribution models. Using field testing, bioaccessibility measurement, Integrated Exposure Uptake and Biokinetic (IEUBK) modeling, and geospatial techniques, we propose a framework for conducting applied risk-based, multiscale assessment. This framework was tested and implemented in Burlington, VT, an area of old housing stock and high Pb burden (up to 15 000 mg kg-1) derived primarily from paint. After analyzing local soil samples for total and bioaccessible Pb, it was determined that bioaccessible and total Pb were well correlated in this area, through which an average bioaccessibility parameter was derived approximating Pb bioaccessibility for this soil type and Pb impact. This parameter was used with the IEUBK to recommend the local limit for residential soil Pb be reduced from 400 to 360 mg kg-1, taking into consideration the lowering of the blood lead level threshold for Pb poisoning from 10 to 5 μg dL-1 by the Centers for Disease Control (CDC). Geospatial investigation incorporated samples collected during this investigation and samples from a high school summer science academy, and relied on three techniques, used at different scales: kriging of total and background Pb alone, kriging of total and background Pb with housing age as a well-sampled, well-correlated secondary variable (cokriging), and inverse distance weighting of total and bioaccessible Pb. Modeling at different scales allowed for characterization of Pb impact at single sites as well as citywide. Model maps show positive correlation between areas of older housing and areas of high Pb burden, as well as potential at different scales for reducing the effects of Pb heterogeneity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Development and preliminary evaluation of culturally specific web-based intervention for parents of adolescents.

    Science.gov (United States)

    Choi, H; Kim, S; Ko, H; Kim, Y; Park, C G

    2016-10-01

    WHAT IS KNOWN ON THE SUBJECT?: Problematic parent-child relationships have been identified as one of the main predictors of adolescents' mental health problems, but there are few existing interventions that address this issue. The format and delivery method of existing interventions for parents are relatively inaccessible for parents with full-time jobs and families living in rural areas. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: The newly developed 'Stepping Stone' culturally specific web-based intervention, which is intended to help Korean parents of adolescents to acquire both knowledge and communication and conflict management skills, was found to be feasible and well-accepted by parents. This study enabled us to identify areas for improvement in the content and format of the intervention and strategies. This will potentially increase effect sizes for the outcome variables of parents' perception and behaviours. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This web-based intervention could be delivered across diverse settings, such as schools and community mental health centers, to increase parents' knowledge of adolescent's mental health and allow for early detection of mental health problems. Mental health nurses working in schools may spend a significant amount of time addressing students' mental health issues; thus, this web-based intervention could be a useful resource to share with parents and children. In this way, the mental health nurses could facilitate parental engagement in the intervention and then help them to continue to apply and practice the knowledge and skills obtained through the program. Introduction There is a need for accessible, culturally specific web-based interventions to address parent-child relationships and adolescents' mental health. Aims This study developed and conducted a preliminary evaluation of a 4-week web-based intervention for parents of adolescents aged 11 to 16 years in Korea. Methods We used a two-group, repeated

  14. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, Leila; Pejtersen, Jan; Gunnarsen, Lars Bo

    2007-01-01

    linear part of the concentration- response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR ¼ 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR ¼ 1.5). No single...... symptoms correlated with the potency of surface dust. The PD was not related to single building factors. The inflammatory PD may be used as an integrated proxy measure of biologically active compounds in dust, reflecting health relevant properties of the dust....

  15. POTENCY OF KIPO, A TRADITIONAL FOOD FROM KOTAGEDE – YOGYAKARTA

    Directory of Open Access Journals (Sweden)

    Wahyu Supartono

    2016-04-01

    Full Text Available Kipo is a traditional food from Kotagede Region – Yogyakarta, which is produced from glutinous rice. It was processed through some steps such as weighing, mixing, melting, roasting and packing. This traditional food is not popular like other traditional foods such as gudeg or yangko. Problems concerning this situation were, the information of kipo was not well delivered to the consumers and people who were doing business with kipo were very limited and only in Kotagede.This research was aimed to disclosure the potency of kipo, if it was developed as industrial foods. The aspects of market, technical and financial were conducted and analyzed. These aspects were used for giving considerations, if this product could be developed in the future. The results depicted, that from the market aspect, value kipoconsumer’s attitude index was good (3.8845 from 5. The technical aspect showed, that this industry was quite small scale with processing capacity only 19 kg product per day, used 5 menpower and 60 m2 area.Based on the financial aspect at actual capacity, the results showed Net Present Value was Rp. 70,180,679; Payback Period 1.21 years; Profitability Index 5.51;Internal Rate of Return 98.5% and Break Even Point was Rp. 505,414 or 212,693 kipo. This industry was very sensitive to the increase of interest level, total cost and decrease of price product. Some challenged aspects of kipo were, it was produced from naural sources such as glutinous rice, coconut, brown sugar and also natural food colouring agent. The traditional process was still kept and the people could enjoy how it was produced. This is the challenge to develop the traditional food as part of culinary or historical tour.

  16. Osteogenic Potency of Nacre on Human Mesenchymal Stem Cells

    Science.gov (United States)

    Green, David W.; Kwon, Hyuk-Jae; Jung, Han-Sung

    2015-01-01

    Nacre seashell is a natural osteoinductive biomaterial with strong effects on osteoprogenitors, osteoblasts, and osteoclasts during bone tissue formation and morphogenesis. Although nacre has shown, in one study, to induce bridging of new bone across large non-union bone defects in 8 individual human patients, there have been no succeeding human surgical studies to confirm this outstanding potency. But the molecular mechanisms associated with nacre osteoinduction and the influence on bone marrow-derived mesenchymal stem cells (BMSC’s), skeletal stem cells or bone marrow stromal cells remain elusive. In this study we highlight the phenotypic and biochemical effects of Pinctada maxima nacre chips and the global nacre soluble protein matrix (SPM) on primary human bone marrow-derived stromal cells (hBMSCs) in vitro. In static co-culture with nacre chips, the hBMSCs secreted Alkaline phosphatase (ALP) at levels that exceeded bone morphogenetic protein (rhBMP-2) treatment. Concentrated preparation of SPM applied to Stro-1 selected hBMSC’s led to rapid ALP secretions, at concentrations exceeding the untreated controls even in osteogenic conditions. Within 21 days the same population of Stro-1 selected hBMSCs proliferated and secreted collagens I–IV, indicating the premature onset of an osteoblast phenotype. The same SPM was found to promote unselected hBMSC differentiation with osteocalcin detected at 7 days, and proliferation increased at 7 days in a dose-dependent manner. In conclusion, nacre particles and nacre SPM induced the early stages of human bone cell differentiation, indicating that they may be promising soluble factors with osteoinductive capacity in primary human bone cell progenitors such as, hBMSC’s. PMID:25666352

  17. Potency of positive gamma-aminobutyric acid(A) modulators to substitute for a midazolam discriminative stimulus in untreated monkeys does not predict potency to attenuate a flumazenil discriminative stimulus in diazepam-treated monkeys.

    Science.gov (United States)

    McMahon, L R; Gerak, L R; France, C P

    2001-09-01

    In monkeys discriminating midazolam (0.56 mg/kg s.c.) from saline, substitution for midazolam was elicited by various positive gamma-aminobutyric acid(A) (GABA(A)) modulators, including the benzodiazepines (BZs) triazolam, midazolam, and diazepam; the BZ(1)-selective ligands zaleplon and zolpidem; the barbiturates amobarbital and pentobarbital; and the neuroactive steroid pregnanolone. In another group of diazepam (5.6 mg/kg/day p.o.)-treated monkeys discriminating flumazenil (0.32 mg/kg s.c.) from vehicle, these positive GABA(A) modulators shifted the flumazenil dose-effect function to the right, i.e., attenuated diazepam withdrawal. The potency of positive GABA(A) modulators to substitute for midazolam in untreated monkeys did not predict their potency to attenuate the flumazenil stimulus in diazepam-treated monkeys. For instance, larger doses of BZs and BZ(1)-selective ligands were required to attenuate the flumazenil stimulus than to substitute for midazolam. The opposite relationship was revealed for non-BZ ligands, i.e., smaller doses of barbiturates and a neuroactive steroid were required to attenuate the flumazenil stimulus than to substitute for midazolam. The greater potency of non-BZ site ligands to attenuate diazepam withdrawal might be due to actions at a subtype of GABA(A) receptor not modulated by BZ site ligands, to the development of BZ tolerance without cross-tolerance to non-BZ site ligands, or to noncompetitive interactions at the GABA(A) receptor complex. Thus, interactions among GABA(A) modulators in BZ-dependent subjects are not predicted by their acute actions in nondependent subjects. It is not clear whether attenuation of BZ withdrawal is determined by subunit specificity or site of action on the GABA(A) receptor complex.

  18. Development and Evaluation of Species-Specific PCR for Detection of Nine Acinetobacter Species.

    Science.gov (United States)

    Li, Xue Min; Choi, Ji Ae; Choi, In Sun; Kook, Joong Ki; Chang, Young-Hyo; Park, Geon; Jang, Sook Jin; Kang, Seong Ho; Moon, Dae Soo

    2016-05-01

    Molecular methods have the potential to improve the speed and accuracy of Acinetobacter species identification in clinical settings. The goal of this study is to develop species-specific PCR assays based on differences in the RNA polymerase beta-subunit gene (rpoB) to detect nine commonly isolated Acinetobacter species including Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter pittii, Acinetobacter nosocomialis, Acinetobacter lwoffii, Acinetobacter ursingii, Acinetobacter bereziniae, Acinetobacter haemolyticus, and Acinetobacter schindleri. The sensitivity and specificity of these nine assays were measured using genomic DNA templates from 55 reference strains and from 474 Acinetobacter clinical isolates. The sensitivity of A. baumannii-specific PCR assay was 98.9%, and the sensitivity of species-specific PCR assays for all other species was 100%. The specificities of A. lwoffii- and A. schindleri-specific PCR were 97.8 and 98.9%, respectively. The specificity of species-specific PCR for all other tested Acinetobacter species was 100%. The lower limit of detection for the nine species-specific PCR assays developed in this study was 20 or 200 pg of genomic DNA from type strains of each species. The Acinetobacter species-specific PCR assay would be useful to determine the correct species among suggested candidate Acinetobacter species when conventional methods including MALDI-TOF MS identify Acinetobacter only to the genus level. The species-specific assay can be used to screen large numbers of clinical and environmental samples obtained for epidemiologic study of Acinetobacter for the presence of target species. © 2016 by the Association of Clinical Scientists, Inc.

  19. An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency.

    Science.gov (United States)

    Dorostkar, Rohollah; Bamdad, Taravat; Parsania, Masoud; Pouriayevali, Hassan

    2012-12-01

    Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (pEL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.

  20. Toxico-Cheminformatics and QSPR Modeling of the Carcinogenic Potency Database

    Science.gov (United States)

    Report on the development of a tiered, confirmatory scheme for prediction of chemical carcinogenicity based on QSAR studies of compounds with available mutagenic and carcinogenic data. For 693 such compounds from the Carcinogenic Potency Database characterized molecular topologic...

  1. Quantitative structure - mesothelioma Potency Model Optimization for Complex Mixtures of Elongated Particles in Rat Pleura

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including fibers from asbestos, are influenced by changes in fiber dose composition, bioavailability and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and com...

  2. Novel view on predicting acute toxicity: decomposing toxicity data in species vulnerability and chemical potency.

    Science.gov (United States)

    Jager, Tjalling; Posthuma, Leo; de Zwart, Dick; van de Meent, Dik

    2007-07-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We use a database for acute aquatic toxicity, and focus on some well-defined chemical classes. Potency is strongly related to hydrophobicity and vulnerability differences between species are small for narcotic compounds. Potencies show less relation with hydrophobicity and interspecies differences are larger for organophosphate- and carbamate insecticides. Photosynthesis inhibitors generally act narcotic to animals, but were more potent for algae. Using these potencies and vulnerabilities, acute toxicity values were well predicted by the proposed approach (within a factor of 3-6). The proposed approach has potential for predicting toxicity for untested species-compound combinations; however, there is a need for a better definition of 'mode of action' in ecotoxicology.

  3. Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

    Science.gov (United States)

    Freeman, T P; Winstock, A R

    2015-11-01

    Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

  4. Boosting oncolytic adenovirus potency with magnetic nanoparticles and magnetic force.

    Science.gov (United States)

    Tresilwised, Nittaya; Pithayanukul, Pimolpan; Mykhaylyk, Olga; Holm, Per Sonne; Holzmüller, Regina; Anton, Martina; Thalhammer, Stefan; Adigüzel, Denis; Döblinger, Markus; Plank, Christian

    2010-08-02

    Oncolytic adenoviruses rank among the most promising innovative agents in cancer therapy. We examined the potential of boosting the efficacy of the oncolytic adenovirus dl520 by associating it with magnetic nanoparticles and magnetic-field-guided infection in multidrug-resistant (MDR) cancer cells in vitro and upon intratumoral injection in vivo. The virus was complexed by self-assembly with core-shell nanoparticles having a magnetite core of about 10 nm and stabilized by a shell containing 68 mass % lithium 3-[2-(perfluoroalkyl)ethylthio]propionate) and 32 mass % 25 kDa branched polyethylenimine. Optimized virus binding, sufficiently stable in 50% fetal calf serum, was found at nanoparticle-to-virus ratios of 5 fg of Fe per physical virus particle (VP) and above. As estimated from magnetophoretic mobility measurements, 3,600 to 4,500 magnetite nanocrystallites were associated per virus particle. Ultrastructural analysis by electron and atomic force microscopy showed structurally intact viruses surrounded by magnetic particles that occasionally bridged several virus particles. Viral uptake into cells at a given virus dose was enhanced 10-fold compared to nonmagnetic virus when infections were carried out under the influence of a magnetic field. Increased virus internalization resulted in a 10-fold enhancement of the oncolytic potency in terms of the dose required for killing 50% of the target cells (IC(50) value) and an enhancement of 4 orders of magnitude in virus progeny formation at equal input virus doses compared to nonmagnetic viruses. Furthermore, the full oncolytic effect developed within two days postinfection compared with six days in a nonmagnetic virus as a reference. Plotting target cell viability versus internalized virus particles for magnetic and nonmagnetic virus showed that the inherent oncolytic productivity of the virus remained unchanged upon association with magnetic nanoparticles. Hence, we conclude that the mechanism of boosting the

  5. Investigations regarding the evaluation of specific intellectual property production risks within Quality Management System

    Science.gov (United States)

    Pakocs, R.; Lupulescu, N. B.

    2016-11-01

    This paper is a theoretical research concerning methods for risk assessment of specific intellectual property production risks that are identified in the product achievement stage within the Quality Management System. In order to realize this, we will start by identifying the specific intellectual property production risks and by proposing some new calculating formulas for minimalizing their negative effects. The theoretical model proposed assessment of specific intellectual property production risks, will be realized based on 3 hypothetical situations. This study intends to reduce the intellectual property risks identified in the production process of commercial societies that have an industrial profile.

  6. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound.

    Science.gov (United States)

    Chouinard, Guy

    2004-01-01

    Low and medium potency benzodiazepines were initially introduced for the treatment of insomnia and anxiety. Their therapeutic actions as anxiolytics, sedative hypnotics, anticonvulsants, and muscle relaxants (with their low toxicity) have led to their use as first-line treatments, and they have become one of the most prescribed classes of drugs. Novel therapeutic uses of benzodiazepines were discovered with the introduction of the high-potency benzodiazepines (e.g., alprazolam, clonazepam, and lorazepam). They were found to be effective in treating panic disorder and panic attacks with or without agoraphobia, as add-on therapy to selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder and panic disorders, and as adjunctive therapy in treating patients with acute mania or acute agitation. High-potency benzodiazepines have replaced low and medium potency benzodiazepines in all benzodiazepine clinical indications due to their greater therapeutic effects and rapid onset of action. Differences in distribution, elimination half-life, and rate of absorption are important considerations when choosing a high-potency benzodiazepine. Typically, a benzodiazepine with long distribution and elimination half-lives is preferred. A maximum dose of 2 mg/day of any of the high-potency benzodiazepines when given for more than 1 week is recommended. Although as a class benzodiazepines act rapidly and are well tolerated, their use presents clinical issues such as dependence, rebound anxiety, memory impairment, and discontinuation syndrome.

  7. Applying multivariate analysis as decision tool for evaluating sediment-specific remediation strategies

    DEFF Research Database (Denmark)

    Pedersen, Kristine B.; Lejon, Tore; Jensen, Pernille Erland

    2016-01-01

    Multivariate methodology was employed for finding optimum remediation conditions for electrodialytic remediation of harbour sediment from an Arctic location in Norway. The parts of the experimental domain in which both sediment- and technology-specific remediation objectives were met were...

  8. Evaluation of the Bonapace Method: a specific educational intervention to reduce pain during childbirth

    Directory of Open Access Journals (Sweden)

    Bonapace J

    2013-09-01

    Full Text Available Julie Bonapace,1 Nils Chaillet,2 Isabelle Gaumond,3,4 Émilie Paul-Savoie,5 Serge Marchand3,41Département des Sciences de l'Éducation, Université du Québec en Abitibi-Témiscamingue, Rouyn-Noranda, Québec, 2Centre de Recherche de l'Hôpital Sainte-Justine, Université de Montréal, Montréal, Québec, 3Département de chirurgie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, 4Département des Sciences de la Santé, Université du Québec en Abitibi-Témiscamingue, Rouyn-Noranda, Québec, 5École des sciences infirmières, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, CanadaObjective: As pain during childbirth is very intense, several educational programs exist to help women prepare for the event. This study evaluates the efficacy of a specific pain management program, the Bonapace Method (BM, to reduce the perception of pain during childbirth. The BM involves the father, or a significant partner, in the use of several pain control techniques based on three neurophysiological pain modulation models: (1 controlling the central nervous system through breathing, relaxation, and cognitive structuring; (2 using non-painful stimuli as described in the Gate Control Theory; and (3 recruiting descending inhibition by hyperstimulation of acupressure trigger points.Methods: A multicenter case control study in Quebec on pain perception during labor and delivery compared traditional childbirth training programs (TCTPs and the BM. Visual analog scales were used to measure pain perception during labor. In all, 25 women (TCTP: n = 12; BM: n = 13 successfully reported their perceptions of pain intensity and unpleasantness every 15 minutes.Results: A positive correlation between the progression of labor and pain was found (pain intensity: P < 0.01; pain unpleasantness: P < 0.01. When compared to TCTP, the BM showed an overall significant lower pain

  9. Functions of Heterogeneous Nuclear Ribonucleoproteins in Stem Cell Potency and Differentiation

    Directory of Open Access Journals (Sweden)

    Qishan Chen

    2013-01-01

    Full Text Available Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they have the remarkable potential for self-renewal and to differentiate into almost all the cell types in the human body. Elucidation of molecular mechanisms regulating stem cell potency and differentiation is essential and critical for extensive application. Heterogeneous nuclear ribonucleoproteins (hnRNPs are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. Multiple roles of hnRNPs in transcriptional and posttranscriptional regulation enable them to be effective gene expression regulators. More recent findings show that hnRNP proteins are crucial factors implicated in maintenance of stem cell self-renewal and pluripotency and cell differentiation. The hnRNPs interact with certain sequences in target gene promoter regions to initiate transcription. In addition, they recognize 3′UTR or 5′UTR of specific gene mRNA forming mRNP complex to regulate mRNA stability and translation. Both of these regulatory pathways lead to modulation of gene expression that is associated with stem cell proliferation, cell cycle control, pluripotency, and committed differentiation.

  10. Anxiety, Sadness, and Emotion Specificity: The Role of Music in Consumer Emotion and Advertisement Evaluation

    Directory of Open Access Journals (Sweden)

    Felix Septianto

    2013-12-01

    Full Text Available Although music could diversely influence consumer judgment process and behavior, it is still unclear whether music can evoke discrete emotions on consumers and influence consumer evaluation toward certain advertisements. This research proposes that music could evoke sad and anxious emotion on consumers; subsequently, consumers would regulate their negative emotions in accordance to their emotion orientations: Consumers who feel sad would show high evaluation toward happy-themed advertisement, while consumers who feel anxious would show high evaluation toward calm-themed advertisement. This paper concludes with the discussion of theoretical and practical implications and conclusion of this study.

  11. In ova angiogenesis analgesic and anti inflammatory potency of Aerva monsoniae (Amaranthaceae

    Directory of Open Access Journals (Sweden)

    Sandhya S

    2012-10-01

    Full Text Available Objective: To evaluate the wound healing potency of aqueous extract of Aerva monsoniae (A. monsoniae by in vitro method using fertilized eggs, in vivo analgesic and anti inflammatory activity in rodents and the anti bacterial activity on the bacterial strains that infect the wound. Methods: The whole plant of A. monsoniae was extracted with water and then subjected to preliminary chemical screening. It was then evaluated for in ova angiogenesis on fertilized white leg horn eggs using the concentrations of 200-600 毺 g/mL. The analgesic activity was evaluated in mice using the dose 100 and 250 mg/kg. The anti inflammatory activity was evaluated in rats using the dose 250 mg/kg and 500 mg/kg. In both the parameters water was used as the control and diclofenac was used the standard. The anti bacterial activity on Staphylococcus aureus and Pseudomonas aerugenosa was performed. Results: The phytochemical screening revealed the presence of tannins, flavonoids and saponins. The in ova angiogenesis revealed a dose dependent activity which proves the wound healing claim of the plant as more number of blood capillaries were formed at the site of the drug. The plant proved to be a potent analgesic and anti inflammatory agent at doses 1 00 mg/kg and 250 mg/kg. The anti bacterial activity was present but at higher doses. Conclusions: The parameters studied in the present investigation proved that the plant is a potent wound healer. Further in vivo wound healing studies on animal model is desired. As the extract showed potent analgesic, anti inflammatory and anti bacterial properties, it can be considered that when formulated into suitable formulation, and it can reduce the pain, inflammation and infections related to wound very well.

  12. Evaluation and specification of high build and special use waterborne pavement markings.

    Science.gov (United States)

    2014-01-01

    High build waterborne traffic paints and highly retro-reflective elements were applied at various locations to evaluate their : practicality for use by NYSDOT Maintenance forces. In addition, highly reflective elements were applied within grooved in ...

  13. Histopathological Evaluation of Skeletal Muscle with Specific Reference to Mouse Models of Muscular Dystrophy.

    Science.gov (United States)

    Terry, Rebecca L; Wells, Dominic J

    2016-12-01

    The muscular dystrophies are a diverse group of degenerative diseases for which many mouse models are available. These models are frequently used to assess potential therapeutic interventions and histological evaluation of multiple muscles is an important part of this assessment. Histological evaluation is especially useful when combined with tests of muscle function. This unit describes a protocol for necropsy, processing, cryosectioning, and histopathological evaluation of murine skeletal muscles, which is applicable to both models of muscular dystrophy and other neuromuscular conditions. Key histopathological features of dystrophic muscle are discussed using the mdx mouse (a model of Duchenne muscular dystrophy) as an example. Optimal handling during dissection, processing and sectioning is vital to avoid artifacts that can confound or prevent future analyses. Muscles carefully processed using this protocol are suitable for further evaluation using immunohistochemistry, immunofluorescence, special histochemical stains, and immuoblotting. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  14. Dog bites in The Netherlands: A study of victims, injuries, circumstances and aggressors to support evaluation of breed specific legislation

    NARCIS (Netherlands)

    Cornelissen, J.M.R.; Hopster, H.

    2010-01-01

    As part of an evaluation of Dutch breed specific legislation, data were collected from dog bite victims (1078) and dog owners (6139) using Internet surveys. The incidence rate of dog bites and details of incidents (victims, injuries, circumstances and aggressors) are reported and the justification

  15. Method to evaluate window products with respect to a specific application

    DEFF Research Database (Denmark)

    Schultz, Jørgen Munthe; Svendsen, Sv Aa Højgaard

    1997-01-01

    A two-node model of a room has been implemented in a computer program, WinSim, de-veloped for evaluation of thermal window performance in new buildings and in case of ret-rofitting. The program calculates the annual heating demand and the number of hours with indoor temperatures higher than a user...... it can be concluded that WinSim is well suited for a fast and realis-tic evaluation of thermal window performance....

  16. Anxiety, Sadness, and Emotion Specificity: The Role of Music in Consumer Emotion and Advertisement Evaluation

    OpenAIRE

    Felix Septianto

    2013-01-01

    Although music could diversely influence consumer judgment process and behavior, it is still unclear whether music can evoke discrete emotions on consumers and influence consumer evaluation toward certain advertisements. This research proposes that music could evoke sad and anxious emotion on consumers; subsequently, consumers would regulate their negative emotions in accordance to their emotion orientations: Consumers who feel sad would show high evaluation toward happy-themed advertisement,...

  17. Detection of estrogen receptor endocrine disruptor potency of commonly used organochlorine pesticides using the LUMI-CELL ER bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J.D.; Chu, A.C.; Clark, G.C. [Xenobiotic Detection Systems, Inc., Durham, NC (United States); Chu, M.D. [Alta Analytical Perspectives, Wilmington, NC (United States); Denison, M.S. [Dept. of Environmental Toxicology, Univ. of California, Davis, CA (United States)

    2004-09-15

    In order to detect the endocrine disrupting potency of organochlorine pesticides and other compounds, BG-1 (human ovarian carcinoma) cells containing a stably transfected estrogenresponsive luciferase reporter gene plasmid (BG1Luc4E2), was used. This cell line, termed the LUMI-CELL trademark ER estrogenic cell bioassay system, responds in a time-, dose dependent- and chemical-specific manner with the induction of luciferase gene expression in response to exposure to estrogen (but not other steroid hormones) and estrogenic chemicals in a high-throughput screening (HTPS) format6. Here we describe studies in which the LUMI-CELL trademark ER estrogenic cell bioassay system was used for high throughput screening (HTPS) analysis of the estrogenic disrupting potency of several commonly used pesticides and organochlorines: p,p'DDT; p,p'-DDE; DDD; {alpha}a-chlordane; {psi}-chlordane; Kepone; Methoxychlor; Vinclozolin; Fenarimol; 2,4,5-Trichlorophenoxyacetic Acid; and Dieldrin. Our results demonstrate the utility of XDS's LUMI-CELL trademark ER bioassay HTPS system for screening chemicals for estrogenic activity.

  18. Evaluation Model of Specific Indoor Environment Overall Comfort Based on Effective-Function Method

    Directory of Open Access Journals (Sweden)

    Tieming Guo

    2017-10-01

    Full Text Available The indoor overall environmental comfort of part limited spaces is studied in this paper. The operative temperature, illumination, and noise intensity are used as objective parameters in order to evaluate the thermal, luminous, and acoustic environment. The thermal, luminous, and acoustic environment are investigated by using the subjective questionnaire in this experiment, and the function relation of the single physical parameter is established. Then, using the effective-function comprehensive evaluation carries on non-dimensional, weighting, and penalty substitution synthesis for the evaluation index of thermal, luminous, and acoustic environment, and establishes the evaluation model of the indoor overall environment. According to the experimental results and evaluation analysis, it is considered that the noise intensity and operative temperature have great influence on the indoor environment overall comfort and the illumination has less effect. Referring to the ISO7730 standard and combining it with the situation of our country, the indoor overall environment is divided into the zone of comfort. The predicted overall comfort vote (POCV, which is greater than or equal to −0.5 is the high comfort zone I. The area of −0.5 > POCV ≥ −1.0 is designated as low comfort zone II. It provides a certain basis for the evaluation of indoor overall environmental comfort.

  19. Aβ seeding potency peaks in the early stages of cerebral β-amyloidosis.

    Science.gov (United States)

    Ye, Lan; Rasmussen, Jay; Kaeser, Stephan A; Marzesco, Anne-Marie; Obermüller, Ulrike; Mahler, Jasmin; Schelle, Juliane; Odenthal, Jörg; Krüger, Christian; Fritschi, Sarah K; Walker, Lary C; Staufenbiel, Matthias; Baumann, Frank; Jucker, Mathias

    2017-09-01

    Little is known about the extent to which pathogenic factors drive the development of Alzheimer's disease (AD) at different stages of the long preclinical and clinical phases. Given that the aggregation of the β-amyloid peptide (Aβ) is an important factor in AD pathogenesis, we asked whether Aβ seeds from brain extracts of mice at different stages of amyloid deposition differ in their biological activity. Specifically, we assessed the effect of age on Aβ seeding activity in two mouse models of cerebral Aβ amyloidosis (APPPS1 and APP23) with different ages of onset and rates of progression of Aβ deposition. Brain extracts from these mice were serially diluted and inoculated into host mice. Strikingly, the seeding activity (seeding dose SD50) in extracts from donor mice of both models reached a plateau relatively early in the amyloidogenic process. When normalized to total brain Aβ, the resulting specific seeding activity sharply peaked at the initial phase of Aβ deposition, which in turn is characterized by a temporary several-fold increase in the Aβ42/Aβ40 ratio. At all stages, the specific seeding activity of the APPPS1 extract was higher compared to that of APP23 brain extract, consistent with a more important contribution of Aβ42 than Aβ40 to seed activity. Our findings indicate that the Aβ seeding potency is greatest early in the pathogenic cascade and diminishes as Aβ increasingly accumulates in brain. The present results provide experimental support for directing anti-Aβ therapeutics to the earliest stage of the pathogenic cascade, preferably before the onset of amyloid deposition. © 2017 The Authors.

  20. MATHEMATICAL MODELING FOR BENZYLPENICILIN POTASSIUM AND STREPTOMYCIN SULPHATE POTENCY DETERMINATION OF ASCOMICIN

    Directory of Open Access Journals (Sweden)

    Viviana Ciuca

    2016-12-01

    Full Text Available Ascomicin is an antibacterial unguent for treatment of local infections of skin, eyes, outer ear, in cattle, sheep, pig, dog and cat. The product contains two active substances: benzylpenicillin potassium (Penicillin G potassium and streptomycin sulphate. The main characteristic of commercial product is benzylpenicillin potassium and streptomycin sulphate potency. The potency is estimated by comparing the inhibition of growth of sensitive micro-organisms produced by known concentrations of the antibiotic to be examined and a reference substance. The validation study aims to demonstrate the determination of the potency of benzylpenicillin potassium and streptomycin sulphate, it is an appropriate analytical method, reproducible and meets the quality requirements of Ascomicin product. The paper establishes the performance characteristics of the method considered and identify the factors that influence these characteristics. The diameters of inhibition zones, directly proportional to the logarithm of the concentration of the antibiotic used for the assay, measured and calculated using statistical methods (Combistats Soft. The assay is designed in such a way that the mathematical model on which the potency equation is based can be proved to be valid. A parallel-line model is chosen. The two log dose response lines of the preparation under examination and the standard preparation are parallel; they are rectilinear over the range of doses used in the calculation. These conditions are verified by validity tests for a given probability (P = 0.05. The test is not valid unless the confidence limits (P = 0.95 are not less than 50 per cent and not more than 200 per cent of the estimated potency. The estimated potency is not less than 95 per cent and not more than 105 per cent of the stated potency. The stated potency is not less than 19400 international units/g benzylpenicillin potassium and 13960 international units/g streptomycin sulphate. The validation

  1. Development and evaluation of task-specific NLP framework in China.

    Science.gov (United States)

    Ge, Caixia; Zhang, Yinsheng; Huang, Zhenzhen; Jia, Zheng; Ju, Meizhi; Duan, Huilong; Li, Haomin

    2015-01-01

    Natural language processing (NLP) has been designed to convert narrative text into structured data. Although some general NLP architectures have been developed, a task-specific NLP framework to facilitate the effective use of data is still a challenge in lexical resource limited regions, such as China. The purpose of this study is to design and develop a task-specific NLP framework to extract targeted information from particular documents by adopting dedicated algorithms on current limited lexical resources. In this framework, a shared and evolving ontology mechanism was designed. The result has shown that such a free text driven platform will accelerate the NLP technology acceptance in China.

  2. The impact of gallium content on degradation, bioactivity, and antibacterial potency of zinc borate bioactive glass.

    Science.gov (United States)

    Rahimnejad Yazdi, Alireza; Torkan, Lawrence; Stone, Wendy; Towler, Mark R

    2017-02-02

    Zinc borate glasses with increasing gallium content (0, 2.5, 5, 10, and 15 Wt % Ga) were synthesized and their degradation, bioactivity in simulated body fluid (SBF), and antibacterial properties were investigated. ICP measurements showed that increased gallium content in the glass resulted in increased gallium ion release and decreased release of other ions. Degradability declined with the addition of gallium, indicating the formation of more symmetric BO3 units with three bridging oxygens and asymmetric BO3 units with two bridging oxygens in the glass network as the gallium content in the series increased. The formation of amorphous CaP on the glass surface after 24 h of incubation in SBF was confirmed by SEM, XRD, and FTIR analyses. Finally, antibacterial evaluation of the glasses using the agar disc-diffusion method demonstrated that the addition of gallium increased the antibacterial potency of the glasses against P. aeruginosa (Gram-negative) while decreasing it against S. epidermidis (Gram-positive); considering the ion release trends, this indicates that the gallium ion is responsible for the glasses' antibacterial behavior against P. aeruginosa while the zinc ion controls the antibacterial activity against S. epidermidis. The statistical significance of the observed trends in the measurements were confirmed by applying the Kruskal-Wallis H Test. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  3. Vulnerability assessment using hazard potency for regions generating industrial hazardous waste.

    Science.gov (United States)

    Das, Arup; Gupta, A K; Mazumder, T N

    2012-03-30

    This study proposes a methodology that would measure the hazardous characteristics of industrial waste based on its physical and chemical properties. A composite hazardous waste index (HWI) is framed using a new aggregation operator proposed in this study. However, HWI alone cannot be used to compare the hazardous characteristics of different wastes. The concept of hazard potency (HP) is introduced in this study in order to address this problem. HP can be calculated not only for a single waste stream but also for multiple industrial processes in an industry. Thus the hazardous wastes generated from two industries can be directly compared using this methodology. The vulnerability arising out of an industrial unit has been evaluated using HP values of the unit and the population residing within its impact area. The industries in a region are prioritized based on the vulnerability of the adjoining population using the non-dominated sorting algorithm. Solutions are ordered into various levels of domination depending on their HP and population values. A case study of Kolkata Metropolitan Area is provided to substantiate the methodology. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Retained Myogenic Potency of Human Satellite Cells from Torn Rotator Cuff Muscles Despite Fatty Infiltration.

    Science.gov (United States)

    Koide, Masashi; Hagiwara, Yoshihiro; Tsuchiya, Masahiro; Kanzaki, Makoto; Hatakeyama, Hiroyasu; Tanaka, Yukinori; Minowa, Takashi; Takemura, Taro; Ando, Akira; Sekiguchi, Takuya; Yabe, Yutaka; Itoi, Eiji

    2018-01-01

    Rotator cuff tears (RCTs) are a common shoulder problem in the elderly that can lead to both muscle atrophy and fatty infiltration due to less physical load. Satellite cells, quiescent cells under the basal lamina of skeletal muscle fibers, play a major role in muscle regeneration. However, the myogenic potency of human satellite cells in muscles with fatty infiltration is unclear due to the difficulty in isolating from small samples, and the mechanism of the progression of fatty infiltration has not been elucidated. The purpose of this study was to analyze the population of myogenic and adipogenic cells in disused supraspinatus (SSP) and intact subscapularis (SSC) muscles of the RCTs from the same patients using fluorescence-activated cell sorting. The microstructure of the muscle with fatty infiltration was observed as a whole mount condition under multi-photon microscopy. Myogenic differentiation potential and gene expression were evaluated in satellite cells. The results showed that the SSP muscle with greater fatty infiltration surrounded by collagen fibers compared with the SSC muscle under multi-photon microscopy. A positive correlation was observed between the ratio of muscle volume to fat volume and the ratio of myogenic precursor to adipogenic precursor. Although no difference was observed in the myogenic potential between the two groups in cell culture, satellite cells in the disused SSP muscle showed higher intrinsic myogenic gene expression than those in the intact SSC muscle. Our results indicate that satellite cells from the disused SSP retain sufficient potential of muscle growth despite the fatty infiltration.

  5. Estimation of Maximum Recommended Therapeutic Dose Using Predicted Promiscuity and Potency.

    Science.gov (United States)

    Liu, T; Oprea, T; Ursu, O; Hasselgren, C; Altman, R B

    2016-12-01

    We report a simple model that predicts the maximum recommended therapeutic dose (MRTD) of small molecule drugs based on an assessment of likely protein-drug interactions. Previously, we reported methods for computational estimation of drug promiscuity and potency. We used these concepts to build a linear model derived from 238 small molecular drugs to predict MRTD. We applied this model successfully to predict MRTDs for 16 nonsteroidal antiinflammatory drugs (NSAIDs) and 14 antiretroviral drugs. Of note, based on the estimated promiscuity of low-dose drugs (and active chemicals), we identified 83 proteins as "high-risk off-targets" (HROTs) that are often associated with low doses; the evaluation of interactions with HROTs may be useful during early phases of drug discovery. Our model helps explain the MRTD for drugs with severe adverse reactions caused by interactions with HROTs. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  6. Development of a Sweetness Sensor for Aspartame, a Positively Charged High-Potency Sweetener

    Directory of Open Access Journals (Sweden)

    Masato Yasuura

    2014-04-01

    Full Text Available Taste evaluation technology has been developed by several methods, such as sensory tests, electronic tongues and a taste sensor based on lipid/polymer membranes. In particular, the taste sensor can individually quantify five basic tastes without multivariate analysis. However, it has proven difficult to develop a sweetness sensor, because sweeteners are classified into three types according to the electric charges in an aqueous solution; that is, no charge, negative charge and positive charge. Using membrane potential measurements, the taste-sensing system needs three types of sensor membrane for each electric charge type of sweetener. Since the commercially available sweetness sensor was only intended for uncharged sweeteners, a sweetness sensor for positively charged high-potency sweeteners such as aspartame was developed in this study. Using a lipid and plasticizers, we fabricated various lipid/polymer membranes for the sweetness sensor to identify the suitable components of the sensor membranes. As a result, one of the developed sensors showed responses of more than 20 mV to 10 mM aspartame and less than 5 mV to any other taste. The responses of the sensor depended on the concentration of aspartame. These results suggested that the developed sweetness sensor had high sensitivity to and high selectivity for aspartame.

  7. Evaluation of Serum Specific Antibody against Recombinant ESAT-6 Antigen in Patients with Tuberculosis and Comparing to Normal Controls

    Directory of Open Access Journals (Sweden)

    Homeira Izadi

    2017-02-01

    Full Text Available Background & Objective: Tuberculosis (TB is a zoonotic disease which is caused by Mycobacterium tuberculosis. Because of common structural and secretory antigens between pathogen and nonpathogenic mycobacterium, the specific diagnosis of TB is difficult. Therefore, it is very important to find a new method with high specificity and sensitivity for accurate and rapid diagnosis of tuberculosis. In this study, the serodiagnostic potential of Mycobacterium tuberculosis recombinant ESAT-6 in TB infected patients was evaluated by Enzyme Linked Immunosorbent Assay (ELISA. Materials & Methods: 55 TB patients with active disease and 28 healthy controls have been collected and evaluated in different dilutions in ELISA methods for the presence of specific anti-ESAT-6 antibody. The specificity and the sensitivity of this method was compared with the culture test. Results: TB patients have high levels of specific antibody against ESAT-6 antigens. The specificity and the sensitivity of this method was calculated as 80.90% and 85.45%, respectively. Conclusion: These findings provide useful information on the importance of ESAT-6 protein and suggested this serologic test as a good alternative method for rapid and prefect diagnosis of tuberculosis.

  8. Development of a problem solving evaluation instrument; untangling of specific problem solving assets

    Science.gov (United States)

    Adams, Wendy Kristine

    The purpose of my research was to produce a problem solving evaluation tool for physics. To do this it was necessary to gain a thorough understanding of how students solve problems. Although physics educators highly value problem solving and have put extensive effort into understanding successful problem solving, there is currently no efficient way to evaluate problem solving skill. Attempts have been made in the past; however, knowledge of the principles required to solve the subject problem are so absolutely critical that they completely overshadow any other skills students may use when solving a problem. The work presented here is unique because the evaluation tool removes the requirement that the student already have a grasp of physics concepts. It is also unique because I picked a wide range of people and picked a wide range of tasks for evaluation. This is an important design feature that helps make things emerge more clearly. This dissertation includes an extensive literature review of problem solving in physics, math, education and cognitive science as well as descriptions of studies involving student use of interactive computer simulations, the design and validation of a beliefs about physics survey and finally the design of the problem solving evaluation tool. I have successfully developed and validated a problem solving evaluation tool that identifies 44 separate assets (skills) necessary for solving problems. Rigorous validation studies, including work with an independent interviewer, show these assets identified by this content-free evaluation tool are the same assets that students use to solve problems in mechanics and quantum mechanics. Understanding this set of component assets will help teachers and researchers address problem solving within the classroom.

  9. Specific surface to evaluate the efficiencies of milling and pretreatment of wood for enzymatic saccharification

    Science.gov (United States)

    Junyong Zhu; G.S. Wang; X.J. Pan; Roland Gleisner

    2009-01-01

    Sieving methods have been almost exclusively used for feedstock size-reduction characterization in the biomass refining literature. This study demonstrates a methodology to properly characterize specific surface of biomass substrates through two dimensional measurement of each fiber of the substrate using a wet imaging technique. The methodology provides more...

  10. Content Specificity in Imaginal Exposure: Evaluation of Subjective and Physiological Responding in Patients with Panic Disorder

    Science.gov (United States)

    1996-06-18

    Diastolic Blood Pressure. Diagnostic Status Predicting Mean Arterial Pressure. Specific Focus Correlations. VI INTRODUCfION Ahhougb Freud described panic...Psychiatric illnesses in the mothers of school-phobic adolescents . British Journal of Psychiatry, 125,466-467. Bond, AJ., James, c., & Lader, M.H

  11. Evaluation of Influenza-Specific Humoral Response by Microbead Array Analysis

    Directory of Open Access Journals (Sweden)

    Yoav Keynan

    2011-01-01

    Full Text Available RATIONALE: Quantitation and determination of antigen specificity of systemic and mucosal immune responses to influenza vaccination is beneficial for future vaccine development. Previous methods to acquire this information were costly, time consuming and sample exhaustive. The benefits of suspension microbead array (MBA analysis are numerous. The multiplex capabilities of the system conserve time, money and sample, while generating statistically powerful data.

  12. An Evaluation of English for Specific Purposes (ESP) As a Modern ...

    African Journals Online (AJOL)

    English Language Teaching (ELT) has come a long way, moving from grammatical or linguistic approach to communicative approach (which ESP is all about). This study looked into the origin, and development of ELT, the concept of English for specific purposes (ESP) as an approach to language teaching, and the ...

  13. Evaluating Specification Tests in the Context of Value-Added Estimation. Working Paper #38

    Science.gov (United States)

    Guarino, Cassandra M.; Reckase, Mark D.; Stacy, Brian W.; Wooldridge, Jeffrey M.

    2014-01-01

    We study the properties of two specification tests that have been applied to a variety of estimators in the context of value-added measures (VAMs) of teacher and school quality: the Hausman test for choosing between random and fixed effects and a test for feedback (sometimes called a "falsification test"). We discuss theoretical…

  14. Evaluating Specification Tests in the Context of Value-Added Estimation

    Science.gov (United States)

    Guarino, Cassandra M.; Reckase, Mark D.; Stacy, Brian W.; Wooldridge, Jeffrey M.

    2015-01-01

    We study the properties of two specification tests that have been applied to a variety of estimators in the context of value-added measures (VAMs) of teacher and school quality: the Hausman test for choosing between student-level random and fixed effects, and a test for feedback (sometimes called a "falsification test"). We discuss…

  15. LED street lighting evaluation -- phase II : LED specification and life-cycle cost analysis.

    Science.gov (United States)

    2015-01-01

    Phase II of this study focused on developing a draft specification for LED luminaires to be used by IDOT : and a life-cycle cost analysis (LCCA) tool for solid state lighting technologies. The team also researched the : latest developments related to...

  16. Evaluation of Populus and Salix continuously irrigated with landfill leachate I. Genotype-specific elemental phytoremediation

    Science.gov (United States)

    Ronald S., Jr. Zalesny; Edmund O. Bauer

    2007-01-01

    There is a need for the identification and selection of specific tree genotypes that can sequester elements from contaminated soils, with elevated rates of uptake. We irrigated Populus (DN17, DN182, DN34, NM2, NM6) and Salix (94003, 94012, S287, S566, SX61) genotypes planted in large soil-filled containers with landfill leachate or...

  17. Balanced RAP/RAS mix design and performance evaluation for project - specific service conditions.

    Science.gov (United States)

    2013-01-01

    This presentation summarizes Projects 0-6092/0-6614. It includes accomplishments, best practices, field performance data of RAP/RAS test sections, balanced RAP/RAS mix design for project-specific conditions, and approaches for improving RAP/RAS mix p...

  18. Enhanced potency of individual and bivalent DNA replicon vaccines or conventional DNA vaccines by formulation with aluminum phosphate.

    Science.gov (United States)

    Yu, Yun-Zhou; Wang, Wen-Bin; Li, Na; Wang, Shuang; Yu, Wei-Yuan; Sun, Zhi-Wei

    2010-11-01

    DNA vaccines against botulinum neurotoxin (BoNTs) induce protective humoral immune responses in mouse model, but when compared with conventional vaccines such as toxoid and protein vaccines, DNA vaccines often induce lower antibody level and protective efficacy and are still necessary to increase their potency. In this study we evaluated the potency of aluminum phosphate as an adjuvant of DNA vaccines to enhance antibody responses and protective efficacy against botulinum neurotoxin serotypes A and B in Balb/c mice. The administration of these individual and bivalent plasmid DNA replicon vaccines against botulinum neurotoxin serotypes A and B in the presence of aluminum phosphate improved both antibody responses and protective efficacy. Furthermore, formulation of conventional plasmid DNA vaccines encoding the same Hc domains of botulinum neurotoxin serotypes A and B with aluminum phosphate adjuvant increased both antibody responses and protective efficacy. These results indicate aluminum phosphate is an effective adjuvant for these two types of DNA vaccines (i.e., plasmid DNA replicon vaccines and conventional plasmid DNA vaccines), and the vaccine formulation described here may be an excellent candidate for further vaccine development against botulinum neurotoxins. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  19. Using marketing research methods to evaluate a stage-specific intervention.

    Science.gov (United States)

    Poscente, Neila; Rothstein, Marsha; Irvine, M Jane

    2002-01-01

    To show how marketing methods can be used to distribute and evaluate a health promotion intervention. Mass media promotion was used to communicate a physical activity resource. Brief telephone interviews were used to screen callers and recruit participants into a controlled trial. Follow-up was conducted 3 months later. Information was gained about the attitudes and motivation of callers. The majority of participants (study and control) made significant changes in their activity levels. The study demonstrated that even when mass media channels are used, market segmentation can be achieved and program evaluation conducted.

  20. Evaluating the Relationship between FRET Changes and Distance Changes Using DNA Length and Restriction Enzyme Specificity

    Science.gov (United States)

    Pazhani, Yogitha; Horn, Abigail E.; Grado, Lizbeth; Kugel, Jennifer F.

    2016-01-01

    FRET (Fo¨rster resonance energy transfer) involves the transfer of energy from an excited donor fluorophore to an acceptor molecule in a manner that is dependent on the distance between the two. A biochemistry laboratory experiment is described that teaches students how to use FRET to evaluate distance changes in biological molecules. Students…

  1. Evaluation of rapid one-step prostate specific antigen test against an ...

    African Journals Online (AJOL)

    Main Objective: To evaluate the analytical performance of the rapid one-step immunochromatographic PSA assay against an established ELISA method. Design: A comparative study was conducted in the Department of Chemical Pathology at the University of Zimbabwe, College Health Sciences, between June 2012 and ...

  2. Field-based evaluation of a male-specific (F+) RNA coliphage concentration method

    Science.gov (United States)

    Fecal contamination of water poses a significant risk to public health due to the potential presence of pathogens, including enteric viruses. Thus, sensitive, reliable and easy to use methods for the detection of microorganisms are needed to evaluate water quality. In this stud...

  3. A BDI Dialogue Agent for Social Support : Specification and Evaluation Method

    NARCIS (Netherlands)

    Van der Zwaan, J.M.; Dignum, V.; Jonker, C.M.

    2012-01-01

    An important task for empathic agents is to provide social support, that is, to help people increase their well-being and decrease the perceived burden of their problems. The contributions of this paper are 1) the specifcation of speech acts for a social support dialogue agent, and 2) an evaluation

  4. A BDI Dialogue Agent for Social Support : Specification and Evaluation Method (extended abstract)

    NARCIS (Netherlands)

    Van der Zwaan, J.M.; Dignum, V.; Jonker, C.M.

    2012-01-01

    An important task for empathic agents is to provide social support, that is, to help alleviate emotional distress. In this paper we specify verbal support types for a dialogue agent that provides social support, and propose an evaluation method for such an agent in a sensitive domain (cyberbullying)

  5. Economic evaluation of vaccines : specificities and future challenges illustrated by recent European examples

    NARCIS (Netherlands)

    Postma, M.J.; Westra, T.A.; Quilici, S.; Largeron, N.

    2013-01-01

    This study reviews the current challenges in the economic evaluation of vaccines with a focus on European countries. In particular, the type of clinical evidence generally available, the impact of discounting for time preference and the use of modeling to derive valid cost-effectiveness assessments

  6. Economic evaluation of vaccines : specificities and future challenges illustrated by recent European examples

    NARCIS (Netherlands)

    Postma, Maarten J; Westra, Tjalke A; Quilici, Sibilia; Largeron, Nathalie

    This study reviews the current challenges in the economic evaluation of vaccines with a focus on European countries. In particular, the type of clinical evidence generally available, the impact of discounting for time preference and the use of modeling to derive valid cost-effectiveness assessments

  7. Utilization and evaluation of CHO-specific sequence databases for mass spectrometry based proteomics.

    Science.gov (United States)

    Meleady, Paula; Hoffrogge, Raimund; Henry, Michael; Rupp, Oliver; Bort, Juan Hernandez; Clarke, Colin; Brinkrolf, Karina; Kelly, Shane; Müller, Benjamin; Doolan, Padraig; Hackl, Matthias; Beckmann, Tim Frederik; Noll, Thomas; Grillari, Johannes; Barron, Niall; Pühler, Alf; Clynes, Martin; Borth, Nicole

    2012-06-01

    Recently released sequence information on Chinese hamster ovary (CHO) cells promises to not only facilitate our understanding of these industrially important cell factories through direct analysis of the sequence, but also to enhance existing methodologies and allow new tools to be developed. In this article we demonstrate the utilization of CHO specific sequence information to improve mass spectrometry (MS) based proteomic identification. The use of various CHO specific databases enabled the identification of 282 additional proteins, thus increasing the total number of identified proteins by 40-50%, depending on the sample source and methods used. In addition, a considerable portion of those proteins that were identified previously based on inter-species sequence homology were now identified by a larger number of peptides matched, thus increasing the confidence of identification. The new sequence information offers improved interpretation of proteomic analyses and will, in the years to come, prove vital to unraveling the CHO proteome. Copyright © 2012 Wiley Periodicals, Inc.

  8. Evaluation of the specificity of antibodies raised against cannabinoid receptor type 2 in the mouse retina

    DEFF Research Database (Denmark)

    Cécyre, Bruno; Thomas, Sébastien; Ptito, Maurice

    2014-01-01

    blot and immunohistochemistry on retinal tissue obtained from wild-type mice and mice lacking CB2R (cnr2 (-/-) ). One of the antibodies tested exhibited a valuable specificity as it marked a single band near the predicted molecular weight in Western blot and produced no staining in cnr2 (-/-) mice...... retina sections. The other antibodies tested detected multiple bands in Western blot and labeled unidentified proteins when used with their immunizing peptide or on cnr2 (-/-) retinal sections. We conclude that many commonly used antibodies raised against CB2R are not specific for use...... because it would mean that in addition to its effects on the peripheral pain pathway, CB2R could also mediate some central effects of cannabinoids. In an attempt to clarify the debate over CB2R expression in the CNS, we tested several commercially or academically produced CB2R antibodies using Western...

  9. Evaluation of site-specific tactics using bifenazate and Neoseiulus californicus for management of Tetranychus urticae (Acari: Tetranychidae) in strawberries.

    Science.gov (United States)

    Liu, Ruohan; Nyoike, Teresia W; Liburd, Oscar E

    2016-10-01

    Greenhouse and field experiments were conducted to evaluate the effectiveness of site-specific tactics for management of the twospotted spider mite, Tetranychus urticae Koch, a major pest of greenhouse and field-grown strawberries (Fragaria x ananassa Duchesne). Two site-specific (spot) treatments, the miticide bifenazate (Acramite(®)) and the predatory mite Neoseiulus californicus McGregor, were compared with whole-plot treatments of bifenazate or N. californicus to determine whether T. urticae could be effectively managed in field-grown strawberry using only site-specific tactics. Additionally, the cost of site-specific tactics was compared with whole-plot treatments to determine the economic value of using site-specific management tactics for T. urticae in strawberries. In the greenhouse, all treatments equivalently reduced the number of T. urticae below control. In the field during the 2011-2012 season, more T. urticae eggs and motiles were in the whole-plot treatments of both N. californicus and bifenazate in the mid-season and late season, respectively, compared with the spot treatments. With the exception of site-specific N. californicus during the 2011-2012 field season, there were no differences in marketable yields between plots with site-specific treatments and whole-plot management. An economic analysis demonstrated a significant cost savings (75.3 %) with site-specific treatments of N. californicus compared with whole-plot application of N. californicus. Similarly, a 24.7 % reduction in cost was achieved in using site-specific bifenazate compared with whole-plot application of bifenazate. The findings indicate that site-specific treatments with N. californicus and bifenazate are competitive alternatives to whole-field application for T. urticae management in strawberries.

  10. Design and evaluation of Bacteroides DNA probes for the specific detection of human fecal pollution

    Energy Technology Data Exchange (ETDEWEB)

    Kreader, C.A. [Environmental Protection Agency, Cincinnati, OH (United States)

    1995-04-01

    Because Bacteroides spp. are obligate anaerobes that dominate the human fecal flora, and because some species may live only in the human intestine, these bacteria might be useful to distinguish human from nonhuman sources of fecal pollution. To test this hypothesis, PCR primers specific for 16S rRNA gene sequences of Bacteroides distasonis, B. thetaiotaomicron, and B. vulgatus were designed. Hybridization with species-specific internal probes was used to detect the intended PCR products. Extracts from 66 known Bacteroides strains, representing 10 related species, were used to confirm the specificity of these PCR-hybridization assays. To test for specificity in feces, procedures were developed to prepare DNA of sufficient purity for PCR. Extracts of feces from 9 humans and 70 nonhumans (cats, dogs, cattle, hogs, horses, sheep, goats, and chickens) were each analyzed with and without an internal positive control to verify that PCR amplification was not inhibited by substances in the extract. In addition, serial dilutions from each extract that tested positive were assayed to estimate the relative abundance of target Bacteroides spp. in the sample. Depending on the primer-probe set used, either 78 or 67% of the human fecal extracts tested had high levels of target DNA. On the other hand, only 7 to 11% of the nonhuman extracts tested had similarly high levels of target DNA. An additional 12 to 20% of the nonhuman extracts had levels of target DNA that were 100- to 1,000-fold lower than those found in humans. Although the B. vulgatus probes detected high levels of their target DNA in most of the house pets, similarly high levels of target DNA were found only in a few individuals from other groups of nonhumans. Therefore, the results indicate that these probes can distinguish human from non human feces in many cases. 50 refs., 5 figs., 2 tabs.

  11. The evaluation-mediation hypothesis: does the specification of potential side effects influence the perceived risk of medication?

    Energy Technology Data Exchange (ETDEWEB)

    Reimer, T. [Universitaet Potsdam, Institut fur Psychologie, Abteilung Sozialpsychologi, Potsdam (Germany)

    1998-07-01

    Full text of publication follows: starting from the assumptions of support theory, this project analyzed the extent to which the specification of potential side effects influences the perceived risk associated, with a particular medication. Respondents were presented with an instruction leaflet for a medication which indicated (a) the overall probability that a side effect will occur or (b) the probability of occurrence of several specific side effects. Support theory predicts that the cognitive availability of potential side effects and therefore the perceived risk increases as a function of the specificity with which the side effects are presented. In contrast the evaluation-mediation hypothesis predicts that a more detailed presentation of potential side effects enhances the perceived quality of the information leaflet and thereby leads to a reduction of perceived risk. Support for the evaluation-mediation hypothesis was found in a series of studies which included the editing hypothesis and the elaboration likelihood model as additional explanations: the more detailed the information about potential side effects, the lower the estimated risk of suffering a side effect on taking the medication. As predicted, the influence of presentation specificity on perceived risk was mediated almost exclusively by the perceived quality of the information leaflet. A current series of studies seeks to support the evaluation-mediation hypothesis in a completely different domain, the perceived risk of environmental pollution by motor vehicles. (author)

  12. [Preparation and immunological evaluation of oral solution of egg yolk-derived hepatitis B virus-specific transfer factor].

    Science.gov (United States)

    Xu, Yanping; Zhang, Qing; Zhan, Xuejun; Xie, Daze; Dai, Ge; Yang, Hui

    2013-12-01

    To prepare the oral solution of egg yolk hepatitis B virus (HBV)-specific transfer factor (EYHBV-TF) and evaluate its immunological activity as an immune regulator against hepatitis B. From hens immunized with the Hepatitis B vaccine the egg yolk was isolated to extract the specific transfer factor EYHBV-TF, and its physicochemical properties were examined. Leukocyte adhesion inhibition test (LAI) was performed to detect the immunogenic activity of EYHBV-TF. The solution of EYHBV-TF was then administered orally in normal mice, and the specific cellular immune activity induced was assayed with delayed type skin hypersensitivity test (DTH), with the non-specific immune activity assessed with immune organ index. The immune responses induced by oral EYHBV-STF solution were compared with those by EYHBV-STF injection and by different dosages (injection and oral) of porcine spleen HBV-specific transfer factor (PSHBV-STF), porcine spleen nonspecific transfer factor, and egg yolk extracts from non-immunized hens. The prepared EYHBV-STF oral solution, which met the standards for biological products, could inhibit leukocyte adhesion in vitro and significantly enhance mouse foot pad swelling, demonstrating its capability of transferring antigen-specific delayed type hypersensitivity reactions to naive recipient. EYHBV-STF oral solution also significantly improved the immune organ index in mice (Pimmune activity and can significantly enhance specific cellular immune responses.

  13. Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weicheng; Liu, Xiawei; Bao, Shaopan; Xiao, Bangding; Fang, Tao, E-mail: fangt@ihb.ac.cn [Chinese Academy of Sciences, Institute of Hydrobiology (China)

    2016-12-15

    For safety and environmental risk assessments of nanomaterials (NMs) and to provide essential toxicity data, nano-specific toxicities, or excess toxicities, of ZnO, CuO, and Ag nanoparticles (NPs) (20, 20, and 30 nm, respectively) to Escherichia coli and Saccharomyces cerevisiae in short-term (6 h) and long-term (48 h) bioassays were quantified based on a toxic ratio. ZnO NPs exhibited no nano-specific toxicities, reflecting similar toxicities as ZnO bulk particles (BPs) (as well as zinc salt). However, CuO and Ag NPs yielded distinctly nano-specific toxicities when compared with their BPs. According to their nano-specific toxicities, the capability of these NPs in eliciting hazardous effects on humans and the environment was as follows: CuO > Ag > ZnO NPs. Moreover, long-term bioassays were more sensitive to nano-specific toxicity than short-term bioassays. Overall, nano-specific toxicity is a meaningful measurement to evaluate the environmental risk of NPs. The log T{sub e}{sup particle} value is a useful parameter for quantifying NP nano-specific toxicity and enabling comparisons of international toxicological data. Furthermore, this value could be used to determine the environmental risk of NPs.

  14. Evaluation of four phloem-specific promoters in vegetative tissues of transgenic citrus plants.

    Science.gov (United States)

    Dutt, M; Ananthakrishnan, G; Jaromin, M K; Brlansky, R H; Grosser, J W

    2012-01-01

    'Mexican' lime (Citrus aurantifolia Swingle) was transformed with constructs that contained chimeric promoter-gus gene fusions of phloem-specific rolC promoter of Agrobacterium rhizogenes, Arabidopsis thaliana sucrose-H(+) symporter (AtSUC2) gene promoter of Arabidopsis thaliana, rice tungro bacilliform virus (RTBV) promoter and sucrose synthase l (RSs1) gene promoter of Oryza sativa (rice). Histochemical β-glucuronidase (GUS) analysis revealed vascular-specific expression of the GUS protein in citrus. The RTBV promoter was the most efficient promoter in this study while the RSs1 promoter could drive low levels of gus gene expression in citrus. These results were further validated by reverse transcription real-time polymerase chain reaction and northern blotting. Southern blot analysis confirmed stable transgene integration, which ranged from a single insertion to four copies per genome. The use of phloem-specific promoters in citrus will allow targeted transgene expression of antibacterial constructs designed to battle huanglongbing disease (HLB or citrus greening disease), associated with a phloem-limited Gram-negative bacterium.

  15. A Methodology for Writing High Quality Requirement Specifications and for Evaluating Existing Ones

    Science.gov (United States)

    Rosenberg, Linda; Hammer, Theodore

    1999-01-01

    Requirements development and management have always been critical in the implementation of software systems-engineers are unable to build what analysts can not define. It is generally accepted that the earlier in the life cycle potential risks are identified the easier it is to eliminate or manage the conditions that introduce that risk. Problems that are not found until testing are approximately 14 times more costly to fix than if the problem was found in the requirement phase. The requirements specification, as the first tangible representation of the capability to be produced, establishes the basis for all of the project's engineering management and assurance functions. If the quality of the requirements specification is poor it can give rise to risks in all areas of the project. Recently, automated tools have become available to support requirements management. The use of these tools not only provides support in the definition and tracing of requirements, but it also opens the door to effective use of metrics in characterizing and assessing the quality of the requirement specifications.

  16. A Methodology for Writing High Quality Requirements Specification and Evaluating Existing Ones

    Science.gov (United States)

    Rosenberg, Linda; Hammer, Theodore

    1999-01-01

    Requirements development and management have always been critical in the implementation of software systems; engineers are unable to build what analysts can't define. It is generally accepted that the earlier in the life cycle potential risks are identified the easier it is to eliminate or manage the conditions that introduce that risk. Problems that are not found until testing are approximately 14 times more costly to fix than if the problem was found in the requirement phase. The requirements specification, as the first tangible representation of the capability to be produced, establishes the basis for all of the project's engineering management and assurance functions. If the quality of the requirements specification is poor it can give rise to risks in all areas of the project. Recently, automated tools have become available to support requirements management. The use of these tools not only provides support in the definition and tracing of requirements, but it also opens the door to effective use of metrics in characterizing and assessing the quality of the requirement specifications.

  17. Measuring Evaluation Fears in Adolescence: Psychometric Validation of the Portuguese Versions of the Fear of Positive Evaluation Scale and the Specific Fear of Negative Evaluation Scale

    Science.gov (United States)

    Vagos, Paula; Salvador, Maria do Céu; Rijo, Daniel; Santos, Isabel M.; Weeks, Justin W.; Heimberg, Richard G.

    2016-01-01

    Modified measures of Fear of Negative Evaluation and Fear of Positive Evaluation were examined among Portuguese adolescents. These measures demonstrated replicable factor structure, internal consistency, and positive relationships with social anxiety and avoidance. Gender differences were found. Implications for evaluation and intervention are…

  18. Validation and evaluation of common large-area display set (CLADS) performance specification

    Science.gov (United States)

    Hermann, David J.; Gorenflo, Ronald L.

    1998-09-01

    Battelle is under contract with Warner Robins Air Logistics Center to design a Common Large Area Display Set (CLADS) for use in multiple Command, Control, Communications, Computers, and Intelligence (C4I) applications that currently use 19- inch Cathode Ray Tubes (CRTs). Battelle engineers have built and fully tested pre-production prototypes of the CLADS design for AWACS, and are completing pre-production prototype displays for three other platforms simultaneously. With the CLADS design, any display technology that can be packaged to meet the form, fit, and function requirements defined by the Common Large Area Display Head Assembly (CLADHA) performance specification is a candidate for CLADS applications. This technology independent feature reduced the risk of CLADS development, permits life long technology insertion upgrades without unnecessary redesign, and addresses many of the obsolescence problems associated with COTS technology-based acquisition. Performance and environmental testing were performed on the AWACS CLADS and continues on other platforms as a part of the performance specification validation process. A simulator assessment and flight assessment were successfully completed for the AWACS CLADS, and lessons learned from these assessments are being incorporated into the performance specifications. Draft CLADS specifications were released to potential display integrators and manufacturers for review in 1997, and the final version of the performance specifications are scheduled to be released to display integrators and manufacturers in May, 1998. Initial USAF applications include replacements for the E-3 AWACS color monitor assembly, E-8 Joint STARS graphics display unit, and ABCCC airborne color display. Initial U.S. Navy applications include the E-2C ACIS display. For these applications, reliability and maintainability are key objectives. The common design will reduce the cost of operation and maintenance by an estimated 3.3M per year on E-3 AWACS

  19. Biological potency evaluation and characterization of rhG-CSF in pharmaceutical products Avaliação biológica da potência e caracterização de rhG-CSF em produtos farmacêuticos

    National Research Council Canada - National Science Library

    Cristiane F. Codevilla; Thiago Barth; Liberato Brum Júnior; Marcio Fronza; Sérgio L. Dalmora

    2004-01-01

    The identification of rhG-CSF was carried out in pharmaceutical preparations by non-reducing polyacrylamide gel electrophoresis and western blotting with specific antibodies, showing a single band in the 19 kDa region...

  20. Designing and evaluating culturally specific smoking cessation interventions for American Indian communities.

    Science.gov (United States)

    Fu, Steven S; Rhodes, Kristine L; Robert, Christina; Widome, Rachel; Forster, Jean L; Joseph, Anne M

    2014-01-01

    American Indians have the highest smoking rates in the United States, yet few randomized controlled trials of culturally specific interventions exist. This study assessed American Indians' opinions about evidence-based treatment and attitudes toward participating in clinical trials. Six focus groups were conducted based on smoking status (current/former smoker), sex, and elder status (55 years and older or younger). Meetings were held at local American Indian community organizations. This project was accomplished in partnership with the American Indian Community Tobacco Projects, a community-academic research partnership at the University of Minnesota. Thematic qualitative data analyses were conducted. Participants desired the following: (a) programs led by trained American Indian community members, (b) the opportunity to connect with other American Indian smokers interested in quitting, and (c) programs promoting healthy lifestyles. Strategies desired for treatment included (a) free pharmacotherapy, including nicotine replacement therapy (NRT); (b) nominal incentives, e.g., gift cards for groceries; and (c) culturally specific program components such as American Indian images, education on traditional tobacco use, and quit-smoking messages that target the value of family and include narratives or story telling in recruitment and program materials. Biochemical verification of smoking abstinence, such as salivary cotinine or carbon monoxide breathalyzers, is likely acceptable. Standard treatment or delayed treatment control groups were viewed as potentially acceptable for randomized study designs. Rigorously conducted randomized controlled trials of culturally specific smoking cessation interventions are sorely needed but will only be accomplished with the commitment of funders, researchers, and collaborative trusting relationships with the community.

  1. [Evaluation of serum specific IgM detection in diagnosis of respiratory viral infections in children].

    Science.gov (United States)

    Song, Qin-wei; Zhu, Ru-nan; Deng, Jie; Wang, Fang; Zhao, Lin-qing; Sun, Yu; Ding, Ya-xin; Qian, Yuan

    2012-06-01

    The present study was designed to explore the practical application of the rapid etiological diagnosis by detecting specific IgM antibody against common respiratory viruses in children with acute lower respiratory infections (ALRI). Clinical specimens including nasopharyngeal aspirates and serum of acute phase from hospitalized children were collected from 207 infants and children with acute lower respiratory infections from March 2009 to September 2010. Seven common respiratory virus antigens were identified from the collected nasopharyngeal aspirates by direct immunofluorescence assay (DFA). ELISA was used to detect specific IgM antibody against RSV, ADV, IFVA, IFVB and PIV, while indirect immunofluorescence assay (IFA) was used to detect specific IgM antibody against RSV, ADV, IFVA, IFVB, PIV1, PIV2 and PIV3 in collected acute phase serum. The overall positive rates to detect viral antigen by using DFA, ELISA and IFA was 67.6%, 57.5% and 39.6%, respectively. The consistent rate of ELISA and IFA versus accepted DFA were 21.7% and 31.4%, respectively. The average days from onset of the symptoms to blood sample collection for those with the consistent results by ELISA and DFA were 12.0 d for ADV, 9.6 d for PIV2, 9.5 d for IFV, and 5.3 d for RSV, respectively, and by IFA and DFA were 15.0 d for PIV3, 9.2 d for ADV, and 7.4 d for RSV, respectively. Among all age groups, the consistent rate of serum viral IgM and antigen detections was highest in children younger than 3 years old. Although there were differences between serum IgM antibody and viral antigen detections, specific IgM antibody detection was of value in early and rapid etiological diagnosis of pediatric ALRI, especially for young children. It could provide serologic evidence of respiratory virus infection. The diagnostic rate of pathogen could be improved if it was used in combination with viral antigen diagnostic methods.

  2. Team Potency and Its Impact on Performance via Self-efficacy and Adaptability

    Directory of Open Access Journals (Sweden)

    Rodrigo Bastos Monteiro

    2016-01-01

    Full Text Available In sales, working together as a team for achieving individual performance is a relevant element. In this paper, we suggest a theoretical framework that analyzes the impact of team potency on subjective performance, according to two mechanisms: self-efficacy and adaptability. The hypotheses suggest that (a team potency has a positive relationship with self-efficacy and adaptability; self-efficacy and adaptability impact performance (b directly and (c indirectly, through a mediating role; and (d interpersonal climate quality moderates these associations. We did a national survey with 290 salespeople organized in 101 teams from a water purification company. We used multilevel analyses and results suggested that sales team potency has a main effect on self-efficacy and adaptability. Second, results showed that self-efficacy and adaptability explain subjective performance. Third, self-efficacy and adaptability mediate the association between team potency and individual performance. Fourth, we did not find support for a moderating role of interpersonal climate quality on team potency. Final remarks and future research are discussed in the paper.

  3. Prospective evaluation of patient satisfaction after the use of brachytherapy specific educational materials for cervical cancer.

    Science.gov (United States)

    Rash, Dominique; Hess, Clayton; Lentz, Susan; Tait, Lauren; Michaud, Anthony; Mayadev, Jyoti

    2016-01-01

    Cervical cancer patients are faced with an enormous amount of medical information in a complex oncology field with sophisticated treatments including brachytherapy. We investigated the use of enhanced vs. standard brachytherapy-specific educational materials on patient-reported satisfaction during the informed consent process for intracavitary high-dose-rate brachytherapy. A single-institution, prospective, randomized trial was performed to study patient-reported satisfaction with novel educational materials for high-dose-rate brachytherapy in women undergoing definitive radiation for cervical cancer. Fourteen women receiving informed consent with a customized educational booklet were randomized between no further intervention and take-home educational materials. The weighted average for 10 of 11 survey questions was higher in the intervention arm but ranged between 4 (agree) and 5 (strongly agree) for all questions in both arms. The mean weighted patient satisfaction scores ± standard deviations in the control arm and the intervention arms were 54.3 ± 6.4 and 57.5 ± 2.7, respectively (p = 0.26). Knowledge acquisition is presumed to be part of the coping process for women facing increased stress during a cancer diagnosis. A brachytherapy-specific, visual, patient-educational booklet and take-home materials used to supplement the informed consent process for high-dose-rate brachytherapy resulted in high levels of patient-reported satisfaction among women treated with cervical cancer. Published by Elsevier Inc.

  4. Evaluation of swell behaviour of expansive clays from specific moisture capacity

    Directory of Open Access Journals (Sweden)

    Pino Alejandro

    2016-01-01

    Full Text Available Current swell characterization techniques used to interpret the mechanical volume change occurring during the swelling process are not successful due to lack of inclusion of influential properties. Accurate prediction of swelling behaviour allows us to design more efficiently and with better reliability. This research aims at developing a more comprehensive framework to predict swell potential. Laboratory studies are conducted on five natural expansive soils with different degree of expansiveness. Initial studies include determination of basic soil characterization, swell strains and swell pressures at their compacted state along with their inherent mineralogy. Later, replicate samples were studied for soil water characteristic curves using standard pressure cell apparatus and filter paper techniques. The path traversed by the specimen during swelling process is representative of the soil water characteristic curve of the same specimen. Hence, studies are pursued to understand the relationship between degree of expansiveness and the specific moisture capacity relative to that particular range of suction head. Test results showed that the degree of expansion represented by swelling strain or swelling pressure is proportional to the specific moisture capacity determined during the swelling process.

  5. Evaluation of Cocktails with Recombinant Proteins of Mycobacterium bovis for a Specific Diagnosis of Bovine Tuberculosis

    Directory of Open Access Journals (Sweden)

    María Laura Mon

    2014-01-01

    Full Text Available The Delayed type hypersensitivity skin test (DTH and interferon-gamma assay are used for the diagnosis of bovine tuberculosis (TBB. The specificity of these diagnoses, however, is compromised because both are based on the response against purified protein derivative of Mycobacterium bovis (PPD-B. In this study, we assessed the potential of two cocktails containing M. bovis recombinant proteins: cocktail 1 (C1: ESAT-6, CFP-10 and MPB83 and cocktail 2 (C2: ESAT-6, CFP-10, MPB83, HspX, TB10.3, and MPB70. C1, C2, and PPD-B showed similar response by DTH in M. bovis-sensitized guinea pigs. Importantly, C1 induced a lower response than PPD-B in M. avium-sensitized guinea pigs. In cattle, C1 displayed better performance than PPD-B and C2; indeed, C1 showed the least detection of animals either vaccinated or Map-infected. To optimize the composition of the cocktails, we obtained protein fractions from PPD-B and tested their immunogenicity in experimentally M. bovis-infected cattle. In one highly reactive fraction, seven proteins were identified. The inclusion of FixB in C1 enhanced the recognition of M. bovis-infected cattle without compromising specificity. Our data provide a promising basis for the future development of a cocktail for TBB detection without interference by the presence of sensitized or infected animals with other mycobacteria.

  6. Therapeutic evaluation of lumbar tender point deep massage for chronic non-specific low back pain.

    Science.gov (United States)

    Zheng, Zhixin; Wang, Jun; Gao, Qian; Hou, Jingshan; Ma, Ling; Jiang, Congbo; Chen, Guohui

    2012-12-01

    To observe the therapeutic effect of lumbar tender point deep tissue massage plus lumbar traction on chronic non-specific low back pain using change in pressure pain threshold, muscle hardness and pain intensity as indices. We randomly divided 64 patients into a treatment group (32 cases) and a control group (32 cases). Two drop-outs occurred in each group. Patients in the treatment group received tender point deep tissue massage plus lumbar traction and patients in the control group received lumbar traction, alone. We used a tissue hardness meter/algometer and visual analog scale (VAS) to assess the pressure pain threshold, muscle hardness and pain intensity. Following treatment, we obtained the following results in the treatment and control groups, respectively: the pressure pain threshold difference was 1.5 +/- 0.8 and 1.1 +/- 0.7; the muscle hardness difference was 4.2 +/- 1.6 and 3.5 +/- 1.3; and the VAS score difference was 1.9 +/- 0.9 and 1.4 +/- 0.8. Compared to the control group, the treatment group had higher pressure pain threshold (t = 2.09, P Lumbar tender point deep tissue massage combined with lumbar traction produced better improvement in pressure pain threshold, muscle hardness and pain intensity in patients with chronic non-specific low back pain than with lumbar traction alone.

  7. Targeting Nanomedicines to Prostate Cancer: Evaluation of Specificity of Ligands to Two Different Receptors In Vivo.

    Science.gov (United States)

    Pearce, Amanda K; Fuchs, Adrian V; Fletcher, Nicholas L; Thurecht, Kristofer J

    2016-10-01

    This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer. Pegylated hyperbranched polymers were labelled with fluorescent markers and targeting ligands against two different prostate cancer markers; prostate specific membrane antigen (PSMA) and the protein kinase, EphrinA2 receptor (EphA2). The PSMA targeted nanomedicine utilised a small molecule glutamate urea inhibitor of the protein, while the EphA2 targeted nanomedicine was conjugated to a single-chain variable fragment based on the antibody 4B3 that has shown high affinity to the receptor. Hyperbranched polymers were synthesised bearing the different targeting ligands. In the case of the EphA2-targeting nanomedicine, significant in vitro uptake was observed in PC3 prostate cancer cells that overexpress the receptor, while low uptake was observed in LNCaP cells (that have minimal expression of this receptor). Conversely, the PSMA-targeted nanomedicine showed high uptake in LNCaP cells, with only minor uptake in the PC3 cells. In a dual-tumour xenograft mouse model, the nanomedicines showed high uptake in tumours in which the receptor was overexpressed, with only minimal non-specific accumulation in the low-expression tumours. This work highlighted the importance of clearly defining the target of interest in next-generation nanomedicines, and suggests that dual-targeting in such nanomedicines may be a means to achieve greater efficacy.

  8. [Specifity of optic disc evaluation in healthy subjects with large optic discs and physiologic cupping using confocal scanning laser ophthalmoscopy].

    Science.gov (United States)

    Plange, N; Hirsch, T; Bienert, M; Remky, A

    2014-02-01

    Imaging methods of the optic nerve head appear to have an increasing impact in glaucoma diagnosis. The aim of this study is to evaluate the specifity of the Heidelberg Retina Tomograph (software version 1.7 and 3.0) in subjects with physiological cupping and large optic discs. 27 eyes of 27 subjects (mean age 41.3 ± 15.8 years) with bilateral physiological cupping and large optic discs (vertical cup-to-disc-ratio > 0.3, optic disc area 2.48 ± 0.45 mm2, max. 3.54 mm2) were included in a clinical study. All subjects had an intraocular pressure cupping by funduscopy and no nerve fibre layer defects (Scanning Laser Ophthalmoscope, Rodenstock, Germany). Standard achromatic perimetry (Humphrey Field Analyzer, Humphrey-Zeiss, 24/2 SITA or full threshold), short-wavelength automated perimetry (Humphrey Field Analyzer, Humphrey-Zeiss), and frequency doubling technology (FDT, Humphrey-Zeiss) revealed no visual field defects. Optic disc imaging was performed in all subjects using the Heidelberg Retina Tomograph II (HRT). Optic disc images were transferred to the software-update of the HRT 3 (Version 3.0, Heidelberg Engineering). Specifity was calculated using the Moorfields regression analysis (MRA, software version 1.7 and 3.0) and the glaucoma probability score (GPS analysis) using all disc sectors and omitting the nasal and 3 nasal sectors. Specifity of the MRA (software version 1.7) was 66.6 % (most specific criteria), and 22.2 % (least specific criteria). Specifity of the MRA (software version 3.0) was 33.3 % (most specific criteria), and 14.8 % (least specific criteria), whereas specifity of the GPS analysis was 37.0 % (most specific criteria), and 11.1 % (least specific criteria). When the nasal sectors were omitted for analysis, specifity increased for the MRA analysis, but not for the GPS analysis. Specifity of the MRA was unsatisfactory using the software version 1.7 and 3.0 in subjects with large optic discs and physiological cupping

  9. Evaluating The State Of Financial Globalization:Ukraine’s Specific Features

    Directory of Open Access Journals (Sweden)

    Natalia Stukalo

    2006-03-01

    Full Text Available This article presents a system for evaluating the state of financial globalization in a given country. It identifies the contemporary distinctive features of globalization in the area of finance. It also systematizes available globalization indicators at all levels of the financial system. It collects and analyzes statistical data with regard to key financial globalization indicators for Ukraine and Russia as countries that will soon become members of the World Trade Organization. Based on this analysis, the article provides an overview of the contemporary distinctive features of the financial sector in these counties in the context of globalization.

  10. The Cost of Crime to Society: New Crime-Specific Estimates for Policy and Program Evaluation

    Science.gov (United States)

    French, Michael T.; Fang, Hai

    2010-01-01

    Estimating the cost to society of individual crimes is essential to the economic evaluation of many social programs, such as substance abuse treatment and community policing. A review of the crime-costing literature reveals multiple sources, including published articles and government reports, which collectively represent the alternative approaches for estimating the economic losses associated with criminal activity. Many of these sources are based upon data that are more than ten years old, indicating a need for updated figures. This study presents a comprehensive methodology for calculating the cost of society of various criminal acts. Tangible and intangible losses are estimated using the most current data available. The selected approach, which incorporates both the cost-of-illness and the jury compensation methods, yields cost estimates for more than a dozen major crime categories, including several categories not found in previous studies. Updated crime cost estimates can help government agencies and other organizations execute more prudent policy evaluations, particularly benefit-cost analyses of substance abuse treatment or other interventions that reduce crime. PMID:20071107

  11. The orbitofrontal oracle: cortical mechanisms for the prediction and evaluation of specific behavioral outcomes.

    Science.gov (United States)

    Rudebeck, Peter H; Murray, Elisabeth A

    2014-12-17

    The orbitofrontal cortex (OFC) has long been associated with the flexible control of behavior and concepts such as behavioral inhibition, self-control, and emotional regulation. These ideas emphasize the suppression of behaviors and emotions, but OFC's affirmative functions have remained enigmatic. Here we review recent work that has advanced our understanding of this prefrontal area and how its functions are shaped through interaction with subcortical structures such as the amygdala. Recent findings have overturned theories emphasizing behavioral inhibition as OFC's fundamental function. Instead, new findings indicate that OFC provides predictions about specific outcomes associated with stimuli, choices, and actions, especially their moment-to-moment value based on current internal states. OFC function thereby encompasses a broad representation or model of an individual's sensory milieu and potential actions, along with their relationship to likely behavioral outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Evaluating the impact of dyslexia laws on the identification of specific learning disability and dyslexia.

    Science.gov (United States)

    Phillips, B Anne Barber; Odegard, Timothy N

    2017-10-01

    Dyslexia is a specific learning disability that impacts word reading accuracy and/or reading fluency. Over half of the states in the USA have passed legislation intended to promote better identification of individuals with dyslexia. To date, no study has been conducted to investigate the potential impact of state laws on the identification of specific learning disability (SLD), and limited data has been presented on the rate at which students in public school settings are identified with dyslexia. The first aim of the current study was to determine if any detectable changes in the identification rates of SLD have occurred in states implementing dyslexia laws because most states do not report number of students identified as dyslexic but rather those students identified with an SLD. The second aim of the study was to characterize the rate of identifying dyslexia in the two states (Texas and Arkansas) that require public schools to report the number of students identified with dyslexia. The third aim was to characterize the identification rate across first to 12th grades. Current SLD rates range from 3.2 to 8.5% in all 50 states. Analysis of SLD prevalence rates did not vary between states with and without dyslexia laws in place. Moreover, there was no change in the identification of SLD once states had implemented these laws. Rates of dyslexia in Arkansas and Texas were less than 5%. Given the persistent levels indicating lack of reading proficiency, our review of data suggests that overall students with dyslexia are being underidentified.

  13. Component- and Alloy-Specific Modeling for Evaluating Aluminum Recycling Strategies for Vehicles

    Science.gov (United States)

    Modaresi, Roja; Løvik, Amund N.; Müller, Daniel B.

    2014-11-01

    Previous studies indicated that the availability of mixed shredded aluminum scrap from end-of-life vehicles (ELV) is likely to surpass the capacity of secondary castings to absorb this type of scrap, which could lead to a scrap surplus unless suitable interventions can be identified and implemented. However, there is a lack of studies analyzing potential solutions to this problem, among others, because of a lack of component- and alloy-specific information in the models. In this study, we developed a dynamic model of aluminum in the global vehicle stock (distinguishing 5 car segments, 14 components, and 7 alloy groups). The forecasts made up to the year 2050 for the demand for vehicle components and alloy groups, for the scrap supply from discarded vehicles, and for the effects of different ELV management options. Furthermore, we used a source-sink diagram to identify alloys that could potentially serve as alternative sinks for the growing scrap supply. Dismantling the relevant components could remove up to two-thirds of the aluminum from the ELV stream. However, the use of these components for alloy-specific recycling is currently limited because of the complex composition of components (mixed material design and applied joining techniques), as well as provisions that practically prevent the production of safety-relevant cast parts from scrap. In addition, dismantling is more difficult for components that are currently penetrating rapidly. Therefore, advanced alloy sorting seems to be a crucial step that needs to be developed over the coming years to avoid a future scrap surplus and prevent negative energy use and emission consequences.

  14. Selection and Evaluation of Tissue Specific Reference Genes in Lucilia sericata during an Immune Challenge.

    Science.gov (United States)

    Baumann, Andre; Lehmann, Rüdiger; Beckert, Annika; Vilcinskas, Andreas; Franta, Zdeněk

    2015-01-01

    The larvae of the common green bottle fly Lucilia sericata (Diptera: Calliphoridae) have been used for centuries to promote wound healing, but the molecular basis of their antimicrobial, debridement and healing functions remains largely unknown. The analysis of differential gene expression in specific larval tissues before and after immune challenge could be used to identify key molecular factors, but the most sensitive and reproducible method qRT-PCR requires validated reference genes. We therefore selected 10 candidate reference genes encoding products from different functional classes (18S rRNA, 28S rRNA, actin, β-tubulin, RPS3, RPLP0, EF1α, PKA, GAPDH and GST1). Two widely applied algorithms (GeNorm and Normfinder) were used to analyze reference gene candidates in different larval tissues associated with secretion, digestion, and antimicrobial activity (midgut, hindgut, salivary glands, crop and fat body). The Gram-negative bacterium Pseudomonas aeruginosa was then used to boost the larval immune system and the stability of reference gene expression was tested in comparison to three immune genes (lucimycin, defensin-1 and attacin-2), which target different pathogen classes. We observed no differential expression of the antifungal peptide lucimycin, whereas the representative targeting Gram-positive bacteria (defensin-1) was upregulated in salivary glands, crop, nerve ganglion and reached its maximum in fat body (up to 300-fold). The strongest upregulation in all immune challenged tissues (over 50,000-fold induction in the fat body) was monitored for attacin-2, the representative targeting Gram-negative bacteria. Here we identified and validated a set of reference genes that allows the accurate normalization of gene expression in specific tissues of L. sericata after immune challenge.

  15. Selection and Evaluation of Tissue Specific Reference Genes in Lucilia sericata during an Immune Challenge.

    Directory of Open Access Journals (Sweden)

    Andre Baumann

    Full Text Available The larvae of the common green bottle fly Lucilia sericata (Diptera: Calliphoridae have been used for centuries to promote wound healing, but the molecular basis of their antimicrobial, debridement and healing functions remains largely unknown. The analysis of differential gene expression in specific larval tissues before and after immune challenge could be used to identify key molecular factors, but the most sensitive and reproducible method qRT-PCR requires validated reference genes. We therefore selected 10 candidate reference genes encoding products from different functional classes (18S rRNA, 28S rRNA, actin, β-tubulin, RPS3, RPLP0, EF1α, PKA, GAPDH and GST1. Two widely applied algorithms (GeNorm and Normfinder were used to analyze reference gene candidates in different larval tissues associated with secretion, digestion, and antimicrobial activity (midgut, hindgut, salivary glands, crop and fat body. The Gram-negative bacterium Pseudomonas aeruginosa was then used to boost the larval immune system and the stability of reference gene expression was tested in comparison to three immune genes (lucimycin, defensin-1 and attacin-2, which target different pathogen classes. We observed no differential expression of the antifungal peptide lucimycin, whereas the representative targeting Gram-positive bacteria (defensin-1 was upregulated in salivary glands, crop, nerve ganglion and reached its maximum in fat body (up to 300-fold. The strongest upregulation in all immune challenged tissues (over 50,000-fold induction in the fat body was monitored for attacin-2, the representative targeting Gram-negative bacteria. Here we identified and validated a set of reference genes that allows the accurate normalization of gene expression in specific tissues of L. sericata after immune challenge.

  16. Design and evaluation of matrices of Eudragit with polycarbophil and carbopol for colon-specific delivery.

    Science.gov (United States)

    Asghar, Laila Fatima Ali; Chandran, Sajeev

    2008-12-01

    The purpose of the present study was to investigate the effect of incorporating pH-responsive polymers Eudragit (L100 or S100) in matrix bases composed of hydrophilic polymers polycarbophil and carbopol to design oral controlled release formulations with sigmoidal release profile for colon-specific delivery. Matrix tablets were prepared by wet granulation technique using indomethacin as model drug and were characterized for physical parameters, in vitro drug release, release kinetics, and stability on storage. The gastrointestinal (GI) transit of selected formulations was also investigated in human subjects using gamma scintigraphy. In vitro release studies indicated that the presence of pH-sensitive polymers in hydrophilic polymer base retarded the initial release significantly (10-15% release in 6 h) followed with controlled release for the next 8-10 h in simulated GI fluid pH (without enzymes). The presence of Eudragit in hydrophilic matrix base retarded the swelling of the matrix base in acidic to weakly acidic pH, but in alkaline pH, enhancement in drug release rate was observed due to the dissolution of Eudragit from the base resulting in a porous matrix structure, resulting in around 80-90% release in 14 h of study. In vivo gamma scintigraphy studies in healthy human subjects proved that the formulations had acceptable matrix strength to withstand gastric and colonic transit. The mean colonic residence time of selected designed formulations varied between 15 and 19 h. Such a matrix design could have potential application as colon-specific drug delivery systems with pH- and time-dependent drug release profile.

  17. Histochemical evaluation of catechins in PEG stressed transgenic tea plants using catechin-specific-diazotized sulfanilamide reagent.

    Science.gov (United States)

    Bhattacharya, A; Sharma, M; Gulati, A; Joshi, R; Chanda, S K; Ahuja, P S

    2015-01-01

    We investigated the applicability of catechin-specific-reagent (CSR) for histochemical evaluation of catechins. The diazotized arylamine moiety in CSR reacts specifically with the A-ring of catechins to yield a golden yellow complex. This makes it highly specific for spectrophotometric quantification of catechins. Therefore, microtome cut sections of untransformed and osmotin-expressing transgenic leaves and stem of tea were stained with CSR. We found catechins in the form of golden yellow globules. The catechin globules increased in the structurally intact and highly turgid cells of osmotin expressing transgenic tea plants after stress treatment with 20% PEG; by contrast, the cells in non-transgenic plants accumulated fewer catechin globules. Spectrophotometric quantification of catechins also confirmed higher levels in transgenics compared to untransformed plants. We found elevated accumulation of catechins in stress tolerant cells of tea leaves.

  18. Translation and psychometric evaluation of Persian versions of Burn Specific Pain Anxiety Scale and Impact of Event Scale.

    Science.gov (United States)

    Ghezeljeh, Tahereh Najafi; Ardebili, Fatimah Mohades; Rafii, Forough; Hagani, Hamid

    2013-09-01

    Burn as a traumatic life incident manifests severe pain and psychological problems. Specific instruments are needed to evaluate burn patients' psychological issues related to the injury. The aim of this study was to translate and evaluate the reliability and validity of the Persian versions of Impact of Burn Specific Pain Anxiety scale (BSPAS) and Impact of Event Scale (IES). In this cross-sectional study, convenience sampling method was utilized to select 55 Iranian hospitalized burn patients. Combined translation was utilized for translating scales. Alpha cronbach, item-total correlation, convergent and discriminative validity were evaluated. The Cronbach's α for both BSPAS- and IES-Persian version was 0.96. Item-total correlation coefficients ranged from 0.70 to 0.90. Convergent construct validity was confirmed by indicating high correlation between the scales designed to measure the same concepts. The mean score of BSPAS- and IES-Persian version was lower for individuals with a lower TBSA burn percentage which assessed discriminative construct validity of scales. BSPAS- and IES-Persian version showed high internal consistency and good validity for the assessment of burn psychological outcome in hospitalized burn patients. Future studies are needed to determine repeatability, factor structure, sensitivity and specificity of the scales. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  19. Prediction of Skin Sensitization Potency Using Machine Learning Approaches

    Science.gov (United States)

    Replacing animal tests currently used for regulatory hazard classification of skin sensitizers is one of ICCVAM’s top priorities. Accordingly, U.S. federal agency scientists are developing and evaluating computational approaches to classify substances as sensitizers or nons...

  20. Acceleromyography and mechanomyography for establishing potency of neuromuscular blocking agents: a randomized-controlled trial

    DEFF Research Database (Denmark)

    Claudius, C; Viby-Mogensen, J; Skovgaard, Lene Theil

    2009-01-01

    BACKGROUND: Acceleromyography (AMG) is increasingly being used in neuromuscular research, including in studies establishing the potency of neuromuscular blocking and reversal agents. However, AMG is insufficiently validated for use interchangeably with the gold standard, mechanomyography (MMG......) for this purpose. The aim of this study was to compare AMG and MMG for establishing dose-response relationship and potency, using rocuronium as an example. METHODS: We included 40 adult patients in this randomized-controlled single-dose response study. Anaesthesia was induced and maintained with propofol...... difference between AMG and MMG is so small that it justifies AMG to be used for establishing the potency of neuromuscular blocking agents. However, the wide CIs show that we cannot rule out a 13% higher ED(50) and a 26% higher ED(95) for AMG....

  1. Development and evaluation of a genus-specific, probe-based, internal-process-controlled real-time PCR assay for sensitive and specific detection of Blastocystis spp.

    Science.gov (United States)

    Stensvold, Christen Rune; Ahmed, Umran Nisar; Andersen, Lee O'Brien; Nielsen, Henrik Vedel

    2012-06-01

    Blastocystis is a common intestinal parasite of unsettled clinical significance, which is not easily detected by standard parasitological methods. The genus comprises at least 13 subtypes (STs) (which likely represent separate species), 9 of which have been found in humans. Recent data indicate that at least one of the subtypes is associated with intestinal disease. A quantitative TaqMan 5' nuclease real-time PCR (TaqMan PCR) including an internal process control (IPC) was developed for the detection of Blastocystis and shown to be applicable to genomic DNAs extracted directly from feces. The assay enabled successful amplification of DNAs from all relevant subtypes within the genus (ST1 to ST9). For assay evaluation, 153 samples previously tested by xenic in vitro culture (XIVC) were screened by the TaqMan assay. A total of 49/51 samples positive by XIVC and 13/102 samples negative by XIVC were positive by the TaqMan assay; samples positive by the TaqMan assay and negative by XIVC were subsequently tested by conventional PCR, and amplicons could be identified to the subtype level by sequencing in 69% of the cases. Compared to the TaqMan assay, XIVC had a sensitivity of 79%. This is the first time that a genus-specific, probe-based, internal-process-controlled real-time PCR assay for the detection Blastocystis has been introduced.

  2. Evaluation of the efficacy of a specific hyperimmune serum in experimental influenza infection in mice.

    Science.gov (United States)

    Marinescu, Bogdan; Coman, Cristin; Iancu, Adina Daniela; Stavaru, Crina; Lupulescu, Emilia; Onu, Adrian; Radu, Dorel Lucian

    2009-01-01

    Serotherapy still remains a way of treatment in some diseases, and it could be consider superior to any other mode of action because the protecting substances of the body are the products of the organism itself. The aim of the study was to establish an "in vivo" method for testing the efficacy of therapeutic serum. Hyperimmune serum for influenza A/PR8/34 viral strain, was prepared in sheep, and tested for inhibition of haemagglutination and microneutralisation. Seroprotection was evaluated in mice one day after being challenged with a lethal dose of the same virus. Our study shows that protection occurred in all mice treated with undiluted hyperimmune serum one day post infection (no clinical signs, faster recovery of the body weight after the first three days of the infection, all mice survived).

  3. Individual radiation therapy patient whole-body phantoms for peripheral dose evaluations: method and specific software

    Energy Technology Data Exchange (ETDEWEB)

    Alziar, I; Vicente, C; Giordana, G; Ben-Harrath, O; De Vathaire, F; Diallo, I [U605 INSERM, Villejuif (France); Bonniaud, G; Couanet, D; Chavaudra, J; Lefkopoulos, D [Institut Gustave-Roussy, Villejuif (France); Ruaud, J B; Diaz, J C; Grandjean, P; Kafrouni, H [DOSIsoft, Cachan (France)], E-mail: ibrahim.diallo@igr.fr

    2009-09-07

    This study presents a method aimed at creating radiotherapy (RT) patient-adjustable whole-body phantoms to permit retrospective and prospective peripheral dose evaluations for enhanced patient radioprotection. Our strategy involves virtual whole-body patient models (WBPM) in different RT treatment positions for both genders and for different age groups. It includes a software tool designed to match the anatomy of the phantoms with the anatomy of the actual patients, based on the quality of patient data available. The procedure for adjusting a WBPM to patient morphology includes typical dimensions available in basic auxological tables for the French population. Adjustment is semi-automatic. Because of the complexity of the human anatomy, skilled personnel are required to validate changes made in the phantom anatomy. This research is part of a global project aimed at proposing appropriate methods and software tools capable of reconstituting the anatomy and dose evaluations in the entire body of RT patients in an adapted treatment planning system (TPS). The graphic user interface is that of a TPS adapted to obtain a comfortable working process. Such WBPM have been used to supplement patient therapy planning images, usually restricted to regions involved in treatment. Here we report, as an example, the case of a patient treated for prostate cancer whose therapy planning images were complemented by an anatomy model. Although present results are preliminary and our research is ongoing, they appear encouraging, since such patient-adjusted phantoms are crucial in the optimization of radiation protection of patients and for follow-up studies. (note)

  4. RECTAL-SPECIFIC MICROBICIDE APPLICATOR: EVALUATION AND COMPARISON WITH A VAGINAL APPLICATOR USED RECTALLY

    Science.gov (United States)

    Carballo-Diéguez, Alex; Giguere, Rebecca; Dolezal, Curtis; Bauermeister, José; Leu, Cheng-Shiun; Valladares, Juan; Rohan, Lisa C.; Anton, Peter A.; Cranston, Ross D.; Febo, Irma; Mayer, Kenneth; McGowan, Ian

    2014-01-01

    An applicator designed for rectal delivery of microbicides was tested for acceptability by 95 young men who have sex with men, who self-administered 4mL of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24 of the participants self-administered rectally 4mL of tenofovir or placebo gel over 7 days using a vaginal applicator, and compared both applicators on a Likert scale of 1–10, with 10 the highest rating. Participants reported high likelihood to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p= ns). Those who tested both liked the vaginal applicator significantly more than the rectal applicator (7.8 vs. 5.2, p=0.003). Improvements in portability, conspicuousness, aesthetics, tip comfort, product assembly and packaging were suggested for both. This rectal-specific applicator was not superior to a vaginal applicator. While likelihood of future use is reportedly high, factors that decrease acceptability may erode product use over time in clinical trials. Further attention is needed to develop user-friendly, quick-acting rectal microbicide delivery systems. PMID:24858481

  5. Wind Power Opportunities in St. Thomas, USVI: A Site-Specific Evaluation and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lantz, E.; Warren, A.; Roberts, J. O.; Gevorgian, V.

    2012-09-01

    This NREL technical report utilizes a development framework originated by NREL and known by the acronym SROPTTC to assist the U.S. Virgin Islands in identifying and understanding concrete opportunities for wind power development in the territory. The report covers each of the seven components of the SROPTTC framework: Site, Resource, Off-take, Permitting, Technology, Team, and Capital as they apply to wind power in the USVI and specifically to a site in Bovoni, St. Thomas. The report concludes that Bovoni peninsula is a strong candidate for utility-scale wind generation in the territory. It represents a reasonable compromise in terms of wind resource, distance from residences, and developable terrain. Hurricane risk and variable terrain on the peninsula and on potential equipment transport routes add technical and logistical challenges but do not appear to represent insurmountable barriers. In addition, integration of wind power into the St. Thomas power system will present operational challenges, but based on experience in other islanded power systems, there are reasonable solutions for addressing these challenges.

  6. Evaluating Quantum Dot Performance in Homogeneous FRET Immunoassays for Prostate Specific Antigen.

    Science.gov (United States)

    Bhuckory, Shashi; Lefebvre, Olivier; Qiu, Xue; Wegner, Karl David; Hildebrandt, Niko

    2016-02-04

    The integration of semiconductor quantum dots (QDs) into homogeneous Förster resonance energy transfer (FRET) immunoassay kits for clinical diagnostics can provide significant advantages concerning multiplexing and sensitivity. Here we present a facile and functional QD-antibody conjugation method using three commercially available QDs with different photoluminescence (PL) maxima (605 nm, 655 nm, and 705 nm). The QD-antibody conjugates were successfully applied for FRET immunoassays against prostate specific antigen (PSA) in 50 µL serum samples using Lumi4-Tb (Tb) antibody conjugates as FRET donors and time-gated PL detection on a KRYPTOR clinical plate reader. Förster distance and Tb donor background PL were directly related to the analytical sensitivity for PSA, which resulted in the lowest limits of detection for Tb-QD705 (2 nM), followed by Tb-QD655 (4 nM), and Tb-QD605 (23 nM). Duplexed PSA detection using the Tb-QD655 and Tb-QD705 FRET-pairs demonstrated the multiplexing ability of our immunoassays. Our results show that FRET based on QD acceptors is suitable for multiplexed and sensitive biomarker detection in clinical diagnostics.

  7. POTENCY OF Trichoderma aureoviride UPM 09 AND Fusarium ...

    African Journals Online (AJOL)

    User

    glucose-6-phosphate in the presence of NADP to gluconate-6- phosphate and NADP is reduced to. NADPH. This reaction is specific to glucose, thus no other carbohydrate in the solution is oxidized. The rate of NADPH formation is directly proportional to the glucose concentration and can be measured photometrically.

  8. [A specific questionnaire to evaluate therapeutic inertia in hypertensive patients: a pilot study].

    Science.gov (United States)

    Pretorean, T; Claisse, G; Delsart, P; Caudrelier, T; Devos, P; Mounier-Vehier, C

    2014-02-01

    Therapeutic inertia (TI) is a recent concept still unknown by many physicians. In chronic diseases such as hypertension, it is defined as the tendency of physicians not to increase or change antihypertensive medications when the target blood pressure is not reached. Acting on TI could improve blood pressure control in France. This was a single-center prospective pilot study conducted by hypertension specialist physicians at the University Cardio-Vascular Center in Lille (France). It was conducted between March and June 2011. Data was collected from 161 hypertensive patients (mean age: 61.64±11.18 years; 98 (60.9%) male; 75 secondary prevention patients). Each physician completed a questionnaire on therapeutic inertia. TI was defined as a consultation in which treatment change was indicated (systolic blood pressure [BP]≥140 and/or diastolic BP≥90mmHg in all patients), but did not occur, with absence of an adapted justification of this choice. We considered as an adapted justification: a white coat effect demonstrated by ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring; scheduled reassessment of the BP by ABPM; recent change in antihypertensive treatment (less than 4 weeks); hospitalization needed for complete evaluation of secondary causes of hypertension and a more detailed assessment of potential target organ damage in patients with grade 1 or 2 hypertension. Our study aimed to evaluate rates of TI, to identify factors associated with TI, and to test the TI questionnaire. Therapeutic inertia as defined in this study occurred in 11 consultations (8.3%) of the 133 hypertensive patients having uncontrolled BP above or equal to 140 and/or 90mmHg. Significant factors associated with TI were older age (Z=2.35, Psleep apnea syndrome (χ(2)=8.33, PP>0.05) and the number of consultations (Z=1.92, 0.1>P>0.05) exhibited a significant trend to be associated with TI. Although the rate of TI was low in our study conducted in a specialized

  9. Rationale for further medical and health research on high-potency sweeteners.

    Science.gov (United States)

    Schiffman, Susan S

    2012-10-01

    High-potency or artificial sweeteners have historically been considered inert compounds without physiological consequences other than taste sensations. However, recent data suggest that some of these sweeteners have biological effects that may impact human health. Furthermore, there are significant gaps in our current knowledge of the pharmacokinetics of these sweeteners, their potential for "sweetener-drug interactions" and their impact on appetite and body weight regulation. Nine research needs are described that address some of the major unknown issues associated with ingestion of high-potency sweeteners.

  10. Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency

    DEFF Research Database (Denmark)

    Martin Gonzalez, Javier; Morgani, Sophie M; Bone, Robert A

    2016-01-01

    Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i) or with ......Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre-implantation embryo. Here we assess the impact of derivation and culture conditions on both functional potency and ESC transcriptional identity. Individual ESCs cultured in either two small-molecule inhibitors (2i...

  11. The spermicidal potency of Coca-Cola and Pepsi-Cola.

    Science.gov (United States)

    Hong, C Y; Shieh, C C; Wu, P; Chiang, B N

    1987-09-01

    The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.

  12. Comparison of Sensitivity & Specificity of Transvaginal Sonography, Saline Infusion Sonohysterography and Hysteroscopy in Evaluation of Women with Abnormal Uterine Bleeding

    Directory of Open Access Journals (Sweden)

    K Shojaie

    2009-10-01

    Full Text Available Introduction: Bleeding disorders are a common problem in daily practice, especially in premenopausal women. In our investigation, we compared the sensitivity and specificity of three different diagnostic methods Trans-vaginal sonography(TVS, saline infusion sonohystrography(SIS and Hysteroscopy. Methods: It was a cross- sectional study with a study population of ninety-nine women suffering fromAUB attending the outpatient clinic of Imam and Razi hospital in Ahvaz- Iran. They were evaluated by three different diagnostic methods and the results were compared. This study started from March 2008 to December 2008. The sensitivity, specificity, positive predictive and negative predictive values were measured in TVS, SIS, and finally these two methods were compared with hysteroscopy (as a gold standard. Results: The sensitivity and specificity of TVS was 74.2% and 49.7%, respectively, while that of SIS was 91.6% and 86%, respectively. The positive predictive value and negative predictive value of TVS was 71.9% and 54.3%, respectively, while that of SIS was 85.9% and 85.75%, respectively. The sensitivity, specificity, the positive predictive and negative predictive values of SIS was more than TVS, and it was similar to hysteroscopy. Conclusion: The findings obtained in the present study indicate that in AUB, sensitivity, specificity, positive and negative predictive value of SIS is more than TVS and therefore can be considered as a first step for diagnosis of AUB.

  13. Evaluating podiatry services: testing a treatment specific measure of health status.

    Science.gov (United States)

    Macran, S; Kind, P; Collingwood, J; Hull, R; McDonald, I; Parkinson, L

    2003-03-01

    This study reports on the preliminary testing of a new measure designed for use alongside EQ-5D in evaluating outcomes in podiatry: the Podiatry Health Questionnaire (PHQ). Individuals aged 18 years or more, receiving podiatry services in clinic or domicilliary locations across four NHS Trusts in Yorkshire and Humberside UK took part in a questionnaire survey. Respondents reported high levels of problems on all six PHQ dimensions. Correlations suggested that the PHQ and EQ-5D were measuring distinct constructs. The levels on each dimension were well defined in terms of self-rated morbidity on the PHQ visual analogue scale (PHQvas) and the EQ-5Dvas, although PHQvas appeared to be slightly more sensitive to changes in health on the dimensions. There was a strong relationship between clinicians' Podiatry Clinical Score rating and reported symptoms for four out of six PHQ dimensions and PHQvas. The PHQ was able to distinguish respondents in terms of their self-reported morbidity in EQ-5D and in terms of their morbidity as assessed by clinicians. It is suggested that the respondent completed PHQ appears to be a useful new measure for assessing foot-related health. However, further investigation of the psychometric properties of the measure is required.

  14. Evaluating operational specifications of point-of-care diagnostic tests: a standardized scorecard.

    Science.gov (United States)

    Lehe, Jonathan D; Sitoe, Nádia E; Tobaiwa, Ocean; Loquiha, Osvaldo; Quevedo, Jorge I; Peter, Trevor F; Jani, Ilesh V

    2012-01-01

    The expansion of HIV antiretroviral therapy into decentralized rural settings will increasingly require simple point-of-care (POC) diagnostic tests that can be used without laboratory infrastructure and technical skills. New POC test devices are becoming available but decisions around which technologies to deploy may be biased without systematic assessment of their suitability for decentralized healthcare settings. To address this, we developed a standardized, quantitative scorecard tool to objectively evaluate the operational characteristics of POC diagnostic devices. The tool scores devices on a scale of 1-5 across 30 weighted characteristics such as ease of use, quality control, electrical requirements, shelf life, portability, cost and service, and provides a cumulative score that ranks products against a set of ideal POC characteristics. The scorecard was tested on 19 devices for POC CD4 T-lymphocyte cell counting, clinical chemistry or hematology testing. Single and multi-parameter devices were assessed in each of test categories. The scores across all devices ranged from 2.78 to 4.40 out of 5. The tool effectively ranked devices within each category (p0.80; ptechnology. It is particularly relevant for countries and testing programs considering the adoption of new POC diagnostic tests.

  15. Rowing ergometer with the slide is more specific to rowers' physiological evaluation.

    Science.gov (United States)

    De Campos Mello, Fernando; Bertuzzi, Rômulo; Franchini, Emerson; Candau, Robin

    2014-01-01

    This study investigated maximal and submaximal performance (power output) and physiological responses (oxygen uptake, heart rate and blood lactate concentration) of eight male rowers to two different incremental tests to exhaustion performed either in a rowing ergometer without (regular) or with the slide, as well as to a 2000 m race simulation, conducted in a randomized order. Peak oxygen uptake ([Formula: see text]O2peak) was statistically higher (3.4%) in the regular test (5.18 ± 0.44 L.min(-1)) compared with the slide condition (5.01 ± 0.37 L.min(-1); P = 0.005). Time for the on-water race simulation was significantly correlated with the slope of the [Formula: see text]O2-power relationship in the slide condition (r = -0.73, P = 0.043) and [Formula: see text]O2peak during the test in the slide condition was correlated to mean [Formula: see text]O2 at the on-water race simulation (r = 0.78; P = 0.024). Thus, the use of the slide is more beneficial than the regular test when evaluating rowers.

  16. Evaluation of Specific Oxygen Uptake Rates with Reference to Biocatalytic D-Sorbitol Oxidation Systems

    Directory of Open Access Journals (Sweden)

    Marijan Bošnjak

    2003-01-01

    Full Text Available Effects of D-sorbitol concentration on the kinetics of D-sorbitol microbial oxidation were studied. The culture of Gluconobacter suboxydans S–22 was applied as a biocatalyst. The study was focused on the determination of oxygen uptake rates and the evaluation of factors affecting them. Special emphasis was given to estimations of dissolved oxygen saturation (Monod constant (KsDO and critical dissolved oxygen concentration. The estimated values of Monod constant (KsDO were correlated with different process kinetics parameters and a series of acceptable relationships was established. Excellent correlation coefficients were found for KsDO as a linear function of (i reciprocal viscosity (R2 = 0.9848, (ii relative diffusion coefficient (R2 = 0.9983, (iii cubic root of dissolved D-sorbitol mass concentration (R2 = 0.9915 and (iv oxygen solubility in D-sorbitol solutions of different D-sorbitol concentrations (R2 = 0.9967. The estimated KsDO values were lower than their corresponding critical dissolved oxygen concentrations.

  17. Formative evaluation of a patient-specific clinical knowledge summarization tool.

    Science.gov (United States)

    Del Fiol, Guilherme; Mostafa, Javed; Pu, Dongqiuye; Medlin, Richard; Slager, Stacey; Jonnalagadda, Siddhartha R; Weir, Charlene R

    2016-02-01

    To iteratively design a prototype of a computerized clinical knowledge summarization (CKS) tool aimed at helping clinicians finding answers to their clinical questions; and to conduct a formative assessment of the usability, usefulness, efficiency, and impact of the CKS prototype on physicians' perceived decision quality compared with standard search of UpToDate and PubMed. Mixed-methods observations of the interactions of 10 physicians with the CKS prototype vs. standard search in an effort to solve clinical problems posed as case vignettes. The CKS tool automatically summarizes patient-specific and actionable clinical recommendations from PubMed (high quality randomized controlled trials and systematic reviews) and UpToDate. Two thirds of the study participants completed 15 out of 17 usability tasks. The median time to task completion was less than 10s for 12 of the 17 tasks. The difference in search time between the CKS and standard search was not significant (median=4.9 vs. 4.5m in). Physician's perceived decision quality was significantly higher with the CKS than with manual search (mean=16.6 vs. 14.4; p=0.036). The CKS prototype was well-accepted by physicians both in terms of usability and usefulness. Physicians perceived better decision quality with the CKS prototype compared to standard search of PubMed and UpToDate within a similar search time. Due to the formative nature of this study and a small sample size, conclusions regarding efficiency and efficacy are exploratory. Published by Elsevier Ireland Ltd.

  18. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Immolation of p-Aminobenzyl Ether Linker and Payload Potency and Stability Determine the Cell-Killing Activity of Antibody-Drug Conjugates with Phenol-Containing Payloads.

    Science.gov (United States)

    Zhang, Donglu; Le, Hoa; Cruz-Chuh, Josefa Dela; Bobba, Sudheer; Guo, Jun; Staben, Leanna; Zhang, Chenghong; Ma, Yong; Kozak, Katherine R; Lewis Phillips, Gail D; Vollmar, Breanna S; Sadowsky, Jack D; Vandlen, Richard; Wei, BinQing; Su, Dian; Fan, Peter; Dragovich, Peter S; Khojasteh, S Cyrus; Hop, Cornelis E C A; Pillow, Thomas H

    2018-02-07

    The valine-citrulline (Val-Cit) dipeptide and p-aminobenzyl (PAB) spacer have been commonly used as a cleavable self-immolating linker in ADC design including in the clinically approved ADC, brentuximab vedotin (Adcetris). When the same linker was used to connect to the phenol of the cyclopropabenzindolone (CBI) (P1), the resulting ADC1 showed loss of potency in CD22 target-expressing cancer cell lines (e.g., BJAB, WSU-DLCL2). In comparison, the conjugate (ADC2) of a cyclopropapyrroloindolone (CPI) (P2) was potent despite the two corresponding free drugs having similar picomolar cell-killing activity. Although the corresponding spirocyclization products of P1 and P2, responsible for DNA alkylation, are a prominent component in buffer, the linker immolation was slow when the PAB was connected as an ether (PABE) to the phenol in P1 compared to that in P2. Additional immolation studies with two other PABE-linked substituted phenol compounds showed that electron-withdrawing groups accelerated the immolation to release an acidic phenol-containing payload (to delocalize the negative charge on the anticipated anionic phenol oxygen during immolation). In contrast, efficient immolation of LD4 did not result in an active ADC4 because the payload (P4) had a low potency to kill cells. In addition, nonimmolation of LD5 did not affect the cell-killing potency of its ADC5 since immolation is not required for DNA alkylation by the center-linked pyrrolobenzodiazepine. Therefore, careful evaluation needs to be conducted when the Val-Cit-PAB linker is used to connect antibodies to a phenol-containing drug as the linker immolation, as well as payload potency and stability, affects the cell-killing activity of an ADC.

  20. Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.

    Science.gov (United States)

    Smith, Heidi L; Cheslock, Peter; Leney, Mark; Barton, Bruce; Molrine, Deborah C

    2016-08-17

    Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16-21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38-59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.

  1. Single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics

    Energy Technology Data Exchange (ETDEWEB)

    Eggerman, T.L.; Hartzell, C.J.; Selfe, S.; Andersen, N.H.

    1987-03-01

    Gel-filtered human platelets (GFP) display only a single binding site for (/sup 3/H)-PGI2: KD = 61nM, 234 fmol/10(8) platelets (1410 sites/platelet). Platelet-rich plasma (PRP) displays the same receptor density but the KD value increases to 123 nM due to protein binding of PGI2 which lowers its effective concentration. The (/sup 3/H)-PGI2/GFP binding assay has been used to evaluate the molecular basis of aggregation inhibition for prostacyclin analogs and mimics, three PGE type structures, and PGD2. Antiaggregatory IC50s and radioligand binding IC50s correlate for PGE2, E1, and six PGI2 analogs. PGD2, and to a lesser extent 6-oxo-PGE1, display greater antiaggregatory potency than expected based on PGI2-binding site affinity data.

  2. Effect of the time of extraction on the potency and allergenic composition of the extract of Parietaria officinalis pollen.

    Science.gov (United States)

    Oreste, U; Santonastaso, V; Ruffilli, A

    1985-01-01

    Five Parietaria officinalis pollen extracts were obtained after respective 0.5, 4, 16, 48, 96 h of extraction in 0.0125 M NH4HCO3 pH 8.7 containing 0.05% NaN3 and 5.7 X 10(-4) M phenylmethylsulphonylfluoride. Conductivity, pH, absorption coefficient at 280 and 360 nm and content in protein and carbohydrates were determined in the extracts. Allergenic potency, evaluated by RAST inhibition was higher for the shorter-time extracts. The allergenic composition of the extracts was analyzed by a combination of gel filtration of the extracts and RAST inhibition of the eluted fractions: low molecular weight allergens were recovered only in longer-time extracts.

  3. MP3 compression and transmission of infrasonic sensor array signals and task-specific metrics for distortion evaluation

    Science.gov (United States)

    Cabrera, Sergio D.; Vidal, Edward, Jr.; Paramanandan, Smitha

    2005-08-01

    Infrasonic sensor arrays are very useful for detecting natural and man-made events. This paper describes part of an ongoing project for compressing and transmitting a set of infrasonic signals that need to be delivered to a remote location for decompression and processing. The project also deals with the evaluation of the effect of the compression distortion on the signals by the use of task-specific distortion metrics. We evaluate the effectiveness of the scheme using one hour worth of signals that were collected during a Space Shuttle launch using a small array of 4 microphones. The approach described here is to combine the 4 signals/channels using a transmultiplexer and to use an off-the-shelf audio compression method, namely the popular MP3 method which is based on subband coding. The transmultiplexer is a 5-channel Cosine-Modulated filterbank from which only the first 4 channels are used.. The codec used in this study is the readily available LAME software package which allows one to choose the output bits per second rate and to turn off the psychoacoustic model. To use an audio coder, the combined signal is first converted to 16 bits per sample and then associated with a 16 KHz. sampling frequency. In the application considered, the microphone signals are used to compute time evolving quantities including: average spectral coherence, beamforming, and phase velocity. These same quantities are used as task-specific metrics that reveal the distortion caused by the application of the MP3 compressor so that the user can evaluate distortion tolerances. From visual evaluation of these metrics we conclude that a compression ratio between 6.4:1 and 8:1 produces negligible distortion in the three task-specific metrics. The beamforming metric is the most sensitive to the compression distortion.

  4. Development of HIV-1 rectal-specific microbicides and colonic tissue evaluation.

    Directory of Open Access Journals (Sweden)

    Charlene S Dezzutti

    Full Text Available The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs. Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid and those that create a deformable, erodible barrier and remain localized at the administration site (gel. Tenofovir (TFV (1% was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1% using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides, respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig. As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation

  5. Development of a 3D optical scanner for evaluating patient-specific dose distributions.

    Science.gov (United States)

    Chang, Kyung Hwan; Lee, Suk; Jung, Hong; Choo, Yeon-Wook; Cao, Yuan Jie; Shim, Jang Bo; Kim, Kwang Hyeon; Lee, Nam Kwon; Park, Young Je; Kim, Chul Yong; Cho, Sam Ju; Lee, Sang Hoon; Min, Chul Kee; Kim, Woo Chul; Cho, Kwang Hwan; Huh, Hyun Do; Lim, Sangwook

    2015-07-01

    This paper describes the hardware and software characteristics of a 3D optical scanner (P3DS) developed in-house. The P3DS consists of an LED light source, diffuse screen, step motor, CCD camera, and scanner management software with 3D reconstructed software. We performed optical simulation, 2D and 3D reconstruction image testing, and pre-clinical testing for the P3DS. We developed the optical scanner with three key characteristics in mind. First, we developed a continuous scanning method to expand possible clinical applications. Second, we manufactured a collimator to improve image quality by reducing scattering from the light source. Third, we developed an optical scanner with changeable camera positioning to enable acquisition of optimal images according to the size of the gel dosimeter. We confirmed ray-tracing in P3DS with optic simulation and found that 2D projection and 3D reconstructed images were qualitatively similar to the phantom images. For pre-clinical tests, the dose distribution and profile showed good agreement among RTP, optical CT, and external beam radiotherapy film data for the axial and coronal views. The P3DS has shown that it can scan and reconstruct for evaluation of the gel dosimeter within 1 min. We confirmed that the P3DS system is a useful tool for the measurement of 3D dose distributions for 3D radiation therapy QA. Further experiments are needed to investigate quantitative analysis for 3D dose distribution. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  6. Evaluation and interpretation of regional and site-specific hydrochemical data bases for water quality assessment

    Directory of Open Access Journals (Sweden)

    M. G. Hutchins

    1999-01-01

    Full Text Available The spatial distribution of stream water composition, as determined by the Geochemical Baseline Survey of the Environment (G-BASE conducted by the British Geological Survey (BGS can be successfully related under baseflow conditions to bedrock geochemistry. Further consideration of results in conjunction with site-specific monitoring data enables factors controlling both spatial and temporal variability in major element composition to be highlighted and allows the value of the survey to be enhanced. Hence, chemical data (i from streams located on Lower Silurian (Llandovery bedrock at 1 km2 resolution collected as part of the G-BASE survey of Wales and the West Midlands and (ii from catchment monitoring studies located in upland mid-Wales (conducted by Institute of Terrestrial Ecology, have been considered together as an example. Classification of the spatial survey data set in terms of potentially controlling factors was carried out so as to illustrate the level of explanation they could give in terms of observed spatial chemical variability. It was therefore hypothesised that on a geological lithostratigraphic series of limited geochemical contrast, altitude and land-use factors provide better explanation of this variability than others such as lithology at sampling site and stream order. At an individual site, temporal variability was also found to be of considerable significance and, at a monthly time-step, is explicable in terms of factors such as antecedent conditions and seasonality. Data suggest that the degree of this variability may show some relationship with stream order and land-use. Monitoring data from the region also reveal that relationships between stream chemistry and land-use may prove to be strong not only at base flow but also in storm flow conditions. In a wider context, predictions of the sensitivity of stream water to acidification based on classifications of soil and geology are successful on a regional scale. However

  7. Compositions and comparisons of antimicrobial potencies of some ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-11-19

    Nov 19, 2008 ... terial activity of the main components of three thyme essential oils. Rivista Italiana EPPOS 13: 13-19. Mangena T, Muyima NYO (1999). Comparative evaluation of the antimicrobial activities of essential oils of Artemisia afra, Pteronia incana and Rosmarinus officinalis on selected bacteria and yeast strains.

  8. Antimicrobial Potency of Hydro, acetone and Ethanolic extracts of ...

    African Journals Online (AJOL)

    The phytochemical constituents of the dried powdered plant parts were extracted using aqueous and organic solvents (acetone and ethanol). The antimicrobial activity of the concentrated extracts was evaluated by determining the diameter of zone of inhibition against both gram negative and gram positive bacteria and ...

  9. The anaesthetic potency of benzocaine-hydrochloride in three ...

    African Journals Online (AJOL)

    References. BULLOCK, T.H. 1955. Compensation for temperature in the metabolisms and activity of poikilotherms. Bioi. Rev. 30: 311- 342. S.-Afr. Tydskr. Dierk. 1984, 19(1). CLARK, M.W. 1948. Topics in the physiological chemistry. Williams. & Wilkens, Baltimore, p.738. FERREIRA, J. T. 1982. The evaluation of benzocaine- ...

  10. Antimicrobial, Cytotoxic and Phytotoxic Potency of Ethyl Acetate ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antimicrobial, cytotoxic and phytotoxic activities of the organic extract of Rhizopus stolonifer whole cell static culture in order to determine the presence of potentially bioactive compounds in the culture. Methods: The organic extract was obtained by extracting the whole cell culture of R. stolonifer ...

  11. THE WORLD-MODELLING POTENCY OF THE INDIVIDUAL METAPHOR

    Directory of Open Access Journals (Sweden)

    Pavlova, M.S.

    2016-03-01

    Full Text Available This article analyzes individual metaphors as a fundamental component of the artistic worldview. The research discusses the correlation between the individual metaphor and interdiscourse markedness that allows identifying some peculiarities of cultural identity of the English-language literary text. The central place belongs to the propositions connected with the ways of reality conceptualization in the minds of the English-speaking mentality, which are necessary for correct interpretation of the cultural-specific information.

  12. Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout.

    Science.gov (United States)

    Tan, Philip K; Liu, Sha; Gunic, Esmir; Miner, Jeffrey N

    2017-04-06

    Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Two of these residues, Ser-35 and Phe-365, are also important for urate transport kinetics. A URAT1 binding assay using radiolabeled verinurad revealed that distinct URAT1 inhibitors benzbromarone, sulfinpyrazone and probenecid all inhibit verinurad binding via a competitive mechanism. However, mutations made within the predicted transporter substrate channel differentially altered the potency for individual URAT1 inhibitors. Overall, our results suggest that URAT1 inhibitors bind to a common site in the core of the transporter and sterically hinder the transit of uric acid through the substrate channel, albeit with vastly different potencies and with differential interactions with specific URAT1 amino acids.

  13. Evaluation of occupational environment in two textile plants in Northern India with specific reference to noise.

    Science.gov (United States)

    Bedi, Raman

    2006-01-01

    Occupational Noise exposure has been linked with a range of negative health effects by various researchers. The resulting injury of occupational hearing loss is also a well recognized and global problem. To protect workers from hearing damage due to noise exposure and other related health effects, a vast store of knowledge has been accumulated till date about its nature, etiology and time course. There is still ignorance, amongst majority of people working in industries in developing and third world countries including India about ill effects of exposure to high values of noise. The study being reported here has been carried out in two textile plants located in Northern Indian state of Punjab. Equivalent sound pressure level L(eq) has been measured in various sections of these plants with the help of a Class-I type digital sound level meter. The noise spectrum has been evaluated with the help of 1/3 octave filter set. A cross sectional study involving 112 workers exposed to different levels of occupational noise has been conducted. The results of the study establish the fact that noise level in certain sections of the plants i.e Loom Shed, Spinning, Ring Frame, TFO Area is more than the acceptable limit of 90 dBA for 8 h exposure stipulated by OSHA. The noise level in other sections like carding, blow room, combing etc., although is less than 90 dB(A), but is quite higher than limits used for assessment of noise for community response. Octave band analysis of the noise shows the presence of high sound level in 4,000 Hz frequency range, which can be a major reason for causing occupational hearing loss. The results of the interview questionnaire which included a number of parameters reveal the following; (i) only 29% workers are aware about the effects of noise on health (ii) 28% workers are using ear protectors (iii) the satisfaction with the working environment is related to noise level, as workers exposed to comparatively less noise level report better

  14. High Specificity in Circulating Tumor Cell Identification Is Required for Accurate Evaluation of Programmed Death-Ligand 1.

    Directory of Open Access Journals (Sweden)

    Jennifer L Schehr

    Full Text Available Expression of programmed-death ligand 1 (PD-L1 in non-small cell lung cancer (NSCLC is typically evaluated through invasive biopsies; however, recent advances in the identification of circulating tumor cells (CTCs may be a less invasive method to assay tumor cells for these purposes. These liquid biopsies rely on accurate identification of CTCs from the diverse populations in the blood, where some tumor cells share characteristics with normal blood cells. While many blood cells can be excluded by their high expression of CD45, neutrophils and other immature myeloid subsets have low to absent expression of CD45 and also express PD-L1. Furthermore, cytokeratin is typically used to identify CTCs, but neutrophils may stain non-specifically for intracellular antibodies, including cytokeratin, thus preventing accurate evaluation of PD-L1 expression on tumor cells. This holds even greater significance when evaluating PD-L1 in epithelial cell adhesion molecule (EpCAM positive and EpCAM negative CTCs (as in epithelial-mesenchymal transition (EMT.To evaluate the impact of CTC misidentification on PD-L1 evaluation, we utilized CD11b to identify myeloid cells. CTCs were isolated from patients with metastatic NSCLC using EpCAM, MUC1 or Vimentin capture antibodies and exclusion-based sample preparation (ESP technology.Large populations of CD11b+CD45lo cells were identified in buffy coats and stained non-specifically for intracellular antibodies including cytokeratin. The amount of CD11b+ cells misidentified as CTCs varied among patients; accounting for 33-100% of traditionally identified CTCs. Cells captured with vimentin had a higher frequency of CD11b+ cells at 41%, compared to 20% and 18% with MUC1 or EpCAM, respectively. Cells misidentified as CTCs ultimately skewed PD-L1 expression to varying degrees across patient samples.Interfering myeloid populations can be differentiated from true CTCs with additional staining criteria, thus improving the

  15. Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity

    NARCIS (Netherlands)

    Louisse, J.; Gönen, S.; Rietjens, I.M.C.M.; Verwei, M.

    2011-01-01

    The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental

  16. A tool for rapid screening of direct DNA agents using reaction rates and relative interaction potency: towards screening environmental contaminants for hazard.

    Science.gov (United States)

    Gavina, Jennilee M A; Rubab, Mamoona; Zhang, Huijuan; Zhu, Jiping; Nong, Andy; Feng, Yong-Lai

    2011-11-01

    DNA damage represents a potential biomarker for determining the exposure risk to chemicals and may provide early warning data for identifying chemical hazards to human health. Here, we have demonstrated a simple chromatography-based method that can be used to rapidly screen for the presence of chemical hazards as well as to determine parameters relevant to hazard assessment. In this proof-of-principle study, a simple in vitro system was used to determine the interaction of pollutants and probable carcinogens, phenyl glycidyl ether (PGE), tetrachlorohydroquinone (Cl(4)HQ), methylmethane sulfonate (MMS), styrene-7,8-oxide (SO), and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), a metabolite of benzo[a]pyrene (B[a]P), with single- and double-stranded DNA probes. Differences in potency and reaction kinetics were studied for chemical and DNA type. A relative interaction potency equivalency (PEQ) of a chemical was determined by ratio of interaction potency of a chemical to BPDE as the reference chemical in the reaction with single- and double-stranded oligodeoxynucleotides. PEQs were found to be BPDE > PGE > SO > MMS > Cl(4)HQ for single-stranded oligodeoxynucleotides while they were found to be BPDE > PGE > Cl(4)HQ > MMS > SO for double-stranded oligodeoxynucleotides. Kinetics evaluation revealed that BPDE reacted with both DNA probes at a significantly faster rate, as compared to the remaining test chemicals. Equilibrium was reached within an hour for BPDE, but required a minimum of 48 h for the remaining chemicals. First-order rate constants were (1.61 ± 0.2) × 10(-3) s(-1) and (3.18 ± 0.4) × 10(-4) s(-1) for reaction of BPDE with double- and single-stranded DNA, respectively. The remaining chemicals possessed rate constants from 2 to 13 × 10(-6) s(-1) with a relative kinetic order for reaction with DNA of BPDE ≫ MMS > SO > PGE > Cl(4)HQ for ds-DNA and BPDE ≫ SO ≈ Cl(4)HQ ≈ MMS > PGE for ss-DNA. We further found that the reaction potency, defined by

  17. Language-Independent and Language-Specific Aspects of Early Literacy: An Evaluation of the Common Underlying Proficiency Model.

    Science.gov (United States)

    Goodrich, J Marc; Lonigan, Christopher J

    2017-08-01

    According to the common underlying proficiency model (Cummins, 1981), as children acquire academic knowledge and skills in their first language, they also acquire language-independent information about those skills that can be applied when learning a second language. The purpose of this study was to evaluate the relevance of the common underlying proficiency model for the early literacy skills of Spanish-speaking language-minority children using confirmatory factor analysis. Eight hundred fifty-eight Spanish-speaking language-minority preschoolers (mean age = 60.83 months, 50.2% female) participated in this study. Results indicated that bifactor models that consisted of language-independent as well as language-specific early literacy factors provided the best fits to the data for children's phonological awareness and print knowledge skills. Correlated factors models that only included skills specific to Spanish and English provided the best fits to the data for children's oral language skills. Children's language-independent early literacy skills were significantly related across constructs and to language-specific aspects of early literacy. Language-specific aspects of early literacy skills were significantly related within but not across languages. These findings suggest that language-minority preschoolers have a common underlying proficiency for code-related skills but not language-related skills that may allow them to transfer knowledge across languages.

  18. Evaluation of a hybrid approach using UBLAST and BLASTX for metagenomic sequences annotation of specific functional genes.

    Directory of Open Access Journals (Sweden)

    Ying Yang

    Full Text Available The fast development of next generation sequencing (NGS has dramatically increased the application of metagenomics in various aspects. Functional annotation is a major step in the metagenomics studies. Fast annotation of functional genes has been a challenge because of the deluge of NGS data and expanding databases. A hybrid annotation pipeline proposed previously for taxonomic assignments was evaluated in this study for metagenomic sequences annotation of specific functional genes, such as antibiotic resistance genes, arsenic resistance genes and key genes in nitrogen metabolism. The hybrid approach using UBLAST and BLASTX is 44-177 times faster than direct BLASTX in the annotation using the small protein database for the specific functional genes, with the cost of missing a small portion (<1.8% of target sequences compared with direct BLASTX hits. Different from direct BLASTX, the time required for specific functional genes annotation using the hybrid annotation pipeline depends on the abundance for the target genes. Thus this hybrid annotation pipeline is more suitable in specific functional genes annotation than in comprehensive functional genes annotation.

  19. Sensitivity and specificity of CT- and MRI-scanning in evaluation of occult fracture of the proximal femur

    DEFF Research Database (Denmark)

    Haubro, M; Stougaard, C; Torfing, T

    2015-01-01

    and a resident in orthopaedic surgery. Sensitivity and specificity were estimated with MRI as the golden standard. Kappa value was used to assess level of agreement in both MRI and CT finding. RESULTS: 15 fractures of the proximal femur were found (7 intertrochanteric-, 3 femoral neck and 5 fractures......OBJECTIVE: To estimate sensitivity and specificity of CT and MRI examinations in patients with fractures of the proximal femur. To determine the interobserver agreement of the modalities among a senior consulting radiologist, a resident in radiology and a resident in orthopaedics surgery. MATERIALS...... AND METHODS: 67 patients (27 males, 40 females, mean age 80.5) seen in the emergency room with hip pain after fall, inability to stand and a primary X-ray without fracture were evaluated with both CT and MRI. The images were analysed by a senior consulting musculoskeletal radiologist, a resident in radiology...

  20. Dog bites in The Netherlands: a study of victims, injuries, circumstances and aggressors to support evaluation of breed specific legislation.

    Science.gov (United States)

    Cornelissen, Jessica M R; Hopster, Hans

    2010-12-01

    As part of an evaluation of Dutch breed specific legislation, data were collected from dog bite victims (1078) and dog owners (6139) using Internet surveys. The incidence rate of dog bites and details of incidents (victims, injuries, circumstances and aggressors) are reported and the justification for using breed specific measurements to deal with dog bites are considered. For aggressors, attack records for breed groups and popular breeds were established by calculating breed risk indices using a reference population. Several breeds and breed groups were over- and under-represented in the biting population and there was a mismatch between risk indices and the then-current legislation. Mitigation strategies should not be based on attack records (since this would lead to the rejection of a significant proportion of the canine population) but on the circumstances of the incidents. Preventative measures must focus on a better understanding of how to handle dogs. Copyright © 2009 Elsevier Ltd. All rights reserved.

  1. A GIS-Based Procedure for Landslide Intensity Evaluation and Specific risk Analysis Supported by Persistent Scatterers Interferometry (PSI

    Directory of Open Access Journals (Sweden)

    Silvia Bianchini

    2017-10-01

    Full Text Available The evaluation of landslide specific risk, defined as the expected degree of loss due to landslides, requires the parameterization and the combination of a number of socio-economic and geological factors, which often needs the interaction of different skills and expertise (geologists, engineers, planners, administrators, etc.. The specific risk sub-components, i.e., hazard and vulnerability of elements at risk, can be determined with different levels of detail depending on the available auxiliary data and knowledge of the territory. These risk factors are subject to short-term variations and nowadays turn out to be easily mappable and evaluable through remotely sensed data and GIS (Geographic Information System tools. In this work, we propose a qualitative approach at municipal scale for producing a “specific risk” map, supported by recent satellite PSI (Persistent Scatterer Interferometry data derived from SENTINEL-1 C-band images in the spanning time 2014–2017, implemented in a GIS environment. In particular, PSI measurements are useful for the updating of a landslide inventory map of the area of interest and are exploited for the zonation map of the intensity of ground movements, needed for evaluating the vulnerability over the study area. Our procedure is presented throughout the application to the Volterra basin and the output map could be useful to support the local authorities with updated basic information required for environmental knowledge and planning at municipal level. Moreover, the proposed procedure is easily managed and repeatable in other case studies, as well as exploiting different SAR sensors in L- or X-band.

  2. Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability.

    Science.gov (United States)

    Charrier, Nicolas; Clarke, Brian; Cutler, Leanne; Demont, Emmanuel; Dingwall, Colin; Dunsdon, Rachel; East, Philip; Hawkins, Julie; Howes, Colin; Hussain, Ishrut; Jeffrey, Phil; Maile, Graham; Matico, Rosalie; Mosley, Julie; Naylor, Alan; O'Brien, Alistair; Redshaw, Sally; Rowland, Paul; Soleil, Virginie; Smith, Kathrine J; Sweitzer, Sharon; Theobald, Pam; Vesey, David; Walter, Daryl S; Wayne, Gareth

    2008-06-12

    BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.

  3. Single-cell entropy for accurate estimation of differentiation potency from a cell's transcriptome

    Science.gov (United States)

    Teschendorff, Andrew E.; Enver, Tariq

    2017-01-01

    The ability to quantify differentiation potential of single cells is a task of critical importance. Here we demonstrate, using over 7,000 single-cell RNA-Seq profiles, that differentiation potency of a single cell can be approximated by computing the signalling promiscuity, or entropy, of a cell's transcriptome in the context of an interaction network, without the need for feature selection. We show that signalling entropy provides a more accurate and robust potency estimate than other entropy-based measures, driven in part by a subtle positive correlation between the transcriptome and connectome. Signalling entropy identifies known cell subpopulations of varying potency and drug resistant cancer stem-cell phenotypes, including those derived from circulating tumour cells. It further reveals that expression heterogeneity within single-cell populations is regulated. In summary, signalling entropy allows in silico estimation of the differentiation potency and plasticity of single cells and bulk samples, providing a means to identify normal and cancer stem-cell phenotypes. PMID:28569836

  4. Steady-state relative potency of aldosterone antagonists: spironolactone and prorenoate.

    Science.gov (United States)

    McInnes, G T; Shelton, J R; Harrison, I R

    1981-05-01

    The dose ratio approach was used to define the steady-state relative potency of the competitive mineralocorticoid antagonists prorenoate potassium and spironolactone in six healthy male subjects using fludrocortisone as mineralocorticoid agonist. Log fludrocortisone dose-response relationships in the presence or absence of antagonists did not differ from linearity and parallelism, supporting the theoretical basis of the method. Urinary sodium and plasma potassium responses appeared to behave according to the law of mass action, which made possible estimation of the potency of prorenoate relative to spironolactone on a weight basis-4.2:1 (95% C.L. 2.7-6.9:1) and 2.68:1 (95% C.L. 0.71-6.57:1, respectively. The steady-state relative potency for sodium excretion was greater than previously estimated after single doses. Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.

  5. Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; Herings, RMC; Roos, RAC; Jansen, PAF; Leufkens, HGM

    Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous

  6. Replacing the NIH test for rabies vaccine potency testing: a synopsis of drivers and barriers

    NARCIS (Netherlands)

    Schiffelers, M.J.; Blaauboer, B.J.|info:eu-repo/dai/nl/068359802; Bakker, W.|info:eu-repo/dai/nl/302335919; Hendriksen, C.F.M.|info:eu-repo/dai/nl/075036266

    Approximately 70% of animal use is utilized to demonstrate quality control of vaccines. Especially rabies vaccine potency testing, using the NIH challenge test, involves objections in terms of scientific relevance, animal welfare concern and costs. Several 3R models have been proposed to refine,

  7. Cold chain facility status and the potency of animal rabies vaccine ...

    African Journals Online (AJOL)

    Rabies vaccine failures were reported in literature. Realising that rabies vaccine is sensitive to temperature change, there is need to assess the storage condition of rabies vaccine from distribution centres to veterinary clinics where they are used. This is to establish the sustained potency from source to use. Cold-Chain ...

  8. Novel view on predicting acute toxicity: Decomposing toxicity data in species vulnerability and chemical potency.

    NARCIS (Netherlands)

    Jager, D.T.; Posthuma, L.; Zwart, D.D.; van de Meent, D.

    2007-01-01

    Chemical risk assessment usually applies empirical methods to predict toxicant effects on different species. We propose a more mechanism-oriented approach, and introduce a method to decompose toxicity data in a contribution from the chemical (potency) and from the exposed species (vulnerability). We

  9. Observations of the effect of atmospheric processes on the genotoxic potency of airborne particulate matter

    DEFF Research Database (Denmark)

    Feilberg, Anders; Nielsen, Torben; Binderup, Mona-Lise

    2002-01-01

    In this study, the relationship between genotoxic potency and the occurrence of polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene (BaP), and nitro-PAH in urban and semi-rural air masses has been investigated. The Salmonella/microsome assay has been used as a measure of genotoxic po...

  10. Antipsychotic-induced extrapyramidal syndromes : Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, I; de Boer, A|info:eu-repo/dai/nl/075097346; Herings, R M; Roos, R A; Jansen, P A; Leufkens, H G|info:eu-repo/dai/nl/075255049

    AIM: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous

  11. Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency

    DEFF Research Database (Denmark)

    Tosco, Paolo; Ahring, Philip K; Dyhring, Tino

    2009-01-01

    Complementary 3D-QSAR modeling of binding affinity and functional potency is proposed as a tool to pinpoint the molecular features of the ligands, and the corresponding amino acids in the receptor, responsible for high affinity binding vs those driving agonist behavior and receptor activation...

  12. Validation of self-reported cannabis dose and potency: an ecological study

    NARCIS (Netherlands)

    van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J.; van den Brink, Wim; van Laar, Margriet

    2013-01-01

    To assess the reliability and validity of self-reported cannabis dose and potency measures. Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Ecological study with assessments at participants' homes or in

  13. Validation of self-reported cannabis dose and potency: an ecological study.

    Science.gov (United States)

    van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

    2013-10-01

    To assess the reliability and validity of self-reported cannabis dose and potency measures. Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Ecological study with assessments at participants' homes or in a coffee shop. Young adult frequent cannabis users (n = 106) from the Dutch Cannabis Dependence (CanDep) study. The objectively measured amount of cannabis per joint (dose in grams) was compared with self-reported estimates using a prompt card and average number of joints made from 1 g of cannabis. In addition, objectively assessed THC concentration in the participant's cannabis was compared with self-reported level of intoxication, subjective estimate of cannabis potency and price per gram of cannabis. Objective estimates of doses per joint (0.07-0.88 g/joint) and cannabis potency (1.1-24.7%) varied widely. Self-reported measures of dose were imprecise, but at group level, average dose per joint was estimated accurately with the number of joints made from 1 g [limit of agreement (LOA) = -0.02 g, 95% confidence interval (CI) = -0.29; 0.26], whereas the prompt card resulted in serious underestimation (LOA = 0.14 g, 95% CI = -0.10; 0.37). THC concentration in cannabis was associated with subjective potency ['average' 3.77% (P = 0.002) and '(very) strong' 5.13% more THC (P Addiction.

  14. Validation of self-reported cannabis dose and potency: an ecological study

    NARCIS (Netherlands)

    van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

    2013-01-01

    Aims To assess the reliability and validity of self-reported cannabis dose and potency measures. Design Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Setting Ecological study with assessments at

  15. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    NARCIS (Netherlands)

    Gibbs, S.; Corsini, E.; Spiekstra, S.W.; Galbiati, V.; Fuchs, H.W.; Degeorge, G.; Troese, M.; Hayden, P.; Deng, W.; Roggen, E.

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low

  16. Comparative Elongated Mineral Particle Toxicology & Erionite’s Apparent  High Potency for Inducing Mesothelioma

    Science.gov (United States)

    Recent NHEERL research under EPA's Libby Action Plan has determined that elongated particle relative potency for rat pleural mesothelioma is best predicted on the basis of total external surface area (TSA) of slightly acid leached test samples which simulate particle bio-durabili...

  17. Single-cell entropy for accurate estimation of differentiation potency from a cell's transcriptome

    Science.gov (United States)

    Teschendorff, Andrew E.; Enver, Tariq

    2017-06-01

    The ability to quantify differentiation potential of single cells is a task of critical importance. Here we demonstrate, using over 7,000 single-cell RNA-Seq profiles, that differentiation potency of a single cell can be approximated by computing the signalling promiscuity, or entropy, of a cell's transcriptome in the context of an interaction network, without the need for feature selection. We show that signalling entropy provides a more accurate and robust potency estimate than other entropy-based measures, driven in part by a subtle positive correlation between the transcriptome and connectome. Signalling entropy identifies known cell subpopulations of varying potency and drug resistant cancer stem-cell phenotypes, including those derived from circulating tumour cells. It further reveals that expression heterogeneity within single-cell populations is regulated. In summary, signalling entropy allows in silico estimation of the differentiation potency and plasticity of single cells and bulk samples, providing a means to identify normal and cancer stem-cell phenotypes.

  18. Pre- and postsynaptic inhibitory potencies of the angiotensin AT(1) receptor antagonists eprosartan and candesartan

    NARCIS (Netherlands)

    Nap, Alexander; Mathy, Marie-Jeanne; Balt, Jippe C.; Pfaffendorf, Martin; van Zwieten, Pieter A.

    2003-01-01

    The aim of the present study was to determine the inhibitory potency of two selective angiotensin AT, receptor antagonists, eprosartan and candesartan, at the level of the sympathetic nerve terminal and the vascular smooth muscle. Male New Zealand White rabbits, weighing 2100-2550 g, were used. To

  19. In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Hamers, T.; Kamstra, J.H. [Inst. for Environmental Studies (IVM), Amsterdam (Netherlands); Sonneveld, E. [BioDetection Systems (BDS), Amsterdam (Netherlands); Murk, A.J. [Wageningen Univ., Toxicology Group, Wageningen (Netherlands); Zegers, B.N.; Boon, J.P. [Royal Netherlands Inst. for Sea Research (NIOZ), Den Burg (Netherlands); Brouwer, A. [Umea Univ., Umea (Sweden)

    2004-09-15

    Substantial evidence is recently becoming available that brominated flame retardants (BFRs) are potential endocrine disruptors. The toxicological profile of BFRs, however, is too incomplete and insufficient to perform human and ecological risk assessment. To fill these gaps, the EU funded research program FIRE was started in December 2002. This program aims at the identification and toxicological characterization of the most potent and environmentally relevant BFRs and their possible risk for human and wildlife health. As part of a hazard identification approach, twenty seven BFRs have been selected within the framework of FIRE for pre-screening their endocrinedisrupting potencies. Selection of test compounds was based on a maximal variation in physicochemical characteristics of BFRs within the test set, allowing the establishment of quantitative structure-activity relationships (QSARs). In addition, environmental relevance (e.g. high production volumes and persistence) and availability for testing were used as selection criteria. BFRs were tested in seven different in vitro bioassays for their potency to interfere via estrogenic, thyroidal, androgenic, progestagenic, and Ah-receptor mediated pathways. Metabolisation rates of BFRs were determined using phenobarbital-induced rat liver microsomes. Finally, the endocrine disrupting potency of the metabolites was determined in the same in vitro bio-assays and compared to the potency of the parent compounds.

  20. Critical evaluation of the nonradiological environmental technical specifications. Volume 4. San Onofre Nuclear Generating Station, Unit 1

    Energy Technology Data Exchange (ETDEWEB)

    Adams, S.M.; Cunningham, P.A.; Gray, D.D.; Kumar, K.D.

    1976-08-10

    A comprehensive study of the data collected as part of the environmental Technical Specifications program for Unit 1 of the San Onofre Nuclear Generating Station (SONGS 1) was conducted for the Office of Nuclear Regulatory Research of the U.S. Nuclear Regulatory Commission. The program included an analysis of the hydrothermal and ecological monitoring data collected during 1975. The hydrothermal analysis includes a discussion of models used in plume predictions prior to plant operation and an evaluation of the present hydrothermal monitoring program. The ecological evaluation was directed toward reviewing the strengths and weaknesses of the various sampling programs designed to monitor the planktonic, benthic, and nektonic communities inhabiting the inshore coastal area in the vicinity of San Onofre.

  1. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  2. Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

    Science.gov (United States)

    Azizi, Ali; Kumar, Ashok; Diaz-Mitoma, Francisco; Mestecky, Jiri

    2010-01-01

    The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells. PMID:21085599

  3. Evaluation of Basketball-Specific Agility: Applicability of Preplanned and Nonplanned Agility Performances for Differentiating Playing Positions and Playing Levels.

    Science.gov (United States)

    Sekulic, Damir; Pehar, Miran; Krolo, Ante; Spasic, Miodrag; Uljevic, Ognjen; Calleja-González, Julio; Sattler, Tine

    2017-08-01

    Sekulic, D, Pehar, M, Krolo, A, Spasic, M, Uljevic, O, Calleja-González, J, and Sattler, T. Evaluation of basketball-specific agility: applicability of preplanned and nonplanned agility performances for differentiating playing positions and playing levels. J Strength Cond Res 31(8): 2278-2288, 2017-The importance of agility in basketball is well known, but there is an evident lack of studies examining basketball-specific agility performances in high-level players. The aim of this study was to determine the reliability and discriminative validity of 1 standard agility test (test of preplanned agility [change-of-direction speed] over T course, T-TEST), and 4 newly developed basketball-specific agility tests, in defining playing positions and performance levels in basketball. The study comprised 110 high-level male basketball players (height: 194.92 ± 8.09 cm; body mass: 89.33 ± 10.91 kg; age: 21.58 ± 3.92 years). The variables included playing position (Guard, Forward, Center), performance level (first division vs. second division), anthropometrics (body height, body mass, and percentage of body fat), T-TEST, nonplanned basketball agility test performed on dominant (BBAGILdom) and nondominant sides (BBAGILnond), and a preplanned (change-of-direction speed) basketball agility test performed on dominant (BBCODSdom) and nondominant sides (BBCODSnond). The reliability of agility tests was high (intraclass correlation coefficient of 0.81-0.95). Forwards were most successful in the T-TEST (F test: 13.57; p = 0.01). Guards outperformed Centers in BBCODSdom, BBCODSndom, BBAGILdom, and BBAGILnond (F test: 5.06, p = 0.01; 6.57, 0.01; 6.26, 0.01; 3.37, 0.04, respectively). First division Guards achieved better results than second division Guards in BBCODSdom (t: 2.55; p = 0.02; moderate effect size differences), BBAGILdom, and BBAGILnond (t: 3.04 and 3.06, respectively; both p = 0.01 and moderate effect size differences). First division Centers outperformed second division

  4. Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity.

    Science.gov (United States)

    Ayala Breton, Camilo; Wikan, Nitwara; Abbuhl, Arinda; Smith, Duncan R; Russell, Stephen J; Peng, Kah-Whye

    2015-01-01

    The hybrid oncolytic vesicular stomatitis virus (VSV-FH) deleted for its G glycoprotein and displaying the measles virus (MV) envelope glycoproteins (hemagglutinin H and fusion F) is fusogenic, infects cells via any of the three MV receptors and has potent oncolytic activity against subcutaneous and disseminated myeloma tumors. To tailor VSV-FH as an oncolytic virus for ovarian cancer, we ablated its natural tropism and retargeted the virus by display of a single-chain antibody (scFv) with specificity to the HER-2/neu receptor. A panel of six VSVFH-αHER2 viruses displaying anti-HER2 scFv that bind to the same HER2 epitope but with different K d (10(-6) to 10(-11) M, VSVFH-αHER2#6 to #11, respectively) were rescued and characterized. A K d of at least 10(-8) M is required for infection of HER-2 positive SKOV3ip.1 cells. The higher affinity viruses (>10(-8) M) were able to infect and fuse SKOV3ip.1 cells more efficiently, inducing more extensive cytopathic effects. We next compared the antitumor potency of the viruses against SKOV3ip.1 tumor xenografts. In contrast to the saline-treated animals, one intratumoral injection of VSVFH-αHER2#9, #10, or #11 resulted in efficient tumor control. There was no significant difference between viruses with an affinity higher than 10(-9) M in terms of oncolytic potency. VSVFH-αHER2 virus may be a promising agent for the treatment of HER-2 positive malignancies.

  5. A QSAR for the Mutagenic Potencies of Twelve 2-Amino-trimethylimidazopyridine Isomers: Structural, Quantum Chemical,and Hydropathic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M G; Hatch, F T; Tanga, M J; Lau, E V; Colvin, M E

    2005-04-23

    An isomeric series of heterocyclic amines related to one found in heated muscle meats was investigated for properties that predict their measured mutagenic potency. Eleven of the 12 possible 2-amino-trimethylimidazopyridine (TMIP) isomers were tested for mutagenic potency in the Ames/Salmonella test with bacterial strain TA98, and resulted in a 600-fold range in potency. Structural, quantum chemical and hydropathic data were calculated on the parent molecules and the corresponding nitrenium ions of all of the tested isomers to establish models for predicting the potency of the unknown isomer. The regression model accounting for the largest fraction of the total variance in mutagenic potency contains four predictor variables: dipole moment, a measure of the gap between amine LUMO and HOMO energies, percent hydrophilic surface, and energy of amine LUMO. The most important determinants of high mutagenic potency in these amines are: (1) a small dipole moment, (2) the combination of b-face ring fusion and N3-methyl group, and (3) a lower calculated energy of the {pi} electron system. Based on predicted potency from the average of five models, the isomer not yet synthesized and tested is expected to have a mutagenic potency of 0.84 revertants/{micro}g in test strain TA98.

  6. Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency.

    Science.gov (United States)

    Albrekt, Ann-Sofie; Johansson, Henrik; Börje, Anna; Borrebaeck, Carl; Lindstedt, Malin

    2014-02-11

    Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency. Recently, we presented the Genomic Allergen Rapid Detection (GARD) assay for assessment of chemical sensitizers. In this paper, we show how the genome wide readout of GARD can be expanded and used to identify differentially regulated pathways relating to individual chemical sensitizers. In this study, we investigated the mechanisms of action of a range of skin sensitizers through pathway identification, pathway classification and transcription factor analysis and related this to the reactive mechanisms and potency of the sensitizing agents. By transcriptional profiling of chemically stimulated MUTZ-3 cells, 33 canonical pathways intimately involved in sensitization to chemical substances were identified. The results showed that metabolic processes, cell cycling and oxidative stress responses are the key events activated during skin sensitization, and that these functions are engaged differently depending on the reactivity mechanisms of the sensitizing agent. Furthermore, the results indicate that the chemical reactivity groups seem to gradually engage more pathways and more molecules in each pathway with increasing sensitizing potency of the chemical used for stimulation. Also, a switch in gene regulation from up to down regulation, with increasing potency, was seen both in genes involved in metabolic functions and cell cycling. These observed pathway patterns were clearly reflected in the regulatory elements identified to drive these processes, where 33 regulatory elements have been proposed for further analysis. This study demonstrates that functional analysis of

  7. NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency.

    Science.gov (United States)

    Burgess, Braydon L; He, Yumin; Baker, Mandie M; Luo, Bing; Carroll, Stephen F; Forte, Trudy M; Oda, Michael N

    2013-01-01

    NanoDisk-amphotericin B (ND-AMB) is a protein-phospholipid bioparticle containing a "super aggregate" form of antifungal AMB. While lipid-based formulations of AMB, including liposomal AMB (L-AMB), are safer than the deoxycholate (DOC) solubilized form (DOC-AMB), the potency of lipid-based formulations is attenuated. We have developed an AMB-based therapy that is both well tolerated and fully efficacious. Potency was determined using broth culture growth-inhibition assays and candidacidal kinetics by quantitative culture plating. Toxicology studies were performed in healthy mice. Efficacy was assessed using both immune-competent and leukopenic murine models of systemic Candida albicans infection. ND-AMB C. albicans and Aspergillus fumigatus minimum inhibitory concentrations were fourfold and sixfold lower, respectively, than that observed for L-AMB. ND-AMB exhibited candidacidal activity at 0.125 mg/L, 16-fold lower than L-AMB. In mice, ND-AMB produced no statistically significant kidney or liver toxicity at 15 mg/kg, the highest dose tested. When evaluated in immune-competent mice infected with C. albicans, ND-AMB was at least as effective as DOC-AMB or L-AMB. In a leukopenic model of candidiasis, the 50% effective dose of ND-AMB was around threefold lower than L-AMB. These results indicate that ND-AMB exhibits a more favorable safety profile while maintaining uncompromised antifungal properties compared to both DOC-AMB and L-AMB. ND-AMB is a promising therapy for the treatment of invasive fungal infections.

  8. Genetic differences in osteogenic differentiation potency in the thoracic ossification of the ligamentum flavum under cyclic mechanical stress.

    Science.gov (United States)

    Ning, Shanglong; Chen, Zhongqiang; Fan, Dongwei; Sun, Chuiguo; Zhang, Chi; Zeng, Yan; Li, Weishi; Hou, Xiaofei; Qu, Xiaochen; Ma, Yunlong; Yu, Huilei

    2017-01-01

    Mechanical stress and genetic factors play important roles in the occurrence of thoracic ossification of ligament flavum (TOLF), which can occur at one, two, or multiple levels of the spine. It is unclear whether single- and multiple-level TOLF differ in terms of osteogenic differentiation potency and osteogenesis-related gene expression under cyclic mechanical stress. This was addressed in the present study using patients with non‑TOLF and single‑ and multiple‑level TOLF (n=8 per group). Primary ligament cells were cultured and osteogenesis was induced by application of cyclic mechanical stress. Osteogenic differentiation was assessed by evaluating alkaline phosphatase (ALP) activity and the mRNA and protein expression of osteogenesis‑related genes, including ALP, bone morphogenetic protein 2 (BMP2), Runt‑related transcription factor‑2 (Runx‑2), osterix, osteopontin (OPN) and osteocalcin. The application of cyclic mechanical stress resulted in higher ALP activity in the multiple‑level than in the single‑level TOLF group, whereas no changes were observed in the non‑TOLF group. The ALP, BMP2, OPN and osterix mRNA levels were higher in the multiple‑level as compared to the single‑level TOLF group, and the levels of all osteogenesis-related genes, apart from Runx2, were higher in the multiple‑level as compared to the non‑TOLF group. The osterix and ALP protein levels were higher in the multiple‑level TOLF group than in the other 2 groups, and were increased with the longer duration of stress. These results highlight the differences in osteogenic differentiation potency between single‑ and multiple‑level TOLF that may be related to the different pathogenesis and genetic background.

  9. An evaluation study of a gender-specific smoking cessation program to help Hong Kong Chinese women quit smoking.

    Science.gov (United States)

    Li, Ho Cheung William; Chan, Sophia Siu Chee; Wan, Zoe Siu Fung; Wang, Man Ping; Lam, Tai Hing

    2015-09-29

    There is a lack of population-based smoking cessation interventions targeting woman smokers in Hong Kong, and in Asia generally. This study aimed to evaluate the effectiveness of a gender-specific smoking cessation program for female smokers in Hong Kong. To evaluate the effectiveness of the service, a total of 457 eligible smokers were recruited. After the baseline questionnaire had been completed, a cessation counseling intervention was given by a trained counselor according to the stage of readiness to quit. Self-reported seven-day point prevalence of abstinence and reduction of cigarette consumption (≥50 %) and self-efficacy in rejecting tobacco were documented at one week and at two, three and six months. The 7-day point prevalence quit rate was 28.4 % (130/457), and 21.9 % (100/457) had reduced their cigarette consumption by at least 50 % at the six-month follow-up. The average daily cigarette consumption was reduced from 8.3 at baseline to 6.3 at six months. Moreover, both internal and external stimuli of anti-smoking self-efficacy increased from baseline to six months. The study provides some evidence for the effectiveness of the gender-specific smoking cessation program for female smokers. Furthermore, helping smokers to improve their self-efficacy in resisting both internal and external stimuli of tobacco use can be a way of enhancing the effectiveness of a smoking cessation intervention.

  10. Evaluation of Investment in Renovation to Increase the Quality of Buildings: A Specific Discounted Cash Flow (DCF Approach of Appraisal

    Directory of Open Access Journals (Sweden)

    Giuseppe Bonazzi

    2016-03-01

    Full Text Available The objective of this article is to develop and apply a specific discounting cash flow (DCF approach to evaluate investment in renovation to improve building quality, thus increasing energy efficiency. In this article, we develop and apply a specific net present value (NPV and an internal rate of return (IRR approach to quantify the value created for the owners of the building by the investment in renovation via energy-saving investments that produce positive externalities. The model has an applied interest because, in recent years, a lot of investments in real estate were made by owners in order to increase the green quality of the buildings, and several funds of public aid were provided by the government to stimulate these energy-saving investments. The model proposed here is applied to a case study of a 16-apartment building located in northern Italy considers the model attempts to quantify the initial investment value, the energy savings, the tax deduction of the initial investment and the terminal value of the investment as the increase in building value. The analysis shows that the model is consistent in evaluating investments to improve building quality, and investments within the context of the specific case study considered in the research have IRRs ranging from a minimum of 4.907% to a maximum of 12.980%. It could even be useful to consider a sample of cases to verify whether our results are representative of this specific case study. The model could represent a useful tool for consumers in evaluating their own investments in building renovation, from a stand-alone perspective and even by comparing them with other types of investment. The research could be developed in the future to quantify the social welfare generated by public spending via tax deductions to reduce the costs of investment in energy savings for buildings and could even be applied to new real estate projects in comparing different construction technologies and even

  11. Evaluation of a Novel Rapid Test System for the Detection of Specific IgE to Hymenoptera Venoms

    Directory of Open Access Journals (Sweden)

    Nikolai Pfender

    2012-01-01

    Full Text Available Background. The Allergy Lateral Flow Assay (ALFA is a novel rapid assay for the detection of sIgE to allergens. The objective of this study is the evaluation of ALFA for the detection of sIgE to bee venom (BV and wasp venom (WV in insect venom allergic patients. Methods. Specific IgE to BV and WV was analyzed by ALFA, ALLERG-O-LIQ, and ImmunoCAP in 80 insect venom allergic patients and 60 control sera. Sensitivity and specificity of ALFA and correlation of ALFA and ImmunoCAP results were calculated. Results. The sensitivity/specificity of ALFA to the diagnosis was 100%/83% for BV and 82%/97% for WV. For insect venom allergic patients, the Spearman correlation coefficient for ALFA versus ImmunoCAP was 0.79 for BV and 0.80 for WV. However, significant differences in the negative control groups were observed. Conclusion. ALFA represents a simple, robust, and reliable tool for the rapid detection of sIgE to insect venoms.

  12. Hemodynamic Evaluation of a Biological and Mechanical Aortic Valve Prosthesis Using Patient-Specific MRI-Based CFD.

    Science.gov (United States)

    Hellmeier, Florian; Nordmeyer, Sarah; Yevtushenko, Pavlo; Bruening, Jan; Berger, Felix; Kuehne, Titus; Goubergrits, Leonid; Kelm, Marcus

    2017-08-29

    Modeling different treatment options before a procedure is performed is a promising approach for surgical decision making and patient care in heart valve disease. This study investigated the hemodynamic impact of different prostheses through patient-specific MRI-based CFD simulations. Ten time-resolved MRI data sets with and without velocity encoding were obtained to reconstruct the aorta and set hemodynamic boundary conditions for simulations. Aortic hemodynamics after virtual valve replacement with a biological and mechanical valve prosthesis were investigated. Wall shear stress (WSS), secondary flow degree (SFD), transvalvular pressure drop (TPD), turbulent kinetic energy (TKE), and normalized flow displacement (NFD) were evaluated to characterize valve-induced hemodynamics. The biological prostheses induced significantly higher WSS (medians: 9.3 vs. 8.6 Pa, P = 0.027) and SFD (means: 0.78 vs. 0.49, P = 0.002) in the ascending aorta, TPD (medians: 11.4 vs. 2.7 mm Hg, P = 0.002), TKE (means: 400 vs. 283 cm2 /s2 , P = 0.037), and NFD (means: 0.0994 vs. 0.0607, P = 0.020) than the mechanical prostheses. The differences between the prosthesis types showed great inter-patient variability, however. Given this variability, a patient-specific evaluation is warranted. In conclusion, MRI-based CFD offers an opportunity to assess the interactions between prosthesis and patient-specific boundary conditions, which may help in optimizing surgical decision making and providing additional guidance to clinicians. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  13. Individualized fetal growth assessment: critical evaluation of key concepts in the specification of third trimester size trajectories.

    Science.gov (United States)

    Deter, Russell L; Lee, Wesley; Sangi-Haghpeykar, Haleh; Tarca, Adi L; Yeo, Lami; Romero, Roberto

    2014-04-01

    To characterize second and third trimester fetal growth using Individualized Growth Assessment methods in a larger cohort of fetuses with normal neonatal growth outcomes. A prospective longitudinal study of 119 pregnancies was performed from 18 weeks, MA, to delivery. Measurements of several 1D and 3D fetal size parameters were obtained from 3D volume data sets at 3-4 week intervals. Regression analyses were used to determine Start Points (SP) and Rossavik model (P = c {t} (k + st)) coefficients c. k and s for each parameter in each fetus. Second trimester growth velocity reference ranges were determined and size model specification functions re-established, the latter used to generate individual size models. Actual measurements were compared to predicted third trimester size trajectories using Percent Deviations. New age-specific reference ranges for the Percent Deviations of each parameter were defined using 2-level statistical modeling. Rossavik models fit the data for all parameters very well (R(2): 99%), with SP's and k values similar to those found in much smaller cohorts. The c* values were strongly related to the second trimester slope (R(2): 97%), as was predicted s* to estimated c* (R(2): 54--95%). Rossavik models predicted third trimester growth with systematic errors close to 0%; random errors (95% range) ranged between 5.7 and 10.9% and 20.0 and 24.3% for 1D and 3D parameters, respectively. IGA procedures for evaluating second and third trimester growth are now established based on a larger cohort (4-6 fold larger). New, more rigorously defined, age-specific standards for the evaluation of third trimester size deviations are now available for nine anatomical parameters and a weight estimation procedure that incorporates a soft tissue parameter (fractional thigh volume). These results provide a means for more reliably assessing fetal growth on an individualized basis, thus minimizing the effect of biological differences in growth.

  14. Clearing the waters: Evaluating the need for site-specific field fluorescence corrections based on turbidity measurements

    Science.gov (United States)

    Saraceno, John F.; Shanley, James B.; Downing, Bryan D.; Pellerin, Brian A.

    2017-01-01

    In situ fluorescent dissolved organic matter (fDOM) measurements have gained increasing popularity as a proxy for dissolved organic carbon (DOC) concentrations in streams. One challenge to accurate fDOM measurements in many streams is light attenuation due to suspended particles. Downing et al. (2012) evaluated the need for corrections to compensate for particle interference on fDOM measurements using a single sediment standard in a laboratory study. The application of those results to a large river improved unfiltered field fDOM accuracy. We tested the same correction equation in a headwater tropical stream and found that it overcompensated fDOM when turbidity exceeded ∼300 formazin nephelometric units (FNU). Therefore, we developed a site-specific, field-based fDOM correction equation through paired in situ fDOM measurements of filtered and unfiltered streamwater. The site-specific correction increased fDOM accuracy up to a turbidity as high as 700 FNU, the maximum observed in this study. The difference in performance between the laboratory-based correction equation of Downing et al. (2012) and our site-specific, field-based correction equation likely arises from differences in particle size distribution between the sediment standard used in the lab (silt) and that observed in our study (fine to medium sand), particularly during high flows. Therefore, a particle interference correction equation based on a single sediment type may not be ideal when field sediment size is significantly different. Given that field fDOM corrections for particle interference under turbid conditions are a critical component in generating accurate DOC estimates, we describe a way to develop site-specific corrections.

  15. Computer program for analysis of the electrical power consumption billing through the A-load and potency hyperboloid in a cold-storage slaughter house; Programa computacional para analise do faturamento do consumo de energia eletrica atraves do A-hiperboloide de carga e potencia em uma empresa frigorifica abatedora de bovinos

    Energy Technology Data Exchange (ETDEWEB)

    Cardim, Delcio [UNESP, Botucatu, SP (Brazil). Faculdade de Ciencias Agronomicas. Programa de Pos-Graduacao em Agronomia]. E-mail: delciocardim@uol.com.br; Gabriel, Luiz Roberto Almeida [UNESP, Presidente Prudente, SP (Brazil). Dept. de Matematica]. E-mail: gabriel@prudente.unesp.br

    2001-12-01

    The purpose of this work was to project and develop a computer program to analyze the billing of the electrical power consumption and the demand of active and reactive potency of a cold-storage slaughter house, by verifying their efficient and rational use of the electrical power. From the electrical standards of a enterprise, it is obtained,during peak and non-peak times, the potency factor (FP), the load factor (FC) and the average active consumption C{sub m}. Basing on the load factor (FC) and potency factor (FP) dta of slaughter house in a specific period, and by means of mathematical models, which govern the electrical consumption billing and demand of both the active and the reactive potency, it was possible to generate the surface denominated A-Load and Potency Hyperboloid. Then, the areas and volumes that were determined by this Hyperboloid were calculated. The results that were obtained through the volumes of the solids, determined by the hyperboloid and the areas of the regions determined by this surface, were used to analyze the situation of the considered slaughter house, regarding the electrical power consumption billing and demand of both the active and the reactive potency. Borland Delphi 5.0 Microsoft Windows environment was used of elaborating the compute program. (author)

  16. Evaluating the influence of plant-specific physiological parameterizations on the partitioning of land surface energy fluxes

    Science.gov (United States)

    Sulis, Mauro; Langensiepen, Matthias; Shrestha, Prabhakar; Schickling, Anke; Simmer, Clemens; Kollet, Stefan

    2015-04-01

    photosynthesis process owing to a better estimation of the Rubisco enzyme kinematics. Finally, to evaluate the effects of the crop-specific parameterizations on the ABL dynamics, we perform a series of semi-idealized land-atmosphere coupled simulations by hypothesizing three cropland configurations. These numerical experiments reveal different heat and moisture budgets of the ABL that clearly impact the evolution of the boundary layer when using the crop-specific physiological properties.

  17. AVALIAÇÃO DO POTENCAL DE PRODUÇÃO DO "PEQUIZEIRO-ANÃO" SOB CONDIÇÕES NATURAIS NA REGIÃO SUL DO ESTADO DE MINAS GERAIS DWARF "PEQUI" PRODUCTION POTENTIAL EVALUATION UNDER NATURAL CONDITIONS IN SOUTHERN MINAS GERAIS STATE

    Directory of Open Access Journals (Sweden)

    DIJALMA BARBOSA DA SILVA

    2001-12-01

    Full Text Available O pequizeiro (Caryocar spp. - Caryocaraceae é uma planta nativa do Cerrado e da Amazônia, cujo fruto é muito rico em óleo e proteína, e bastante apreciado pelos povos que vivem nestes ecossistemas. O objetivo desse trabalho foi avaliar o potencial de produção do "pequizeiro-anão", (Caryocar brasiliense subsp. intermedium, em seu habitat. Foram realizadas duas prospecções botânicas na região Sul do Estado de Minas Gerais, em 1997 e 1998, em áreas de vegetação de cerrado, nas proximidades do município de Ingaí-MG, onde se observou a ocorrência de pequizeiro de porte baixo. Foi observado que os frutos apresentam deiscência e grande heterogeneidade em relação ao número de frutos/planta. Nas plantas com tronco, encontraram-se até 86 frutos/planta e, nas sem tronco, até 16 frutos/planta. A época de maturação dos frutos concentra-se nos meses de fevereiro e março. O fruto de cor esverdeada e polpa amarelo-alaranjada possui em média duas sementes/endocarpo, com peso médio de 8g. Em plantios realizados no Distrito Federal, foi observado que as plantas de "pequizeiro-anão", oriundas de sementes, iniciaram a frutificação com altura de 60 cm, aos 18 a 24 meses após o plantio, evidenciando que são também precoces. O "pequizeiro-anão" apresenta potencial para sua exploração em cultivos comerciais e em programas de melhoramento genético.The pequi tree (Caryocar spp. -- Caryocaraceae, a wild specie of Brazilian savannah and Amazon region, is an edible fruit for people living in these ecosystems. The "dwarf pequi tree" (Cariocar brasiliense subsp. intermedium, has a restricted occurrence in some parts of Brasilian savanna which is an incorporated process to arable farm, treating the survival of this specie. The objective of this work was to evaluate the production potencial of "dwarf pequi tree" in its natural habitat. The fruits can be harvested from February to March. In the plant with and without trunk there are up to

  18. Detection of Echinococcus multilocularis by MC-PCR: evaluation of diagnostic sensitivity and specificity without gold standard

    Directory of Open Access Journals (Sweden)

    Helene Wahlström

    2016-03-01

    Full Text Available Introduction: A semi-automated magnetic capture probe-based DNA extraction and real-time PCR method (MC-PCR, allowing for a more efficient large-scale surveillance of Echinococcus multilocularis occurrence, has been developed. The test sensitivity has previously been evaluated using the sedimentation and counting technique (SCT as a gold standard. However, as the sensitivity of the SCT is not 1, test characteristics of the MC-PCR was also evaluated using latent class analysis, a methodology not requiring a gold standard. Materials and methods: Test results, MC-PCR and SCT, from a previous evaluation of the MC-PCR using 177 foxes shot in the spring (n=108 and autumn 2012 (n=69 in high prevalence areas in Switzerland were used. Latent class analysis was used to estimate the test characteristics of the MC-PCR. Although it is not the primary aim of this study, estimates of the test characteristics of the SCT were also obtained. Results and discussion: This study showed that the sensitivity of the MC-PCR was 0.88 [95% posterior credible interval (PCI 0.80–0.93], which was not significantly different than the SCT, 0.83 (95% PCI 0.76–0.88, which is currently considered as the gold standard. The specificity of both tests was high, 0.98 (95% PCI 0.94–0.99 for the MC-PCR and 0.99 (95% PCI 0.99–1 for the SCT. In a previous study, using fox scats from a low prevalence area, the specificity of the MC-PCR was higher, 0.999% (95% PCI 0.997–1. One reason for the lower estimate of the specificity in this study could be that the MC-PCR detects DNA from infected but non-infectious rodents eaten by foxes. When using MC-PCR in low prevalence areas or areas free from the parasite, a positive result in the MC-PCR should be regarded as a true positive. Conclusion: The sensitivity of the MC-PCR (0.88 was comparable to the sensitivity of SCT (0.83.

  19. Functional Capacity Evaluation: Performance of Patients with Chronic Non-specific Low Back Pain Without Waddell Signs.

    Science.gov (United States)

    Oesch, Peter; Meyer, Kathrin; Jansen, Beatrice; Kool, Jan

    2015-06-01

    The primary objective of this study is to evaluate the effect of Waddell signs (WS) on Functional Capacity Evaluation (FCE) in patients with chronic non-specific low back pain (CNSLBP) undergoing fitness for work evaluation. If an effect is observed, the secondary objective is to report performance of patients without WS in a standardized 1 day FCE protocol. Survey of patients with CNSLBP as their primary complaint, referred for fitness for work evaluation, age between 20 and 60 years. Main outcome measures were WS and performance during manual handling assessed with lifting from floor to waist, waist to crown, horizontal and one handed carry; grip strength with Jamar hand held Dynamometer; ambulation with stair climbing and six minute walking test; work postures with elevated work, forward bend standing, kneeling, and sitting. 145 male with a mean age of 44.5 years (±10.1), and 53 females with a mean age of 43.6 years (±11.0) were included. Mean days off work were in male 658 (±1,056) and in female 642 (±886). 33% of all patients presented positive WS. FCE performance in male and female patients with positive and negative WS differed significantly in all comparisons except grip strength of the dominant hand and sitting in female. Performance of patients with negative WS indicated a mean physical capacity corresponding to lightmedium work in females and medium work in males for both age groups. WS should be assessed for interpretation of FCE results. Despite long work absence, patients with CNSLBP with negative WS demonstrated a physical capacity corresponding to substantial physical work demands.

  20. Validación del método de valoración biológica de gonadotrofina coriónica humana Validation of the biological potency test for human chorionic gonadotropin

    Directory of Open Access Journals (Sweden)

    Alicia Lagarto Parra

    2012-06-01

    Full Text Available Introducción: en el Centro de Investigación y Desarrollo de Medicamentos se cuenta con una serie de ensayos biológicos para el control de calidad que deben ser sujetos a validación, entre ellos se encuentra la valoración biológica de gonadotrofina coriónica humana. Objetivo: evaluar el desempeño del método de valoración biológica de gonadotrofina coriónica humana. Métodos: se evaluaron la exactitud, la precisión y la especificidad como parámetros de validación siguiendo la metodología descrita en la Regulación 41-2007 del Centro para el Control Estatal de la Calidad de los Medicamentos (CECMED para la Validación de métodos de análisis. Resultados: en el estudio de exactitud no se observaron diferencias significativas entre los valores de peso del útero obtenidos al ensayar la muestra y el material de referencia a las tres dosis administradas. En el estudio de la repetibilidad se alcanzaron coeficientes de variación menor del 50 %. No se observaron diferencias significativas entre las precisiones alcanzadas por dos analistas diferentes en días diferentes. El estudio de especificidad mostró que los excipientes o sustancias auxiliares de la formulación no interfieren en la valoración biológica del producto. Conclusiones: el método biológico validado resultó ser específico, exacto y preciso en el rango de concentraciones estudiadas, lo que corrobora su calidad, teniendo un valor agregado.Introduction: a number of biological tests for quality control used in the Center for Drug Research and Development should be validated. Biological potency test of human chorionic gonadotropin is one of them. Objective: to evaluate the performance of the human chorionic gonadotropin biological potency test. Methods: the accuracy, precision and specificity were evaluated as validation parameters according to the 41-2007 Regulation of the Center for the State Control of Drug Quality (CEDMED for analysis method validation. Results: in

  1. Early Evaluation and Monitoring of Critical Patients with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms.

    Science.gov (United States)

    Horhat, Florin G; Gundogdu, Fuat; David, Laurentiu V; Boia, Eugen S; Pirtea, Laurentiu; Horhat, Razvan; Cucui-Cozma, Alexandru; Ciuca, Ioana; Diaconu, Mircea; Nitu, Razvan; Licker, Monica; Horhat, Delia I; Rogobete, Alexandru F; Moise, Marius L; Tataru, Calin

    2017-06-01

    A high percentage of critical patients are found to develop acute respiratory distress syndrome (ARDS). Several studies have reported high mortality rates in these cases which are most frequently associated with multiple organ dysfunctions syndrome. Lately, many efforts have been made to evaluate and monitor ARDS in critical patients. In this regard, the assessment of genetic polymorphisms responsible for developing ARDS present as a challenge and are considered future biomarkers. Early detection of the specific polymorphic gene responsible for ARDS in critically ill patients can prove to be a useful tool in the future, able to help decrease the mortality rates in these cases. Moreover, identifying the genetic polymorphism in these patients can help in the implementation of a personalized intensive therapy scheme for every type of patient, based on its genotype.

  2. Evaluation of accuracy of virtual surgical planning for patient-specific pre-contoured plate in acetabular fracture fixation.

    Science.gov (United States)

    Maini, Lalit; Verma, Tarun; Sharma, Amit; Sharma, Ankur; Mishra, Abhishek; Jha, Sunil

    2018-01-24

    Acetabular fractures are amongst the most challenging fractures to treat because of complex anatomy. Open reduction and internal fixation remains the standard treatment for displaced acetabular fractures to achieve anatomical reduction as in any other intra-articular fracture. Patient-specific pre-contoured reconstruction plate template made by a pre-operative virtual surgical planning can be useful to respect patient's morphology, reduce surgical invasiveness and simplify the surgical procedure. Proper evaluation and surgical planning is necessary to achieve these goals. The goal of this study was to evaluate the outcomes of using virtual surgical planning and virtually pre-contoured plate template in comparison with the conventional method of intra-operative contouring of reconstruction plate for acetabular fracture fixation. Twenty-five patients were categorized into group A and B by computerized randomization. In group A (12 patients), CT-based virtual surgical planning was done using Mimics and 3-Matic software to form virtually pre-contoured plates, which were 3D printed to act as templates over which 3.5 mm reconstruction plates were manually contoured pre-operatively and used for fixation. In group B (13 patient), conventional method of intra-operative contouring to adapt the plate to the fracture region was followed. Blood loss, surgical time, reduction on X-rays and post-operative computed tomography were compared between two groups. Duration of surgery and total blood loss were found to be less while reduction was found to satisfactory/anatomical in higher percentage of Group A than Group B patients. Virtual surgical planning, patient-specific virtually pre-contoured plate template and 3D printing technology improve the outcomes of acetabular fracture surgery by reducing duration and invasiveness of surgery and improving the quality of reduction. However, studies with larger sample size are required to further validate it.

  3. A Prospective Evaluation of Lymphedema-Specific Quality-of-Life Outcomes Following Vascularized Lymph Node Transfer.

    Science.gov (United States)

    Patel, Ketan M; Lin, Chia-Yu; Cheng, Ming-Huei

    2015-07-01

    Microsurgical techniques for the treatment of lymphedema rapidly increased in popularity. Although surgical success with vascularized lymph node (VLN) transfer has been demonstrated, limited studies have investigated the influence of microsurgical treatments on health-related quality-of-life (HRQoL) parameters. The aim of this study was to prospectively evaluate changes in HRQoL following VLN transfer for upper- and lower-extremity lymphedema using a validated instrument. An Institutional Review Board-approved prospective study was performed of patients who underwent VLN transfer for symptomatic upper- or lower-limb lymphedema. A validated lymphedema-specific questionnaire-lymphoedema quality-of-life study-was utilized to assess specific quality-of-life parameters at multiple time points during the 12-month perioperative period. For a comparison with HRQoL metrics, limb circumference measurements were obtained to assess circumference differentiation. Twenty-five patients met the study criteria. Limb circumference analysis revealed significant early improvements following VLN transfer, with continued improvement during the study period (upper-limb lymphedema: 24.4 %; lower-limb lymphedema: 35.2 %). These improvements were mirrored by improvements in all HRQoL domains and overall quality of life (p lymphedema with VLN transfer procedures effectively decrease limb circumference. This improvement is mirrored by improvements in patient-reported outcomes and quality of life. These changes can be observed as soon as 1 month postoperatively, and continued steady improvement can be expected.

  4. [Clinical and electroencephalographic characteristics of specific language impairment in children and an evaluation of the efficacy of cerebrolysin].

    Science.gov (United States)

    Chutko, L S; Surushkina, S Yu; Yakovenko, E A; Sergeev, A V; Rozhkova, A V; Anosova, L V; Chistyakova, N P

    2015-01-01

    To study different forms of specific language impairment in children and to evaluate the efficacy of cerebrolysin in clinical and electroencephalographic aspects. Authors examined 60 children, aged 5-7 years, with a specific language impairment (SLI). The study showed the significantly higher severity of speech disorders, a higher degree of asthenia and dyspraxia/dysgnosia in a group of children with a disorder of receptive language (SLI-R) compared to children with a disorder of expressive speech (SLI-E). A comparative analysis of the EEG power spectra showed large values of slow theta-band EEG in children with SLI compared with healthy children. Children with SLI-R were characterized by the increase in theta rhythm power in the occipital region compared with children with SLI-E. The high efficacy of cerebrolysin in the treatment of this disease (an improvement was obtained in 73.3% of cases) was demonstrated, with the best effect in children with SLI-E (80.0% of cases).

  5. In vitro evaluation of Lactobacillus gasseri strains of infant origin on adhesion and aggregation of specific pathogens.

    Science.gov (United States)

    Ferreira, Celia Lucia; Grześkowiak, Lukasz; Collado, Maria Carmen; Salminen, Seppo

    2011-09-01

    Numerous Lactobacillus species are members of the normal healthy human intestinal microbiota, and members of the Lactobacillus family predominate among the current marketed probiotic strains. Most of the current commercial probiotic strains have not been selected for specific applications but rather have been chosen based on their technological properties. Often the ability of such strains to temporarily colonize the gastrointestinal tract may be lacking, and the interactions with intestinal microbiota are few. Furthermore, the competitive exclusion properties of potential probiotic bacteria are strain specific and vary greatly. Thus, it is highly desirable that new candidate probiotic isolates originate from the healthy target population. In this study, seven newly isolated strains of Lactobacillus gasseri originating from feces of a healthy newborn child were evaluated for their ability to adhere to intestinal mucus, to autoaggregate and coaggregate with the model pathogens Cronobacter sakazakii (ATCC 29544) and Clostridium difficile (1296). All the bacterial strains, single or in combination, in viable and nonviable forms, were able to autoaggregate. The coaggregation with C. sakazakii or C. difficile was higher (P gasseri strains showed similar adhesion abilities to intestinal colon mucus. The seven L. gasseri strains when combined were also able to significantly compete with, displace, and inhibit the adhesion of C. sakazakii and C. difficile in the mucus model. This study demonstrates that the studied L. gasseri strains fulfill the basic adhesion and aggregation properties for probiotics and could be considered for potential future use in children.

  6. Evaluation of specificity and sensitivity of gastric aspirate shake test to predict surfactant deficiency in Iranian premature infants.

    Science.gov (United States)

    Mehrpisheh, Shahrokh; Mosayebi, Ziba; Memarian, Azadeh; Kadivar, Malihe; Nariman, Shahin; Ostadrahimi, Pouya; Dalili, Hosein

    2015-04-01

    Respiratory failure secondary to pulmonary surfactant deficiency is an important cause of severe respiratory distress in term and preterm infants. The aim of this study was to evaluate the specificity and sensitivity of gastric aspirate shake test (GAST) to predict surfactant deficiency in newly born premature infants in Arash Hospital (Iran) during 2012-13. In this case-control study, the case group comprised 69 premature infants (gestational ageneonatal intensive care unit due to respiratory distress. The control group included 50 healthy infants .GAST test was done. The subjects were finally categorized as healthy or surfactant-deficient based on clinical and radiological assessments. Using statistical methods the sensitivity, specificity, and positive and negative predictive values of GAST were 60%, 75%, 15%, and 52%, respectively. There was a significant difference between respiratory distress syndrome (RDS) scores and receiving surfactant in neonates with gestational age below 34 weeks. Moreover, there were significant differences between GAST results and both radiological findings of RDS and receiving oxygen in premature infants (gestational ageneonates who were born to mothers with hypothyroidism, preeclampsia, diabetes mellitus, and premature rupture of membranes. However, this difference was not significant. According to our findings, the application of GAST on gastric aspirate secretions is not a useful method to predict surfactant deficiency. Therefore, decisions for RDS management must be made based on clinical and radiological findings. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  7. Risk assessment of oncogenic potency of pesticide residues in fruits and vegetables.

    Science.gov (United States)

    Keikotlhaile, B M; Spanoghe, P; Steurbaut, W

    2011-01-01

    Pesticides are used in agriculture to improve food security by assuring good harvest, however, they can have harmful effects in human beings and animals. One of the harmful effects of pesticides is their carcinogenicity. Exposure to oncogenic compounds may result in cancer to the exposed animal or person. In this paper, exposure assessment of oncogenic potency of pesticides was performed from raw and processed fruits and vegetables. The oncogenic risk was calculated by multiplying the estimated daily intake (EDI) of the pesticide residue with the oncogenic potency factor (Q*) of the concerned pesticide. The total potential oncogenic risk was calculated to be 2.76 x 10(-3) before processing and 8.97 x 10(-4) after processing. The risk was higher than the EPA acceptable limit of 1 x10(-6). Despite the calculated levels exceeding the EPA acceptable limit, food processing activities reduced the dietary oncogenic risk to an average 33.8%.

  8. Evaluating species-specific changes in hydrologic regimes: an iterative approach for salmonids in the Greater Yellowstone Area (USA)

    Science.gov (United States)

    Al-Chokhachy, Robert K.; Sepulveda, Adam; Ray, Andrew M.; Thoma, David P.; Tercek, Michael T.

    2017-01-01

    Despite the importance of hydrologic regimes to the phenology, demography, and abundance of fishes such as salmonids, there have been surprisingly few syntheses that holistically assess regional, species-specific trends in hydrologic regimes within a framework of climate change. Here, we consider hydrologic regimes within the Greater Yellowstone Area in the Rocky Mountains of western North America to evaluate changes in hydrologic metrics anticipated to affect salmonids, a group of fishes with high regional ecological and socioeconomic value. Our analyses assessed trends across different sites and time periods (1930–, 1950–, and 1970–2015) as means to evaluate spatial and temporal shifts. Consistent patterns emerged from our analyses indicating substantial shifts to (1) earlier peak discharge events; (2) reductions of summer minimum streamflows; (3) declines in the duration of river ice; and (4) decreases in total volume of water. We found accelerated trends in hydrologic change for the 1970–2015 period, with an average peak discharge 7.5 days earlier, 27.5% decline in summer minimum streamflows, and a 15.6% decline in the annual total volume of water (1 October–September 30) across sites. We did observe considerable variability in magnitude of change across sites, suggesting different levels of vulnerability to a changing climate. Our analyses provide an iterative means for assessing climate predictions and an important step in identifying the climate resilience of landscapes.

  9. Ready for goal setting? Process evaluation of a patient-specific goal-setting method in physiotherapy.

    Science.gov (United States)

    Stevens, Anita; Köke, Albère; van der Weijden, Trudy; Beurskens, Anna

    2017-08-31

    Patient participation and goal setting appear to be difficult in daily physiotherapy practice, and practical methods are lacking. An existing patient-specific instrument, Patient-Specific Complaints (PSC), was therefore optimized into a new Patient Specific Goal-setting method (PSG). The aims of this study were to examine the feasibility of the PSG in daily physiotherapy practice, and to explore the potential impact of the new method. We conducted a process evaluation within a non-controlled intervention study. Community-based physiotherapists were instructed on how to work with the PSG in three group training sessions. The PSG is a six-step method embedded across the physiotherapy process, in which patients are stimulated to participate in the goal-setting process by: identifying problematic activities, prioritizing them, scoring their abilities, setting goals, planning and evaluating. Quantitative and qualitative data were collected among patients and physiotherapists by recording consultations and assessing patient files, questionnaires and written reflection reports. Data were collected from 51 physiotherapists and 218 patients, and 38 recordings and 219 patient files were analysed. The PSG steps were performed as intended, but the 'setting goals' and 'planning treatment' steps were not performed in detail. The patients and physiotherapists were positive about the method, and the physiotherapists perceived increased patient participation. They became aware of the importance of engaging patients in a dialogue, instead of focusing on gathering information. The lack of integration in the electronic patient system was a major barrier for optimal use in practice. Although the self-reported actual use of the PSG, i.e. informing and involving patients, and client-centred competences had improved, this was not completely confirmed by the objectively observed behaviour. The PSG is a feasible method and tends to have impact on increasing patient participation in the goal

  10. Treatment of hypergranulation tissue with high potency topical corticosteroids in children.

    Science.gov (United States)

    McShane, Diana B; Bellet, Jane S

    2012-01-01

    Hypergranulation is having more granulation tissue than needed to fill a wound defect. Some pediatric dermatologists and most dermatologic surgeons will encounter this complication during their careers. Associated factors include wound site, prolonged inflammation, an imbalance in matrix metalloproteinases, and excessive angiogenesis. Reported treatments have included silver nitrate, excision, laser ablation, and topical corticosteroids. Our case series supports the use of medium- to high-potency topical corticosteroids in the treatment of hypergranulation tissue. © 2012 Wiley Periodicals, Inc.

  11. BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells.

    Science.gov (United States)

    Beswick, Paul; Charrier, Nicolas; Clarke, Brian; Demont, Emmanuel; Dingwall, Colin; Dunsdon, Rachel; Faller, Andrew; Gleave, Robert; Hawkins, Julie; Hussain, Ishrut; Johnson, Christopher N; MacPherson, David; Maile, Graham; Matico, Rosalie; Milner, Peter; Mosley, Julie; Naylor, Alan; O'Brien, Alistair; Redshaw, Sally; Riddell, David; Rowland, Paul; Skidmore, John; Soleil, Virginie; Smith, Kathrine J; Stanway, Steven; Stemp, Geoffrey; Stuart, Alistair; Sweitzer, Sharon; Theobald, Pam; Vesey, David; Walter, Daryl S; Ward, John; Wayne, Gareth

    2008-02-01

    This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

  12. Traditional marijuana, high-potency cannabis and synthetic cannabinoids:increasing risk for psychosis

    OpenAIRE

    Murray, Robin M.; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

    2016-01-01

    Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose-response relationship between the level of use and the risk of later psychosis. High-potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co-administration of cannabidiol....

  13. Parametric Effect of Sodium Hydroxide and Sodium Carbonate on the Potency of a Degreaser

    OpenAIRE

    Babatope Abimbola Olufemi

    2016-01-01

    Experimental and statistical analysis was carried out on the comparative effect of sodium hydroxide and sodium carbonate on the potency of a laboratory produced degreaser in this work. The materials used include; octadecyl benzene sulphonic acid, sodium hydroxide, sodium carbonate, sodium metasilicate, carboxyl methyl cellulose (C.M.C), formadelhyde, perfume, colourant and distilled water. Different samples of degreaser were produced with varying composition of sodium hydroxide and sodium car...

  14. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance

    Directory of Open Access Journals (Sweden)

    Nishant A. Dafale

    2016-08-01

    Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC, minimum bactericidal concentration (MBC, mutation prevention concentration (MPC and critical concentration (Ccr which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

  15. Monitoring blend potency in a tablet press feed frame using near infrared spectroscopy.

    Science.gov (United States)

    Ward, Howard W; Blackwood, Daniel O; Polizzi, Mark; Clarke, Hugh

    2013-06-01

    A near-infrared (NIR) probe was installed into the feed frame of a rotary tablet press to monitor API concentration as a function of time. A series of step change experimental trials were completed, where a placebo blend was initially charged into the feed frame, and an active blend was layered above. The compression process was initiated, and process parameters, such as mass throughput rate, and feed frame paddle wheel speed were systematically varied. For the range of mass throughput rates studied, excellent correlations were shown between the NIR signal and weight corrected tablet potency from stratified tablet samples. A similar correlation was demonstrated for higher feed frame paddle wheel speeds. However, for lower feed frame paddle wheel speeds, a bias was observed between weight corrected tablet potency and the NIR signal. This finding suggests that compression process parameters, such as paddle wheel rotational speed and NIR probe location, must be optimized for different tablet press geometries to ensure that the NIR process signal can be related to tablet potency. This emerging application of Process Analytical Technology (PAT) may be used to identify powder segregation events during discharge of powder from an intermediate bulk container (IBC) or as a development tool to further understand powder mixing dynamics occurring within the feed frame. This may also be used as a diagnostic tool for fault detection during tablet compression. Finally, this PAT application may also be integrated with the tablet press control system as a gating or reject device for sub or super-potent tablets or enable Real-Time-Release testing (RTRt) through the continuous monitoring of the potency and homogeneity of powder circulating within the feed frame. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Nutrient Potency of Rice Straw Processed with Amofer as Cattle Feed Stuff in East Kalimantan

    OpenAIRE

    Hamdi Mayulu; Suhardi Suhardi

    2015-01-01

    Forage demand can be supplied from rice straw which processed with certain feed technology innovation. Some advantages can be derived under this technology i.e. increasing nutrient content, optimizing the utilization, improving the efficiency and reducing production cost by minimizing feed cost. Ammoniation fermentation (amofer) as an applied technology could give solution over the limitation of rice straw availability. The objective of this research was to determine the potency of rice straw...

  17. Carboxylic ionophores enhance the cytotoxic potency of ligand- and antibody-delivered ricin A chain

    Science.gov (United States)

    1984-01-01

    The highly selective cytotoxicity of site-directed ricin A chain conjugates can be potentiated by membrane-active carboxylic ionophores. The combined use of the two agents results in much faster inactivation of ribosomes and subsequent cell death and lysis. The potency of A chain cytotoxins is correspondingly increased by several orders of magnitude and cells that sparsely express the target antigen or receptor can be killed. PMID:6090575

  18. How Precise Are Preinterventional Measurements Using Centerline Analysis Applications? Objective Ground Truth Evaluation Reveals Software-Specific Centerline Characteristics.

    Science.gov (United States)

    Hoegen, Philipp; Wörz, Stefan; Müller-Eschner, Matthias; Geisbüsch, Philipp; Liao, Wei; Rohr, Karl; Schmitt, Matthias; Rengier, Fabian; Kauczor, Hans-Ulrich; von Tengg-Kobligk, Hendrik

    2017-08-01

    To evaluate different centerline analysis applications using objective ground truth from realistic aortic aneurysm phantoms with precisely defined geometry and centerlines to overcome the lack of unknown true dimensions in previously published in vivo validation studies. Three aortic phantoms were created using computer-aided design (CAD) software and a 3-dimensional (3D) printer. Computed tomography angiograms (CTAs) of phantoms and 3 patients were analyzed with 3 clinically approved and 1 research software application. The 3D centerline coordinates, intraluminal diameters, and lengths were validated against CAD ground truth using a dedicated evaluation software platform. The 3D centerline position mean error ranged from 0.7±0.8 to 2.9±2.5 mm between tested applications. All applications calculated centerlines significantly different from ground truth. Diameter mean errors varied from 0.5±1.2 to 1.1±1.0 mm among 3 applications, but exceeded 8.0±11.0 mm with one application due to an unsteady distortion of luminal dimensions along the centerline. All tested commercially available software tools systematically underestimated centerline total lengths by -4.6±0.9 mm to -10.4±4.3 mm (maximum error -14.6 mm). Applications with the highest 3D centerline accuracy yielded the most precise diameter and length measurements. One clinically approved application did not provide reproducible centerline-based analysis results, while another approved application showed length errors that might influence stent-graft choice and procedure success. The variety and specific characteristics of endovascular aneurysm repair planning software tools require scientific evaluation and user awareness.

  19. Evaluation of a subject-specific female gymnast model and simulation of an uneven parallel bar swing.

    Science.gov (United States)

    Sheets, Alison L; Hubbard, Mont

    2008-11-14

    A gymnast model and forward dynamics simulation of a dismount preparation swing on the uneven parallel bars were evaluated by comparing experimental and predicted joint positions throughout the maneuver. The bar model was a linearly elastic spring with a frictional bar/hand interface, and the gymnast model consisted of torso/head, arm and two leg segments. The hips were frictionless balls and sockets, and shoulder movement was planar with passive compliant structures approximated by a parallel spring and damper. Subject-specific body segment moments of inertia, and shoulder compliance were estimated. Muscles crossing the shoulder and hip were represented as torque generators, and experiments quantified maximum instantaneous torques as functions of joint angle and angular velocity. Maximum torques were scaled by joint torque activations as functions of time to produce realistic motions. The downhill simplex method optimized activations and simulation initial conditions to minimize the difference between experimental and predicted bar-center, shoulder, hip, and ankle positions. Comparing experimental and simulated performances allowed evaluation of bar, shoulder compliance, joint torque, and gymnast models. Errors in all except the gymnast model are random, zero mean, and uncorrelated, verifying that all essential system features are represented. Although the swing simulation using the gymnast model matched experimental joint positions with a 2.15cm root-mean-squared error, errors are correlated. Correlated errors indicate that the gymnast model is not complex enough to exactly reproduce the experimental motion. Possible model improvements including a nonlinear shoulder model with active translational control and a two-segment torso would not have been identified if the objective function did not evaluate the entire system configuration throughout the motion. The model and parameters presented in this study can be effectively used to understand and improve an uneven

  20. Design and Kinematic Evaluation of a Novel Joint-Specific Play Controller: Application for Wrist and Forearm Therapy.

    Science.gov (United States)

    Crisco, Joseph J; Schwartz, Joel B; Wilcox, Bethany; Costa, Laura; Kerman, Karen

    2015-07-01

    The wrist extensors and flexors are profoundly affected in most children with hemiparetic cerebral palsy (CP) and are the major target of physical therapists' and occupational therapists' efforts to restore useful hand functions. A limitation of any therapeutic or exercise program can be the level of the child's engagement or adherence. The proposed approach capitalizes on the primary learning avenue for children: toy play. This study aimed to develop and evaluate the measurement accuracy of innovative, motion-specific play controllers that are engaging rehabilitative devices for enhancing therapy and promoting neural plasticity and functional recovery in children with CP. Design objectives of the play controller included a cost-effective, home-based supplement to physical therapy, the ability to calibrate the controller so that play can be accomplished with any active range of motion, and the capability of logging play activity and wrist motion over week-long periods. Accuracy of the play controller in measuring wrist flexion-extension was evaluated in 6 children who were developing in a typical manner, using optical motion capture of the wrist and forearm as the gold standard. The error of the play controller was estimated at approximately 5 degrees in both maximum wrist flexion and extension. Measurements were taken during a laboratory session, with children without CP, and no toy or computer game was interfaced with the play controller. Therefore, the potential engagement of the proposed approach for therapy remains to be evaluated. This study presented the concept, development, and wrist tracking accuracy of an inexpensive approach to extremity therapy that may have a health benefit for children with hemiparesis, and potentially for patients of any age with a wide range of extremity neuromotor impairments. © 2015 American Physical Therapy Association.

  1. Laboratory evaluation of the molluscicidal potency of a butanol extract of Phytolacca dodecandra (endod) berries.

    Science.gov (United States)

    Baalawy, S S

    1972-01-01

    The effect of butanol extracts of endod against Biomphalaria choanomphala, B. pfeifferi, and Bulinus (Physopsis) nasutus was tested at different concentrations and for different exposure periods. Exposure to 19-25 ppm for 6 hours or to 6-7 ppm for 24 hours caused about 100% mortality.

  2. Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure.

    Science.gov (United States)

    Wang, Zimian; Ying, Zhiliang; Bosy-Westphal, Anja; Zhang, Junyi; Schautz, Britta; Later, Wiebke; Heymsfield, Steven B; Müller, Manfred J

    2010-12-01

    The specific resting metabolic rates (K(i); in kcal · kg(-1 )· d(-1)) of major organs and tissues in adults were suggested by Elia (in Energy metabolism: tissue determinants and cellular corollaries. New York, NY: Raven Press, 1992) to be as follows: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue, and 12 for residual organs and tissues. However, Elia's K(i) values have never been fully evaluated. The objectives of the present study were to evaluate the applicability of Elia's K(i) values across adulthood and to explore the potential influence of age on the K(i) values. A new approach was developed to evaluate the K(i) values of major organs and tissues on the basis of a mechanistic model: REE = Σ(K(i) × T(i)), where REE is whole-body resting energy expenditure measured by indirect calorimetry, and T(i) is the mass of individual organs and tissues measured by magnetic resonance imaging. With measured REE and T(i), marginal 95% CIs for K(i) values were calculated by stepwise univariate regression analysis. An existing database of nonobese, healthy adults [n = 131; body mass index (in kg/m²) middle-age, n = 51), and > 50 y (n = 37). Elia's K(i) values were within the range of 95% CIs in the young and middle-age groups. However, Elia's K(i) values were outside the right boundaries of 95% CIs in the >50-y group, which indicated that Elia's study overestimated K(i) values by 3% in this group. Age-adjusted K(i) values for adults aged >50 y were 194 for liver, 233 for brain, 426 for heart and kidneys, 12.6 for skeletal muscle, 4.4 for adipose tissue, and 11.6 for residuals. The general applicability of Elia's K(i) values was validated across adulthood, although age adjustment is appropriate for specific applications.

  3. Diseño y simulación de un potenciómetro digital de 6 bits

    OpenAIRE

    Díaz-Regañón Guerra, Armando Jesús

    2012-01-01

    En el presente documento se detalla el diseño y la simulación de un potenciómetro digital lineal de resolución seis bits junto con el correspondiente diseño del circuito impreso (PCB) para su posterior montaje y fabricación. El potenciómetro digital se ha diseñado utilizando componentes analógicos y dispositivos electrónicos como los optoacopladores y un regulador de tensión. La utilidad del potenciómetro, es obtener una corriente de salida del sistema configurable en 26 valores de corrientes...

  4. A common genetic influence on human intensity ratings of sugars and high-potency sweeteners.

    Science.gov (United States)

    Hwang, Liang-Dar; Zhu, Gu; Breslin, Paul A S; Reed, Danielle R; Martin, Nicholas G; Wright, Margaret J

    2015-08-01

    The perception of sweetness varies among individuals but the sources of this variation are not fully understood. Here, in a sample of 1,901 adolescent and young adults (53.8% female; 243 MZ and 452 DZ twin pairs, 511 unpaired individuals; mean age 16.2±2.8, range 12–26 years), we studied the variation in the perception of sweetness intensity of two monosaccharides and two high-potency sweeteners: glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame. Perceived intensity for all sweeteners decreased with age (2–5% per year) and increased with the history of otitis media (6–9%). Males rated aspartame slightly stronger than females (7%). We found similar heritabilities for sugars (glucose: h2=0.31, fructose: h2=0.34) and high-potency sweeteners (NHDC: h2=0.31, aspartame: h2=0.30); all were in the modest range. Multivariate modeling showed that a common genetic factor accounted for >75% of the genetic variance in the four sweeteners, suggesting that individual differences in perceived sweet intensity, which are partly due to genetic factors, may be attributed to a single set of genes. This study provided evidence of the shared genetic pathways between the perception of sugars and high-potency sweeteners.

  5. α-Conotoxin dendrimers have enhanced potency and selectivity for homomeric nicotinic acetylcholine receptors.

    Science.gov (United States)

    Wan, Jingjing; Huang, Johnny X; Vetter, Irina; Mobli, Mehdi; Lawson, Joshua; Tae, Han-Shen; Abraham, Nikita; Paul, Blessy; Cooper, Matthew A; Adams, David J; Lewis, Richard J; Alewood, Paul F

    2015-03-11

    Covalently attached peptide dendrimers can enhance binding affinity and functional activity. Homogenous di- and tetravalent dendrimers incorporating the α7-nicotinic receptor blocker α-conotoxin ImI (α-ImI) with polyethylene glycol spacers were designed and synthesized via a copper-catalyzed azide-alkyne cycloaddition of azide-modified α-ImI to an alkyne-modified polylysine dendron. NMR and CD structural analysis confirmed that each α-ImI moiety in the dendrimers had the same 3D structure as native α-ImI. The binding of the α-ImI dendrimers to binding protein Ac-AChBP was measured by surface plasmon resonance and revealed enhanced affinity. Quantitative electrophysiology showed that α-ImI dendrimers had ∼100-fold enhanced potency at hα7 nAChRs (IC50 = 4 nM) compared to native α-ImI (IC50 = 440 nM). In contrast, no significant potency enhancement was observed at heteromeric hα3β2 and hα9α10 nAChRs. These findings indicate that multimeric ligands can significantly enhance conotoxin potency and selectivity at homomeric nicotinic ion channels.

  6. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  7. USDA regulatory guidelines and practices for veterinary Leptospira vaccine potency testing.

    Science.gov (United States)

    Srinivas, G B; Walker, A; Rippke, B

    2013-09-01

    Batch-release potency testing of leptospiral vaccines licensed by the United States Department of Agriculture (USDA) historically was conducted through animal vaccination-challenge models. The hamster vaccination-challenge assay was Codified in 1974 for bacterins containing Leptospira pomona, Leptospira icterohaemorrhagiae, and Leptospira canicola, and in 1975 for bacterins containing Leptospira grippotyphosa. In brief, 10 hamsters are vaccinated with a specified dilution of bacterin. After a holding period, the vaccinated hamsters, as well as nonvaccinated controls, are challenged with virulent Leptospira and observed for mortality. Eighty percent of vaccinated hamsters must survive in the face of a valid challenge. The high cost of the Codified tests, in terms of monetary expense and animal welfare, prompted the Center for Veterinary Biologics (CVB) to develop ELISA alternatives for them. Potency tests for other serogroups, such as Leptospira hardjo-bovis, that do not have Codified requirements for potency testing continue to be examined on a case-by-case basis. Published by Elsevier Ltd.

  8. Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis

    Science.gov (United States)

    Murray, Robin M.; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

    2016-01-01

    Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose‐response relationship between the level of use and the risk of later psychosis. High‐potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co‐administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high‐potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high‐potency cannabis and synthetic cannabinoids. PMID:27717258

  9. Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis.

    Science.gov (United States)

    Murray, Robin M; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

    2016-10-01

    Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose-response relationship between the level of use and the risk of later psychosis. High-potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co-administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high-potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids. © 2016 World Psychiatric Association.

  10. Estimation of the minimum motor blocking potency ratio for intrathecal bupivacaine and lidocaine.

    Science.gov (United States)

    Camorcia, M; Capogna, G; Columb, M O

    2008-07-01

    The up-down sequential allocation model has been adapted to investigate a variety of clinical and pharmacological issues in neuraxial anaesthesia including the estimation of relative potency ratios for analgesia and motor block of the most commonly used epidural and intrathecal local anaesthetics. The aim of this study was to establish the median effective doses (ED50) for motor block with intrathecal lidocaine and bupivacaine and to define the relative motor blocking potency ratio. In this prospective, randomised, double blind, parallel group, up-down sequential allocation study, we enrolled 71 parturients undergoing elective caesarean section under combined spinal-epidural anaesthesia. The women received either intrathecal lidocaine 2% w/v or bupivacaine 0.5% w/v. The initial dose was 4 mg for bupivacaine and 12 mg for lidocaine. Subsequent doses were determined by the outcome in the previous parturient, according to the up-down sequential allocation technique. The end point was the occurrence of any motor block in either lower limb within 5 min. The intrathecal ED50 for motor block was 13.7 mg for lidocaine (95% CI, 13.1 to 14.4) and 3.4 mg for bupivacaine (95% CI, 2.6 to 4.1) (Pmotor blocking potency ratio was 4.1 (95% CI 3.3 to 5.2). Intrathecal bupivacaine was 4.1 times more potent than lidocaine for motor block.

  11. Modulating potency: Physicochemical characteristics are a determining factor of TLR4-agonist nanosuspension activity.

    Science.gov (United States)

    Dowling, Quinton M; Sivananthan, Sandra J; Guderian, Jeff A; Moutaftsi, Magdalini; Chesko, James D; Fox, Christopher B; Vedvick, Thomas S; Kramer, Ryan M

    2014-03-01

    Activity of adjuvanted vaccines is difficult to predict in vitro and in vivo. The wide compositional and conformational range of formulated adjuvants, from aluminum salts to oil-in-water emulsions, makes comparisons between physicochemical and immunological properties difficult. Even within a formulated adjuvant class, excipient selection and concentration can alter potency and physicochemical properties of the mixture. Complete characterization of physicochemical properties of adjuvanted vaccine formulations and relationship to biological response is necessary to move beyond a guess-and-check paradigm toward directed development. Here we present a careful physicochemical characterization of a two-component nanosuspension containing synthetic TLR-4 agonist glucopyranosyl lipid adjuvant (GLA) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at various molar ratios. Physicochemical properties were compared with potency, as measured by stimulation of cytokine production in human whole blood. We found a surprising, nonlinear relationship between physicochemical properties and GLA-DPPC ratios that corresponded well with changes in biological activity. We discuss these data in light of the current understanding of TLR4 activation and the conformation-potency relationship in development of adjuvanted vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Bioassays for evaluation of medical products derived from bacterial toxins.

    Science.gov (United States)

    Sesardic, Thea

    2012-06-01

    Bioassays play central role in evaluation of biological products and those derived from bacterial toxins often rely exclusively on in vivo models for assurance of safety and potency. This chapter reviews existing regulatory approved methods designed to provide information on potency and safety of complex biological medicines with an insight into strategies considered for alternative procedures. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Experimental evaluation and design of unfilled and concrete-filled FRP composite piles : Task 4B : material & construction specifications : final report.

    Science.gov (United States)

    2015-07-01

    The overall goal of this project is the experimental evaluation and design of unfilled and concrete-filled FRP composite piles for load-bearing in bridges. This report covers Task 4B, Materials and Construction Specifications. : This technical report...

  14. THE POTENCY OF DAIRY CATTLE AGRIBUSINESS DEVELOPMENT IN SEMARANG REGENCY, CENTRAL JAVA

    Directory of Open Access Journals (Sweden)

    M. Mukson

    2014-10-01

    Full Text Available The study aimed to analyze the potency of dairy cattle agribusiness development in SemarangRegency and the factors influencing the potency of dairy cattle agribusiness development. The studywas conducted from September to December 2008 in Semarang Regency, Central Java, using surveymethod. Three districts were purposively chosen based on the largest population of dairy cattle in theSemarang Regency. Of the three districts selected, six villages were chosen based on the largestpopulation of dairy cattle. The respondents were chosen randomly using simple random, hence thesample size in this study was 90. Data were gathered through primary and secondary data. The data wereanalyzed descriptively and statistically. The analysis of LQ (Location Quotient was used to analyze thepotency of dairy cattle agribusiness development, while the multiple regression model was used todetermine the factors affecting the potency of dairy cattle agribusiness development, with the followingregression equation: Y = a + b1x1 + b2x2 + b3x3 + b4x4 + b5x5 b7x7 b6x6 + + + e, whereas Y = is theproduction of milk, and x1 to X7, respectively, are x1 (age, x2 (education, x3 (Number of familymembers, x4 (number of lactating cows, x5 ( amount of feed, forage, x6 (amount of feed concentrateand X7 (calving interval. The results showed that the potency of dairy cattle agribusiness developmentin Semarang Regency is potential (LQ> 1 with the value of 4.67 and LQ Population GDP = 1.71. Thisstudy indicated that socio, economic and demographic resources are important factors that can helpdevelop and improve dairy cattle farming. Meanwhile, there were significant relationships between 7independent factors and the potency of dairy cattle agribusiness development, with the followingregression equation: Y = -6.082 + 0.032 x1 + 0.223 x2 + 0.717 x3 + 9.221 x4 + 0.067 x5 x6 + 0.486 -0.323 X7 + e. Moreover, the value of R2 = 0.886, it is indicated that 88.6% of the variation in the thedependent

  15. Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine.

    Science.gov (United States)

    Brelsford, Jill B; Plieskatt, Jordan L; Yakovleva, Anna; Jariwala, Amar; Keegan, Brian P; Peng, Jin; Xia, Pengjun; Li, Guangzhao; Campbell, Doreen; Periago, Maria Victoria; Correa-Oliveira, Rodrigo; Bottazzi, Maria Elena; Hotez, Peter J; Diemert, David; Bethony, Jeffrey M

    2017-02-01

    A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2-8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines.

  16. Evaluation of a multiple food specific IgE antibody test compared to parental perception, allergy skin tests and RAST.

    Science.gov (United States)

    Adler, B R; Assadullahi, T; Warner, J A; Warner, J O

    1991-11-01

    This study was set up to evaluate the food panel of a multiple specific IgE antibody assay in 67 atopic asthmatic children by comparing it to the conventional radioallergosorbent test (RAST) and skin-prick tests (SPT) and then comparing the results of these investigations with the parents' perceptions of food related problems. Fifteen food specific IgE antibodies were measured using the multiple chemiluminescence assay (MAST-CLA). IgE antibodies to five of these food allergens were also measured by conventional RAST and SPTs were performed in 43 using 11 standardized food extracts matched to the multiple allergosorbent chemiluminescent assay (MAST-CLA) profile. SPT and MAST-CLA results showed good agreement with one another, range 68.8-96.7% (average 87%), with significant correlation for most allergens tested. MAST-CLA was discrepant with RAST and/or SPTs in 58/210 (27.6%). A questionnaire was sent to the parents to determine their perception of food related symptoms. Sixty-two (92%) questionnaire replies were received, of which 56% reported symptoms with food. The most frequent symptom perceived to be due to food intolerance was behavioural disturbance. The commonest foods implicated were additives (39%), egg (27%), milk (26%), chocolate (23%) and orange (15%). History, SPT, MAST-CLA and RAST were compared for five allergens in 42 patients (210 values). In 14/210 (6.7%), all the tests were negative despite reported symptoms. Conversely in 49/210 (23.3%) at least one test was positive without symptoms. This study did not support a benefit of multipole testing instead of individually selected RASTs or SPTs.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Evaluation of a subject-specific finite-element model of the equine metacarpophalangeal joint under physiological load.

    Science.gov (United States)

    Harrison, Simon M; Whitton, R Chris; Kawcak, Chris E; Stover, Susan M; Pandy, Marcus G

    2014-01-03

    The equine metacarpophalangeal (MCP) joint is frequently injured, especially by racehorses in training. Most injuries result from repetitive loading of the subchondral bone and articular cartilage rather than from acute events. The likelihood of injury is multi-factorial but the magnitude of mechanical loading and the number of loading cycles are believed to play an important role. Therefore, an important step in understanding injury is to determine the distribution of load across the articular surface during normal locomotion. A subject-specific finite-element model of the MCP joint was developed (including deformable cartilage, elastic ligaments, muscle forces and rigid representations of bone), evaluated against measurements obtained from cadaver experiments, and then loaded using data from gait experiments. The sensitivity of the model to force inputs, cartilage stiffness, and cartilage geometry was studied. The FE model predicted MCP joint torque and sesamoid bone flexion angles within 5% of experimental measurements. Muscle-tendon forces, joint loads and cartilage stresses all increased as locomotion speed increased from walking to trotting and finally cantering. Perturbations to muscle-tendon forces resulted in small changes in articular cartilage stresses, whereas variations in joint torque, cartilage geometry and stiffness produced much larger effects. Non-subject-specific cartilage geometry changed the magnitude and distribution of pressure and the von Mises stress markedly. The mean and peak cartilage stresses generally increased with an increase in cartilage stiffness. Areas of peak stress correlated qualitatively with sites of common injury, suggesting that further modelling work may elucidate the types of loading that precede joint injury and may assist in the development of techniques for injury mitigation. © 2013 Published by Elsevier Ltd.

  18. Biological evaluation of a novel Herceptin-platinum (II) conjugate for efficient and cancer cell specific delivery.

    Science.gov (United States)

    Huang, Rong; Sun, Yu; Zhang, Xiang-yang; Sun, Bai-wang; Wang, Qiu-cui; Zhu, Jin

    2015-07-01

    Platinum-based drugs have been widely used for the treatment of malignant tumors. However, their applications are limited by severe side effects for their lack of selectivity for cancer cells. The development of antibody drug conjugates (ADCs) have provided a platform to reduce drug toxicity and improve drug efficacy. Here we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and platinum drug via a cathepsin B cleavable dipetide for enhancing drug accumulation and HER2-positive cancer cell specific delivery. This conjugate is believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and activation of drug release. Herceptin-Pt(II) is evaluated to have approximately loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR-3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary, Herceptin-platinum (II) conjugate is a remarkable and potent platform for efficient and cancer cell specific delivery. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Clinimetric evaluation of methods to measure muscle functioning in patients with non-specific neck pain: a systematic review.

    Science.gov (United States)

    de Koning, Chantal H P; van den Heuvel, Sylvia P; Staal, J Bart; Smits-Engelsman, Bouwien C M; Hendriks, Erik J M

    2008-10-19

    Neck pain is a significant health problem in modern society. There is evidence to suggest that neck muscle strength is reduced in patients with neck pain. This article provides a critical analysis of the research literature on the clinimetric properties of tests to measure neck muscle strength or endurance in patients with non-specific neck pain, which can be used in daily practice. A computerised literature search was performed in the Medline, CINAHL and Embase databases from 1980 to January 2007. Two reviewers independently assessed the clinimetric properties of identified measurement methods, using a checklist of generally accepted criteria for reproducibility (inter- and intra-observer reliability and agreement), construct validity, responsiveness and feasibility. The search identified a total of 16 studies. The instruments or tests included were: muscle endurance tests for short neck flexors, craniocervical flexion test with an inflatable pressure biofeedback unit, manual muscle testing of neck musculature, dynamometry and functional lifting tests (the cervical progressive iso-inertial lifting evaluation (PILE) test and the timed weighted overhead test). All the articles included report information on the reproducibility of the tests. Acceptable intra- and inter-observer reliability was demonstrated for t enduranctest for short neck flexors and the cervical PILE test. Construct validity and responsiveness have hardly been documented for tests on muscle functioning. The endurance test of the short neck flexors and the cervical PILE test can be regarded as appropriate instruments for measuring different aspects of neck muscle function in patients with non-specific neck pain. Common methodological flaws in the studies were their small sample size and an inappropriate description of the study design.

  20. Clinimetric evaluation of methods to measure muscle functioning in patients with non-specific neck pain: a systematic review

    Directory of Open Access Journals (Sweden)

    Smits-Engelsman Bouwien CM

    2008-10-01

    Full Text Available Abstract Background Neck pain is a significant health problem in modern society. There is evidence to suggest that neck muscle strength is reduced in patients with neck pain. This article provides a critical analysis of the research literature on the clinimetric properties of tests to measure neck muscle strength or endurance in patients with non-specific neck pain, which can be used in daily practice. Methods A computerised literature search was performed in the Medline, CINAHL and Embase databases from 1980 to January 2007. Two reviewers independently assessed the clinimetric properties of identified measurement methods, using a checklist of generally accepted criteria for reproducibility (inter- and intra-observer reliability and agreement, construct validity, responsiveness and feasibility. Results The search identified a total of 16 studies. The instruments or tests included were: muscle endurance tests for short neck flexors, craniocervical flexion test with an inflatable pressure biofeedback unit, manual muscle testing of neck musculature, dynamometry and functional lifting tests (the cervical progressive iso-inertial lifting evaluation (PILE test and the timed weighted overhead test. All the articles included report information on the reproducibility of the tests. Acceptable intra- and inter-observer reliability was demonstrated for t enduranctest for short neck flexors and the cervical PILE test. Construct validity and responsiveness have hardly been documented for tests on muscle functioning. Conclusion The endurance test of the short neck flexors and the cervical PILE test can be regarded as appropriate instruments for measuring different aspects of neck muscle function in patients with non-specific neck pain. Common methodological flaws in the studies were their small sample size and an inappropriate description of the study design.

  1. Evaluation of the sensitivity and specificity of bovine tuberculosis diagnostic tests in naturally infected cattle herds using a Bayesian approach.

    Science.gov (United States)

    Alvarez, Julio; Perez, Andrés; Bezos, Javier; Marqués, Sergio; Grau, Anna; Saez, Jose Luis; Mínguez, Olga; de Juan, Lucía; Domínguez, Lucas

    2012-02-24

    Test-and-slaughter strategies have been the basis of bovine tuberculosis (BT) eradication programs worldwide; however, eradication efforts have not succeeded in certain regions, and imperfect sensitivity and specificity of applied diagnostic techniques have been deemed as one of the possible causes for such failure. Evaluation of tuberculosis diagnostic tools has been impaired by the lack of an adequate gold standard to define positive and negative individuals. Here, a Bayesian approach was formulated to estimate for the first time sensitivity (Se) and specificity (Sp) of the tests [single intradermal tuberculin (SIT) test, and interferon-gamma (IFN-γ) assay] currently used in Spain. Field data from the first implementation of IFN-γ assay (used in parallel with SIT test 2-6months after a first disclosure SIT test) in infected beef, dairy and bullfighting cattle herds from the region of Castilla and Leon were used for the analysis. Model results suggested that in the described situation: (i) Se of SIT test was highly variable (40.1-92.2% for severe interpretation, median=66-69%), and its Sp was high (>99%) regardless interpretation criteria; (ii) IFN-γ assay showed a high Se (median=89-90% and 83.5% for 0.05 and 0.1 cut-off points respectively) and an acceptable Sp (85.7% and 90.3% for 0.05 and 0.1 thresholds) and (iii) parallel application of both tests maximized the combined Se (95.6% using severe SIT and 0.05 cut-off point in the IFN-γ assay). These results support the potential use of the IFN-γ assay as an ancillary technique for routine BT diagnosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Osteogenic potency of human bone marrow mesenchymal stem cells from femoral atrophic non-union fracture site

    Directory of Open Access Journals (Sweden)

    Ismail Hadisoebroto Dilogo

    2014-06-01

    Full Text Available Objective: Mesenchymal stem cells (MSCs exist in the site of atrophic non-union fracture. The aim of this study was to evaluate the osteogenic potency of MSCs in order to have a better understanding of the unclear pathophysiology of atrophic non-union fracture Methods: This is an in vitro experimental study. Sample was obtained from the non-union site of a patient with a 6-years-history of atrophic non-union fracture of right femur. The MSCs was isolated from the fracture site and was cultured in the growth medium. Confirmation of the MSCs was performed and then osteogenic differentiation was performed in mono-layered MSC grown in both home-made and commercial osteogenic media. To evaluate the osteogenic differentiation, we performed Alizarin red staining and colorimetric assay for alkaline phosphatase (ALP. Results: From Alizarin red staining, most cells in the osteoblast medium were stained red by the staining. The result of colorimetric assessment of ALP shows that peak concentration was reached after 4 minutes in osteogenic group and control group. Conclusion: The presence of ALP activity and positive Alizarin red staining in our study showed that MSCs stem cells obtained from site of atrophic non-union is capable to be differentiated into osteogenic cells. . J Clin Exp Invest 2014; 5 (2: 159-163

  3. Formatted anti-tumor necrosis factor alpha VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritis.

    Science.gov (United States)

    Coppieters, Ken; Dreier, Torsten; Silence, Karen; de Haard, Hans; Lauwereys, Marc; Casteels, Peter; Beirnaert, Els; Jonckheere, Heidi; Van de Wiele, Christophe; Staelens, Ludovicus; Hostens, Jeroen; Revets, Hilde; Remaut, Erik; Elewaut, Dirk; Rottiers, Pieter

    2006-06-01

    The advent of tumor necrosis factor (TNF)-blocking drugs has provided rheumatologists with an effective, but highly expensive, treatment for the management of established rheumatoid arthritis (RA). Our aim was to explore preclinically the application of camelid anti-TNF VHH proteins, which are single-domain antigen binding (VHH) proteins homologous to human immunoglobulin V(H) domains, as TNF antagonists in a mouse model of RA. Llamas were immunized with human and mouse TNF, and antagonistic anti-TNF VHH proteins were isolated and cloned for bacterial production. The resulting anti-TNF VHH proteins were recombinantly linked to yield bivalent mouse and human TNF-specific molecules. To increase the serum half-life and targeting properties, an anti-serum albumin anti-TNF VHH domain was incorporated into the bivalent molecules. The TNF-neutralizing potential was analyzed in vitro. Mouse TNF-specific molecules were tested in a therapeutic protocol in murine collagen-induced arthritis (CIA). Disease progression was evaluated by clinical scoring and histologic evaluation. Targeting properties were evaluated by 99mTc labeling and gamma camera imaging. The bivalent molecules were up to 500 times more potent than the monovalent molecules. The antagonistic potency of the anti-human TNF VHH proteins exceeded even that of the anti-TNF antibodies infliximab and adalimumab that are used clinically in RA. Incorporation of binding affinity for albumin into the anti-TNF VHH protein significantly prolonged its serum half-life and promoted its targeting to inflamed joints in the murine CIA model of RA. This might explain the excellent therapeutic efficacy observed in vivo. These data suggest that because of the flexibility of their format, camelid anti-TNF VHH proteins can be converted into potent therapeutic agents that can be produced and purified cost-effectively.

  4. Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.

    Science.gov (United States)

    Sperber, Jesper; Lipcsey, Miklós; Larsson, Anders; Larsson, Anders; Sjölin, Jan; Castegren, Markus

    2015-05-10

    Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome. 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels. TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb. Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia

  5. Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15

    NARCIS (Netherlands)

    Niesink, Raymond J. M.; Rigter, Sander; Koeter, Maarten W.; Brunt, Tibor M.

    2015-01-01

    Between 2000 and 2005 the average percentage of Δ(9) -tetrahydrocannabinol (THC) in marijuana as sold in Dutch coffeeshops has increased substantially; the potency of domestic products (Nederwiet and Nederhasj) has particularly increased. In contrast with imported marijuana, Nederwiet hardly

  6. Quantitative structure - mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and compreh...

  7. Conditionally replicative adenovirus expressing a targeting adapter molecule exhibits enhanced oncolytic potency on CAR-deficient tumors

    NARCIS (Netherlands)

    van Beusechem, V.W.; Mastenbroek, D.C.; Van den Doel, P.B.; Lamfers, M.L.; Grill, J.; Wurdinger, T.; Haisma, H.J.; Pinedo, H.M.; Gerritsen, W.R.

    2003-01-01

    Conditionally replicative adenoviruses (CRAds) are potentially useful agents for anticancer virotherapy approaches. However, lack of coxsackievirus and adenovirus receptor ( CAR) expression on many primary tumor cells limits the oncolytic potency of CRAds. This makes the concept of targeting, that

  8. Antecedents of team potency and team effectiveness: an examination of goal and process clarity and servant leadership.

    Science.gov (United States)

    Hu, Jia; Liden, Robert C

    2011-07-01

    Integrating theories of self-regulation with team and leadership literatures, this study investigated goal and process clarity and servant leadership as 3 antecedents of team potency and subsequent team effectiveness, operationalized as team performance and organizational citizenship behavior. Our sample of 304 employees represented 71 teams in 5 banks. Results showed that team-level goal and process clarity as well as team servant leadership served as 3 antecedents of team potency and subsequent team performance and team organizational citizenship behavior. Furthermore, we found that servant leadership moderated the relationships between both goal and process clarity and team potency, such that the positive relationships between both goal and process clarity and team potency were stronger in the presence of servant leadership.

  9. Transformational leadership and group potency in small military units: The mediating role of group identification and cohesion

    National Research Council Canada - National Science Library

    García-Guiu, Carlos; Moya, Miguel; Molero, Fernando; Moriano, Juan Antonio

    2016-01-01

    In the present study, we examined an exploratory model to assess the relationship between transformational leadership and group potency and analyze the mediating role of group identification and cohesion...

  10. Self-evaluation and peer-feedback of medical students' communication skills using a web-based video annotation system. Exploring content and specificity.

    Science.gov (United States)

    Hulsman, Robert L; van der Vloodt, Jane

    2015-03-01

    Self-evaluation and peer-feedback are important strategies within the reflective practice paradigm for the development and maintenance of professional competencies like medical communication. Characteristics of the self-evaluation and peer-feedback annotations of medical students' video recorded communication skills were analyzed. Twenty-five year 4 medical students recorded history-taking consultations with a simulated patient, uploaded the video to a web-based platform, marked and annotated positive and negative events. Peers reviewed the video and self-evaluations and provided feedback. Analyzed were the number of marked positive and negative annotations and the amount of text entered. Topics and specificity of the annotations were coded and analyzed qualitatively. Students annotated on average more negative than positive events. Additional peer-feedback was more often positive. Topics most often related to structuring the consultation. Students were most critical about their biomedical topics. Negative annotations were more specific than positive annotations. Self-evaluations were more specific than peer-feedback and both show a significant correlation. Four response patterns were detected that negatively bias specificity assessment ratings. Teaching students to be more specific in their self-evaluations may be effective for receiving more specific peer-feedback. Videofragmentrating is a convenient tool to implement reflective practice activities like self-evaluation and peer-feedback to the classroom in the teaching of clinical skills. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Development of a stringent ELISA protocol to evaluate anti-viral hemorrhagic septicemia virus-specific antibodies in olive flounder Paralichthys olivaceus with improved specificity.

    Science.gov (United States)

    Kim, Hyoung Jun; Park, Jeong Su; Kwon, Se Ryun

    2015-07-01

    Olive flounder were vaccinated with polyinosinic:polycytidylic acid [Poly (I:C)] to prevent viral hemorrhagic septicemia (VHS). Vaccine efficacy was verified by detection of anti- VHS virus (VHSV) antibodies using enzyme-linked immunosorbent assay (ELISA). In the study, ELISA absorbance values of the negative control group [Poly (I:C)-MEM10] were saturated when an ELISA protocol, that includes pretreatment of the fish sera with 5% skim milk, was used. However, the saturated OD values in the negative control did not correlate with a specific immune response against VHSV, because the group showed low survival rate (only 10%) following the VHSV challenge. Also, OD values of Poly (I:C)- VHSV group were high, and the group showed high survival rate (97.5%) against VHSV challenge test. It was suggested that the high OD values were possibly due to the presence of anti-fetal bovine serum (FBS) cross-reactivity. To compensate this, we subtracted the absorbance of infectious hematopoietic necrosis (IHNV)-Ag plates from those of the VHSV-Ag plates. However, the average value for the Poly (I:C)-VHSV group (0.167) was lower than expected even though high survival rate. We used an advanced ELISA system to pre-treat fish sera with 5% skim milk and two novirhabdoviruses as capture antigens as well as 50% FBS. The corrected absorbance values for pre-treated fish sera from the negative control Poly (I:C)-MEM10 and experimental Poly (I:C)-VHSV groups averaged 0.033 and 0.579, respectively. The specific VHSV antibody response of the vaccinated group was assessed using fish sera pretreated with skim milk and FBS and by calculating the corrected absorbance values from ELISA with two novirhabdovirus capture antigens.

  12. Overexpressing cell systems are a competitive option to primary adipocytes when predicting in vivo potency of dual GPR81/GPR109A agonists.

    Science.gov (United States)

    Almquist, Joachim; Hovdal, Daniel; Ahlström, Christine; Fjellström, Ola; Gennemark, Peter; Sundqvist, Monika

    2017-11-24

    Mathematical models predicting in vivo pharmacodynamic effects from in vitro data can accelerate drug discovery, and reduce costs and animal use. However, data integration and modeling is non-trivial when more than one drug-target receptor is involved in the biological response. We modeled the inhibition of non-esterified fatty acid release by dual G-protein-coupled receptor 81/109A (GPR81/GPR109A) agonists in vivo in the rat, to estimate the in vivo EC50 values for 12 different compounds. We subsequently predicted those potency estimates using EC50 values obtained from concentration-response data in isolated primary adipocytes and cell systems overexpressing GPR81 or GPR109A in vitro. A simple linear regression model based on data from primary adipocytes predicted the in vivo EC50 better than simple linear regression models based on in vitro data from either of the cell systems. Three models combining the data from the overexpressing cell systems were also evaluated: two piecewise linear models defining logical OR- and AND-circuits, and a multivariate linear regression model. All three models performed better than the simple linear regression model based on data from primary adipocytes. The OR-model was favored since it is likely that activation of either GPR81 or GPR109A is sufficient to deactivate the cAMP pathway, and thereby inhibit non-esterified fatty acid release. The OR-model was also able to predict the in vivo selectivity between the two receptors. Finally, the OR-model was used to predict the in vivo potency of 1651 new compounds. This work suggests that data from the overexpressing cell systems are sufficient to predict in vivo potency of GPR81/GPR109A agonists, an approach contributing to faster and leaner drug discovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Design, synthesis, and biological evaluation of a dual tumor-specific motive containing integrin-targeted plasmin-cleavable doxorubicin prodrug

    NARCIS (Netherlands)

    de Groot, FMH; Broxterman, HJ; Adams, HPHM; van Vliet, A; Tesser, GI; Elderkamp, YW; Leegte - Schraa, Astrid; Kok, RJ; Molema, G; Pinedo, HM; Scheeren, H.W.

    The design, synthesis, and initial biological evaluation of a doxorubicin prodrug that contains a dual tumor specific moiety, which allows enhanced tumor recognition potential, is reported. Both a tumor-specific recognition site and a tumor selective enzymatic activation sequence are incorporated in

  14. General and specific self-efficacy reports of patients with chronic low back pain : Are they related to performances in a functional capacity evaluation?

    NARCIS (Netherlands)

    Reneman, Michiel F.; Geertzen, Jan H. B.; Groothoff, Johan W.; Brouwer, Sandra

    Introduction The objective of this study was to analyze the relationship of general and specific self-efficacy (SE) beliefs with functional capacity evaluation (FCE) performances in patients with chronic non-specific low back pain (CLBP), while controlling for influence of gender, age, and

  15. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies

    Science.gov (United States)

    Glenn, Jolene; Stamatatos, Leonidas; Sather, D. Noah

    2014-01-01

    We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses. PMID:24466285

  16. A multimedia campaign to improve back beliefs in patients with non-specific low back pain: a process evaluation.

    Science.gov (United States)

    Suman, Arnela; Schaafsma, Frederieke G; Bamarni, Jiman; van Tulder, Maurits W; Anema, Johannes R

    2017-05-18

    Low back pain (LBP) is one of the most prevalent and costly disorders worldwide. To reduce its burden in the Netherlands, implementation of a multidisciplinary guideline for LBP was supported by a multifaceted eHealth campaign for patients with LBP. The current study aims 1) to evaluate whether the implementation strategy was performed as planned; 2) to assess the feasibility, barriers and facilitators of the patient based eHealth campaign; 3) to gain insight into the satisfaction and experiences of patients with various ethnic backgrounds with the implementation strategy and to make a comparison between them; and 4) to explore the association between exposure to and satisfaction with the implementation strategy. This process evaluation was performed using the Linnan and Steckler framework, and used a mixed methods approach for data collection and analysis. The relationship between satisfaction of patients and exposure to the strategy was statistically examined. Semi-structured interviews were analysed using qualitative data analysis methods. Two hundred and fourteen patients participated in the quantitative, and 44 in the qualitative analysis. Most were female and had a high level of education. Many patients did not use the campaign at all or only once, and those that did rated it as reasonable. Patient satisfaction with the campaign increased significantly with an increase in its use. Qualitative analysis showed that four main themes played a role in campaign rating and use: satisfaction with intervention components, perceived benefits of the intervention, usage of the intervention, and satisfaction with the medium used. This process evaluation showed that the eHealth campaign was used only by a small proportion of patients with non-specific LBP. It seemed that the campaign was offered to the patients too late, that the lay-out of the campaign did not meet patient needs, and that healthcare providers rarely discussed the campaign with their patients, while

  17. Evaluation of 3 analyte-specific reagents for detection of Bordetella pertussis and Bordetella parapertussis in clinical specimens.

    Science.gov (United States)

    Hassan, Ferdaus; Hays, Lindsay; Bell, Jeremiah; Selvarangan, Rangaraj

    2014-11-01

    The performance of 3 analyte-specific reagents (ASRs), Elitech Biosciences, EraGen Biosciences, and Focus Diagnostic, was evaluated for detection of Bordetella pertussis (BP) and Bordetella parapertussis (BPP) in nasopharyngeal swab specimens. A total of 104 frozen, leftover clinical specimens obtained from pediatric patients during 2011-2012 were included in this study. Performance was compared to the Bordetella real-time polymerase chain reaction (PCR) laboratory-developed test (LDT). The positive percent agreement for detection of BP by Elitech was 96% (95% confidence interval [CI]: 85.14-99.30); EraGen and Focus was 98% (95% CI: 87.99-99.89) in comparison to LDT PCR assay. The negative percent agreement of Elitech, EraGen, and Focus in comparison to LDT was 96% (95% CI: 85.14-99.30), 92% (95% CI: 79.89-97.41), and 96% (95% CI: 85.14-99.30), respectively. Limit of detection (LOD) for BP was 0.1 CFU/reaction by both Focus and EraGen and 1.0 CFU/reaction by Elitech. However, LOD for BPP was lower by EraGen (0.1 CFU/reaction) compared to Focus (1.0 CFU/reaction) and Elitech (1.0 CFU/reaction). These results demonstrate that all 3 ASRs tested are comparable and reliable for routine clinical diagnosis of pertussis and parapertussis. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Burn Specific Health Scale-Brief in Pregnant Burned Women: Translation and Psychometric Evaluation of the Persian Version

    Directory of Open Access Journals (Sweden)

    Amir Hossein Goudarzian

    2017-07-01

    Full Text Available Background   The aim of this study was to investigate the validity and reliability of the Persian version of Burn Specific Health Scale-Brief (BSHS-B in pregnant women suffering from burns.   Materials and Methods   This cross-cultural psychometrics study was done in 2015 to 2016 and included 410 pregnant burned patients. Participants completed BSHS-B. The face, content and construct validity of the scale were ascertained. Reliability was also assessed using internal consistency, construct reliability and intra-class correlation coefficient (ICC.   Results   Construct validity determined nine factors with an eigenvalue greater than 1. The model had a good fit [(c2(68 = 412.038, p < .05, c2/df= 4.612, GFI = .893, CFI = .912, NFI = .902, IFI = .931, RMSEA (90% C.I. = .091 (.088 - .112] with all factors loadings greater than 0.5 and statistically significant. The internal consistency, construct reliability and ICC were greater than 0.70.   Conclusion   Findings revealed that the Persian version of the BSHS-B is valid and reliable, and may be used to assess and evaluate quality of life in Iranian pregnant burned patients.

  19. Use of computerized tests to evaluate psychomotor performance in children with specific learning disabilities in comparison to normal children

    Directory of Open Access Journals (Sweden)

    Santosh Taur

    2014-01-01

    Full Text Available Background & objectives: Children with specific learning disabilities (SpLD have an unexplained difficulty in acquiring basic academic skills resulting in a significant discrepancy between their academic potential and achievements. This study was undertaken to compare the performance on a battery of six psychomotor tests of children with SpLD and those without any learning disabilities (controls using computerized tests. Methods: In this study, 25 children with SpLD and 25 controls (matched for age, socio-economic status and medium of instruction were given three training sessions over one week. Then children were asked to perform on the six computerized psychomotor tests. Results were compared between the two groups. Results: Children with SpLD fared significantly worse on finger tapping test, choice reaction test, digit picture substitution test and card sorting test compared to the controls ( p <0.05. Interpretation & conclusions: Children with SpLD have impairment of psychomotor skills like attention, sensory-motor coordination and executive functioning. Further research is needed to evaluate if the remedial education plan results in improvement in psychomotor performance of children with SpLD on these selected tests.

  20. Evaluation of the performance of high temperature conversion reactors for compound-specific oxygen stable isotope analysis.

    Science.gov (United States)

    Hitzfeld, Kristina L; Gehre, Matthias; Richnow, Hans-Hermann

    2017-05-01

    In this study conversion conditions for oxygen gas chromatography high temperature conversion (HTC) isotope ratio mass spectrometry (IRMS) are characterised using qualitative mass spectrometry (IonTrap). It is shown that physical and chemical properties of a given reactor design impact HTC and thus the ability to accurately measure oxygen isotope ratios. Commercially available and custom-built tube-in-tube reactors were used to elucidate (i) by-product formation (carbon dioxide, water, small organic molecules), (ii) 2nd sources of oxygen (leakage, metal oxides, ceramic material), and (iii) required reactor conditions (conditioning, reduction, stability). The suitability of the available HTC approach for compound-specific isotope analysis of oxygen in volatile organic molecules like methyl tert-butyl ether is assessed. Main problems impeding accurate analysis are non-quantitative HTC and significant carbon dioxide by-product formation. An evaluation strategy combining mass spectrometric analysis of HTC products and IRMS (18)O/(16)O monitoring for future method development is proposed.