Sample records for ic50 values decreased

  1. ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

    PubMed

    Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

    2015-02-01

    IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

  2. Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values.

    PubMed

    Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

    2014-01-01

    Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×10(6) parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4-9%) at their respective IC50 values. For assays with high cell concentrations (2×10(9) parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis.

  3. Terpenes Increase the Lipid Dynamics in the Leishmania Plasma Membrane at Concentrations Similar to Their IC50 Values

    PubMed Central

    Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

    2014-01-01

    Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (2×109 parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis. PMID:25101672

  4. AVP-IC50 Pred: Multiple machine learning techniques-based prediction of peptide antiviral activity in terms of half maximal inhibitory concentration (IC50).

    PubMed

    Qureshi, Abid; Tandon, Himani; Kumar, Manoj

    2015-11-01

    Peptide-based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non-redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino-acid compositions, binary profile of N8-C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance-based classifier, and K-Star were employed. During 10-fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP-IC50 Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp. © 2015 Wiley Periodicals, Inc.

  5. Development of Quantum Chemical Method to Calculate Half Maximal Inhibitory Concentration (IC50 ).

    PubMed

    Bag, Arijit; Ghorai, Pradip Kr

    2016-05-01

    Till date theoretical calculation of the half maximal inhibitory concentration (IC50 ) of a compound is based on different Quantitative Structure Activity Relationship (QSAR) models which are empirical methods. By using the Cheng-Prusoff equation it may be possible to compute IC50 , but this will be computationally very expensive as it requires explicit calculation of binding free energy of an inhibitor with respective protein or enzyme. In this article, for the first time we report an ab initio method to compute IC50 of a compound based only on the inhibitor itself where the effect of the protein is reflected through a proportionality constant. By using basic enzyme inhibition kinetics and thermodynamic relations, we derive an expression of IC50 in terms of hydrophobicity, electric dipole moment (μ) and reactivity descriptor (ω) of an inhibitor. We implement this theory to compute IC50 of 15 HIV-1 capsid inhibitors and compared them with experimental results and available other QASR based empirical results. Calculated values using our method are in very good agreement with the experimental values compared to the values calculated using other methods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Classification of drug molecules considering their IC50 values using mixed-integer linear programming based hyper-boxes method.

    PubMed

    Armutlu, Pelin; Ozdemir, Muhittin E; Uney-Yuksektepe, Fadime; Kavakli, I Halil; Turkay, Metin

    2008-10-03

    A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC50 values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC50 values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naïve Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed.

  7. Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug-Drug Interaction Risk Assessment Decision Criteria

    PubMed Central

    Bentz, Joe; O’Connor, Michael P.; Bednarczyk, Dallas; Coleman, JoAnn; Lee, Caroline; Palm, Johan; Pak, Y. Anne; Perloff, Elke S.; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K.; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E.; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei

    2013-01-01

    A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells—Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations

  8. A novel application of t-statistics to objectively assess the quality of IC50 fits for P-glycoprotein and other transporters.

    PubMed

    O'Connor, Michael; Lee, Caroline; Ellens, Harma; Bentz, Joe

    2015-02-01

    Current USFDA and EMA guidance for drug transporter interactions is dependent on IC50 measurements as these are utilized in determining whether a clinical interaction study is warranted. It is therefore important not only to standardize transport inhibition assay systems but also to develop uniform statistical criteria with associated probability statements for generation of robust IC50 values, which can be easily adopted across the industry. The current work provides a quantitative examination of critical factors affecting the quality of IC50 fits for P-gp inhibition through simulations of perfect data with randomly added error as commonly observed in the large data set collected by the P-gp IC50 initiative. The types of errors simulated were (1) variability in replicate measures of transport activity; (2) transformations of error-contaminated transport activity data prior to IC50 fitting (such as performed when determining an IC50 for inhibition of P-gp based on efflux ratio); and (3) the lack of well defined "no inhibition" and "complete inhibition" plateaus. The effect of the algorithm used in fitting the inhibition curve (e.g., two or three parameter fits) was also investigated. These simulations provide strong quantitative support for the recommendations provided in Bentz et al. (2013) for the determination of IC50 values for P-gp and demonstrate the adverse effect of data transformation prior to fitting. Furthermore, the simulations validate uniform statistical criteria for robust IC50 fits in general, which can be easily implemented across the industry. A calibration of the t-statistic is provided through calculation of confidence intervals associated with the t-statistic.

  9. A novel application of t-statistics to objectively assess the quality of IC50 fits for P-glycoprotein and other transporters

    PubMed Central

    O'Connor, Michael; Lee, Caroline; Ellens, Harma; Bentz, Joe

    2015-01-01

    Current USFDA and EMA guidance for drug transporter interactions is dependent on IC50 measurements as these are utilized in determining whether a clinical interaction study is warranted. It is therefore important not only to standardize transport inhibition assay systems but also to develop uniform statistical criteria with associated probability statements for generation of robust IC50 values, which can be easily adopted across the industry. The current work provides a quantitative examination of critical factors affecting the quality of IC50 fits for P-gp inhibition through simulations of perfect data with randomly added error as commonly observed in the large data set collected by the P-gp IC50 initiative. The types of errors simulated were (1) variability in replicate measures of transport activity; (2) transformations of error-contaminated transport activity data prior to IC50 fitting (such as performed when determining an IC50 for inhibition of P-gp based on efflux ratio); and (3) the lack of well defined “no inhibition” and “complete inhibition” plateaus. The effect of the algorithm used in fitting the inhibition curve (e.g., two or three parameter fits) was also investigated. These simulations provide strong quantitative support for the recommendations provided in Bentz et al. (2013) for the determination of IC50 values for P-gp and demonstrate the adverse effect of data transformation prior to fitting. Furthermore, the simulations validate uniform statistical criteria for robust IC50 fits in general, which can be easily implemented across the industry. A calibration of the t-statistic is provided through calculation of confidence intervals associated with the t-statistic. PMID:25692007

  10. Identification of a novel malonyl-CoA IC(50) for CPT-I: implications for predicting in vivo fatty acid oxidation rates.

    PubMed

    Smith, Brennan K; Perry, Christopher G R; Koves, Timothy R; Wright, David C; Smith, Jeffrey C; Neufer, P Darrell; Muoio, Deborah M; Holloway, Graham P

    2012-11-15

    Published values regarding the sensitivity (IC(50)) of CPT-I (carnitine palmitoyltransferase I) to M-CoA (malonyl-CoA) inhibition in isolated mitochondria are inconsistent with predicted in vivo rates of fatty acid oxidation. Therefore we have re-examined M-CoA inhibition kinetics under various P-CoA (palmitoyl-CoA) concentrations in both isolated mitochondria and PMFs (permeabilized muscle fibres). PMFs have an 18-fold higher IC(50) (0.61 compared with 0.034 μM) in the presence of 25 μM P-CoA and a 13-fold higher IC(50) (6.3 compared with 0.49 μM) in the presence of 150 μM P-CoA compared with isolated mitochondria. M-CoA inhibition kinetics determined in PMFs predicts that CPT-I activity is inhibited by 33% in resting muscle compared with >95% in isolated mitochondria. Additionally, the ability of M-CoA to inhibit CPT-I appears to be dependent on P-CoA concentration, as the relative inhibitory capacity of M-CoA is decreased with increasing P-CoA concentrations. Altogether, the use of PMFs appears to provide an M-CoA IC(50) that better reflects the predicted in vivo rates of fatty acid oxidation. These findings also demonstrate that the ratio of [P-CoA]/[M-CoA] is critical for regulating CPT-I activity and may partially rectify the in vivo disconnect between M-CoA content and CPT-I flux within the context of exercise and Type 2 diabetes.

  11. Validation and Clinical Utility of the hERG IC50:Cmax Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis.

    PubMed

    Lehmann, David F; Eggleston, William D; Wang, Dongliang

    2018-03-01

    Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (C max ) is used during drug development to screen out chemical entities likely to cause TdP. To validate the use of the hERG IC50:C max ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. Medline (between 1966 and March 2017) was accessed for hERG IC50 and C max values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. Negligible risk drugs were defined by an hERG IC50:C max ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). The hERG IC50:C max ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001), a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. The hERG IC50:C max ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C max ratio for clinical decision making in instances of drug selection where TdP risk is a concern. © 2018

  12. In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2015-16 season: Comparison with the 2010-11 to 2014-15 seasons.

    PubMed

    Ikematsu, Hideyuki; Kawai, Naoki; Iwaki, Norio; Kashiwagi, Seizaburo

    2017-09-01

    To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) in the viruses epidemic in the 2015-2016 influenza season in Japan, we measured the 50% inhibitory concentration (IC 50 ) of NAIs for influenza virus isolates and compared them with the results from the 2010-11 to 2014-15 influenza seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. Influenza viruses were isolated: 210 influenza A(H1N1)pdm09 (67.3%), 20 A(H3N2) (6.4%), and 82 B (26.3%), and for the Victoria and Yamagata lineages the numbers were 53 (64.6%) and 28 (34.1%), respectively, with one unknown. Two A(H1N1)pdm09 isolates showed a high IC50 for oseltamivir (130 and 150 nM). No isolate showed a very high IC50 for A(H3N2) or B. The ratios of geometric mean IC50 of the 2015-2016 influenza season to those of the 2010-2011 to 2014-2015 influenza seasons ranged from 0.62 to 1.78 for A(H1N1) pdm09. The range was 0.73-1.35 for A(H3N2) and 0.48-1.12 for B. No significant trend of increase or decrease in IC50 was found for any of the four NAIs. Although some isolates showed highly reduced sensitivity to oseltamivir among the A(H1N1)pdm09 isolates, the currently epidemic influenza A(H1N1)pdm09, A(H3N2), and B viruses are susceptible to all four NAIs, with no trend toward decreased sensitivity. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Ketone EC50 values in the Microtox test.

    PubMed

    Chen, H F; Hee, S S

    1995-03-01

    The Microtox EC50 values for the following ketones are reported in the following homologous series: straight chain methyl ketones (acetone, 2-butanone, 2-pentanone, 2-hepatonone, 2-octanone, 2-decanone, and 2-tridecanone); methyl ketones substituted at one alpha carbon (3-methyl-2-butanone; 3,3-dimethyl-2-butanone); methyl substituted at two alpha carbons (2,4-dimethyl-3-pentanone; 2,2,4,4-tetramethyl-3-pentanone); phenyl groups replacing methyl in acetone (acetophenone; benzophenone); methyl groups substituted at the alpha carbons of cyclohexanone; and 2,3- 2,4-, and 2,5-hexanediones, most for the first time. While there were linear relationships between log EC50 and MW for the straight chain methyl ketones, and for methyl substitution at the alpha carbon for methyl ketones, there were no other linear relationships. As molecular weight increased, the EC50 values of soluble ketones decreased; as distance between two carbonyl groups decreased so too did EC50 values. Thus, for the ketones the geometry around the carbonyl group is an important determinant of toxicity as well as MW, water solubility, and octanol/water coefficient.

  14. In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2016-17 season: Comparison with the 2010-11 to 2015-16 seasons.

    PubMed

    Ikematsu, Hideyuki; Kawai, Naoki; Iwaki, Norio; Kashiwagi, Seizaburo; Ishikawa, Yusuke; Yamaguchi, Hiroki; Shiosakai, Kazuhito

    2018-05-11

    To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) in the viruses epidemic in the 2016-17 Japanese influenza season, we measured the 50% inhibitory concentration (IC 50 ) of these NAIs for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2015-16 seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC 50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 276 virus isolates, 6 A (H1N1)pdm09 (2.2%), 249 A (H3N2) (90.2%), and 21 B (7.6%), had the IC 50 measured for the four NAIs. B isolates included 11 (52.4%), 9 (42.9%), and one (4.8%) of the Victoria, Yamagata, and undetermined strains, respectively. No A (H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2016-17 season. No isolate with highly reduced sensitivity to the four NAIs have been found for A (H3N2) or B from the 2010-11 to 2016-17 seasons. No significant trend of increase or decrease was found in the geometric mean IC 50 s of the four NAIs during the seven studied seasons. These results indicate that the sensitivity to the four commonly used NAIs has been maintained and that any change in the effectiveness of these NAIs would be minute. Common usage of NAIs for patient treatment has not been a driving force in the selection of NAI resistant viruses. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 Japanese influenza seasons.

    PubMed

    Ikematsu, Hideyuki; Kawai, Naoki; Iwaki, Norio; Kashiwagi, Seizaburo

    2016-09-01

    To assess the extent of viral resistance to the four neuraminidase inhibitors (NAIs), we measured their 50% inhibitory concentration (IC50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 influenza seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. IC50 was measured for 200 influenza A(H3N2) and 19 influenza B in the 2014-2015 season, and no virus with highly reduced sensitivity to the four NAIs was detected. The ratios of the geometric means of the A(H3N2) IC50s of 2014-2015 to those of the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 seasons ranged from 0.72 to 1.05, 0.82 to 1.22, 0.69 to 1.00, and 0.70 to 1.03, respectively. The ratios of the geometric mean of the B IC50s to the previous four seasons ranged from 0.59 to 1.28, 0.66 to 1.34, 0.84 to 1.21, and 1.06 to 1.47, respectively. There was no trend in the change of the IC50s for A(H3N2) or B. Significant differences were found in some seasons, but the differences in the IC50s were all less than two fold. These results show change in the geometric mean IC50 by season but with no trend, which indicates that the influence of viral mutation on the effectiveness of these NAIs was minute for A(H3N2) and B over the past five seasons. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Publications - IC 50 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    Mapping Advisory Board STATEMAP Publications Geophysics Program Information Geophysical Survey ic050.pdf (999.0 K) Keywords Aeromagnetic; Aeromagnetic Map; Aeromagnetic Survey; Alaska Peninsula ; Coal; Conductivity Survey; Construction Materials; Copper; Cretaceous; Delta River; Diamonds; Drilling

  17. Development of brain injury criteria (BrIC).

    PubMed

    Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas

    2013-11-01

    between CSDM - BrIC and MPS - BrIC respectively. AIS 3+, 4+ and 5+ field risk of anatomic brain injuries was also estimated using the National Automotive Sampling System - Crashworthiness Data System (NASS-CDS) database for crash conditions similar to the frontal NCAP and side impact conditions that the ATDs were tested in. This was done to assess the risk curve ratios derived from HIC risk curves. The results of the study indicated that: (1) the two available human head models - SIMon and GHBMC - were found to be highly correlated when CSDMs and max principal strains were compared; (2) BrIC correlates best to both - CSDM and MPS, and rotational velocity (not rotational acceleration) is the mechanism for brain injuries; and (3) the critical values for angular velocity are directionally dependent, and are independent of the ATD used for measuring them. The newly developed brain injury criterion is a complement to the existing HIC, which is based on translational accelerations. Together, the two criteria may be able to capture most brain injuries and skull fractures occurring in automotive or any other impact environment. One of the main limitations for any brain injury criterion, including BrIC, is the lack of human injury data to validate the criteria against, although some approximation for AIS 2+ injury is given based on the angular velocities calculated at 50% probability of concussion in college football players instrumented with 5 DOF helmet system. Despite the limitations, a new kinematic rotational brain injury criterion - BrIC - may offer a way to capture brain injuries in situations when using translational accelerations based HIC alone may not be sufficient.

  18. Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin.

    PubMed

    Srinivas, N R

    2016-08-01

    Linear regression models utilizing a single time point (Cmax) has been reported for pravastatin and simvastatin. A new model was developed for the prediction of AUC of statins that utilized the slopes of the above 2 models, with pharmacokinetic (Cmax) and a pharmacodynamic (IC50 value) components for the statins. The prediction of AUCs for various statins (pravastatin, atorvastatin, simvastatin and rosuvastatin) was carried out using the newly developed dual pharmacokinetic and pharmacodynamic model. Generally, the AUC predictions were contained within 0.5 to 2-fold difference of the observed AUC suggesting utility of the new models. The root mean square error predictions were<45% for the 2 models. On the basis of the present work, it is feasible to utilize both pharmacokinetic (Cmax) and pharmacodynamic (IC50) data for effectively predicting the AUC for statins. Such a new concept as described in the work may have utility in both drug discovery and development stages. © Georg Thieme Verlag KG Stuttgart · New York.

  19. 30 CFR 57.22102 - Smoking (I-C mines).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

  20. 30 CFR 57.22102 - Smoking (I-C mines).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

  1. 30 CFR 57.22102 - Smoking (I-C mines).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

  2. 30 CFR 57.22102 - Smoking (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

  3. Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

    PubMed

    Price, David B; Colice, Gene; Israel, Elliot; Roche, Nicolas; Postma, Dirkje S; Guilbert, Theresa W; van Aalderen, Willem M C; Grigg, Jonathan; Hillyer, Elizabeth V; Thomas, Victoria; Martin, Richard J

    2016-04-01

    Asthma management guidelines recommend adding a long-acting β 2 -agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.

  4. DECONVOLUTION OF IMAGES FROM BLAST 2005: INSIGHT INTO THE K3-50 AND IC 5146 STAR-FORMING REGIONS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roy, Arabindo; Netterfield, Calvin B.; Ade, Peter A. R.

    2011-04-01

    We present an implementation of the iterative flux-conserving Lucy-Richardson (L-R) deconvolution method of image restoration for maps produced by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). Compared to the direct Fourier transform method of deconvolution, the L-R operation restores images with better-controlled background noise and increases source detectability. Intermediate iterated images are useful for studying extended diffuse structures, while the later iterations truly enhance point sources to near the designed diffraction limit of the telescope. The L-R method of deconvolution is efficient in resolving compact sources in crowded regions while simultaneously conserving their respective flux densities. We have analyzed itsmore » performance and convergence extensively through simulations and cross-correlations of the deconvolved images with available high-resolution maps. We present new science results from two BLAST surveys, in the Galactic regions K3-50 and IC 5146, further demonstrating the benefits of performing this deconvolution. We have resolved three clumps within a radius of 4.'5 inside the star-forming molecular cloud containing K3-50. Combining the well-resolved dust emission map with available multi-wavelength data, we have constrained the spectral energy distributions (SEDs) of five clumps to obtain masses (M), bolometric luminosities (L), and dust temperatures (T). The L-M diagram has been used as a diagnostic tool to estimate the evolutionary stages of the clumps. There are close relationships between dust continuum emission and both 21 cm radio continuum and {sup 12}CO molecular line emission. The restored extended large-scale structures in the Northern Streamer of IC 5146 have a strong spatial correlation with both SCUBA and high-resolution extinction images. A dust temperature of 12 K has been obtained for the central filament. We report physical properties of ten compact sources, including six associated protostars

  5. Deconvolution of Images from BLAST 2005: Insight into the K3-50 and IC 5146 Star-forming Regions

    NASA Astrophysics Data System (ADS)

    Roy, Arabindo; Ade, Peter A. R.; Bock, James J.; Brunt, Christopher M.; Chapin, Edward L.; Devlin, Mark J.; Dicker, Simon R.; France, Kevin; Gibb, Andrew G.; Griffin, Matthew; Gundersen, Joshua O.; Halpern, Mark; Hargrave, Peter C.; Hughes, David H.; Klein, Jeff; Marsden, Gaelen; Martin, Peter G.; Mauskopf, Philip; Netterfield, Calvin B.; Olmi, Luca; Patanchon, Guillaume; Rex, Marie; Scott, Douglas; Semisch, Christopher; Truch, Matthew D. P.; Tucker, Carole; Tucker, Gregory S.; Viero, Marco P.; Wiebe, Donald V.

    2011-04-01

    We present an implementation of the iterative flux-conserving Lucy-Richardson (L-R) deconvolution method of image restoration for maps produced by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). Compared to the direct Fourier transform method of deconvolution, the L-R operation restores images with better-controlled background noise and increases source detectability. Intermediate iterated images are useful for studying extended diffuse structures, while the later iterations truly enhance point sources to near the designed diffraction limit of the telescope. The L-R method of deconvolution is efficient in resolving compact sources in crowded regions while simultaneously conserving their respective flux densities. We have analyzed its performance and convergence extensively through simulations and cross-correlations of the deconvolved images with available high-resolution maps. We present new science results from two BLAST surveys, in the Galactic regions K3-50 and IC 5146, further demonstrating the benefits of performing this deconvolution. We have resolved three clumps within a radius of 4farcm5 inside the star-forming molecular cloud containing K3-50. Combining the well-resolved dust emission map with available multi-wavelength data, we have constrained the spectral energy distributions (SEDs) of five clumps to obtain masses (M), bolometric luminosities (L), and dust temperatures (T). The L-M diagram has been used as a diagnostic tool to estimate the evolutionary stages of the clumps. There are close relationships between dust continuum emission and both 21 cm radio continuum and 12CO molecular line emission. The restored extended large-scale structures in the Northern Streamer of IC 5146 have a strong spatial correlation with both SCUBA and high-resolution extinction images. A dust temperature of 12 K has been obtained for the central filament. We report physical properties of ten compact sources, including six associated protostars, by fitting

  6. Using the Climbing Drum Peel (CDP) Test to Obtain a G(sub IC) value for Core/Facesheet Bonds

    NASA Technical Reports Server (NTRS)

    Nettles, A. T.; Gregory, Elizabeth D.; Jackson, Justin R.

    2006-01-01

    A method of measuring the Mode I fracture toughness of core/facesheet bonds in sandwich Structures is desired, particularly with the widespread use of models that need this data as input. This study examined if a critical strain energy release rate, G(sub IC), can be obtained from the climbing drum peel (CDP) test. The CDP test is relatively simple to perform and does not rely on measuring small crack lengths such as required by the double cantilever beam (DCB) test. Simple energy methods were used to calculate G(sub IC) from CDP test data on composite facesheets bonded to a honeycomb core. Facesheet thicknesses from 2 to 5 plies were tested to examine the upper and lower bounds on facesheet thickness requirements. Results from the study suggest that the CDP test, with certain provisions, can be used to find the GIG value of a core/facesheet bond.

  7. Quantitative Spectroscopy of Supergiants in the Local Group Dwarf Galaxy IC 1613: Metallicity and Distance

    NASA Astrophysics Data System (ADS)

    Berger, Travis A.; Kudritzki, Rolf-Peter; Urbaneja, Miguel A.; Bresolin, Fabio; Gieren, Wolfgang; Pietrzyński, Grzegorz; Przybilla, Norbert

    2018-06-01

    We present a spectral analysis of 21 blue supergiant stars of spectral types late B to early A within the Local Group dwarf galaxy IC 1613, based on VLT Focal Reducer and Low Dispersion Spectrograph 2 low-resolution spectra. Combining our results with studies of early B-type blue supergiants, we report a wide bimodal distribution of metallicities with two peaks around [Z] ∼ ‑0.50 dex and [Z] ∼ ‑0.85 dex. The bimodal distribution correlates with spatial location, when compared with column densities of neutral hydrogen in IC 1613. While the low [Z] objects appear in regions of relatively high ISM H I column densities or close to them, the high [Z] supergiants are found in the central H I hole that is almost devoid of hydrogen. This suggests there are varied chemical evolution histories for the young stellar populations in IC 1613. Utilizing the flux-weighted gravity–luminosity relation, we determine IC 1613's distance modulus as m ‑ M = 24.39 ± 0.11 mag. This value is in agreement within previous distance measurements using the near-infrared period–luminosity relationship of Cepheids and the tip of the red giant branch.

  8. Mod 1 ICS TI Report: ICS Conversion of a 140% HPGe Detector

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bounds, John Alan

    This report evaluates the Mod 1 ICS, an electrically cooled 140% HPGe detector. It is a custom version of the ORTEC Integrated Cooling System (ICS) modified to make it more practical for us to use in the field. Performance and operating characteristics of the Mod 1 ICS are documented, noting both pros and cons. The Mod 1 ICS is deemed a success. Recommendations for a Mod 2 ICS, a true field prototype, are provided.

  9. TDR method for determine IC's parameters

    NASA Astrophysics Data System (ADS)

    Timoshenkov, V.; Rodionov, D.; Khlybov, A.

    2016-12-01

    Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

  10. Application of Receiver Operating Characteristic Analysis to Refine the Prediction of Potential Digoxin Drug Interactions

    PubMed Central

    Ellens, Harma; Deng, Shibing; Coleman, JoAnn; Bentz, Joe; Taub, Mitchell E.; Ragueneau-Majlessi, Isabelle; Chung, Sophie P.; Herédi-Szabó, Krisztina; Neuhoff, Sibylle; Palm, Johan; Balimane, Praveen; Zhang, Lei; Jamei, Masoud; Hanna, Imad; O’Connor, Michael; Bednarczyk, Dallas; Forsgard, Malin; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hillgren, Kathleen M.; Li, LiBin; Pak, Anne Y.; Perloff, Elke S.; Rajaraman, Ganesh; Salphati, Laurent; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yamagata, Tetsuo

    2013-01-01

    In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits P-glycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when the maximum concentration of inhibitor at steady state divided by IC50 ([I1]/IC50) is ≥0.1 or concentration of inhibitor based on highest approved dose dissolved in 250 ml divide by IC50 ([I2]/IC50) is ≥10. In this article, refined criteria are presented, determined by receiver operating characteristic analysis, using IC50 values generated by 23 laboratories. P-gp probe substrates were digoxin for polarized cell-lines and N-methyl quinidine or vinblastine for P-gp overexpressed vesicles. Inhibition of probe substrate transport was evaluated using 15 known P-gp inhibitors. Importantly, the criteria derived in this article take into account variability in IC50 values. Moreover, they are statistically derived based on the highest degree of accuracy in predicting true positive and true negative digoxin DDI results. The refined criteria of [I1]/IC50 ≥ 0.03 and [I2]/IC50 ≥ 45 and FDA criteria were applied to a test set of 101 in vitro-in vivo digoxin DDI pairs collated from the literature. The number of false negatives (none predicted but DDI observed) were similar, 10 and 12%, whereas the number of false positives (DDI predicted but not observed) substantially decreased from 51 to 40%, relative to the FDA criteria. On the basis of estimated overall variability in IC50 values, a theoretical 95% confidence interval calculation was developed for single laboratory IC50 values, translating into a range of [I1]/IC50 and [I2]/IC50 values. The extent by which this range falls above the criteria is a measure of risk associated with the decision, attributable to variability in IC50 values. PMID:23620486

  11. Assessment of vandetanib as an inhibitor of various human renal transporters: inhibition of multidrug and toxin extrusion as a possible mechanism leading to decreased cisplatin and creatinine clearance.

    PubMed

    Shen, Hong; Yang, Zheng; Zhao, Weiping; Zhang, Yueping; Rodrigues, A David

    2013-12-01

    Vandetanib was evaluated as an inhibitor of human organic anion transporter 1 (OAT1), OAT3, organic cation transporter 2 (OCT2), and multidrug and toxin extrusion (MATE1 and MATE2K) transfected (individually) into human embryonic kidney 293 cells (HEK293). Although no inhibition of OAT1 and OAT3 was observed, inhibition of OCT2-mediated uptake of 1-methyl-4-phenylpyridinium (MPP(+)) and metformin was evident (IC(50) of 73.4 ± 14.8 and 8.8 ± 1.9 µM, respectively). However, vandetanib was an even more potent inhibitor of MATE1- and MATE2K-mediated uptake of MPP(+) (IC(50) of 1.23 ± 0.05 and 1.26 ± 0.06 µM, respectively) and metformin (IC(50) of 0.16 ± 0.05 and 0.30 ± 0.09 µM, respectively). Subsequent cytotoxicity studies demonstrated that transport inhibition by vandetanib (2.5 µM) significantly decreased the sensitivity [right shift in concentration of cisplatin giving rise to 50% cell death; IC(50(CN))] of MATE1-HEK and MATE2K-HEK cells to cisplatin [IC(50(CN)) of 1.12 ± 0.13 versus 2.39 ± 0.44 µM; 0.85 ± 0.09 versus 1.99 ± 0.16 µM; P < 0.05), but not OCT2-HEK cells (1.36 ± 0.19 versus 1.47 ± 0.24 µM) versus vandetanib untreated cells and Mock-HEK cells [IC(50(CN)) of 2.34 ± 0.31 µM]. In summary, the results show that vandetanib is a potent inhibitor of MATE1 and MATE2K (versus OCT2). Inhibition of the two transporters may explain why there are reports of decreased creatinine clearance, and increased cisplatin nephrotoxicity (reduced cisplatin clearance), in some subjects receiving vandetanib therapy.

  12. Reliability and validity of a new scale on internal coherence (ICS) of cancer patients

    PubMed Central

    Kröz, Matthias; Büssing, Arndt; von Laue, Hans Broder; Reif, Marcus; Feder, Gene; Schad, Friedemann; Girke, Matthias; Matthes, Harald

    2009-01-01

    Background Current inventories on quality of life used in oncology mainly focus on functional aspects of patients in the context of disease adaption and treatments (side) effects (EORTC QLQ C30) or generically the status of common functions (Medical Outcome Study SF 36). Beyond circumscribed dimensions of quality of life (i.e., physical, emotional, social, cognitive etc.), there is a lack of inventories which also address other relevant dimensions such as the 'sense of coherence' (SOC) in cancer patients. SOC is important because of its potential prognostic relevance in cancer patients, but the current SOC scale has mainly been validated for psychiatric and psychosomatic patients. Our two-step validation study addresses the internal coherence (ICS) scale, which is based on expert rating, using specific items for oncological patients, with respect to its reliability, validity and sensitivity to chemotherapy. Methods The items were tested on 114 participants (57 cancer patients and a matched control group), alongside questions on autonomic regulation (aR), the Hospital Anxiety and Depression Scale (HADS), self-regulation (SRQ) and Karnofsky the Performance-Index (KPI). A retest of 65 participants was carried out after a median time span of four weeks. In the second part of the study, the ICS was used to assess internal coherence during chemotherapy in 25 patients with colorectal carcinoma (CRC) and 17 breast cancer patients. ICS was recorded before, during and 4 – 8 weeks after treatment. Results The 10-item scale of 'internal coherence' (ICS) shows good to very good reliability: Cronbach-α r = 0.91, retest-reliability r = 0.80. The ICS correlates with r = 0.43 – 0.72 to the convergence criteria (all p < 0.001). We are able to show decreased ICS-values after the third cycle for CRC and breast cancer patients, with a subsequent increase of ICS scores after the end of chemotherapy. Conclusion The ICS has good to very good reliability, validity and sensitivity to

  13. Estimation of the IC to CG Ratio Using JEM-GLIMS and Ground-based Lightning Network Data

    NASA Astrophysics Data System (ADS)

    Bandholnopparat, K.; Sato, M.; Takahashi, Y.; Adachi, T.; Ushio, T.

    2017-12-01

    The ratio between intracloud (IC) discharge and cloud-to-ground (CG) discharge, which is denoted by Z, is the important parameter for the studies on the climatological differences of thunderstorm structures and for the quantitative evaluation of lightning contributions to the global electric circuit. However, the latitudinal, regional, and seasonal dependences of Z-value are not fully clarified. The purposes of this study are (i) to develop new methods to identify IC and CG discharges using optical data obtained by the Global Lightning and Sprite Measurements on Japanese Experiment Module (JEM-GLIMS) from space and ground-based lightning data, (ii) to estimate Z-value and its latitudinal, regional, and seasonal dependences. As a first step, we compared the JEM-GLIMS data to the ground-based lightning data obtained by JLDN, NLDN, WWLLN, and GEON in order to distinguish the lightning discharge type detected by JEM-GLIMS. As a next step, we have calculated intensity ratios between the blue and red PH channels, that is, PH2(337 nm)/PH3(762 nm), PH5(316 nm)/PH3, PH6(392 nm)/PH3, PH2/PH4(599-900 nm), PH5/PH4, and PH6/PH4 for each lightning event. From these analyses, it is found that 447 and 454 of 8355 lightning events were identified to be CG and IC discharges, respectively. It is also found that the PH intensity ratio of IC discharges is clearly higher than that of CG discharges. In addition, the difference of the PH2/PH3, PH2/PH4, and PH6/PH4 ratio between IC and CG cases is relatively large, which means these three ratios are the useful proxy to classify the discharge types for other 7454 lightning events. Finally, the estimated Z-value varies from 0.18 - 0.84 from the equator to the higher latitude. The decrease of the Z-value from the equator to the higher latitude is confirmed both in the northern and the southern hemispheres. Although this latitudinal dependence of the Z-value is similar to previous studies, i.e., Boccippio et al. (2001), the estimated absolute

  14. 50 CFR 34.7 - Fair market value appraisals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Fair market value appraisals. 34.7 Section... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM REFUGE REVENUE SHARING WITH COUNTIES § 34.7 Fair market value... procedures in order to estimate the fair market value of each area as a whole. The evaluation will be...

  15. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in human myocytes.

    PubMed

    Nishimoto, Tomoyuki; Tozawa, Ryuichi; Amano, Yuichiro; Wada, Takeo; Imura, Yoshimi; Sugiyama, Yasuo

    2003-12-01

    TAK-475 is a squalene synthase inhibitor, rapidly metabolized to T-91485 in vivo. We investigated the myotoxicities of T-91485 and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in a human rhabdomyosarcoma cell line, RD, and in human skeletal myocytes. In differentiated RD cells, T-91485, atorvastatin (ATV) and simvastatin acid (SIM) inhibited cholesterol biosynthesis, with IC(50) values of 36, 2.8 and 3.8 nM, respectively. ATV and SIM decreased the intracellular ATP content, with IC(25) values (concentrations giving a 25% decrease in intracellular ATP content) of 0.61 and 0.44 microM, respectively. Although T-91485 potently inhibited cholesterol synthesis in RD cells, the IC(25) value exceeded 100 microM. In human skeletal myocytes, T-91485, ATV and SIM concentration-dependently inhibited cholesterol biosynthesis, with IC(50) values of 45, 8.6 and 8.4 nM, respectively. ATV and SIM decreased intracellular ATP content, with IC(25) values of 2.1 and 0.72 microM, respectively. Although T-91485 potently inhibited cholesterol synthesis, the IC(25) value exceeded 100 microM. Myotoxicity induced by ATV was prevented by mevalonate or geranylgeranyl-PP, but not by squalene in skeletal cells. Furthermore, T-91485 attenuated the myotoxicity of ATV. These findings suggest that TAK-475 and T-91485 may not only be far from myotoxic, they may also decrease statin-induced myotoxicity in lipid-lowering therapy.

  16. Persimmon Tannin Decreased the Glycemic Response through Decreasing the Digestibility of Starch and Inhibiting α-Amylase, α-Glucosidase, and Intestinal Glucose Uptake.

    PubMed

    Li, Kaikai; Yao, Fen; Du, Jing; Deng, Xiangyi; Li, Chunmei

    2018-02-21

    Regulation of postprandial blood glucose levels is an effective therapeutic proposal for type 2 diabetes treatment. In this study, the effect of persimmon tannin on starch digestion with different amylose levels was investigated both in vitro and in vivo. Oral administration of persimmon tannin-starch complexes significantly suppressed the increase of blood glucose levels and the area under the curve (AUC) in a dose-dependent manner compared with starch treatment alone in an in vivo rat model. Further study proved that persimmon tannin could not only interact with starch directly but also inhibit α-amylase and α-glucosidase strongly, with IC 50 values of 0.35 and 0.24 mg/mL, separately. In addition, 20 μg/mL of persimmon tannin significantly decreased glucose uptake and transport in Caco-2 cells model. Overall, our data suggested that persimmon tannin may alleviate postprandial hyperglycemia through limiting the digestion of starch as well as inhibiting the uptake and transport of glucose.

  17. An ultra low-power front-end IC for wearable health monitoring system.

    PubMed

    Yu-Pin Hsu; Zemin Liu; Hella, Mona M

    2016-08-01

    This paper presents a low-power front-end IC for wearable health monitoring systems. The IC, designed in a standard 0.13μm CMOS technology, fully integrates a low-noise analog front-end (AFE) to process the weak bio-signals, followed by an analog-to-digital converter (ADC) to digitize the extracted signals. An AC-coupled driving buffer, that interfaces between the AFE and the ADC is introduced to scale down the power supply of the ADC. The power consumption decreases by 50% compared to the case without power supply scaling. The AFE passes signals from 0.5Hz to 280Hz and from 0.7Hz to 160Hz with a simulated input referred noise of 1.6μVrms and achieves a maximum gain of 35dB/41dB respectively, with a noise-efficiency factor (NEF) of the AFE is 1. The 8-bit ADC achieves a simulated 7.96-bit resolution at 10KS/s sampling rate under 0.5V supply voltage. The overall system consumes only 0.86μW at dual supply voltages of 1V (AFE) and 0.5 V (ADC).

  18. R&D100: IC ID

    ScienceCinema

    Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

    2018-06-25

    Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

  19. Detection of kanamycin and gentamicin residues in animal-derived food using IgY antibody based ic-ELISA and FPIA.

    PubMed

    Li, Cui; Zhang, Yaoyao; Eremin, Sergei A; Yakup, Omar; Yao, Gang; Zhang, Xiaoying

    2017-07-15

    Our aim in this study is to show that IgY antibody based immunoassays could be used to detect antibiotic residues in animal-derived food. Briefly, full antigens of gentamicin (Gent) and kanamycin (Kana) were used to immunize the laying chickens to prepare IgY antibodies. Then, these antibodies were evaluated by FPIA and ic-ELISA to detect Gent/Kana in animal-derived samples. The IC 50 of FPIA and ic-ELISA based anti-Gent IgY were 7.70±0.6μg/mL and 0.32±0.06μg/mL, respectively. The IC 50 of FPIA and ic-ELISA based anti-Kana IgY were 7.97±0.9μg/mL and 0.15±0.01μg/mL. The limits of detection (LOD, IC 10 ) for FPIA based anti-Gent/Kana IgY were 0.17 and 0.007μg/mL, respectively. The LOD for ic-ELISA were both 0.001μg/mL. These results indicated that the ic-ELISA might more suitable for antibiotic residues detection than FPIA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Malaysian brown seaweeds Sargassum siliquosum and Sargassum polycystum: Low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase inhibition activities.

    PubMed

    Nagappan, Hemlatha; Pee, Poh Ping; Kee, Sandra Hui Yin; Ow, Ji Tsong; Yan, See Wan; Chew, Lye Yee; Kong, Kin Weng

    2017-09-01

    Two Malaysian brown seaweeds, Sargassum siliquosum and Sargassum polycystum were first extracted using methanol to get the crude extract (CE) and further fractionated to obtain fucoxanthin-rich fraction (FRF). Samples were evaluated for their phenolic, flavonoid, and fucoxanthin contents, as well as their inhibitory activities towards low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase. In LDL oxidation assay, an increasing trend in antioxidant activity was observed as the concentration of FRF (0.04-0.2mg/mL) and CE (0.2-1.0mg/mL) increased, though not statistically significant. As for serum oxidation assay, significant decrease in antioxidant activity was observed as concentration of FRF increased, while CE showed no significant difference in inhibitory activity across the concentrations used. The IC 50 values for ACE inhibitory activity of CE (0.03-0.42mg/mL) were lower than that of FRF (0.94-1.53mg/mL). When compared to reference drug Voglibose (IC 50 value of 0.61mg/mL) in the effectiveness in inhibiting α-amylase, CE (0.58mg/mL) gave significantly lower IC 50 values while FRF (0.68-0.71mg/mL) had significantly higher IC 50 values. The α-glucosidase inhibitory activity of CE (IC 50 value of 0.57-0.69mg/mL) and FRF (IC 50 value of 0.50-0.53mg/mL) were comparable to that of reference drug (IC 50 value of 0.54mg/mL). Results had shown the potential of S. siliquosum and S. polycystum in reducing cardiovascular diseases related risk factors following their inhibitory activities on ACE, α-amylase and α-glucosidase. In addition, it is likelihood that FRF possessed antioxidant activity at low concentration level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Estimation of Ksub Ic from slow bend precracked Charpy specimen strength ratios

    NASA Technical Reports Server (NTRS)

    Succop, G.; Brown, W. F., Jr.

    1976-01-01

    Strength ratios are reported which were derived from slow bend tests on 0.25 inch thick precracked Charpy specimens of steels, aluminum alloys, and a titanium alloy for which valid K sub Ic values were established. The strength ratios were used to develop calibration curves typical of those that could be useful in estimating K sub Ic for the purposes of alloy development of quality control.

  2. Langmuir wave damping decreases slowly

    NASA Astrophysics Data System (ADS)

    Rose, Harvey

    2006-10-01

    The onset of stimulated Raman scatter in a single laser speckle occurs (D. S. Montgomery et al., Phys. Plasmas, 9, 2311 (2002)) at lower laser intensity, I, than predicted by linear theory based on classical Landau damping, νL, of the SRS daughter Langmuir wave. Does this imply that SRS onset in a speckled laser beam, propagating through long scale length plasma, is also at odds with linear theory? It has been shown (Harvey A. Rose and D. F. DuBois, Phys. Rev. Lett. 72, 2883 (1994)) that linear convective gain in speckles with large fluctuations of I about the average, , leads to onset at a value of , Ic, small compared to that for onset in a uniform beam. While nonlinear electron trapping effects may occur in very intense speckles, whether or not these effects are sufficient to lower the onset value of below Ic depends on how strongly electrons must be trapped before there is significant reduction in νL. As the amplitude of an SRS daughter Langmuir wave increases, its νL decreases by the factor ν/φb, due to the competition between electron trapping, with electron bounce frequency, φb, and escape of these trapped electrons by advection out of a speckle's side, at rate ν. This result (Harvey A. Rose and David A. Russell, Phys. Plasmas, 8, 4784 (2001)) is valid for ν/φb 1. In this talk I present a nonlinear, transit time damping, calculation of νL and find that reduction by a factor of two does not occur until φb/ν 5. This slow turn on of trapping effects suggests that the linear calculation of Ic is NIF relevant.

  3. Mechanism of the effect of pH and biochar on the phytotoxicity of the weak acid herbicides imazethapyr and 2,4-D in soil to rice (Oryza sativa) and estimation by chemical methods.

    PubMed

    Liu, Kailin; He, Ying; Xu, Shiji; Hu, Lifeng; Luo, Kun; Liu, Xiangying; Liu, Min; Zhou, Xiaomao; Bai, Lianyang

    2018-06-18

    The existing form of an ionizable organic compound can simultaneously affect its soil adsorption and plant bioactivity. In this experiment, the adsorption and bioactivity of two weak acid herbicides (WAHs), imazethapyr and 2,4-D, were studied to explore the predominant mechanism by which the soil pH and the addition of biochar can influence the phytotoxicity of WAHs in soil. Then, the WAH concentration extracted by hollow fiber-based liquid-phase microextraction (C HF-LPME ), the in situ pore water concentration (C IPW ) and the added concentration (C AC ) were employed to estimate the phytotoxicity. The results showed that with increased pH from 5.5 to 8.5, the phytotoxicity of the WAHs to rice increased about 1-fold in the soil, but decreased in aqueous solutions, the IC 50 values for imazethapyr and 2,4-D at pH 5.0 were 3- and 2-fold higher than that at pH 8.0. In addition, the soil adsorption decreased, indicating that the adsorption process was the dominant factor for the variation of the phytotoxicity of the WAHs in the tested soil instead of the decreasing bioactivity. The concentration that inhibits plant growth by 50% (IC 50 ) calculated by the C AC in different pH and biochar soils ranged from 0.619 to 3.826 mg/kg for imazethapyr and 1.871-72.83 mg/kg for 2,4-D. The coefficient of variation (CV) of the IC 50 values reached 65.61% for imazethapyr and 130.0% for 2,4-D. However, when IC 50 was calculated by C IPW and C HF-LPME , the CVs of the IC 50 values decreased to 23.51% and 36.23% for imazethapyr and 40.21% and 50.93% for 2,4-D, respectively. These results suggested that C IPW and C HF-LPME may be more appropriate than C AC for estimating the phytotoxicity of WAHs. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Phytochemical constituents, nutritional values, phenolics, flavonols, flavonoids, antioxidant and cytotoxicity studies on Phaleria macrocarpa (Scheff.) Boerl fruits

    PubMed Central

    2014-01-01

    Background The edible fruits of Phaleria macrocarpa (Scheff.) Boerl are widely used in traditional medicine in Indonesia. It is used to treat a variety of medical conditions such as - cancer, diabetes mellitus, allergies, liver and heart diseases, kidney failure, blood diseases, high blood pressure, stroke, various skin diseases, itching, aches, and flu. Therefore, it is of great interest to determine the biochemical and cytotoxic properties of the fruit extracts. Methods The methanol, hexane, chloroform, ethyl acetate, and water extracts of P. macrocarpa fruits were examined for phytochemicals, physicochemicals, flavonols, flavonoids and phenol content. Its nutritional value (A.O.A.C method), antioxidant properties (DPPH assay) and cytotoxicity (MTT cell proliferation assay) were also determined. Results A preliminary phyotochemical screening of the different crude extracts from the fruits of P. macrocarpa showed the presence secondary metabolites such as of flavonoids, phenols, saponin glycosides and tannins. The ethyl acetate and methanol extracts displayed high antioxidant acitivity (IC50 value of 8.15±0.02 ug/mL) in the DPPH assay comparable to that of the standard gallic acid (IC50 value of 10.8±0.02 ug/mL). Evaluation of cytotoxic activity showed that the crude methanol extract possessed excellent anti-proliferative activity against SKOV-3 (IC50 7.75±2.56 μg/mL) after 72 hours of treatment whilst the hexane and ethyl acetate extracts displayed good cytotoxic effect against both SKOV-3 and MDA-MB231 cell lines. The chloroform extract however, showed selective inhibitory activity in the breast cancer cell line MDA-MB231 (IC50 7.80±1.57 μg/mL) after 48 hours of treatment. There was no cytotoxic effect observed in the Ca Ski cell line and the two normal cell lines (MRC-5 and WRL-68). Conclusion The methanol extract and the ethyl acetate fraction of P. macrocarpa fruits exhibited good nutritional values, good antioxidant and cytotoxic activities, and merits

  5. The Anti-Inflammatory Activity of Boron Derivatives in Rodents

    PubMed Central

    Hall, Iris H.; Burnham, Bruce S.; Chen, Shang Y.; Sood, Anup; Spielvogel, Bernard F.; Morse, Karen W.

    1995-01-01

    Acyclic amine-carboxyboranes were effective anti-inflammatory agents in mice at 8 mg/kg x 2. These amine-carboxyboranes were more effective than the standard indomethacin at 8 mg/kg x 2, pentoxifylline at 50 mg/kg x 2, and phenylbutazone at 50 mg/kg x 2. The heterocyclic amine derivatives as well as amine-carbamoylboranes, carboalkoxyboranes, and cyanoboranes were generally less active. However, selected aminomethyl-phosphonate-N-cyanoboranes demonstrated greater than 60% reduction of induced inflammation. The boron compounds were also active in the rat induced edema, chronic arthritis, and pleurisy screens, demonstrating activity similar to the standard indomethacin. The compounds were effecive in reducing local pain and decreased the tail flick reflex to pain. The derivatives which demonstrated good anti-inflammatory activity were effective inhibitors of hydrolytic lysosomal, and proteolytic enzyme activities with IC50 50 values equal to -6M in mouse macrophages, human leukocytes, and Be Sal osteofibrolytic cells. In these same cell lines, the agents blocked prostaglandin cyclooxygenase activity with IC50 values of -6M. In mouse macrophage and human leukocytes, 5′ lipoxygenase activity was also inhibited by the boron derivatives with IC50 values of 10-6M. These IC50 values for inhibition of these enzyme activities are consistent with published values of known anti-inflammatory agents which target these enzymes. PMID:18472741

  6. Rotational Periods and Starspot Activity of Young Solar-Type Dwarfs in the Open Cluster IC 4665

    NASA Technical Reports Server (NTRS)

    Allain, S.; Bouvier, J.; Prosser, C.; Marschall, L. A.; Laaksonen, B. D.

    1995-01-01

    We present the results of a V-band photometric monitoring survey of 15 late-type dwarfs in the young open cluster IC 4665. Low-amplitude periodic light variations are found for 8 stars and ascribed to the modulation by starspots that cover typically a few percent of the stellar disk. Periods range from 0.6 to 3.7 d, translating to equatorial velocities between 13 and 93 km/s. That no period longer than 4 d was detected suggests a relative paucity of extremely slow rotators (V(sub eq) much less than 10 km/s) among late-type dwarfs in IC 4665. The fractional number of slow rotators in IC 4665 is similar to that of Alpha Per cluster, suggesting that IC 4665 is close in age to Alpha Per (approx. 50 Myr).

  7. Projected Changes in Temperature and Precipitation Extremes over China as Measured by 50-yr Return Values and Periods Based on a CMIP5 Ensemble

    NASA Astrophysics Data System (ADS)

    Xu, Ying; Gao, Xuejie; Giorgi, Filippo; Zhou, Botao; Shi, Ying; Wu, Jie; Zhang, Yongxiang

    2018-04-01

    Future changes in the 50-yr return level for temperature and precipitation extremes over mainland China are investigated based on a CMIP5 multi-model ensemble for RCP2.6, RCP4.5 and RCP8.5 scenarios. The following indices are analyzed: TXx and TNn (the annual maximum and minimum of daily maximum and minimum surface temperature), RX5day (the annual maximum consecutive 5-day precipitation) and CDD (maximum annual number of consecutive dry days). After first validating the model performance, future changes in the 50-yr return values and return periods for these indices are investigated along with the inter-model spread. Multi-model median changes show an increase in the 50-yr return values of TXx and a decrease for TNn, more specifically, by the end of the 21st century under RCP8.5, the present day 50-yr return period of warm events is reduced to 1.2 yr, while extreme cold events over the country are projected to essentially disappear. A general increase in RX5day 50-yr return values is found in the future. By the end of the 21st century under RCP8.5, events of the present RX5day 50-yr return period are projected to reduce to < 10 yr over most of China. Changes in CDD-50 show a dipole pattern over China, with a decrease in the values and longer return periods in the north, and vice versa in the south. Our study also highlights the need for further improvements in the representation of extreme events in climate models to assess the future risks and engineering design related to large-scale infrastructure in China.

  8. β -decay Q values among the A = 50 Ti-V-Cr isobaric triplet and atomic masses of Ti 46 , 47 , 49 , 50 , V 50 , 51 , and Cr 50 , 52 – 54

    DOE PAGES

    Kandegedara, R. M. E. B.; Bollen, G.; Eibach, M.; ...

    2017-10-20

    This manuscript describes a measurement of the Q value for the highly forbidden beta-decays of 50V and the double electron capture decay of 50Cr. The Q value corresponds to the total energy released during the decay and is equivalent to the mass difference between parent and daughter atoms. This mass difference was measured using high precision Penning trap mass spectrometry with the Low Energy Beam and Ion Trap facility at the National Superconducting Cyclotron Laboratory. The Q value enters into theoretical calculations of the half-life and beta-decay spectrum for the decay, so improves these calculations. In addition the Q valuemore » corresponds to the end point energy of the beta-decay spectrum, which has been precisely measured for several highly-forbidden decays using modern low background detector techniques. Hence, our Q value measurements provide a test of systematics for these detectors. In addition, we have measured the absolute atomic masses of 46,47,49,50Ti, 50,51V, and 50,52-52Cr, providing improvements in precision by factors of up to 3. These atomic masses help to strengthen global evaluations of all atomic mass data, such as the Atomic Mass Evaluation.« less

  9. β -decay Q values among the A = 50 Ti-V-Cr isobaric triplet and atomic masses of Ti 46 , 47 , 49 , 50 , V 50 , 51 , and Cr 50 , 52 – 54

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kandegedara, R. M. E. B.; Bollen, G.; Eibach, M.

    This manuscript describes a measurement of the Q value for the highly forbidden beta-decays of 50V and the double electron capture decay of 50Cr. The Q value corresponds to the total energy released during the decay and is equivalent to the mass difference between parent and daughter atoms. This mass difference was measured using high precision Penning trap mass spectrometry with the Low Energy Beam and Ion Trap facility at the National Superconducting Cyclotron Laboratory. The Q value enters into theoretical calculations of the half-life and beta-decay spectrum for the decay, so improves these calculations. In addition the Q valuemore » corresponds to the end point energy of the beta-decay spectrum, which has been precisely measured for several highly-forbidden decays using modern low background detector techniques. Hence, our Q value measurements provide a test of systematics for these detectors. In addition, we have measured the absolute atomic masses of 46,47,49,50Ti, 50,51V, and 50,52-52Cr, providing improvements in precision by factors of up to 3. These atomic masses help to strengthen global evaluations of all atomic mass data, such as the Atomic Mass Evaluation.« less

  10. The Prevalence of Nocturia and Nocturnal Polyuria: Can New Cutoff Values Be Suggested According to Age and Sex?

    PubMed Central

    2016-01-01

    Purpose The aims of this study were to assess the prevalence of nocturia and nocturnal polyuria (NP) and to define new cutoff values according to age and sex for both conditions. Methods Data from a population-based prevalence survey conducted among a random sample of 2,128 adults were analyzed in this study. Participants were requested to fill out a questionnaire including the International Continence Society (ICS) definitions of lower urinary tract symptoms and the International Consultation on Incontinence Questionnaire - Short Form. Additionally, a 1-day bladder diary was given to each individual. The participants were divided into 5 age groups. The prevalence of nocturia was calculated based on definitions of nocturia as ≥1 voiding episodes, ≥2 episodes, and ≥3 episodes. NP was evaluated according to the ICS definition. The mean±standard errors and 95th percentile values were calculated in each group as new cutoff values for NP. Results The prevalence of nocturia was estimated as 28.4%, 17.6%, and 8.9% for ≥1, ≥2, and ≥3 voiding episodes each night, respectively. When nocturia was defined as 2 or more voiding episodes at night, the prevalence decreased significantly. The mean NP index was 29.4%±15.0% in men and 23.1%±11.8% in women. For the age groups of <50 years, 50–59 years, and ≥60 years, the new cutoff values for the diagnosis of NP were calculated as 48%, 69%, and 59% for men and 41%, 50%, and 42% for women, respectively. Conclusions We found that the definition of nocturia was still controversial and that waking up once for voiding might be within the normal spectrum of behavior. The definition of NP should be modified, and new cutoff values should be defined using the data presented in our study and in other forthcoming studies. PMID:28043108

  11. Reduced red cell 2,3-diphosphoglycerate concentrations in critical illness without decreased in vivo P50.

    PubMed

    Morgan, T J; Koch, D; Morris, D; Clague, A; Purdie, D M

    2001-10-01

    We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores >20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2+/-1.3 mmol/l vs 4.9+/-0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO2=75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r2 < or = 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

  12. Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

    PubMed

    Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

    2007-04-01

    The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

  13. Sensitivity Analysis of Digital I&C Modules in Protection and Safety Systems

    NASA Astrophysics Data System (ADS)

    Khalil Ur, Rahman; Zubair, M.; Heo, G.

    2013-12-01

    This research is performed to examine the sensitivity of digital Instrumentation and Control (I&C) components and modules used in regulating and protection systems architectures of nuclear industry. Fault Tree Analysis (FTA) was performed for four configurations of RPS channel architecture. The channel unavailability has been calculated by using AIMS-PSA, which comes out 4.517E-03, 2.551E-03, 2.246E-03 and 2.7613-04 for architecture configuration I, II, III and IV respectively. It is observed that unavailability decreases by 43.5 % & 50.4% by inserting partial redundancy whereas maximum reduction of 93.9 % in unavailability happens when double redundancy is inserted in architecture. Coincidence module output failure and bi-stable output failures are identified as sensitive failures by Risk Reduction Worth (RRW) and Fussell-Vesely (FV) importance. RRW highlights that risk from coincidence processor output failure can reduced by 48.83 folds and FV indicates that BP output is sensitive by 0.9796 (on a scale of 1).

  14. Ultrafast VHE Gamma-Ray Flares of IC 310

    NASA Astrophysics Data System (ADS)

    Barkov, Maxim V.; Aharonian, Felix; Khangulyan, Dmitriy V.

    In 2012 November MAGIC detected a bright flare from IC 310. The flare consisted of two sharp peaks with a typical duration of ~ 5 min. The energy released during that event has been estimated to be at the level of 2 × 1044 erg s-1. In this work we derive an upper limit on the possible luminosity of flares generated in black hole (BH) magnetosphere, which depends very weakly on the mass of BH and is determined by disk magnetisation, viewing angle, and pair multiplicity. Since all these parameters are smaller than a unit, the luminosity 2 × 1043 erg s-1 can be taken as a strict upper limit for flare luminosity for several minutes variability time. This upper limit appears to be approximately an order of magnitude below the value measured with MAGIC. Thus, we conclude that it seems very unfeasible that the magnetospheric processes can be indeed behind the bright flaring activity recorded from IC 310.

  15. SPROC: A multiple-processor DSP IC

    NASA Technical Reports Server (NTRS)

    Davis, R.

    1991-01-01

    A large, single-chip, multiple-processor, digital signal processing (DSP) integrated circuit (IC) fabricated in HP-Cmos34 is presented. The innovative architecture is best suited for analog and real-time systems characterized by both parallel signal data flows and concurrent logic processing. The IC is supported by a powerful development system that transforms graphical signal flow graphs into production-ready systems in minutes. Automatic compiler partitioning of tasks among four on-chip processors gives the IC the signal processing power of several conventional DSP chips.

  16. SEM probe of IC radiation sensitivity

    NASA Technical Reports Server (NTRS)

    Gauthier, M. K.; Stanley, A. G.

    1979-01-01

    Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

  17. Present, future of automotive hybrid IC applications discussed

    NASA Astrophysics Data System (ADS)

    Matsuda, Nobuyoshi; Fukuoka, Atuhisa

    1987-09-01

    Hybrid ICs are presently utilized in various fields such as commercial televisions, VTRs, and audio devices, industrial usage of communication equipment, computers, terminals, and automobiles. Its applications and environments are various and diverse. The functions required for hybrid ICs vary from simple high density mounting for a system to the realization of high mechanisms with the application of function timing. The functions are properly used depending upon the system with its hybrid ICs and its circuit composition. Considering structure and reliability requirements for automotive hybrid ICs, an application example for hybrid ICs which use the package (COMPACT), will be discussed.

  18. The Magnetics Information Consortium (MagIC)

    NASA Astrophysics Data System (ADS)

    Johnson, C.; Constable, C.; Tauxe, L.; Koppers, A.; Banerjee, S.; Jackson, M.; Solheid, P.

    2003-12-01

    The Magnetics Information Consortium (MagIC) is a multi-user facility to establish and maintain a state-of-the-art relational database and digital archive for rock and paleomagnetic data. The goal of MagIC is to make such data generally available and to provide an information technology infrastructure for these and other research-oriented databases run by the international community. As its name implies, MagIC will not be restricted to paleomagnetic or rock magnetic data only, although MagIC will focus on these kinds of information during its setup phase. MagIC will be hosted under EarthRef.org at http://earthref.org/MAGIC/ where two "integrated" web portals will be developed, one for paleomagnetism (currently functional as a prototype that can be explored via the http://earthref.org/databases/PMAG/ link) and one for rock magnetism. The MagIC database will store all measurements and their derived properties for studies of paleomagnetic directions (inclination, declination) and their intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). Ultimately, this database will allow researchers to study "on the internet" and to download important data sets that display paleo-secular variations in the intensity of the Earth's magnetic field over geological time, or that display magnetic data in typical Zijderveld, hysteresis/FORC and various magnetization/remanence diagrams. The MagIC database is completely integrated in the EarthRef.org relational database structure and thus benefits significantly from already-existing common database components, such as the EarthRef Reference Database (ERR) and Address Book (ERAB). The ERR allows researchers to find complete sets of literature resources as used in GERM (Geochemical Earth Reference Model), REM (Reference Earth Model) and MagIC. The ERAB contains addresses for all contributors to the EarthRef.org databases, and also for those who participated in data collection, archiving and

  19. New generation QuIC assays for prion seeding activity.

    PubMed

    Orrù, Christina D; Wilham, Jason M; Vascellari, Sarah; Hughson, Andrew G; Caughey, Byron

    2012-01-01

    The ability of abnormal TSE-associated forms of PrP to seed the formation of amyloid fibrils from recombinant PrP(Sen) has served as the basis for several relatively rapid and highly sensitive tests for prion diseases. These tests include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we summarize recent improvements in the RT-QuIC-based assays that enhance the practicality, sensitivity and quantitative attributes of assays QuIC and promote the detection of prion seeding activity in dilute, inhibitor-laden fluids such as blood plasma.

  20. The Associate Program on Ethnobiology, Socio-Economic Value Assessment and Community Based Conservation

    DTIC Science & Technology

    2000-10-01

    resistant isolates of Trichomonas vaginalis and a Tritrichomonas foetus isolate. Of these, five had MIC values of < 0.1 mg/ml including an extract...significance was the low IC50 values obtained for the T. foetus extracts (SU-1461, 1464). Further studies will examine secondary extracts of the...nitroimidazole resistance in Tritrichomonas foetus . Anitmicrob. Agents Chemother. 13:1-13. 22 13. Urbina, J.A., Lazardi, K., Marchan, E., Visbal, G., Aguirre

  1. Decreased value-sensitivity in schizophrenia.

    PubMed

    Martinelli, Cristina; Rigoli, Francesco; Dolan, Ray J; Shergill, Sukhwinder S

    2018-01-01

    Pathophysiology in schizophrenia has been linked to aberrant incentive salience, namely the dysfunctional processing of value linked to abnormal dopaminergic activity. In line with this, recent studies showed impaired learning of value in schizophrenia. However, how value is used to guide behaviour independently from learning, as in risky choice, has rarely been examined in this disorder. We studied value-guided choice under risk in patients with schizophrenia and in controls using a task requiring a choice between a certain monetary reward, varying trial-by-trial, and a gamble offering an equal probability of getting double this certain amount or nothing. We observed that patients compared to controls exhibited reduced sensitivity to values, implying that their choices failed to flexibly adapt to the specific values on offer. Moreover, the degree of this value sensitivity inversely correlated with aberrant salience experience, suggesting that the inability to tune choice to value may be a key element of aberrant salience in the illness. Our results help clarify the cognitive mechanisms underlying improper attribution of value in schizophrenia and may thus inform cognitive interventions aimed at reinstating value sensitivity in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Dynamical Competition of IC-Industry Clustering from Taiwan to China

    NASA Astrophysics Data System (ADS)

    Tsai, Bi-Huei; Tsai, Kuo-Hui

    2009-08-01

    Most studies employ qualitative approach to explore the industrial clusters; however, few research has objectively quantified the evolutions of industry clustering. The purpose of this paper is to quantitatively analyze clustering among IC design, IC manufacturing as well as IC packaging and testing industries by using the foreign direct investment (FDI) data. The Lotka-Volterra system equations are first adopted here to capture the competition or cooperation among such three industries, thus explaining their clustering inclinations. The results indicate that the evolution of FDI into China for IC design industry significantly inspire the subsequent FDI of IC manufacturing as well as IC packaging and testing industries. Since IC design industry lie in the upstream stage of IC production, the middle-stream IC manufacturing and downstream IC packing and testing enterprises tend to cluster together with IC design firms, in order to sustain a steady business. Finally, Taiwan IC industry's FDI amount into China is predicted to cumulatively increase, which supports the industrial clustering tendency for Taiwan IC industry. Particularly, the FDI prediction of Lotka-Volterra model performs superior to that of the conventional Bass model after the forecast accuracy of these two models are compared. The prediction ability is dramatically improved as the industrial mutualism among each IC production stage is taken into account.

  3. Tuberculosis vaccine candidate: Characterization of H4-IC31 formulation and H4 antigen conformation.

    PubMed

    Deshmukh, Sasmit S; Magcalas, Federico Webster; Kalbfleisch, Kristen N; Carpick, Bruce W; Kirkitadze, Marina D

    2018-08-05

    Tuberculosis (TB) is one of the leading causes of death worldwide, making the development of effective TB vaccines a global priority. A TB vaccine consisting of a recombinant fusion protein, H4, combined with a novel synthetic cationic adjuvant, IC31 ® , is currently being developed. The H4 fusion protein consists of two immunogenic mycobacterial antigens, Ag85 B and TB10.4, and the IC31 ® adjuvant is a mixture of KLK, a leucine-rich peptide (KLKL5KLK), and the oligodeoxynucleotide ODN1a, a TLR9 ligand. However, efficient and robust methods for assessing these formulated components are lacking. Here, we developed and optimized phase analysis light scattering (PALS), electrical sensing zone (ESZ), and Raman, FTIR, and CD spectroscopy methods to characterize the H4-IC31 vaccine formulation. PALS-measured conductivity and zeta potential values could differentiate between the similarly sized particles of IC31 ® adjuvant and the H4-IC31 vaccine candidate and could thereby serve as a control during vaccine formulation. In addition, zeta potential is indicative of the adjuvant to antigen ratio which is the key in the immunomodulatory response of the vaccine. ESZ was used as an orthogonal method to measure IC31 ® and H4-IC31 particle sizes. Raman, FTIR, and CD spectroscopy revealed structural changes in H4 protein and IC31 ® adjuvant, inducing an increase in both the β-sheet and random coil content as a result of adsorption. Furthermore, nanoDSF showed changes in the tertiary structure of H4 protein as a result of adjuvantation to IC31 ® . Our findings demonstrate the applicability of biophysical methods to characterize vaccine components in the final H4-IC31 drug product without the requirement for desorption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. High performance MPEG-audio decoder IC

    NASA Technical Reports Server (NTRS)

    Thorn, M.; Benbassat, G.; Cyr, K.; Li, S.; Gill, M.; Kam, D.; Walker, K.; Look, P.; Eldridge, C.; Ng, P.

    1993-01-01

    The emerging digital audio and video compression technology brings both an opportunity and a new challenge to IC design. The pervasive application of compression technology to consumer electronics will require high volume, low cost IC's and fast time to market of the prototypes and production units. At the same time, the algorithms used in the compression technology result in complex VLSI IC's. The conflicting challenges of algorithm complexity, low cost, and fast time to market have an impact on device architecture and design methodology. The work presented in this paper is about the design of a dedicated, high precision, Motion Picture Expert Group (MPEG) audio decoder.

  5. Fig latex (Ficus carica L. cultivar Dottato) in combination with UV irradiation decreases the viability of A375 melanoma cells in vitro.

    PubMed

    Menichini, Giulio; Alfano, Carmine; Provenzano, Eugenio; Marrelli, Mariangela; Statti, Giancarlo A; Somma, Francesco; Menichini, Francesco; Conforti, Filomena

    2012-10-01

    Melanoma and nonmelanoma skin cancers are among the most prevalent cancers in the human population. In the present work latex of Ficus carica cultivar Dottato from Italy collected from fruits and leaves was examined to assess its free radical-scavenging activity with 1,1-diphenyl-2 picrylhydrazyl (DPPH) and its phototoxicity on A375 human melanoma cells. The latex obtained from the fruits of Ficus carica cv. Dottato showed the best antiradical activity with an IC50 value of 0.05 mg/ml while the latex obtained from the leaves showed the best antiproliferative activity with an IC50 value of 1.5 μg/ml on the human tumor cell line A375 (melanoma) after irradiation at a specific UVA dose (1.08 J/cm2). Control experiments with UVA light or drugs alone were carried out without significant cytotoxic effects. Polyphenolic content of the samples was also evaluated. This is the first study comparing F. carica latex of leaves and fruits. Plant derived natural products have long been and will continue to be an important source for anticancer drug development.

  6. Neurotoxicity screening of new psychoactive substances (NPS): Effects on neuronal activity in rat cortical cultures using microelectrode arrays (MEA).

    PubMed

    Zwartsen, Anne; Hondebrink, Laura; Westerink, Remco Hs

    2018-05-01

    While the prevalence and the use of new psychoactive substances (NPS) is steadily increasing, data on pharmacological, toxicological and clinical effects is limited. Considering the large number of NPS available, there is a clear need for efficient in vitro screening techniques that capture multiple mechanisms of action. Neuronal cultures grown on multi-well microelectrode arrays (mwMEAs) have previously proven suitable for neurotoxicity screening of chemicals, pharmaceuticals and (illicit) drugs. We therefore used rat primary cortical cultures grown on mwMEA plates to investigate the effects of eight NPS (PMMA, α-PVP, methylone, MDPV, 2C-B, 25B-NBOMe, BZP and TFMPP) and two 'classic' illicit drugs (cocaine, methamphetamine) on spontaneous neuronal activity. All tested drugs rapidly and concentration-dependently decreased the weighted mean firing rate (wMFR) and the weighted mean burst rate (wMBR) during a 30 min acute exposure. Of the 'classic' drugs, cocaine most potently inhibited the wMFR (IC 50 9.8 μM), whereas methamphetamine and the structurally-related NPS PMMA were much less potent (IC 50 100 μM and IC 50 112 μM, respectively). Of the cathinones, MDPV and α-PVP showed comparable IC 50 values (29 μM and 21 μM, respectively), although methylone was 10-fold less potent (IC 50 235 μM). Comparable 10-fold differences in potency were also observed between the hallucinogenic phenethylamines 2C-B (IC 50 27 μM) and 25B-NBOMe (IC 50 2.4 μM), and between the piperazine derivatives BZP (IC 50 161 μM) and TFMPP (IC 50 19 μM). All drugs also inhibited the wMBR and concentration-response curves for wMBR and wMFR were comparable. For most drugs, IC 50 values are close to the estimated human brain concentrations following recreational doses of these drugs, highlighting the importance of this efficient in vitro screening approach for classification and prioritization of emerging NPS. Moreover, the wide range of IC 50 values observed for

  7. Information Commons for Rice (IC4R)

    PubMed Central

    2016-01-01

    Rice is the most important staple food for a large part of the world's human population and also a key model organism for plant research. Here, we present Information Commons for Rice (IC4R; http://ic4r.org), a rice knowledgebase featuring adoption of an extensible and sustainable architecture that integrates multiple omics data through community-contributed modules. Each module is developed and maintained by different committed groups, deals with data collection, processing and visualization, and delivers data on-demand via web services. In the current version, IC4R incorporates a variety of rice data through multiple committed modules, including genome-wide expression profiles derived entirely from RNA-Seq data, resequencing-based genomic variations obtained from re-sequencing data of thousands of rice varieties, plant homologous genes covering multiple diverse plant species, post-translational modifications, rice-related literatures and gene annotations contributed by the rice research community. Unlike extant related databases, IC4R is designed for scalability and sustainability and thus also features collaborative integration of rice data and low costs for database update and maintenance. Future directions of IC4R include incorporation of other omics data and association of multiple omics data with agronomically important traits, dedicating to build IC4R into a valuable knowledgebase for both basic and translational researches in rice. PMID:26519466

  8. On Patarin's Attack against the lIC Scheme

    NASA Astrophysics Data System (ADS)

    Ogura, Naoki; Uchiyama, Shigenori

    In 2007, Ding et al. proposed an attractive scheme, which is called the l-Invertible Cycles (lIC) scheme. lIC is one of the most efficient multivariate public-key cryptosystems (MPKC); these schemes would be suitable for using under limited computational resources. In 2008, an efficient attack against lIC using Gröbner basis algorithms was proposed by Fouque et al. However, they only estimated the complexity of their attack based on their experimental results. On the other hand, Patarin had proposed an efficient attack against some multivariate public-key cryptosystems. We call this attack Patarin's attack. The complexity of Patarin's attack can be estimated by finding relations corresponding to each scheme. In this paper, we propose an another practical attack against the lIC encryption/signature scheme. We estimate the complexity of our attack (not experimentally) by adapting Patarin's attack. The attack can be also applied to the lIC- scheme. Moreover, we show some experimental results of a practical attack against the lIC/lIC- schemes. This is the first implementation of both our proposed attack and an attack based on Gröbner basis algorithm for the even case, that is, a parameter l is even.

  9. Simulation of a class of hazardous situations in the ICS «INM RAS - Baltic Sea»

    NASA Astrophysics Data System (ADS)

    Zakharova, Natalia; Agoshkov, Valery; Aseev, Nikita; Parmuzin, Eugene; Sheloput, Tateana; Shutyaev, Victor

    2017-04-01

    Development of Informational Computational Systems (ICS) for data assimilation procedures is one of multidisciplinary problems. To study and solve these problems one needs to apply modern results from different disciplines and recent developments in mathematical modeling, theory of adjoint equations and optimal control, inverse problems, numerical methods theory, numerical algebra, scientific computing and processing of satellite data. In this work the results on the ICS development for PC-ICS "INM RAS - Baltic Sea" are presented. We discuss practical problems studied by ICS. The System includes numerical model of the Baltic Sea thermodynamics, the new oil spill model describing the propagation of a slick at the Sea surface (Agoshkov, Aseev et al., 2014) and the optimal ship route calculating block (Agoshkov, Zayachkovsky et al., 2014). The ICS is based on the INMOM numerical model of the Baltic Sea thermodynamics (Zalesny et al., 2013). It is possible to calculate main hydrodynamic parameters (temperature, salinity, velocities, sea level) using user-friendly interface of the ICS. The System includes data assimilation procedures (Agoshkov, 2003, Parmuzin, Agoshkov, 2012) and one can use the block of variational assimilation of the sea surface temperature in order to obtain main hydrodynamic parameters. Main possibilities of the ICS and several numerical experiments are presented in the work. By the problem of risk control is meant a problem of determination of optimal resources quantity which are necessary for decreasing the risk to some acceptable value. Mass of oil slick is chosen as a function of control. For the realization of the random variable the quadratic "functional of cost" is introduced. It comprises cleaning costs and deviation of damage of oil pollution from its acceptable value. The problem of minimization of this functional is solved based on the methods of optimal control and the theory of adjoint equations. The solution of this problem is

  10. Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.

    PubMed

    Fawcett, William P; Aracava, Yasco; Adler, Michael; Pereira, Edna F R; Albuquerque, Edson X

    2009-02-01

    This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.

  11. Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells

    PubMed Central

    2012-01-01

    Background Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. Methods The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT) assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells), and propidium iodide (for necrotic cells) dyes were employed. Results Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. Conclusions We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines. PMID:23351548

  12. Improvements to the Magnetics Information Consortium (MagIC) Paleo and Rock Magnetic Database

    NASA Astrophysics Data System (ADS)

    Jarboe, N.; Minnett, R.; Tauxe, L.; Koppers, A. A. P.; Constable, C.; Jonestrask, L.

    2015-12-01

    The Magnetic Information Consortium (MagIC) database (http://earthref.org/MagIC/) continues to improve the ease of data uploading and editing, the creation of complex searches, data visualization, and data downloads for the paleomagnetic, geomagnetic, and rock magnetic communities. Online data editing is now available and the need for proprietary spreadsheet software is therefore entirely negated. The data owner can change values in the database or delete entries through an HTML 5 web interface that resembles typical spreadsheets in behavior and uses. Additive uploading now allows for additions to data sets to be uploaded with a simple drag and drop interface. Searching the database has improved with the addition of more sophisticated search parameters and with the facility to use them in complex combinations. A comprehensive summary view of a search result has been added for increased quick data comprehension while a raw data view is available if one desires to see all data columns as stored in the database. Data visualization plots (ARAI, equal area, demagnetization, Zijderveld, etc.) are presented with the data when appropriate to aid the user in understanding the dataset. MagIC data associated with individual contributions or from online searches may be downloaded in the tab delimited MagIC text file format for susbsequent offline use and analysis. With input from the paleomagnetic, geomagnetic, and rock magnetic communities, the MagIC database will continue to improve as a data warehouse and resource.

  13. Observation of supernova remnant IC 443 with the Fermi Large Area Telescope

    DOE PAGES

    Abdo, A. A.

    2010-03-03

    Here, we report observation of the supernova remnant (SNR) IC 443 (G189.1+3.0) with the Fermi Gamma-ray Space Telescope Large Area Telescope (LAT) in the energy band between 200 MeV and 50 GeV. IC 443 is a shell-type SNR with mixed morphology located off the outer Galactic plane where high-energy emission has been detected in the X-ray, GeV and TeV gamma-ray bands. Past observations suggest IC 443 has been interacting with surrounding interstellar matter. Proximity between dense shocked molecular clouds and GeV-TeV gamma-ray emission regions detected by EGRET, MAGIC, and VERITAS suggests an interpretation that cosmic-ray (CR) particles are accelerated by the SNR. We accurately characterize the gamma-ray emission produced by the CRs accelerated at IC 443 using the high gamma-ray statistics and broad energy coverage provided by the LAT. The emission region is extended in the energy band with θ 68 = 0more » $$°\\atop{.}$$27 ± 0fdg01(stat) ± 0$$°\\atop{.}$$03(sys) for an assumed two-dimensional Gaussian profile and overlaps almost completely with the extended source region of VERITAS. Its centroid is displaced significantly from the known pulsar wind nebula (PWN) which suggests the PWN is not the major contributor in the present energy band. The observed spectrum changes its power-law slope continuously and continues smoothly to the MAGIC and VERITAS data points. Furthermore, the combined gamma-ray spectrum (200 MeV« less

  14. Evaluation of in vitro aldose reductase inhibitory potential of alkaloidal fractions of Piper nigrum, Murraya koenigii, Argemone mexicana, and Nelumbo nucifera.

    PubMed

    Gupta, Sakshi; Singh, Nirmal; Jaggi, Amteshwar Singh

    2014-05-01

    Aldose reductase is primarily involved in development of long-term diabetic complications due to increased polyol pathway activity. The synthetic aldose reductase inhibitors are not very successful clinically. Therefore, the natural sources may be exploited for safer and effective aldose reductase inhibitors. In the present study, the aldose reductase inhibitory potential of hydroalcoholic and alkaloidal extracts of Piper nigrum, Murraya koenigii, Argemone mexicana, and Nelumbo nucifera was evaluated. The hydroalcoholic and alkaloidal extracts of the selected plants were prepared. The different concentrations of hydroalcoholic and alkaloidal extracts of these plants were evaluated for their goat lens aldose reductase inhibitory activity using dl-glyceraldehyde as substrate. The aldose reductase inhibitory potential of extracts was assessed in terms of their IC50 value. Amongst the hydroalcoholic extracts, the highest aldose reductase inhibitory activity was shown by P. nigrum (IC50 value 35.64±2.7 μg/mL) followed by M. koenigii (IC50 value 45.67±2.57 μg/mL), A. mexicana (IC50 value 56.66±1.30 μg/mL), and N. nucifera (IC50 value 59.78±1.32 μg/mL). Among the alkaloidal extracts, highest inhibitory activity was shown by A. mexicana (IC50 value 25.67±1.25 μg/mL), followed by N. nucifera (IC50 value 28.82±1.85 μg/mL), P. nigrum (IC50 value 30.21±1.63 μg/mL), and M. koenigii (IC50 value 35.66±1.64 μg/mL). It may be concluded that the alkaloidal extracts of these plants possess potent aldose reductase inhibitory activity and may be therapeutically exploited in diabetes-related complications associated with increased activity of aldose reductase.

  15. Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides

    PubMed Central

    Forghani, Bita; Ebrahimpour, Afshin; Bakar, Jamilah; Abdul Hamid, Azizah; Hassan, Zaiton; Saari, Nazamid

    2012-01-01

    Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE) inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH) and peptide profiling (SDS-PAGE) of Stichopus horrens hydrolysates (SHHs) was also assessed. Alcalase hydrolysate showed the highest DH value (39.8%) followed by flavourzyme hydrolysate (32.7%). Overall, alcalase hydrolysate exhibited the highest ACE inhibitory activity (IC50 value of 0.41 mg/mL) followed by flavourzyme hydrolysate (IC50 value of 2.24 mg/mL), trypsin hydrolysate (IC50 value of 2.28 mg/mL), papain hydrolysate (IC50 value of 2.48 mg/mL), bromelain hydrolysate (IC50 value of 4.21 mg/mL), and protamex hydrolysate (IC50 value of 6.38 mg/mL). The SDS-PAGE results showed that alcalase hydrolysate represented a unique pattern compared to others, which yielded potent ACE inhibitory peptides with molecular weight distribution lower than 20 kDa. The evaluation of the relationship between DH and IC50 values of alcalase and flavourzyme hydrolysates revealed that the trend between those parameters was related to the type of the protease used. We concluded that the tested SHHs would be used as a potential source of functional ACE inhibitory peptides for physiological benefits. PMID:22927875

  16. Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides.

    PubMed

    Forghani, Bita; Ebrahimpour, Afshin; Bakar, Jamilah; Abdul Hamid, Azizah; Hassan, Zaiton; Saari, Nazamid

    2012-01-01

    Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE) inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH) and peptide profiling (SDS-PAGE) of Stichopus horrens hydrolysates (SHHs) was also assessed. Alcalase hydrolysate showed the highest DH value (39.8%) followed by flavourzyme hydrolysate (32.7%). Overall, alcalase hydrolysate exhibited the highest ACE inhibitory activity (IC(50) value of 0.41 mg/mL) followed by flavourzyme hydrolysate (IC(50) value of 2.24 mg/mL), trypsin hydrolysate (IC(50) value of 2.28 mg/mL), papain hydrolysate (IC(50) value of 2.48 mg/mL), bromelain hydrolysate (IC(50) value of 4.21 mg/mL), and protamex hydrolysate (IC(50) value of 6.38 mg/mL). The SDS-PAGE results showed that alcalase hydrolysate represented a unique pattern compared to others, which yielded potent ACE inhibitory peptides with molecular weight distribution lower than 20 kDa. The evaluation of the relationship between DH and IC(50) values of alcalase and flavourzyme hydrolysates revealed that the trend between those parameters was related to the type of the protease used. We concluded that the tested SHHs would be used as a potential source of functional ACE inhibitory peptides for physiological benefits.

  17. The open cluster IC 4665

    NASA Technical Reports Server (NTRS)

    Prosser, Charles F.

    1993-01-01

    The results of a combined astrometric, photometric, and spectroscopic program to identify members of the open cluster IC 4665 are presented. Numerous new proper motion/photometric candidate members and at least 23 M dwarfs with H-alpha emission have been identified. A reanalysis of IC 4665 age using different methods yields conflicting results ranging from about 3 X 10 exp 7 yr to the age of the Pleiades. This study provides a list of candidate cluster members in the intermediate and low-mass regime of this cluster. Future spectroscopic observations of these candidates should eventually identify true cluster members.

  18. Semiconductor/High-Tc-Superconductor Hybrid ICs

    NASA Technical Reports Server (NTRS)

    Burns, Michael J.

    1995-01-01

    Hybrid integrated circuits (ICs) containing both Si-based semiconducting and YBa(2)Cu(3)O(7-x) superconducting circuit elements on sapphire substrates developed. Help to prevent diffusion of Cu from superconductors into semiconductors. These hybrid ICs combine superconducting and semiconducting features unavailable in superconducting or semiconducting circuitry alone. For example, complementary metal oxide/semiconductor (CMOS) readout and memory devices integrated with fast-switching Josephson-junction super-conducting logic devices and zero-resistance interconnections.

  19. A Way to End the IC Designer Shortage.

    ERIC Educational Resources Information Center

    Robinson, Arthur L.

    1980-01-01

    Discusses the problem of the shortage of engineers capable of designing advanced integrated circuits (IC) and presents some suggestions for increasing the number of IC designers in universities and semiconductor companies. (HM)

  20. Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors.

    PubMed

    Maksay, Gábor; Vincze, Zoltán; Nemes, Péter

    2009-10-01

    Heteroaromatic carboxylic esters of (nor)tropine were synthesized. Tropine esters displaced [(3)H]strychnine binding to glycine receptors of rat spinal cord with low Hill slopes. Two-site displacement resulted in nanomolar IC(50,1) and micromolar IC(50,2) values, and IC(50,2)/IC(50,1) ratios up to 615 depending on the heteroaromatic rings and N-methyl substitution. Nortropeines displayed high affinity and low heterogeneity. IC(50,1) and IC(50,2) values of tropeines did not correlate suggesting different binding modes/sites. Glycine potentiated only the nanomolar displacement reflecting positive allosteric interactions and potentiation of ionophore function. Affinities of three (nor)tropeines were different for glycine receptors but identical for 5-HT(3) receptors.

  1. Thackeray's Globules in IC 2944

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Strangely glowing dark clouds float serenely in this remarkable and beautiful image taken with NASA's Hubble Space Telescope. These dense, opaque dust clouds - known as 'globules' - are silhouetted against nearby bright stars in the busy star-forming region, IC 2944. These globules were first found in IC 2944 by astronomer A.D. Thackeray in 1950. Although globules like these have been known since Dutch-American astronomer Bart Bok first drew attention to such objects in 1947, little is still known about their origin and nature, except that they are generally associated with areas of star formation, called 'HII regions' due to the presence of hydrogen gas. The largest of the globules in this image is actually two separate clouds that gently overlap along our line of sight. Each cloud is nearly 1.4 light-years (50 arcseconds) along its longest dimension, and collectively, they contain enough material to equal over 15 solar masses. IC 2944, the surrounding HII region, is filled with gas and dust that is illuminated and heated by a loose cluster of O-type stars. These stars are much hotter and much more massive than our Sun. IC 2944 is relatively close by, located only 5900 light-years (1800 parsecs) away in the constellation Centaurus. Thanks to the remarkable resolution offered by the Hubble Space Telescope, astronomers can for the first time study the intricate structure of these globules. The globules appear to be heavily fractured, as if major forces were tearing them apart. When radio astronomers observed the faint hiss of molecules within the globules, they realized that the globules are actually in constant, churning motion, moving supersonically among each other. This may be caused by the powerful ultraviolet radiation from the luminous, massive stars, which also heat up the gas in the HII region, causing it to expand and stream against the globules, leading to their destruction. Despite their serene appearance, the globules may actually be likened to clumps

  2. The defective nature of ice Ic and its implications for atmospheric science

    NASA Astrophysics Data System (ADS)

    Kuhs, W. F.; Hansen, T. C.

    2009-04-01

    The possible atmospheric implication of ice Ic (cubic ice) has already been suggested some time ago in the context of snow crystal formation [1]. New findings from air-borne measurements in cirrus clouds and contrails have put ice Ic into the focus of interest to understand the so-called "supersaturation puzzle" [2,3,4,5]. Our recent microstructural work on ice Ic [6,7] appears to be highly relevant in this context. We have found that ice Ic is characterized by a complex stacking fault pattern, which changes as a function of temperature as well as time. Indeed, from our own [8] and other group's work [9] one knows that (in contrast to earlier believe) ice Ic can form up to temperatures at least as high as 240K - thus in the relevant range for cirrus clouds. We have good preliminary evidence that the "cubicity" (which can be related to stacking fault probabilities) as well as the particle size of ice Ic are the relevant parameters for this correlation. The "cubicity" of stacking faulty ice Ic (established by diffraction) correlates nicely with the increased supersaturation at decreasing temperatures observed in cirrus clouds and contrails, a fact, which may be considered as further evidence for the presence of ice Ic. Moreover, the stacking faults lead to kinks in the outer shapes of the minute ice Ic crystals as seen by cryo scanning electron microscopy (cryo-SEM); these defective sites are likely to play some role in heterogeneous reactions in the atmosphere. The cryo-SEM work suggests that stacking-faulty ice Ic has many more active centres for such reactions than the usually considered thermodynamically stable form, ice Ih. [1] T Kobayashi & T Kuroda (1987) Snow Crystals. In: Morphology of Crystals (ed. I Sunagawa), Terra Scientific Publishing, Tokyo, pp.649-743. [2] DM Murphy (2003) Dehydration in cold clouds is enhanced by a transition from from cubic to hexagonal ice. Geophys.Res.Lett.,30, 2230, doi:10.1029/2003GL018566. [3] RS Gao & 19 other authors (2004

  3. Embedded I&C for Extreme Environments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kisner, Roger A.

    2016-04-01

    This project uses embedded instrumentation and control (I&C) technologies to demonstrate potential performance gains of nuclear power plant components in extreme environments. Extreme environments include high temperature, radiation, high pressure, high vibration, and high EMI conditions. For extreme environments, performance gains arise from moment-to-moment sensing of local variables and immediate application of local feedback control. Planning for embedding I&C during early system design phases contrasts with the traditional, serial design approach that incorporates minimal I&C after mechanical and electrical design is complete. The demonstration application involves the development and control of a novel, proof-of-concept motor/pump design. The motor and pumpmore » combination operate within the fluid environment, eliminating the need for rotating seals. Actively controlled magnetic bearings also replace failure-prone mechanical contact bearings that typically suspend rotating components. Such as design has the potential to significantly enhance the reliability and life of the pumping system and would not be possible without embedded I&C.« less

  4. Molecular Hydrogen Fluorescence in IC 63

    NASA Technical Reports Server (NTRS)

    Andersson, B-G

    2005-01-01

    This grant has supported the acquisition, reduction and analysis of data targeting the structure and excitation of molecular hydrogen in the reflection nebula IC 63 and in particular the fluorescent emission seen in the UV. In addition to manpower for analyzing the FUSE data, the grant supported the (attempted) acquisition of supporting ground-based data. We proposed for and received observing time for two sets of ground based, data; narrow band imaging ([S II], [O III) at KPNO (July 2002; Observer: Burgh) and imaging spectro-photometry of several of the near-infrared rotation-vibration lines of H2 at the IRTF (October 2003; Observer: Andersson). Unfortunately, both of these runs were failures, primarily because of bad weather, and did not result in any useful data. We combined the FUSE observations with rocket borne observations of the star responsible for exciting the H2 fluorescence in IC 63: gamma Cas, and with archival HUT observations of IC 63, covering the long-wavelength part of the molecular hydrogen fluorescence.

  5. Inhibition of lipoxygenases and cyclooxygenase-2 enzymes by extracts isolated from Bacopa monniera (L.) Wettst.

    PubMed

    Viji, V; Helen, A

    2008-07-23

    Bacopa monniera Linn is described in the Ayurvedic Materia Medica, as a therapeutically useful herb for the treatment of inflammation. In the current study, we investigated the anti-inflammatory activity of methanolic extract of Bacopa monniera (BME). For some experiments EtOAc and bacoside fractions were prepared from BME. The effect of these extracts in modulating key mediators of inflammation was evaluated. Carrageenan-induced rat paw edema, rat mononuclear cells and human whole blood assay were employed as in vivo and in vitro models. In carrageenan-induced rat paw edema, BME brought about 82% edema inhibition at a dose of 100mg/kg i.p. when compared to indomethacin (INDO) (3mg/kg) that showed 70% edema inhibition. BME also significantly inhibited 5-lipoxygenase (5-LOX), 15-LOX and cyclooxygenase-2 (COX-2) activities in rat monocytes in vivo. Among the fractions tested in vitro, EtOAc fraction possessed significant 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity with IC(50) value of 30 microg/ml compared to butylated hydroxyl toluene (IC(50) = 13 microg/ml). This fraction also exerted significant hydroxyl radical scavenging activity with IC(50) value of 25 microg/ml in comparison with quercetin (IC(50) = 5 microg/ml). Inhibitory effects of EtOAc and bacoside fractions on LOX and COX activities in Ca-A23187 stimulated rat mononuclear cells were also assessed. 5-LOX IC(50) values were 25 microg/ml for EtOAc, 68 microg/ml for bacosides and 2 microg/ml for nordihydroguaiaretic acid (NDGA) where as COX-2 IC(50) values were 1.32 microg/ml for EtOAc, 1.19 microg/ml for bacoside fraction and 0.23 microg/ml for indomethacin. EtOAc and bacoside fractions also brought about significant decrease in TNF-alpha release ex vivo. Bacopa monniera possesses anti-inflammatory activity through inhibition of COX and LOX and downregulation of TNF-alpha.

  6. Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice.

    PubMed

    Sheng, Rong; Xu, Xianxiang; Tang, Qin; Bian, Difei; Li, Ying; Qian, Cheng; He, Xin; Gao, Xinghua; Pan, Rong; Wang, Chong; Luo, Yubin; Xia, Yufeng; Dai, Yue

    2011-01-01

    Radix Pseudostellariae is used as a tonic drug in traditional Chinese medicine with immunomodulating and anti-fatigue activities, and the polysaccharide is considered as the main active component. The purpose of this study is to examine the effect of the polysaccharide isolated from Radix Pseudostellariae (PRP) on mouse chronic fatigue syndrome (CFS) induced by intraperitoneal injection of polyriboinosinic:polyribocytidylic acid (poly I:C), a double-stranded synthetic RNA. It has shown that the fatigue symptom of mice lasted at least 1 week as evaluated by forced swimming time. PRP (100, 200, 400 mg kg(-1)), orally administered 3 days before poly I:C injection, showed dose-dependent anti-fatigue effects. In addition, poly I:C led to evident alternations in neuroendocrine and immune systems of mice, such as reduced spontaneous activity and learning ability, declined serum level of corticosterone, increased weight indexes and T lymphocyte numbers in thymuses and spleens, and increased CD4(+)/CD8(+) ratio but decreased proliferation ability of T lymphocytes in spleens. PRP alleviated the abnormalities caused by poly I:C, and restored the function of hosts to normal conditions. The findings suggest that PRP is beneficial to CFS, and the underlying mechanisms of action involve neuroendocrine and immune systems.

  7. H I debris in the IC 1459 galaxy group

    NASA Astrophysics Data System (ADS)

    Saponara, Juliana; Koribalski, Bärbel S.; Benaglia, Paula; Fernández López, Manuel

    2018-01-01

    We present H I synthesis imaging of the giant elliptical galaxy IC 1459 and its surroundings with the Australia Telescope Compact Array. Our search for extended H I emission revealed a large complex of H I clouds near IC 1459, likely to be the debris from tidal interactions with neighbouring galaxies. The total H I mass (∼109 M⊙) in the detected clouds spans 250 kpc from the north-east of the gas-rich spiral NGC 7418A to the south-east of IC 1459. The extent and mass of the H I debris, which shows rather irregular morphology and kinematics, are similar to those in other nearby groups. Together with H I clouds recently detected near two other IC 1459 group members, namely IC 5270 and NGC 7418, using phased-array feeds on the Australian Square Kilometre Array Pathfinder, the detected debris make up a significant fraction of the group's intergalactic medium.

  8. The remarkable infrared galaxy Arp 220 = IC 4553

    NASA Technical Reports Server (NTRS)

    Soifer, B. T.; Neugebauer, G.; Helou, G.; Lonsdale, C. J.; Hacking, P.; Rice, W.; Houck, J. R.; Low, F. J.; Rowan-Robinson, M.

    1984-01-01

    IRAS observations of the peculiar galaxy Arp 220 = IC 4553 show that it is extremely luminous in the far-infrared, with a total luminosity of 2 x 10 to the 12th solar luminosities. The infrared-to-blue luminosity ratio of this galaxy is about 80, which is the largest value of the ratio for galaxies in the UGC catalog, and places it in the range of the 'unidentified' infrared sources recently reported by Houck et al. in the IRAS all-sky survey. Other observations of Arp 220, combined with the luminosity in the infrared, allow either a Seyfert-like or starburst origin for this luminosity.

  9. N-cinnamoylation of antimalarial classics: quinacrine analogues with decreased toxicity and dual-stage activity.

    PubMed

    Gomes, Ana; Pérez, Bianca; Albuquerque, Inês; Machado, Marta; Prudêncio, Miguel; Nogueira, Fátima; Teixeira, Cátia; Gomes, Paula

    2014-02-01

    Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50 =17.0-39.0 nM) and chloroquine-resistant W2 and Dd2 strains (IC50 =3.2-41.2 and 27.1-131.0 nM, respectively), and liver-stage P.berghei (IC50 =1.6-4.9 μM) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Saturn V S-IC (First) Stage

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This cutaway illustration shows the Saturn V S-IC (first) stage with detailed callouts of the components. The S-IC Stage is 138 feet long and 33 feet in diameter, producing 7,500,000 pounds of thrust through five F-1 engines that are powered by liquid oxygen and kerosene. Four of the engines are mounted on an outer ring and gimbal for control purposes. The fifth engine is rigidly mounted in the center. When ignited, the roar produced by the five engines equals the sound of 8,000,000 hi-fi sets.

  11. 2,4,6-Trichlorophenylhydrazine Schiff bases as DPPH radical and super oxide anion scavengers.

    PubMed

    Khan, Khalid Mohammed; Shah, Zarbad; Ahmad, Viqar Uddin; Khan, Momin; Taha, Muhammad; Rahim, Fazal; Ali, Sajjad; Ambreen, Nida; Perveen, Shahnaz; Choudhary, M Iqbal; Voelter, Wolfgang

    2012-05-01

    Syntheses of thirty 2,4,6-trichlorophenylhydrazine Schiff bases 1-30 were carried out and evaluated for their in vitro DPPH radical and super oxide anion scavenging activities. Compounds 1-30 have shown a varying degree of DPPH radical scavenging activity and their IC50 values range between 4.05-369.30 µM. The compounds 17, 28, 18, 14, 8, 15, 12, 2, 29, and 7 exhibited IC50 values ranging between 4.05±0.06-24.42±0.86 µM which are superior to standard n-propylgallate (IC50=30.12±0.27 µM). Selected compounds have shown a varying degree of superoxide anion radical scavenger activity and their IC50 values range between 91.23-406.90 µM. The compounds 28, 8, 17, 15, and 14, showed IC50 values between 91.23±1.2-105.31±2.29 µM which are superior to standard n-propylgallate (IC50=106.34±1.6 µM).

  12. Growing Aligned Carbon Nanotubes for Interconnections in ICs

    NASA Technical Reports Server (NTRS)

    Li, Jun; Ye, Qi; Cassell, Alan; Ng, Hou Tee; Stevens, Ramsey; Han, Jie; Meyyappan, M.

    2005-01-01

    A process for growing multiwalled carbon nanotubes anchored at specified locations and aligned along specified directions has been invented. Typically, one would grow a number of the nanotubes oriented perpendicularly to a silicon integrated-circuit (IC) substrate, starting from (and anchored on) patterned catalytic spots on the substrate. Such arrays of perpendicular carbon nanotubes could be used as electrical interconnections between levels of multilevel ICs. The process (see Figure 1) begins with the formation of a layer, a few hundred nanometers thick, of a compatible electrically insulating material (e.g., SiO(x) or Si(y)N(z) on the silicon substrate. A patterned film of a suitable electrical conductor (Al, Mo, Cr, Ti, Ta, Pt, Ir, or doped Si), having a thickness between 1 nm and 2 m, is deposited on the insulating layer to form the IC conductor pattern. Next, a catalytic material (usually, Ni, Fe, or Co) is deposited to a thickness between 1 and 30 nm on the spots from which it is desired to grow carbon nanotubes. The carbon nanotubes are grown by plasma-enhanced chemical vapor deposition (PECVD). Unlike the matted and tangled carbon nanotubes grown by thermal CVD, the carbon nanotubes grown by PECVD are perpendicular and freestanding because an electric field perpendicular to the substrate is used in PECVD. Next, the free space between the carbon nanotubes is filled with SiO2 by means of CVD from tetraethylorthosilicate (TEOS), thereby forming an array of carbon nanotubes embedded in SiO2. Chemical mechanical polishing (CMP) is then performed to remove excess SiO2 and form a flat-top surface in which the outer ends of the carbon nanotubes are exposed. Optionally, depending on the application, metal lines to connect selected ends of carbon nanotubes may be deposited on the top surface. The top part of Figure 2 is a scanning electron micrograph (SEM) of carbon nanotubes grown, as described above, on catalytic spots of about 100 nm diameter patterned by

  13. Decreasing trend in severe weather occurrence over China during the past 50 years.

    PubMed

    Zhang, Qinghong; Ni, Xiang; Zhang, Fuqing

    2017-02-17

    Understanding the trend of localized severe weather under the changing climate is of great significance but remains challenging which is at least partially due to the lack of persistent and homogeneous severe weather observations at climate scales while the detailed physical processes of severe weather cannot be resolved in global climate models. Based on continuous and coherent severe weather reports from over 500 manned stations, for the first time, this study shows a significant decreasing trend in severe weather occurrence across China during the past five decades. The total number of severe weather days that have either thunderstorm, hail and/or damaging wind decrease about 50% from 1961 to 2010. It is further shown that the reduction in severe weather occurrences correlates strongly with the weakening of East Asian summer monsoon which is the primary source of moisture and dynamic forcing conducive for warm-season severe weather over China.

  14. Decreasing trend in severe weather occurrence over China during the past 50 years

    PubMed Central

    Zhang, Qinghong; Ni, Xiang; Zhang, Fuqing

    2017-01-01

    Understanding the trend of localized severe weather under the changing climate is of great significance but remains challenging which is at least partially due to the lack of persistent and homogeneous severe weather observations at climate scales while the detailed physical processes of severe weather cannot be resolved in global climate models. Based on continuous and coherent severe weather reports from over 500 manned stations, for the first time, this study shows a significant decreasing trend in severe weather occurrence across China during the past five decades. The total number of severe weather days that have either thunderstorm, hail and/or damaging wind decrease about 50% from 1961 to 2010. It is further shown that the reduction in severe weather occurrences correlates strongly with the weakening of East Asian summer monsoon which is the primary source of moisture and dynamic forcing conducive for warm-season severe weather over China. PMID:28211465

  15. Decreasing trend in severe weather occurrence over China during the past 50 years

    NASA Astrophysics Data System (ADS)

    Zhang, Qinghong; Ni, Xiang; Zhang, Fuqing

    2017-04-01

    Understanding the trend of localized severe weather under the changing climate is of great significance but remains challenging which is at least partially due to the lack of persistent and homogeneous severe weather observations at climate scales while the detailed physical processes of severe weather cannot be resolved in global climate models. Based on continuous and coherent severe weather reports from over 500 manned stations, for the first time, this study shows a significant decreasing trend in severe weather occurrence across China during the past five decades. The total number of severe weather days that have either thunderstorm, hail and/or damaging wind decrease about 50% from 1961 to 2010. It is further shown that the reduction in severe weather occurrences correlates strongly with the weakening of East Asian summer monsoon which is the primary source of moisture and dynamic forcing conducive for warm-season severe weather over China.

  16. Decreasing trend in severe weather occurrence over China during the past 50 years

    NASA Astrophysics Data System (ADS)

    Zhang, Qinghong; Ni, Xiang; Zhang, Fuqing

    2017-02-01

    Understanding the trend of localized severe weather under the changing climate is of great significance but remains challenging which is at least partially due to the lack of persistent and homogeneous severe weather observations at climate scales while the detailed physical processes of severe weather cannot be resolved in global climate models. Based on continuous and coherent severe weather reports from over 500 manned stations, for the first time, this study shows a significant decreasing trend in severe weather occurrence across China during the past five decades. The total number of severe weather days that have either thunderstorm, hail and/or damaging wind decrease about 50% from 1961 to 2010. It is further shown that the reduction in severe weather occurrences correlates strongly with the weakening of East Asian summer monsoon which is the primary source of moisture and dynamic forcing conducive for warm-season severe weather over China.

  17. Comparative performance of a combined injectable contraceptive (50 mg norethisterone enanthate plus 5mg estradiol valerate) and a combined oral contraceptive (0.15 mg levonorgestrel plus 0.03 mg ethinyl estradiol) in adolescents.

    PubMed

    Molina, Ramiro C; Sandoval, Jorge Z; Montero, Adela V; Oyarzún, Pamela G; Molina, Temístocles G; González, Electra A

    2009-02-01

    To compare in a regular non-clinical trial experience the efficacy, acceptability, and continuation rates of an injectable contraceptive containing 50 mg norethisterone enanthate plus 5mg estradiol valerate (IC) and an oral contraceptive containing 0.15 mg levonorgestrel plus 0.03 mg ethinyl estradiol (OC), among adolescent users. A total of 251 adolescents ages 14-19 were followed during 12 months. The IC group (124 subjects) was studied for 1044 cycles and the OC group (127 subjects) was studied for 1368 cycles. The users were not assigned in a random selection. Information was collected from clinical records. Groups were compared using Pearson chi-square, odds ratio (95% confidence interval), t-test, and proportion difference test. The IC group had significant differences in baseline social risk, confidence, psychiatric problems, consumption of alcohol, and number of sexual partners. At 12 months, the IC group showed significant decrease in weight and increase in hypermenorrhea. In the OC group, dysmenorrhea decreased, and hypomenorrhea and regular cycles were significantly more frequent. One pregnancy occurred in the OC group (Pearl Index: 0.88). Final continuation rates at 12 months were 41.9% and 37.8% for IC and OC, respectively. The monthly injectable is a recommended contraceptive option for adolescents, especially for those facing psychosocial risk factors.

  18. Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

    PubMed

    Jin, Meihua; Lu, Yue; Yang, Ju Hye; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil; Park, Sang-Jo; Son, Kun Ho; Chang, Hyeun Wook

    2011-09-01

    6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.

  19. Dynamical histories of the IC 348 and NGC 1333 star-forming regions in Perseus

    NASA Astrophysics Data System (ADS)

    Parker, Richard J.; Alves de Oliveira, Catarina

    2017-07-01

    We present analyses of the spatial distributions of stars in the young (1-3 Myr) star-forming regions IC 348 and NGC 1333 in the Perseus giant molecular cloud. We quantify the spatial structure using the Q-parameter and find that both IC 348 and NGC 1333 are smooth and centrally concentrated with Q-parameters of 0.98 and 0.89, respectively. Neither region exhibits mass segregation (Λ _MSR = 1.1^{+0.2}_{-0.3} for IC 348 and Λ _MSR = 1.2^{+0.4}_{-0.3} for NGC 1333, where ΛMSR ˜ 1 corresponds to no mass segregation) nor do the most massive stars reside in areas of enhanced stellar surface density compared to the average surface density, according to the ΣLDR method. We then constrain the dynamical histories and hence initial conditions of both regions by comparing the observed values to N-body simulations at appropriate ages. Stars in both regions likely formed with subvirial velocities that contributed to merging of substructure and the formation of smooth clusters. The initial stellar densities were no higher than ρ ˜ 100-500 M⊙ pc-3 for IC 348 and ρ ˜ 500-2000 M⊙ pc-3 for NGC 1333. These initial densities, in particular that of NGC 1333, are high enough to facilitate dynamical interactions that would likely affect ˜10 per cent of protoplanetary discs and binary stars.

  20. Towards a better understanding of the evolution of Wolf-Rayet stars and Type Ib/Ic supernova progenitors

    NASA Astrophysics Data System (ADS)

    Yoon, Sung-Chul

    2017-10-01

    Hydrogen-deficient Wolf-Rayet (WR) stars are potential candidates of Type Ib/Ic supernova (SN Ib/Ic) progenitors and their evolution is governed by mass-loss. Stellar evolution models with the most popular prescription for WR mass-loss rates given by Nugis & Lamers have difficulties in explaining the luminosity distribution of WR stars of WC and WO types and the SN Ic progenitor properties. Here, we suggest some improvements in the WR mass-loss rate prescription and discuss its implications for the evolution of WR stars and SN Ib/Ic progenitors. Recent studies on Galactic WR stars clearly indicate that the mass-loss rates of WC stars are systematically higher than those of WNE stars for a given luminosity. The luminosity and initial metallicity dependences of WNE mass-loss rates are also significantly different from those of WC stars. These factors have not been adequately considered together in previous stellar evolution models. We also find that an overall increase of WR mass-loss rates by about 60 per cent compared to the empirical values obtained with a clumping factor of 10 is needed to explain the most faint WC/WO stars. This moderate increase with our new WR mass-loss rate prescription results in SN Ib/Ic progenitor models more consistent with observations than those given by the Nugis & Lamers prescription. In particular, our new models predict that the properties of SN Ib and SN Ic progenitors are distinctively different, rather than they form a continuous sequence.

  1. Interband cascade (IC) photovoltaic (PV) architecture for PV devices

    DOEpatents

    Yang, Rui Q.; Tian, Zhaobing; Mishima, Tetsuya D.; Santos, Michael B.; Johnson, Matthew B.; Klem, John F.

    2015-10-20

    A photovoltaic (PV) device, comprising a PV interband cascade (IC) stage, wherein the IC PV stage comprises an absorption region with a band gap, the absorption region configured to absorb photons, an intraband transport region configured to act as a hole barrier, and an interband tunneling region configured to act as an electron barrier. An IC PV architecture for a photovoltaic device, the IC PV architecture comprising an absorption region, an intraband transport region coupled to the absorption region, and an interband tunneling region coupled to the intraband transport region and to the adjacent absorption region, wherein the absorption region, the intraband transport region, and the interband tunneling region are positioned such that electrons will flow from the absorption region to the intraband transport region to the interband tunneling region.

  2. EXTRACTION AND DETECTION OF A NEW ARSINE SULFIDE CONTAINING ARSENOSUGAR IN MOLLUSCS BY IC-ICP-MS AND IC-ESI-MS/MS

    EPA Science Inventory

    Using IC-ICP-MS and IC-ESI-MS/MS, an unknown arsenical compound in mollusks has been identified as a new arsine sulfide containing analog of a known arsenosugar and is referred to as As(498). This species has been observed in four separate shellfish species following a mild metha...

  3. High-precision QEC values of superallowed 0+ → 0+β-emitters 46Cr, 50Fe and 54Ni

    NASA Astrophysics Data System (ADS)

    Zhang, P.; Xu, X.; Shuai, P.; Chen, R. J.; Yan, X. L.; Zhang, Y. H.; Wang, M.; Litvinov, Yu. A.; Blaum, K.; Xu, H. S.; Bao, T.; Chen, X. C.; Chen, H.; Fu, C. Y.; He, J. J.; Kubono, S.; Lam, Y. H.; Liu, D. W.; Mao, R. S.; Ma, X. W.; Sun, M. Z.; Tu, X. L.; Xing, Y. M.; Yang, J. C.; Yuan, Y. J.; Zeng, Q.; Zhou, X.; Zhou, X. H.; Zhan, W. L.; Litvinov, S.; Audi, G.; Uesaka, T.; Yamaguchi, Y.; Yamaguchi, T.; Ozawa, A.; Sun, B. H.; Sun, Y.; Xu, F. R.

    2017-04-01

    Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are - 29471 (11) keV, - 34477 (6) keV and - 39278 (4) keV, respectively. The superallowed 0+ →0+β-decay Q values were derived to be QEC (46Cr) = 7604 (11) keV, QEC (50Fe) = 8150 (6) keV and QEC (54Ni) = 8731 (4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected Ft values to be Ft (50Fe) = 3103 (70) s and Ft (54Ni) = 3076 (50) s. The main contribution to the Ft uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.

  4. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

    PubMed

    Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

    2016-04-05

    Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.

    PubMed Central

    Heuschneider, G; Schwartz, R D

    1989-01-01

    The effects of the cyclic nucleotide cAMP on gamma-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner (IC50 = 1.3 mM). The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the gamma-aminobutyric acid-gated Cl- channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36Cl- uptake and generated cAMP with similar potencies (IC50 = 14.3 microM; EC50 = 6.2 microM, respectively). Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl- channel directly. Indeed, forskolin inhibition of muscimol-induced 36Cl- uptake was extremely rapid (within 5 sec), preceding the accumulation of sufficient levels of cAMP. After 5 min, a slower phase of inhibition was seen, similar to the time course for cAMP accumulation. The data suggest that gamma-aminobutyric acid (GABAA) receptor function in brain can be regulated by cAMP-dependent phosphorylation. PMID:2468163

  6. Quinazolin-4-one derivatives as selective histone deacetylase-6 inhibitors for the treatment of Alzheimer's disease.

    PubMed

    Yu, Chao-Wu; Chang, Pei-Teh; Hsin, Ling-Wei; Chern, Ji-Wang

    2013-09-12

    Novel quinazolin-4-one derivatives containing a hydroxamic acid moiety were designed and synthesized. All compounds were subjected to histone deacetylase (HDAC) enzymatic assays to identify selective HDAC6 inhibitors with nanomolar IC50 values. (E)-3-(2-Ethyl-7-fluoro-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-N-hydroxyacrylamide, 4b, is the most potent HDAC6 inhibitor (IC50, 8 nM). In vitro, these compounds induced neurite outgrowth accompanied by growth-associated protein 43 expression, and they enhanced the synaptic activities of PC12 and SH-SY5Y neuronal cells without producing toxic or mitogenic effects. Several of the compounds dramatically increased nonhistone protein acetylation, specifically of α-tubulin. Some of the more potent HDAC6 inhibitors decreased zinc-mediated β-amyloid aggregation in vitro. N-Hydroxy-3-(2-methyl-4-oxo-3-phenethyl-3,4-dihydro-quinazolin-7-yl)-acrylamide, 3f, the most promising drug candidate, selectively inhibits HDAC6 (IC50, 29 nM), practically does not affect human ether-a-go-go-related membrane channel activity (IC50 >10 μM) or cytochrome P450 activity (IC50 >6.5 μM) in vitro, and significantly improves learning-based performances of mice with β-amyloid-induced hippocampal lesions.

  7. A radial velocity survey of the open cluster IC 4665

    NASA Technical Reports Server (NTRS)

    Prosser, Charles F.; Giampapa, Mark S.

    1994-01-01

    A radial velocity survey of the open cluster IC 4665 is reported for a group of candidate members previously identified on the basis of proper motion and photometry. Of those candidates observed, 20 out of 42 have radial velocities consistent with membership; these cluster members populate the F5-K0 dwarf region and represent the first relatively conclusive membership determinations for such solar-type stars in IC 4665. Three new spectroscopic binary members of the cluster have been identified. Rotational velocities have also been derived; the v sin i distribution among IC 4665 members reveals that most apparent G dwarf members of IC 4665 are seen to exhibit substantial rotation (v sin i greater than 10 km/s). When compared to evolutionary isochrones, the current list of intermediate-mass members appears to support earlier suggestions that IC 4665 has an age comparable to the Pleiades.

  8. Bioactive components from the heartwood of Pterocarpus santalinus.

    PubMed

    Wu, Shou-Fang; Hwang, Tsong-Long; Chen, Shu-Li; Wu, Chin-Chung; Ohkoshi, Emika; Lee, Kuo-Hsiung; Chang, Fang-Rong; Wu, Yang-Chang

    2011-09-15

    One new phenanthrenedione, pterolinus K (1), and one new chalcone, pterolinus L (2) were isolated from the heartwood extract of Pterocarpus santalinus. The structures were elucidated by spectroscopic methods. Both 1 and 2 showed inhibitory effect on elastase release by human neutrophils in response to fMLP with an IC(50) value of 4.24 and 0.95 μM, and compound 1 also inhibited superoxide anion generation with IC(50) value of 0.99 μM. In addition, compound 1 showed selective cytotoxicity against HepG2 with IC(50) value of 10.86 μM, while compound 2 showed a moderate cytotoxicity against KB with IC(50) values of 17.18 μM. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

    PubMed

    Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

    2006-10-01

    An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC(50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

  10. Interpretation of two compact planetary nebulae, IC 4997 and NGC 6572, with aid of theoretical models.

    PubMed Central

    Hyung, S; Aller, L H

    1993-01-01

    Observations of two dense compact planetary nebulae secured with the Hamilton Echelle spectrograph at Lick Observatory combined with previously published UV spectra secured with the International Ultraviolet Explorer enable us to probe the electron densities and temperatures (plasma diagnostics) and ionic concentrations in these objects. The diagnostic diagrams show that no homogenous model will work for these nebulae. NGC 6572 may consist of an inner torordal ring of density 25,000 atoms/cm3 and an outer conical shell of density 10,000 atoms/cm3. The simplest model of IC 4997 suggests a thick inner shell with a density of about 107 atoms/cm3 and an outer envelope of density 10,000 atoms/cm3. The abundances of all elements heavier than He appear to be less than the solar values in NGC 6572, whereas He, C, N, and O may be more abundant in IC 4997 than in the sun. IC 4997 presents puzzling problems. PMID:11607347

  11. Itraconazole decreases left ventricular contractility in isolated rabbit heart: Mechanism of action

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qu, Yusheng, E-mail: yqu@amgen.com; Fang, Mei; Gao, BaoXi

    Itraconazole (ITZ) is an approved antifungal agent that carries a “black box warning” in its label regarding a risk of negative cardiac inotropy based on clinical findings. Since the mechanism of the negative inotropic effect is unknown, we performed a variety of preclinical and mechanistic studies to explore the pharmacological profile of ITZ and understand the negative inotropic mechanism. ITZ was evaluated in: (1) an isolated rabbit heart (IRH) preparation using Langendorff retrograde perfusion; (2) ion channel studies; (3) a rat heart mitochondrial function profiling screen; (4) a mitochondrial membrane potential (MMP) assay; (5) in vitro pharmacology profiling assays (148more » receptors, ion channels, transporters, and enzymes); and (6) a kinase selectivity panel (451 kinases). In the IRH, ITZ decreased cardiac contractility (> 30%) at 0.3 μM, with increasing effect at higher concentrations, which indicated a direct negative inotropic effect upon the heart. It also decreased heart rate and coronary flow (≥ 1 μM) and prolonged PR/QRS intervals (3 μM). In mechanistic studies, ITZ inhibited the cardiac NaV channel (IC{sub 50}: 4.2 μM) and was devoid of any functional inhibitory effect at the remaining pharmacological targets. Lastly, ITZ did not affect MMP, nor interfere with mitochondrial enzymes or processes involved with fuel substrate utilization or energy formation. Overall, the cardiovascular and mechanistic data suggest that ITZ-induced negative inotropy is a direct effect on the heart, in addition, the potential involvement of mitochondria function and L-type Ca{sup 2+} channels are eliminated. The exact mechanism underlying the negative inotropy is uncertain, and requires further study. - Highlights: ► Effect of itraconazole (ITZ) was assessed in the isolated rabbit heart (IRH) assay. ► ITZ decreased ventricular contractility in IRH, indicating a direct effect. ► IC{sub 50} of ITZ on L-type I{sub Ca} was greater than 30 μM, on I

  12. Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

    PubMed

    Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

    2011-08-09

    Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.

  13. The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial.

    PubMed

    Geldenhuys, Hennie; Mearns, Helen; Miles, David J C; Tameris, Michele; Hokey, David; Shi, Zhongkai; Bennett, Sean; Andersen, Peter; Kromann, Ingrid; Hoff, Søren T; Hanekom, Willem A; Mahomed, Hassan; Hatherill, Mark; Scriba, Thomas J; van Rooyen, Michele; Bruce McClain, J; Ryall, Robert; de Bruyn, Guy

    2015-07-09

    New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31 adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis-uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500nmol IC31, two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ(+)TNF-α(+)IL-2(+) or TNF-α(+)IL-2(+) cells. These memory responses persisted up to the end of follow up, on study day 182. H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Evaluation of Acanthamoeba Myosin-IC as a Potential Therapeutic Target

    PubMed Central

    Lorenzo-Morales, Jacob; López-Arencibia, Atteneri; Reyes-Batlle, María; Piñero, José E.; Valladares, Basilio; Maciver, Sutherland K.

    2014-01-01

    Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a fatal encephalitis. We have targeted myosin-IC by using small interfering RNA (siRNA) silencing as a therapeutic approach, since it is known that the function of this protein is vital for the amoeba. In this work, specific siRNAs against the Acanthamoeba myosin-IC gene were developed. Treated and control amoebae were cultured in growth and encystment media to evaluate the induced effects after myosin-IC gene knockdown, as we have anticipated that cyst formation may be impaired. The effects of myosin-IC gene silencing were inhibition of cyst formation, inhibition of completion of cytokinesis, inhibition of osmoregulation under osmotic stress conditions, and death of the amoebae. The finding that myosin-IC silencing caused incompletion of cytokinesis is in agreement with earlier suggestions that the protein plays a role in cell locomotion, which is necessary to pull daughter cells apart after mitosis in a process known as “traction-mediated cytokinesis”. We conclude that myosin-IC is a very promising potential drug target for the development of much-needed antiamoebal drugs and that it should be further exploited for Acanthamoeba therapy. PMID:24468784

  15. Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

    PubMed Central

    Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

    2014-01-01

    Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. Conclusions: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity. Citation: Attene-Ramos MS, Huang R, Michael S, Witt KL, Richard A, Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox

  16. Decrease in incidence of colorectal cancer among individuals 50 years or older following recommendations for population-based screening

    PubMed Central

    Murphy, Caitlin C.; Sandler, Robert S.; Sanoff, Hanna K.; Yang, Y. Claire; Lund, Jennifer L.; Baron, John A.

    2016-01-01

    Background & Aims The incidence of colorectal cancer (CRC) in the U.S. is increasing among adults younger than age 50 years, but incidence has decreased among older populations after population-based screening was recommended in the late 1980s. Blacks have higher incidence than whites. These patterns have prompted suggestions to lower the screening age for average-risk populations or in blacks. At the same time, there has been controversy over whether reductions in CRC incidence can be attributed to screening. We examined age- and race-related differences in CRC incidence over a 40-year time period. Methods We determined the age-standardized incidence of CRC, from 1975 through 2013, using the population-based Surveillance, Epidemiology, and End Results (SEER) program of cancer registries. We calculated incidence for 5-year age categories (20—24 years through 80—84 years and 85 years or older) for different time periods (1975—1979, 1980—1984, 1985—1989, 1990—1994, 1995—1999, 2000—2004, 2005—2009, and 2010—2013), tumor subsite (proximal colon, descending colon, and rectum), and stages at diagnosis (localized, regional, and distant). Analyses were stratified by race (white vs. black). Results There were 450,682 incident cases of CRC reported to the SEER registries over the entire period (1975—2013). Overall incidence was 75.5/100,000 white persons and 83.6/100,000 black persons. CRC incidence peaked during 1980 through 1989 and began to decrease in 1990. In whites and blacks, the decreases in incidence between the time periods of 1980—1984 and 2010—2013 were limited to the screening-age population (ages 50 years or older). Between these time periods, there was a 40% decrease in incidence among whites compared with a 26% decrease in incidence among blacks. Decreases in incidence were greater for cancers of the distal colon and rectum, and reductions in these cancers were greater among whites than blacks. CRC incidence among persons younger

  17. Inhibition of P-glycoprotein in Caco-2 cells: effects of herbal remedies frequently used by cancer patients.

    PubMed

    Engdal, S; Nilsen, O G

    2008-06-01

    1. The herbal products Natto K2, Agaricus, mistletoe, noni juice, green tea and garlic were investigated for in vitro inhibitory potential on P-glycoprotein (P-gp)-mediated transport of digoxin (30 nM) in differentiated and polarized Caco-2 cells. 2. Satisfactory cell functionality was demonstrated through measurements of assay linearity, transepithelial electric resistance (TEER), cytotoxicity, mannitol permeability, and inclusion of the positive inhibition control verapamil. 3. The most potent inhibitors of the net digoxin flux (IC(50)) were mistletoe > Natto K2 > Agaricus > green tea (0.022, 0.62, 3.81, >4.5 mg ml(-1), respectively). Mistletoe also showed the lowest IC(25) value, close to that obtained by verapamil (1.0 and 0.5 microg ml(-1), respectively). The IC(50)/IC(25) ratio was found to be a good parameter for the determination of inhibition profiles. Garlic and noni juice were classified as non-inhibitors. 4. This study shows that mistletoe, Natto K2, Agaricus and green tea inhibit P-gp in vitro. Special attention should be paid to mistletoe due to very low IC(50) and IC(25) values and to Natto K2 due to a low IC(50) value and a low IC(50)/IC(25) ratio.

  18. Effects of pyrogallol, hydroquinone and duroquinone on responses to nitrergic nerve stimulation and NO in the rat anococcygeus muscle

    PubMed Central

    La, Mylinh; Rand, Michael J

    1999-01-01

    The hypothesis that endogenous superoxide dismutase (SOD) protects the nitrergic transmitter from inactivation by superoxide and that this explains the lack of sensitivity of the transmitter to superoxide generators was tested in the rat isolated anococcygeus muscle.Responses to nitrergic nerve stimulation or to NO were not significantly affected by exogenous SOD or by the Cu/Zn SOD inhibitor diethyldithiocarbamic acid (DETCA).Hydroquinone produced a concentration-dependent reduction of responses to NO with an IC50 of 27 μM, and higher concentrations reduced relaxant responses to nitrergic nerve stimulation with an IC50 of 612 μM. The effects of hydroquinone were only slightly reversed by SOD, so it does not appear to be acting as a superoxide generator.Pyrogallol produced a concentration-dependent reduction in responses to NO with an IC50 value of 39 μM and this effect was reversed by SOD (100–1000 u ml−1). Pyrogallol did not affect responses to nitrergic nerve stimulation. Treatment with DETCA did not alter the differentiating action of pyrogallol.Duroquinone produced a concentration-dependent reduction of relaxations to NO with an IC50 value of 240 μM and 100 μM slightly decreased nitrergic relaxations. After treatment with DETCA, duroquinone produced greater reductions of relaxant responses to NO and to nitrergic stimulation, the IC50 values being 8.5 μM for NO and 40 μM for nitrergic nerve stimulation: these reductions were reversed by SOD.The findings do not support the hypothesis that the presence of Cu/Zn SOD explains the greater susceptibility of NO than the nitrergic transmitter to the superoxide generator pyrogallol, but suggest that it may play a role in the effects of duroquinone. PMID:10051154

  19. [Effects of ethanol extract of Rhizome Pinelliae Preparata on intracellular pH value of human gastric adenocarcinoma cells].

    PubMed

    Zhang, Ci-an; Wu, Feng; Mao, Zhu-jun; Wei, Zhen; Li, Yong-jin; Wei, Pin-kang

    2011-08-01

    To observe the effects of ethanol extract of Rhizome Pinelliae Preparata on the intracellular pH value of human gastric cancer SGC7901 cells. After coculturing SGC7901 cells with ethanol extract of Rhizome Pinelliae Preparata (1, 0.5, 0.25 and 0.125 mg/mL), cell viability was evaluated by chromatometry with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. Intracellular pH value of SGC7901 cells was measured in the monolayer by using the pH-sensitive fluorescent probe 2,7-bis-(2-carboxyethyl)-5-carboxyfluorescein-acetoxymethyl ester. The extracellular pH value of culture medium was measured by a pH211 Calibration Check Microprocessor pH Meter. Half-inhibitory concentration (IC(50)) of ethanol extract culture to SGC7901 cells was decided by the MTT method and expressions of vacuolar-H(+)-ATPase (V-ATPase) and Na(+)/H(+) exchanger isoform 1 (NHE1) mRNAs were examined by the method of fluorescence quantitative-polymerase chain reaction after 72 h of drug treatment. Ethanol extract of Rhizome Pinelliae Preparata at different concentrations significantly inhibited the proliferation of SGC7901 cells, lowered the intracellular pH values and heightened the extracellular pH values. The IC(50) of 72 h culture was 0.5mg/mL and it inhibited the expressions of V-ATPase and NHE1 mRNAs. Ethanol extract of Rhizome Pinelliae Preparata can lower down the intracellular pH value of SGC7901 cells. The mechanism may be related to inhibiting the expressions of V-ATPase and NHE1 mRNAs.

  20. ICS logging solution for network-based attacks using Gumistix technology

    NASA Astrophysics Data System (ADS)

    Otis, Jeremy R.; Berman, Dustin; Butts, Jonathan; Lopez, Juan

    2013-05-01

    Industrial Control Systems (ICS) monitor and control operations associated with the national critical infrastructure (e.g., electric power grid, oil and gas pipelines and water treatment facilities). These systems rely on technologies and architectures that were designed for system reliability and availability. Security associated with ICS was never an inherent concern, primarily due to the protections afforded by network isolation. However, a trend in ICS operations is to migrate to commercial networks via TCP/IP in order to leverage commodity benefits and cost savings. As a result, system vulnerabilities are now exposed to the online community. Indeed, recent research has demonstrated that many exposed ICS devices are being discovered using readily available applications (e.g., ShodanHQ search engine and Google-esque queries). Due to the lack of security and logging capabilities for ICS, most knowledge about attacks are derived from real world incidents after an attack has already been carried out and the damage has been done. This research provides a method for introducing sensors into the ICS environment that collect information about network-based attacks. The sensors are developed using an inexpensive Gumstix platform that can be deployed and incorporated with production systems. Data obtained from the sensors provide insight into attack tactics (e.g., port scans, Nessus scans, Metasploit modules, and zero-day exploits) and characteristics (e.g., attack origin, frequency, and level of persistence). Findings enable security professionals to draw an accurate, real-time awareness of the threats against ICS devices and help shift the security posture from reactionary to preventative.

  1. A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs.

    PubMed

    Quashie, Neils B; Duah, Nancy O; Abuaku, Benjamin; Quaye, Lydia; Ayanful-Torgby, Ruth; Akwoviah, George A; Kweku, Margaret; Johnson, Jacob D; Lucchi, Naomi W; Udhayakumar, Venkatachalam; Duplessis, Christopher; Kronmann, Karl C; Koram, Kwadwo A

    2013-12-17

    Based on report of declining efficacy of chloroquine, Ghana shifted to the use of artemisinin-based combination therapy (ACT) in 2005 as the first-line anti-malarial drug. Since then, there has not been any major evaluation of the efficacy of anti-malarial drugs in Ghana in vitro. The sensitivity of Ghanaian Plasmodium falciparum isolates to anti-malarial drugs was, therefore, assessed and the data compared with that obtained prior to the change in the malaria treatment policy. A SYBR Green 1 fluorescent-based in vitro drug sensitivity assay was used to assess the susceptibility of clinical isolates of P. falciparum to a panel of 12 anti-malarial drugs in three distinct eco-epidemiological zones in Ghana. The isolates were obtained from children visiting health facilities in sentinel sites located in Hohoe, Navrongo and Cape Coast municipalities. The concentration of anti-malarial drug inhibiting parasite growth by 50% (IC50) for each drug was estimated using the online program, ICEstimator. Pooled results from all the sentinel sites indicated geometric mean IC50 values of 1.60, 3.80, 4.00, 4.56, 5.20, 6.11, 10.12, 28.32, 31.56, 93.60, 107.20, and 8952.50 nM for atovaquone, artesunate, dihydroartemisin, artemether, lumefantrine, amodiaquine, mefloquine, piperaquine, chloroquine, tafenoquine, quinine, and doxycycline, respectively. With reference to the literature threshold value indicative of resistance, the parasites showed resistance to all the test drugs except the artemisinin derivatives, atovaquone and to a lesser extent, lumefantrine. There was nearly a two-fold decrease in the IC50 value determined for chloroquine in this study compared to that determined in 2004 (57.56 nM). This observation is important, since it suggests a significant improvement in the efficacy of chloroquine, probably as a direct consequence of reduced drug pressure after cessation of its use. Compared to that measured prior to the change in treatment policy, significant elevation of

  2. Pre-incubation with cyclosporine A potentiates its inhibitory effects on pitavastatin uptake mediated by recombinantly expressed cynomolgus monkey hepatic organic anion transporting polypeptide.

    PubMed

    Takahashi, Tsuyoshi; Ohtsuka, Tatsuyuki; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi; Kume, Toshiyuki

    2016-11-01

    Cyclosporine A, an inhibitor of hepatic organic anion transporting polypeptides (OATPs), reportedly increased plasma concentrations of probe substrates, although its maximum unbound blood concentrations were lower than the experimental half-maximal inhibitory (IC 50 ) concentrations. Pre-incubation with cyclosporine A in vitro before simultaneous incubation with probes has been reported to potentiate its inhibitory effects on recombinant human OATP-mediated probe uptake. In the present study, the effects of cyclosporine A and rifampicin on recombinant cynomolgus monkey OATP-mediated pitavastatin uptake were investigated in pre- and simultaneous incubation systems. Pre-incubation with cyclosporine A, but not with rifampicin, decreased the apparent IC 50 values on recombinant cynomolgus monkey OATP1B1- and OATP1B3-mediated pitavastatin uptake. Application of the co-incubated IC 50 values toward R values (1 + [unbound inhibitor] inlet to the liver, theoretically maximum /inhibition constant) in static models, 1.1 in monkeys and 1.3 in humans, for recombinant cynomolgus monkey and human OATP1B1-mediated pitavastatin uptake might result in the poor prediction of drug interaction magnitudes. In contrast, the lowered IC 50 values after pre-incubation with cyclosporine A provided better prediction with R values of 3.9 for monkeys and 2.7 for humans when the estimated maximum cyclosporine A concentrations at the inlet to the liver were used. These results suggest that the enhanced inhibitory potential of perpetrator medicines by pre-incubation on cynomolgus monkey OATP-mediated pitavastatin uptake in vitro could be of value for the precise estimation of drug interaction magnitudes in silico, in accordance with the findings from pre-administration of inhibitors on pitavastatin pharmacokinetics validated in monkeys. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.

    PubMed

    Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S

    2016-02-08

    This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.

  4. Diagnostic value of immunoglobulin G antibodies against Candida enolase and fructose-bisphosphate aldolase for candidemia

    PubMed Central

    2013-01-01

    Background The yeast Candida is one of the most frequent pathogens isolated from bloodstream infections and is associated with significant morbidity and mortality. Problems with clinical and microbiological diagnosis of invasive candidiasis (IC) have prompted the development of non-culture-based laboratory methods. Previous reports suggest that serological detection of antibodies might be useful for diagnosing systemic candidiasis. Methods Diagnosis of IC using antibodies against recombinant Candida albicans enolase (Eno) and fructose-bisphosphate aldolase (Fba1) was evaluated. Using recombinant Eno and Fba1 as coating antigens, enzyme-linked immunosorbent assays (ELISAs) were used to analyze sera from patients with candidemia (n = 101), Candida colonization (n = 50), bacteremia (n = 84), invasive aspergillosis (n = 40); and from healthy controls (n = 200). Results The results demonstrated that ELISA detection of anti-Eno and anti-Fba1 IgG distinguished IC from other pathogenic infections in patients and healthy individuals. The sensitivity, specificity, and positive and negative predictive values were 72.3%, 94.7%, 78.5% and 93% for anti-Eno, and 87.1%, 92.8%, 76.5% and 96.4% for anti-Fba1 antibodies, respectively. Combining these two tests improved sensitivity up to 90.1% and negative predictive value up to 97.1%, with specificity and positive predictive values of 90.6% and 72.2%. The tests were specific to the Candida genus and antibody titers were higher for candidemia patients than for controls. Positive antibody tests were obtained before blood culture results for 42.2% of patients for anti-Eno and 51.1% for anti-Fba1. Conclusion These data suggest that tests that detect IgG antibodies against Candida enolase and fructose-bisphosphate aldolase, especially when used in combination, could be a powerful tool for diagnosing IC. PMID:23725337

  5. Diagnostic value of immunoglobulin G antibodies against Candida enolase and fructose-bisphosphate aldolase for candidemia.

    PubMed

    Li, Fang-Qiu; Ma, Chun-Fang; Shi, Li-Ning; Lu, Jing-Fen; Wang, Ying; Huang, Mei; Kong, Qian-Qian

    2013-05-31

    The yeast Candida is one of the most frequent pathogens isolated from bloodstream infections and is associated with significant morbidity and mortality. Problems with clinical and microbiological diagnosis of invasive candidiasis (IC) have prompted the development of non-culture-based laboratory methods. Previous reports suggest that serological detection of antibodies might be useful for diagnosing systemic candidiasis. Diagnosis of IC using antibodies against recombinant Candida albicans enolase (Eno) and fructose-bisphosphate aldolase (Fba1) was evaluated. Using recombinant Eno and Fba1 as coating antigens, enzyme-linked immunosorbent assays (ELISAs) were used to analyze sera from patients with candidemia (n = 101), Candida colonization (n = 50), bacteremia (n = 84), invasive aspergillosis (n = 40); and from healthy controls (n = 200). The results demonstrated that ELISA detection of anti-Eno and anti-Fba1 IgG distinguished IC from other pathogenic infections in patients and healthy individuals. The sensitivity, specificity, and positive and negative predictive values were 72.3%, 94.7%, 78.5% and 93% for anti-Eno, and 87.1%, 92.8%, 76.5% and 96.4% for anti-Fba1 antibodies, respectively. Combining these two tests improved sensitivity up to 90.1% and negative predictive value up to 97.1%, with specificity and positive predictive values of 90.6% and 72.2%. The tests were specific to the Candida genus and antibody titers were higher for candidemia patients than for controls. Positive antibody tests were obtained before blood culture results for 42.2% of patients for anti-Eno and 51.1% for anti-Fba1. These data suggest that tests that detect IgG antibodies against Candida enolase and fructose-bisphosphate aldolase, especially when used in combination, could be a powerful tool for diagnosing IC.

  6. IC-Finder: inferring robustly the hierarchical organization of chromatin folding

    PubMed Central

    Haddad, Noelle

    2017-01-01

    Abstract The spatial organization of the genome plays a crucial role in the regulation of gene expression. Recent experimental techniques like Hi-C have emphasized the segmentation of genomes into interaction compartments that constitute conserved functional domains participating in the maintenance of a proper cell identity. Here, we propose a novel method, IC-Finder, to identify interaction compartments (IC) from experimental Hi-C maps. IC-Finder is based on a hierarchical clustering approach that we adapted to account for the polymeric nature of chromatin. Based on a benchmark of realistic in silico Hi-C maps, we show that IC-Finder is one of the best methods in terms of reliability and is the most efficient numerically. IC-Finder proposes two original options: a probabilistic description of the inferred compartments and the possibility to explore the various hierarchies of chromatin organization. Applying the method to experimental data in fly and human, we show how the predicted segmentation may depend on the normalization scheme and how 3D compartmentalization is tightly associated with epigenomic information. IC-Finder provides a robust and generic ‘all-in-one’ tool to uncover the general principles of 3D chromatin folding and their influence on gene regulation. The software is available at http://membres-timc.imag.fr/Daniel.Jost/DJ-TIMC/Software.html. PMID:28130423

  7. A CMOS IC-based multisite measuring system for stimulation and recording in neural preparations in vitro

    PubMed Central

    Tateno, Takashi; Nishikawa, Jun

    2014-01-01

    In this report, we describe the system integration of a complementary metal oxide semiconductor (CMOS) integrated circuit (IC) chip, capable of both stimulation and recording of neurons or neural tissues, to investigate electrical signal propagation within cellular networks in vitro. The overall system consisted of three major subunits: a 5.0 × 5.0 mm CMOS IC chip, a reconfigurable logic device (field-programmable gate array, FPGA), and a PC. To test the system, microelectrode arrays (MEAs) were used to extracellularly measure the activity of cultured rat cortical neurons and mouse cortical slices. The MEA had 64 bidirectional (stimulation and recording) electrodes. In addition, the CMOS IC chip was equipped with dedicated analog filters, amplification stages, and a stimulation buffer. Signals from the electrodes were sampled at 15.6 kHz with 16-bit resolution. The measured input-referred circuitry noise was 10.1 μ V root mean square (10 Hz to 100 kHz), which allowed reliable detection of neural signals ranging from several millivolts down to approximately 33 μ Vpp. Experiments were performed involving the stimulation of neurons with several spatiotemporal patterns and the recording of the triggered activity. An advantage over current MEAs, as demonstrated by our experiments, includes the ability to stimulate (voltage stimulation, 5-bit resolution) spatiotemporal patterns in arbitrary subsets of electrodes. Furthermore, the fast stimulation reset mechanism allowed us to record neuronal signals from a stimulating electrode around 3 ms after stimulation. We demonstrate that the system can be directly applied to, for example, auditory neural prostheses in conjunction with an acoustic sensor and a sound processing system. PMID:25346683

  8. A CMOS IC-based multisite measuring system for stimulation and recording in neural preparations in vitro.

    PubMed

    Tateno, Takashi; Nishikawa, Jun

    2014-01-01

    In this report, we describe the system integration of a complementary metal oxide semiconductor (CMOS) integrated circuit (IC) chip, capable of both stimulation and recording of neurons or neural tissues, to investigate electrical signal propagation within cellular networks in vitro. The overall system consisted of three major subunits: a 5.0 × 5.0 mm CMOS IC chip, a reconfigurable logic device (field-programmable gate array, FPGA), and a PC. To test the system, microelectrode arrays (MEAs) were used to extracellularly measure the activity of cultured rat cortical neurons and mouse cortical slices. The MEA had 64 bidirectional (stimulation and recording) electrodes. In addition, the CMOS IC chip was equipped with dedicated analog filters, amplification stages, and a stimulation buffer. Signals from the electrodes were sampled at 15.6 kHz with 16-bit resolution. The measured input-referred circuitry noise was 10.1 μ V root mean square (10 Hz to 100 kHz), which allowed reliable detection of neural signals ranging from several millivolts down to approximately 33 μ Vpp. Experiments were performed involving the stimulation of neurons with several spatiotemporal patterns and the recording of the triggered activity. An advantage over current MEAs, as demonstrated by our experiments, includes the ability to stimulate (voltage stimulation, 5-bit resolution) spatiotemporal patterns in arbitrary subsets of electrodes. Furthermore, the fast stimulation reset mechanism allowed us to record neuronal signals from a stimulating electrode around 3 ms after stimulation. We demonstrate that the system can be directly applied to, for example, auditory neural prostheses in conjunction with an acoustic sensor and a sound processing system.

  9. Adaptation of Lorke's method to determine and compare ED50 values: the cases of two anticonvulsants drugs.

    PubMed

    Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio Enrique; Anguiano-Robledo, Liliana; Valencia-Hernández, Ignacio; Chamorro-Cevallos, Germán

    2014-01-01

    We determined the median effective dose (ED50) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested. The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED50 values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED50 calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED50. The ED50 for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively. These results are similar to those found using the traditional methods of finding ED50, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD50) or ED50 for compounds with other pharmacological activities. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Long-term prediction test procedure for most ICs, based on linear response theory

    NASA Technical Reports Server (NTRS)

    Litovchenko, V.; Ivakhnenko, I.

    1991-01-01

    Experimentally, thermal annealing is known to be a factor which enables a number of different integrated circuits (IC's) to recover their operating characteristics after suffering radiation damage in the space radiation environment; thus, decreasing and limiting long term cumulative total-dose effects. This annealing is also known to be accelerated at elevated temperatures both during and after irradiation. Linear response theory (LRT) was applied, and a linear response function (LRF) to predict the radiation/annealing response of sensitive parameters of IC's for long term (several months or years) exposure to the space radiation environment were constructed. Compressing the annealing process from several years in orbit to just a few hours or days in the laboratory is achieved by subjecting the IC to elevated temperatures or by increasing the typical spaceflight dose rate by several orders of magnitude for simultaneous radiation/annealing only. The accomplishments are as follows: (1) the test procedure to make predictions of the radiation response was developed; (2) the calculation of the shift in the threshold potential due to the charge distribution in the oxide was written; (3) electron tunneling processes from the bulk Si to the oxide region in an MOS IC were estimated; (4) in order to connect the experimental annealing data to the theoretical model, constants of the model of the basic annealing process were established; (5) experimental data obtained at elevated temperatures were analyzed; (6) time compression and reliability of predictions for the long term region were shown; (7) a method to compress test time and to make predictions of response for the nonlinear region was proposed; and (8) nonlinearity of the LRF with respect to log(t) was calculated theoretically from a model.

  11. Hubble Space Telescope Image: Planetary Nebula IC 4406

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This Hubble Space Telescope image reveals a rainbow of colors in this dying star, called IC 446. Like many other so-called planetary nebulae, IC 4406 exhibits a high degree of symmetry. The nebula's left and right halves are nearly mirror images of the other. If we could fly around IC 446 in a spaceship, we would see that the gas and dust form a vast donut of material streaming outward from the dying star. We do not see the donut shape in this photograph because we are viewing IC 4406 from the Earth-orbiting HST. From this vantage point, we are seeing the side of the donut. This side view allows us to see the intricate tendrils of material that have been compared to the eye's retina. In fact, IC 4406 is dubbed the 'Retina Nebula.' The donut of material confines the intense radiation coming from the remnant of the dying star. Gas on the inside of the donut is ionized by light from the central star and glows. Light from oxygen atoms is rendered blue in this image; hydrogen is shown as green, and nitrogen as red. The range of color in the final image shows the differences in concentration of these three gases in the nebula. This image is a composite of data taken by HST's Wide Field Planetary Camera 2 in June 2001 and in January 2002 by Bob O'Dell (Vanderbilt University) and collaborators, and in January by the Hubble Heritage Team (STScI). Filters used to create this color image show oxygen, hydrogen, and nitrogen gas glowing in this object.

  12. Comparison of soil moisture retrieval algorithms based on the synergy between SMAP and SMOS-IC

    NASA Astrophysics Data System (ADS)

    Ebrahimi-Khusfi, Mohsen; Alavipanah, Seyed Kazem; Hamzeh, Saeid; Amiraslani, Farshad; Neysani Samany, Najmeh; Wigneron, Jean-Pierre

    2018-05-01

    This study was carried out to evaluate possible improvements of the soil moisture (SM) retrievals from the SMAP observations, based on the synergy between SMAP and SMOS. We assessed the impacts of the vegetation and soil roughness parameters on SM retrievals from SMAP observations. To do so, the effects of three key input parameters including the vegetation optical depth (VOD), effective scattering albedo (ω) and soil roughness (HR) parameters were assessed with the emphasis on the synergy with the VOD product derived from SMOS-IC, a new and simpler version of the SMOS algorithm, over two years of data (April 2015 to April 2017). First, a comprehensive comparison of seven SM retrieval algorithms was made to find the best one for SM retrievals from the SMAP observations. All results were evaluated against in situ measurements over 548 stations from the International Soil Moisture Network (ISMN) in terms of four statistical metrics: correlation coefficient (R), root mean square error (RMSE), bias and unbiased RMSE (UbRMSE). The comparison of seven SM retrieval algorithms showed that the dual channel algorithm based on the additional use of the SMOS-IC VOD product (selected algorithm) led to the best results of SM retrievals over 378, 399, 330 and 271 stations (out of a total of 548 stations) in terms of R, RMSE, UbRMSE and both R & UbRMSE, respectively. Moreover, comparing the measured and retrieved SM values showed that this synergy approach led to an increase in median R value from 0.6 to 0.65 and a decrease in median UbRMSE from 0.09 m3/m3 to 0.06 m3/m3. Second, using the algorithm selected in a first step and defined above, the ω and HR parameters were calibrated over 218 rather homogenous ISMN stations. 72 combinations of various values of ω and HR were used for the calibration over different land cover classes. In this calibration process, the optimal values of ω and HR were found for the different land cover classes. The obtained results indicated that the

  13. The potential medicinal value of plants from Asteraceae family with antioxidant defense enzymes as biological targets.

    PubMed

    Koc, Suheda; Isgor, Belgin S; Isgor, Yasemin G; Shomali Moghaddam, Naznoosh; Yildirim, Ozlem

    2015-05-01

    Plants and most of the plant-derived compounds have long been known for their potential pharmaceutical effects. They are well known to play an important role in the treatment of several diseases from diabetes to various types of cancers. Today most of the clinically effective pharmaceuticals are developed from plant-derived ancestors in the history of medicine. The aim of this study was to evaluate the free radical scavenging activity and total phenolic and flavonoid contents of methanol, ethanol, and acetone extracts from flowers and leaves of Onopordum acanthium L., Carduus acanthoides L., Cirsium arvense (L.) Scop., and Centaurea solstitialis L., all from the Asteraceae family, for investigating their potential medicinal values of biological targets that are participating in the antioxidant defense system such as catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx). In this study, free radical scavenging activity and total phenolic and flavonoid contents of the plant samples were assayed by DPPH, Folin-Ciocalteu, and aluminum chloride colorimetric methods. Also, the effects of extracts on CAT, GST, and GPx enzyme activities were investigated. The highest phenolic and flavonoid contents were detected in the acetone extract of C. acanthoides flowers, with 90.305 mg GAE/L and 185.43 mg Q/L values, respectively. The highest DPPH radical scavenging was observed with the methanol leaf extracts of C. arvense with an IC50 value of 366 ng/mL. The maximum GPx and GST enzyme inhibition activities were observed with acetone extracts from the flower of C. solstitialis with IC50 values of 79 and 232 ng/mL, respectively.

  14. 30 CFR 57.22104 - Open flames (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

  15. 30 CFR 57.22104 - Open flames (I-C mines).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

  16. 30 CFR 57.22104 - Open flames (I-C mines).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

  17. 30 CFR 57.22104 - Open flames (I-C mines).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

  18. Lithium Abundances in the Young Open Cluster IC 2602

    NASA Technical Reports Server (NTRS)

    Randich, S.; Aharpour, N.; Pallavicini, R.; Prosser, C. F.; Stauffer, J. R.

    1997-01-01

    We have obtained high-resolution spectra for 28 candidate late-type stars in the 30 Myr old cluster IC 2602. NLTE Li abundances have been derived from measured equivalent widths. The log n(Li) - T(sub eff) and log n(Li) - mass distributions for our sample stars have been compared with those of the Pleiades and alpha Persei. Our data show that F stars in the three clusters have the same lithium content, which corresponds to the initial content for Pop. I stars. G and early-K IC 2602 stars are, on average, somewhat more Li-rich than their counterparts in the two slightly older clusters. Finally, the latest-type IC 2602 stars are heavily Li depleted, with their Li content being as low as the lowest measured among the Pleiades. As in the Pleiades and alpha Per, a star-to-star scatter in lithium is observed among 30 Myr old late-K/early-K dwarfs in IC 2602, indicating that this spread develops in the pre-main sequence phases.

  19. Decreased 2,3-diphosphoglycerate concentration in low cardiac output patients and its influence on the determination of in vivo p50.

    PubMed

    Piccioni, Marilde A; Cestari, Idágene A; Strunz, Célia M C; Auler, José O

    2003-08-01

    We investigated whether 2,3-diphosphoglycerate (2,3-DPG) is altered in patients with low cardiac output and the influence of its concentration on the calculation of in vivo P(50). Biochemical and blood gas analysis were performed along with the measurement of cardiac output and body temperature in 13 patients submitted to cardiopulmonary bypass surgeries without the use of donor blood. In vivo P(50) was calculated using the measured (P(50m)) and the estimated 2,3-DPG (P(50e)). 2,3-DPG concentration was lower in these patients when compared to the values obtained in normal volunteers (6.9 +/- 2.2 vs. 11.9 +/- 2.4 microm/gHb). P(50m) was lower than P(50e) (21.6 +/- 1.1 vs. 30.1 +/- 1.2 mm Hg) at all time points. Our data show that in patients with low cardiac output, 2,3-DPG concentration is reduced. Therefore, in these patients, the use of standard values for this variable may introduce an error in the calculation of in vivo P(50).

  20. ASASSN-16fp (SN 2016coi): a transitional supernova between Type Ic and broad-lined Ic

    NASA Astrophysics Data System (ADS)

    Kumar, Brajesh; Singh, A.; Srivastav, S.; Sahu, D. K.; Anupama, G. C.

    2018-01-01

    We present results based on a well-sampled optical (UBVRI) and ultraviolet (Swift/UVOT) imaging, and low-resolution optical spectroscopic follow-up observations of the nearby Type Ic supernova (SN) ASASSN-16fp (SN 2016coi). The SN was monitored during the photospheric phase (-10 to +33 d with respect to the B-band maximum light). The rise to maximum light and early post-maximum decline of the light curves are slow. The peak absolute magnitude (MV = -17.7 ± 0.2 mag) of ASASSN-16fp is comparable with broad-lined Ic SN 2002ap, SN 2012ap and transitional Ic SN 2004aw but considerably fainter than the gamma-ray burst/X-ray flash associated SNe (e.g. SN 1998bw, 2006aj). Similar to the light curve, the spectral evolution is also slow. ASASSN-16fp shows distinct photospheric phase spectral lines along with the C II features. The expansion velocity of the ejecta near maximum light reached ∼16 000 km s-1 and settled to ∼8000 km s-1, ∼1 month post-maximum. Analytical modelling of the quasi-bolometric light curve of ASASSN-16fp suggests that ∼0.1 M⊙ 56Ni mass was synthesized in the explosion, with a kinetic energy of 6.9^{+1.5}_{-1.3} × 1051 erg and total ejected mass of ∼4.5 ± 0.3 M⊙.

  1. Zoledronic acid induces dose-dependent increase of antigen-specific CD8 T-cell responses in combination with peptide/poly-IC vaccine.

    PubMed

    Park, Hye-Mi; Cho, Hyun-Il; Shin, Chang-Ae; Shon, Hyun-Jung; Kim, Tai-Gyu

    2016-03-04

    Zoledronic acid (ZA) is used for treating osteoporosis and for preventing skeletal fractures in cancer patients suffering from myeloma and prostate cancer. It is also reported to directly induce cancer cell apoptosis and indirectly modulate T-cell immune response as an antitumor agent. In this study, the effect of ZA following peptide/polyinosinic-polycytidylic acid (poly-IC) vaccination was investigated in a murine tumor model. The combination of ZA with peptide/poly-IC vaccine showed a synergistic effect on the induction of antigen-specific CD8 T-cell response. Three consecutive intravenous administrations of ZA was defined to induce the highest CD8 T-cell response. Further, total splenocyte counts and antigen-specific CD8 T-cell response gradually increased depending on the dose of ZA. In tumor-bearing mice, ZA showed a dose-dependent decrease of growth and prolonged survival. Treatment with ZA only decreased the number of CD11b(+)Gr1(+) myeloid cells in blood. Our results demonstrate that the use of ZA could improve antitumor immune responses induced by the peptide/poly-IC vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Enhancing the efficiency of bortezomib conjugated to pegylated gold nanoparticles: an in vitro study on human pancreatic cancer cells and adenocarcinoma human lung alveolar basal epithelial cells.

    PubMed

    Coelho, Sílvia Castro; Almeida, Gabriela M; Santos-Silva, Filipe; Pereira, Maria Carmo; Coelho, Manuel A N

    2016-08-01

    Gold nanoparticles have become promising vectors for cancer diagnosis and treatment. The present study investigates the effect of bortezomib (BTZ), a proteasome inhibitor, conjugated with pegylated gold nanoparticles (PEGAuNPs) in pancreatic and lung cancer cells. Synthesized gold nanoparticles (PEGAuNPs) were conjugated with bortezomib antitumor drug. We investigated the cytotoxicity induced by BTZ conjugated with functionalized gold nanoparticles in vitro, in the human pancreatic (S2-013) and lung (A549) cancer cell lines. We found an efficient of conjugation of BTZ with PEGAuNPs. In vitro assays showed that after 72 h' incubation with PEGAuNPs-BTZ cancer cells revealed alterations in morphology; also for S2-013 and A549 cancer cells, the IC50 value of free BTZ is respectively 1.5 and 4.3 times higher than the IC50 value of PEGAuNPs-BTZ. Furthermore, for TERT-HPNE, the IC50 value is around 63 times lower for free BTZ than the conjugated nanovehicle. Cell growth inhibition results showed a remarkable enhancement in the effect of BTZ when conjugated with AuNPs. Our findings showed that conjugation with PEGAuNPs enhance the BTZ growth-inhibition effect on human cancer cells (S2-013 and A549) and decreases its toxicity against normal cells (TERT-HPNE).

  3. High-precision Q EC values of superallowed 0 + → 0 + β-emitters 46Cr, 50Fe and 54Ni

    DOE PAGES

    Zhang, P.; Xu, X.; Shuai, P.; ...

    2017-01-23

    Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are -29471(11) keV, -34477(6) keV and -39278(4) keV, respectively. The superallowed 0 +→0+β-decay Q values were derived to be Q EC( 46Cr) =7604(11) keV, Q EC( 50Fe) =8150(6) keV and Q EC( 54Ni) =8731(4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected ℱt values to be ℱt(more » 50Fe) =3103(70) s and ℱt( 54Ni) =3076(50) s. The main contribution to the ℱt uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.« less

  4. High-precision Q EC values of superallowed 0 + → 0 + β-emitters 46Cr, 50Fe and 54Ni

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, P.; Xu, X.; Shuai, P.

    Short-lived 46Cr, 50Fe and 54Ni were studied by isochronous mass spectrometry at the HIRFL-CSR facility in Lanzhou. The measured precision mass excesses (ME) of 46Cr, 50Fe and 54Ni are -29471(11) keV, -34477(6) keV and -39278(4) keV, respectively. The superallowed 0 +→0+β-decay Q values were derived to be Q EC( 46Cr) =7604(11) keV, Q EC( 50Fe) =8150(6) keV and Q EC( 54Ni) =8731(4) keV. The values for 50Fe and 54Ni are by one order of magnitude more precise than the adopted literature values. By combining the existing half-lives and branching ratios, we obtained the corrected ℱt values to be ℱt(more » 50Fe) =3103(70) s and ℱt( 54Ni) =3076(50) s. The main contribution to the ℱt uncertainties is now due to β-decay branching ratios, still, more high-precision measurements of the half-lives, the masses, and especially the branching ratios are needed in order to satisfy the requirements for a stringent CVC test.« less

  5. Study on Mine Emergency Mechanism based on TARP and ICS

    NASA Astrophysics Data System (ADS)

    Xi, Jian; Wu, Zongzhi

    2018-01-01

    By analyzing the experiences and practices of mine emergency in China and abroad, especially the United States and Australia, normative principle, risk management principle and adaptability principle of constructing mine emergency mechanism based on Trigger Action Response Plans (TARP) and Incident Command System (ICS) are summarized. Classification method, framework, flow and subject of TARP and ICS which are suitable for the actual situation of domestic mine emergency are proposed. The system dynamics model of TARP and ICS is established. The parameters such as evacuation ratio, response rate, per capita emergency capability and entry rate of rescuers are set up. By simulating the operation process of TARP and ICS, the impact of these parameters on the emergency process are analyzed, which could provide a reference and basis for building emergency capacity, formulating emergency plans and setting up action plans in the emergency process.

  6. Droplet-Wall/Film Impact in IC Engine Applications

    DTIC Science & Technology

    2017-08-14

    Report: Droplet-Wall/Film Impact in IC Engine Applications (ARO Topic 1.4.1 under ARO’s Dr. Ralph A. Anthenien) The views, opinions and/or findings...in IC Engine Applications (ARO Topic 1.4.1 under ARO’s Dr. Ralph A. Anthenien) Report Term: 0-Other Email: cklaw@princeton.edu Distribution Statement...associated with spraying in internal combustion engines (ICEs). Fuels sprayed inside engines can impact with the internal surfaces and thus not only

  7. “Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice

    PubMed Central

    Swenson, Luke C.; Pollock, Graham; Wynhoven, Brian; Mo, Theresa; Dong, Winnie; Hogg, Robert S.; Montaner, Julio S. G.; Harrigan, P. Richard

    2011-01-01

    Background ‘Virtual’ or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. Methods All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the “dynamic range” (defined here by the 10th and 90th percentiles for fold-change in IC50 amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort. Results The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC50 of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small “dynamic ranges” with values of <4-fold change observed in >99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges. Conclusion We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner. PMID:21390218

  8. The jet-ISM interactions in IC 5063

    NASA Astrophysics Data System (ADS)

    Mukherjee, Dipanjan; Wagner, Alexander Y.; Bicknell, Geoffrey V.; Morganti, Raffaella; Oosterloo, Tom; Nesvadba, Nicole; Sutherland, Ralph S.

    2018-05-01

    The interstellar medium of the radio galaxy IC 5063 is highly perturbed by an AGN jet expanding in the gaseous disc of the galaxy. We model this interaction with relativistic hydrodynamic simulations and multiphase initial conditions for the interstellar medium and compare the results with recent observations. As the jets flood through the intercloud channels of the disc, they ablate, accelerate, and disperse clouds to velocities exceeding 400 km s-1. Clouds are also destroyed or displaced in bulk from the central regions of the galaxy. Our models with jet powers of 1044 and 1045 erg s-1 are capable of reproducing many of the observed features in the position velocity diagram of IC 5063, and confirm the notion that the jet is responsible for the strongly perturbed gas dynamics seen in the ionized, neutral, and molecular gas phases. In our simulations, we also see strong venting of the jet plasma perpendicular to the disc, which entrains clumps and diffuse filaments into the halo of the galaxy. Our simulations are the first 3D hydrodynamic simulations of the jet and interstellar matter of IC 5063.

  9. The Search for Wolf-Rayet Stars in IC10

    NASA Astrophysics Data System (ADS)

    Tehrani, Katie; Crowther, Paul; Archer, Isabelle

    2017-11-01

    We present a deep imaging and spectroscopic survey of the Local Group starburst galaxy IC10 using Gemini North/GMOS to unveil the global Wolf-Rayet population. It has previously been suggested that for IC10 to follow the WC/WN versus metallicity dependence seen in other Local Group galaxies, a large WN population must remain undiscovered. Our search revealed 3 new WN stars, and 5 candidates awaiting confirmation, providing little evidence to support this claim. We also compute an updated nebular derived metallicity of log(O/H)+12=8.40 +/- 0.04 for the galaxy using the direct method. Inspection of IC10 WR average line luminosities show these stars are more similar to their LMC, rather than SMC counterparts.

  10. Purification, Crystallization And Preliminary X-Ray Analysis of Aminoglycoside-2 ''-Phosphotransferase-Ic [APH(2 '')-Ic] From Enterococcus Gallinarum

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Byrnes, L.J.; /SLAC, SSRL; Badarau, A.

    2009-04-30

    Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2{double_prime}-phosphotransferase-Ic [APH(2{double_prime})-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and three mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2{double_prime})-Ic variants were crystallized in the presence of 14-20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris-HClmore » pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 {angstrom}, {beta} = 108.8{sup o}. X-ray diffraction data were collected to approximately 2.15 {angstrom} resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.« less

  11. Individualism-Collectivism: Links to Occupational Plans and Work Values

    ERIC Educational Resources Information Center

    Hartung, Paul J.; Fouad, Nadya A.; Leong, Frederick T. L.; Hardin, Erin E.

    2010-01-01

    Individualism-collectivism (IC) constitutes a cultural variable thought to influence a wide variety of variables including career planning and decision making. To examine this possibility, college students (216 women, 106 men, 64% racial-ethnic minorities) responded to measures of IC, occupational plans, and work values. Multivariate analysis of…

  12. 6-Nitrobenzimidazole derivatives: potential phosphodiesterase inhibitors: synthesis and structure-activity relationship.

    PubMed

    Khan, K M; Shah, Zarbad; Ahmad, V U; Ambreen, N; Khan, M; Taha, M; Rahim, F; Noreen, S; Perveen, S; Choudhary, M I; Voelter, W

    2012-02-15

    6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 μM. Compounds 30 (IC(50)=1.5±0.043 μM), 1 (IC(50)=2.4±0.049 μM), 11 (IC(50)=5.7±0.113 μM), 13 (IC(50)=6.4±0.148 μM), 14 (IC(50)=10.5±0.51 μM), 9 (IC(50)=11.49±0.08 μM), 3 (IC(50)=63.1±1.48 μM), 10 (IC(50)=120.0±4.47 μM), and 6 (IC(50)=153.2±5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. 75 FR 54940 - Agency Information Collection (IC) Activities; Revision of an Approved IC; Accident Recordkeeping...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... include the Agency name and the docket number for this Notice. Note that DOT posts all comments received... underlying this IC is 49 CFR 390.15, ``Assistance in investigations and special studies.'' It requires motor... Information Technology. [FR Doc. 2010-22456 Filed 9-8-10; 8:45 am] BILLING CODE 4910-EX-P ...

  14. Correlation between in vitro and in vivo antimalarial activity of compounds using CQ-sensitive and CQ-resistant strains of Plasmodium falciparum and CQ-resistant strain of P. yoelii.

    PubMed

    Srivastava, Kumkum; Agarwal, Pooja; Soni, Awakash; Puri, S K

    2017-07-01

    Present efforts have been made to establish a correlation between in vitro and in vivo antimalarial activity using MIC, IC 50 and IC 90 values against CQ-sensitive (3D7) and CQ-resistant (K1) strains of Plasmodium falciparum and in vivo activity against Plasmodium yoelii. The method of discriminant function analysis (DFA) was applied to analyze the data. It was observed that in vitro IC 90 values against both 3D7 and K1 strains (p < 0.001) have strong correlation with in vivo curative activity. The respective IC 50 and IC 90 values of compounds, which cured mice (i.e., animals did not show recrudescence of parasitemia even after 60 days posttreatment), ranged between 3 and 14 nM and 14 and 186 nM against 3D7 and between 9 and 65 nM and 24 and 359 nM against the K1 strain of P. falciparum. Whereas the IC 50 and IC 90 values of compounds which exhibited in vivo suppressive activity in mice ranged between 10 and 307 nm and 61 and >965 nM, respectively, against 3D7 and 75 and >806 nm and 241 and >1232 nM against the K1 strain of P. falciparum. The findings suggest that IC 90 values against both 3D7 and K1 strains (p < 0.02) are the main contributors for the prediction of in vivo curative activity of a new molecule. Apart from this, a reasonable correlation between MIC and IC 50 values of compounds has also been established.

  15. Wide-Field Structure of Local Group Dwarf Irregular Galaxy IC1613

    NASA Astrophysics Data System (ADS)

    Pucha, Ragadeepika; Carlin, Jeffrey; Willman, Beth; Sand, David J.; Bechtol, Keith

    2018-01-01

    IC1613 is a typical dwarf irregular galaxy in the Local Group. Being an isolated dwarf, as opposed to the dwarfs around the Milky Way, it is likely to be subjected to fewer strong environmental effects. As a result, it serves as a good prototype for the study of the structure and evolution of dwarf galaxies. We present g- and i- band photometry from deep imaging of four fields around IC1613, that resolved stars up to ~ 4 magnitudes fainter than the tip of the RGB. This photometry was obtained using Hyper-Suprime Cam (HSC) on the Subaru Telescope. The large (1.5o) field-of-view of HSC provides us with a unique opportunity to study the wide-field structure of this dwarf galaxy. This project explores the structure of IC1613 to radii of about ~ 25 kpc using different types of stellar tracers. The aim is to search for evidence of a stellar halo or stellar over-densities around IC1613. The relative contributions of the different stellar populations as a function of position in IC1613 are also shown.

  16. 30 CFR 57.22203 - Main fan operation (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation (I-C mines). 57.22203... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22203 Main fan operation (I-C mines). Main fans shall be operated continuously while ore production is in progress. ...

  17. Simultaneous detection of three lily viruses using Triplex IC-RT-PCR.

    PubMed

    Zhang, Yubao; Wang, Yajun; Xie, Zhongkui; Yang, Guo; Guo, Zhihong; Wang, Le

    2017-11-01

    Viruses commonly infecting lily (Lilium spp.) include: Lily symptomless virus (LSV), Cucumber mosaic virus (CMV) and Lily mottle virus (LMoV). These viruses usually co-infect lilies causing severe economic losses in terms of quantity and quality of flower and bulb production around the world. Reliable and precise detection systems need to be developed for virus identification. We describe the development of a triplex immunocapture (IC) reverse transcription (RT) polymerase chain reaction (PCR) assay for the simultaneous detection of LSV, CMV and LMoV. The triplex IC-RT-PCR was compared with a quadruplex RT-PCR assay. Relative to the quadruplex RT-PCR, the specificity of the triplex IC-RT-PCR system for LSV, CMV and LMoV was 100% for field samples. The sensitivity of the triplex IC-RT-PCR system was 99.4%, 81.4% and 98.7% for LSV, CMV and LMoV, respectively. Agreement (κ) between the results obtained from the two tests was 0.968, 0.844 and 0.984 for LSV, CMV and LMoV, respectively. This is the first report of the simultaneous detection of LSV, CMV and LMoV in a triplex IC-RT-PCR assay. In particular we believe this convenient and reliable triplex IC-RT-PCR method could be used routinely for large-scale field surveys or crop health monitoring of lily. Copyright © 2017. Published by Elsevier B.V.

  18. Host-pathogen-interaction reconstituted in 3-dimensional cocultures of mucosa and <i>C. albicans.

    PubMed

    Buchs, Romina; Lehner, Bruno; Meuwly, Phillippe; Schnyder, Bruno

    2018-06-14

    <i>C. albicans frequently causes recurrent intimal infectious disease (ID). This demands the treatment of multiple phases of the infection. The objective of this study was to uncover the host-pathogen-interaction using 2D epithelium cell-barrier and 3D subepithelium tissue cells of human mucosa. The 2D cell cultures assessed <i>C. albicans adhesion. Addition of the anti-fungal drug Fluconazol did not inhibit the adhesion, despite its pathogen growth inhibition (MIC value 0.08μg/mL). A 3D tissue was engineered in multi-transwells by placing human fibroblast cultures on a thick porous scaffold. This contained the yeast placed in the top compartment and prevented passive penetration. After 28h the pathogen transmigrated the barrier and was collected in the bottom compartment. A change in pathogen morphology was observed where hypha formed and grew to be 231μm long after 28h. The hypha was thus long enough to cross the 200μm thick 3D tissue. The 3D infection was inhibited by addition of Fluconazol (0.08μg/mL), confirming that penetration is dependent on pathogen growth. In conclusion, ID was reconstituted step-by-step on 2D epithelium surface and in 3D connective tissue of human mucosa. Fluconazol growth-inhibition of the pathogen <i>C. albicans was confirmed in the 3D tissue. We thus propose that this ID in vitro test is suitable for the identification and characterization of new treatments against <i>C. albicans..

  19. Illuminating the Depths of the MagIC (Magnetics Information Consortium) Database

    NASA Astrophysics Data System (ADS)

    Koppers, A. A. P.; Minnett, R.; Jarboe, N.; Jonestrask, L.; Tauxe, L.; Constable, C.

    2015-12-01

    The Magnetics Information Consortium (http://earthref.org/MagIC/) is a grass-roots cyberinfrastructure effort envisioned by the paleo-, geo-, and rock magnetic scientific community. Its mission is to archive their wealth of peer-reviewed raw data and interpretations from magnetics studies on natural and synthetic samples. Many of these valuable data are legacy datasets that were never published in their entirety, some resided in other databases that are no longer maintained, and others were never digitized from the field notebooks and lab work. Due to the volume of data collected, most studies, modern and legacy, only publish the interpreted results and, occasionally, a subset of the raw data. MagIC is making an extraordinary effort to archive these data in a single data model, including the raw instrument measurements if possible. This facilitates the reproducibility of the interpretations, the re-interpretation of the raw data as the community introduces new techniques, and the compilation of heterogeneous datasets that are otherwise distributed across multiple formats and physical locations. MagIC has developed tools to assist the scientific community in many stages of their workflow. Contributors easily share studies (in a private mode if so desired) in the MagIC Database with colleagues and reviewers prior to publication, publish the data online after the study is peer reviewed, and visualize their data in the context of the rest of the contributions to the MagIC Database. From organizing their data in the MagIC Data Model with an online editable spreadsheet, to validating the integrity of the dataset with automated plots and statistics, MagIC is continually lowering the barriers to transforming dark data into transparent and reproducible datasets. Additionally, this web application generalizes to other databases in MagIC's umbrella website (EarthRef.org) so that the Geochemical Earth Reference Model (http://earthref.org/GERM/) portal, Seamount Biogeosciences

  20. Critical body-residues for lethal and sublethal effects of sediment-associated PAH on benthic copepods

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lotufo, G.R.

    1995-12-31

    Adult females of the meiobenthic copepod Schizopera knabeni were exposed to sediment-associated fluoranthene for 3, 6, 12, 24, 96, and 240 h. Sediment concentrations ranged from 25 to 1,661 nmol (5--336 {micro}g)/gdw and the TOC was 1.5%. Body burden increased to an apparent steady state after only 6 h. Elimination half-lives were 4.6 and 3.2 h in uncontaminated water and sediment, respectively. Toxic effects were only detected after 240 h as increased mortality and decreased offspring production. Significant mortality was observed only at the highest concentration; the LC50 was 1,011 nmol (204 {micro}g)/dgw. In contrast, offspring production was decreased atmore » much lower concentrations, yielding an IC25 value of 148 nmol (30 {micro}g)/dgw. Lethal critical body residue (CBR) was determined as a 10-d LD50 of 15.5 {micro}mol/g dry tissue. By measuring PAH concentrations in the body and eggs of females, CBRs for reproductive output were determined as IC25 values of 2 and 3.1 {micro}mol/gdw, respectively. PAH sublethal effects on feeding rate were also investigated Adult copepods were exposed to {sup 14}C sediment-associated fluoranthene for 24 h were fed {sup 3}H-labeled algae for 3 h. Ingestion rate was significantly decreased at tissue concentrations as low as 1 {micro}mol/gdw and yielded an IC25 value of 0.6 {micro}mol/gdw. Similar findings were obtained using another species of estuarine copepod, Coullana sp. Non-polar narcotic compounds such as PAH cause a nonspecific disturbance of the functioning of cell membrane which results in decreased overall activity. Measurement of CBR associated with decreased feeding is proposed as a direct method to quantify sublethal narcotizing effects of organic compounds.« less

  1. XMM-Newton observations of the supernova remnant IC 443. II. Evidence of stellar ejecta in the inner regions

    NASA Astrophysics Data System (ADS)

    Troja, E.; Bocchino, F.; Miceli, M.; Reale, F.

    2008-07-01

    Aims: We investigate the spatial distribution of the physical and chemical properties of the hot X-ray emitting plasma of the supernova remnant IC 443, to derive important constraints on its ionization stage, on the progenitor supernova explosion, on the age of the remnant, and its physical association with a close pulsar wind nebula. Methods: We present XMM-Newton images of IC 443, a median photon energy map, silicon and sulfur equivalent width maps, and a spatially resolved spectral analysis of a set of homogeneous regions. Results: The hard X-ray thermal emission (1.4-5.0 keV) of IC 443 displays a centrally-peaked morphology, its brightness peaks being associated with hot (kT > 1 keV) X-ray emitting plasma. A ring-shaped structure, characterized by high values of equivalent widths and median photon energy, encloses the PWN. Its hard X-ray emission is spectrally characterized by a collisional ionization equilibrium model, and strong emission lines of Mg, Si, and S, requiring oversolar metal abundances. Dynamically, the location of the ejecta ring suggests an SNR age of ~4000 yr. The presence of overionized plasma in the inner regions of IC 443, addressed in previous works, is much less evident in our observations.

  2. Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

    PubMed

    Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

    2011-01-01

    The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

  3. Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: in vitro and in silico study.

    PubMed

    Alvi, Sahir Sultan; Iqbal, Danish; Ahmad, Saheem; Khan, M Salman

    2016-09-01

    This study initially aimed to depict the molecular rationale evolving the role of lycopene in inhibiting the enzymatic activity of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase via in vitro and in silico analysis. Our results illustrated that lycopene exhibited strong HMG-CoA reductase inhibitory activity (IC50 value of 36 ng/ml) quite better than pravastatin (IC50 = 42 ng/ml) and strong DPPH free radical scavenging activity (IC50 value = 4.57 ± 0.23 μg/ml) as compared to ascorbic acid (IC50 value = 9.82 ± 0.42 μg/ml). Moreover, the Ki value of lycopene (36 ng/ml) depicted via Dixon plot was well concurred with an IC50 value of 36 ± 1.8 ng/ml. Moreover, molecular informatics study showed that lycopene exhibited binding energy of -5.62 kcal/mol indicating high affinity for HMG-CoA reductase than HMG-CoA (ΔG: -5.34 kcal/mol). Thus, in silico data clearly demonstrate and support the in vitro results that lycopene competitively inhibit HMG-CoA reductase activity by binding at the hydrophobic portion of HMG-CoA reductase.

  4. The beautiful side of IC 335

    NASA Image and Video Library

    2017-12-08

    Hubble sees a galaxy 60 million light-years away This new NASA/ESA Hubble Space Telescope image shows the galaxy IC 335 in front of a backdrop of distant galaxies. IC 335 is part of a galaxy group containing three other galaxies, and located in the Fornax Galaxy Cluster 60 million light-years away. As seen in this image, the disk of IC 335 appears edge-on from the vantage point of Earth. This makes it harder for astronomers to classify it, as most of the characteristics of a galaxy’s morphology — the arms of a spiral or the bar across the center — are only visible on its face. Still, the 45 000 light-year-long galaxy could be classified as an S0 type. These lenticular galaxies are an intermediate state in galaxy morphological classification schemes between true spiral and elliptical galaxies. They have a thin stellar disk and a bulge, like spiral galaxies, but in contrast to typical spiral galaxies they have used up most of the interstellar medium. Only a few new stars can be created out of the material that is left and the star formation rate is very low. Hence, the population of stars in S0 galaxies consists mainly of aging stars, very similar to the star population in elliptical galaxies. As S0 galaxies have only ill-defined spiral arms they are easily mistaken for elliptical galaxies if they are seen inclined face-on or edge-on as IC 335 here. And indeed, despite the morphological differences between S0 and elliptical class galaxies, they share some common characteristics, like typical sizes and spectral features. Both classes are also deemed "early-type" galaxies, because they are evolving passively. However, while elliptical galaxies may be passively evolving when we observe them, they have usually had violent interactions with other galaxies in their past. In contrast, S0 galaxies are either aging and fading spiral galaxies, which never had any interactions with other galaxies, or they are the aging result of a single merger between two spiral galaxies

  5. VCSEL-based optical transceiver module operating at 25 Gb/s and using a single CMOS IC

    NASA Astrophysics Data System (ADS)

    Afriat, Gil; Horwitz, Lior; Lazar, Dror; Issachar, Assaf; Pogrebinsky, Alexander; Ran, Adee; Shoor, Ehud; Bar, Roi; Saba, Rushdy

    2012-01-01

    We present here a low cost, small form factor, optical transceiver module composed of a CMOS IC transceiver, 850 nm emission wavelength VCSEL modulated at 25 Gb/s, and an InGaAs/InP PIN Photo Diode (PD). The transceiver IC is fabricated in a standard 28 nm CMOS process and integrates the analog circuits interfacing the VCSEL and PD, namely the VCSEL driver and Transimpedance Amplifier (TIA), as well as all other required transmitter and receiver circuits like Phase Locked Loop (PLL), Post Amplifier and Clock & Data Recovery (CDR). The transceiver module couples into a 62.5/125 um multi-mode (OM1) TX/RX fiber pair via a low cost plastic cover realizing the transmitter and receiver lens systems and demonstrates BER < 10-12 at the 25 Gb/s data rate over a distance of 3 meters. Using a 50/125 um laser optimized multi-mode fiber (OM3), the same performance was achieved over a distance of 30 meters.

  6. International Space Agency CIO Forum Industrial Control System (ICS) and Cyber

    NASA Technical Reports Server (NTRS)

    Powell, Robert

    2017-01-01

    This briefing covers Industrial Control System (ICS) best practices for enhancing cyber protection. The briefing provides a very high-level overview of best practices currently being pursued by NASA as well as by other US government agencies such as NIST and DHS ICS-CERT. All information presented in this slide deck is publicly available and no sensitive information is provided in these slides. These slides will be used to generate discussion around best practices within the international community in the area of ICS cyber protections.

  7. Decreasing the Preincision Time for Pulmonary Lobectomy: The Process of Lean and Value Stream Mapping.

    PubMed

    Cerfolio, Robert James; Steenwyk, Brad L; Watson, Caroline; Sparrow, James; Belopolsky, Victoria; Townsley, Matthew; Lyerly, Ralph; Downing, Michelle; Bryant, Ayesha; Gurley, William Quinton; Henling, Colleen; Crawford, Jack; Gayeski, Thomas E

    2016-03-01

    Our objective was to evaluate our results after the implementation of lean (the elimination of wasteful parts of a process). After meetings with our anesthesiologists, we standardized our "in the operating room-to-skin incision protocols" before pulmonary lobectomy. Patients were divided into consecutive cohorts of 300 lobectomy patients. Several protocols were slowly adopted and outcomes were evaluated. One surgeon performed 2,206 pulmonary lobectomies, of which 84% were for cancer. Protocols for lateral decubitus positioning changed over time. We eliminated axillary rolls, arm boards, and beanbags. Monitoring devices were slowly eliminated. Central catheters decreased from 75% to 0% of patients, epidurals from 84% to 3%, arterial catheters from 93% to 4%, and finally, Foley catheters were reduced from 99% to 11% (p ≤ 0.001 for all). A protocol for the insertion of double-lumen endotracheal tubes was established and times decreased (mean, 14 minutes to 1 minute; p = 0.001). After all changes were made, the time between operating room entry and incision decreased from a mean of 64 minutes to 37 minutes (p < 0.001). Outcomes improved, mortality decreased from 3.2% to 0.26% (p = 0.015), and major morbidity decreased from 15.2% to 5.3% (p = 0.042). Lean and value stream mapping can be safely applied to the clinical algorithms of high-risk patient care. We demonstrate that elimination of non-value-added steps can safely decrease preincision time without increasing patient risk in patients who undergo pulmonary lobectomy. Selected centers may be able to adopt some of these lean-driven protocols. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. AGB stars as tracers to IC 1613 evolution.

    NASA Astrophysics Data System (ADS)

    Hashemi, S. A.; Javadi, A.; van Loon, J. Th.

    We are going to apply AGB stars to find star formation history for IC 1613 galaxy; this a new and simple method that works well for nearby galaxies. IC 1613 is a Local Group dwarf irregular galaxy that is located at distance of 750 kpc, a gas rich and isolated dwarf galaxy that has a low foreground extinction. We use the long period variable stars (LPVs) that represent the very final stage of evolution of stars with low and intermediate mass at the AGB phase and are very luminous and cool so that they emit maximum brightness in near-infrared bands. Thus near-infrared photometry with using stellar evolutionary models help us to convert brightness to birth mass and age and from this drive star formation history of the galaxy. We will use the luminosity distribution of the LPVs to reconstruct the star formation history-a method we have successfully applied in other Local Group galaxies. Our analysis shows that the IC 1613 has had a nearly constant star formation rate, without any dominant star formation episode.

  9. Use of optical technique for inspection of warpage of IC packages

    NASA Astrophysics Data System (ADS)

    Toh, Siew-Lok; Chau, Fook S.; Ong, Sim Heng

    2001-06-01

    The packaging of IC packages has changed over the years, form dual-in-line, wire-bond, and pin-through-hole in printed wiring board technologies in the 1970s to ball grid array, chip scale and surface mount technologies in the 1990s. Reliability has been a big problem for manufacturers for some moisture-sensitive packages. One of the potential problems in plastic IC packages is moisture-induced popcorn effect which can arise during the reflow process. Shearography is a non-destructive inspection technique that may be used to detect the delamination and warpage of IC packages. It is non-contacting and permits a full-field observation of surface displacement derivatives. Another advantage of this technique is that it is able to give the real-time formation of the fringes which indicate flaws in the IC package under real-time simulation condition of Surface Mount Technology (SMT) IR reflow profile. It is extremely fast and convenient to study the true behavior of the packaging deformation during the SMT process. It can be concluded that shearography has the potential for the real- time detection, in situ and non-destructive inspection of IC packages during the surface mount process.

  10. Student Definitions of Intercultural Competence (IC)--Are They Context-Specific?

    ERIC Educational Resources Information Center

    Binder, Nadine; Odag, Ozen; Leiser, Anne; Ludders, Lisa; Kedzior, Karina Karolina

    2018-01-01

    Higher education institutions increasingly seek to promote students' intercultural competence (IC), yet its conceptualization remains a challenge. The first aim of this study was to explore how a purposive sample of n = 77 domestic, undergraduate students at a public university in Germany define IC. The second aim was to assess to what extent such…

  11. 30 CFR 57.22210 - In-line filters (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

  12. 30 CFR 57.22210 - In-line filters (I-C mines).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

  13. 30 CFR 57.22210 - In-line filters (I-C mines).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

  14. 30 CFR 57.22210 - In-line filters (I-C mines).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

  15. 30 CFR 57.22210 - In-line filters (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

  16. Ganoboninketals A-C, Antiplasmodial 3,4-seco-27-Norlanostane Triterpenes from Ganoderma boninense Pat.

    PubMed

    Ma, Ke; Ren, Jinwei; Han, Junjie; Bao, Li; Li, Li; Yao, Yijian; Sun, Chen; Zhou, Bing; Liu, Hongwei

    2014-08-22

    Three new nortriterpenes, ganoboninketals A-C (1-3), featuring rearranged 3,4-seco-27-norlanostane skeletons and highly complex polycyclic systems were isolated from the medicinal mushroom Ganoderma boninense. The structures of the new metabolites were established by spectroscopic methods. The absolute configurations in 1-3 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1-3 showed antiplasmodial activity against Plasmodium falciparum with IC50 values of 4.0, 7.9, and 1.7 μM, respectively. Compounds 1 and 3 also displayed weak cytotoxicity against A549 cell line with IC50 values of 47.6 and 35.8 μM, respectively. Compound 2 showed weak cytotoxicity toward HeLa cell line with an IC50 value of 65.5 μM. Compounds 1-3 also presented NO inhibitory activity in the LPS-induced macrophages with IC50 values of 98.3, 24.3, and 60.9 μM, respectively.

  17. Industry-Oriented Laboratory Development for Mixed-Signal IC Test Education

    ERIC Educational Resources Information Center

    Hu, J.; Haffner, M.; Yoder, S.; Scott, M.; Reehal, G.; Ismail, M.

    2010-01-01

    The semiconductor industry is lacking qualified integrated circuit (IC) test engineers to serve in the field of mixed-signal electronics. The absence of mixed-signal IC test education at the collegiate level is cited as one of the main sources for this problem. In response to this situation, the Department of Electrical and Computer Engineering at…

  18. 30 CFR 57.22241 - Advance face boreholes (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Boreholes shall be drilled in such a manner to insure that the advancing face will not accidently break into... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines...

  19. 30 CFR 57.22241 - Advance face boreholes (I-C mines).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

  20. 30 CFR 57.22241 - Advance face boreholes (I-C mines).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

  1. 30 CFR 57.22241 - Advance face boreholes (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

  2. 30 CFR 57.22241 - Advance face boreholes (I-C mines).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

  3. A Novel Two-Step Hierarchial Quantitative Structure-Activity ...

    EPA Pesticide Factsheets

    Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET ; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments) . The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models t

  4. Steroidal constituents from the edible sea urchin Diadema savignyi Michelin induce apoptosis in human cancer cells.

    PubMed

    Thao, Nguyen Phuong; Luyen, Bui Thi Thuy; Kim, Eun Ji; Kang, Jung Il; Kang, Hee Kyoung; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Kiem, Phan Van; Minh, Chau Van; Kim, Young Ho

    2015-01-01

    Bioassay-directed fractionation and purification were used to isolate 12 steroids (1-12) from a CH(2)Cl(2) extract of the edible Vietnamese sea urchin Diadema savignyi Michelin. The cytotoxic activity of the CH(2)Cl(2) extract and 12 steroids was evaluated in three human cancer cell lines (HL-60, PC-3, and SNU-C5). Relative to the effects of the positive control, mitoxantrone, the CH(2)Cl(2) extract (with an inhibitory concentration of 50% [IC(50)] values ranging from 1.37±0.15 to 3.11±0.15 μg/mL) and compounds 2 (with IC(50) values ranging from 5.29±0.11 to 6.80±0.67 μM) and 11 (with IC(50) values ranging from 4.95±0.07 to 6.99±0.28 μM) exhibited potent cytotoxic effects against all three tested human cancer cell lines. In addition, the CH(2)Cl(2) extract and compounds 2 and 11 were found to induce apoptosis. The induction of apoptosis was accompanied by alterations of the apoptosis-related protein expression, inactivation of ERK1/2 mitogen-activated protein kinase signaling, and decreased c-Myc expression. These data suggest that compounds 2 and 11 from the edible sea urchin D. savignyi may have potential for the treatment of colon cancer, leukemia, and prostate cancer as complementary cancer remedies.

  5. The antioxidant activity test by using DPPH method from the white tea using different solvents

    NASA Astrophysics Data System (ADS)

    Darmajana, Doddy A.; Hadiansyah, Firman; Desnilasari, Dewi

    2017-11-01

    The solvents used in this study are: aquades, ethanol and glacial acetic acid. The raw material as the source of antioxidants is white tea. Pure Quercetin is used as a comparing antioxidant. The treatment design was the solvent type for extraction, while the antioxidant activity was tested using DPPH method, with IC50 as the reference of antioxidant activity value. The results of antioxidant activity tests with three different solvent types are IC50 of 22,499 µg/mL for aquades, IC50 of 13,317 µg/mL for Ethanol and IC50 of 60,555 µg/mL for Glacial Acetic Acid. As a control of the standard antioxidant activity value of Quercetin is 4,313 µg/mL.

  6. MagIC, a genetically encoded fluorescent indicator for monitoring cellular Mg2+ using a non-Förster resonance energy transfer ratiometric imaging approach

    NASA Astrophysics Data System (ADS)

    Koldenkova, Vadim Pérez; Matsuda, Tomoki; Nagai, Takeharu

    2015-10-01

    Intracellular Mg roles are commensurate with its abundance in the cell cytoplasm. However, little is known about Mg subcellular dynamics, primarily due to the lack of suitable Mg-selective tools to monitor this ion in intracellular compartments. To cope with this lack, we developed a Mg-sensitive indicator-MagIC (indicator for Magnesium Imaging in Cell) -composed of a functionalized yellow fluorescent protein (FP) variant fused to a red-emitting FP serving as a reference, thus allowing ratiometric imaging of Mg. MagIC expressed in mammalian cells is homogeneously distributed between the cytosol and nucleus but its fusion with appropriate targeting sequences redirects it to mitochondria or the endoplasmic reticulum. MagIC shows little interference by intracellular Ca [Kd(Mg2+)=5.1 mM Kd(Ca2+)=4.8 mM] and its kinetic properties (k=84 s-1) approach those of indicator dyes. With MagIC, as reported previously, we also observed a cytosolic Mg increase provoked by application of 50 mM MgCl2 in the medium. This effect is, however, mimicked by 75 mM KCl or 150 mM D-sorbitol addition, indicating that it is a response to the associated hyperosmotic shock and not to Mg itself. Our results confirm the functionality of MagIC as a useful tool for the long-awaited possibility of prolonged and organelle-specific monitoring of cellular Mg.

  7. In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus.

    PubMed

    Arbab, Ahmed Hassan; Parvez, Mohammad Khalid; Al-Dosari, Mohammed Salem; Al-Rehaily, Adnan Jathlan

    2017-07-01

    Currently, >35 Saudi Arabian medicinal plants are traditionally used for various liver disorders without a scientific rationale. This is the first experimental evaluation of the anti-hepatitis B virus (HBV) potential of the total ethanolic and sequential organic extracts of 60 candidate medicinal plants. The extracts were tested for toxicity on HepG2.2.15 cells and cytotoxicity concentration (CC 50 ) values were determined. The extracts were further investigated on HepG2.2.15 cells for anti-HBV activities by analyzing the inhibition of HBsAg and HBeAg production in the culture supernatants, and their half maximal inhibitory concentration (IC 50 ) and therapeutic index (TI) values were determined. Of the screened plants, Guiera senegalensis (dichloromethane extract, IC 50 =10.65), Pulicaria crispa (ethyl acetate extract, IC 50 =14.45), Coccinea grandis (total ethanol extract, IC 50 =31.57), Fumaria parviflora (hexane extract, IC 50 =35.44), Capparis decidua (aqueous extract, IC 50 =66.82), Corallocarpus epigeus (total ethanol extract, IC 50 =71.9), Indigofera caerulea (methanol extract, IC 50 =73.21), Abutilon figarianum (dichloromethane extract, IC 50 =99.76) and Acacia oerfota (total ethanol extract, IC 50 =101.46) demonstrated novel anti-HBV activities in a time- and dose-dependent manner. Further qualitative phytochemical analysis of the active extracts revealed the presence of alkaloids, tannins, flavonoids and saponins, which are attributed to antiviral efficacies. In conclusion, P. crispa, G. senegalensis and F. parviflora had the most promising anti-HBV potentials, including those of C. decidua , C. epigeus, A. figarianum , A. oerfota and I. caerulea with marked activities. However, a detailed phytochemical study of these extracts is essential to isolate the active principle(s) responsible for their novel anti-HBV potential.

  8. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus

    PubMed Central

    Bandara, Suren B.; Eubig, Paul A.; Sadowski, Renee N.; Schantz, Susan L.

    2016-01-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID:26543103

  9. Men Working on Mock-Up of S-IC Thrust Structure

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This photograph depicts Marshall Space Flight Center employees, James Reagin, machinist (top); Floyd McGinnis, machinist; and Ernest Davis, experimental test mechanic (foreground), working on a mock up of the S-IC thrust structure. The S-IC stage is the first stage, or booster, of the 364-foot long Saturn V rocket that ultimately took astronauts to the Moon. The S-IC stage, burned over 15 tons of propellant per second during its 2.5 minutes of operation to take the vehicle to a height of about 36 miles and to a speed of about 6,000 miles per hour. The stage was 138 feet long and 33 feet in diameter. Operating at maximum power, all five of the engines produced 7,500,000 pounds of thrust.

  10. J{sub IC} evaluation of the smooth and the side-grooved CT specimen in the reactor pressure vessel steel (SA508-3)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oh, S.W.; Lim, M.B.; Kim, T.H.

    1993-12-31

    The elastic-plastic fracture toughness J{sub IC} of SA508-3 forging steel was investigated by using CT-type specimens. The thickness of the smooth specimen is B{sub 0} = 25.4 mm and the side groove specimen is B{sub N} = 20.4 mm and the side groove deep is S{center_dot}G = [(B{sub 0} {minus} B{sub N})/B{sub 0}] {times} 100 = 19.7% and the groove angle is 90{degree}. The J{sub IC} tests estimated according to the method proposed in the ASTM E813-81 and JSME S001-81. The side-grooved specimen have the advantage of J{sub IC} estimation, it is much easier to determine the onset of ductilemore » tearing by the R-curve method and it improved accuracy and scatter of the toughness values thus determined, provided all the size-requirements for the specimen prescribed in the JSME method were satisfied. But it is difficult to find by the ASTM method. The critical stretched zone width (SZW{sub C}) of the side-grooved specimens found to be smaller than that previously determined for the standard CT specimens without side-grooves. This was attributed to higher triaxiality produced by the side-grooves. The stretched zone width method gave slightly larger J{sub IC} values than those by the R-curve method for SA508-3, as has been observed for the standard specimen without side-groove.« less

  11. Analysis of radiological parameters associated with decreased fractional anisotropy values on diffusion tensor imaging in patients with lumbar spinal stenosis.

    PubMed

    Wang, Xiandi; Wang, Hongli; Sun, Chi; Zhou, Shuyi; Meng, Tao; Lv, Feizhou; Ma, Xiaosheng; Xia, Xinlei; Jiang, Jianyuan

    2018-04-26

    Previous studies have indicated that decreased fractional anisotropy (FA) values on diffusion tensor imaging (DTI) are well correlated with the symptoms of nerve root compression. The aim of our study is to determine primary radiological parameters associated with decreased FA values in patients with lumbar spinal stenosis involving single L5 nerve root. Patients confirmed with single L5 nerve root compression by transforaminal nerve root blocks were included in this study. FA values of L5 nerve roots on both symptomatic and asymptomatic side were obtained. Conventional radiological parameters, such as disc height, degenerative scoliosis, dural sac cross-sectional area (DSCSA), foraminal height (FH), hypertrophic facet joint degeneration (HFJD), sagittal rotation (SR), sedimentation sign, sagittal translation and traction spur were measured. Correlation and regression analyses were performed between the radiological parameters and FA values of the symptomatic L5 nerve roots. A predictive regression equation was established. Twenty-one patients were included in this study. FA values were significantly lower at the symptomatic side comparing to the asymptomatic side (0.263 ± 0.069 vs. 0.334 ± 0.080, P = 0.038). DSCSA, FH, HFJD, and SR were significantly correlated with the decreased FA values, with r = 0.518, 0.443, 0.472 and - 0.910, respectively (P < 0.05). DSCSA and SR were found to be the primary radiological parameters related to the decreased FA values, and the regression equation is FA = - 0.012 × SR + 0.002 × DSCSA. DSCSA and SR were primary contributors to decreased FA values in LSS patients involving single L5 nerve root, indicating that central canal decompression and segmental stability should be the first considerations in preoperative planning of these patients. These slides can be retrieved under Electronic Supplementary Material.

  12. Metal transport capabilities of anticancer copper chelators.

    PubMed

    Gaál, Anikó; Orgován, Gábor; Mihucz, Victor G; Pape, Ian; Ingerle, Dieter; Streli, Christina; Szoboszlai, Norbert

    2018-05-01

    In the present study, several Cu chelators [2,2'-biquinoline, 8-hydroxiquinoline (oxine), ammonium pyrrolidinedithiocarbamate (APDTC), Dp44mT, dithizone, neocuproine] were used to study Cu uptake, depletion and localization in different cancer cell lines. To better understand the concentration dependent fluctuations in the Cu intracellular metal content and Cu-dependent in vitro antiproliferative data, the conditional stability constants of the Cu complex species of the investigated ligands were calculated. Each investigated chelator increased the intracellular Cu content on HT-29 cells causing Cu accumulation depending on the amount of the free Cu(II). Copper accumulation was 159 times higher for Dp44mT compared to the control. Investigating a number of other transition metals, intracellular accumulation of Cd was observed only for two chelators. Intracellular Zn content slightly decreased (cca. 10%) for MCF-7 cells, while a dramatic decrease was observed on MDA-MB-231 ones (cca. 50%). A similar decrease was observed for HCT-116, while Zn depletion for HT-29 corresponded to cca. 20%. The IC 50 values were registered for the investigated four cell lines at increasing external Cu(II) concentration, namely, MDA-MB-231 cells had the lowest IC 50 values for Dp44mT ranging between 7 and 35 nM. Thus, Zn depletion could be associated with lower IC 50 values. Copper depletion was observed for all ligands being less pronounced for Dp44mT and neocuproine. Copper localization and its colocalization with Zn were determined by μ-XRF imaging. Loose correlation (0.57) was observed for the MCF-7 cells independently of the applied chelator. Similarly, a weak correlation (0.47) was observed for HT-29 cells treated with Cu(II) and oxine. Colocalization of Cu and Zn in the nucleus of HT-29 cells was observed for Dp44mT (correlation coefficient of 0.85). Copyright © 2018 Elsevier GmbH. All rights reserved.

  13. 3D-ICs created using oblique processing

    NASA Astrophysics Data System (ADS)

    Burckel, D. Bruce

    2016-03-01

    This paper demonstrates that another class of three-dimensional integrated circuits (3D-ICs) exists, distinct from through silicon via centric and monolithic 3D-ICs. Furthermore, it is possible to create devices that are 3D at the device level (i.e. with active channels oriented in each of the three coordinate axes), by performing standard CMOS fabrication operations at an angle with respect to the wafer surface into high aspect ratio silicon substrates using membrane projection lithography (MPL). MPL requires only minimal fixturing changes to standard CMOS equipment, and no change to current state-of-the-art lithography. Eliminating the constraint of 2D planar device architecture enables a wide range of new interconnect topologies which could help reduce interconnect resistance/capacitance, and potentially improve performance.

  14. IC [Interior Communications] Electrician 3 and 2: Rate Training Manual. Revised.

    ERIC Educational Resources Information Center

    Naval Education and Training Command, Pensacola, FL.

    The rate training manual provides information related to the tasks assigned to the Interior Communications (IC) Electricians Third and Second Class who operate and maintain the interior communications systems and associated equipment. Chapter one discusses career challenges for the IC Electrician in terms of responsibilities, advancement…

  15. PTP1B, α-glucosidase, and DPP-IV inhibitory effects for chromene derivatives from the leaves of Smilax china L.

    PubMed

    Zhao, Bing Tian; Le, Duc Dat; Nguyen, Phi Hung; Ali, Md Yousof; Choi, Jae-Sue; Min, Byung Sun; Shin, Heung Mook; Rhee, Hae Ik; Woo, Mi Hee

    2016-06-25

    Two new flavonoids, bismilachinone (11) and smilachinin (14), were isolated from the leaves of Smilax china L. together with 14 known compounds. Their structures were elucidated using spectroscopic methods. The PTP1B, α-glucosidase, and DPP-IV inhibitory activities of compounds 1-16 were evaluated at the molecular level. Among them, compounds 4, 7, and 10 showed moderate DPP-IV inhibitory activities with IC50 values of 20.81, 33.12, and 32.93 μM, respectively. Compounds 3, 4, 6, 11, 12, and 16 showed strong PTP1B inhibitory activities, with respective IC50 values of 7.62, 10.80, 0.92, 2.68, 9.77, and 24.17 μM compared with the IC50 value for the positive control (ursolic acid: IC50 = 1.21 μM). Compounds 2-7, 11, 12, 15, and 16 showed potent α-glucosidase inhibitory activities, with respective IC50 values of 8.70, 81.66, 35.11, 35.92, 7.99, 26.28, 11.28, 62.68, 44.32, and 70.12 μM. The positive control, acarbose, displayed an IC50 value of 175.84 μM. In the kinetic study for the PTP1B enzyme, compounds 6, 11, and 12 displayed competitive inhibition with Ki values of 3.20, 8.56, and 5.86 μM, respectively. Compounds 3, 4, and 16 showed noncompetitive inhibition with Ki values of 18.75, 5.95, and 22.86 μM, respectively. Molecular docking study for the competitive inhibitors (6, 11, and 12) radically corroborates the binding affinities and inhibition of PTP1B enzymes. These results indicated that the leaves of Smilax china L. may contain compounds with anti-diabetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Polysaccharide peptides from COV-1 strain of Coriolus versicolor inhibit tolbutamide 4-hydroxylation in the rat in vitro and in vivo.

    PubMed

    Yeung, John H K; Chan, Siu-Lung; Or, Penelope M Y

    2006-08-01

    Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. In this study, the effects of whole PSP extract and water extract of PSP on 4-hydroxylation of tolbutamide were investigated in rat liver microsomes in vitro and in vivo in the rat. Both the whole PSP extract and the water soluble fraction (0.5-20 microM) decreased the metabolism of tolbutamide to 4-hydroxytolbutamide in vitro. Enzyme kinetics studies showed that PSP inhibited tolbutamide 4-hydroxylase activity in a competitive, concentration-dependent manner. The whole PSP extract had a Ki value of 12.6 microM and IC50 at 18.4 microM, while the water extract had a Ki value of 6.9 microM and IC50 at 9.8 microM. Sulphaphenazole, a specific human CYP2C9 inhibitor, showed a Ki value of 30.8 microM and IC50 at 44.0 microM in the test system. In the pharmacokinetic studies in vivo, acute PSP (4 micromol/kg, i.p.) treatment did not produce significant changes in tolbutamide clearance, but produced a decrease in the Cinitial (7.4%) and an increase in the Vd (7.4%). Sub-chronic pre-treatment of PSP (1-2 micromol/kg/day, i.p.) for three days did not affect the clearance and AUC of tolbutamide, but the Cinitial was decreased, together with increases in the T1/2, and Vd. The formation of 4-hydroxytolbutamide in vivo was decreased in both acute and sub-chronic studies. Taken together, this study demonstrated the PSP can inhibit tolbutamide 4-hydroxylation both in vitro and in vivo. Despite the fact that CYP isoforms that metabolise tolbutamide are different between rat and human liver due to different catalytic characteristics, and rat studies may not be directly extrapolatable to man, the concomitant use of PSP with other CYP2C substrates should be carefully monitored.

  17. The Association Between Low 50 g Glucose Challenge Test Values and Adverse Pregnancy Outcomes.

    PubMed

    Kwon, Hayan; Lee, Joonho; Lee, Byung-Wan; Kwon, Ja-Young; Kim, Young-Han

    2018-01-11

    The implications of low values on the 50 g glucose challenge test (GCT) in pregnancy are not clearly defined. Few studies have evaluated the influence of maternal low GCT values on obstetrical outcomes. This study aimed to compare pregnancy outcomes between women with low 50 g GCT values and those with normal values. Women undergoing gestational diabetes mellitus screening at 24-28 weeks of gestational age between January 2010 and December 2016 were retrospectively evaluated. Women with multifetal pregnancies, prepregnancy type I or II diabetes, GCT performed before 24 or after 28 weeks of gestational age, and women undergoing multiple GCTs in the same pregnancy were excluded. Low GCT values and normal GCT values were defined as ≤85 mg/dL and 86-130 mg/dL, respectively. Of 3875 screened subjects, 519 (13.4%) women were included in the low GCT group and 3356 (86.6%) in the normal GCT group. Low GCT women had a significantly higher rate of small for gestational age (SGA) infants than normal GCT women (10.8% vs. 7.9%, p = 0.02). Cesarean section and postpartum hemorrhage (PPH) were less frequent in low GCT women than in normal women (32.6% vs. 42.8%, p < 0.01 and 0.2% vs. 1.2%, p = 0.03, respectively). Low GCT women had a 1.38-fold increased risk of bearing SGA infants (95% confidence intervals: 1.01-1.88, p = 0.04). Rate of SGA infants was significantly higher and cesarean delivery and PPH rates were significantly lower in women with low GCT values. Low GCT values were independently associated with an increased risk of SGA.

  18. Unveiling the AGN in IC 883: discovery of a parsec-scale radio jet

    NASA Astrophysics Data System (ADS)

    Romero-Cañizales, C.; Alberdi, A.; Ricci, C.; Arévalo, P.; Pérez-Torres, M. Á.; Conway, J. E.; Beswick, R. J.; Bondi, M.; Muxlow, T. W. B.; Argo, M. K.; Bauer, F. E.; Efstathiou, A.; Herrero-Illana, R.; Mattila, S.; Ryder, S. D.

    2017-05-01

    IC 883 is a luminous infrared galaxy (LIRG) classified as a starburst-active galactic nucleus (AGN) composite. In a previous study, we detected a low-luminosity AGN (LLAGN) radio candidate. Here, we report on our radio follow-up at three frequencies that provides direct and unequivocal evidence of the AGN activity in IC 883. Our analysis of archival X-ray data, together with the detection of a transient radio source with luminosity typical of bright supernovae, gives further evidence of the ongoing star formation activity, which dominates the energetics of the system. At sub-parsec scales, the radio nucleus has a core-jet morphology with the jet being a newly ejected component showing a subluminal proper motion of 0.6-1 c. The AGN contributes less than 2 per cent of the total IR luminosity of the system. The corresponding Eddington factor is ˜10-3, suggesting this is a low-accretion rate engine, as often found in LLAGNs. However, its high bolometric luminosity (˜1044 erg s-1) agrees better with a normal AGN. This apparent discrepancy may just be an indication of the transition nature of the nucleus from a system dominated by star formation, to an AGN-dominated system. The nucleus has a strongly inverted spectrum and a turnover at ˜4.4 GHz, thus qualifying as a candidate for the least luminous (L5.0 GHz ˜ 6.3 × 1028 erg s-1 Hz-1) and one of the youngest (˜3 × 103 yr) gigahertz-peaked spectrum (GPS) sources. If the GPS origin for the IC 883 nucleus is confirmed, then advanced mergers in the LIRG category are potentially key environments to unveil the evolution of GPS sources into more powerful radio galaxies.

  19. A Green Synthesis of Chalcones As an Antioxidant and Anticancer

    NASA Astrophysics Data System (ADS)

    Susanti VH, Elfi; Agustina Eko Setyowati, Widiastuti

    2018-01-01

    Three chalcones (4’-amino-4-methoxy chalcone, 4’-amino-3,4-dimethoxy chalcone and 4’-amino-3,4,5-trimethoxy chalcone) has been synthesized by a green chemistry approach using grinding technique. Antioxidant activity of the chalcones were assessed using 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. Cytotoxicity of chalcones sythesized was evaluated using a tetrazolium (MTT) colorimetric assay against cervical cancer cell line, HeLa. The antioxidant activity test showed that 4’-amino-4-methoxy chalcone had a stronger activity than the 4’-amino-3,4-dimethoxy chalcone and 4’-amino-3,4,5-trimethoxy chalcone, respectively with IC50 58.85, 64.79 and 210.3 μg/mL. These results indicate that there is a relationship between the structure of chalcone with antioxidant activity, the more methoxy groups in the ring B of the chalcone, antioxidant activity is getting smaller. The chalcone synthesized showed cytotoxicity against HeLa cell line with IC50 value of 31.75, 36.65, 49.04 μg/mL, respectively. It was observed that the highest cytotoxic activity was found at 4’-amino-4-methoxy chalcone (IC50 31.75 μg/mL). Lower activity was showed by 4’-amino-3,4,5-trimethoxy chalcone with IC50 value of 49,04 μg/mL. There is a relationship cytotoxicity with chalcone structure, the more the number of methoxy groups in ring B chalcone, will decrease the activity of cytotoxicity.

  20. The effects of acute pesticide exposure on neuroblastoma cells chronically exposed to diazinon.

    PubMed

    Axelrad, J C; Howard, C V; McLean, W G

    2003-03-14

    Speculation about potential neurotoxicity due to chronic exposure to low doses of organophosphate (OP) pesticides is not yet supported by experimental evidence. The objective of this work was to use a cell culture model of chronic OP exposure to determine if such exposure can alter the sensitivity of nerve cells to subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then withdrawn and the cells were induced to differentiate in the presence of various other pesticides or herbicides, including OPs and OP-containing formulations. The resulting outgrowth of neurite-like structures was measured by light microscopy and quantitative image analysis and the IC(50) for each OP or formulation was calculated. The IC(50) values in diazinon-pre-exposed cells were compared with the equivalent values in cells not pre-exposed to diazinon. The IC(50) for inhibition of neurite outgrowth by acute application of diazinon, pyrethrum, glyphosate or a commercial formulation of glyphosate was decreased by between 20 and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos methyl was unaffected and those for phosmet or chlorpyrifos were increased by between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second glyphosate-containing formulation led to the formation of abnormal neurite-like structures in diazinon-pre-exposed cells. The data support the view that chronic exposure to an OP may reduce the threshold for toxicity of some, but by no means all, environmental agents.

  1. Edwards nXDS15iC Vacuum Scroll Pump Pressure Testing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sessions, H.; Morgan, G. A.

    2013-07-17

    The SRNL High Pressure Laboratory performed testing on an Edwards Model nXDS15iC Vacuum Scroll Pump on July 10th and 11th of 2013 at 723-A. This testing was done in an attempt to obtain initial compression ratio information for the nXDS15iC pump, with compression ratio defined as discharge pressure of the pump divided by suction pressure. Pressure burst testing was also done on the pump to determine its design pressure for pressure safety reasons. The Edwards nXDS15iC pump is being evaluated by SRNL for use part of the SHINE project being executed by SRNL.

  2. Construction Progress of the S-IC Test Stand Complex Bunker House

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the S-IC stand, additional related facilities were built during this time frame. Built to the east of the S-IC stand, the block house served as the control room. To the south of the blockhouse was a newly constructed pump house used for delivering water to the S-IC stand during testing. North of the massive test stand, the F-1 Engine test stand was built for testing a single F-1 engine. Just southeast of the S-IC stand a concrete bunker house was constructed. The bunker housed

  3. Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract.

    PubMed

    Abe, Masayuki; Ito, Yoshihiko; Oyunzul, Luvsandorj; Oki-Fujino, Tomomi; Yamada, Shizuo

    2009-04-01

    Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine (1,4-DHP) calcium channel antagonist receptors. Major constituents of SPE are lauric acid, oleic acid, myristic acid, palmitic acid and linoleic acid. The aim of this study was to investigate binding affinities of these fatty acids for pharmacologically relevant (alpha(1)-adrenergic, muscarinic and 1,4-DHP) receptors. The fatty acids inhibited specific [(3)H]prazosin binding in rat brain in a concentration-dependent manner with IC(50) values of 23.8 to 136 microg/ml, and specific (+)-[(3)H]PN 200-110 binding with IC(50) values of 24.5 to 79.5 microg/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [(3)H]N-methylscopolamine ([(3)H]NMS) binding in rat brain with IC(50) values of 56.4 to 169 microg/ml. Palmitic acid had no effect on specific [(3)H]NMS binding. The affinity of oleic acid, myristic acid and linoleic acid for each receptor was greater than the affinity of SPE. Scatchard analysis revealed that oleic acid and lauric acid caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]prazosin, [(3)H]NMS and (+)-[(3)H]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to alpha(1)-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5alpha-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5alpha-reductase activity in rat liver with an IC(50) of 101 microg/ml. Similarly, all the fatty acids except palmitic acid inhibited 5alpha-reductase activity, with IC(50) values of 42.1 to 67.6 microg/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of alpha(1)-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5

  4. Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

    ERIC Educational Resources Information Center

    Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

    2010-01-01

    This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

  5. ICS classification system of infected osteosynthesis: Long-term results.

    PubMed

    Romanò, Carlo L; Morelli, Ilaria; Romanò, Delia; Meani, Enzo; Drago, Lorenzo

    2018-03-01

    The best treatment strategy for infected osteosyntheses is still debated. While hardware removal or eventually early device exchange may be necessary in most of the cases, temporary hardware retention until fracture healing can be a valid alternative option in others. Aim of the present study is to report the long-term results of 215 patients with infected osteosyntheses, treated according to the ICS (Infection, Callus, Stability) classification in two Italian hospitals. Patients classified as ICS Type 1 (N = 83) feature callus progression and hardware stability, in spite of the presence of infection; these patients were treated with suppressive antibiotic therapy coupled with local debridement in 18.1% of the cases, and no hardware removal until bone healing. Type 2 patients (N = 75) are characterized by the presence of infection and hardware stability, but no callus progression; these patients were treated as Type 1 patients, but with additional callus stimulation therapies. Type 3 patients (N = 57), showing infection, no callus progression and loss of hardware stability, underwent removal and exchange of the fixation device. Considering only the initial treatment, performed according to the ICS classification, at a minimum 5 years follow up, 89.3% achieved bone healing and 93.5% did not show infection recurrence. The ICS classification appears as a useful and reliable tool to help standardizing the decision-making process in treating infected osteosynthesis with the most conservative approach. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

    PubMed

    Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

    2017-08-03

    The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

  7. ICS-II USA research design and methodology.

    PubMed

    Rana, H; Andersen, R M; Nakazono, T T; Davidson, P L

    1997-05-01

    The purpose of the WHO-sponsored International Collaborative Study of Oral Health Outcomes (ICS-II) was to provide policy-markers and researchers with detailed, reliable, and valid data on the oral health situation in their countries or regions, together with comparative data from other dental care delivery systems. ICS-II used a cross-sectional design with no explicit control groups or experimental interventions. A standardized methodology was developed and tested for collecting and analyzing epidemiological, sociocultural, economic, and delivery system data. Respondent information was obtained by household interviews, and clinical examinations were conducted by calibrated oral epidemiologists. Discussed are the sampling design characteristics for the USA research locations, response rates, samples size for interview and oral examination data, weighting procedures, and statistical methods. SUDAAN was used to adjust variance calculations, since complex sampling designs were used.

  8. Multicolor CCD Photometry of the Open Cluster IC361

    DTIC Science & Technology

    2010-01-01

    journal Volume 19 Numbers 1/2 2010 Contents V. Straizys, A. Kazlauskas. Young stars in the Camelopardalis dust and molecular clouds. VI. YSOs...Vilnius + I system for 7250 stars down to 1= 19.6 mag has been obtained in the 20’ x 26’ field of the open cluster IC 361 in Camelopardalis . The catalog...1= 19.6 mag has been obtained in the 20’ x 26’ field of the open cluster IC 361 in Camelopardalis . The catalog of 1420 stars down to V ~ 18.5 mag

  9. Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers.

    PubMed

    De Martino, Federico; Gentile, Francesco; Esposito, Fabrizio; Balsi, Marco; Di Salle, Francesco; Goebel, Rainer; Formisano, Elia

    2007-01-01

    We present a general method for the classification of independent components (ICs) extracted from functional MRI (fMRI) data sets. The method consists of two steps. In the first step, each fMRI-IC is associated with an IC-fingerprint, i.e., a representation of the component in a multidimensional space of parameters. These parameters are post hoc estimates of global properties of the ICs and are largely independent of a specific experimental design and stimulus timing. In the second step a machine learning algorithm automatically separates the IC-fingerprints into six general classes after preliminary training performed on a small subset of expert-labeled components. We illustrate this approach in a multisubject fMRI study employing visual structure-from-motion stimuli encoding faces and control random shapes. We show that: (1) IC-fingerprints are a valuable tool for the inspection, characterization and selection of fMRI-ICs and (2) automatic classifications of fMRI-ICs in new subjects present a high correspondence with those obtained by expert visual inspection of the components. Importantly, our classification procedure highlights several neurophysiologically interesting processes. The most intriguing of which is reflected, with high intra- and inter-subject reproducibility, in one IC exhibiting a transiently task-related activation in the 'face' region of the primary sensorimotor cortex. This suggests that in addition to or as part of the mirror system, somatotopic regions of the sensorimotor cortex are involved in disambiguating the perception of a moving body part. Finally, we show that the same classification algorithm can be successfully applied, without re-training, to fMRI collected using acquisition parameters, stimulation modality and timing considerably different from those used for training.

  10. Construction Progress of the S-IC Test Stand-Pumps

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken April 4, 1961, shows the S-IC test stand dry once again when workers resumed construction after a 6 month delay due to booster size reconfiguration back in September of 1961. The disturbance of a natural spring during the excavation of the site required water to be pumped from the site continuously. The site was completely flooded after the pumps were shut down during the construction delay.

  11. Galaxy IC 3639 with Obscured Active Galactic Nucleus

    NASA Image and Video Library

    2017-01-07

    IC 3639, a galaxy with an active galactic nucleus, is seen in this image combining data from the Hubble Space Telescope and the European Southern Observatory. This galaxy contains an example of a supermassive black hole hidden by gas and dust. Researchers analyzed NuSTAR data from this object and compared them with previous observations from NASA's Chandra X-Ray Observatory and the Japanese-led Suzaku satellite. The findings from NuSTAR, which is more sensitive to higher energy X-rays than these observatories, confirm the nature of IC 3639 as an active galactic nucleus that is heavily obscured, and intrinsically much brighter than observed. http://photojournal.jpl.nasa.gov/catalog/PIA21087

  12. A linear acoustic model for intake wave dynamics in IC engines

    NASA Astrophysics Data System (ADS)

    Harrison, M. F.; Stanev, P. T.

    2004-01-01

    In this paper, a linear acoustic model is described that has proven useful in obtaining a better understanding of the nature of acoustic wave dynamics in the intake system of an internal combustion (IC) engine. The model described has been developed alongside a set of measurements made on a Ricardo E6 single cylinder research engine. The simplified linear acoustic model reported here produces a calculation of the pressure time-history in the port of an IC engine that agrees fairly well with measured data obtained on the engine fitted with a simple intake system. The model has proved useful in identifying the role of pipe resonance in the intake process and has led to the development of a simple hypothesis to explain the structure of the intake pressure time history: the early stages of the intake process are governed by the instantaneous values of the piston velocity and the open area under the valve. Thereafter, resonant wave action dominates the process. The depth of the early depression caused by the moving piston governs the intensity of the wave action that follows. A pressure ratio across the valve that is favourable to inflow is maintained and maximized when the open period of the valve is such to allow at least, but no more than, one complete oscillation of the pressure at its resonant frequency to occur while the valve is open.

  13. Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs.

    PubMed

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Khan, Huma; Ullah, Hayat; Salar, Uzma; Khan, Khalid Mohammed

    2016-10-01

    Hybrid bisindole-thiosemicarbazides analogs (1-18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2±0.75, 21.4±0.30 and 28.12±0.25μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

    PubMed

    Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

    2010-09-22

    In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

  15. 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.

    PubMed

    Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H; Brun, Reto; Carballeira, Néstor M

    2010-11-01

    Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC(50) value 6.6 μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC(50) value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescence analysis (IC(50) 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC(50) values of 0.38 and 0.58 μg/ml (IC(50) control drugs 14 and 30 ng/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC(50) values 3.7-31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC(50) 20.2 μg/ml), and Leishmania donovani (IC(50) values 4.1-13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to

  16. 2-Hexadecynoic Acid Inhibits Plasmodial FAS-II Enzymes and Arrest Erythrocytic and Liver Stage Plasmodium Infections

    PubMed Central

    Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L.; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H.; Brun, Reto; Carballeira, Néstor M.

    2010-01-01

    Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of P. yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC50 value 6.6. μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC50 value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescense analysis (IC50 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory against the PfFAS-II enzymes PfFabI and PfFabZ with IC50 values of 0.38 and 0.58 μg/ml (IC50 control drugs 14 and 30 ng/ml) respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC50 values 3.7–31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC50 20.2 μg/ml), and Leishmania donovani (IC50 values 4.1–13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature and calculated pharmacokinetic properties suggest that 2-HDA could be a useful compound to study the interaction of fatty

  17. Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series.

    PubMed

    Roussaki, Marina; Hall, Belinda; Lima, Sofia Costa; da Silva, Anabela Cordeiro; Wilkinson, Shane; Detsi, Anastasia

    2013-12-01

    A series of novel quinolinone-chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone-chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC50 value of 1.3±0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC50 values of 2.1±0.6 and 3.1±1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC50 values of 2.6±0.1 and 3.3±0.1 μM, respectively) as well as 6 and 9 (both having IC50 values of <5 μM). Chemical modifications on the quinolinone-chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit.

    PubMed

    Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nabekura, J; Noguchi, K; Akaike, N; Witt, M R; Nielsen, M

    1997-06-25

    Recombinant human GABA(A) receptors were investigated in vitro by coexpression of cDNAs coding for alpha1, beta2, and gamma2 subunits in the baculovirus/Sf-9 insect cell system. We report that a single amino acid exchange (isoleucine 121 to valine 121) in the N-terminal, extracellular part of the alpha1 subunit induces a marked decrease in agonist GABA(A) receptor ligand sensitivity. The potency of muscimol and GABA to inhibit the binding of the GABA(A) receptor antagonist [3H]SR 95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide) was higher in receptor complexes of alpha1(ile 121) beta2gamma2 than in those of alpha1(val 121) beta2gamma2 (IC50 values were 32-fold and 26-fold lower for muscimol and GABA, respectively). The apparent affinity of the GABA(A) receptor antagonist bicuculline methiodide to inhibit the binding of [3H]SR 95531 did not differ between the two receptor complex variants. Electrophysiological measurements of GABA induced whole-cell Cl- currents showed a ten-fold decrease in the GABA(A) receptor sensitivity of alpha1 (val 121) beta2gamma2 as compared to alpha1(ile 121) beta2gamma2 receptor complexes. Thus, a relatively small change in the primary structure of the alpha1 subunit leads to a decrease selective for GABA(A) receptor sensitivity to agonist ligands, since no changes were observed in a GABA(A) receptor antagonist affinity and benzodiazepine receptor binding.

  19. 50 Years of ``Scaling'' Jack Kilby's Invention

    NASA Astrophysics Data System (ADS)

    Doering, Robert

    2008-03-01

    This year is the 50th anniversary of Jack Kilby's 1958 invention of the integrated circuit (IC), for which he won the 2000 Nobel Prize in Physics. Since that invention in a laboratory at Texas Instruments, IC components have been continuously miniaturized, which has resulted in exponential improvement trends in their performance, energy efficiency, and cost per function. These improvements have created a semiconductor industry that has grown to over 250B in annual sales. The process of reducing integrated-circuit component size and associated parameters in a coordinated fashion is traditionally called ``feature-size scaling.'' Kilby's original circuit had active (transistor) and passive (resistor, capacitor) components with dimensions of a few millimeters. Today, the minimum feature sizes on integrated circuits are less than 30 nanometers for patterned line widths and down to about one nanometer for film thicknesses. Thus, we have achieved about five orders of magnitude in linear-dimension scaling over the past fifty years, which has resulted in about ten orders of magnitude increase in the density of IC components, a representation of ``Moore's Law.'' As IC features are approaching atomic dimensions, increasing emphasis is now being given to the parallel effort of further diversifying the types of components in integrated circuits. This is called ``functional scaling'' and ``more then Moore.'' Of course, the enablers for both types of scaling have been developed at many laboratories around the world. This talk will review a few of the highlights in scaling and its applications from R&D projects at Texas Instruments.

  20. Linalool, a Piper aduncum essential oil component, has selective activity against Trypanosoma cruzi trypomastigote forms at 4°C

    PubMed Central

    Villamizar, Luz Helena; Cardoso, Maria das Graças; de Andrade, Juliana; Teixeira, Maria Luisa; Soares, Maurilio José

    2017-01-01

    BACKGROUND Recent studies showed that essential oils from different pepper species (Piper spp.) have promising leishmanicidal and trypanocidal activities. OBJECTIVES In search for natural compounds against Trypanosoma cruzi, different forms of the parasite were incubated for 24 h at 28ºC or 4ºC with Piper aduncum essential oil (PaEO) or its main constituents linalool and nerolidol. METHODS PaEO chemical composition was obtained by GC-MS. Drug activity assays were based on cell counting, MTT data or infection index values. The effect of PaEO on the T. cruzi cell cycle and mitochondrial membrane potential was evaluated by flow cytometry. FINDINGS PaEO was effective against cell-derived (IC50/24 h: 2.8 μg/mL) and metacyclic (IC50/24 h: 12.1 μg/mL) trypomastigotes, as well as intracellular amastigotes (IC50/24 h: 9 μg/mL). At 4ºC - the temperature of red blood cells (RBCs) storage in blood banks - cell-derived trypomastigotes were more sensitive to PaEO (IC50/24 h = 3.8 μg/mL) than to gentian violet (IC50/24 h = 24.7 mg/mL). Cytotoxicity assays using Vero cells (37ºC) and RBCs (4ºC) showed that PaEO has increased selectivity for cell-derived trypomastigotes. Flow cytometry analysis showed that PaEO does not affect the cell cycle of T. cruzi epimastigotes, but decreases their mitochondrial membrane potential. GC-MS data identified nerolidol and linalool as major components of PaEO, and linalool had trypanocidal effect (IC50/24 h: 306 ng/mL) at 4ºC. MAIN CONCLUSION The trypanocidal effect of PaEO is likely due to the presence of linalool, which may represent an interesting candidate for use in the treatment of potentially contaminated RBCs bags at low temperature. PMID:28177047

  1. Linalool, a Piper aduncum essential oil component, has selective activity against Trypanosoma cruzi trypomastigote forms at 4°C.

    PubMed

    Villamizar, Luz Helena; Cardoso, Maria das Graças; Andrade, Juliana de; Teixeira, Maria Luisa; Soares, Maurilio José

    2017-02-01

    Recent studies showed that essential oils from different pepper species (Piper spp.) have promising leishmanicidal and trypanocidal activities. In search for natural compounds against Trypanosoma cruzi, different forms of the parasite were incubated for 24 h at 28ºC or 4ºC with Piper aduncum essential oil (PaEO) or its main constituents linalool and nerolidol. PaEO chemical composition was obtained by GC-MS. Drug activity assays were based on cell counting, MTT data or infection index values. The effect of PaEO on the T. cruzi cell cycle and mitochondrial membrane potential was evaluated by flow cytometry. PaEO was effective against cell-derived (IC50/24 h: 2.8 μg/mL) and metacyclic (IC50/24 h: 12.1 μg/mL) trypomastigotes, as well as intracellular amastigotes (IC50/24 h: 9 μg/mL). At 4ºC - the temperature of red blood cells (RBCs) storage in blood banks - cell-derived trypomastigotes were more sensitive to PaEO (IC50/24 h = 3.8 μg/mL) than to gentian violet (IC50/24 h = 24.7 mg/mL). Cytotoxicity assays using Vero cells (37ºC) and RBCs (4ºC) showed that PaEO has increased selectivity for cell-derived trypomastigotes. Flow cytometry analysis showed that PaEO does not affect the cell cycle of T. cruzi epimastigotes, but decreases their mitochondrial membrane potential. GC-MS data identified nerolidol and linalool as major components of PaEO, and linalool had trypanocidal effect (IC50/24 h: 306 ng/mL) at 4ºC. The trypanocidal effect of PaEO is likely due to the presence of linalool, which may represent an interesting candidate for use in the treatment of potentially contaminated RBCs bags at low temperature.

  2. Using in situ pore water concentrations to estimate the phytotoxicity of nicosulfuron in soils to corn (Zea mays L.).

    PubMed

    Liu, Kailin; Cao, Zhengya; Pan, Xiong; Yu, Yunlong

    2012-08-01

    The phytotoxicity of an herbicide in soil is typically dependent on the soil characteristics. To obtain a comparable value of the concentration that inhibits growth by 50% (IC50), 0.01 M CaCl(2) , excess pore water (EPW) and in situ pore water (IPW) were used to extract the bioavailable fraction of nicosulfuron from five different soils to estimate the nicosulfuron phytotoxicity to corn (Zea mays L.). The results indicated that the phytotoxicity of nicosulfuron in soils to corn depended on the soil type, and the IC50 values calculated based on the amended concentration of nicosulfuron ranged from 0.77 to 9.77 mg/kg among the five tested soils. The range of variation in IC50 values for nicosulfuron was smaller when the concentrations of nicosulfuron extracted with 0.01 M CaCl(2) and EPW were used instead of the amended concentration. No significant difference was observed among the IC50 values calculated from the IPW concentrations of nicosulfuron in the five tested soils, suggesting that the concentration of nicosulfuron in IPW could be used to estimate the phytotoxicity of residual nicosulfuron in soils. Copyright © 2012 SETAC.

  3. Purification, crystallization and preliminary X-ray analysis of aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Byrnes, Laura J.; Badarau, Adriana; Vakulenko, Sergei B.

    2008-02-01

    APH(2′′)-Ic is an enzyme that is responsible for high-level gentamicin resistance in E. gallinarum isolates. Crystals of the wild-type enzyme and three mutants have been prepared and a complete X-ray diffraction data set was collected to 2.15 Å resolution from an F108L crystal. Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and threemore » mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2′′)-Ic variants were crystallized in the presence of 14–20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris–HCl pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 Å, β = 108.8°. X-ray diffraction data were collected to approximately 2.15 Å resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.« less

  4. Antiviral activity of four types of bioflavonoid against dengue virus type-2.

    PubMed

    Zandi, Keivan; Teoh, Boon-Teong; Sam, Sing-Sin; Wong, Pooi-Fong; Mustafa, Mohd Rais; Abubakar, Sazaly

    2011-12-28

    Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for each compound. The half maximal inhibitory concentration (IC50) of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids, including daidzein, naringin and

  5. The effect of electroacupuncture at the MA-IC 3 endocrine ear acupoint on fasting blood glucose levels in type 2 diabetes mellitus patients

    NASA Astrophysics Data System (ADS)

    Simadibrata, C.; Budihardjo, F. A.; Srilestari, A.

    2017-08-01

    The management of diabetes mellitus (DM) involves education, nutritional intervention, and physical exercise, in addition to pharmacological interventions, with the long-term goal of preventing complications through the control of blood glucose levels. Several studies have shown that acupuncture, both conventional acupuncture and electroacupuncture, is useful for lowering blood glucose levels in patients with DM. This study aimed to determine the additional effect of electroacupuncture at the MA-IC 3 Endocrine ear acupoint on fasting blood glucose levels in patients with Type 2 DM who were receiving oral hypoglycemic agents at Banjar General Hospital. In this randomized controlled study, fifty-four study participants who were being treated with oral antidiabetics were allocated into two groups, receiving either electroacupuncture (EA) at the MA-IC 3 ear acupoint with dense disperse wave for 30 minutes or acupuncture at the same point and for the same duration but without EA (No EA). Fasting blood glucose levels were measured before and after the intervention. In Group A (EA), the mean fasting blood glucose (FBG) level decreased from 157.26±24.485 to 142.59±26.771 (p < 0.05), whereas in Group B (No EA), the mean FBG decreased from 149.67±21.485 to 148.74±21.326 (p < 0.05). The difference in the amount of FBG decrease between Group A (EA) and Group B (No EA) was statistically significant (p < 0.05). EA at the MA-IC 3 Endocrine lowers FBG levels to a greater degree than acupuncture with no EA in patients with type 2 DM.

  6. Module comprising IC memory stack dedicated to and structurally combined with an IC microprocessor chip

    NASA Technical Reports Server (NTRS)

    Carson, John C. (Inventor); Indin, Ronald J. (Inventor); Shanken, Stuart N. (Inventor)

    1994-01-01

    A computer module is disclosed in which a stack of glued together IC memory chips is structurally integrated with a microprocessor chip. The memory provided by the stack is dedicated to the microprocessor chip. The microprocessor and its memory stack may be connected either by glue and/or by solder bumps. The solder bumps can perform three functions--electrical interconnection, mechanical connection, and heat transfer. The electrical connections in some versions are provided by wire bonding.

  7. Flavocoxid Inhibits Phospholipase A2, Peroxidase Moieties of the Cyclooxygenases (COX), and 5-Lipoxygenase, Modifies COX-2 Gene Expression, and Acts as an Antioxidant

    PubMed Central

    Burnett, Bruce P.; Bitto, Alessandra; Altavilla, Domenica; Squadrito, Francesco; Levy, Robert M.; Pillai, Lakshmi

    2011-01-01

    The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA) formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA2) (IC50 = 60 μg/mL). In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO) activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC50 = 12.3) and COX-2 (IC50 = 11.3 μg/mL) peroxidase (PO) moieties as well as 5-lipoxygenase (5-LOX) (IC50 = 110 μg/mL). No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC50 = 38 μg/mL) in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA) are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS). PMID:21765617

  8. Flavocoxid inhibits phospholipase A2, peroxidase moieties of the cyclooxygenases (COX), and 5-lipoxygenase, modifies COX-2 gene expression, and acts as an antioxidant.

    PubMed

    Burnett, Bruce P; Bitto, Alessandra; Altavilla, Domenica; Squadrito, Francesco; Levy, Robert M; Pillai, Lakshmi

    2011-01-01

    The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA) formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA(2)) (IC(50) = 60 μg/mL). In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO) activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC(50) = 12.3) and COX-2 (IC(50) = 11.3 μg/mL) peroxidase (PO) moieties as well as 5-lipoxygenase (5-LOX) (IC(50) = 110 μg/mL). No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC(50) = 38 μg/mL) in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA) are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS).

  9. Multi-Wavelength Views of Protostars in IC 1396

    NASA Image and Video Library

    2003-12-18

    This archival image from 2003 captured by NASA Spitzer Space Telescope captured the Elephant Trunk Nebula, an elongated dark globule within the emission nebula IC 1396 in the constellation of Cepheus.

  10. Validating the Implementation Climate Scale (ICS) in Child Welfare Organizations

    PubMed Central

    Ehrhart, Mark G.; Torres, Elisa M.; Wright, Lisa A.; Martinez, Sandra Y.; Aarons, Gregory A.

    2015-01-01

    There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization’s climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. PMID:26563643

  11. Validating the Implementation Climate Scale (ICS) in child welfare organizations.

    PubMed

    Ehrhart, Mark G; Torres, Elisa M; Wright, Lisa A; Martinez, Sandra Y; Aarons, Gregory A

    2016-03-01

    There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization's climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia.

    PubMed

    Shah, Krupa; Mirza, Sheefa; Desai, Urja; Jain, Nayan; Rawal, Rakesh

    2016-01-01

    The aim of the study was to find a role of Curcumin from natural source to overcome drug resistance as well as to reduce cytotoxicity profile of the drug in Acute Myeloid Leukemia patients. Primary leukemic cells were obtained from AML patient's bone marrow. These cells were then exposed to different concentration of cytarabine and curcumin to find out IC50 values and also its effect on MDR genes like MDR1, BCRP, LRP and FLT3 by RT-PCR method. Our results suggested that curcumin down regulates MDR genes. Gene expression was decreased by 35.75, 31.30, 27.97 % for MDR1, LRP, BCRP respectively. In FLT3, it was 65.86 % for wild type and 31.79 % for FLT3-ITD. In addition to this, curcumin has also shown anti-proliferative effect as well as synergistic effect in combination with Cytarabine on primary leukemic cells. Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC50 value decreases when treated in combination.

  13. Is higher population-level use of ICS/LABA combination associated with better asthma outcomes? Cross-sectional surveys of nationally representative populations in New Zealand and Australia.

    PubMed

    Reddel, Helen K; Beckert, Lutz; Moran, Angela; Ingham, Tristram; Ampon, Rosario D; Peters, Matthew J; Sawyer, Susan M

    2017-11-01

    New Zealand (NZ) and Australia (AU) have similarly high asthma prevalence; both have universal public health systems, but different criteria for subsidized medicines. We explored differences in asthma management and asthma-related outcomes between these countries. A web-based survey was administered in AU (2012) and NZ (2013) to individuals aged ≥16 years with current asthma, drawn randomly from web-based panels, stratified by national population proportions. Symptom control was assessed with the Asthma Control Test (ACT). Healthcare utilization was assessed from reported urgent doctor/hospital visits in the previous year. NZ (n = 537) and Australian (n = 2686) participants had similar age and gender distribution. More NZ than Australian participants used inhaled corticosteroid (ICS)-containing medication (68.8% vs 60.9%; P = 0.006) but ICS/long-acting β 2 -agonist (LABA) constituted 44.4% of NZ and 81.5% of Australian total ICS use (P < 0.0001). Adherence was higher with ICS/LABA than ICS-alone (P < 0.0001), and higher in NZ than in AU (P < 0.0001). ACT scores were similar (P = 0.41), with symptoms well controlled in 58.6% and 54.4% participants, respectively. More NZ participants reported non-urgent asthma reviews (56.6% vs 50.4%; P = 0.009). Similar proportions had urgent asthma visits (27.9% and 28.6%, respectively, P = 0.75). This comparison, which included the first nationally representative data for asthma control in NZ, showed that poorly controlled asthma is common in both NZ and AU, despite subsidized ICS-containing medications. The greater use of ICS-alone in NZ relative to ICS/LABA does not appear to have compromised population-level asthma outcomes, perhaps due to better adherence in NZ. Different ICS/LABA subsidy criteria and different patient copayments may also have contributed to these findings. © 2017 Asian Pacific Society of Respirology.

  14. Brazilian Red Propolis Induces Apoptosis-Like Cell Death and Decreases Migration Potential in Bladder Cancer Cells

    PubMed Central

    Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Moura, Sidnei; Padilha, Francine F.; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

    2014-01-01

    Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment. PMID:25530785

  15. Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells.

    PubMed

    Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Martins Rodrigues, Fernanda; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Roesch-Ely, Mariana; Moura, Sidnei; Padilha, Francine F; Collares, Tiago; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

    2014-01-01

    Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

  16. Inhibitors of 15-lipoxygenase from orange peel.

    PubMed

    Malterud, K E; Rydland, K M

    2000-11-01

    A series of polymethoxylated flavonoids has been isolated from orange peel, and their inhibitory activity toward soybean 15-lipoxygenase was determined. The strongest inhibition was shown by 3,5,6,7,3',4'-hexamethoxyflavone (IC(50) = 49 +/- 5 microM). Sinensetin, nobiletin, tangeretin, tetramethylscutellarein, and 3,5, 6,7,8,3',4'-heptamethoxyflavone were somewhat less active, with IC(50) values of 70-86 microM, comparable to the positive control quercetin (IC(50) = 68 +/- 5 microM). Demethylation apparently results in less active compounds, with 5-O-demethylsinensetin having an IC(50) value of 144 +/- 10 microM. Some other orange peel constituents were isolated and tested as well, hesperidin (IC(50) = 180 +/- 10 microM) and ferulic acid (111 +/- 2 microM), showing moderate activity. The polymethoxylated flavonoids were virtually inactive as scavengers of the diphenylpicrylhydrazyl radical. Hesperidin was only slightly active (24.2 +/- 0.7% scavenged at a concentration of 2 mM), and ferulic acid showed good activity (IC(50) = 86.4 +/- 0.7 microM). From this, it appears that orange peel constituents may counteract enzymatic lipid peroxidation processes catalyzed by 15-lipoxygenase in vitro. The radical scavenging activity of orange peel extracts is only modest.

  17. Two new cytotoxic stilbenoid dimers isolated from Cajanus cajan.

    PubMed

    Zhang, Nenling; Shen, Xiangchun; Jiang, Xiaofei; Cai, Jiazhong; Shen, Xiaoling; Hu, Yingjie; Qiu, Samuel X

    2018-01-01

    Two new stilbenoid dimers, cajanstilbenoids A (1) and B (2), were isolated from the leaves of Cajanus cajan. Planar structures of these compounds were verified by NMR (1D and 2D) and high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Absolute configurations were assigned by comparing experimental and calculated electronic CD values. The cytotoxicity of 1 and 2 against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7), and human lung cancer (A549) cells were evaluated in vitro. Compound 1 showed strong cytotoxicity against all the tested cell lines (IC 50 values: 2.14-2.56 µM), whereas compound 2 showed strong toxicity only against HepG2 (IC 50 value: 5.99 µM) and A549 cells (IC 50 value: 6.18 µM).

  18. A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity.

    PubMed

    Sadashiva, Maralinganadoddi P; Gowda, Raghavendra; Wu, Xianzhu; Inamdar, Gajanan S; Kuzu, Omer F; Rangappa, Kanchugarakoppal S; Robertson, Gavin P; Gowda, D Channe

    2015-08-01

    Malaria caused by the Plasmodium parasites continues to be an enormous global health problem owing to wide spread drug resistance of parasites to many of the available antimalarial drugs. Therefore, development of new classes of antimalarial agents is essential to effectively treat malaria. In this study, the efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic acid, and their synthetic derivatives was assessed for antimalarial activity. Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N-benzyl derivatives showed excellent activity against P. falciparum parasites with IC50 values of 0.36 to 2.6 µM. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100 µM) to mammalian cells; thus, this compound can be an important antimalarial drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50 value of ~82 µM. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of ~8.2 to ~13.3 µM. These results suggest that a detailed understanding of the structure-activity relationship of abietane diterpenoids might provide strategies to exploit this class of compounds for malaria treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. IC97 Is a Novel Intermediate Chain of I1 Dynein That Interacts with Tubulin and Regulates Interdoublet Sliding

    PubMed Central

    Wirschell, Maureen; Yang, Chun; Yang, Pinfen; Fox, Laura; Yanagisawa, Haru-aki; Kamiya, Ritsu; Witman, George B.; Porter, Mary E.

    2009-01-01

    Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 is part of a regulatory complex that contains IC138. Microtubule sliding assays, using axonemes containing I1 dynein but devoid of IC97, show reduced microtubule sliding velocities that are not rescued by kinase inhibitors, revealing a critical role for IC97 in I1-dynein function and control of dynein-driven motility. PMID:19420136

  20. SN2005da: A Spectroscopic and Photometric Analysis of a Peculiar Type Ic Supernova

    NASA Astrophysics Data System (ADS)

    Williamson, Jacob

    2017-12-01

    Core collapse supernovae are an important class of objects in stellar evolution research as they are the final life stage of high mass stars. Supernovae in general are classified into several spectral types; this paper explores SN 2005da, classified as a Type Ic, meaning it lacks hydrogen and helium lines. The supernova was originally classified as a broad-lined Type Ic (Type Ic-BL), with expansion velocities near maximum light greater than or approximately equal to 15000 km/s. However, some of the elements present in the spectrum, namely carbon and oxygen, have narrower lines (FWHM approximately equal to 2300 km/s) than other elements, indicating an interaction with a previously ejected envelope. The supernova is also found to have a decay time, with a change in magnitude over 15 days following maximum light of about 1.4 magnitudes, that is significantly faster than typical Type Ic or Ic-BL. This is more akin to a rarer object type known as a Type Ibn, although it lacks the characteristic narrow helium lines of this type. Therefore, SN 2005da appears to be unlike known examples of Type Ic supernovae.

  1. Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.

    PubMed

    Monatrakul, Preeyaporn; Mungthin, Mathirut; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Wilairatana, Polrat; White, Nicholas J; Chotivanich, Kesinee

    2010-11-16

    The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake. Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not significantly affected; median (range) IC90 448.0 (65

  2. A Solder Based Self Assembly Project in an Introductory IC Fabrication Course

    ERIC Educational Resources Information Center

    Rao, Madhav; Lusth, John C.; Burkett, Susan L.

    2015-01-01

    Integrated circuit (IC) fabrication principles is an elective course in a senior undergraduate and early graduate student's curriculum. Over the years, the semiconductor industry relies heavily on students with developed expertise in the area of fabrication techniques, learned in an IC fabrication theory and laboratory course. The theory course…

  3. TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

    PubMed

    Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

    1994-09-01

    We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation.

  4. Pulsed laser ablation of IC packages for device failure analyses

    NASA Astrophysics Data System (ADS)

    Hong, Ming Hui; Mai, ZhiHong; Chen, G. X.; Thiam, Thomas; Song, Wen D.; Lu, Yongfeng; Soh, Chye E.; Chong, Tow Chong

    2002-06-01

    Pulsed laser ablation of mold compounds for IC packaging in air and with steam assistance is investigated. It is applied to decap IC packages and expose computer CPU dies for the device failure analyses. Compared with chemical decapping, the laser ablation has advantages of being fast speed, non- contact and dry processing. Laser ablation with the steam assistance results in higher ablation rate and wider ablated crater with much smoother surface morphology. It implies that the steam assisted laser ablation can achieve a faster and better quality laser processing. Audible acoustic wave and plasma optical signal diagnostics are also carried out to have a better understanding of the mechanisms behind. Light wavelength and laser fluence applied in the decapping are two important parameters. The 532 nm Nd:YAG laser decapping at a low laser fluence can achieve a large decapping area with a fine ablation profile. IC packages decapped by the laser ablation show good quality for the device failure analyses.

  5. Inhibitory Effects of Amorphigenin on the Mitochondrial Complex I of Culex pipiens pallens Coquillett (Diptera: Culicidae)

    PubMed Central

    Ji, Mingshan; Liang, Yaping; Gu, Zumin; Li, Xiuwei

    2015-01-01

    Previous studies in our laboratory found that the extract from seeds of Amorpha fruticosa in the Leguminosae family had lethal effects against mosquito larvae, and an insecticidal compound amorphigenin was isolated. In this study, the inhibitory effects of amorphigenin against the mitochondrial complex I of Culex pipiens pallens (Diptera: Culicidae) were investigated and compared with that of rotenone. The results showed that amorphigenin and rotenone can decrease the mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50 values (the inhibitor concentrations leading to 50% of the enzyme activity lost) were determined to be 2.4329 and 2.5232 μmol/L, respectively, while the in vitro IC50 values were 2.8592 and 3.1375 μmol/L, respectively. Both amorphigenin and rotenone were shown to be reversible and mixed-I type inhibitors of the mitochondrial complex I of Cx. pipiens pallens, indicating that amorphigenin and rotenone inhibited the enzyme activity not only by binding with the free enzyme but also with the enzyme-substrate complex, and the values of KI and KIS for amorphigenin were determined to be 20.58 and 87.55 μM, respectively, while the values for rotenone were 14.04 and 69.23 μM, respectively. PMID:26307964

  6. Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus.

    PubMed

    Bandara, Suren B; Eubig, Paul A; Sadowski, Renee N; Schantz, Susan L

    2016-02-01

    Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

    EPA Science Inventory

    Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

  8. Inhaled corticosteroids (ICS) and risk of mycobacterium in patients with chronic respiratory diseases: a meta-analysis.

    PubMed

    Ni, Songshi; Fu, Zhenxue; Zhao, Jing; Liu, Hua

    2014-07-01

    Studies have indicated that therapy with inhaled corticosteroids (ICS) can be associated with a higher risk of pneumonia. However, it is not known whether ICS increases the risk of mycobacterium. Most of these published studies were small, and the conclusions were inconsistent. A meta-analysis was conducted into whether ICS increases the risk of mycobacterium in patients with chronic respiratory diseases. PubMed, OVID, EMBASE and Cochrane Library databases were searched. Five studies involving 4,851 cases and 28,477 controls were considered in the meta-analysis. From the pooled analyses, there was significant association between ICS and risk of mycobacterium in all patients with chronic respiratory diseases [risk ratio (RR) =1.81; 95% confidence interval (CI), 1.23-2.68; P=0.003]. Among patients with chronic respiratory diseases, the relationship between ICS and risk of tuberculosis (TB) was also significant (RR =1.34; 95% CI, 1.15-1.55; P=0.0001). And meta-analysis of four studies in patients with chronic obstructive pulmonary disease (COPD) (RR =1.42; 95% CI, 1.18-1.72; P=0.0003) or two studies in patients who have prior pulmonary TB (RR =1.61; 95% CI, 1.35-1.92; P<0.00001) or three studies in patients with high-dose ICS (RR =1.60; 95% CI, 1.28-1.99; P<0.0001) showed a relationship between ICS and risk of mycobacterium. Significant relationship has been shown between ICS use and risk of mycobacterium in all patients with chronic respiratory diseases. ICS use also increases the risk of TB among the patients with chronic respiratory diseases. Use of ICS increases the risk of mycobacterium in patients with COPD or patients with prior pulmonary TB or patients inhaling high-dose corticosteroids. Further research is required to establish the potential adverse effect of ICS as a therapy for chronic respiratory diseases.

  9. The German Intelligibility in Context Scale (ICS-G): Reliability and Validity Evidence

    ERIC Educational Resources Information Center

    Neumann, Sandra; Rietz, Christian; Stenneken, Prisca

    2017-01-01

    Background: In 2012 the Intelligibility in Context Scale (ICS) was published as a parent-report screening assessment that considers parents' perceptions of their children's functional intelligibility with a range of communication partners that differ in levels of authority and familiarity in real-life situations. To date, the ICS has been…

  10. Some new results on shock chemistry in IC 443

    NASA Technical Reports Server (NTRS)

    Denoyer, L. K.; Frerking, M. A.

    1981-01-01

    New observations have been made of CO, CO-13, SiO, SO, H2CO, HCO(+), N2H(+), CS, OCS, HCN, and OH in the shocked clouds of IC 443. It is found that at position IC 443 B, (1) the shocked CO is optically thin; (2) the HCO(+)/CO abundance ratio is 4-9 x 10 to the -4 th, representing a tenfold enhancement over that of normal interstellar clouds; (3) there is no enhancement of SO or SIO, as occurs in Orion KL; and (4) there is optically thin preshock OH, confirming a hundredfold enhancement of the OH/CO ratio in the shock.

  11. MagIC: Fluid dynamics in a spherical shell simulator

    NASA Astrophysics Data System (ADS)

    Wicht, J.; Gastine, T.; Barik, A.; Putigny, B.; Yadav, R.; Duarte, L.; Dintrans, B.

    2017-09-01

    MagIC simulates fluid dynamics in a spherical shell. It solves for the Navier-Stokes equation including Coriolis force, optionally coupled with an induction equation for Magneto-Hydro Dynamics (MHD), a temperature (or entropy) equation and an equation for chemical composition under both the anelastic and the Boussinesq approximations. MagIC uses either Chebyshev polynomials or finite differences in the radial direction and spherical harmonic decomposition in the azimuthal and latitudinal directions. The time-stepping scheme relies on a semi-implicit Crank-Nicolson for the linear terms of the MHD equations and a Adams-Bashforth scheme for the non-linear terms and the Coriolis force.

  12. In Vitro Drug-Induced Liver Injury Prediction: Criteria Optimization of Efflux Transporter IC50 and Physicochemical Properties.

    PubMed

    Yucha, Robert W; He, Kan; Shi, Qin; Cai, Lining; Nakashita, Yukie; Xia, Cindy Q; Liao, Mingxiang

    2017-06-01

    Drug-induced liver injury (DILI) is a severe drug adverse response, which cannot always be reliably predicted in preclinical or clinical studies. Lack of observation of DILI during preclinical and clinical drug development has led to DILI being a leading cause of drug withdrawal from the market. As DILI is potentially fatal, pharmaceutical companies have been developing in vitro tools to screen for potential liver injury. Screens for physicochemical properties, mitochondrial function, and transport protein inhibition have all been employed to varying degrees of success. In vitro inhibition of the bile salt export pump (BSEP) has become a major risk factor for in vivo DILI predictions, yet discrepancies exist in which methods to use and the extent to which BSEP inhibition predicts clinical DILI. The presented work focuses on optimizing DILI predictions by comparing BSEP inhibition via the membrane vesicle assay and the hepatocyte-based BSEPcyte assay, as well as dual and triple liabilities. BSEP transport inhibition of taurcholic acids and glycocholic acids were similar for up to 29 drugs tested, in both the vesicle and hepatocyte-based assays. Positive and negative DILI predictions were optimized at a 50-µM cutoff value for 50 drugs using both NIH Livertox and PharmaPendium databases. Additionally, dual inhibition of BSEP and other efflux transporters (multidrug resistance-associated protein [MRP]2, MRP3, or MRP4) provided no observable predictive benefit compared with BSEP inhibition alone. Eighty-five percent of drugs with high molecular weight (>600 Da), high cLogP (>3), or a daily dose >100 mg and BSEP inhibition were associated with DILI. Triple liability of BSEP inhibition, high molecular weight, and high cLogP attained a 100% positive prediction rate. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Evaluation of in vitro anti-Leishmanial activity of some brown, green and red algae from the Persian Gulf.

    PubMed

    Fouladvand, M; Barazesh, A; Farokhzad, F; Malekizadeh, H; Sartavi, K

    2011-06-01

    Leishmaniasis is a protozoan parasitic disease which is transmitted by the female Phlebotomus sand fly and is prevalent in four continents.The first-choice treatment for the leishmaniasis is pentavalent antimonials, which are potentially toxic and often ineffective and use of them exhibit therapeutic failure. These pharmaceutical problems point towards the need to develop novel chemotherapeutic agents. Seaweeds are considered as source of bioactive metabolites characterized by a broad spectrum of biological activities. In this experimental study, cold and hot water crude extracts of four species of green, brown and red marine algae "Caulerpa sertularioides, Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" collected along the Bushehr coast of the Persian Gulf (southwest of Iran), prepared and their in vitro activities against Leishmania major promastigote were evaluated by using the MTT assay test. The cold and hot water crude extracts of four algae species exhibited different anti-Leishmanial activities. The minimum inhibitory concentration of hot water extracts calculated as IC50 was as follows: Caulerpa sertularioides (IC50 < or =85 microg/ml), Gracilaria corticata (IC50 < or =38 microg/ml), Gracillaria salicornia (IC50 < or =46 microg/ml) and Sargassum oligocystum (IC(50)9 < or =78 microg/ml, while these values for cold water extracts were (IC50 >125 microg/ml) for Caulerpa Sertularioides (IC50 >65 microg/ml) for Gracilaria corticata (IC50 >74 microg/ml) for Gracilaria salicornia and (IC50 >105 microg/ml) for Sargassum oligocystum, IC50 values for reference drug (Amphotericin B) was (0.16-0.2 microg/ml). According to the results, inhibitory effects of the crude extracts from these four species algae specially hot water crude extracts from "Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" are significant and in accordance with other studies that has been done on different algae species. So these results are

  14. Decreased expression of zonula occludens-1 and occludin in the bladder urothelium of patients with interstitial cystitis/painful bladder syndrome.

    PubMed

    Lee, Jane-Dar; Lee, Ming-Huei

    2014-01-01

    Unique barrier properties of the urothelial surface membrane permit urine storage without contents leak into the bloodstream. Previous reports suggested that the bladder urothelial barrier might be compromised in interstitial cystitis/painful bladder syndrome (IC/PBS). We examined the changes of tight junction proteins (zonula occludens-1 (ZO-1) and occludin) in IC/PBS patients. Bladder samples were derived from of 32 patients with IC/PBS and eight controls. We detected the tight junction proteins of ZO-1 and occludin expression by immunoblotting, immunohistochemical (IHC) staining and double immunofluorescent (IF) staining with confocal microscopy. Data were analyzed using the Mann-Whitney U-test. Expression of ZO-1 and occludin in the IC/PBS group was reduced compared to the control group by immunoblotting and IHC staining. Also, the thinning and denudation of urothelium were demonstrated in the IC/PBS group by histological study. IF staining showed the interruption of bladder urothelium in IC/PBS patients under confocal microscopy. Our data showed that decreased expression of tight junction proteins (ZO-1 and occludin) and interruption of bladder urothelium in IC/PBS patients. Treatment to repair the discontinuous urothelium may be useful to relieve some clinical symptoms of patients with IC/PBS. Copyright © 2012. Published by Elsevier B.V.

  15. Direct led-fluorescence method for Mao-B inactivation in the treatment of Parkinson's

    NASA Astrophysics Data System (ADS)

    Castillo, Jimmy A.; Hung, Jannett; Rodriguez, M.; Bastidas, E.; Laboren, I.; Jaimes, A.

    2004-10-01

    A led-fluorescence spectroscopy method determinate the inhibitory effects of probe compounds on MAO-B activity is described. In this assay, we demonstrate the possibility of determinate the activity of MAO-B efficiently and rapidly without the use of reference substrate. Measuring variations in fluorescence intensity of MAO-B enzyme during the reaction with inhibitors, L-deprenyl and berberine IC50 and KI values were obtained. For L-deprenyl (IC50 = 0.017 μM and KI = 0.019 μM) and berberine (IC50 = 90 μM and KI = 47 μM) were in agreement to the values obtained with a standard method and literature reported.

  16. Incentive memory: evidence the basolateral amygdala encodes and the insular cortex retrieves outcome values to guide choice between goal-directed actions.

    PubMed

    Parkes, Shauna L; Balleine, Bernard W

    2013-05-15

    Choice between goal-directed actions is determined by the relative value of their consequences. Such values are encoded during incentive learning and later retrieved to guide performance. Although the basolateral amygdala (BLA) and the gustatory region of insular cortex (IC) have been implicated in these processes, their relative contribution is still a matter of debate. Here we assessed whether these structures interact during incentive learning and retrieval to guide choice. In these experiments, rats were trained on two actions for distinct outcomes after which one of the two outcomes was devalued by specific satiety immediately before a choice extinction test. We first confirmed that, relative to appropriate controls, outcome devaluation recruited both the BLA and IC based on activation of the immediate early gene Arc; however, we found that infusion of the NMDAr antagonist ifenprodil into the BLA only abolished outcome devaluation when given before devaluation. In contrast, ifenprodil infusion into the IC was effective whether made before devaluation or test. We hypothesized that the BLA encodes and the IC retrieves incentive value for choice and, to test this, developed a novel sequential disconnection procedure. Blocking NMDAr activation unilaterally in the BLA before devaluation and then contralaterally in the IC before test abolished selective devaluation. In contrast, reversing the order of these infusions left devaluation intact. These results confirm that the BLA and IC form a circuit mediating the encoding and retrieval of outcome values, with the BLA encoding and the IC retrieving such values to guide choice.

  17. On a decrease of high-latitude corona temperature of the Sun in the last 50 years

    NASA Astrophysics Data System (ADS)

    Makarov, V. I.; Tlatov, A. G.

    2002-03-01

    The ground-based observations of the green Fe XIV 5303 Å and red Fe X 6374 Å corona forbidden lines obtained at the Kislovodsk Solar Station since 1952 are used to determine the temperature variations of the solar corona. The observations of the solar corona at the Arosa, Pic du Midi, Kislovodsk, Norikura, Kanzelhöhe, Wendelstein and Lomnický Stit have been used to receive the Kislovodsk series of the green K I5303 and red K I6374 corona intensities for 1947-2000. Comparison of the K I5303 with the Wolf numbers W(t) shows high correlation factor 0.91. The mean monthly corona intensity has been calculated in the sunspot (0° - 45°) and at the high-latitude (45° - 90°) zones. We found a decrease of the K I5303 in 1.5 times at the high-latitudes in this period. It was shown that the ratio K I6374/K I5303 increased more than two times. We have found a decrease of temperature in polar zones of the Sun of order 0.1×106 during the last 50 years. It is supposed that a decrease of polar corona temperature connected with an increase of magnetic flux from high-latitude regions of the Sun during the last 120 years.

  18. New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres.

    PubMed

    Attia, Mohamed I; Eldehna, Wagdy M; Afifi, Samar A; Keeton, Adam B; Piazza, Gary A; Abdel-Aziz, Hatem A

    2017-01-01

    The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.

  19. Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant.

    PubMed

    Kinnier, Christine V; Martinu, Tereza; Gowdy, Kymberly M; Nugent, Julia L; Kelly, Francine L; Palmer, Scott M

    2011-01-15

    Respiratory viral infections cause significant morbidity and increase the risk for chronic pulmonary graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). Our overall hypothesis is that local innate immune activation potentiates adaptive alloimmunity. In this study, we hypothesized that a viral pathogen-associated molecular pattern (PAMP) alone can potentiate pulmonary GVHD after allogeneic HCT. We, therefore, examined the effect of pulmonary exposure to polyinosinic:polycytidylic acid (poly I:C), a viral mimetic that activates innate immunity, in an established murine HCT model. Poly I:C-induced a marked pulmonary T cell response in allogeneic HCT mice as compared to syngeneic HCT, with increased CD4+ cells in the lung fluid and tissue. This lymphocytic inflammation persisted at 2 weeks post poly I:C exposure in allogeneic mice and was associated with CD3+ cell infiltration into the bronchiolar epithelium and features of epithelial injury. In vitro, poly I:C enhanced allospecific proliferation in a mixed lymphocyte reaction. In vivo, poly I:C exposure was associated with an early increase in pulmonary monocyte recruitment and activation as well as a decrease in CD4+FOXP3+ regulatory T cells in allogeneic mice as compared to syngeneic. In contrast, intrapulmonary poly I:C did not alter the extent of systemic GVHD in either syngeneic or allogeneic mice. Collectively, our results suggest that local activation of pulmonary innate immunity by a viral molecular pattern represents a novel pathway that contributes to pulmonary GVHD after allogeneic HCT, through a mechanism that includes increased recruitment and maturation of intrapulmonary monocytes. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Properties of Protostars in the Elephant Trunk in the Globule IC 1396A

    NASA Astrophysics Data System (ADS)

    Reach, William T.; Faied, Dohy; Rho, Jeonghee; Boogert, Adwin; Tappe, Achim; Jarrett, Thomas H.; Morris, Patrick; Cambrésy, Laurent; Palla, Francesco; Valdettaro, Riccardo

    2009-01-01

    Extremely red objects, identified in the early Spitzer Space Telescope observations of the bright-rimmed globule IC 1396A and photometrically classified as Class I protostars and Class II T Tauri stars based on their mid-infrared (mid-IR) colors, were spectroscopically observed at 5.5-38 μm (Spitzer Infrared Spectrograph), at the 22 GHz water maser frequency (National Radio Astronomy Observatory Green Bank Telescope), and in the optical (Palomar Hale 5 m) to confirm their nature and further elucidate their properties. The sources photometrically identified as Class I, including IC 1396A:α, γ, δ, epsilon, and ζ, are confirmed as objects dominated by accretion luminosity from dense envelopes, with accretion rates 1-10 × 10-6 M sun yr-1 and present stellar masses 0.1-2 M sun. The Class I sources have extremely red continua, still rising at 38 μm, with a deep silicate absorption at 9-11 μm, weaker silicate absorption around 18 μm, and weak ice features including CO2 at 15.2 μm and H2O at 6 μm. The ice/silicate absorption ratio in the envelope is exceptionally low for the IC 1396A protostars, compared to those in nearby star-forming regions, suggesting that the envelope chemistry is altered by the radiation field or globule pressure. Only one 22 GHz water maser was detected in IC 1396A; it is coincident with a faint mid-IR source, offset from near the luminous Class I protostar IC 1396A:γ. The maser source, IC 1396A:γ b , has luminosity less than 0.1 L sun, the first H2O maser from such a low-luminosity object. Two near-infrared (NIR) H2 knots on opposite sides of IC 1396A:γ reveal a jet, with an axis clearly distinct from the H2O maser of IC 1396A:γ b . The objects photometrically classified as Class II, including IC 1396A:β, θ, Two Micron All Sky Survey (2MASS)J 21364964+5722270, 2MASSJ 21362507+5727502, LkHα 349c, Tr 37 11-2146, and Tr 37 11-2037, are confirmed as stars with warm, luminous disks, with a silicate emission feature at 9-11 μm, and

  1. Institutional computing (IC) information session

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koch, Kenneth R; Lally, Bryan R

    2011-01-19

    The LANL Institutional Computing Program (IC) will host an information session about the current state of unclassified Institutional Computing at Los Alamos, exciting plans for the future, and the current call for proposals for science and engineering projects requiring computing. Program representatives will give short presentations and field questions about the call for proposals and future planned machines, and discuss technical support available to existing and future projects. Los Alamos has started making a serious institutional investment in open computing available to our science projects, and that investment is expected to increase even more.

  2. TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

    PubMed Central

    Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

    1994-01-01

    We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation. Images PMID:8076598

  3. Acetylcholinesterase and butyrylcholinesterase inhibitory activity of Pinus species essential oils and their constituents.

    PubMed

    Bonesi, Marco; Menichini, Federica; Tundis, Rosa; Loizzo, Monica R; Conforti, Filomena; Passalacqua, Nicodemo G; Statti, Giancarlo A; Menichini, Francesco

    2010-10-01

    This study aimed to investigate the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity of the essential oils from Pinus nigra subsp. nigra, P. nigra var. calabrica, and P. heldreichii subsp. leucodermis. This activity is relevant to the treatment of Alzheimer's disease (AD), since cholinesterase drugs are currently the only drugs available to treat AD. P. heldreichii subsp. leucodermis exhibited the most promising activity, with IC(50) values of 51.1 and 80.6 microg/mL against AChE and BChE, respectively. An interesting activity against AChE was also observed with P. nigra subsp. nigra essential oil, with an IC(50) value of 94.4 microg/mL. Essential oils were analyzed by GC and GC-MS with the purpose of investigating their relationships with the observed activities. Among the identified constituents, terpinolene, beta-phellandrene, linalyl acetate, trans-caryophyllene, and terpinen-4-ol were tested. trans-Caryophyllene and terpinen-4-ol inhibited BChE with IC(50) values of 78.6 and 107.6 microg/mL, respectively. beta-Phellandrene was selective against AChE (IC(50) value of 120.2 microg/mL).

  4. Nira acidity and antioxidant activity of Palm sugar in Sumowono Village

    NASA Astrophysics Data System (ADS)

    Winarni, Sri; Arifan, Fahmi; Wisnu Broto, RTD.; Fuadi, Ariza; Alviche, Lola

    2018-05-01

    The palm sugar not only has potential as natural sweetener but also has antioxidant. The purpose of this study was to analyze antioxidant and pH of the nira in palm sugar. The sample in this study was palm sugar from 6 different production sites. Test of antioxidant activity used DPPH method (1.1-diphenyl-2-picrylhydrazyl) with a wavelength of 517 nm. The value of absorbance solution was measured using spectrophotometry and the value of effective concentration (IC50) was counted. The pH test was measured using a pH meter. Pearson’s correlation test revealed r=-0.045 with significant value 0.932 (>0.005). There was no correlation between pH value and antioxidant activity of palm sugar. IC50 value of palm sugar in Sumowono village revealed that it had a strong antioxidant activity (50 μg/ml - 100 μg/ml) that is 74,73 μg/ml 83.94 μg/ml 82.31 μg/ml 83.94 μg/ml 86.10 μg/ml 82.13 μg/ml 89.17 μg/ml 89.71 μg/ml 89.17 μg/ml and 84.84 μg/ml). Lower IC50 values indicate higher antioxidant activity. Palm sugar with the best antioxidant activity came from the production sites which had IC50 values of 74.73 μg/ml. Potential antioxidants can be optimized by making improvements to the processing system.

  5. Religiosity, values, and horizontal and vertical individualism-collectivism: a study of Turkey, the United States, and the Philippines.

    PubMed

    Cukur, Cem Safak; de Guzman, Maria Rosario T; Carlo, Gustavo

    2004-12-01

    The authors examined the links between two dimensions that have been useful in understanding cross-cultural differences and similarities, namely, individualism-collectivism (I-C) and value orientations. The authors examined the relations and parallels between the two variables by directly relating them and examining the patterns of relations that both have with a third variable, religiosity. Participants were 475 college students from the Philippines, the United States, and Turkey who responded to measures of horizontal and vertical I-C, value orientations, and religiosity. The authors found partial support for the parallels between I-C and value types, particularly for collectivism and conservative values. Moreover, religiosity was associated positively with conservative values and collectivism, across all three cultures. The authors found individualism to also relate to openness-to-change values, though the patterns were not as consistent as those that they found between collectivism and conservation. Differences and similarities emerged in links of I-C-values to religiosity across the three samples.

  6. Protein adsorption to poly(ethylenimine)-modified Sepharose FF: I. a critical ionic capacity for drastically enhanced capacity and uptake kinetics.

    PubMed

    Yu, Lin-Ling; Tao, Shi-Peng; Dong, Xiao-Yan; Sun, Yan

    2013-08-30

    To explore the details of protein uptake to polymer-grafted ion exchangers, Sepharose FF was modified with poly(ethylenimine) (PEI) to prepare anion exchanger of 10 different ionic capacities (ICs, 100-1220mmol/L). Adsorption equilibria and kinetics of bovine serum albumin (BSA) were then studied. It is found that ionic capacity, i.e., the coupling density of PEI, had significant effect on both adsorption capacity (qm) and effective protein diffusivity (De). With increasing ionic capacity, the qm value increased rapidly at IC<260mmol/L and then increased slowly till reaching a plateau at IC=600mmol/L. In the IC range of 100-600mmol/L, however, the De values kept at a low level (De/D0<0.07); it first decreased from 0.05±0.01 at IC=100mmol/L to 0.01±0.01 at IC=260mmol/L and then increased to 0.06±0.01 at IC=600mmol/L. Thereafter, sharp increases of the qm and De values [36% (from 201 to 273mg/mL) and 670% (from 0.06±0.01 to 0.49±0.04), respectively] were observed in the narrow range of IC from 600 to 740mmol/L. Finally, at IC>740mmol/L, the qm value decreased significantly while the De value increased moderately with increasing the IC. The results indicate that PEI chains played an important role in protein adsorption and transport. In brief, there was a critical IC (cIC) or PEI chain density, above which protein adsorption and transport behaviors changed drastically. The cIC was identified to be about 600mmol/L. Estimation of PEI grafting-layer thickness suggests that PEI chains formed an extended three-dimensional grafting-layer at IC>cIC, which provided high flexibility as well as accessibility of the chains for protein binding. Therefore, at IC>cIC, the adjacent PEI chains became close and flexible enough, leading to facilitated transport of adsorbed protein molecules by the interactions of neighboring chains mediated by the bound molecules. It is regarded as "chain delivery" effect. At the same time, improved accessibility of binding sites led the

  7. The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms

    PubMed Central

    Natarajan, Karthika; Bhullar, Jasjeet; Shukla, Suneet; Burcu, Mehmet; Chen, Zhe-Sheng; Ambudkar, Suresh V.; Baer, Maria R.

    2013-01-01

    Overexpression of the ATP-binding cassette (ABC) drug efflux proteins P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on malignant cells is associated with inferior chemotherapy outcomes. Both, ABCB1 and ABCG2, are substrates of the serine/threonine kinase Pim-1; Pim-1 knockdown decreases their cell surface expression, but SGI-1776, the first clinically tested Pim inhibitor, was shown to reverse drug resistance by directly inhibiting ABCB1-mediated transport. We sought to characterize Pim-1-dependent and -independent effects of SGI-1776 on drug resistance. SGI-1776 at the Pim-1-inhibitory and non-cytotoxic concentration of 1 μM decreased the IC50s of the ABCG2 and ABCB1 substrate drugs in cytotoxicity assays in resistant cells, with no effect on the IC50 of non-substrate drug, nor in parental cells. SGI-1776 also increased apoptosis of cells overexpressing ABCG2 or ABCB1 exposed to substrate chemotherapy drugs and decreased their colony formation in the presence of substrate, but not non-substrate, drugs, with no effect on parental cells. SGI-1776 decreased ABCB1 and ABCG2 surface expression on K562/ABCB1 and K562/ABCG2 cells, respectively, with Pim-1 overexpression, but not HL60/VCR and 8226/MR20 cells, with lower-level Pim-1 expression. Finally, SGI-1776 inhibited uptake of ABCG2 and ABCB1 substrates in a concentration-dependent manner irrespective of Pim-1 expression, inhibited ABCB1 and ABCG2 photoaffinity labeling with the transport substrate [125I]iodoarylazidoprazosin ([125I]IAAP) and stimulated ABCB1 and ABCG2 ATPase activity. Thus SGI-1776 decreases cell surface expression of ABCB1 and ABCG2 and inhibits drug transport by Pim-1-dependent and -independent mechanisms, respectively. Decrease in ABCB1 and ABCG2 cell surface expression mediated by Pim-1 inhibition represents a novel mechanism of chemosensitization. PMID:23261525

  8. The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms.

    PubMed

    Natarajan, Karthika; Bhullar, Jasjeet; Shukla, Suneet; Burcu, Mehmet; Chen, Zhe-Sheng; Ambudkar, Suresh V; Baer, Maria R

    2013-02-15

    Overexpression of the ATP-binding cassette (ABC) drug efflux proteins P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on malignant cells is associated with inferior chemotherapy outcomes. Both, ABCB1 and ABCG2, are substrates of the serine/threonine kinase Pim-1; Pim-1 knockdown decreases their cell surface expression, but SGI-1776, the first clinically tested Pim inhibitor, was shown to reverse drug resistance by directly inhibiting ABCB1-mediated transport. We sought to characterize Pim-1-dependent and -independent effects of SGI-1776 on drug resistance. SGI-1776 at the Pim-1-inhibitory and non-cytotoxic concentration of 1 μM decreased the IC(50)s of the ABCG2 and ABCB1 substrate drugs in cytotoxicity assays in resistant cells, with no effect on the IC(50) of non-substrate drug, nor in parental cells. SGI-1776 also increased apoptosis of cells overexpressing ABCG2 or ABCB1 exposed to substrate chemotherapy drugs and decreased their colony formation in the presence of substrate, but not non-substrate, drugs, with no effect on parental cells. SGI-1776 decreased ABCB1 and ABCG2 surface expression on K562/ABCB1 and K562/ABCG2 cells, respectively, with Pim-1 overexpression, but not HL60/VCR and 8226/MR20 cells, with lower-level Pim-1 expression. Finally, SGI-1776 inhibited uptake of ABCG2 and ABCB1 substrates in a concentration-dependent manner irrespective of Pim-1 expression, inhibited ABCB1 and ABCG2 photoaffinity labeling with the transport substrate [(125)I]iodoarylazidoprazosin ([(125)I]IAAP) and stimulated ABCB1 and ABCG2 ATPase activity. Thus SGI-1776 decreases cell surface expression of ABCB1 and ABCG2 and inhibits drug transport by Pim-1-dependent and -independent mechanisms, respectively. Decrease in ABCB1 and ABCG2 cell surface expression mediated by Pim-1 inhibition represents a novel mechanism of chemosensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Optical Spectrum of the Compact Planetary Nebula IC 5117

    NASA Technical Reports Server (NTRS)

    Hyung, Siek; Aller, Lawrence H.; Feibelman, Walter A.; Lee, Seong-Jae; Fisher, Richard R. (Technical Monitor)

    2001-01-01

    High resolution spectroscopic data of the very compact planetary nebula IC 5117 are obtained in the optical wavelengths, 3700A - 10050A, with the Hamilton Echelle Spectrograph at Lick Observatory, and which have been analyzed along with the International Ultraviolet Explorer (IUE) UV archive data. Although a diagnostic diagram shows significant density and temperature fluctuations, our analysis indicates that the nebular gas may be represented by a homogeneous shell of extremely high density gas, N(sub epsilon) approx. 90 000 /cu cm. The average electron temperatures, e.g. indicated by the [OIII] diagnostics, are around 12 000 K. We construct a photoionization model to represent most of the observed line intensities, and the physical condition of this compact nebulosity. Based on the semi-empirical ionization correction approach, and model indications, we derived the elemental abundances: He, C, N, O, Ne, and Ar appear to be normal or marginally depleted compared to the average planetary nebula, while the remaining elements, S, Cl, and K appear to be enhanced. IC 5117 is perhaps a very young compact planetary nebula, slightly more evolved than the other well-known compact planetary nebula IC 4997. The central stellar temperature is likely to be around 120 000 K, evolved from a C-rich AGB progenitor.

  10. New N-phenylpyrrolamide DNA gyrase B inhibitors: Optimization of efficacy and antibacterial activity.

    PubMed

    Durcik, Martina; Lovison, Denise; Skok, Žiga; Durante Cruz, Cristina; Tammela, Päivi; Tomašič, Tihomir; Benedetto Tiz, Davide; Draskovits, Gábor; Nyerges, Ákos; Pál, Csaba; Ilaš, Janez; Peterlin Mašič, Lucija; Kikelj, Danijel; Zidar, Nace

    2018-06-25

    The ATP binding site located on the subunit B of DNA gyrase is an attractive target for the development of new antibacterial agents. In recent decades, several small-molecule inhibitor classes have been discovered but none has so far reached the market. We present here the discovery of a promising new series of N-phenylpyrrolamides with low nanomolar IC 50 values against DNA gyrase, and submicromolar IC 50 values against topoisomerase IV from Escherichia coli and Staphylococcus aureus. The most potent compound in the series has an IC 50 value of 13 nM against E. coli gyrase. Minimum inhibitory concentrations (MICs) against Gram-positive bacteria are in the low micromolar range. The oxadiazolone derivative 11a, with an IC 50 value of 85 nM against E. coli DNA gyrase displays the most potent antibacterial activity, with MIC values of 1.56 μM against Enterococcus faecalis, and 3.13 μM against wild type S. aureus, methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The activity against wild type E. coli in the presence of efflux pump inhibitor phenylalanine-arginine β-naphthylamide (PAβN) is 4.6 μM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. A GRB and Broad-lined Type Ic Supernova from a Single Central Engine

    NASA Astrophysics Data System (ADS)

    Barnes, Jennifer; Duffell, Paul C.; Liu, Yuqian; Modjaz, Maryam; Bianco, Federica B.; Kasen, Daniel; MacFadyen, Andrew I.

    2018-06-01

    Unusually high velocities (≳0.1c) and correspondingly high kinetic energies have been observed in a subset of Type Ic supernovae (so-called “broad-lined Ic” supernovae; SNe Ic-BL), prompting a search for a central engine model capable of generating such energetic explosions. A clue to the explosion mechanism may lie in the fact that all supernovae that accompany long-duration gamma-ray bursts (GRBs) belong to the SN Ic-BL class. Using a combination of two-dimensional relativistic hydrodynamics and radiation transport calculations, we demonstrate that the central engine responsible for long GRBs can also trigger an SN Ic-BL. We find that a reasonable GRB engine injected into a stripped Wolf–Rayet progenitor produces a relativistic jet with energy ∼1051 erg, as well as an SN whose synthetic light curves and spectra are fully consistent with observed SNe Ic-BL during the photospheric phase. As a result of the jet’s asymmetric energy injection, the SN spectra and light curves depend on viewing angle. The impact of viewing angle on the spectrum is particularly pronounced at early times, while the viewing-angle dependence for the light curves (∼10% variation in bolometric luminosity) persists throughout the photospheric phase.

  12. Phenolic, flavonoid contents, anticholinesterase and antioxidant evaluation of Iris germanica var; florentina.

    PubMed

    Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul; Hussain, Abid; Ahmad, Sajjad; Imran, Muhammad; Zeb, Anwar

    2016-06-01

    This study was designed to investigate antioxidant and anticholinesterase potential of Iris germanica var; florentina. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential of plant samples were investigated by Ellman's assay. Antioxidant activity was performed using DPPH, H2O2 and ABTS free radical scavenging assays. Total phenolics and flavonoids contents were expressed in mg GAE/g dry weight and mg RTE/g, respectively. In AChE inhibition assay, Ig.Fl, Ig.Sp and Ig.Cf fractions exhibited highest activity with IC50 values of < 0.1, 5.64 and 19 μg/mL, respectively. In BChE inhibitory assay, Ig.Fl, Ig.Sp, Ig.Cf and Ig.Cr were most active with IC50 of < 0.1, < 0.1, 31 and 78 μg/mL, respectively. In DPPH assay, Ig.Fl and Ig.Cf exhibited highest inhibition of free radicals, 80.52% (IC50 = 9 μg/mL) and 78.30% (IC50 = 8 μg/mL), respectively. In ABTS assay Ig.Cr, Ig.Cf, Ig.Fl and Ig.Sp exhibited IC50 values of < 0.1, 2, 2 and 3 μg/mL, respectively.

  13. In vitro antileishmanial activity of fisetin flavonoid via inhibition of glutathione biosynthesis and arginase activity in Leishmania infantum.

    PubMed

    Adinehbeigi, Keivan; Razi Jalali, Mohammad Hossein; Shahriari, Ali; Bahrami, Somayeh

    2017-06-01

    With the increasing emergence of drug resistant Leishmania sp. in recent years, combination therapy has been considered as a useful way to treat and control of Leishmaniasis. The present study was designed to evaluate the antileishmanial effects of the fisetin alone and combination of fisetin plus Meglumine antimoniate (Fi-MA) against Leishmania infantum. The IC50 values for fisetin were obtained 0.283 and 0.102 μM against promastigotes and amastigote forms, respectively. Meglumine antimoniate (MA, Glucantime) as control drug also revealed IC50 values of 0.247 and 0.105 μM for promastigotes and amastigotes of L. infantum, respectively. In order to determine the mode of action of fisetin and Meglumine antimoniate (MA, Glucantime), the activities of arginase (ARG), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. Moreover, intracellular glutathione (GSH) and nitric oxide (NO) levels in L. infantum-infected macrophages and L. infantum promastigotes which were treated with IC50 concentrations of fisetin, MA and Fi-MA were investigated. Our results showed that MA decreased CAT and SOD activity and increased NO levels in L. infantum-infected macrophages. In promastigotes, MA inhibited parasite SOD activity and reduced parasite NO production. The decreased levels of most of the antioxidant enzymes, accompanying by the raised level of NO in treated macrophages with MA, were observed to regain their normal profiles due to Fi-MA treatment. Furthermore, fisetin could prevent the growth of promastigotes by inhibition of ARG activity and reduction of GSH levels and NO production. In conclusion, these findings showed that fisetin improves MA side effects.

  14. In vitro antileishmanial activity of fisetin flavonoid via inhibition of glutathione biosynthesis and arginase activity in Leishmania infantum

    PubMed Central

    Razi Jalali, Mohammad Hossein; Shahriari, Ali; Bahrami, Somayeh

    2017-01-01

    With the increasing emergence of drug resistant Leishmania sp. in recent years, combination therapy has been considered as a useful way to treat and control of Leishmaniasis. The present study was designed to evaluate the antileishmanial effects of the fisetin alone and combination of fisetin plus Meglumine antimoniate (Fi-MA) against Leishmania infantum. The IC50 values for fisetin were obtained 0.283 and 0.102 μM against promastigotes and amastigote forms, respectively. Meglumine antimoniate (MA, Glucantime) as control drug also revealed IC50 values of 0.247 and 0.105 μM for promastigotes and amastigotes of L. infantum, respectively. In order to determine the mode of action of fisetin and Meglumine antimoniate (MA, Glucantime), the activities of arginase (ARG), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. Moreover, intracellular glutathione (GSH) and nitric oxide (NO) levels in L. infantum-infected macrophages and L. infantum promastigotes which were treated with IC50 concentrations of fisetin, MA and Fi-MA were investigated. Our results showed that MA decreased CAT and SOD activity and increased NO levels in L. infantum-infected macrophages. In promastigotes, MA inhibited parasite SOD activity and reduced parasite NO production. The decreased levels of most of the antioxidant enzymes, accompanying by the raised level of NO in treated macrophages with MA, were observed to regain their normal profiles due to Fi-MA treatment. Furthermore, fisetin could prevent the growth of promastigotes by inhibition of ARG activity and reduction of GSH levels and NO production. In conclusion, these findings showed that fisetin improves MA side effects. PMID:28385129

  15. Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review.

    PubMed

    McKernan, Lindsey C; Walsh, Colin G; Reynolds, William S; Crofford, Leslie J; Dmochowski, Roger R; Williams, David A

    2018-03-01

    Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment. Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics. Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465). The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful. © 2017 Wiley Periodicals, Inc.

  16. Potential amoebicidal activity of hydrazone derivatives: synthesis, characterization, electrochemical behavior, theoretical study and evaluation of the biological activity.

    PubMed

    Toledano-Magaña, Yanis; García-Ramos, Juan Carlos; Navarro-Olivarria, Marisol; Flores-Alamo, Marcos; Manzanera-Estrada, Mayra; Ortiz-Frade, Luis; Galindo-Murillo, Rodrigo; Ruiz-Azuara, Lena; Meléndrez-Luevano, Ruth Ma; Cabrera-Vivas, Blanca M

    2015-05-29

    Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis.

  17. Evaluation of Antileishmanial Activity of Selected Brazilian Plants and Identification of the Active Principles

    PubMed Central

    Filho, Valdir Cechinel; Meyre-Silva, Christiane; Niero, Rivaldo; Bolda Mariano, Luisa Nathália; Gomes do Nascimento, Fabiana; Vicente Farias, Ingrid; Gazoni, Vanessa Fátima; dos Santos Silva, Bruna; Giménez, Alberto; Gutierrez-Yapu, David; Salamanca, Efrain; Malheiros, Angela

    2013-01-01

    This study evaluated extracts, fractions, and isolated compounds from some selected Brazilian medicinal plants against strains of promastigotes of Leishmania amazonensis and L. brasiliensis in vitro. The cell viability was determined, comparing the results with reference standards. The dichloromethane fractions of the roots, stems, and leaves of Allamanda schottii showed IC50 values between 14.0 and 2.0 μg/mL. Plumericin was the main active compound, with IC50 of 0.3 and 0.04 μg/mL against the two species of Leishmania analyzed. The hexane extract of Eugenia umbelliflora fruits showed IC50 of 14.3 and 5.7 μg/mL against L. amazonensis and L. brasiliensis, respectively. The methanolic extracts of the seeds of Garcinia achachairu and guttiferone A presented IC50 values of 35.9 and 10.4 μg/mL, against L. amazonensis, respectively. The ethanolic extracts of the stem barks of Rapanea ferruginea and the isolated compound, myrsinoic acid B, presented activity against L. brasiliensis with IC50 of 24.1 and 6.1 μg/mL. Chloroform fraction of Solanum sisymbriifolium exhibited IC50 of 33.8 and 20.5 μg/mL, and cilistol A was the main active principle, with IC50 of 6.6 and 3.1 μg/mL against L. amazonensis and L. brasiliensis, respectively. It is concluded that the analyzed plants are promising as new and effective antiparasitic agents. PMID:23840252

  18. Neopetrosiquinones A and B, Sesquiterpene Benzoquinones Isolated from the Deep-water Sponge Neopetrosia cf. proxima

    PubMed Central

    Winder, Priscilla L.; Baker, Heather L.; Linley, Patricia; Guzmán, Esther; Pomponi, Shirley A.; Diaz, M. Cristina; Reed, John K.; Wright, Amy E.

    2011-01-01

    Two new marine-derived sesquiterpene benzoquinones which we designate as neopetrosiquinone A (1) and B (2), have been isolated from a deep-water sponge of the family Petrosiidae. The structures were elucidated on the basis of their spectroscopic data. Compounds 1 and 2 inhibit the in vitro proliferation of the DLD-1 human colorectal adenocarcinoma cell line with IC50 values of 3.7 and 9.8 μM, respectively, and the PANC-1 human pancreatic carcinoma cell line with IC50 values of 6.1 and 13.8 μM, respectively. Neopetrosiquinone A (1) also inhibited the in vitro proliferation of the AsPC-1 human pancreatic carcinoma cell line with an IC50 value of 6.1 μM. The compounds are structurally related to alisiaquinone A, cyclozonarone and xestoquinone. PMID:22014756

  19. Docking analysis targeted to the whole enzyme: an application to the prediction of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives.

    PubMed

    Ganou, C A; Eleftheriou, P Th; Theodosis-Nobelos, P; Fesatidou, M; Geronikaki, A A; Lialiaris, T; Rekka, E A

    2018-02-01

    PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b has become a drug target for the treatment of type II diabetes. In the present study, prediction of inhibition using docking analysis targeted specifically to the active or allosteric site was performed on 87 compounds structurally belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and 10 thiazolyl derivatives exhibiting the best prediction results, were selected for in vitro evaluation. All thiomorpholines showed inhibitory action (with IC 50 = 4-45 μΜ, Ki = 2-23 μM), while only three thiazolyl derivatives showed low inhibition (best IC 50 = 18 μΜ, Ki = 9 μΜ). However, free binding energy (E) was in accordance with the IC 50 values only for some compounds. Docking analysis targeted to the whole enzyme revealed that the compounds exhibiting IC 50 values higher than expected could bind to other peripheral sites with lower free energy, E o , than when bound to the active/allosteric site. A prediction factor, E- (Σ Eo × 0.16), which takes into account lower energy binding to peripheral sites, was proposed and was found to correlate well with the IC 50 values following an asymmetrical sigmoidal equation with r 2 = 0.9692.

  20. The connection Between Plasma Protein Binding and Acute Toxicity as Determined by the LD50 Value.

    PubMed

    Svennebring, Andreas

    2016-02-01

    Preclinical Research A dataset of three drug classes (acids, bases, and neutrals) with LD50 values in mice was analysed to investigate a possible connection between high plasma protein binding and acute toxicity. Initially, it was found that high plasma protein binding was associated with toxicity for acids and neutrals, but after compensating for differences in lipophilicity, plasma protein binding was found not to be associated with toxicity. The therapeutic index established by the quotient between mouse LD50 and the defined daily dose was unaffected by both lipophilicity and plasma protein binding. © 2015 Wiley Periodicals, Inc.

  1. Tests of shock chemistry in IC 443G

    NASA Technical Reports Server (NTRS)

    Turner, B. E.; Chan, Kin-Wing; Green, S.; Lubowich, D. A.

    1992-01-01

    Eight molecular species, in the hot dense clump IC 443G, believed to be impacted by the shock wave from the SNR IC 443, are investigated. The clump consists of two distinct regions, one relatively cool, and one hotter and denser. Region 1 contains CO, HCO(+), HCN, and CN, whose abundances may be explained either by ion-molecule chemistry, or by a D shock of 60-90 km/s, passing through a clump of about 100,000/cu cm. Region 2 gives rise to SiO, CS, SO, and H2CO, and requires an ND shock of 5-15 km/s passing through a region of about 1,000,000/cu cm. Observed fractional abundances fit ND shock models if L is about 6.6 x 10 exp 15 cm. In general, observed line widths vary inversely with derived excitation density, while centroid velocities of all species are essentially identical.

  2. Antimicrobial and antileishmanial activities of diterpenoids isolated from the roots of Salvia deserta

    USDA-ARS?s Scientific Manuscript database

    Four diterpenes with biological activity were isolated from Salvia deserta roots. Taxodione was considered leishmanicidal, with IC50 value of 0.46 µg/mL against Leishimania donovani and also exhibited antifungal and antimicrobial activities. Ferruginol displayed the greatest activity (24-h IC50 1.29...

  3. Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties.

    PubMed

    Fukuda, Takashi; Yamaguchi, Yuichi; Masuma, Rokuro; Tomoda, Hiroshi; Omura, Satoshi

    2005-05-01

    New phenylfuropyridinones and related compounds, designated citridones A, B, B' and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 microM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5 to approximately 6.3 nM.

  4. Synthesis of novel fluorinated chalcones derived from 4‧-morpholinoacetophenone and their antiproliferative effects

    NASA Astrophysics Data System (ADS)

    Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Demirtaş, Ibrahim; Yaglioglu, Ayse Sahin; Guler, Caglar; Adem, Sevki; Karaküçük Iyidoğan, Ayşegül

    2017-12-01

    The fluorinated chalcones were synthesized by Claisen-Schmidt condensation between 4‧-morpholineacetophenone and various fluorinated benzaldehydes in the presence of NaOH in methanol. The synthesized compounds [1-7] were evaluated their antiproliferative activity against HeLa and C6 cell lines. Among them, compounds 4 and 5 were determined to have anticancer activity against HeLa cells line (IC50 values of 7.74 and 6.10 μg/mL, respectively). The anticancer activity results were shown that compounds 3, and 6 had inhibitory against C6 cells (IC50 values of 12.80 and 4.16 μg/mL, respectively). The compounds 1 and 2 had high antiproliferative activity with non-cytotoxicity. All of the new compounds, except for compound 4 showed inhibition against the human isozyme hCA I with IC50 in the range of 0.5-1,16 mM. Pyruvate kinase M2 (PKM2) was effectively inhibited by compound 4 with IC50 = 26 μM.

  5. Broad-line Type Ic supernova SN 2014ad

    NASA Astrophysics Data System (ADS)

    Sahu, D. K.; Anupama, G. C.; Chakradhari, N. K.; Srivastav, S.; Tanaka, Masaomi; Maeda, Keiichi; Nomoto, Ken'ichi

    2018-04-01

    We present optical and ultraviolet photometry and low-resolution optical spectroscopy of the broad-line Type Ic supernova SN 2014ad in the galaxy PGC 37625 (Mrk 1309), covering the evolution of the supernova during -5 to +87 d with respect to the date of maximum in the B band. A late-phase spectrum obtained at +340 d is also presented. With an absolute V-band magnitude at peak of MV = -18.86 ± 0.23 mag, SN 2014ad is fainter than supernovae associated with gamma ray bursts (GRBs), and brighter than most of the normal and broad-line Type Ic supernovae without an associated GRB. The spectral evolution indicates that the expansion velocity of the ejecta, as measured using the Si II line, is as high as ˜33 500 km s-1 around maximum, while during the post-maximum phase it settles at ˜15 000 km s-1. The expansion velocity of SN 2014ad is higher than that of all other well-observed broad-line Type Ic supernovae except for the GRB-associated SN 2010bh. The explosion parameters, determined by applying Arnett's analytical light-curve model to the observed bolometric light-curve, indicate that it was an energetic explosion with a kinetic energy of ˜(1 ± 0.3) × 1052 erg and a total ejected mass of ˜(3.3 ± 0.8) M⊙, and that ˜0.24 M⊙ of 56Ni was synthesized in the explosion. The metallicity of the host galaxy near the supernova region is estimated to be ˜0.5 Z⊙.

  6. TRIM25 is associated with cisplatin resistance in non-small-cell lung carcinoma A549 cell line via downregulation of 14-3-3σ.

    PubMed

    Qin, Xia; Qiu, Feng; Zou, Zhen

    2017-11-04

    Lung cancer, in particular, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related mortality. Cis-Diamminedichloroplatinum (cisplatin, CDDP) as first-line chemotherapy for NSCLC, but resistance occurs frequently. We previously reported that Tripartite motif protein 25 (TRIM25) was highly expressed in cisplatin-resistant human lung adenocarcinoma A549 cells (A549/CDDP) in comparison with its parental A549 cells. Herein, we take a further step to demonstrate the association of TRIM25 and cisplatin resistance and also the underlying mechanisms. Knockdown of TRIM25 by RNA interference in A549/CDDP cells decreased half maximal inhibitory concentration (IC 50 ) values and promoted apoptosis in response to cisplatin, whereas overexpression of TRIM25 had opposite effects. More importantly, we found that concomitant knockdown of 14-3-3σ and TRIM25 absolutely reversed the decreased MDM2, increased p53, increased cleaved-Capsese3 and decreased IC 50 value induced by knockdown of TRIM25 individually, suggesting that TRIM25 mediated cisplatin resistance primarily through downregulation of 14-3-3σ. Our results indicate that TRIM25 is associated with cisplatin resistance and 14-3-3σ-MDM2-p53 signaling pathway is involved in this process, suggesting targeting TRIM25 may be a potential strategy for the reversal of cisplatin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Publications - IC 35 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 35 Publication Details Title: Alaska's mineral industry 1991: A summary Authors: Bundtzen, T.K ., 1992, Alaska's mineral industry 1991: A summary: Alaska Division of Geological & Geophysical

  8. Publications - IC 36 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 36 Publication Details Title: Alaska's mineral industry 1992: A summary Authors: Swainbank, R.C ., 1993, Alaska's mineral industry 1992: A summary: Alaska Division of Geological & Geophysical

  9. Publications - IC 40 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 40 Publication Details Title: Alaska's mineral industry 1994: A summary Authors: Swainbank, R.C mineral industry 1994: A summary: Alaska Division of Geological & Geophysical Surveys Information

  10. Biofunctional Properties of Enzymatic Squid Meat Hydrolysate

    PubMed Central

    Choi, Joon Hyuk; Kim, Kyung-Tae; Kim, Sang Moo

    2015-01-01

    Squid is one of the most important commercial fishes in the world and is mainly utilized or consumed as sliced raw fish or as processed products. The biofunctional activities of enzymatic squid meat hydrolysate were determined to develop value-added products. Enzymatic squid hydrolysate manufactured by Alcalase effectively quenched 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and hydrogen peroxide radical with IC50 values of 311, 3,410, and 111.5 μg/mL, respectively. Angiotensin I-converting enzyme inhibitory activity of squid hydrolysate was strong with an IC50 value of 145.1 μg/mL, while tyrosinase inhibitory activity with an IC50 value of 4.72 mg/mL was moderately low. Overall, squid meat hydrolysate can be used in food or cosmetic industries as a bioactive ingredient and possibly be used in the manufacture of seasoning, bread, noodle, or cosmetics. PMID:25866752

  11. Watching AGN feedback at its birth: HST observations of nascent outflow host IC860

    NASA Astrophysics Data System (ADS)

    Alatalo, Katherine

    2016-10-01

    IC860 is a nearby IR-luminous early-type spiral with a unique set of properties: it is a shocked, poststarburst galaxy that hosts an AGN-driven neutral wind and a compact core of molecular gas. IC860 can serve as a rosetta stone for the early stages of triggering AGN feedback. We propose to use WFC3 on HST to obtain NUV, optical and near-IR imaging of IC860. We will create a spatially-resolved history of star formation quenching through SED-fitting of 7 requested broadband filters, and compare the spatially resolved star formation histories to in different positions within the underlying stellar features (such as spiral structure) that might define a narrative of how star formation is quenching in IC860. These observations will also resolve the super-star cluster sites to trace the most recent star formation. Finally, these observations will trace the mass of the outflow by building an absorption map of the dust. IC860 presents a unique opportunity to study a galaxy at an early stage of transitioning from blue spiral to red early-type galaxy, that also hosts an AGN-driven neutral wind and a compact, turbulent molecular gas core.

  12. A high ratio of IC31® adjuvant to antigen is necessary for H4 TB vaccine immunomodulation

    PubMed Central

    Aboutorabian, Sepideh; Hakimi, Jalil; Boudet, Florence; Montano, Sandrine; Dookie, Annie; Roque, Cristopher; Ausar, Salvador F; Rahman, Nausheen; Brookes, Roger H

    2015-01-01

    A tuberculosis (TB) vaccine consisting of a recombinant fusion protein (H4) and a novel TLR9 adjuvant (IC31) is in clinical development. To better understand the H4-IC31 ratio, we measured the binding capacity of IC31 for H4 protein and immunized mice with formulations that contained limiting to excess ratios of IC31 to H4. An immunomodulated H4-specific IFNγ response was only observed when IC31 was present in excess of H4. Since TLR expression is species-specific and the vaccine is intended to boost BCG-primed immunity, we questioned whether data in mice would translate to humans. To address this question, we used the fresh human Whole Blood (hWB) recovered from BCG-vaccinated subjects to screen H4-IC31 formulations. We found IC31 modulation in hWB to be quite distinct from the TLR4-Adjuvant. Unlike TLR4-Adjuvant, IC31 formulations did not induce the pro-inflammatory cytokine TNFα, but modulated a robust H4-specific IFNγ response after 12 d of culture. We then re-stimulated the fresh hWB of 5 BCG-primed subjects with formulations that had excess or limiting IC31 binding for H4 protein and again found that an immunomodulated H4-specific IFNγ response needed an excess of IC31. Finally, we monitored the zeta (ζ) potential of H4-IC31 formulations and found that the overall charge of H4-IC31 particles changes from negative to positive once IC31 is in greater than 9-fold excess. Using two diverse yet mutually supportive approaches, we confirm the need for an excess of IC31 adjuvant in H4 TB vaccine formulations and suggest surface potential may be an important factor. PMID:25997147

  13. A high ratio of IC31(®) adjuvant to antigen is necessary for H4 TB vaccine immunomodulation.

    PubMed

    Aboutorabian, Sepideh; Hakimi, Jalil; Boudet, Florence; Montano, Sandrine; Dookie, Annie; Roque, Cristopher; Ausar, Salvador F; Rahman, Nausheen; Brookes, Roger H

    2015-01-01

    A tuberculosis (TB) vaccine consisting of a recombinant fusion protein (H4) and a novel TLR9 adjuvant (IC31) is in clinical development. To better understand the H4-IC31 ratio, we measured the binding capacity of IC31 for H4 protein and immunized mice with formulations that contained limiting to excess ratios of IC31 to H4. An immunomodulated H4-specific IFNγ response was only observed when IC31 was present in excess of H4. Since TLR expression is species-specific and the vaccine is intended to boost BCG-primed immunity, we questioned whether data in mice would translate to humans. To address this question, we used the fresh human Whole Blood (hWB) recovered from BCG-vaccinated subjects to screen H4-IC31 formulations. We found IC31 modulation in hWB to be quite distinct from the TLR4-Adjuvant. Unlike TLR4-Adjuvant, IC31 formulations did not induce the pro-inflammatory cytokine TNFα, but modulated a robust H4-specific IFNγ response after 12 d of culture. We then re-stimulated the fresh hWB of 5 BCG-primed subjects with formulations that had excess or limiting IC31 binding for H4 protein and again found that an immunomodulated H4-specific IFNγ response needed an excess of IC31. Finally, we monitored the zeta (ζ) potential of H4-IC31 formulations and found that the overall charge of H4-IC31 particles changes from negative to positive once IC31 is in greater than 9-fold excess. Using two diverse yet mutually supportive approaches, we confirm the need for an excess of IC31 adjuvant in H4 TB vaccine formulations and suggest surface potential may be an important factor.

  14. Young Low-Mass Stars and Brown Dwarfs in IC 348

    NASA Astrophysics Data System (ADS)

    Luhman, K. L.

    1999-11-01

    I present new results from a continuing program to identify and characterize the low-mass stellar and substellar populations in the young cluster IC 348 (0.5-10 Myr). Optical spectroscopy has revealed young objects with spectral types as late as M8.25. The intrinsic J-H and H-K colors of these sources are dwarflike, whereas the R-I and I-J colors appear intermediate between the colors of dwarfs and giants. Furthermore, the spectra from 6500 to 9500 Å are reproduced well with averages of standard dwarf and giant spectra, suggesting that such averages should be used in the classification of young late-type sources. An H-R diagram is constructed for the low-mass population in IC 348 (K6-M8). The presumably coeval components of the young quadruple system GG Tau (White et al.) and the locus of stars in IC 348 are used as empirical isochrones to test the theoretical evolutionary models. The calculations of Burrows et al. do not appear to be consistent with the data at these earliest stages of stellar evolution. There is fair agreement between the data and the model isochrones of D'Antona & Mazzitelli, except near the hydrogen-burning limit. The agreement cannot be improved by changing the conversion between spectral types and effective temperatures. On the other hand, for the models of Baraffe et al., an adjustment of the temperature scale to progressively warmer temperatures at later M types, intermediate between dwarfs and giants, brings all components of GG Tau onto the same model isochrone and gives the population of IC 348 a constant age and age spread as a function of mass. When other observational constraints are considered, such as the dynamical masses of GM Aur, DM Tau, and GG Tau A, the models of Baraffe et al. are the most consistent with observations of young systems. With compatible temperature scales, the models of both D'Antona & Mazzitelli and Baraffe et al. suggest that the hydrogen-burning mass limit occurs near M6 at ages of <~10 Myr. Thus, several

  15. Recent Progresses in Laboratory Astrophysics with Ames’ COSmIC Facility

    NASA Astrophysics Data System (ADS)

    Salama, Farid; Contreras, Cesar; Sciamma-O'Brien, Ella; Bejaoui, Salma

    2016-06-01

    We present and discuss the characteristics and the capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory [1]. COSmIC stands for “Cosmic Simulation Chamber” and is dedicated to the study of neutral and ionized molecules and nano particles under the low temperature and high vacuum conditions that are required to simulate space environments. COSmIC integrates a variety of state-of-the-art instruments that allow forming, processing and monitoring simulated space conditions for planetary, circumstellar and interstellar materials in the laboratory. COSmIC is composed of a Pulsed Discharge Nozzle (PDN) expansion that generates a plasma in free supersonic jet expansion coupled to two high-sensitivity, complementary in situ diagnostics: a Cavity Ring Down Spectroscopy (CRDS) and laser induced fluorescence (LIF) systems for photonic detection and a Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection [2].Recent laboratory results that were obtained using COSmIC will be presented, in particular the progress that has been achieved in the domain of the diffuse interstellar bands (DIBs) [3] and in monitoring, in the laboratory, the formation of dust grains and aerosols from their gas-phase molecular precursors in environments as varied as stellar/circumstellar outflows [4] and planetary atmospheres [5]. Plans for future, next generation, laboratory experiments on cosmic molecules and grains in the growing field of laboratory astrophysics will also be addressed as well as the implications of the current studies for astronomy.References: [1] Salama F., In Organic Matter in Space, IAU Symposium 251, Kwok & Sandford Eds.Cambridge University Press, Vol. 4, S251, p. 357 (2008) and references therein.[2] Ricketts C., Contreras C., Walker, R., Salama F., Int. J. Mass Spec, 300, 26 (2011)[3] Salama F., Galazutdinov G., Krelowski J

  16. IC 751: A New Changing Look AGN Discovered by NuSTAR

    NASA Technical Reports Server (NTRS)

    Ricci, C.; Bauer, F. E.; Arevalo, P.; Boggs, S.; Brandt, W. N.; Christensen, F. E.; Craig, W. W.; Ghandi, P.; Hailey, C. J.; Harrison, F. A.; hide

    2016-01-01

    We present results of five Nuclear Spectroscopic Telescope Array (NuSTAR) observations of the type 2 active galactic nucleus (AGN) in IC 751, three of which were performed simultaneously with XMM-Newton or Swift/ X-Ray Telescope. We find that the nuclear X-ray source underwent a clear transition from a Compton-thick (NH approx. = 2 x10(exp 24)/sq cm) to a Compton-thin ( N(sub H) approx. = 4 x10(exp 23)/sq cm) state on timescales of < or approx.3 months, which makes IC 751 the first changing look AGN discovered by NuSTAR. Changes of the line of sight column density at the approx.2 (sigma) level are also found on a timescale of approx. 48 hr (delta N(sub H approx. 10(exp 23)/sq cm). From the lack of spectral variability on timescales of approx.100 ks, we infer that the varying absorber is located beyond the emission-weighted average radius of the broad-line region (BLR), and could therefore be related either to the external part of the BLR or a clumpy molecular torus. By adopting a physical torus X-ray spectral model, we are able to disentangle the column density of the non-varying absorber (N(sub H) approx. 3.8 x10(exp 23)/sq cm) from that of the varying clouds [N(sub H) approx. (1- 150) x 10(exp 22)/sq cm], and to constrain that of the material responsible for the reprocessed X-ray radiation (N(sub H approx. 6 x 10(exp 24)/sq cm).24 -2). We find evidence of significant intrinsic X-ray variability, with the flux varying by a factor of five on timescales of a few months in the 2-10 and 10-50 keV band.

  17. Antiviral activity of four types of bioflavonoid against dengue virus type-2

    PubMed Central

    2011-01-01

    Background Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for each compound. Results The half maximal inhibitory concentration (IC50) of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids

  18. Protecting ICS Systems Within the Energy Sector from Cyber Attacks

    NASA Astrophysics Data System (ADS)

    Barnes, Shaquille

    Advance persistent threat (APT) groups are continuing to attack the energy sector through cyberspace, which poses a risk to our society, national security, and economy. Industrial control systems (ICSs) are not designed to handle cyber-attacks, which is why asset owners need to implement the correct proactive and reactive measures to mitigate the risk to their ICS environments. The Industrial Control Systems Cyber Emergency Response Team (ICS-CERT) responded to 290 incidents for fiscal year 2016, where 59 of those incidents came from the Energy Sector. APT groups know how vulnerable energy sector ICS systems are and the destruction they can cause when they go offline such as loss of production, loss of life, and economic impact. Defending against APT groups requires more than just passive controls such as firewalls and antivirus solutions. Asset owners should implement a combination of best practices and active defense in their environment to defend against APT groups. Cyber-attacks against critical infrastructure will become more complex and harder to detect and respond to with traditional security controls. The purpose of this paper was to provide asset owners with the correct security controls and methodologies to help defend against APT groups.

  19. Definition of intercultural competence (IC) in undergraduate students at a private university in the USA: A mixed-methods study

    PubMed Central

    Gierke, Lioba; Binder, Nadine; Heckmann, Mark; Odağ, Özen; Leiser, Anne

    2018-01-01

    Introduction Intercultural competence (IC) is an important skill to be gained from higher education. However, it remains unclear what IC means to students and what factors might influence their definitions of IC. The aim of the current study was to qualitatively assess how students at one higher education institution in the USA define IC and to quantitatively test for relationships among IC components and various demographic characteristics, including intercultural experience and study context. A further aim was to descriptively compare the IC definitions from the US sample with the definitions obtained from another sample of university students in Germany. Materials and methods A purposive sample of n = 93 undergraduate, second semester students at Dickinson College, USA, participated in the study by completing an online questionnaire. The qualitative data were content-analyzed to define the dimensions of IC. The quantitative data were cluster-analyzed to assess the multivariate relationships among the IC components and the demographic characteristics of the sample. Results The most important dimensions of IC were Knowledge, External Outcomes (interaction, communication), and Attitudes (respect, tolerance) according to the US sample. The most frequently chosen dimensions of IC differed between both samples: Knowledge was chosen by the sample in the USA while External Outcomes was chosen by the sample in Germany. Relative to the US sample, significantly more students chose Attitudes, External Outcomes, and Intrapersonal Skills in the sample in Germany. The relationships among IC components and demographic characteristics were only weak in the US sample. A person with IC was rated as Open-minded and Respectful by students who lived predominantly in the USA or Tolerant and Curious by those who lived outside the USA for at least six months. Discussion The current results suggest that students residing in two countries (USA or Germany) define IC using similar

  20. Definition of intercultural competence (IC) in undergraduate students at a private university in the USA: A mixed-methods study.

    PubMed

    Gierke, Lioba; Binder, Nadine; Heckmann, Mark; Odağ, Özen; Leiser, Anne; Kedzior, Karina Karolina

    2018-01-01

    Intercultural competence (IC) is an important skill to be gained from higher education. However, it remains unclear what IC means to students and what factors might influence their definitions of IC. The aim of the current study was to qualitatively assess how students at one higher education institution in the USA define IC and to quantitatively test for relationships among IC components and various demographic characteristics, including intercultural experience and study context. A further aim was to descriptively compare the IC definitions from the US sample with the definitions obtained from another sample of university students in Germany. A purposive sample of n = 93 undergraduate, second semester students at Dickinson College, USA, participated in the study by completing an online questionnaire. The qualitative data were content-analyzed to define the dimensions of IC. The quantitative data were cluster-analyzed to assess the multivariate relationships among the IC components and the demographic characteristics of the sample. The most important dimensions of IC were Knowledge, External Outcomes (interaction, communication), and Attitudes (respect, tolerance) according to the US sample. The most frequently chosen dimensions of IC differed between both samples: Knowledge was chosen by the sample in the USA while External Outcomes was chosen by the sample in Germany. Relative to the US sample, significantly more students chose Attitudes, External Outcomes, and Intrapersonal Skills in the sample in Germany. The relationships among IC components and demographic characteristics were only weak in the US sample. A person with IC was rated as Open-minded and Respectful by students who lived predominantly in the USA or Tolerant and Curious by those who lived outside the USA for at least six months. The current results suggest that students residing in two countries (USA or Germany) define IC using similar dimensions. However, IC definitions may depend on the

  1. Publications - IC 58 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 58 Publication Details Title: Alaska's mineral industry 2008: A summary Authors: Szumigala, D.J summary: Alaska Division of Geological & Geophysical Surveys Information Circular 58, 15 p. http

  2. Effect of electronic cigarettes on human middle ear.

    PubMed

    Song, Jae-Jun; Go, Yoon Young; Mun, Ji Yoen; Lee, Sehee; Im, Gi Jung; Kim, Yoo Yon; Lee, Jun Ho; Chang, Jiwon

    2018-06-01

    Electronic cigarettes (e-cigarettes) are the most commonly used electronic nicotine delivery systems and are a relatively new product designed for smoking cessation. The market scale of electronic cigarettes is growing rapidly, but the potential impact of e-cigarettes on public health has not yet been verified. In this study, we examined the effect of e-liquids on a human middle ear epithelial cell (HMEEC) line. The main components of e-liquids are propylene glycol, vegetable glycerin and flavoring agents with or without nicotine. We analyzed 73 bottles of e-liquids from 12 different manufacturers, evaluated the trace elements in e-liquids, and identified the cytotoxicity of e-liquids on HMEECs in the presence or absence of nicotine. In the trace elements analysis, nickel, arsenic, cadmium, and lead were detected in the e-liquids. E-liquids without nicotine decreased cell viability, and the average IC 50 value of total e-liquids (n = 73) was 2.48 ± 0.93%. Among the different flavors, menthol-flavored e-liquids significantly reduced cell viability, and their average IC 50 value (n = 28) was 1.85 ± 0.80%. The average IC 50 values were distinct among manufacturers and the proportion of the solvents. The present study provides evidence that e-cigarettes influence and reduce human middle ear cell viability even without the application of nicotine. Additionally, the cytotoxicity of e-liquids was affected by the flavoring agents. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. 30 CFR 57.22102 - Smoking (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a...

  4. Poly IC therapy in aleutian disease of mink.

    PubMed Central

    Russell, A S; Percy, J S; Cho, H J

    1975-01-01

    Twenty-four virgin female aleutian mink were infected with aleutian disease agent and after 24 hours, 12 of these were treated with a course of polyinosinic acid-polycytidilic acid (Poly IC) injections. After six weeks the gammaglobulin level was significantly lower in the treated group but at 12 weeks this difference was no longer present. Four of the treated mink had normal target organ histology when killed at 20 weeks. The untreated group all showed moderate to marked changes but this difference was not statistically significant. There was a marked increase in the reactive lymphocyte blastogenesis index during the first weeks of infection and the phytohaemagglutinin response was seen to fall progressively. The antiglobulin reaction usually became positive after infection but neither antinuclear nor antierythrocyte antibodies were found. Precipitating antibodies to several polynucleotides were frequently present and were unrelated to infection or to Poly IC treatment. Images Fig. 1. Fig. 2A Fig. 2B. PMID:1095164

  5. The time-dependence of the defective nature of ice Ic (cubic ice) and its implications for atmospheric science

    NASA Astrophysics Data System (ADS)

    Sippel, Christian; Koza, Michael M.; Hansen, Thomas C.; Kuhs, Werner F.

    2010-05-01

    The possible atmospheric implication of ice Ic (cubic ice) has already been suggested some time ago in the context of snow crystal formation [1]. New findings from air-borne measurements in cirrus clouds and contrails have put ice Ic into the focus of interest to understand the so-called "supersaturation puzzle" [2,3,4]. Our recent microstructural work on ice Ic [5,6] appears to be highly relevant in this context. We have found that ice Ic is characterized by a complex stacking fault pattern, which changes as a function of temperature as well as time. Indeed, from our own [7] and other group's work [8] one knows that (in contrast to earlier believe) ice Ic can form up to temperatures at least as high as 240K - thus in the relevant range for cirrus clouds. We have good preliminary evidence that the "cubicity" (which can be related to stacking fault probabilities) as well as the particle size of ice Ic are the relevant parameters for this correlation. The "cubicity" of stacking faulty ice Ic (established by diffraction) correlates nicely with the increased supersaturation at decreasing temperatures observed in cirrus clouds and contrails, a fact, which may be considered as further evidence for the presence of ice Ic. Recently, we have studied the time-dependency of the changes in both "cubicity" and particle size at various temperatures of relevance for cirrus clouds and contrails by in-situ neutron powder diffraction. The timescales over which changes occur (several to many hours) are similar to the life-time of cirrus clouds and contrails and suggest that the supersaturation situation may change within this time span in the natural environment too. Some accompanying results obtained by cryo-SEM (scanning electron microscopy) work will also be presented and suggest that stacking-faulty ice Ic has kinky surfaces providing many more active centres for heterogeneous reactions on the surface than in the usually assumed stable hexagonal form of ice Ih with its rather

  6. In vitro anti-plasmodial activity of some traditionally used medicinal plants against Plasmodium falciparum.

    PubMed

    Venkatesalu, V; Gopalan, N; Pillai, C R; Singh, Vineeta; Chandrasekaran, M; Senthilkumar, A; Chandramouli, N

    2012-07-01

    The anti-plasmodial activity of different solvent extracts of Adhatoda vasica (root), Caesalpinia pulcherrima (leaf), Carica papaya (pulp), Erythroxylum monogynum (leaf), Lantana camara (whole plant), Ocimum sanctum (root) and Phyllanthus niruri (whole plant) were studied against Plasmodium falciparum. Of the 35 extracts tested, seven extracts showed good anti-plasmodial activity. Methanol extract of C. pulcherrima showed the lowest IC50 value (10.96 μg/mL) followed by methanol extract of A. vasica (IC(50)=11.1 μg/mL), chloroform extract of O. sanctum (IC(50)=11.47 μg/mL), methanol extract of E. monogynum (IC(50)=12.23 μg/mL), acetone extract of C. pulcherrima (IC(50)=12.49 μg/mL), methanol extract of O. sanctum and acetone extract of A. vasica (IC(50)=14.04 μg/mL). The results of the present study justify the use of these medicinal plants in traditional practice, and also, a further study on the isolation of anti-plasmodial molecules from their active crude extracts is in progress.

  7. VizieR Online Data Catalog: Optical & Spitzer photometry in IC 1805 (Sung+, 2017)

    NASA Astrophysics Data System (ADS)

    Sung, H.; Bessell, M. S.; Chun, M.-Y.; Yi, J.; Naze, Y.; Lim, B.; Karimov, R.; Rauw, G.; Park, B.-G.; Hur, H.

    2017-06-01

    For a study of the IMF and the star-formation history of the young open cluster IC 1805, we obtained deep wide-field VRI and Hα images of IC 1805 using the CFH12K mosaic CCD camera of the CFHT on 2002 January 6 and 7. We also observed several regions in IC 1805, for a study of the reddening and massive star content, using the SITe 2000x800 CCD (Maidanak 2k CCD) and standard UBVRI filters of the AZT-22 1.5m telescope at the Maidanak Astronomical Observatory in Uzbekistan on 2003 August 18 and 2004 december 25,30. Later, we obtained additional images of the central region of IC 1805 with the Fairchild 486 CCD (SNUCam) and UBVI and Hα filters of the AZT-22 telescope on 2007 October 7 and 2009 January 19. The Spitzer mapping observations were performed on 2006 September 20 under program ID 20052 (PI: S. Wolff). For complete photometry of stars in the CFH12K FOV in 3.6 and 4.5um, we also downloaded and reduced the GLIMPSE360 data (AOR: 38753280, 38763264, 38769408, 38799104, 38798592, 38784512, PI: B. A. Whitney). MIPS scans of IC 1805 were obtained on 2005 August 31 and 2005 September 2 (PID 3234, PI: J. S. Greeves). The Chandra X-ray Observatory Observations of IC 1805 (ObsID: 7033, PI: L. Townley) were made on 2006 November 25. The total exposure time was about 79ks. The properties of 647 X-ray sources were published in Townsley+ (2014,J/ApJS/213/1). We searched for the optical and MIR counterparts of these X-ray sources with a matching radius of up to 1.5". (4 data files).

  8. Publications - IC 39 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 39 Publication Details Title: Alaska's mineral industry 1993: A summary Authors: Bundtzen, T.K 1993: A summary: Alaska Division of Geological & Geophysical Surveys Information Circular 39, 11 p

  9. Publications - IC 41 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 41 Publication Details Title: Alaska's mineral industry 1995: A summary Authors: Bundtzen, T.K 1995: A summary: Alaska Division of Geological & Geophysical Surveys Information Circular 41, 12 p

  10. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist.

    PubMed

    Arai, Kiyoshi; Homma, Tsuyoshi; Morikawa, Yuka; Ubukata, Naoko; Tsuruoka, Hiyoyuki; Aoki, Kazumasa; Ishikawa, Hirokazu; Mizuno, Makoto; Sada, Toshio

    2015-08-15

    The present study was designed to characterize the pharmacological profile of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist. In the radioligand-binding assay, CS-3150 inhibited (3)H-aldosterone binding to mineralocorticoid receptor with an IC50 value of 9.4nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 36 and 713nM, respectively. CS-3150 also showed at least 1000-fold higher selectivity for mineralocorticoid receptor over other steroid hormone receptors, glucocorticoid receptor, androgen receptor and progesterone receptor. In the reporter gene assay, CS-3150 inhibited aldosterone-induced transcriptional activation of human mineralocorticoid receptor with an IC50 value of 3.7nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 66 and 970nM, respectively. CS-3150 had no agonistic effect on mineralocorticoid receptor and did not show any antagonistic or agonistic effect on glucocorticoid receptor, androgen receptor and progesterone receptor even at the high concentration of 5μM. In adrenalectomized rats, single oral administration of CS-3150 suppressed aldosterone-induced decrease in urinary Na(+)/K(+) ratio, an index of in vivo mineralocorticoid receptor activation, and this suppressive effect was more potent and longer-lasting than that of spironolactone and eplerenone. Chronic treatment with CS-3150 inhibited blood pressure elevation induced by deoxycorticosterone acetate (DOCA)/salt-loading to rats, and this antihypertensive effect was more potent than that of spironolactone and eplerenone. These findings indicate that CS-3150 is a selective and highly potent mineralocorticoid receptor antagonist with long-lasting oral activity. This agent could be useful for the treatment of hypertension, cardiovascular and renal disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A Novel Two-Step Hierarchical Quantitative Structure–Activity Relationship Modeling Work Flow for Predicting Acute Toxicity of Chemicals in Rodents

    PubMed Central

    Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A.; Rusyn, Ivan; Tropsha, Alexander

    2009-01-01

    Background Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Objective A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. Methods and results A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD50 values from chemical descriptors. All models were extensively validated using special protocols. Conclusions The novelty of this modeling approach is that it uses the relationships

  12. A novel two-step hierarchical quantitative structure-activity relationship modeling work flow for predicting acute toxicity of chemicals in rodents.

    PubMed

    Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A; Rusyn, Ivan; Tropsha, Alexander

    2009-08-01

    Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols. The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only

  13. Rapid and multiband variability of the TeV bright active nucleus of the galaxy IC 310

    DOE PAGES

    Aleksić, J.; Antonelli, L. A.; Antoranz, P.; ...

    2014-03-14

    Recently the radio galaxy IC 310 was identified as a γ-ray emitter based on observations at GeV energies with Fermi-LAT and at very high energies (VHE, E > 100 GeV) with the MAGIC telescopes. Originally classified as a head-tail radio galaxy, the nature of this object is subject of controversy since its nucleus shows blazar-like behavior. In order to understand the nature of IC 310 and the origin of the VHE emission, we studied the spectral and flux variability of IC 310 from the X-ray band to the VHE γ-ray regime. The light curve of IC 310 above 300 GeVmore » has been measured with the MAGIC telescopes from 2009 October to 2010 February. Contemporaneous Fermi-LAT data (2008-2011) in the 10-500 GeV energy range were also analyzed. In the X-ray regime, archival observations from 2003 to 2007 with XMM-Newton, Chandra, and Swift-XRT in the 0.5-10 keV band were studied. The VHE light curve reveals several high-amplitude and short-duration flares. Day-to-day flux variability is clearly present (>5σ). The photon index between 120 GeV and 8 TeV remains at the value Γ ~ 2.0 during both low and high flux states. The VHE spectral shape does not show significant variability, whereas the flux at 1 TeV changes by a factor of ~7. Fermi-LAT detected only eight γ-ray events in the energy range 10 GeV–500 GeV in three years of observation. Moreover, the measured photon index of Γ = 1.3 ± 0.5 in the Fermi-LAT range is very hard. The X-ray measurements show strong variability in both flux and photon index. The latter varied from 1.76 ± 0.07 to 2.55 ± 0.07. The rapid variability measured in γ-rays and X-rays confirms the blazar-like behavior of IC 310. The multi-TeV γ-ray emission seems to originate from scales of less than 80 Schwarzschild radii (for a black hole mass of 2 × 10 8 M⊙) within the compact core of its FR I radio jet with orientation angle 10°-38°. The spectral energy distribution resembles that of an extreme blazar, albeit the luminosity is more than

  14. Antioxidant and Anti-Inflammatory Activities of Hydrolysates and Peptide Fractions Obtained by Enzymatic Hydrolysis of Selected Heat-Treated Edible Insects.

    PubMed

    Zielińska, Ewelina; Baraniak, Barbara; Karaś, Monika

    2017-09-02

    This study investigated the effect of heat treatment of edible insects on antioxidant and anti-inflammatory activities of peptides obtained by in vitro gastrointestinal digestion and absorption process thereof. The antioxidant potential of edible insect hydrolysates was determined as free radical-scavenging activity, ion chelating activity, and reducing power, whereas the anti-inflammatory activity was expressed as lipoxygenase and cyclooxygenase-2 inhibitory activity. The highest antiradical activity against DPPH • (2,2-diphenyl-1-picrylhydrazyl radical) was noted for a peptide fraction from baked cricket Gryllodes sigillatus hydrolysate (IC 50 value 10.9 µg/mL) and that against ABTS •+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical) was the highest for raw mealworm Tenebrio molitor hydrolysate (inhibitory concentration (IC 50 value) 5.3 µg/mL). The peptides obtained from boiled locust Schistocerca gregaria hydrolysate showed the highest Fe 2+ chelation ability (IC 50 value 2.57 µg/mL); furthermore, the highest reducing power was observed for raw G. sigillatus hydrolysate (0.771). The peptide fraction from a protein preparation from the locust S. gregaria exhibited the most significant lipoxygenase and cyclooxygenase-2 inhibitory activity (IC 50 value 3.13 µg/mL and 5.05 µg/mL, respectively).

  15. Screening of selected indigenous plants of Cambodia for antiplasmodial activity.

    PubMed

    Hout, Sotheara; Chea, Aun; Bun, Sok-Siya; Elias, Riad; Gasquet, Monique; Timon-David, Pierre; Balansard, Guy; Azas, Nadine

    2006-08-11

    The in vitro antiplasmodial activity of 117 aqueous, methanol and dichloromethane extracts derived from different parts of 28 indigenous wild plant species was studied. These plants are commonly used in Cambodian traditional medicine. The plant extracts were tested for in vitro activity against a chloroquine resistant Plasmodium falciparum strain (W2). Nine extracts were moderately active with IC(50) values ranging between 5 and 10 microg/ml, 17 extracts were active with IC(50) values ranging between 1 and 5 microg/ml. These 26 extracts derived from eight plants belong to six families. The most active extracts were dichloromethane and came from Stephania rotunda and Brucea javanica with IC(50) values of 1 microg/ml and a selectivity index > or = 25. It is interesting to note that some aqueous extracts were as active as dichloromethane extracts especially aqueous extracts of Stephania rotunda, Brucea javanica, Phyllanthus urinaria and Eurycoma longifolia with IC(50) values of < or = 4 microg/ml. These results are in agreement with statements of healers on traditional uses of these plants for the treatment of malaria and/or fever. In this study, we report the antiplasmodial potential activity of eight plant species from Cambodia. Among them four are tested for the first time.

  16. Antioxidant and Anti-Inflammatory Activities of Hydrolysates and Peptide Fractions Obtained by Enzymatic Hydrolysis of Selected Heat-Treated Edible Insects

    PubMed Central

    Zielińska, Ewelina; Baraniak, Barbara; Karaś, Monika

    2017-01-01

    This study investigated the effect of heat treatment of edible insects on antioxidant and anti-inflammatory activities of peptides obtained by in vitro gastrointestinal digestion and absorption process thereof. The antioxidant potential of edible insect hydrolysates was determined as free radical-scavenging activity, ion chelating activity, and reducing power, whereas the anti-inflammatory activity was expressed as lipoxygenase and cyclooxygenase-2 inhibitory activity. The highest antiradical activity against DPPH• (2,2-diphenyl-1-picrylhydrazyl radical) was noted for a peptide fraction from baked cricket Gryllodes sigillatus hydrolysate (IC50 value 10.9 µg/mL) and that against ABTS•+ (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical) was the highest for raw mealworm Tenebrio molitor hydrolysate (inhibitory concentration (IC50 value) 5.3 µg/mL). The peptides obtained from boiled locust Schistocerca gregaria hydrolysate showed the highest Fe2+ chelation ability (IC50 value 2.57 µg/mL); furthermore, the highest reducing power was observed for raw G. sigillatus hydrolysate (0.771). The peptide fraction from a protein preparation from the locust S. gregaria exhibited the most significant lipoxygenase and cyclooxygenase-2 inhibitory activity (IC50 value 3.13 µg/mL and 5.05 µg/mL, respectively). PMID:28869499

  17. Dexmedetomidine reduces pain associated with rocuronium injection without causing a decrease in BIS values: a dose-response study.

    PubMed

    Joo, Jin; Baek, Jungwon; Lee, Jaemin

    2014-09-01

    To examine whether dexmedetomidine reduces the injection pain of propofol and rocuronium and to investigate whether the decrease in injection pain is associated with the known sedative action of dexmedetomidine. Randomized, double-blind, placebo-controlled clinical comparison study. Patients undergoing general anesthesia with intubation received 40 mg of 1% lidocaine (lidocaine group; n = 28), 0.25 μg/kg of dexmedetomidine (low-dose group; n = 27), 0.5 μg/kg of dexmedetomidine (subclinical dose group; n = 28), 1.0 μg/kg of dexmedetomidine (clinical dose group, n = 27), or normal saline (saline group; n = 28) before anesthetic induction. Pain associated with propofol and rocuronium injection was assessed using a 10-point verbal analog scale (VAS) and a 4-point withdrawal movement scale, respectively. The BIS value was measured 60 seconds after administration of the study drug, and at the time of rocuronium injection and intubation. The overall incidence of withdrawal movements due to rocuronium decreased significantly as the dose of dexmedetomidine increased (92.8%, 85.2%, 78.6%, and 51.9% in the saline, low-dose, subclinical dose, and clinical dose groups, respectively; P = 0.001). There was no significant difference in BIS values among the groups 60 seconds after study drug administration or at the time of rocuronium injection. Dexmedetomidine reduced pain associated with rocuronium injection in a dose-dependent manner. This effect was not associated with the decrease in BIS value. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. IC 5181: An S0 Galaxy with Ionized Gas on Polar Orbits

    NASA Astrophysics Data System (ADS)

    Pizzella, A.; Morelli, L.; Corsini, E. M.; Dalla Bontá, E.; Cesetti, M.

    2014-05-01

    The nearby S0 galaxy IC 5181 is studied to address the origin of the ionized gas component that orbits the galaxy on polar orbit. We perform detailed photometric and spectroscopic observations measuring the surface brightness distribution of the stars (I band), ionized gas of IC 5181 (Hα narrow band), the ionized-gas and stellar kinematics along both the major and minor axis, and the corresponding line strengths of the Lick indices. We conclude that the galaxy hosts a geometrically and kinematically decoupled component of ionized gas. It is elongated along the galaxy minor axis and in orthogonal rotation with respect to the galaxy disk. The result is suggesting that the gas component is not related to the stars having an external origin. The gas was accreted by IC 5181 on polar orbits from the surrounding environment.

  19. 30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation changes...

  20. 30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation changes...

  1. Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors.

    PubMed

    Kia, Yalda; Osman, Hasnah; Suresh Kumar, Raju; Basiri, Alireza; Murugaiyah, Vikneswaran

    2014-04-01

    Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 μM, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 μM, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Neopetrosiquinones A and B, sesquiterpene benzoquinones isolated from the deep-water sponge Neopetrosia cf. proxima.

    PubMed

    Winder, Priscilla L; Baker, Heather L; Linley, Patricia; Guzmán, Esther A; Pomponi, Shirley A; Diaz, M Cristina; Reed, John K; Wright, Amy E

    2011-11-15

    Two new marine-derived sesquiterpene benzoquinones which we designate as neopetrosiquinones A (1) and B (2), have been isolated from a deep-water sponge of the family Petrosiidae. The structures were elucidated on the basis of their spectroscopic data. Compounds 1 and 2 inhibit the in vitro proliferation of the DLD-1 human colorectal adenocarcinoma cell line with IC(50) values of 3.7 and 9.8 μM, respectively, and the PANC-1 human pancreatic carcinoma cell line with IC(50) values of 6.1 and 13.8 μM, respectively. Neopetrosiquinone A (1) also inhibited the in vitro proliferation of the AsPC-1 human pancreatic carcinoma cell line with an IC(50) value of 6.1 μM. The compounds are structurally related to alisiaquinone A, cyclozonarone, and xestoquinone. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. First detection of 3He+ in the planetary nebula IC 418

    NASA Astrophysics Data System (ADS)

    Guzman-Ramirez, L.; Rizzo, J. R.; Zijlstra, A. A.; García-Miró, C.; Morisset, C.; Gray, M. D.

    2016-07-01

    The 3He isotope is important to many fields of astrophysics, including stellar evolution, chemical evolution, and cosmology. The isotope is produced in low-mass stars which evolve through the planetary nebula (PN) phase. 3He abundances in PNe can help test models of the chemical evolution of the Galaxy. We present the detection of the 3He+ emission line using the single dish Deep Space Station 63, towards the PN IC 418. We derived a 3He/H abundance in the range 1.74 ± 0.8 × 10-3 to 5.8 ± 1.7 × 10-3, depending on whether part of the line arises in an outer ionized halo. The lower value for 3He/H ratio approaches values predicted by stellar models which include thermohaline mixing, but requires that large amounts of 3He are produced inside low-mass stars which enrich the interstellar medium (ISM). However, this overpredicts the 3He abundance in H II regions, the ISM, and protosolar grains, which is known to be of the order of 10-5. This discrepancy questions our understanding of the evolution of the 3He, from circumstellar environments to the ISM.

  4. BCH codes for large IC random-access memory systems

    NASA Technical Reports Server (NTRS)

    Lin, S.; Costello, D. J., Jr.

    1983-01-01

    In this report some shortened BCH codes for possible applications to large IC random-access memory systems are presented. These codes are given by their parity-check matrices. Encoding and decoding of these codes are discussed.

  5. Publications - IC 54 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 54 Publication Details Title: Alaska's mineral industry 2006: A summary Authors: Szumigala, D.J Bibliographic Reference Szumigala, D.J., and Hughes, R.A., 2007, Alaska's mineral industry 2006: A summary

  6. Properties of the molecular gas in the fast outflow in the Seyfert galaxy IC 5063

    NASA Astrophysics Data System (ADS)

    Oosterloo, Tom; Raymond Oonk, J. B.; Morganti, Raffaella; Combes, Françoise; Dasyra, Kalliopi; Salomé, Philippe; Vlahakis, Nektarios; Tadhunter, Clive

    2017-12-01

    We present a detailed study of the properties of the molecular gas in the fast outflow driven by the active galactic nucleus (AGN) in the nearby radio-loud Seyfert galaxy IC 5063. By using ALMA observations of a number of tracers of the molecular gas (12CO(1-0), 12CO(2-1), 12CO(3-2), 13CO(2-1) and HCO+(4-3)), we map the differences in excitation, density and temperature of the gas as function of position and kinematics. The results show that in the immediate vicinity of the radio jet, a fast outflow, with velocities up to 800 km s-1, is occurring of which the gas has high excitation with excitation temperatures in the range 30-55 K, demonstrating the direct impact of the jet on the ISM. The relative brightness of the 12CO lines, as well as that of 13CO(2-1) vs. 12CO(2-1), show that the outflow is optically thin. We estimate the mass of the molecular outflow to be at least 1.2 × 106 M⊙ and likely to be a factor between two and three larger than this value. This is similar to that of the outflow of atomic gas, but much larger than that of the ionised outflow, showing that the outflow in IC 5063 is dominated by cold gas. The total mass outflow rate we estimated to be 12 M⊙ yr-1. The mass of the outflow is much smaller than the total gas mass of the ISM of IC 5063. Therefore, although the influence of the AGN and its radio jet is very significant in the inner regions of IC 5063, globally speaking the impact will be very modest. We used RADEX non-LTE modelling to explore the physical conditions of the molecular gas in the outflow. Models with the outflowing gas being quite clumpy give the most consistent results and our preferred solutions have kinetic temperatures in the range 20-100 K and densities between 105 and 106 cm-3. The resulting pressures are 106-107.5 K cm-3, about two orders of magnitude higher than in the outer quiescent disk. The highest densities and temperatures are found in the regions with the fastest outflow. The results strongly suggest that

  7. Forearm muscle oxygenation decreases with low levels of voluntary contraction

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Kahan, N. J.; Hargens, A. R.; Rempel, D. M.

    1997-01-01

    The purpose of our investigation was to determine if the near infrared spectroscopy technique was sensitive to changes in tissue oxygenation at low levels of isometric contraction in the extensor carpi radialis brevis muscle. Nine subjects were seated with the right arm abducted to 45 degrees, elbow flexed to 85 degrees, forearm pronated 45 degrees, and wrist and forearm supported on an armrest throughout the protocol. Altered tissue oxygenation was measured noninvasively with near infrared spectroscopy. The near infrared spectroscopy probe was placed over the extensor carpi radialis brevis of the subject's right forearm and secured with an elastic wrap. After 1 minute of baseline measurements taken with the muscle relaxed, four different loads were applied just proximal to the metacarpophalangeal joint such that the subjects isometrically contracted the extensor carpi radialis brevis at 5, 10, 15, and 50% of the maximum voluntary contraction for 1 minute each. A 3-minute recovery period followed each level of contraction. At the end of the protocol, with the probe still in place, a value for ischemic tissue oxygenation was obtained for each subject. This value was considered the physiological zero and hence 0% tissue oxygenation. Mean tissue oxygenation (+/-SE) decreased from resting baseline (100% tissue oxygenation) to 89 +/- 4, 81 +/- 8, 78 +/- 8, and 47 +/- 8% at 5, 10, 15, and 50% of the maximum voluntary contraction, respectively. Tissue oxygenation levels at 10, 15, and 50% of the maximum voluntary contraction were significantly lower (p < 0.05) than the baseline value. Our results indicate that tissue oxygenation significantly decreases during brief, low levels of static muscle contraction and that near infrared spectroscopy is a sensitive technique for detecting deoxygenation noninvasively at low levels of forearm muscle contraction. Our findings have important implications in occupational medicine because oxygen depletion induced by low levels of muscle

  8. Antiproliferative Activity of Xanthones Isolated from Artocarpus obtusus

    PubMed Central

    Hashim, Najihah Mohd; Rahmani, Mawardi; Ee, Gwendoline Cheng Lian; Sukari, Mohd Aspollah; Yahayu, Maizatulakmal; Oktima, Winda; Ali, Abd Manaf; Go, Rusea

    2012-01-01

    An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC50 values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC50 values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC50 values of more than 30 μg/mL. PMID:21960741

  9. Hypoxia affects cellular responses to plant extracts.

    PubMed

    Liew, Sien-Yei; Stanbridge, Eric J; Yusoff, Khatijah; Shafee, Norazizah

    2012-11-21

    Microenvironmental conditions contribute towards varying cellular responses to plant extract treatments. Hypoxic cancer cells are known to be resistant to radio- and chemo-therapy. New therapeutic strategies specifically targeting these cells are needed. Plant extracts used in Traditional Chinese Medicine (TCM) can offer promising candidates. Despite their widespread usage, information on their effects in hypoxic conditions is still lacking. In this study, we examined the cytotoxicity of a series of known TCM plant extracts under normoxic versus hypoxic conditions. Pereskia grandifolia, Orthosiphon aristatus, Melastoma malabathricum, Carica papaya, Strobilanthes crispus, Gynura procumbens, Hydrocotyle sibthorpioides, Pereskia bleo and Clinacanthus nutans leaves were dried, blended into powder form, extracted in methanol and evaporated to produce crude extracts. Human Saos-2 osteosarcoma cells were treated with various concentrations of the plant extracts under normoxia or hypoxia (0.5% oxygen). 24h after treatment, an MTT assay was performed and the IC(50) values were calculated. Effect of the extracts on hypoxia inducible factor (HIF) activity was evaluated using a hypoxia-driven firefly luciferase reporter assay. The relative cytotoxicity of each plant extract on Saos-2 cells was different in hypoxic versus normoxic conditions. Hypoxia increased the IC(50) values for Pereskia grandifola and Orthosiphon aristatus extracts, but decreased the IC(50) values for Melastoma malabathricum and Carica papaya extracts. Extracts of Strobilanthes crispus, Gynura procumbens, Hydrocotyle sibthorpioides had equivalent cytotoxic effects under both conditions. Pereskia bleo and Clinacanthus nutans extracts were not toxic to cells within the concentration ranges tested. The most interesting result was noted for the Carica papaya extract, where its IC(50) in hypoxia was reduced by 3-fold when compared to the normoxic condition. This reduction was found to be associated with HIF

  10. An abundance study of IC 418 using high-resolution, signal-to-noise emission spectra

    NASA Astrophysics Data System (ADS)

    Sharpee, Brian David

    2003-11-01

    there is no evidence in our data that either process is responsible for the observed overabundances in all recombination lines as opposed to their collisionally excited counterparts. The calculated levels of temperature fluctuations in the zones in which these ion reside are dubious, and significantly exceed model predicted values. In summary, no satisfactory, single universally applicable answer to the abundance discrepancy problem shown to exist by us in IC 418, is revealed by our observations. We developed several new techniques to analyze these data. Of particular interest is EMILI (Emission Line Identifier), a public-domain program that utilizes a comprehensive atomic transition list and a set of simple tests and criteria, to quickly provide its user with a list of rank ordered IDs for unidentified emission lines found in deep, high resolution spectra. Presented here are the results of applying EMILI to the identification of weak emission lines in the spectra of IC 418 and other PNe.

  11. A New Interface for the Magnetics Information Consortium (MagIC) Paleo and Rock Magnetic Database

    NASA Astrophysics Data System (ADS)

    Jarboe, N.; Minnett, R.; Koppers, A. A. P.; Tauxe, L.; Constable, C.; Shaar, R.; Jonestrask, L.

    2014-12-01

    The Magnetic Information Consortium (MagIC) database (http://earthref.org/MagIC/) continues to improve the ease of uploading data, the creation of complex searches, data visualization, and data downloads for the paleomagnetic, geomagnetic, and rock magnetic communities. Data uploading has been simplified and no longer requires the use of the Excel SmartBook interface. Instead, properly formatted MagIC text files can be dragged-and-dropped onto an HTML 5 web interface. Data can be uploaded one table at a time to facilitate ease of uploading and data error checking is done online on the whole dataset at once instead of incrementally in an Excel Console. Searching the database has improved with the addition of more sophisticated search parameters and with the ability to use them in complex combinations. Searches may also be saved as permanent URLs for easy reference or for use as a citation in a publication. Data visualization plots (ARAI, equal area, demagnetization, Zijderveld, etc.) are presented with the data when appropriate to aid the user in understanding the dataset. Data from the MagIC database may be downloaded from individual contributions or from online searches for offline use and analysis in the tab delimited MagIC text file format. With input from the paleomagnetic, geomagnetic, and rock magnetic communities, the MagIC database will continue to improve as a data warehouse and resource.

  12. EI-2128-1, a novel interleukin-1beta converting enzyme inhibitor produced by Penicillium sp. E-2128.

    PubMed

    Koizumi, Fumito; Agatsuma, Tsutomu; Ando, Katsuhiko; Kondo, Hidemasa; Saitoh, Yutaka; Matsuda, Yuzuru; Nakanishi, Satoshi

    2003-11-01

    EI-2128-1, a novel interleukin-1beta converting enzyme (ICE) inhibitor, was isolated from the culture broths of Penicillium sp. E-2128. EI-2128-1 selectively inhibited human recombinant ICE activity with IC50 value of 0.59 microM, without inhibiting elastase and cathepsin B. EI-2128-1 also inhibited mature interleukin-1beta secretion from THP-1 cells induced by LPS with IC50 value of 0.28 microM.

  13. Construction Progress of the S-IC Test Stand-Steel Reinforcements

    NASA Technical Reports Server (NTRS)

    1961-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 15, 1961, shows the installation of the reinforcing steel prior to the pouring of the concrete foundation walls.

  14. Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening.

    PubMed

    Castillo-Garit, Juan Alberto; del Toro-Cortés, Oremia; Vega, Maria C; Rolón, Miriam; Rojas de Arias, Antonieta; Casañola-Martin, Gerardo M; Escario, José A; Gómez-Barrio, Alicia; Marrero-Ponce, Yovani; Torrens, Francisco; Abad, Concepción

    2015-01-01

    Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bond-based bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Both models show a good agreement between theoretical predictions and experimental results. Three compounds showed IC50 values for epimastigote elimination (AE) lower than 50 μM, while for the benznidazole the IC50 = 54.7 μM which was used as reference compound. The value of IC50 for cytotoxicity of these compounds is at least 5 times greater than their value of IC50 for AE. Finally, we can say that, the present algorithm constitutes a step forward in the search for efficient ways of discovering new antitrypanosomal compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Inhibitory Effects of Commonly Used Herbal Extracts on UDP-Glucuronosyltransferase 1A4, 1A6, and 1A9 Enzyme Activities

    PubMed Central

    Mohamed, Mohamed-Eslam F.

    2011-01-01

    The aim of this study was to investigate the effect of commonly used botanicals on UDP-glucuronosyltransferase (UGT) 1A4, UGT1A6, and UGT1A9 activities in human liver microsomes. The extracts screened were black cohosh, cranberry, echinacea, garlic, ginkgo, ginseng, milk thistle, saw palmetto, and valerian in addition to the green tea catechin epigallocatechin gallate (EGCG). Formation of trifluoperazine glucuronide, serotonin glucuronide, and mycophenolic acid phenolic glucuronide was used as an index reaction for UGT1A4, UGT1A6, and UGT1A9 activities, respectively, in human liver microsomes. Inhibition potency was expressed as the concentration of the inhibitor at 50% activity (IC50) and the volume in which the dose could be diluted to generate an IC50-equivalent concentration [volume/dose index (VDI)]. Potential inhibitors were EGCG for UGT1A4, milk thistle for both UGT1A6 and UGT1A9, saw palmetto for UGT1A6, and cranberry for UGT1A9. EGCG inhibited UGT1A4 with an IC50 value of (mean ± S.E.) 33.8 ± 3.1 μg/ml. Milk thistle inhibited both UGT1A6 and UGT1A9 with IC50 values of 59.5 ± 3.6 and 33.6 ± 3.1 μg/ml, respectively. Saw palmetto and cranberry weakly inhibited UGT1A6 and UGT1A9, respectively, with IC50 values >100 μg/ml. For each inhibition, VDI was calculated to determine the potential of achieving IC50-equivalent concentrations in vivo. VDI values for inhibitors indicate a potential for inhibition of first-pass glucuronidation of UGT1A4, UGT1A6, and UGT1A9 substrates. These results highlight the possibility of herb-drug interactions through modulation of UGT enzyme activities. Further clinical studies are warranted to investigate the in vivo extent of the observed interactions. PMID:21632963

  16. Characterization and antioxidative activities of rare C(50) carotenoids-sarcinaxanthin, sarcinaxanthin monoglucoside, and sarcinaxanthin diglucoside-obtained from Micrococcus yunnanensis.

    PubMed

    Osawa, Ayako; Ishii, Yoko; Sasamura, Nao; Morita, Marie; Kasai, Hiroaki; Maoka, Takashi; Shindo, Kazutoshi

    2010-01-01

    While screening for antioxidative carotenoids from marine bacteria, we isolated and identified sarcinaxanthin and its glucosylated compounds (sarcinaxanthin monoglucoside and sarcinaxanthin diglucoside) from a moderately halophilic bacterium-Micrococcus yunnanensis strain AOY-1. In the singlet oxygen ((¹O₂) quenching model, the IC(50) values of the antioxidative activities of these carotenoids were as follows: sarcinaxanthin , 57 µM; sarcinaxanthin monoglucoside, 54 µM; and sarcinaxanthin diglucoside, 74 µM. In addition, the complete proton nuclear magnetic resonance (¹H NMR) assignments of sarcinaxanthin monoglucoside pentaacetate and sarcinaxanthin diglucoside octaacetate, and fast atom bombardment mass spectrometry/mass spectrometry (FAB-MS/MS) analyses of sarcinaxanthin and sarcinaxanthin monoglucoside are reported for the first time.

  17. Metabolism of the tropine indole-3-carboxylate ICS 205-930 by differentiated rat and human hepatoma cells.

    PubMed

    Fischer, V; Baldeck, J P; Wiebel, F J

    The metabolism of the tropine indole-3-carboxylate ICS 205-930 (ICS), a highly potent and selective antagonist of 5-HT3 receptors, was investigated in continuous cell lines derived from rat or human liver and compared to the in vivo metabolism in rat and human. The well-differentiated rat hepatoma line 2sFou extensively metabolized ICS by hydroxylation of the indole moiety and subsequent conjugation to form the corresponding glucuronides and sulfates. The 2sFou cells also oxidized ICS at the tropinyl moiety to form both N-demethyl and N-oxide derivatives. The relative amount of the various metabolites was dependent on the substrate concentration. Pretreatment of the cells with dexamethasone increased the rate of metabolism for all pathways, while benz[a]anthracene caused an increase in hydroxylation at the indole moiety at the expense of N-oxidation. Phenobarbital pretreatment had no effect on ICS metabolism. The pattern of metabolites formed in 2sFou cells was qualitatively similar to that formed in rat urine. The human hepatoma line HepG2 metabolized ICS only to a small extent. The HepG2 cells failed to form detectable amounts of ICS conjugates found in human urine. The N-oxide-ICS was not found in HepG2 cells or in human urine. Virtually no ICS metabolites were found in human lung adenocarcinoma lines NCI-H358 or NCI-H322. The results suggest that continuous cell lines such as the differentiated rat hepatoma cells 2sFou might be used to mimic the metabolism of xenobiotics in rat and to clarify their complex metabolic pathways.

  18. Leveraging family values to decrease unhealthy alcohol use in aging Latino day laborers.

    PubMed

    del Pino, Homero E; Méndez-Luck, Carolyn; Bostean, Georgiana; Ramírez, Karina; Portillo, Marlom; Moore, Alison A

    2013-10-01

    In one Los Angeles study, 20 % of day laborers reported excessive drinking. Older adults are more sensitive to alcohol's effects, yet heavy drinking persists among Latinos until they are in their 60s. No interventions to reduce heavy drinking exist for aging day laborers. We recruited 14 day laborers aged 50 and older in Los Angeles. We identified their unhealthy alcohol use behaviors and comorbidities and conducted semi-structured interviews to understand their perceptions of unhealthy alcohol use. We found social disadvantages and conditions exacerbated by alcohol use, like depression. Participants were concerned with dying and premature aging, and reported that family could influence behavior change. An intervention should consider (1) integrating family values and (2) increasing knowledge about alcohol use and comorbidities. Further studies are needed to explore family influence on aging Latino day laborers.

  19. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Lane, H. W.; Stuart, C. A.; Davis-Street, J.; Wolfe, R. R.

    1996-01-01

    We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

  20. Molecular target of decursins in the inhibition of lipid droplet accumulation in macrophages.

    PubMed

    Ohshiro, Taichi; Namatame, Ichiji; Lee, Eun Woo; Kawagishi, Hirokazu; Tomoda, Hiroshi

    2006-05-01

    During screening for inhibitors of lipid droplet accumulation in mouse peritoneal macrophages, two coumarins identified as decursin and decursinol angelate were isolated from the roots of Angelicae gigantis. The cellular molecular target of these inhibitors in macrophages was studied. Decursin and decursinol angelate inhibited cholesteryl ester (CE) synthesis with IC50 values of 9.7 and 10.1 microM, respectively, whereas they enhanced triacylglycerol (TG) synthesis. Lysosomal metabolism of cholesterol to CE was inhibited by the compounds, indicating that the site of inhibition is one of the steps between the exiting of cholesterol from the lysosomes and CE synthesis in the endoplasmic reticulum. Therefore, acyl-CoA:cholesterol acyltransferase (ACAT) activity in the microsomal fractions prepared from mouse macrophages was studied, and the results showed inhibition of this activity by decursin and decursinol angelate with IC50 values of 43 and 22 microM, respectively. Thus, it was concluded that the compounds inhibit macrophage ACAT activity to decrease CE synthesis, leading to a reduction of lipid droplets in macrophages.

  1. Publications - IC 42 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 42 Publication Details Title: Alaska's mineral industry 1996: A summary Authors: Swainbank, R.C ., Bundtzen, T.K., Clough, A.H., and Henning, M.W., 1997, Alaska's mineral industry 1996: A summary: Alaska

  2. Classification of PSN J12015272-1852183 as a young type Ic SN

    NASA Astrophysics Data System (ADS)

    Harutyunyan, A.; Benetti, S.; Pastorello, A.; Cappellaro, E.; Tomasella, L.; Ochner, P.; Turatto, M.

    2013-06-01

    We report the spectroscopic classification (range 335-785 nm; resolution 1.5 nm) of PSN J12015272-1852183 discovered by the CHASE project on June 22.12 UT. The spectrogram obtained on June 23.88 UT with the TNG Telescope (+Dolores), shows that this is a type-Ic supernova. A good match is found with the type-Ic supernova 1994I (Millard et al 1999, ApJ 527, 746) at about six days before maximum light.

  3. Characterization of poly(allylamine) as a polymeric ligand for ion-exchange protein chromatography.

    PubMed

    Li, Ming; Li, Yanying; Yu, Linling; Sun, Yan

    2017-02-24

    This work reports poly(allylamine) (PAA), as a polymeric ion-exchange ligand for protein chromatography. Sepharose FF was modified with PAA, and six anion exchangers with ionic capacities (ICs) from 165 to 618mmol/L were prepared. Inverse size exclusion chromatography, adsorption equilibrium, uptake kinetics and column elution were performed. It was found that both the adsorption capacity and effective diffusivity maintained low values in the IC range of 165-373mmol/L, but they started to increase beyond 373mmol/L, and increased by 80% and 23 times, respectively, when the IC reached 618mmol/L. Interestingly, a drastic decrease of pore size was observed around the IC of 373mmol/L. The results suggest that the PAA chains played an important role in protein adsorption by altering the inner pore structure of the gels. It is considered that, PAA chains turn from inextensible states with multipoint-grafting on the pore surface at low coupling densities (IC<373mmol/L) to closer, extended and flexible grafting states with less coupling points at higher coupling densities (IC>373mmol/L). These characters of the grafted chains at higher IC values benefit in protein adsorption by three-dimensional binding and encouraged the happening of "chain delivery" of bound proteins on the chains. Besides, the ion exchangers showed favorable adsorption and uptake properties in a wide ionic strength range, 0-500mmol/L NaCl, indicating much better salt tolerance feature than the so-far reported ion exchangers. Moreover, a mild condition of pH 5.0 offered effective recovery of bound proteins in elution chromatography. The results indicate that the PAA-based anion exchanger of a high IC value is promising for high-capacity protein chromatography dealing with feedstock of a wide range of ionic strengths. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Efficacy of intraoperative cell salvage in decreasing perioperative blood transfusion rates in first-time cardiac surgery patients: a retrospective study.

    PubMed

    Côté, Claudia L; Yip, Alexandra M; MacLeod, Jeffrey B; O'Reilly, Bill; Murray, Joshua; Ouzounian, Maral; Brown, Craig D; Forgie, Rand; Pelletier, Marc P; Hassan, Ansar

    2016-09-01

    Evidence regarding the safety and efficacy of intraoperative cell salvage (ICS) in transfusion reduction during cardiac surgery remains conflicting. We sought to evaluate the impact of routine ICS on outcomes following cardiac surgery. We conducted a retrospective analysis of patients who underwent nonemergent, first-time cardiac surgery 18 months before and 18 months after the implementation of routine ICS. Perioperative transfusion rates, postoperative bleeding, clinical and hematological outcomes, and overall cost were examined. We used multivariable logistic regression modelling to determine the risk-adjusted effect of ICS on likelihood of perioperative transfusion. A total of 389 patients formed the final study population (186 undergoing ICS and 203 controls). Patients undergoing ICS had significantly lower perioperative transfusion rates of packed red blood cells (pRBCs; 33.9% v. 45.3% p = 0.021), coagulation products (16.7% v. 32.5% p < 0.001) and any blood product (38.2% v. 52.7%, p = 0.004). Patients receiving ICS had decreased mediastinal drainage at 12 h (mean 320 [range 230-550] mL v. mean 400 [range 260-690] mL, p = 0.011) and increased postoperative hemoglobin (mean 104.7 ± 13.2 g/L v. 95.0 ± 11.9 g/L, p < 0.001). Following adjustment for other baseline and intraoperative covariates, ICS emerged as an independent predictor of lower perioperative transfusion rates of pRBCs (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31-0.87), coagulation products (OR 0.41, 95% CI 0.24-0.71) and any blood product (OR 0.47, 95% CI 0.29-0.77). Additionally, ICS was associated with a cost benefit of $116 per patient. Intraoperative cell salvage could represent a clinically cost-effective way of reducing transfusion rates in patients undergoing cardiac surgery. Further research on systematic ICS is required before recommending it for routine use.

  5. The Iron-Responsive Fur/RyhB Regulatory Cascade Modulates the Shigella Outer Membrane Protease IcsP ▿ †

    PubMed Central

    Africa, Lia A. A.; Murphy, Erin R.; Egan, Nicholas R.; Wigley, Amanda F.; Wing, Helen J.

    2011-01-01

    Actin-based motility is central to the pathogenicity of the intracellular bacterial pathogen Shigella. Two Shigella outer membrane proteins, IcsA and IcsP, are required for efficient actin-based motility in the host cell cytoplasm, and the genes encoding both proteins are carried on the large virulence plasmid. IcsA triggers actin polymerization on the surface of the bacterium, leading to the formation of an actin tail that allows both intra- and intercellular spread. IcsP, an outer membrane protease, modulates the amount and distribution of the IcsA protein on the bacterial surface through proteolytic cleavage of IcsA. Transcription of icsP is increased in the presence of VirB, a DNA-binding protein that positively regulates many genes carried on the large virulence plasmid. In Shigella dysenteriae, the small regulatory RNA RyhB, which is a member of the iron-responsive Fur regulon, suppresses several virulence-associated phenotypes by downregulating levels of virB in response to iron limitation. Here we show that the Fur/RyhB regulatory pathway downregulates IcsP levels in response to low iron concentrations in Shigella flexneri and that this occurs at the level of transcription through the RyhB-dependent regulation of VirB. These observations demonstrate that in Shigella species the Fur/RyhB regulatory pathway provides a mechanism to finely tune the expression of icsP in response to the low concentrations of free iron predicted to be encountered within colonic epithelial cells. PMID:21859852

  6. Installation of C-6533(XE-2)/ARC ICS in UH-1H helicopter

    NASA Astrophysics Data System (ADS)

    Hnat, J. A.

    1980-07-01

    This report documents the results of the installation of the C-6533(XE-2)/ARC ICS in UH-1H helicopter. Installation was performed at the AEL, Inc., Monmouth County Airport facility. Design of each installation was coordinated and approved by the Government. The mechanical and electrical installation drawings for the helicopter are attached as Appendix A of this report. The new ICS system consisted of new cabling, new intercoms and helmets rewired with new microphones. All four crew stations of the helicopter were reconfigured with the new system. Existing cabling for the standard ICS system remained in the aircraft but was securely stowed for later restoration of the aircraft. The helmets (4) were rewired using separate jacks for headphones and microphone lines. Transmit and receive cables were installed in the aircraft with a minimum separation of one inch between cables. A junction box was fabricated and installed on the aft end of the console to house the fan-out terminal strips. Transmit and receive lines' separation was maintained in the junction box. During the test phase the onboard radios were used with the new ICS system.

  7. SN 2017dio: A Type-Ic Supernova Exploding in a Hydrogen-rich Circumstellar Medium

    NASA Astrophysics Data System (ADS)

    Kuncarayakti, Hanindyo; Maeda, Keiichi; Ashall, Christopher J.; Prentice, Simon J.; Mattila, Seppo; Kankare, Erkki; Fransson, Claes; Lundqvist, Peter; Pastorello, Andrea; Leloudas, Giorgos; Anderson, Joseph P.; Benetti, Stefano; Bersten, Melina C.; Cappellaro, Enrico; Cartier, Régis; Denneau, Larry; Della Valle, Massimo; Elias-Rosa, Nancy; Folatelli, Gastón; Fraser, Morgan; Galbany, Lluís; Gall, Christa; Gal-Yam, Avishay; Gutiérrez, Claudia P.; Hamanowicz, Aleksandra; Heinze, Ari; Inserra, Cosimo; Kangas, Tuomas; Mazzali, Paolo; Melandri, Andrea; Pignata, Giuliano; Rest, Armin; Reynolds, Thomas; Roy, Rupak; Smartt, Stephen J.; Smith, Ken W.; Sollerman, Jesper; Somero, Auni; Stalder, Brian; Stritzinger, Maximilian; Taddia, Francesco; Tomasella, Lina; Tonry, John; Weiland, Henry; Young, David R.

    2018-02-01

    SN 2017dio shows both spectral characteristics of a type-Ic supernova (SN) and signs of a hydrogen-rich circumstellar medium (CSM). Prominent, narrow emission lines of H and He are superposed on the continuum. Subsequent evolution revealed that the SN ejecta are interacting with the CSM. The initial SN Ic identification was confirmed by removing the CSM interaction component from the spectrum and comparing with known SNe Ic and, reversely, adding a CSM interaction component to the spectra of known SNe Ic and comparing them to SN 2017dio. Excellent agreement was obtained with both procedures, reinforcing the SN Ic classification. The light curve constrains the pre-interaction SN Ic peak absolute magnitude to be around {M}g=-17.6 mag. No evidence of significant extinction is found, ruling out a brighter luminosity required by an SN Ia classification. These pieces of evidence support the view that SN 2017dio is an SN Ic, and therefore the first firm case of an SN Ic with signatures of hydrogen-rich CSM in the early spectrum. The CSM is unlikely to have been shaped by steady-state stellar winds. The mass loss of the progenitor star must have been intense, \\dot{M}∼ 0.02{({ε }{{H}α }/0.01)}-1 ({v}{wind}/500 km s‑1) ({v}{shock}/10,000 km s‑1)‑3 M ⊙ yr‑1, peaking at a few decades before the SN. Such a high mass-loss rate might have been experienced by the progenitor through eruptions or binary stripping. Based on observations made with the NOT, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This work is based (in part) on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO program 188.D-3003, 191.D-0935, 197.D-1075. Based on observations made with the Liverpool Telescope operated on the

  8. Recent Progress in Laboratory Astrophysics and Astrochemistry Achieved with the COSmIC Facility

    NASA Technical Reports Server (NTRS)

    Salama, Farid; Sciamma-O'Brien, Ella; Bejaoui, Salma

    2017-01-01

    We describe the characteristics and the capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory. COSmIC stands for "Cosmic Simulation Chamber" and is dedicated to the study of neutral and ionized molecules and nanoparticles under the low temperature and high vacuum conditions that are required to simulate various space environments such as diffuse interstellar clouds, circumstellar outflows and planetary atmospheres. COSmIC integrates a variety of state-of-the-art instruments that allow recreating simulated space conditions to generate, process and monitor cosmic analogs in the laboratory. The COSmIC experimental setup is composed of a Pulsed Discharge Nozzle (PDN) expansion, that generates a plasma in the stream of a free supersonic jet expansion, coupled to high-sensitivity, complementary in situ diagnostics: cavity ring down spectroscopy (CRDS) and laser induced fluorescence (LIF) systems for photonic detection, and Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection. Recent results obtained using COSmIC will be highlighted. In particular, the progress that has been achieved in the domain of the diffuse interstellar bands (DIBs) and in monitoring, in the laboratory, the formation of circumstellar dust grains and planetary atmosphere aerosols from their gas-phase molecular precursors. Plans for future laboratory experiments on interstellar and planetary molecules and grains will also be addressed, as well as the implications of the studies underway for astronomical observations and past and future space mission data analysis.

  9. Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors.

    PubMed

    Li, Yingjun; Yu, Yang; Jin, Kun; Gao, Lixin; Luo, Tongchuan; Sheng, Li; Shao, Xin; Li, Jia

    2014-09-01

    A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC50=1.18-8.01 μg/mL) and PTP1B (IC50=0.85-8.75 μg/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC50 values of 1.18 and 0.85 μg/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na3VO4 (IC50=0.93 μg/mL) and oleanolic acid (IC50=0.85 μg/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. High ESD Breakdown-Voltage InP HBT Transimpedance Amplifier IC for Optical Video Distribution Systems

    NASA Astrophysics Data System (ADS)

    Sano, Kimikazu; Nagatani, Munehiko; Mutoh, Miwa; Murata, Koichi

    This paper is a report on a high ESD breakdown-voltage InP HBT transimpedance amplifier IC for optical video distribution systems. To make ESD breakdown-voltage higher, we designed ESD protection circuits integrated in the TIA IC using base-collector/base-emitter diodes of InP HBTs and resistors. These components for ESD protection circuits have already existed in the employed InP HBT IC process, so no process modifications were needed. Furthermore, to meet requirements for use in optical video distribution systems, we studied circuit design techniques to obtain a good input-output linearity and a low-noise characteristic. Fabricated InP HBT TIA IC exhibited high human-body-model ESD breakdown voltages (±1000V for power supply terminals, ±200V for high-speed input/output terminals), good input-output linearity (less than 2.9-% duty-cycle-distortion), and low noise characteristic (10.7pA/√Hz averaged input-referred noise current density) with a -3-dB-down higher frequency of 6.9GHz. To the best of our knowledge, this paper is the first literature describing InP ICs with high ESD-breakdown voltages.

  11. The effects of immunological castration and corn dried distillers grains with solubles withdrawal on growth performance, carcass characteristics, fatty acid analysis, and iodine value of pork fat depots.

    PubMed

    Asmus, M D; Tavarez, M A; Tokach, M D; Dritz, S S; Schroeder, A L; Nelssen, J L; Goodband, R D; DeRouchey, J M

    2014-05-01

    A total of 1,360 pigs were used in a 125-d study to determine the effects of corn dried distillers grains with solubles (DDGS) withdrawal after immunological castration (Improvest, Zoetis, Kalamazoo, MI) on growth performance and carcass fat quality of pigs. Pens of male pigs (initially 24 kg) were randomly allotted by BW and castration method (physically castrated [PC] or immunologically castrated [IC] barrows) to 1 of 3 diets with 8 replications per treatment and 27 to 29 pigs per pen. Treatments were arranged in a 2 × 3 factorial with main effects of castration method and diet (0% DDGS throughout, 30% DDGS throughout, or 30% DDGS through d 75 then no DDGS to d 125). Intact males were injected with Improvest on d 39 and 74 (IC). No castration method × diet interactions (P > 0.12) were observed for growth performance. Before the second Improvest injection (d 0 to 74), PC barrows had increased (P < 0.05) ADFI but were less efficient (P < 0.05) than intact males. After the second Improvest injection until the first marketing event (d 74 to 107), IC barrows had improved (P < 0.05) ADG and G:F compared with PC barrows. From d 0 to 107, IC barrows had improved (P < 0.05) ADG, G:F, and lower ADFI than PC barrows. The inclusion of 30% DDGS decreased (P < 0.05) G:F compared with pigs fed the control diet. For the period after the second Improvest injection (d 74 to 125), IC barrows had increased (P < 0.05) ADG, ADFI, and G:F compared with PC barrows. Overall (d 0 to 125), IC barrows had improved (P < 0.05) ADG and G:F and lower ADFI than PC barrows. The inclusion of 30% DDGS decreased (P < 0.05) G:F. Carcass yield was lower (P < 0.05) for IC than PC barrows. Pigs fed 30% DDGS throughout had decreased (P < 0.05) carcass yield; however, withdrawing DDGS from the diet on d 74 was effective at fully recovering the yield loss. Carcass fat iodine values (IV) were consistently higher (P < 0.05), regardless of fat depot or harvest time when 30% DDGS were included in the diet

  12. Antitumor Activity and Induction of TP53-Dependent Apoptosis toward Ovarian Clear Cell Adenocarcinoma by the Dual PI3K/mTOR Inhibitor DS-7423

    PubMed Central

    Kashiyama, Tomoko; Oda, Katsutoshi; Ikeda, Yuji; Shiose, Yoshinobu; Hirota, Yasuhide; Inaba, Kanako; Makii, Chinami; Kurikawa, Reiko; Miyasaka, Aki; Koso, Takahiro; Fukuda, Tomohiko; Tanikawa, Michihiro; Shoji, Keiko; Sone, Kenbun; Arimoto, Takahide; Wada-Hiraike, Osamu; Kawana, Kei; Nakagawa, Shunsuke; Matsuda, Koichi; McCormick, Frank; Aburatani, Hiroyuki; Yano, Tetsu; Osuga, Yutaka; Fujii, Tomoyuki

    2014-01-01

    DS-7423, a novel, small-molecule dual inhibitor of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), is currently in phase I clinical trials for solid tumors. Although DS-7423 potently inhibits PI3Kα (IC50 = 15.6 nM) and mTOR (IC50 = 34.9 nM), it also inhibits other isoforms of class I PI3K (IC50 values: PI3Kβ = 1,143 nM; PI3Kγ = 249 nM; PI3Kδ = 262 nM). The PI3K/mTOR pathway is frequently activated in ovarian clear cell adenocarcinomas (OCCA) through various mutations that activate PI3K-AKT signaling. Here, we describe the anti-tumor effect of DS-7423 on a panel of nine OCCA cell lines. IC50 values for DS-7423 were <75 nM in all the lines, regardless of the mutational status of PIK3CA. In mouse xenograft models, DS-7423 suppressed the tumor growth of OCCA in a dose-dependent manner. Flow cytometry analysis revealed a decrease in S-phase cell populations in all the cell lines and an increase in sub-G1 cell populations following treatment with DS-7423 in six of the nine OCCA cell lines tested. DS-7423-mediated apoptosis was induced more effectively in the six cell lines without TP53 mutations than in the three cell lines with TP53 mutations. Concomitantly with the decreased phosphorylation level of MDM2 (mouse double minute 2 homolog), the level of phosphorylation of TP53 at Ser46 was increased by DS-7423 in the six cell lines with wild-type TP53, with induction of genes that mediate TP53-dependent apoptosis, including p53AIP1 and PUMA at 39 nM or higher doses. Our data suggest that the dual PI3K/mTOR inhibitor DS-7423 may constitute a promising molecular targeted therapy for OCCA, and that its antitumor effect might be partly obtained by induction of TP53-dependent apoptosis in TP53 wild-type OCCAs. PMID:24504419

  13. 20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

    EPA Science Inventory

    Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

  14. Revealing the nebular properties and Wolf-Rayet population of IC10 with Gemini/GMOS

    NASA Astrophysics Data System (ADS)

    Tehrani, Katie; Crowther, Paul A.; Archer, I.

    2017-12-01

    We present a deep imaging and spectroscopic survey of the Local Group irregular galaxy IC10 using Gemini North and GMOS to unveil its global Wolf-Rayet (WR) population. We obtain a star formation rate (SFR) of 0.045 ± 0.023 M⊙ yr-1, for IC10 from the nebular H α luminosity, which is comparable to the Small Magellanic Cloud. We also present a revised nebular oxygen abundance of log(O/H) + 12 = 8.40 ± 0.04, comparable to the LMC. It has previously been suggested that for IC10 to follow the WR subtype-metallicity dependance seen in other Local Group galaxies, a large WN population awaits discovery. Our search revealed three new WN stars, and six candidates awaiting confirmation, providing little evidence to support this claim. The new global WR star total of 29 stars is consistent with the Large Magellanic Cloud population when scaled to the reduced SFR of IC10. For spectroscopically confirmed WR stars, the WC/WN ratio is lowered to 1.0; however, including all potential candidates, and assuming those unconfirmed to be WN stars, would reduce the ratio to ∼0.7. We attribute the high WC/WN ratio to the high star formation surface density of IC10 relative to the Magellanic Clouds, which enhances the frequency of high-mass stars capable of producing WC stars.

  15. Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism.

    PubMed

    Mohamed, Elsnoussi Ali Hussin; Siddiqui, Mohammad Jamshed Ahmad; Ang, Lee Fung; Sadikun, Amirin; Chan, Sue Hay; Tan, Soo Choon; Asmawi, Mohd Zaini; Yam, Mun Fei

    2012-10-08

    In the present study, we tested a 50% ethanolic extract of Orthosiphon stamineus plants and its isolated bioactive compound with respect to their α-glucosidase and α-amylase inhibitory activities. Bioactive flavonoid sinensetin was isolated from 50% ethanolic extract of Orthosiphon stamineus. The structure of this pure compound was determined on the NMR data and the α-glucosidase and α-amylase inhibitory activities of isolated sinensetin and 50% ethanolic extract of Orthosiphon stamineus were evaluated. In vitro studies of a 50% ethanolic extract of O. stamineus and the isolated sinensetin compound showed inhibitory activity on α-glucosidase (IC50: 4.63 and 0.66 mg/ml, respectively) and α-amylase (IC50: 36.70 mg/ml and 1.13 mg/ml, respectively). Inhibition of these enzymes provides a strong biochemical basis for the management of type 2 diabetes via the control of glucose absorption. Alpha-glucosidase and α-amylase inhibition could the mechanisms through which the 50% ethanolic extract of O. stamineus and sinensetin exert their antidiabetic activity, indicating that it could have potential use in the management of non-insulin-dependent diabetes.

  16. Relocation of blood gas laboratory to the emergency department helps decrease lactic acid values.

    PubMed

    Brazg, Jared; Huang, Phyllis; Weiner, Corey; Singh, Guneet; Likourezos, Antonios; Salem, Linda; Dickman, Eitan; Marshall, John

    2018-03-20

    lactate values decreased when measured in an ED blood gas laboratory and may provide more accurate LA results than blood gas samples analyzed at an SL blood gas laboratory within the same institution. Hospitals may consider moving blood gas laboratories to the ED to improve accuracy of one of the most important early blood markers used in the definition of sepsis and in the identification of the critically ill. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Relocation of blood gas laboratory to the emergency department helps decrease lactic acid values.

    PubMed

    Brazg, Jared; Huang, Phyllis; Weiner, Corey; Singh, Guneet; Likourezos, Antonios; Salem, Linda; Dickman, Eitan; Marshall, John

    2018-03-12

    lactate values decreased when measured in an ED blood gas laboratory and may provide more accurate LA results than blood gas samples analyzed at an SL blood gas laboratory within the same institution. Hospitals may consider moving blood gas laboratories to the ED to improve accuracy of one of the most important early blood markers used in the definition of sepsis and in the identification of the critically ill. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Implications of a decrease in the precipitation area for the past and the future

    NASA Astrophysics Data System (ADS)

    Benestad, Rasmus E.

    2018-04-01

    The total area with 24 hrs precipitation has shrunk by 7% between 50°S–50°N over the period 1998–2016, according to the satellite-based Tropical Rain Measurement Mission data. A decrease in the daily precipitation area is an indication of profound changes in the hydrological cycle, where the global rate of precipitation is balanced by the global rate of evaporation. This decrease was accompanied by increases in total precipitation, evaporation, and wet-day mean precipitation. If these trends are real, then they suggest increased drought frequencies and more intense rainfall. Satellite records, however, may be inhomogeneous because they are synthesised from a number of individual missions with improved technology over time. A linear dependency was also found between the global mean temperature and the 50°S–50°N daily precipitation area with a slope value of ‑17 × 106 km 2/°C. This dependency was used with climate model simulations to make future projections which suggested a continued decrease that will strengthen in the future. The precipitation area evolves differently when the precipitation is accumulated over short and long time scales, however, and there has been a slight increase in the monthly precipitation area while the daily precipitation area decreased. An increase on monthly scale may indicate more pronounced variations in the rainfall patterns due to migrating rain-producing phenomena.

  19. The effects of dynamic compressive loading on biodegradable implants of 50-50% polylactic Acid-polyglycolic Acid.

    PubMed

    Thompson, D E; Agrawal, C M; Athanasiou, K

    1996-01-01

    Biodegradable implants that release growth factors or other bioactive agents in a controlled manner are investigated to enhance the repair of musculoskeletal tissues. In this study, the in vitro release characteristics and mechanical properties of a 50:50 polylactic acid/polyglycolic acid two phase implant were examined over a 6-week period under no-load conditions or under a cyclic compressive load, such as that experienced when walking slowly during rehabilitation. The results demonstrated that a cyclic compressive load significantly slows the decrease of molecular chain size during the first week, significantly increases protein release for the first 2-3 weeks, and significantly stiffens the implant for the first 3 weeks. It was also shown that protein release is initially high and steadily decreases with time until the molecular weight declines to about 20% of its original value (approximately 4 weeks). Once this threshold is reached, increased protein release, surface deformation, and mass loss occurs. This study also showed that dynamic loading and the environment in which an implant is placed affect its biodegradation. Therefore, it may be essential that in vitro degradation studies of these or similar implants include a dynamic functional environment.

  20. Cytotoxic constituents of propolis from Myanmar and their structure-activity relationship.

    PubMed

    Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

    2009-12-01

    Thirteen cycloartane-type tritepenes (1-13) and four prenylated flavanones (14-17) isolated from propolis collected in Myanmar, were evaluated for their cytotoxic activity against a panel of six different cancer cell lines; three murine cancer cell lines (colon 26-L5 carcinoma, B16-BL6 melanoma, and Lewis lung carcinoma) and three human cancer cell lines (lung A549 adenocarcinoma, cervix HeLa adenocarcinoma and HT-1080 fibrosarcoma). Among them, a cycloartane-type triterpene, 3alpha,27-dihydroxycycloart-24E-en-26-oic acid (3), showed the most potent cytotoxicity against B16-BL6 cells with an IC(50) value of 5.91 microM, comparable to those of positive controls, doxorubicin (IC(50), 5.66 microM) and 5-fluorouracil (IC(50), 4.88 microM). In addition, (2S)-5,7-dihydroxy-4'-methoxy-8,3'-diprenylflavanone (14) exhibited strong cytotoxicity against all the tested cancer cell lines with the IC(50) values ranging from 14.0 to 26.4 microM. Based on the observed results, the structure-activity relationships are discussed.

  1. Phytochemical profile and biological activities of Deverra tortuosa (Desf.)DC.: a desert aromatic shrub widespread in Northern Region of Saudi Arabia.

    PubMed

    Guetat, Arbi; Boulila, Abdennacer; Boussaid, Mohamed

    2018-04-16

    The present study describes the chemical composition of the essential oil of different plant parts of Devrra tortuosa; in vivo and in vitro biological activities of plant extract and essential oils. Apiol was found to be the major component of the oil (between 65.73% and 74.41%). The best antioxidant activities were observed for the oil of flowers (IC50 = 175 μg/ml). The samples of stems and roots exhibit lower antioxidant activity (IC50 = 201 μg/ml and 182 μg/ml, respectively). The values of IC50 showed that the extracts of methanol exhibit the highest antioxidants activities (IC50 = 64.8 102 μg/ml). EOs showed excellent antifungal activity against yeasts with low azole susceptibilities (i.e. Malassezia spp. and Candida krusei). The MIC values of oils varied between 2.85 mg/mL and 27 mg/mL. The obtained results also showed that the plant extracts inhibited the germination and the shoot and root growth of Triticum æstivum seedlings.

  2. Modernizing the MagIC Paleomagnetic and Rock Magnetic Database Technology Stack to Encourage Code Reuse and Reproducible Science

    NASA Astrophysics Data System (ADS)

    Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Jonestrask, L.; Tauxe, L.; Constable, C.

    2016-12-01

    The Magnetics Information Consortium (https://earthref.org/MagIC/) develops and maintains a database and web application for supporting the paleo-, geo-, and rock magnetic scientific community. Historically, this objective has been met with an Oracle database and a Perl web application at the San Diego Supercomputer Center (SDSC). The Oracle Enterprise Cluster at SDSC, however, was decommissioned in July of 2016 and the cost for MagIC to continue using Oracle became prohibitive. This provided MagIC with a unique opportunity to reexamine the entire technology stack and data model. MagIC has developed an open-source web application using the Meteor (http://meteor.com) framework and a MongoDB database. The simplicity of the open-source full-stack framework that Meteor provides has improved MagIC's development pace and the increased flexibility of the data schema in MongoDB encouraged the reorganization of the MagIC Data Model. As a result of incorporating actively developed open-source projects into the technology stack, MagIC has benefited from their vibrant software development communities. This has translated into a more modern web application that has significantly improved the user experience for the paleo-, geo-, and rock magnetic scientific community.

  3. Copper (II) and zinc (II) complexes with flavanone derivatives: Identification of potential cholinesterase inhibitors by on-flow assays.

    PubMed

    Sarria, André Lucio Franceschini; Vilela, Adriana Ferreira Lopes; Frugeri, Bárbara Mammana; Fernandes, João Batista; Carlos, Rose Maria; da Silva, Maria Fátima das Graças Fernandes; Cass, Quezia Bezerra; Cardoso, Carmen Lúcia

    2016-11-01

    Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEIs with inhibitory potency (IC 50 ) and inhibitory constant (K i ) ranging from 0.02 to 4.5μM. Copper complexes with flavanone-bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC 50 and K i values of 0.012±0.002 and 0.07±0.01μM for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC 50 =206±30.0 and K i =126±18.0μM). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC 50 and K i values of 8.0±1.4 and 2.0±0.1μM, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC 50 and K i values and the type of mechanism for the best inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

    PubMed Central

    Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

  5. Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

    PubMed

    Araya, Romina E; Jury, Jennifer; Bondar, Constanza; Verdu, Elena F; Chirdo, Fernando G

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

  6. Joint NuSTAR and Chandra analysis of the obscured quasar in IC 2497 - Hanny's Voorwerp system

    NASA Astrophysics Data System (ADS)

    Sartori, Lia F.; Schawinski, Kevin; Koss, Michael J.; Ricci, Claudio; Treister, Ezequiel; Stern, Daniel; Lansbury, George; Maksym, W. Peter; Baloković, Mislav; Gandhi, Poshak; Keel, William C.; Ballantyne, David R.

    2018-02-01

    We present new Nuclear Spectroscopic Telescope Array (NuSTAR) observations of the core of IC 2497, the galaxy associated with Hanny's Voorwerp. The combined fits of the Chandra (0.5-8 keV) and NuSTAR (3-24 keV) X-ray spectra, together with WISE mid-IR photometry, optical longslit spectroscopy and optical narrow-band imaging, suggest that the galaxy hosts a Compton-thick active galactic nucleus (AGN) (NH ˜ 2 × 1024 cm-2, current intrinsic luminosity Lbol ˜ 2-5 × 1044 erg s-1) whose luminosity dropped by a factor of ˜50 within the last ˜100 kyr. This corresponds to a change in Eddington ratio (ER) from λEdd ˜ 0.35 to λEdd ˜ 0.007. We argue that the AGN in IC 2497 should not be classified as a changing-look AGN, but rather we favour the interpretation where the AGN is undergoing a change in accretion state (from radiatively efficient to radiatively inefficient). In this scenario, the observed drop in luminosity and ER corresponds to the final stage of an AGN accretion phase. Our results are consistent with previous studies in the optical, X-ray and radio although the magnitude of the drop is lower than previously suggested. In addition, we discuss a possible analogy between X-ray binaries and an AGN.

  7. Solving the 56Ni Puzzle of Magnetar-powered Broad-lined Type IC Supernovae

    NASA Astrophysics Data System (ADS)

    Wang, Ling-Jun; Han, Yan-Hui; Xu, Dong; Wang, Shan-Qin; Dai, Zi-Gao; Wu, Xue-Feng; Wei, Jian-Yan

    2016-11-01

    Broad-lined Type Ic supernovae (SNe Ic-BL) are of great importance because their association with long-duration gamma-ray bursts (LGRBs) holds the key to deciphering the central engine of LGRBs, which refrains from being unveiled despite decades of investigation. Among the two popularly hypothesized types of central engine, I.e., black holes and strongly magnetized neutron stars (magnetars), there is mounting evidence that the central engine of GRB-associated SNe (GRB-SNe) is rapidly rotating magnetars. Theoretical analysis also suggests that magnetars could be the central engine of SNe Ic-BL. What puzzled the researchers is the fact that light-curve modeling indicates that as much as 0.2{--}0.5 {M}⊙ of 56Ni was synthesized during the explosion of the SNe Ic-BL, which is unfortunately in direct conflict with current state-of-the-art understanding of magnetar-powered 56Ni synthesis. Here we propose a dynamic model of magnetar-powered SNe to take into account the acceleration of the ejecta by the magnetar, as well as the thermalization of the injected energy. Assuming that the SN kinetic energy comes exclusively from the magnetar acceleration, we find that although a major fraction of the rotational energy of the magnetar is to accelerate the SN ejecta, a tiny fraction of this energy deposited as thermal energy of the ejecta is enough to reduce the needed 56Ni to 0.06 M ⊙ for both SN 1997ef and SN 2007ru. We therefore suggest that magnetars could power SNe Ic-BL in aspects both of energetics and of 56Ni synthesis.

  8. Cancer targeting potential of folate targeted nanocarrier under comparative influence of tretinoin and dexamethasone.

    PubMed

    Dhakad, Raghvendra Singh; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2013-08-01

    The objective of this investigation was aimed to explore the cancer targeting potential of folate conjugated dendrimer (polypropylene imine, PPI) under strategic influence of folate receptor up-regulators (all trans Retinoic acid, ATRA and Dexamethasone, DEXA). The folate conjugated dendrimer nanoconjugate (FPPI) was synthesized and characterized by FTIR, and (1)H-NMR spectroscopy. The cell line studies investigations were performed on MCF-7 cells. ATRA and DEXA caused 2.17 and 1.65 folds selective up-regulation of folate receptor respectively, when compared with untreated control, after 48 h of pretreatment. ATRA caused 50.47±2.11% more up regulation of folate receptor, than DEXA treated cell. Both up regulators showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC50 values of naked docetaxel (DTX) and DTX loaded dendrimer (PPI-DTX) were found to be 678.93±11.99 nM and 663.51±15.23 nM, respectively, while DTX loaded folate-anchored dendrimer (FPPI-DTX) showed a selectively lowered IC50 value of 468.56±20.86 nM. FPPI-DTX further showed a significant reduction in IC50 value in ATRA and DEXA pretreated cells, wherein IC50 values of 184.21 nM and 290.40±14.05 nM, respectively were observed. The study also concludes ATRA to be a superior receptor up-regulator as well as promoter of folate based targeting compared to DEXA.

  9. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

    PubMed Central

    Sakuda, Shohei; Prabowo, Diyan Febri; Takagi, Keiko; Shiomi, Kazuro; Mori, Mihoko; Ōmura, Satoshi; Nagasawa, Hiromichi

    2014-01-01

    Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III) and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control. PMID:24674936

  10. Microbial toxicity of the insensitive munitions compound, 2,4-dinitroanisole (DNAN), and its aromatic amine metabolites.

    PubMed

    Liang, Jidong; Olivares, Christopher; Field, Jim A; Sierra-Alvarez, Reyes

    2013-11-15

    2,4-Dinitroanisole (DNAN) is an insensitive munitions compound considered to replace conventional explosives such as 2,4,6-trinitrotoluene (TNT). DNAN undergoes facile microbial reduction to 2-methoxy-5-nitroaniline (MENA) and 2,4-diaminoanisole (DAAN). This study investigated the inhibitory effect of DNAN, MENA, and DAAN toward various microbial targets in anaerobic (acetoclastic methanogens) and aerobic (heterotrophs and nitrifiers) sludge, and the bioluminescent bacterium, Aliivibrio fischeri, used in the Microtox assay. Aerobic heterotrophic and nitrifying batch experiments with DAAN could not be performed because the compound underwent extensive autooxidation in these assays. DNAN severely inhibited methanogens, nitrifying bacteria, and A. fischeri (50% inhibitory concentrations (IC50) ranging 41-57μM), but was notably less inhibitory to aerobic heterotrophs (IC50>390 μM). Reduction of DNAN to MENA and DAAN lead to a marked decrease in methanogenic inhibition (i.e., DNAN>MENA≈DAAN). Reduction of all nitro groups in DNAN also resulted in partial detoxification in assays with A. fischeri. In contrast, reduction of a single nitro group did not alter the inhibitory impact of DNAN toward A. fischeri and nitrifying bacteria given the similar IC50 values determined for MENA and DNAN in these assays. These results indicate that reductive biotransformation could reduce the inhibitory potential of DNAN. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Naphthoquinones from the leaves of Rhinacanthus nasutus having acetylcholinesterase inhibitory and cytotoxic activities.

    PubMed

    Boonyaketgoson, Sirada; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak; Trisuwan, Kongkiat

    2018-01-01

    Four new naphthoquinones (1-4), named rhinacanthins S (1), T (2), U (3) and V (4), together with 13 known naphthoquinones were isolated from the leaf extract of Rhinacanthus nasutus. The structures of isolated compounds were elucidated by spectroscopic methods, especially 1D and 2D NMR spectroscopy and mass spectrometry. Rhinacanthin S (1) exhibited acetylcholinesterase inhibition activity with a % inhibition value of 48.04±3.25. The known rhinacanthin A (5) showed cytotoxicity against a MCF-7 cell line with an IC 50 value of 8.79μM, while rhinacanthin N (15) was active against the NCI-H187 cell line with an IC 50 =2.24μM and Vero cells (IC 50 =3.00μM). Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Voluntary Running-Wheel Exercise Decreases the Threshold for Rewarding Intracranial Self-Stimulation

    PubMed Central

    Morris, Michael J.; Na, Elisa S.; Johnson, Alan Kim

    2015-01-01

    Physical exercise has mood-enhancing and antidepressant properties although the mechanisms underlying these effects are not known. The present experiment investigated the effects of prolonged access to a running wheel on electrical self-stimulation of the lateral hypothalamus (LHSS), a measure of hedonic state, in rats. Rats with continuous voluntary access to a running wheel for either 2 or 5 weeks exhibited dramatic leftward shifts in the effective current 50 (ECu50; current value that supports half of maximum responding) of their LHSS current-response functions compared to their baselines, indicating a decrease in reward threshold, whereas control rats current-response functions after 2 or 5 weeks were not significantly different from baseline. An inverse correlation existed between the change in ECu50 from baseline and the amount an animal had run in the day prior to LHSS testing, indicating that animals that exhibited higher levels of running showed a more robust decrease in LHSS threshold. We conclude that long-term voluntary exercise increases sensitivity to rewarding stimuli, which may contribute to its antidepressant properties. PMID:22845707

  13. Voluntary running-wheel exercise decreases the threshold for rewarding intracranial self-stimulation.

    PubMed

    Morris, Michael J; Na, Elisa S; Johnson, Alan Kim

    2012-08-01

    Physical exercise has mood-enhancing and antidepressant properties although the mechanisms underlying these effects are not known. The present experiment investigated the effects of prolonged access to a running wheel on electrical self-stimulation of the lateral hypothalamus (LHSS), a measure of hedonic state, in rats. Rats with continuous voluntary access to a running wheel for either 2 or 5 weeks exhibited dramatic leftward shifts in the effective current 50 (ECu50; current value that supports half of maximum responding) of their LHSS current-response functions compared to their baselines, indicating a decrease in reward threshold, whereas control rats current-response functions after 2 or 5 weeks were not significantly different from baseline. An inverse correlation existed between the change in ECu50 from baseline and the amount an animal had run in the day prior to LHSS testing, indicating that animals that exhibited higher levels of running showed a more robust decrease in LHSS threshold. We conclude that long-term voluntary exercise increases sensitivity to rewarding stimuli, which may contribute to its antidepressant properties.

  14. Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5.

    PubMed

    Arakawa, Hiroshi; Shirasaka, Yoshiyuki; Haga, Makoto; Nakanishi, Takeo; Tamai, Ikumi

    2012-09-01

    Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K(m) value of 140 µm, and naringin inhibited the uptake with an IC(50) value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC(50) value of 7.5 µm by the Ussing-type chamber method. The estimated IC(50) values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp. Copyright © 2012 John Wiley & Sons, Ltd.

  15. [Effects of methomyl on acetylcholinesterase in erythrocyte membrane and various brain areas].

    PubMed

    Zhao, Fei; Li, Tao; Zhang, Changchun; Xu, Yiping; Xu, Hangong; Shi, Nian

    2015-06-01

    To study the toxicity of methomyl to acetylcholinesterase (AChE) in different regions. The optimal temperature and time for measurement of AChE activity were determined in vitro. The dose- and time-response relationships of methomyl with AChE activity in human erythrocyte membrane, rat erythrocyte membrane, cortical synapses, cerebellar synapses, hippocampal synapses, and striatal synapses were evaluated. The half maximal inhibitory concentration (IC50) and bimolecular rate constant (K) of methomyl for AChE activity in different regions were calculated, and the type of inhibition of AChE activity by methomyl was determined. AChE achieved the maximum activity at 370 °C, and the optimal time to determine initial reaction velocity was 0-17 min. There were dose- and time-response relationships between methomyl and AChE activity in the erythrocyte membrane and various brain areas. The IC50 value of methomyl for AChE activity in human erythrocyte membrane was higher than that in rat erythrocyte membrane, while the Ki value of methomyl for AChE activity in rat erythrocyte membrane was higher than that in human erythrocyte membrane. Among synapses in various brain areas, the striatum had the highest IC50 value, followed by the cerebellum, cerebral cortex, and hippocampus, while the cerebral cortex had the highest Ki value, followed by the hippocampus, striatum, and cerebellum. Lineweaver-Burk diagram demonstrated that with increasing concentration of methomyl, the maximum reaction velocity (Vmax) of AChE decreased, and the Michaelis constant (Km) remained the same. Methomyl is a reversible non-competitive inhibitor of AChE. AChE of rat erythrocyte membrane is more sensitive to methomyl than that of human erythrocyte membrane; the cerebral cortical synapses have the most sensitive AChE to methomyl among synapses in various brain areas.

  16. 75 FR 51499 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Digital I&C...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Digital I&C Systems The ACRS Subcommittee on Digital Instrumentation and Controls (I&C) Systems...: Wednesday, September 8, 2010--8:30 a.m. until 12 p.m. The Subcommittee will review Digital I&C Interim Staff...

  17. [Eosinophilic spongiosis and ICS antibodies in a child with strophulus-like dermatosis].

    PubMed

    Klein, G F; Hintner, H; Fristch, P O

    1984-01-01

    Eosinophilic spongiosis associated with in vivo-bound antibodies to the epidermal intercellular space (ICS) were consistently observed in a recurrent strophulus-like eruption in an 11-year-old boy, thus suggesting pemphigus. The clinical course, however, ruled this diagnosis out since neither acantholysis nor the clinical picture of pemphigus developed in a period of 2.5 years. Since in vivo-bound ICS-antibodies have been described in several case reports of bullous impetigo we speculate that immune reactions to bacterial antigens may be involved in producing eruptions mimicking pemphigus vulgaris.

  18. Spatially Resolved Spectroscopy of the SNR IC443

    NASA Astrophysics Data System (ADS)

    Gorenstein, P.

    1998-07-01

    IC 443 is a supernova remnant of intermediate age, i.e. a few thousand years. It is especially interesting because part of its periphery is expanding into a molecular cloud while other sections are expanding into a typical interstellar medium of much lower density. Since the evolution of a supernova remnant through its various phases is affected by the density of the medium it expands into with the reasonable assumption that the supernova explosion was approximately symmetric we have an opportunity to observe a single object in two phases simultaneously. It was observed by ASCA in April, 1993 for a short period during the PV phase and more thoroughly in a 42 ksec exposure in March, 1994. The latter measurement provides most of the results that have been reported. Most of the analysis took place after the grant ended but is included here for completeness. The data was sent simultaneously to US and Japanese Pls. We worked independently. The software set of FTOOLs was used to construct images and spectra. They were judged to be rather unintuitive and not at all user friendly. I found I was using one FTOOL to read the header to obtain information that would only be provided to another FTOOL. The Japanese investigators were more successful. They analyzed the data and published results more rapidly. The scientific results summarized below are based primarily on their publications. Since IC 443 is an interesting example of a middle aged SNR in which a variety of processes are occurring it is one of a class. IC 443 exhibits shell-like emission in hard X-rays and extended soft X-rays with thin thermal spectra. It resembles SN 1006 in these respects. IC 443 contains hard X-rays in a semi-circular shell surrounding the thermal component. The total hard X-ray flux in the ASCA FOV is only a half of the Ginga hard component; which suggests that the hard X-rays are not confined only in the shell but some are extended larger than the ASCA FOV of eq 1 degree diameter. Japanese

  19. Spatially Resolved Spectroscopy of the SNR IC443

    NASA Technical Reports Server (NTRS)

    Gorenstein, P.

    1998-01-01

    IC 443 is a supernova remnant of intermediate age, i.e. a few thousand years. It is especially interesting because part of its periphery is expanding into a molecular cloud while other sections are expanding into a typical interstellar medium of much lower density. Since the evolution of a supernova remnant through its various phases is affected by the density of the medium it expands into with the reasonable assumption that the supernova explosion was approximately symmetric we have an opportunity to observe a single object in two phases simultaneously. It was observed by ASCA in April, 1993 for a short period during the PV phase and more thoroughly in a 42 ksec exposure in March, 1994. The latter measurement provides most of the results that have been reported. Most of the analysis took place after the grant ended but is included here for completeness. The data was sent simultaneously to US and Japanese Pls. We worked independently. The software set of FTOOLs was used to construct images and spectra. They were judged to be rather unintuitive and not at all user friendly. I found I was using one FTOOL to read the header to obtain information that would only be provided to another FTOOL. The Japanese investigators were more successful. They analyzed the data and published results more rapidly. The scientific results summarized below are based primarily on their publications. Since IC 443 is an interesting example of a middle aged SNR in which a variety of processes are occurring it is one of a class. IC 443 exhibits shell-like emission in hard X-rays and extended soft X-rays with thin thermal spectra. It resembles SN 1006 in these respects. IC 443 contains hard X-rays in a semi-circular shell surrounding the thermal component. The total hard X-ray flux in the ASCA FOV is only a half of the Ginga hard component; which suggests that the hard X-rays are not confined only in the shell but some are extended larger than the ASCA FOV of eq 1 degree diameter. Japanese

  20. Publications - IC 17 | Alaska Division of Geological & Geophysical Surveys

    Science.gov Websites

    DGGS IC 17 Publication Details Title: Coal resources of Alaska Authors: Alaska Division of Geological Statewide Bibliographic Reference Alaska Division of Geological & Geophysical Surveys, 1983, Coal Alaska Statewide Maps; Coal; Healy; Resource Assessment; Usibelli Mine Top of Page Department of Natural

  1. 30 CFR 57.22104 - Open flames (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....22104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C...

  2. New Risk Curves for NHTSA's Brain Injury Criterion (BrIC): Derivations and Assessments.

    PubMed

    Laituri, Tony R; Henry, Scott; Pline, Kevin; Li, Guosong; Frankstein, Michael; Weerappuli, Para

    2016-11-01

    The National Highway Traffic Safety Administration (NHTSA) recently published a Request for Comments regarding a potential upgrade to the US New Car Assessment Program (US NCAP) - a star-rating program pertaining to vehicle crashworthiness. Therein, NHTSA (a) cited two metrics for assessing head risk: Head Injury Criterion (HIC15) and Brain Injury Criterion (BrIC), and (b) proposed to conduct risk assessment via its risk curves for those metrics, but did not prescribe a specific method for applying them. Recent studies, however, have indicated that the NHTSA risk curves for BrIC significantly overstate field-based head injury rates. Therefore, in the present three-part study, a new set of BrIC-based risk curves was derived, an overarching head risk equation involving risk curves for both BrIC and HIC15 was assessed, and some additional candidatepredictor- variable assessments were conducted. Part 1 pertained to the derivation. Specifically, data were pooled from various sources: Navy volunteers, amateur boxers, professional football players, simple-fall subjects, and racecar drivers. In total, there were 4,501 cases, with brain injury reported in 63. Injury outcomes were approximated on the Abbreviated Injury Scale (AIS). The statistical analysis was conducted subject to ordinal logistic regression analysis (OLR), such that the various levels of brain injury were cast as a function of BrIC. The resulting risk curves, with Goodman Kruksal Gamma=0.83, were significantly different than those from NHTSA. Part 2 pertained to the assessment relative to field data. Two perspectives were considered: "aggregate" (ΔV=0-56 km/h) and "point" (high-speed, regulatory focus). For the aggregate perspective, the new risk curves for BrIC were applied in field models pertaining to belted, mid-size, adult drivers in 11-1 o'clock, full-engagement frontal crashes in the National Automotive Sampling System (NASS, 1993-2014 calendar years). For the point perspective, BrIC data from tests

  3. Chemical Constituents of Muehlenbeckia tamnifolia (Kunth) Meisn (Polygonaceae) and Its In Vitro α-Amilase and α-Glucosidase Inhibitory Activities.

    PubMed

    Torres-Naranjo, María; Suárez, Alirica; Gilardoni, Gianluca; Cartuche, Luis; Flores, Paola; Morocho, Vladimir

    2016-11-02

    The phytochemical investigation of Muehlenbeckia tamnifolia , collected in Loja-Ecuador, led to the isolation of nine known compounds identified as: lupeol acetate ( 1 ); cis - p -coumaric acid ( 2 ); lupeol ( 3 ); β-sitosterol ( 4 ) trans - p -coumaric acid ( 5 ); linoleic acid ( 6 ) (+)-catechin ( 7 ); afzelin ( 8 ) and quercitrin ( 9 ). The structures of the isolated compounds were determined based on analysis of NMR and MS data, as well as comparison with the literature. The hypoglycemic activity of crude extracts and isolated compounds was assessed by the ability to inhibit α-amylase and α-glucosidase enzymes. The hexane extract showed weak inhibitory activity on α-amylase, with an IC 50 value of 625 µg·mL -1 , while the other extracts and isolated compounds were inactive at the maximum dose tested. The results on α-glucosidase showed more favorable effects; the hexanic and methanolic extracts exhibited a strong inhibitory activity with IC 50 values of 48.22 µg·mL -1 and 19.22 µg·mL -1 , respectively. Four of the nine isolated compounds exhibited strong inhibitory activity with IC 50 values below 8 µM, much higher than acarbose (377 uM). Linoleic acid was the most potent compound (IC 50 = 0.42 µM) followed by afzelin, (+)-catechin and quercitrin.

  4. A remarkably large depleted core in the Abell 2029 BCG IC 1101

    NASA Astrophysics Data System (ADS)

    Dullo, Bililign T.; Graham, Alister W.; Knapen, Johan H.

    2017-10-01

    We report the discovery of an extremely large (Rb ˜2.77 arcsec ≈ 4.2 kpc) core in the brightest cluster galaxy, IC 1101, of the rich galaxy cluster Abell 2029. Luminous core-Sérsic galaxies contain depleted cores - with sizes (Rb) typically 20-500 pc - that are thought to be formed by coalescing black hole binaries. We fit a (double nucleus) + (spheroid) + (intermediate-scale component) + (stellar halo) model to the Hubble Space Telescope surface brightness profile of IC 1101, finding the largest core size measured in any galaxy to date. This core is an order of magnitude larger than those typically measured for core-Sérsic galaxies. We find that the spheroid's V-band absolute magnitude (MV) of -23.8 mag (˜25 per cent of the total galaxy light, I.e. including the stellar halo) is faint for the large Rb, such that the observed core is 1.02 dex ≈ 3.4σs (rms scatter) larger than that estimated from the Rb-MV relation. The suspected scouring process has produced a large stellar mass deficit (Mdef) ˜4.9 × 1011 M⊙, I.e. a luminosity deficit ≈28 per cent of the spheroid's luminosity prior to the depletion. Using IC 1101's black hole mass (MBH) estimated from the MBH-σ, MBH-L and MBH-M* relations, we measure an excessive and unrealistically high number of 'dry' major mergers for IC 1101 (I.e. N ≳ 76) as traced by the large Mdef/MBH ratios of 38-101. The large core, high mass deficit and oversized Mdef/MBH ratio of IC 1101 suggest that the depleted core was scoured by overmassive SMBH binaries with a final coalesced mass MBH ˜ (4-10) × 1010 M⊙, I.e. ˜ (1.7-3.2) × σs larger than the black hole masses estimated using the spheroid's σ, L and M*. The large core might be partly due to oscillatory core passages by a gravitational radiation-recoiled black hole.

  5. MMB-4 Inhibition of Aceylcholinesterase Is Similar across Species

    DTIC Science & Technology

    2014-11-01

    version 5.4). An IC50 value was determined for AChE from each animal species by fitting the percent of AChE activity with respect to MMB 4 concentration...in GraphPad Prism (version 5) using a nonlinear regression dose response model for inhibition (normalized response with variable slope). Assessing the...Therefore, AChE activity and inhibition studies were carried out at 435 nm to reduce interference from MMB 4. Comparison of IC50 Values for MMB 4 with AChE

  6. Synthesis of 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone as a candidate anticancer against cervical (WiDr), colon (HeLa), and breast (T47d) cancer cell lines in vitro

    NASA Astrophysics Data System (ADS)

    Matsjeh, Sabirin; Swasono, Respati Tri; Anwar, Chairil; Solikhah, Eti Nurwening; Lestari, Endang

    2017-03-01

    The compound 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone have been synthesized through Claisen-Schmidt reaction from 2-hydroxyacetophenone and 2,4-dihydroxyacetophenone with 4-hydroxy-3-methoxy benzaldehida (vanillin) in aqueous KOH 40% and KSF montmorillonite as catalyst in methanol. All these products were characterized by FT-IR, TLC Scanner, GC-MS, MS-Direct, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical, colon, and breast cancer cells (Hela, WiDr, and T47D cell lines) using MTT assay in vitro. Dose series given test solution concentration on Hela, WiDr, and T47D cells started from 6,25; 25; 50 and 100 µg/mL with incubation treatment for 24 hours. The result of study showed that the 2',4-dihydroxy-3-methoxychalcone as bright yellow crystal with the melting point of 114-115 °C and the yield of 13.77% and the 2',4',4-trihydroxy-3-methoxychalcone as bright yellow crystals with the melting point of 195-197 °C and the yield of 6%. Other 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone also exhibited cytotoxic activity against the cancer cell lines, with the 2',4',4-trihydroxy-3-methoxychalcone showed greater activities than the 2',4-dihydroxy-3-methoxychalcone in WiDr cell lines. The 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone exhibited strong anticancer activities with IC50 value below 20 µg/mL. The activity of 2',4',4-trihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 8.53 and 2.66 µg/mL respectively, than T47D cell lines with IC50 value 24.61 µg/mL. The test results cytotoxic of 2',4-dihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 12.80, 19.57 µg/mL than T47D cell lines with IC50 value of 20.73 µg/mL. IC50 value indicated that 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3

  7. Comparative Study of Erythrina indica Lam. (Febaceae) Leaves Extracts for Antioxidant Activity

    PubMed Central

    Sakat, SS; Juvekar, AR

    2010-01-01

    The present study was designed to investigate the antioxidant activity of aqueous and methanol extracts of Erythrina indica Lam leaves by in vitro methods viz. 1, 1-Diphenyl-2-Picrylhydrazyl, nitric oxide radical scavenging activity, and inhibition of lipid peroxidation by thiobarbituric acid reactive substances (TBARS) method on isolated rat liver tissues. Quantitative analysis of antioxidative components like total amount of phenolics, flavonoids, and flavonols were estimated using the spectrophotometric method. Linear regression analysis was used to calculate the IC50 value. Results showed that the aqueous and methanol extracts exhibited significant DPPH radicals scavenging activity with an IC50 value 342.59 ± 19.59, 283.24 ± 12.28 µg/mL respectively. Nitric oxide radicals were significantly scavenged by the aqueous and methanol extracts (IC50 = 250.12 ± 10.66; 328.29 ± 3.74 µg/mL). Lipid peroxidation induced by the Fe2+ was inhibited by the aqueous extract with low IC50 value (97.29 ± 2.05 µg/mL) as compared to methanol extract (IC50 = 283.74 ± 5.70 µg/mL). Both the extracts were exhibited similar quantities of total phenolics. Total flavonoids were found to be in higher quantities than total flavonols in aqueous extract as compared to methanol extract. From the results, it is concluded that the aqueous and methanol extracts of E. indica leaves possesses significant antioxidant activity that may be due to the presence of flavonoids and related polyphenolic compounds. PMID:21331194

  8. Structure-activity relationships and docking studies of synthetic 2-arylindole derivatives determined with aromatase and quinone reductase 1.

    PubMed

    Prior, Allan M; Yu, Xufen; Park, Eun-Jung; Kondratyuk, Tamara P; Lin, Yan; Pezzuto, John M; Sun, Dianqing

    2017-12-15

    In our ongoing effort of discovering anticancer and chemopreventive agents, a series of 2-arylindole derivatives were synthesized and evaluated toward aromatase and quinone reductase 1 (QR1). Biological evaluation revealed that several compounds (e.g., 2d, IC 50  = 1.61 μM; 21, IC 50  = 3.05 μM; and 27, IC 50  = 3.34 μM) showed aromatase inhibitory activity with half maximal inhibitory concentration (IC 50 ) values in the low micromolar concentrations. With regard to the QR1 induction activity, 11 exhibited the highest QR1 induction ratio (IR) with a low concentration to double activity (CD) value (IR = 8.34, CD = 2.75 μM), while 7 showed the most potent CD value of 1.12 μM. A dual acting compound 24 showed aromatase inhibition (IC 50  = 9.00 μM) as well as QR1 induction (CD = 5.76 μM) activities. Computational docking studies using CDOCKER (Discovery Studio 3.5) provided insight in regard to the potential binding modes of 2-arylindoles within the aromatase active site. Predominantly, the 2-arylindoles preferred binding with the 2-aryl group toward a small hydrophobic pocket within the active site. The C-5 electron withdrawing group on indole was predicted to have an important role and formed a hydrogen bond with Ser478 (OH). Alternatively, meta-pyridyl analogs may orient with the pyridyl 3'-nitrogen coordinating with the heme group. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Air flow (I-C, II-A, and V-A mines). 57.22212 Section 57.22212 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines...

  10. bop5 mutations reveal new roles for the IC138 phosphoprotein in the regulation of flagellar motility and asymmetric waveforms

    PubMed Central

    VanderWaal, Kristyn E.; Yamamoto, Ryosuke; Wakabayashi, Ken-ichi; Fox, Laura; Kamiya, Ritsu; Dutcher, Susan K.; Bayly, Phillip V.; Sale, Winfield S.; Porter, Mary E.

    2011-01-01

    I1 dynein, or dynein f, is a highly conserved inner arm isoform that plays a key role in the regulation of flagellar motility. To understand how the IC138 IC/LC subcomplex modulates I1 activity, we characterized the molecular lesions and motility phenotypes of several bop5 alleles. bop5-3, bop5-4, and bop5-5 are null alleles, whereas bop5-6 is an intron mutation that reduces IC138 expression. I1 dynein assembles into the axoneme, but the IC138 IC/LC subcomplex is missing. bop5 strains, like other I1 mutants, swim forward with reduced swimming velocities and display an impaired reversal response during photoshock. Unlike mutants lacking the entire I1 dynein, however, bop5 strains exhibit normal phototaxis. bop5 defects are rescued by transformation with the wild-type IC138 gene. Analysis of flagellar waveforms reveals that loss of the IC138 subcomplex reduces shear amplitude, sliding velocities, and the speed of bend propagation in vivo, consistent with the reduction in microtubule sliding velocities observed in vitro. The results indicate that the IC138 IC/LC subcomplex is necessary to generate an efficient waveform for optimal motility, but it is not essential for phototaxis. These findings have significant implications for the mechanisms by which IC/LC complexes regulate dynein motor activity independent of effects on cargo binding or complex stability. PMID:21697502

  11. Temporal Decrease in Upper Atmospheric Chlorine

    NASA Technical Reports Server (NTRS)

    Froidevaux, L.; Livesey, N. J.; Read, W. G.; Salawitch, R. J.; Waters, J. W.; Drouin, B.; MacKenzie, I. A.; Pumphrey, H. C.; Bernath, P.; Boone, C.; hide

    2006-01-01

    We report a steady decrease in the upper stratospheric and lower mesospheric abundances of hydrogen chloride (HCl) from August 2004 through January 2006, as measured by the Microwave Limb Sounder (MLS) aboard the Aura satellite. For 60(deg)S to 60(deg)N zonal means, the average yearly change in the 0.7 to 0.1 hPa (approx.50 to 65 km) region is -27 +/- 3 pptv/year, or -0.78 +/- 0.08 percent/year. This is consistent with surface abundance decrease rates (about 6 to 7 years earlier) in chlorine source gases. The MLS data confirm that international agreements to reduce global emissions of ozone-depleting industrial gases are leading to global decreases in the total gaseous chlorine burden. Tracking stratospheric HCl variations on a seasonal basis is now possible with MLS data. Inferred stratospheric total chlorine (CITOT) has a value of 3.60 ppbv at the beginning of 2006, with a (2-sigma) accuracy estimate of 7%; the stratospheric chlorine loading has decreased by about 43 pptv in the 18-month period studied here. We discuss the MLS HCl measurements in the context of other satellite-based HCl data, as well as expectations from surface chlorine data. A mean age of air of approx. 5.5 years and an age spectrum width of 2 years or less provide a fairly good fit to the ensemble of measurements.

  12. Phytochemical and cytotoxic studies on the roots of Euphorbia fischeriana.

    PubMed

    Shi, Qun; Sun, Yi-Wei; Meng, Dali

    2017-01-15

    With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1-3) and six known ones (4-9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC 50 8.1μmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC 50 values of 12.5, 12.0 and 18.7μmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC 50 11.9μmol/L) and 8 (IC 50 9.4μmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC 50 values of 28.2 and 29.8μmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. LC and LD50 values of Bacillus thuringiensis Serovar japonensis strain buibui toxin to Oriental beetle and northern masked chafer larvae (Coleoptera: Scarabaeidae).

    PubMed

    Mashtoly, Tamer A; El-Zemaity, Mohamed El-Said; Hussien, Mohamed I; Alm, Steven R

    2009-10-01

    Bacillus thuringiensis serovar japonensis strain Buibui has the potential to be an important control agent for pest scarabs. Bioassays were designed to test B. t. japonensis against two of the major turf and ornamental scarab pests infesting turfgrasses and ornamentals and to serve as a basis for further tests against other scarab pests. LC and LD50 values of B. t. serovarjaponensis strain Buibui toxin and spores were determined by four different bioassays for the oriental beetle, Anomala orientalis (Waterhouse), and northern masked chafer, Cyclocephala borealis Arrow. Oriental beetle larvae were bioassayed in autoclaved and nonautoclaved soil from where they were collected (Kingston, RI [native]), in nonautoclaved soil from where the northern masked chafer larvae were collected (Groton, CT [foreign]), and per os. Northern masked chafer larvae were bioassayed in autoclaved and nonautoclaved soil from where they were collected (Groton, CT [native]), in nonautoclaved soil from where the oriental beetle larvae were collected (Kingston, RI [foreign]) and per os. LC50 values of 3.93 microg toxin/g autoclaved native soil, 1.80 microg toxin/g nonautoclaved native soil, and 0.42 microg toxin/g nonautoclaved foreign soil and an LD50 value of 0.41 microg per os were determined at 14 d forA. orientalis. LC50 values of 588.28 microg toxin/g autoclaved native soil, 155.10 microg toxin/g nonautoclaved native soil, 265.32 microg toxin/g nonautoclaved foreign soil, and LD50 of 5.21 microg per os were determined at 14 d (soils) and 10 d (per os) for C. borealis. There were significant differences in LC50 values for oriental beetles in autoclaved, nonautoclaved native soil and nonautoclaved foreign soil. There were significant differences in LCo values for northern masked chafers in autoclaved and nonautoclaved native soil. B. t. japonensis can be applied now for control of oriental beetles at rates that are economically competitive with synthetic chemicals. If we can determine the

  14. Modeling the spectral energy distribution of the radio galaxy IC310

    NASA Astrophysics Data System (ADS)

    Fraija, N.; Marinelli, A.; Galván-Gámez, A.; Aguilar-Ruiz, E.

    2017-03-01

    The radio galaxy IC310 located in the Perseus Cluster is one of the brightest objects in the radio and X-ray bands, and one of the closest active galactic nuclei observed in very-high energies. In GeV - TeV γ-rays, IC310 was detected in low and high flux states by the MAGIC telescopes from October 2009 to February 2010. Taking into account that the spectral energy distribution (SED) up to a few GeV seems to exhibit a double-peak feature and that a single-zone synchrotron self-Compton (SSC) model can explain all of the multiwavelength emission except for the non-simultaneous MAGIC emission, we interpret, in this work, the multifrequency data set of the radio galaxy IC310 in the context of homogeneous hadronic and leptonic models. In the leptonic framework, we present a multi-zone SSC model with two electron populations to explain the whole SED whereas for the hadronic model, we propose that a single-zone SSC model describes the SED up to a few GeVs and neutral pion decay products resulting from pγ interactions could describe the TeV - GeV γ-ray spectra. These interactions occur when Fermi-accelerated protons interact with the seed photons around the SSC peaks. We show that, in the leptonic model the minimum Lorentz factor of second electron population is exceedingly high γe ∼ 105 disfavoring this model, and in the hadronic model the required proton luminosity is not extremely high ∼1044 erg/s, provided that charge neutrality between the number of electrons and protons is given. Correlating the TeV γ-ray and neutrino spectra through photo-hadronic interactions, we find that the contribution of the emitting region of IC310 to the observed neutrino and ultra-high-energy cosmic ray fluxes are negligible.

  15. An NFC-Enabled CMOS IC for a Wireless Fully Implantable Glucose Sensor.

    PubMed

    DeHennis, Andrew; Getzlaff, Stefan; Grice, David; Mailand, Marko

    2016-01-01

    This paper presents an integrated circuit (IC) that merges integrated optical and temperature transducers, optical interface circuitry, and a near-field communication (NFC)-enabled digital, wireless readout for a fully passive implantable sensor platform to measure glucose in people with diabetes. A flip-chip mounted LED and monolithically integrated photodiodes serve as the transduction front-end to enable fluorescence readout. A wide-range programmable transimpedance amplifier adapts the sensor signals to the input of an 11-bit analog-to-digital converter digitizing the measurements. Measurement readout is enabled by means of wireless backscatter modulation to a remote NFC reader. The system is able to resolve current levels of less than 10 pA with a single fluorescent measurement energy consumption of less than 1 μJ. The wireless IC is fabricated in a 0.6-μm-CMOS process and utilizes a 13.56-MHz-based ISO15693 for passive wireless readout through a NFC interface. The IC is utilized as the core interface to a fluorescent, glucose transducer to enable a fully implantable sensor-based continuous glucose monitoring system.

  16. How fast can an AGN shut down? XMM-Newton observation of IC 2497

    NASA Astrophysics Data System (ADS)

    Schawinski, Kevin

    2008-10-01

    We propose to observe IC 2497 with XMM-Newton to detect, or rule out, an obscured AGN that might account for the illumination of `Hanny's Voorwerp'. The Voorwerp is a highly ionised cloud of gas extended over 15-25 kpc next to the spiral galaxy IC 2497. There is no source of ionisation within the Voorwerp, implicating a luminous 1E44 erg/s AGN in IC 2497 as the source. Swift XRT observations do not yield a detection, allowing the presence of a highly obscured, sufficiently luminous AGN. With 34 ksec of XMM observations, we could detect an obscured AGN down to 1E42 erg/s. We can thus either locate an obscured AGN, or we can for the first time constrain the shutdown time scale for a powerful AGN, as it drops by a factor of 100 in luminosity in 1E5 years.

  17. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    PubMed

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  18. Development of voice navigation system for the visually impaired by using IC tags.

    PubMed

    Takatori, Norihiko; Nojima, Kengo; Matsumoto, Masashi; Yanashima, Kenji; Magatani, Kazushige

    2006-01-01

    There are about 300,000 visually impaired persons in Japan. Most of them are old persons and, cannot become skillful in using a white cane, even if they make effort to learn how to use a white cane. Therefore, some guiding system that supports the independent activities of the visually impaired are required. In this paper, we will describe about a developed white cane system that supports the independent walking of the visually impaired in the indoor space. This system is composed of colored navigation lines that include IC tags and an intelligent white cane that has a navigation computer. In our system colored navigation lines that are put on the floor of the target space from the start point to the destination and IC tags that are set at the landmark point are used for indication of the route to the destination. The white cane has a color sensor, an IC tag transceiver and a computer system that includes a voice processor. This white cane senses the navigation line that has target color by a color sensor. When a color sensor finds the target color, the white cane informs a white cane user that he/she is on the navigation line by vibration. So, only following this vibration, the user can reach the destination. However, at some landmark points, guidance is necessary. At these points, an IC tag is set under the navigation line. The cane makes communication with the tag and informs the user about the land mark pint by pre recorded voice. Ten normal subjects who were blindfolded were tested with our developed system. All of them could walk along navigation line. And the IC tag information system worked well. Therefore, we have concluded that our system will be a very valuable one to support activities of the visually impaired.

  19. Synthesis of 4-thiazolidinone analogs as potent in vitro anti-urease agents.

    PubMed

    Rahim, Fazal; Zaman, Khalid; Ullah, Hayat; Taha, Muhammad; Wadood, Abdul; Javed, Muhammad Tariq; Rehman, Wajid; Ashraf, Muhammad; Uddin, Reaz; Uddin, Imad; Asghar, Humna; Khan, Aftab Ahmad; Khan, Khalid M

    2015-12-01

    4-Thiazolidinone analogs 1-20 were synthesized, characterized by (1)H NMR and EI-MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC50 values 1.73-69.65μM, if compared with standard thiourea having IC50 value of 21.25±0.15μM. Among the series, eight derivatives 3, 6, 8, 10, 15, 17, 19, and 20 showed outstanding urease inhibitory potential with IC50 values of 9.34±0.02, 14.62±0.03, 8.43±0.01, 7.3±0.04, 2.31±0.002, 5.75±0.003, 8.81±0.005, and 1.73±0.001μM, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Fermi Non-detections of Four X-Ray Jet Sources and Implications for the IC/CMB Mechanism

    NASA Astrophysics Data System (ADS)

    Breiding, Peter; Meyer, Eileen T.; Georganopoulos, Markos; Keenan, M. E.; DeNigris, N. S.; Hewitt, Jennifer

    2017-11-01

    Since its launch in 1999, the Chandra X-ray observatory has discovered several dozen X-ray jets associated with powerful quasars. In many cases, the X-ray spectrum is hard and appears to come from a second spectral component. The most popular explanation for the kpc-scale X-ray emission in these cases has been inverse-Compton (IC) scattering of Cosmic Microwave Background (CMB) photons by relativistic electrons in the jet (the IC/CMB model). Requiring the IC/CMB emission to reproduce the observed X-ray flux density inevitably predicts a high level of gamma-ray emission, which should be detectable with the Fermi Large Area Telescope (LAT). In previous work, we found that gamma-ray upper limits from the large-scale jets of 3C 273 and PKS 0637-752 violate the predictions of the IC/CMB model. Here, we present Fermi/LAT flux density upper limits for the X-ray jets of four additional sources: PKS 1136-135, PKS 1229-021, PKS 1354+195, and PKS 2209+080. We show that these limits violate the IC/CMB predictions at a very high significance level. We also present new Hubble Space Telescope observations of the quasar PKS 2209+080 showing a newly detected optical jet, and Atacama Large Millimeter/submillimeter Array band 3 and 6 observations of all four sources, which provide key constraints on the spectral shape that enable us to rule out the IC/CMB model.

  1. A Twisted Star-Forming Web in the Galaxy IC 342

    NASA Image and Video Library

    2011-07-20

    Looking like a spider web swirled into a spiral, galaxy IC 342 presents its delicate pattern of dust in this infrared light image from NASA Spitzer Space Telescope. The very center glows especially brightly in the infrared.

  2. Decreased natural killer cell activity in atopic eczema.

    PubMed Central

    Hall, T J; Rycroft, R; Brostoff, J

    1985-01-01

    We have studied NK cell activity in atopic and non-atopic subjects using a standard 51Cr-release assay and K562 target cells. In atopics (AT) with allergic rhinitis and/or asthma, NK cell activity was similar to that in non-atopic (N) subjects, whilst patients with severe atopic eczema (AE) had depressed NK cell activity compared to AT or N subjects. In addition, circulating T-cell numbers and Con A responsiveness was decreased in AE, although neither parameter was correlated with decreased NK cell activity. However, decreased NK cell activity in atopic eczema was positively correlated with decreased numbers of Fc gamma + lymphocytes (P = 0.01) and decreased effector: target cell binding (P = 0.05), and negatively correlated with increased monocytes in AE (P = 0.09). AE NK cell activity was equally or more sensitive to the inhibitory effects of drugs such as dibutyryl cyclic AMP, prostaglandins (PG) D2,E2 and histamine. The relative percentage increase in NK cell activity by the interferon inducer poly I:C was similar in AE patients and controls. The results suggest that reduced numbers of circulating NK cells and pre-NK cells account for the depressed level of NK cell activity in subjects with severe atopic eczema. PMID:3876984

  3. Changes in the structure of nuclei between the magic neutron numbers 50 and 82 as indicated by a rotating-cluster analysis of the energy values of the first 2+ excited states of isotopes of cadmium, tin, and tellurium

    PubMed Central

    Pauling, Linus

    1981-01-01

    Values of R, the radius of rotation of the rotating cluster, are calculated from the observed values of the energy of the lowest 2+ states of the even isotopes of 48Cd, 50Sn, and 52Te with the assumption that the cluster is α, p2, and α, respectively. R shows a maximum at ≈N = 58, a minimum at ≈N = 62, and a second maximum at ≈N = 70. The increase to the first maximum is interpreted as resulting from the overcrowding of spherons (alphas and tritons) in the mantle (outer layer) of the nuclei, causing the cluster to change from rotating in the mantle to skimming over its surface; the decrease to the minimum results from the addition of three dineutrons to the core, expanding the mantle and permitting the rotating cluster to begin to drop back into it; and the increase to the second maximum results from the overcrowding of the larger mantle surrounding the core containing the semi-magic number 14 of neutrons rather than the magic number 8 for N = 50. The decrease after the second maximum results from the further increase in the number of core neutrons to 20, corresponding to the magic number 82. Some additional evidence for the change to an intermediate structure between N = 50 and N = 82 is also discussed. PMID:16593084

  4. The gene ICS3 from the yeast Saccharomyces cerevisiae is involved in copper homeostasis dependent on extracellular pH.

    PubMed

    Alesso, C A; Discola, K F; Monteiro, G

    2015-09-01

    In the yeast Saccharomyces cerevisiae, many genes are involved in the uptake, transport, storage and detoxification of copper. Large scale studies have noted that deletion of the gene ICS3 increases sensitivity to copper, Sortin 2 and acid exposure. Here, we report a study on the Δics3 strain, in which ICS3 is related to copper homeostasis, affecting the intracellular accumulation of this metal. This strain is sensitive to hydrogen peroxide and copper exposure, but not to other tested transition metals. At pH 6.0, the Δics3 strain accumulates a larger amount of intracellular copper than the wild-type strain, explaining the sensitivity to oxidants in this condition. Unexpectedly, sensitivity to copper exposure only occurs in acidic conditions. This can be explained by the fact that the exposure of Δics3 cells to high copper concentrations at pH 4.0 results in over-accumulation of copper and iron. Moreover, the expression of ICS3 increases in acidic pH, and this is correlated with CCC2 gene expression, since both genes are regulated by Rim101 from the pH regulon. CCC2 is also upregulated in Δics3 in acidic pH. Together, these data indicate that ICS3 is involved in copper homeostasis and is dependent on extracellular pH. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Good Trellises for IC Implementation of Viterbi Decoders for Linear Block Codes

    NASA Technical Reports Server (NTRS)

    Moorthy, Hari T.; Lin, Shu; Uehara, Gregory T.

    1997-01-01

    This paper investigates trellis structures of linear block codes for the integrated circuit (IC) implementation of Viterbi decoders capable of achieving high decoding speed while satisfying a constraint on the structural complexity of the trellis in terms of the maximum number of states at any particular depth. Only uniform sectionalizations of the code trellis diagram are considered. An upper-bound on the number of parallel and structurally identical (or isomorphic) subtrellises in a proper trellis for a code without exceeding the maximum state complexity of the minimal trellis of the code is first derived. Parallel structures of trellises with various section lengths for binary BCH and Reed-Muller (RM) codes of lengths 32 and 64 are analyzed. Next, the complexity of IC implementation of a Viterbi decoder based on an L-section trellis diagram for a code is investigated. A structural property of a Viterbi decoder called add-compare-select (ACS)-connectivity which is related to state connectivity is introduced. This parameter affects the complexity of wire-routing (interconnections within the IC). The effect of five parameters namely: (1) effective computational complexity; (2) complexity of the ACS-circuit; (3) traceback complexity; (4) ACS-connectivity; and (5) branch complexity of a trellis diagram on the very large scale integration (VISI) complexity of a Viterbi decoder is investigated. It is shown that an IC implementation of a Viterbi decoder based on a nonminimal trellis requires less area and is capable of operation at higher speed than one based on the minimal trellis when the commonly used ACS-array architecture is considered.

  6. Good trellises for IC implementation of viterbi decoders for linear block codes

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Moorthy, Hari T.; Uehara, Gregory T.

    1996-01-01

    This paper investigates trellis structures of linear block codes for the IC (integrated circuit) implementation of Viterbi decoders capable of achieving high decoding speed while satisfying a constraint on the structural complexity of the trellis in terms of the maximum number of states at any particular depth. Only uniform sectionalizations of the code trellis diagram are considered. An upper bound on the number of parallel and structurally identical (or isomorphic) subtrellises in a proper trellis for a code without exceeding the maximum state complexity of the minimal trellis of the code is first derived. Parallel structures of trellises with various section lengths for binary BCH and Reed-Muller (RM) codes of lengths 32 and 64 are analyzed. Next, the complexity of IC implementation of a Viterbi decoder based on an L-section trellis diagram for a code is investigated. A structural property of a Viterbi decoder called ACS-connectivity which is related to state connectivity is introduced. This parameter affects the complexity of wire-routing (interconnections within the IC). The effect of five parameters namely: (1) effective computational complexity; (2) complexity of the ACS-circuit; (3) traceback complexity; (4) ACS-connectivity; and (5) branch complexity of a trellis diagram on the VLSI complexity of a Viterbi decoder is investigated. It is shown that an IC implementation of a Viterbi decoder based on a non-minimal trellis requires less area and is capable of operation at higher speed than one based on the minimal trellis when the commonly used ACS-array architecture is considered.

  7. Interaction of Silymarin Flavonolignans with Organic Anion-Transporting Polypeptides

    PubMed Central

    Köck, Kathleen; Xie, Ying; Oberlies, Nicholas H.; Brouwer, Kim L. R.

    2013-01-01

    Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption and elimination, including the intestine and liver. Silymarin is a popular herbal supplement often used by patients with chronic liver disease; higher oral doses than those customarily used (140 mg three times/day) are being evaluated clinically. The present study examined the effect of silymarin flavonolignans on OATP1B1-, OATP1B3-, and OATP2B1-mediated transport in cell lines stably expressing these transporters and in human hepatocytes. In overexpressing cell lines, OATP1B1- and OATP1B3-mediated estradiol-17β-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated. OATP1B1-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC50 values of 1.3, 2.2 and 0.3 µM, respectively), silybin A (IC50 values of 9.7, 2.7 and 4.5 µM, respectively), silybin B (IC50 values of 8.5, 5.0 and 0.8 µM, respectively), and silychristin (IC50 values of 9.0, 36.4, and 3.6 µM, respectively). Furthermore, silymarin, silybin A, and silybin B (100 µM) significantly inhibited OATP-mediated estradiol-17β-glucuronide and rosuvastatin uptake into human hepatocytes. Calculation of the maximal unbound portal vein concentrations/IC50 values indicated a low risk for silymarin-drug interactions in hepatic uptake with a customary silymarin dose. The extent of silymarin-drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport. Higher than customary doses of silymarin, or formulations with improved bioavailability, may increase the risk of flavonolignan interactions with OATP substrates in patients. PMID:23401473

  8. Protective effect of unsymmetrical dichalcogenide, a novel antioxidant agent, in vitro and an in vivo model of brain oxidative damage.

    PubMed

    Prigol, Marina; Wilhelm, Ethel A; Schneider, Caroline C; Nogueira, Cristina W

    2008-11-25

    Unsymmetrical dichalcogenides, a class of organoselenium compounds, were screened for antioxidant activity in rat brain homogenates in vitro. Unsymmetrical dichalcogenides (1-3) were tested against lipid peroxidation induced by sodium nitroprusside (SNP) or malonate, and reactive species (RS) production induced by sodium azide in rat brain homogenates. Compounds 1 (without a substituent at the phenyl group), 2 (chloro substituent at the phenyl group bounded to the sulfur atom) and 3 (chloro substituent at the phenyl group bounded to the selenium atom) protected against lipid peroxidation induced by SNP. The IC50 values followed the order 3<2<1. Lipid peroxidation induced by malonate was also reduced by dichalcogenides 1, 2 and 3. The IC50 values were 3IC50 values were 3<2value of IC50 23.5 microM (IC50 values were 3<250 mg/kg, oral route, p.o). After 30 min, mice received SNP (0.35 microM/site i.c.v.). The levels of lipid peroxidation and the activity of catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) were carried out in brain homogenates of SNP-injected mice. Compound 3 protected against the increase in lipid peroxidation levels and the reduction of GST and GR activities in brain homogenate of mice exposed to SNP, suggesting the potential beneficial activity of dichalcogenides against deleterious oxidations in an in vivo model.

  9. The next generation in optical transport semiconductors: IC solutions at the system level

    NASA Astrophysics Data System (ADS)

    Gomatam, Badri N.

    2005-02-01

    In this tutorial overview, we survey some of the challenging problems facing Optical Transport and their solutions using new semiconductor-based technologies. Advances in 0.13um CMOS, SiGe/HBT and InP/HBT IC process technologies and mixed-signal design strategies are the fundamental breakthroughs that have made these solutions possible. In combination with innovative packaging and transponder/transceiver architectures IC approaches have clearly demonstrated enhanced optical link budgets with simultaneously lower (perhaps the lowest to date) cost and manufacturability tradeoffs. This paper will describe: *Electronic Dispersion Compensation broadly viewed as the overcoming of dispersion based limits to OC-192 links and extending link budgets, *Error Control/Coding also known as Forward Error Correction (FEC), *Adaptive Receivers for signal quality monitoring for real-time estimation of Q/OSNR, eye-pattern, signal BER and related temporal statistics (such as jitter). We will discuss the theoretical underpinnings of these receiver and transmitter architectures, provide examples of system performance and conclude with general market trends. These Physical layer IC solutions represent a fundamental new toolbox of options for equipment designers in addressing systems level problems. With unmatched cost and yield/performance tradeoffs, it is expected that IC approaches will provide significant flexibility in turn, for carriers and service providers who must ultimately manage the network and assure acceptable quality of service under stringent cost constraints.

  10. 30 CFR 57.22209 - Auxiliary fans (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22209 Auxiliary fans (I-C mines.... Tests for methane shall be made at electric auxiliary fans before they are started. Such fans shall not be operated when air passing over or through them contains 0.5 percent or more methane. ...

  11. 30 CFR 57.22310 - Electrical cables (I-C mines).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

  12. 30 CFR 57.22310 - Electrical cables (I-C mines).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

  13. 30 CFR 57.22310 - Electrical cables (I-C mines).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

  14. 30 CFR 57.22310 - Electrical cables (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

  15. 30 CFR 57.22310 - Electrical cables (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

  16. 30 CFR 57.22209 - Auxiliary fans (I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22209 Auxiliary fans (I-C mines.... Tests for methane shall be made at electric auxiliary fans before they are started. Such fans shall not be operated when air passing over or through them contains 0.5 percent or more methane. ...

  17. iPTF15dtg: a double-peaked Type Ic supernova from a massive progenitor

    DOE PAGES

    Taddia, Francesco; Fremling, C.; Sollerman, J.; ...

    2016-08-04

    Type Ic supernovae (SNe Ic) arise from the core-collapse of H- (and He-) poor stars, which could either be single Wolf-Rayet (WR) stars or lower-mass stars stripped of their envelope by a companion. Their light curves are radioactively powered and usually show a fast rise to peak (~10-15 d), without any early (in the first few days) emission bumps (with the exception of broad-lined SNe Ic) as sometimes seen for other types of stripped-envelope SNe (e.g., Type IIb SN 1993J and Type Ib SN 2008D). Here, we have studied iPTF15dtg, a spectroscopically normal SN Ic with an early excess inmore » the optical light curves followed by a long (~30 d) rise to the main peak. It is the first spectroscopically-normal double-peaked SN Ic to be observed. Our aim is to determine the properties of this explosion and of its progenitor star. Methods. Optical photometry and spectroscopy of iPTF15dtg was obtained with multiple telescopes. The resulting light curves and spectral sequence are analyzed and modeled with hydrodynamical and analytical models, with particular focus on the early emission. iPTF15dtg is a slow rising SN Ic, similar to SN 2011bm. Hydrodynamical modeling of the bolometric properties reveals a large ejecta mass (~10 M ⊙) and strong 56Ni mixing. The luminous early emission can be reproduced if we account for the presence of an extended (≳500 R ⊙), low-mass (≳0.045 M ⊙) envelope around the progenitor star. Alternative scenarios for the early peak, such as the interaction with a companion, a shock-breakout (SBO) cooling tail from the progenitor surface, or a magnetar-driven SBO are not favored. In conclusion, the large ejecta mass and the presence of H- and He-free extended material around the star suggest that the progenitor of iPTF15dtg was a massive (≳35 M ⊙) WR star that experienced strong mass loss.« less

  18. Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism

    PubMed Central

    2012-01-01

    Background In the present study, we tested a 50% ethanolic extract of Orthosiphon stamineus plants and its isolated bioactive compound with respect to their α-glucosidase and α-amylase inhibitory activities. Methods Bioactive flavonoid sinensetin was isolated from 50% ethanolic extract of Orthosiphon stamineus. The structure of this pure compound was determined on the NMR data and the α-glucosidase and α-amylase inhibitory activities of isolated sinensetin and 50% ethanolic extract of Orthosiphon stamineus were evaluated. Results In vitro studies of a 50% ethanolic extract of O. stamineus and the isolated sinensetin compound showed inhibitory activity on α-glucosidase (IC50: 4.63 and 0.66 mg/ml, respectively) and α-amylase (IC50: 36.70 mg/ml and 1.13 mg/ml, respectively). Inhibition of these enzymes provides a strong biochemical basis for the management of type 2 diabetes via the control of glucose absorption. Conclusion Alpha-glucosidase and α-amylase inhibition could the mechanisms through which the 50% ethanolic extract of O. stamineus and sinensetin exert their antidiabetic activity, indicating that it could have potential use in the management of non-insulin-dependent diabetes. PMID:23039079

  19. Androgen receptor (AR) degradation enhancer ASC-J9® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth.

    PubMed

    Cheng, Max A; Chou, Fu-Ju; Wang, Keliang; Yang, Rachel; Ding, Jie; Zhang, Qiaoxia; Li, Gonghui; Yeh, Shuyuan; Xu, Defeng; Chang, Chawnshang

    2018-03-28

    ASC-J9 ® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC 50 ) of ASC-J9 ® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC 50 values for ASC-J9 ® increased with increasing cell confluency. The IC 50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells. This suggests that ASC-J9 ® may function mainly via targeting the AR-positive PCa cells with limited unwanted side-effects to suppress the surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9 ® might function via altering the apoptosis signals to suppress the PCa AR-negative PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells demonstrated that ASC-J9 ® has similar AR degradation effects when dissolved in FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5), DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together, results from preclinical studies suggest a potential new therapy with AR-degradation enhancer ASC-J9 ® may potentially be ready to be used in human clinical trials in order to better suppress PCa at later castration resistant stages. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Novel 1, 3-N, O-Spiroheterocyclic compounds inhibit heparanase activity and enhance nedaplatin-induced cytotoxicity in cervical cancer cells.

    PubMed

    Song, Yanan; Hu, Bin; Qu, Hongjie; Wang, Lu; Zhang, Yunxiao; Tao, Jinchao; Cui, Jinquan

    2016-06-14

    Heparanase (HPA) is an enzyme that plays an important role in cancer metastasis and angiogenesis and is a potential target for molecular treatment of tumors. We previously found that abnormally high HPA expression in cervical cancer tissues is associated with poor survival and increased lymph node metastasis. The present study was conducted to assess the utility of inhibiting HPA enzyme activity in cervical cancer treatment. Two series of 13 novel HPA inhibitors were synthesized and optimized. All tested inhibitors reduced HPA enzyme activity (IC50 values ranged from 4.47 μM to 47.19 μM) and inhibited the growth of HeLa cells (IC50 values ranged from 48.16 μM to 96.64 μM). The No. 16 inhibitor inhibited the migration and growth of HeLa and Siha cells in a dose- and time-dependent manner, and increased cell apoptosis and cell cycle G0/G1 and G2/M phase arrest, while decreasing the S phase cell population. More importantly, No. 16 sensitized cervical cancer cells to low concentrations of nedaplatin, decreased HPA, c-Myc and h-TERT levels, and increased p53 levels in HeLa and Siha cells. These results suggest that this HPA inhibitor reduced proliferation and HPA expression in cervical cancer cells by restoring p53 activity and downregulating h-TERT and c-Myc expression.

  1. Inhibition of monoamine oxidase A and B activities by imidazol(ine)/guanidine drugs, nature of the interaction and distinction from I2-imidazoline receptors in rat liver

    PubMed Central

    Ozaita, Andrés; Olmos, Gabriel; Assumpció Boronat, M; Miguel Lizcano, José; Unzeta, Mercedes; García-Sevilla, Jesús A

    1997-01-01

    I2-Imidazoline sites ([3H]-idazoxan binding) have been identified on monoamine oxidase (MAO) and proposed to modulate the activity of the enzyme through an allosteric inhibitory mechanism (Tesson et al., 1995). The main aim of this study was to assess the inhibitory effects and nature of the inhibition of imidazol(ine)/guanidine drugs on rat liver MAO-A and MAO-B isoforms and to compare their inhibitory potencies with their affinities for the sites labelled by [3H]-clonidine in the same tissue. Competition for [3H]-clonidine binding in rat liver mitochondrial fractions by imidazol(ine)/guanidine compounds revealed that the pharmacological profile of the interaction (2 - styryl - 2 - imidazoline, LSL 61112>idazoxan>2 - benzofuranyl - 2 - imidazoline, 2-BFI=cirazoline>guanabenz>oxymetazoline>>clonidine) was typical of that for I2-sites. Clonidine inhibited rat liver MAO-A and MAO-B activities with very low potency (IC50s: 700 μM and 6 mM, respectively) and displayed the typical pattern of competitive enzyme inhibition (Lineweaver-Burk plots: increased Km and unchanged Vmax values). Other imidazol(ine)/guanidine drugs also were weak MAO inhibitors with the exception of guanabenz, 2-BFI and cirazoline on MAO-A (IC50s: 4–11 μM) and 2-benzofuranyl-2-imidazol (LSL 60101) on MAO-B (IC50: 16 μM). Idazoxan was a full inhibitor, although with rather low potency, on both MAO-A and MAO-B isoenzymes (IC50s: 280 μM and 624 μM, respectively). Kinetic analyses of MAO-A inhibition by these drugs revealed that the interactions were competitive. For the same drugs acting on MAO-B the interactions were of the mixed type inhibition (increased Km and decreased Vmax values), although the greater inhibitory effects on the apparent value of Vmax/Km than on the Vmax value indicated that the competitive element of the MAO-B inhibition predominated. Competition for [3H]-Ro 41-1049 binding to MAO-A or [3H]-Ro 19-6327 binding to MAO-B in rat liver

  2. Inhibition of the recombinant cattle tick Rhipicephalus (Boophilus) annulatus glutathione S-transferase.

    PubMed

    Guneidy, Rasha A; Shahein, Yasser E; Abouelella, Amira M K; Zaki, Eman R; Hamed, Ragaa R

    2014-09-01

    Rhipicephalus (Boophilus) annulatus is a bloodsucking ectoparasite that causes severe production losses in the cattle industry. This study aims to evaluate the in vitro effects of tannic acid, hematin (GST inhibitors) and different plant extracts (rich in tannic acid) on the activity of the recombinant glutathione S-transferase enzyme of the Egyptian cattle tick R. annulatus (rRaGST), in order to confirm their ability to inhibit the parasitic essential detoxification enzyme glutathione S-transferase. Extraction with 70% ethanol of Hibiscus cannabinus (kenaf flowers), Punica granatum (red and white pomegranate peel), Musa acuminata (banana peel) (Musaceae), Medicago sativa (alfalfa seeds), Tamarindus indicus (seed) and Cuminum cyminum (cumin seed) were used to assess: (i) inhibitory capacities of rRaGST and (ii) their phenolic and flavonoid contents. Ethanol extraction of red pomegranate peel contained the highest content of phenolic compounds (29.95mg gallic acid/g dry tissue) compared to the other studied plant extracts. The highest inhibition activities of rRaGST were obtained with kenaf and red pomegranate peel (P. granatum) extracts with IC50 values of 0.123 and 0.136mg dry tissue/ml, respectively. Tannic acid was the more effective inhibitor of rRaGST with an IC50 value equal to 4.57μM compared to delphinidine-HCl (IC50=14.9±3.1μM). Gossypol had a weak inhibitory effect (IC50=43.7μM), and caffeic acid had almost no effect on tick GST activity. The IC50 values qualify ethacrynic acid as a potent inhibitor of rRaGST activity (IC50=0.034μM). Cibacron blue and hematin showed a considerable inhibition effect on rRaGST activity, and their IC50 values were 0.13μM and 7.5μM, respectively. The activity of rRaGST was highest for CDNB (30.2μmol/min/mg protein). The enzyme had also a peroxidatic activity (the specific activity equals 26.5μmol/min/mg protein). Both tannic acid and hematin inhibited rRaGST activity non-competitively with respect to GSH and

  3. Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase.

    PubMed

    Choi, Eu Jin; Park, Jung Bae; Yoon, Kee Dong; Bae, Soo Kyung

    2014-10-01

    In this study, we evaluated inhibitory potentials of popularly-consumed berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) as herbal supplements on UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 in vitro. We also investigated the potential herb-drug interaction via UGT1A1 inhibition by blueberry in vivo. We demonstrated that these berries had only weak inhibitory effects on the five UGTs. Bilberry and elderberry had no apparent inhibitions. Blueberry weakly inhibited UGT1A1 with an IC50 value of 62.4±4.40 μg/mL and a Ki value of 53.1 μg/mL. Blueberry also weakly inhibited UGT2B7 with an IC50 value of 147±11.1 μg/mL. In addition, cranberry weakly inhibited UGT1A9 activity (IC50=458±49.7 μg/mL) and raspberry ketones weakly inhibited UGT2B7 activity (IC50=248±28.2 μg/mL). Among tested berries, blueberry showed the lowest IC50 value in the inhibition of UGT1A1 in vitro. However, the co-administration of blueberry had no effect on the pharmacokinetics of irinotecan and its active metabolite, SN-38, which was mainly eliminated via UGT1A1, in vivo. Our data suggests that these five berries are unlikely to cause clinically significant herb-drug interactions mediated via inhibition of UGT enzymes involved in drug metabolism. These findings should enable an understanding of herb-drug interactions for the safe use of popularly-consumed berries. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Anand constitutive model of lead-free solder joints in 3D IC device

    NASA Astrophysics Data System (ADS)

    Zhang, Liang; Liu, Zhi-quan; Ji, Yu-tong

    2016-08-01

    Anand constitutive relation of SnAgCu and SnAgCu-nano Al solders were studied under uniaxial tension, and the constitutive model was used in the finite element simulation to analyze the stress-strain response of lead-free solder joints in 3D IC devices. The results showed that the nine parameters of the Anand model can be determined from separated constitutive relations and experimental results. Based on Anand model, the finite element method was selected to calculate the stress-strain response of lead-free solder joints, it was found that in the 3D IC device the maximum stress-strain concentrated in the concern solder joints, the stress-strain of SnAgCu-nano Al solder joints was lower than that of SnAgCu solder joints, which represented that the addition of nano Al particles can enhance the reliability of lead-free solder joints in 3D IC devices.

  5. Triptolide inhibits cell growth and GRP78 protein expression but induces cell apoptosis in original and radioresistant NPC cells

    PubMed Central

    Lv, Wuwu; Lai, Chen; Chen, Zhikang; Wang, Ran; Long, Xueying; Feng, Xueping

    2016-01-01

    The radioresistance is the key factor to hamper curative effect and survival of nasopharyngeal carcinoma (NPC) patients. Nature triptolide (TPL) has been found to circumvent drug-resistant effect of cancer, but its effect on NPC radioresistance has been rarely studied. In the present study, the 10 Gy-resistant CNE2 subclones (CNE2-SR) were used as a NPC radioresistant model. The IC50 of TPL in CNE2 and CNE2-SR cells was measured by MTT assay, cell cycle was analyzed by flow cytometry, and protein expression was examined by western blot. Our data showed that TPL treatment decreased the percentage of viable cells, and IC50 value in CNE2 and CNE2-SR cells was 23.6 ± 1.41 nmol/L and 31.2 ± 1.16 nmol/L, respectively. Six Gy was a moderate dosage of X-ray for CNE2, and 25 nM TPL was close to IC50 value of CNE2 and CNE2-SR. Six Gy X-ray and/or 25 nM TPL significantly inhibited tumor growth in nude mice. Furthermore, 6 Gy X-ray and/or 25 nM TPL significantly inhibited cell growth and induced cell apoptosis and M/G2 phase arrest in CNE2 and CNE2-SR cells. Moreover, TPL treatment significantly inhibited the expression of GRP78 protein in CNE2 and CNE2-SR cells. These results suggest that TPL may serve as a potential radiosensitizer agent for NPC treatment. PMID:27391061

  6. Flavonoids of Cynara scolymus possess potent xanthinoxidase inhibitory activity in vitro but are devoid of hypouricemic effects in rats after oral application.

    PubMed

    Sarawek, Sasiporn; Feistel, Bjoern; Pischel, Ivo; Butterweck, Veronika

    2008-02-01

    Artichoke (Cynara scolymus L.) leaves have been historically used for the treatment of hyperuricemia and gout, however whether artichoke is truly efficacious for this indication, is still a matter of debate. Thus, the goal of the present study was first to examine the xanthine oxidase (XO) inhibitory activity of an artichoke leaf extract (ALE) and some of its main compounds in vitro and then further test potentially active substances for possible hypouricemic effects using an in vivo rat model. The in vitro study showed that ALE inhibited XO with only minimal inhibitory action (< 5 %) at 100 microg/mL. However, when selected compounds were tested, the caffeic acid derivatives revealed a weak XO inhibitory effect with IC (50) > 100 microM. From the tested flavones the aglycone luteolin potently inhibited XO with an IC (50) value of 1.49 microM. Luteolin 7-O-glucoside and luteolin 7-O-glucuronide showed lower XO inhibition activities with IC (50) values of 19.90 microM and 20.24 microM, respectively. However, oral administration of an aqueous ALE, luteolin, and luteolin 7-O-glucoside did not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate-treated rats. After intraperitoneal injection of luteolin a decrease in uric acid levels was detected suggesting that the hypouricemic effects of luteolin are due to its original form rather than its metabolites produced by the gut flora. In conclusion, an aqueous ALE, caffeic acid derivatives and flavones exerted XO inhibitory effects in vitro but a hypouricemic activity could not be confirmed after oral administration.

  7. Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.

    PubMed

    Xiao, Y; Smith, R D; Caruso, F S; Kellar, K J

    2001-10-01

    The opioid agonist properties of (+/-)-methadone are ascribed almost entirely to the (-)-methadone enantiomer. To extend our knowledge of the pharmacological actions of methadone at ligand-gated ion channels, we investigated the effects of the two enantiomers of methadone and its metabolites R-(+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium perchlorate (EDDP) and R-(+)-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline hydrochloride (EMDP), as well as structural analogs of methadone, including (-)-alpha-acetylmethadol hydrochloride (LAAM) and (+)-alpha-propoxyphene, on rat alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs) stably expressed in a human embryonic kidney 293 cell line, designated KXalpha3beta4R2. (+/-)-methadone inhibited nicotine-stimulated 86Rb+ efflux from the cells in a concentration-dependent manner with an IC50 value of 1.9 +/- 0.2 microM, indicating that it is a potent nAChR antagonist. The (-)- and (+)-enantiomers of methadone have similar inhibitory potencies on nicotine-stimulated 86Rb+ efflux, with IC50 values of approximately 2 microM. EDDP, the major metabolite of methadone, is even more potent, with an IC50 value of approximately 0.5 microM, making it one of the most potent nicotinic receptor blockers reported. In the presence of (+/-)-methadone, EDDP, or LAAM, the maximum nicotine-stimulated 86Rb+ efflux was markedly decreased, but the EC50 value for nicotine stimulation was altered only slightly, if at all, indicating that these compounds block alpha3beta4 nicotinic receptor function by a noncompetitive mechanism. Consistent with a noncompetitive mechanism, (+/-)-methadone, its metabolites, and structural analogs have very low affinity for nicotinic receptor agonist binding sites in membrane homogenates from KXalpha3beta4R2 cells. We conclude that both enantiomers of methadone and its metabolites as well as LAAM and (+)-alpha-propoxyphene are potent noncompetitive antagonists of alpha3beta4 nAChRs.

  8. Experimental and theoretical analysis of integrated circuit (IC) chips on flexible substrates subjected to bending

    NASA Astrophysics Data System (ADS)

    Chen, Ying; Yuan, Jianghong; Zhang, Yingchao; Huang, Yonggang; Feng, Xue

    2017-10-01

    The interfacial failure of integrated circuit (IC) chips integrated on flexible substrates under bending deformation has been studied theoretically and experimentally. A compressive buckling test is used to impose the bending deformation onto the interface between the IC chip and the flexible substrate quantitatively, after which the failed interface is investigated using scanning electron microscopy. A theoretical model is established based on the beam theory and a bi-layer interface model, from which an analytical expression of the critical curvature in relation to the interfacial failure is obtained. The relationships between the critical curvature, the material, and the geometric parameters of the device are discussed in detail, providing guidance for future optimization flexible circuits based on IC chips.

  9. Migration to Current Open Source Technologies by MagIC Enables a More Responsive Website, Quicker Development Times, and Increased Community Engagement

    NASA Astrophysics Data System (ADS)

    Jarboe, N.; Minnett, R.; Koppers, A.; Constable, C.; Tauxe, L.; Jonestrask, L.

    2017-12-01

    The Magnetics Information Consortium (MagIC) supports an online database for the paleo, geo, and rock magnetic communities ( https://earthref.org/MagIC ). Researchers can upload data into the archive and download data as selected with a sophisticated search system. MagIC has completed the transition from an Oracle backed, Perl based, server oriented website to an ElasticSearch backed, Meteor based thick client website technology stack. Using JavaScript on both the sever and the client enables increased code reuse and allows easy offloading many computational operations to the client for faster response. On-the-fly data validation, column header suggestion, and spreadsheet online editing are some new features available with the new system. The 3.0 data model, method codes, and vocabulary lists can be browsed via the MagIC website and more easily updated. Source code for MagIC is publicly available on GitHub ( https://github.com/earthref/MagIC ). The MagIC file format is natively compatible with the PmagPy ( https://github.com/PmagPy/PmagPy) paleomagnetic analysis software. MagIC files can now be downloaded from the database and viewed and interpreted in the PmagPy GUI based tool, pmag_gui. Changes or interpretations of the data can then be saved by pmag_gui in the MagIC 3.0 data format and easily uploaded to the MagIC database. The rate of new contributions to the database has been increasing with many labs contributing measurement level data for the first time in the last year. Over a dozen file format conversion scripts are available for translating non-MagIC measurement data files into the MagIC format for easy uploading. We will continue to work with more labs until the whole community has a manageable workflow for contributing their measurement level data. MagIC will continue to provide a global repository for archiving and retrieving paleomagnetic and rock magnetic data and, with the new system in place, be able to more quickly respond to the community

  10. A Chemical Investigation of the Leaves of Morus alba L.

    PubMed

    Chen, Xiao-Yan; Zhang, Ting; Wang, Xin; Hamann, Mark T; Kang, Jie; Yu, De-Quan; Chen, Ruo-Yun

    2018-04-26

    The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis and the absolute configuration was determined based on electronic circular dichroism (ECD) spectroscopic data and hydrolysis experiments. Their biological activity was evaluated using different biological assays, such as the assessment of their capacity to inhibit the aldose reductase enzyme; the determination of their cytotoxic activity and the evaluation of their neuroprotective effects against the deprivation of serum or against the presence of nicouline. Chemical investigation of the leaves of Morus alba L. resulted in four new structures 1 ⁻ 4 and a known molecule 5 . Compounds 2 and 5 inhibited aldose reductase with IC 50 values of 4.33 μM and 6.0 μM compared with the potent AR inhibitor epalrestat (IC 50 1.88 × 10 −3 μM). Pretreatment with compound 3 decreased PC12 cell apoptosis subsequent serum deprivation condition and pretreatment with compound 5 decreased nicouline-induced PC12 cell apoptosis as compared with control cells ( p < 0.001).

  11. Free Radical Scavenging Activity and Total Phenolic Content of Methanolic Extracts from Male Inflorescence of Salix aegyptiaca Grown in Iran

    PubMed Central

    Sonboli, Ali; Mojarrad, Mehran; Nejad Ebrahimi, Samad; Enayat, Shabnam

    2010-01-01

    This study was designed to examine the in vitro antioxidant activities and total phenolic contents of the methanolic extracts from male inflorescence of Salix aegyptiaca L. grown in Iran. The methanolic extract (ME) and its three fractions including water (WF), butanol (BF) and chloroform (CF) were prepared and then their antioxidant activities, as well as total phenolic contents, were evaluated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and the Folin–Ciocalteu method, respectively. Among the different fractions of methanol extract, BF indicated the most antioxidant activity with an IC50 value of 27.7 μg/mL and total phenols of 313.8 ppm, which is comparable with the synthetic antioxidant BHT (IC50 = 26.5μg/mL). The antioxidant activities of the other fractions decreased in the order of ME >WF > CF. The potent antioxidant activity of S. aegyptiaca supported its possible use as a natural antioxidant in food industries and other pharmaceutical preparations. PMID:24363740

  12. Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

    PubMed

    Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

    2010-05-15

    The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  13. Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

    PubMed

    Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

    2013-01-01

    Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

  14. Sensitivity limits and EC50 values of the Vibrio fischeri test for organic micropollutants in natural and spiked extracts from sediments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Salizzato, M.; Bertato, V.; Pavoni, B.

    1998-04-01

    Chemical analyses and bioassays were used in conjunction to assess the quality of sediments of the Venice lagoon. Organic micropollutants (polycyclic aromatic hydrocarbons [PAHs] polychlorinated biphenyls [PCBs], and chlorinated pesticides) were extracted from sediment samples and analyzed by gas chromatography after fractionation into classes of compounds. The Vibrio fischeri test was used to assess the acute toxicity of sediment extracts. The test was applied to organic extracts before cleanup and to extracts purified from sulfur and fractionated into single classes of compounds. Extracts before purification were much more toxic than single fractions. In particular, sulfur was toxic to V. fischeri.more » For PAHs and PCBs the 50% effective concentration (EC50) and EC20 values were determined using natural and spiked extracts. Sensitivity limits of the method for these compounds were also estimated as was in EC50 value of elemental sulfur dissolved in ethanol. A mathematical model was used to fit the concentration-response data to a sigmoid curve.« less

  15. 30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

  16. 30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

  17. The spectrum of the variable planetary nebula IC 4997

    NASA Technical Reports Server (NTRS)

    Hyung, Siek; Aller, Lawrence H.; Feibelman, Walter A.

    1994-01-01

    The compact, dusty, presumably young planetary nebula (PN) IC 4997 has been studied extensively since the variability of the lambda 4363/lambda 4340 ratio was established in 1956. Since 1938, other nebular lines have shown changes. IC 4997 is also unique because of the great density range revealed by its spectrum which goes in excitation from Mg I to (Ar IV). We present a detailed listing of spectral lines from 360 to 1005 nm. The diagnostic diagram shows that the spectrum can be interpreted only in terms of strata with a huge density gamut. Essential spectral features can be reproduced approximately by a model consisting of a geometrically thin shell of density around 10(exp 7) atoms cm(exp -3), surrounded by a much larger shell with a density of about 10(exp 4) atoms cm(exp -3). The actual, certainly more complex structure can be evaluated only when high resolution spatial imaging is at hand. The usual method of getting abundances from N(ion)/N(H(+)) and ionization correction factors (ICFs) cannot be applied here. It is argued that a reasonable theoretical model that represents the spectrum provides a valid initial approximation to nebular abundances. We propose that the chemical composition of IC 4997 does not differ greatly from that of the Sun. The finally adopted model suggests that the ejection of the material destined to form the inner shell occurred between 1900 and 1960, but observational evidence of such an ejection event is lacking. Perhaps the shell was accelerated. A need for further study is emphasized, especially the role of dust which appears to contribute 2% of the total mass. More attention to this object is recommended. An accurate measurement of its distance is especially desirable.

  18. Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases.

    PubMed

    Rahim, Fazal; Ullah, Hayat; Taha, Muhammad; Wadood, Abdul; Javed, Muhammad Tariq; Rehman, Wajid; Nawaz, Mohsan; Ashraf, Muhammad; Ali, Muhammad; Sajid, Muhammad; Ali, Farman; Khan, Muhammad Naseem; Khan, Khalid Mohammed

    2016-10-01

    To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12±0.01, 8.12±0.01 and 8.41±0.06μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85±0.0001μM). Three compounds 13, 24 and 3 having IC50 values 6.51±0.01, 9.22±0.07 and 37.82±0.14μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04±0.0001μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Chemical and biological analyses of the essential oils and main constituents of Piper species.

    PubMed

    Moura do Carmo, Dominique F; Amaral, Ana Cláudia Fernandes; Machado, Gérzia M C; Leon, Leonor Laura; Silva, Jefferson Rocha de Andrade

    2012-02-13

    The essential oils obtained from leaves of Piper duckei and Piper demeraranum by hydrodistillation were analyzed by gas chromatography-mass spectrometry. The main constituents found in P. demeraranum oil were limonene (19.3%) and β-elemene (33.1%) and in P. duckei oil the major components found were germacrene D (14.7%) and trans-caryophyllene (27.1%). P. demeraranum and P. duckei oils exhibited biological activity, with IC(50) values between 15 to 76 μg mL(-1) against two Leishmania species, P. duckei oil being the most active. The cytotoxicity of the essential oils on mice peritoneal macrophage cells was insignificant, compared with the toxicity of pentamidine. The main mono- and sesquiterpene, limonene (IC(50) = 278 μM) and caryophyllene (IC(50) = 96 μM), were tested against the strains of Leishmania amazonensis, and the IC(50) values of these compounds were lower than those found for the essential oils of the Piper species. The HET-CAM test was used to evaluate the irritation potential of these oils as topical products, showing that these oils can be used as auxiliary medication in cases of cutaneous leishmaniasis, with less side effects and lower costs.

  20. New efficient artemisinin derived agents against human leukemia cells, human cytomegalovirus and Plasmodium falciparum: 2nd generation 1,2,4-trioxane-ferrocene hybrids.

    PubMed

    Reiter, Christoph; Fröhlich, Tony; Zeino, Maen; Marschall, Manfred; Bahsi, Hanife; Leidenberger, Maria; Friedrich, Oliver; Kappes, Barbara; Hampel, Frank; Efferth, Thomas; Tsogoeva, Svetlana B

    2015-06-05

    In our ongoing search for highly active hybrid molecules exceeding their parent compounds in anticancer, antimalaria as well as antiviral activity and being an alternative to the standard drugs, we present the synthesis and biological investigations of 2nd generation 1,2,4-trioxane-ferrocene hybrids. In vitro tests against the CCRF-CEM leukemia cell line revealed di-1,2,4-trioxane-ferrocene hybrid 7 as the most active compound (IC50 of 0.01 μM). Regarding the activity against the multidrug resistant subline CEM/ADR5000, 1,2,4-trioxane-ferrocene hybrid 5 showed a remarkable activity (IC50 of 0.53 μM). Contrary to the antimalaria activity of hybrids 4-8 against Plasmodium falciparum 3D7 strain with slightly higher IC50 values (between 7.2 and 30.2 nM) than that of their parent compound DHA, hybrids 5-7 possessed very promising activity (IC50 values lower than 0.5 μM) against human cytomegalovirus (HCMV). The application of 1,2,4-trioxane-ferrocene hybrids against HCMV is unprecedented and demonstrated here for the first time. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Antileishmanial and antitrypanosomal activities of the 8-aminoquinoline tafenoquine.

    PubMed

    Yardley, Vanessa; Gamarro, Francisco; Croft, Simon L

    2010-12-01

    The 8-aminoquinoline tafenoquine showed significant in vitro activity against Leishmania species, including L. donovani amastigotes in macrophages, with 50% inhibitory concentrations (IC(50)s) between 0.1 and 4.0 μM for both pentavalent antimony (SbV)-sensitive and SbV-resistant strains and by oral administration in BALB/c mice, with 50% effective dose (ED(50)) values of 1.2 to 3.5 mg/kg for 5 days. Tafenoquine was less active against intracellular Trypanosoma cruzi amastigotes, with an IC(50) of 21.9 μM.

  2. Antileishmanial and Antitrypanosomal Activities of the 8-Aminoquinoline Tafenoquine ▿

    PubMed Central

    Yardley, Vanessa; Gamarro, Francisco; Croft, Simon L.

    2010-01-01

    The 8-aminoquinoline tafenoquine showed significant in vitro activity against Leishmania species, including L. donovani amastigotes in macrophages, with 50% inhibitory concentrations (IC50s) between 0.1 and 4.0 μM for both pentavalent antimony (SbV)-sensitive and SbV-resistant strains and by oral administration in BALB/c mice, with 50% effective dose (ED50) values of 1.2 to 3.5 mg/kg for 5 days. Tafenoquine was less active against intracellular Trypanosoma cruzi amastigotes, with an IC50 of 21.9 μM. PMID:20837750

  3. Inhibition of Procarcinogen Activating Enzyme CYP1A2 Activity and Free Radical Formation by Caffeic Acid and its Amide Analogues.

    PubMed

    Narongchai, Paitoon; Niwatananun, Kanokporn; Narongchai, Siripun; Kusirisin, Winthana; Jaikang, Churdsak

    2016-01-01

    Caffeic acid (CAF) and its amide analogues, ethyl 1-(3',4'-dihydroxyphenyl) propen amide (EDPA), phenethyl 1-(3',4'-dihydroxyphenyl) propen amide (PEDPA), phenmethyl 1- (3',4'-dihydroxyphenyl) propen amide (PMDPA) and octyl 1-(3',4'-dihydroxyphenyl) propen amide (ODPA) were investigated for the inhibition of procarcinogen activating enzyme. CYP1A2 and scavenging activity on formation of nitric oxide, superoxide anion, DPPH radical and hydroxyl radical. It was found that they inhibited CYP1A2 enzyme by uncompetitive inhibition. Apparent Ki values of CAF, EDPA, PEDPA, PMDPA and ODPA were 0.59, 0.39, 0.45, 0.75 and 0.80 µM, respectively suggesting potent inhibitors of CYP1A2. Moreover, they potentially scavenged nitric oxide radical with IC 50 values of 0.12, 0.22, 0.28, 0.22 and 0.51 mM, respectively. The IC50 values of superoxide anion scavenging were 0.20, 0.22, 0.44, 2.18 and 2.50 mM, respectively. 1, 1- diphenyl-2- picrylhydrazyl (DPPH) radical-scavenging ability, shown as IC50 values, were 0.41, 0.29, 0.30, 0.89 and 0.84 mM, respectively. Moreover, the hydroxyl radical scavenging in vitro model was shown as IC50 values of 23.22, 21.06, 17.10, 17.21 and 15.81 µM, respectively. From our results, caffeic acid and its amide analogues are in vitro inhibitors of human CYP1A2 catalytic activity and free radical formation. They may be useful to be developed as potential chemopreventive agents that block CYP1A2-mediated chemical carcinogenesis.

  4. PREFACE: IC-MSQUARE 2012: International Conference on Mathematical Modelling in Physical Sciences

    NASA Astrophysics Data System (ADS)

    Kosmas, Theocharis; Vagenas, Elias; Vlachos, Dimitrios

    2013-02-01

    The first International Conference on Mathematical Modelling in Physical Sciences (IC-MSQUARE) took place in Budapest, Hungary, from Monday 3 to Friday 7 September 2012. The conference was attended by more than 130 participants, and hosted about 290 oral, poster and virtual papers by more than 460 pre-registered authors. The first IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields in which mathematical modelling is used, such as theoretical/mathematical physics, neutrino physics, non-integrable systems, dynamical systems, computational nanoscience, biological physics, computational biomechanics, complex networks, stochastic modelling, fractional statistics, DNA dynamics, and macroeconomics. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, two parallel sessions ran every day. However, according to all attendees, the program was excellent with a high level of talks and the scientific environment was fruitful; thus all attendees had a creative time. The mounting question is whether this occurred accidentally, or whether IC-MSQUARE is a necessity in the field of physical and mathematical modelling. For all of us working in the field, the existing and established conferences in this particular field suffer from two distinguished and recognized drawbacks: the first is the increasing orientation, while the second refers to the extreme specialization of the meetings. Therefore, a conference which aims to promote the knowledge and development of high-quality research in mathematical fields concerned with applications of other scientific fields as well as modern technological trends in physics, chemistry, biology, medicine, economics, sociology, environmental sciences etc., appears to be a necessity. This is the key role that IC-MSQUARE will play. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contributions to IC-MSQUARE. We would also

  5. Interdisciplinary Collaboration amongst Colleagues and between Initiatives with the Magnetics Information Consortium (MagIC) Database

    NASA Astrophysics Data System (ADS)

    Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.; Shaar, R.

    2014-12-01

    Earth science grand challenges often require interdisciplinary and geographically distributed scientific collaboration to make significant progress. However, this organic collaboration between researchers, educators, and students only flourishes with the reduction or elimination of technological barriers. The Magnetics Information Consortium (http://earthref.org/MagIC/) is a grass-roots cyberinfrastructure effort envisioned by the geo-, paleo-, and rock magnetic scientific community to archive their wealth of peer-reviewed raw data and interpretations from studies on natural and synthetic samples. MagIC is dedicated to facilitating scientific progress towards several highly multidisciplinary grand challenges and the MagIC Database team is currently beta testing a new MagIC Search Interface and API designed to be flexible enough for the incorporation of large heterogeneous datasets and for horizontal scalability to tens of millions of records and hundreds of requests per second. In an effort to reduce the barriers to effective collaboration, the search interface includes a simplified data model and upload procedure, support for online editing of datasets amongst team members, commenting by reviewers and colleagues, and automated contribution workflows and data retrieval through the API. This web application has been designed to generalize to other databases in MagIC's umbrella website (EarthRef.org) so the Geochemical Earth Reference Model (http://earthref.org/GERM/) portal, Seamount Biogeosciences Network (http://earthref.org/SBN/), EarthRef Digital Archive (http://earthref.org/ERDA/) and EarthRef Reference Database (http://earthref.org/ERR/) will benefit from its development.

  6. Realization of MEMS-IC Vertical Integration Utilizing Smart Bumpless Bonding

    NASA Astrophysics Data System (ADS)

    Shiozaki, Masayoshi; Moriguchi, Makoto; Sasaki, Sho; Oba, Masatoshi

    This paper reports fundamental technologies, properties, and new experimental results of SBB (Smart Bumpless Bonding) to realize MEMS-IC vertical integration. Although conventional bonding technologies have had difficulties integrating MEMS and its processing circuit because of their rough bonding surfaces, fragile structures, and thermal restriction, SBB technology realized the vertical integration without thermal treatment, any adhesive materials including bumps, and chemical mechanical polishing. The SBB technology bonds sealing parts for vacuum sealing and electrodes for electrical connection simultaneously as published in previous experimental study. The plasma CVD SiO2 is utilized to realize vacuum sealing as sealing material. And Au projection studs are formed on each electrode and connected electrically between two wafers by compressive plastic deformation and surface activation. In this paper, new experimental results including vacuum sealing properties, electrical improvement, IC bonding results on the described fundamental concept and properties are reported.

  7. Reversal of in vitro cellular MRP1 and MRP2 mediated vincristine resistance by the flavonoid myricetin.

    PubMed

    van Zanden, Jelmer J; de Mul, Anika; Wortelboer, Heleen M; Usta, Mustafa; van Bladeren, Peter J; Rietjens, Ivonne M C M; Cnubben, Nicole H P

    2005-06-01

    In the present study, the effects of myricetin on either MRP1 or MRP2 mediated vincristine resistance in transfected MDCKII cells were examined. The results obtained show that myricetin can inhibit both MRP1 and MRP2 mediated vincristine efflux in a concentration dependent manner. The IC50 values for cellular vincristine transport inhibition by myricetin were 30.5+/-1.7 microM for MRP1 and 24.6+/-1.3 microM for MRP2 containing MDCKII cells. Cell proliferation analysis showed that the MDCKII control cells are very sensitive towards vincristine toxicity with an IC50 value of 1.1+/-0.1 microM. The MDCKII MRP1 and MRP2 cells are less sensitive towards vincristine toxicity with IC50 values of 33.1+/-1.9 and 22.2+/-1.4 microM, respectively. In both the MRP1 and MRP2 cells, exposure to 25 microM myricetin enhances the sensitivity of the cells towards vincristine toxicity to IC50 values of 7.6+/-0.5 and 5.8+/-0.5 microM, respectively. The increase of sensitivity represents a reversal of the resistance towards vincristine as a result of MRP1 and MRP2 inhibition. Thus, the present study demonstrates the ability of the flavonoid myricetin to modulate MRP1 and MRP2 mediated resistance to the anticancer drug vincristine in transfected cells, indicating that flavonoids might be a valuable adjunct to chemotherapy to block MRP mediated resistance.

  8. Antimicrobial and antiprotozoal activities of secondary metabolites from the fungus Eurotium repens

    PubMed Central

    Gao, Jiangtao; Radwan, Mohamed M.; León, Francisco; Wang, Xiaoning; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Lupien, Shari; Hill, Robert A.; Dugan, Frank M.; Cutler, Horace G.

    2011-01-01

    In this study, we examined in vitro antibacterial, antifungal, antimalarial, and antileishmanial activities of secondary metabolites (1–8) isolated from the fungus Eurotium repens. All compounds showed mild to moderate antibacterial or antifungal or both activities except 7. The activity of compound 6 was the best of the group tested. The in vitro antimalarial evaluation of these compounds revealed that compounds 1–3, 5, and 6 showed antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC50 values in the range of 1.1–3.0 μg/ml without showing any cytotoxicity to the mammalian cells. Compound 5 displayed the highest antimalarial activity. Antileishmanial activity against Leishmania donovani promastigotes was observed for compounds 1–6 with IC50 values ranging from 6.2 to 23 μg/ml. Antileishmanial activity of compounds 5 and 6 (IC50 values of 7.5 and 6.2 μg/ml, respectively) was more potent than 1–4 (IC50 values ranging from 19–23 μg/ml). Compounds 7 and 8 did not show any antiprotozoal effect. Preliminary structure and activity relationship studies indicated that antibacterial, antifungal, antimalarial, and antileishmanial activities associated with phenol derivates (1–6) seem to be dependent on the number of double bonds in the side chain, which would be important for lead optimization in the future. PMID:23024574

  9. Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).

    PubMed

    Schwalenberg, Thilo; Stolzenburg, Jens-Uwe; Ho, Thi Phuc; Mallock, Tobias; Hartenstein, Siegurd; Alexander, Henry; Zimmermann, Gerolf; Hohenfellner, Rudolf; Denzinger, Stefan; Burger, Maximilian; Horn, Lars-Christian; Neuhaus, Jochen

    2012-06-01

    Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

  10. Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.

    PubMed

    Genberg, M; Andrén, B; Lind, L; Hedenström, H; Malinovschi, A

    2018-01-01

    Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (V O 2 ) and CO 2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared V O 2 at maximal load (peakV O 2 ) and anaerobic threshold (V O 2@ AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakV O 2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakV O 2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakV O 2 most: 112·5%. Furthermore, underestimation of peakV O 2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakV O 2 , while men had 104%. PeakV O 2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min -1 , P = 0·11). Lower BR (≤30%) related to significantly higher peakV O 2 (P<0·001). In conclusion, peakV O 2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  11. Ionized and Molecular Gas in IC 860: Evidence for an Outflow

    NASA Astrophysics Data System (ADS)

    Adams, Carson; Alatalo, Katherine; Medling, Anne M.

    2018-01-01

    Galaxies at present-day fall predominantly in two distinct populations, as either blue, star-forming spirals or red, quiescent early-type galaxies. Blue galaxies appear to evolve onto the red sequence as star formation is quenched. The absence of a significant population falling in the intermediate ‘green valley’ implies that these transitions must occur rapidly. Identifying the initial properties of and pathways taken by these ‘dying galaxies’ is essential to building a complete understanding of galactic evolution. In this work, we investigate these phenomena in action within IC860 — a nearby, early-type spiral in the initial stages of undergoing a rapid transition in the presence of a powerful AGN-driven molecular outflow. As a shocked, post-starburst galaxy with an intermediate-age stellar population which lies on the blue end of the green valley, IC860 provides a window into the early stages of galaxy transition and AGN feedback. We present Hubble Space Telescope imaging of IC860 showing a violent, dusty outflow originating from a compact core. We find that the mean velocity map of the CO(1-0) from CARMA suggests a dynamically excited bar funneling molecular gas into the galactic center. Finally, we present kinematic maps of ionized gas emission lines as well as sodium D absorption tracing neutral winds obtained by the Wide-Field Spectrograph.

  12. Helichrysum and grapefruit extracts inhibit carbohydrate digestion and absorption, improving postprandial glucose levels and hyperinsulinemia in rats.

    PubMed

    de la Garza, Ana Laura; Etxeberria, Usune; Lostao, María Pilar; San Román, Belén; Barrenetxe, Jaione; Martínez, J Alfredo; Milagro, Fermín I

    2013-12-11

    Several plant extracts rich in flavonoids have been reported to improve hyperglycemia by inhibiting digestive enzyme activities and SGLT1-mediated glucose uptake. In this study, helichrysum ( Helichrysum italicum ) and grapefruit ( Citrus × paradisi ) extracts inhibited in vitro enzyme activities. The helichrysum extract showed higher inhibitory activity of α-glucosidase (IC50 = 0.19 mg/mL) than α-amylase (IC50 = 0.83 mg/mL), whereas the grapefruit extract presented similar α-amylase and α-glucosidase inhibitory activities (IC50 = 0.42 mg/mL and IC50 = 0.41 mg/mL, respectively). Both extracts reduced maltose digestion in noneverted intestinal sacs (57% with helichrysum and 46% with grapefruit). Likewise, both extracts inhibited SGLT1-mediated methylglucoside uptake in Caco-2 cells in the presence of Na(+) (56% of inhibition with helichrysum and 54% with grapefruit). In vivo studies demonstrated that helichrysum decreased blood glucose levels after an oral maltose tolerance test (OMTT), and both extracts reduced postprandial glucose levels after the oral starch tolerance test (OSTT). Finally, both extracts improved hyperinsulinemia (31% with helichrysum and 50% with grapefruit) and HOMA index (47% with helichrysum and 54% with grapefruit) in a dietary model of insulin resistance in rats. In summary, helichrysum and grapefruit extracts improve postprandial glycemic control in rats, possibly by inhibiting α-glucosidase and α-amylase enzyme activities and decreasing SGLT1-mediated glucose uptake.

  13. Anti-Inflammatory Components of the Starfish Astropecten polyacanthus

    PubMed Central

    Thao, Nguyen Phuong; Cuong, Nguyen Xuan; Luyen, Bui Thi Thuy; Quang, Tran Hong; Hanh, Tran Thi Hong; Kim, Sohyun; Koh, Young-Sang; Nam, Nguyen Hoai; Kiem, Phan Van; Minh, Chau Van; Kim, Young Ho

    2013-01-01

    Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 μM) and 6 (IC50 = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 μM) and 4 (IC50 = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively. PMID:23945602

  14. Prognostic value of decreased FOXP1 protein expression in various tumors: a systematic review and meta-analysis

    PubMed Central

    Xiao, Jian; He, Bixiu; Zou, Yong; Chen, Xi; Lu, Xiaoxiao; Xie, Mingxuan; Li, Wei; He, Shuya; You, Shaojin; Chen, Qiong

    2016-01-01

    The prognostic value of forkhead box protein P1 (FOXP1) protein expression in tumors remains controversial. Therefore, we conducted a systematic review and meta-analysis, searching the PubMed, Embase and Web of Science databases to identify eligible studies. In total, we analyzed 22 articles that examined 9 tumor types and included 2468 patients. Overall, decreased expression of FOXP1 protein was associated with favorable overall survival (OS) in lymphoma patients (HR = 0.38, 95%CI: 0.30–0.48, p < 0.001). In patients with solid tumors, decreased FOXP1 expression correlated with unfavorable OS (HR = 1.82, 95%CI: 1.18–2.83, p = 0.007). However, when FOXP1 protein expression was nuclear, decreased expression was also associated with favorable OS (HR = 0.53, 95%CI: 0.32–0.86, p = 0.011). Furthermore, decreased FOXP1 expression resulted in the best OS in patients with mucosa-associated lymphoid tissue (MALT) lymphomas (HR = 0.26, 95%CI: 0.11–0.59, p = 0.001), but the worst OS was observed in non-small cell lung cancer (NSCLC) patients (HR = 3.11, 95%CI: 1.87–5.17, p < 0.001). In addition, decreased FOXP1 expression was significantly correlated with an unfavorable relapse-free survival (RFS) in breast cancer patients (HR = 1.93, 95%CI: 1.33–2.80, p = 0.001). PMID:27457567

  15. 15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and Technology...

  16. 15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and Technology...

  17. 15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and Technology...

  18. A Monte Carlo Approach to Magnetar-powered Transients. II. Broad-lined Type Ic Supernovae Not Associated with GRBs

    NASA Astrophysics Data System (ADS)

    Wang, L. J.; Cano, Z.; Wang, S. Q.; Zheng, W. K.; Liu, L. D.; Deng, J. S.; Yu, H.; Dai, Z. G.; Han, Y. H.; Xu, D.; Qiu, Y. L.; Wei, J. Y.; Li, B.; Song, L. M.

    2017-12-01

    Broad-lined type Ic supernovae (SNe Ic-BL) are a subclass of rare core-collapse SNe whose energy source is debated in the literature. Recently, a series of investigations on SNe Ic-BL with the magnetar (plus 56Ni) model were carried out. Evidence for magnetar formation was found for the well-observed SNe Ic-BL 1998bw and 2002ap. In this paper, we systematically study a large sample of SNe Ic-BL not associated with gamma-ray bursts (GRBs). We use photospheric velocity data determined in a homogeneous way. We find that the magnetar+56Ni model provides a good description of the light curves and velocity evolution of our sample of SNe Ic-BL, although some SNe (not all) can also be described by the pure-magnetar model or by the two-component pure-56Ni model (three out of 12 are unlikely to be explained by two-component model). In the magnetar+56Ni model, the amount of 56Ni required to explain their luminosity is significantly reduced, and the derived initial explosion energy is, in general, in accordance with neutrino heating. Some correlations between different physical parameters are evaluated, and their implications regarding magnetic field amplification and the total energy reservoir are discussed.

  19. Three new triterpenoids from Ganoderma theaecolum.

    PubMed

    Liu, Li-Ying; Yan, Zheng; Kang, Jie; Chen, Ruo-Yun; Yu, De-Quan

    2017-09-01

    Three new triterpenoids (1-3), together with four known triterpenoids (4-7), were isolated from the fruiting bodies of Ganoderma theaecolum. Their structures were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds 4 and 6 exhibited antitumor activities against H460 cells with IC 50 values of 22.4 and 43.1 μM, respectively. And the cytotoxic activities of compounds 4 and 5 against MDA-MB-231 cancer cell lines were assayed with IC 50 values of 49.1 and 75.8 μM, respectively.

  20. Antitumor and antiangiogenic effects of GA-13315, a gibberellin derivative.

    PubMed

    Zhang, Yanli; Zhang, Hui; Chen, Jingbo; Zhao, Haixia; Zeng, Xianghui; Zhang, Hongbin; Qing, Chen

    2012-02-01

    This study showed that 13-chlorine-3,15-dioxy-gibberellic acid methyl ester (GA-13315), a gibberellin derivative, possessed high antitumor and antiangiogenic activity in vitro and in vivo. Cytotoxicity assays showed that GA-13315 was a potential and efficient antitumor compound, with inhibitory concentration 50 (IC(50)) values ranging from 0.13 to 30.28 μg/ml in 12 human tumor cell lines, and it showed moderate toxicity to peripheral blood mononuclear cells with an IC(50) value of 14.2 μg/ml. Administration of 0.5 or 2.5 mg/kg GA-13315 for 23 days significantly inhibited tumor growth of human non-small cell lung tumor (A549) xenografts, with relative growth rates ranging from 29.91% to 35.05%. Acute toxicity was determined in ICR mice, and the lethal dose 50 (LD(50)) was 4.19 g/kg after intragastric administration. The high antitumor potency of GA-13315 occurred in parallel with its antiangiogenic activity. In vitro, GA-13315 inhibited recombinant human epithelial growth factor-induced chemotactic motility and capillary-like tube formation of primary cultured human endothelial cells. Furthermore, GA-13315 decreased the factor VIII(+) microvessel density and vascular endothelial growth factor expression in A549 tumors, indicating its antiangiogenic efficacy in vivo. These results indicate that the antiangiogenic activity of GA-13315 contributes to its anticancer properties. Further studies are needed to investigate the use of GA-13315 as an anticancer drug.

  1. Identification of New Human Malaria Parasite Plasmodium Falciparum Dihydroorotate Dehydrogenase Inhibitors by Pharmacophore and Structure-Based Virtual Screening

    PubMed Central

    Pavadai, Elumalai; El Mazouni, Farah; Wittlin, Sergio; de Kock, Carmen; Phillips, Margaret A.; Chibale, Kelly

    2016-01-01

    Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway, which the Plasmodium falciparum relies on exclusively for survival, has emerged as a promising target for antimalarial drugs. In an effort to discover new and potent PfDHODH inhibitors, 3D-QSAR pharmacophore models were developed based on the structures of known PfDHODH inhibitors and the validated Hypo1 model was used as a 3D search query for virtual screening of the National Cancer Institute database. The virtual hit compounds were further filtered based on molecular docking and Molecular Mechanics/Generalized Born Surface Area binding energy calculations. The combination of the pharmacophore and structure-based virtual screening resulted in the identification of nine new compounds that showed >25% inhibition of PfDHODH at a concentration of 10 μM, three of which exhibited IC50 values in the range of 0.38–20 μM. The most active compound, NSC336047, displayed species-selectivity for PfDHODH over human DHODH and inhibited parasite growth with an IC50 of 26 μM. In addition to this, thirteen compounds inhibited parasite growth with IC50 values of ≤ 50 μM, four of which showed IC50 values in the range of 5–12 μM. These compounds could be further explored in the identification and development of more potent PfDHODH and parasite growth inhibitors. PMID:26915022

  2. X-Ray Activity in the Open Cluster IC 4665

    NASA Technical Reports Server (NTRS)

    Giamapapa, Mark S.; Prosser, Charles F.; Fleming, Thomas A.

    1997-01-01

    We present the results of a joint ROSAT High Resolution Imager (HRI) and optical investigation of the open cluster IC 4665. The ROSAT data contains detections for 28 stellar sources in the field, including 22 cluster members and candidate members spanning the color range -0.18 less than or equal to (B - V(sub o)) less than or equal to +1.63 (approx. B3 - M3). Upper limits are given for the remaining members (or candidate members) in the HRI field. Keck HIRES spectra have been obtained that yield radial and rotational velocity measures, respectively, for faint, low mass candidate members located within the field of the ROSAT HRI observation. In addition, photometry of possible optical counterparts to previously uncatalogued X-ray sources in the HRI field is presented. The trends in X-ray properties with (B - V) color in IC 4665 are found to be quite similar to that for other, more nearby young clusters such as the Pleiades and alpha Persei. In particular, a maximum in normalized X-ray luminosity of log (L(sub x)/L(sub bol)) approx. equal 3 is observed, beginning in the color range of (B - V)(sub o) = 0.7 - 0.8. This is similar to the corresponding color range among Pleiades members, in agreement with the earlier estimate, that the age of IC 4665 is similar to the age of the Pleiades. The correlation of rotation and X-ray emission levels is consistent with that in other young clusters. Among the high mass stars in IC 4665, five B stars are detected as X-ray sources. Of these, one is a spectroscopic binary while the remaining objects are apparently single staxs. The level of intrinsic X-ray emission observed in the rapidly rotating (v sini greater than 200 km/ s), single B stars is consistent with an origin due to shock heating of the ambient medium by radiatively driven, rotationally enhanced winds. On the basis of these observations and the results for other clusters, we argue that observed levels of X-ray emission in high mass stars of log (L(sub x)/L(sub bol

  3. Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability.

    PubMed

    Paine, Tracie A; Swedlow, Nathan; Swetschinski, Lucien

    2017-01-15

    Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior. Rats were implanted with cannulae aimed at either the medial PFC or the BLA and then were tested on up to 4 behavioral tests following bilateral infusions of 0.5μl bicuculline methiodide (BMI, a GABA A receptor antagonist) at doses of 0, 25, or 50ng/μl. Rats were tested in the social interaction test, the social preference test, the sucrose preference test and for locomotor activity (BLA infusions only). Intra-BLA or PFC BMI infusions decreased the amount of time and the number of social interactions in the social interaction test. Further, in the social preference test, rats infused with 50ng BMI no longer exhibited a preference to explore a social over a non-social stimulus. The change in sociability was not due to a change in reward processing or locomotor behavior. Decreasing GABA transmission in either the medial PFC or BLA decreased sociability. Thus, changes in GABA signaling observed in conditions such as autism or schizophrenia may mediate the social withdrawal characteristic of these conditions. Moreover, they suggest that social withdrawal may be treated by drugs that potentiate GABA transmission. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Transforming and differentiation-inducing potential of constitutively activated c-kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line.

    PubMed Central

    Hashimoto, K.; Tsujimura, T.; Moriyama, Y.; Yamatodani, A.; Kimura, M.; Tohya, K.; Morimoto, M.; Kitayama, H.; Kanakura, Y.; Kitamura, Y.

    1996-01-01

    Two mutations of c-kit receptor tyrosine kinase (KIT), valine-559 to glycine (G559) and aspartic acid-814 to valine (V814), resulted in its constitutive activation. To examine the transforming and differentiation-inducing potential of the mutant KIT, we used the murine interleukin-3-dependent IC-2 mast cell line as a transfectant. The IC-2 cells contained few basophilic granules and did not express KIT on the surface. The KITG559 or KITV814 gene was introduced into IC-2 cells using a retroviral vector. KITG559 and KITV814 expressed in IC-2 cells were constitutively phosphorylated on tyrosine and demonstrated kinase activity in the absence of stem cell factor, which is a ligand for KIT. IC-2 cells expressing either KITG559 or KITV814 (IC-2G559 or IC-2V814 cells) showed factor-independent growth in suspension culture and produced tumors in nude athymic mice. In addition, IC-2G559 and IC-2V814 cells showed a more mature phenotype compared with the phenotype of the original IC-2 cells, especially after transplantation into nude mice. The number of basophilic granules and the content of histamine increased remarkably. KITG559 and KITV814 also influenced the transcriptional phenotype of mouse mast cell proteases (MMCP) in IC-2 cells. The expression of MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than in the original IC-2 cells. The results indicated that constitutively activated KIT had not only oncogenic activity but also differentiation-inducing activity in mast cells. Images Figure 1 Figure 4 Figure 5 Figure 6 PMID:8546206

  5. A study of H-alpha velocities in NGC 1499, NGC 7000, and IC 1318B/C

    NASA Technical Reports Server (NTRS)

    Fountain, W. F.; Gary, G. A.; Odell, C. R.

    1983-01-01

    Multiple slit echelle spectrograph observations of the H-alpha emission line are used to map the radial velocities of the California Nebula (NGC 1499), the North American Nebula complex (NGC 7000 and IC 5070), and IC 1318B/C. The California Nebula is singularly constant in velocity, considering its geometry. The North American Nebula complex reflects a very simple, classical dynamical picture. The expansion discovered earlier in IC 1318B/C is confirmed, detailed, and the model refined. The new data, along with that in earlier papers of this series, show that stellar wind acceleration and champagne flow mechanisms both play important roles in determining the evolution of H II regions.

  6. 15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... Controller of Imports and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and...

  7. 15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... Controller of Imports and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and...

  8. Biological activities of aqueous extract from Cinnamomum porrectum

    NASA Astrophysics Data System (ADS)

    Farah, H. Siti; Nazlina, I.; Yaacob, W. A.

    2013-11-01

    A study was carried out to evaluate biological activities of an extract obtained from Cinnamomum porrectum under reflux using water. Aqueous extract of Cinnamomum porrectum was tested for antibacterial activity against six Gram-positive and eight Gram-negative bacteria as well as MRSA. The results confirmed that the aqueous extract of Cinnamomum porrectum was bactericidal. Cytotoxic tests on Vero cell culture revealed that Cinnamomum porrectum was non-toxic which IC50 value higher than 0.02 mg/mL. Antiviral activity was tested based on the above IC50 values together with the measured EC50 values to obtain Therapeutic Index. The result showed that Cinnamomum porrectum has the ability to inhibit viral replication of HSV-1 in Vero cells.

  9. Decreased cyclooxygenase inhibition by aspirin in polymorphic variants of human prostaglandin H synthase-1

    PubMed Central

    Liu, Wen; Poole, Elizabeth M.; Ulrich, Cornelia M.; Kulmacz, Richard J.

    2012-01-01

    Objectives Aspirin, a major anti-platelet and cancer preventing drug, irreversibly blocks the cyclooxygenase activity of prostaglandin H synthase-1 (PGHS-1). Considerable differences in aspirin effectiveness are observed between individuals, and some of this variability may be due to PGHS-1 protein variants. Our overall aim is to determine which, if any, of the known variants in the mature PGHS-1 protein lead to functional alterations in cyclooxygenase catalysis or inhibition by aspirin. The present study targeted four PGHS-1 variants: R53H, R108Q, L237M and V481I. Methods Wildtype human PGHS-1 and the four polymorphic variants were expressed as histidine-tagged, homodimeric proteins in insect cells using baculovirus vectors, solubilized with detergent, and purified by affinity chromatography. The purified proteins were characterized in vitro to evaluate cyclooxygenase and peroxidase catalytic parameters and the kinetics of cyclooxygenase inhibition by aspirin and NS-398. Results Compared to wildtype, several variants exhibited a higher COX/POX ratio (up to 1.5-fold, for R108Q), an elevated arachidonate Km (up to 1.9-fold, for R108Q), and/or a lower aspirin reactivity (up to 60% less, for R108Q). The decreased aspirin reactivity in R108Q reflected both a 70% increase in the Ki for aspirin and a 30% decrease in the rate constant for acetyl group transfer to the protein. Computational modeling of the brief aspirin pulses experienced by PGHS-1 in circulating platelets during daily aspirin dosing predicted that the 60% lower aspirin reactivity in R108Q gives a 15-fold increase in surviving cyclooxygenase activity; smaller, ~2-fold increases in surviving cyclooxygenase activity were predicted for L237M and V481I. NS-398 competitively inhibited cyclooxygenase catalysis of the wildtype (Ki = 6 μM) and inhibited cyclooxygenase inactivation by 1.0 mM aspirin in both wildtype (IC50 = 0.8 μM) and R108Q (IC50 = 2.1 μM). Conclusions Of the four PGHS-1 variants examined, R108

  10. In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barile, F.A.; Arjun, S.; Borges, L.

    1991-03-11

    This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 valuesmore » suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.« less

  11. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zaczek, R.; Culp, S.; De Souza, E.B.

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain regionmore » with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.« less

  12. Investigating the high-frequency spectral features of SNRs Tycho, W44 and IC443 with the Sardinia Radio Telescope

    NASA Astrophysics Data System (ADS)

    Loru, S.; Pellizzoni, A.; Egron, E.; Righini, S.; Iacolina, M. N.; Mulas, S.; Cardillo, M.; Marongiu, M.; Ricci, R.; Bachetti, M.; Pilia, M.; Trois, A.; Ingallinera, A.; Petruk, O.; Murtas, G.; Serra, G.; Concu, F. Buffa R.; Gaudiomonte, F.; Melis, A.; Navarrini, A.; Perrodin, D.; Valente, G.

    2018-05-01

    The main characteristics in the radio continuum spectra of Supernova Remnants (SNRs) result from simple synchrotron emission. In addition, electron acceleration mechanisms can shape the spectra in specific ways, especially at high radio frequencies. These features are connected to the age and the peculiar conditions of the local interstellar medium interacting with the SNR. Whereas the bulk radio emission is expected at up to 20 - 50 GHz, sensitive high-resolution images of SNRs above 10 GHz are lacking and are not easily achievable, especially in the confused regions of the Galactic Plane. In the framework of the early science observations with the Sardinia Radio Telescope in February-March 2016, we obtained high-resolution images of SNRs Tycho, W44 and IC443 that provided accurate integrated flux density measurements at 21.4 GHz: 8.8 ± 0.9 Jy for Tycho, 25 ± 3 Jy for W44 and 66 ± 7 Jy for IC443. We coupled the SRT measurements with radio data available in the literature in order to characterise the integrated and spatially-resolved spectra of these SNRs, and to find significant frequency- and region-dependent spectral slope variations. For the first time, we provide direct evidence of a spectral break in the radio spectral energy distribution of W44 at an exponential cutoff frequency of 15 ± 2 GHz. This result constrains the maximum energy of the accelerated electrons in the range 6 - 13 GeV, in agreement with predictions indirectly derived from AGILE and Fermi-LAT gamma-ray observations. With regard to IC443, our results confirm the noticeable presence of a bump in the integrated spectrum around 20 - 70 GHz that could result from a spinning dust emission mechanism.

  13. Protein adsorption to poly(ethylenimine)-modified Sepharose FF: VI. Partial charge neutralization drastically increases uptake rate.

    PubMed

    Zhao, Yangyang; Dong, Xiaoyan; Yu, Linling; Sun, Yan

    2016-01-04

    The adsorption and elution behaviors of bovine serum albumin (BSA) on poly(ethylenimine) (PEI)-grafted Sepharose FF resins were recently studied and a critical ionic capacity (cIC; 600 mmol/L) was found, above which the uptake rate increased drastically due to the occurrence of significant "chain delivery" effect. Moreover, above the cIC value, higher salt concentrations were required for protein elution due to the high charge density of the resins. In this work, we have reduced the charge density on the PEI chains of a PEI-grafted resin by neutralization of the amine groups with sodium acetate. PEI-modified resin with IC of 740 mmol/L (FF-PEI-L740, IC>cIC) was chosen as the starting material, and three resins with residual IC values of 660, 560 and 440 mmol/L (FF-PEI-R440) were obtained. The adsorption and chromatographic behaviors of these resins for BSA were investigated. It was found that, with IC decreasing from 740 to 440 mmol/L, the adsorption capacity kept almost unchanged; the effective protein diffusivity (De) also showed negligible variations as IC decreased from 740 to 560 mmol/L (De/D0=0.38 ± 0.04). However, it was interesting to observe a three-fold increase of the De value for FF-PEI-R440 (De/D0=1.23 ± 0.08). It is considered that the occurrence of the drastic uptake rate increase in FF-PEI-R440 was attributed to the decreased available binding sites for protein molecule, which led to the decrease of binding strength, thus facilitated the happenings of "chain delivery" effect of bound proteins. Besides, a study on the effect of ionic strength clarified that the lower the IC value, the higher the sensitivity of protein binding to salt concentration due to the easily screened electrostatic interactions at low surface charge densities. The ionic strength at the elution peak also decreased with decreasing IC in accordance with the salt sensitivity order. Column breakthrough studies demonstrated that the dynamic adsorption capacity of FF-PEI-R440 was

  14. Evaluation of Phenolic Content Variability along with Antioxidant, Antimicrobial, and Cytotoxic Potential of Selected Traditional Medicinal Plants from India.

    PubMed

    Singh, Garima; Passsari, Ajit K; Leo, Vincent V; Mishra, Vineet K; Subbarayan, Sarathbabu; Singh, Bhim P; Kumar, Brijesh; Kumar, Sunil; Gupta, Vijai K; Lalhlenmawia, Hauzel; Nachimuthu, Senthil K

    2016-01-01

    Plants have been used since ancient times as an important source of biologically active substances. The aim of the present study was to investigate the phytochemical constituents (flavonoids and phenolics), antioxidant potential, cytotoxicity against HepG2 (human hepato carcinoma) cancer cell lines, and the antimicrobial activity of the methanol extract of selected traditional medicinal plants collected from Mizoram, India. A number of phenolic compounds were detected using HPLC-DAD-ESI-TOF-MS, mainly Luteolin, Kaempferol, Myricetin, Gallic Acid, Quercetin and Rutin, some of which have been described for the first time in the selected plants. The total phenolic and flavonoid contents showed high variation ranging from 4.44 to 181.91 μg of Gallic Acid equivalent per milligram DW (GAE/mg DW) and 3.17 to 102.2 μg of Quercetin/mg, respectively. The antioxidant capacity was determined by DPPH (IC50 values ranges from 34.22 to 131.4 μg/mL), ABTS (IC50 values ranges from 24.08 to 513.4 μg/mL), and reducing power assays. Antimicrobial activity was assayed against gram positive (Staphylococcus aureus), gram negative (Escherichia coli, Pseudomonas aeruginosa), and yeast (Candida albicans) demonstrating that the methanol extracts of some plants were efficacious antimicrobial agents. Additionally, cytotoxicity was assessed on human hepato carcinoma (HepG2) cancer cell lines and found that the extracts of Albizia lebbeck, Dillenia indica, and Bombax ceiba significantly decreased the cell viability at low concentrations with IC50 values of 24.03, 25.09, and 29.66 μg/mL, respectively. This is the first report of detection of phenolic compounds along with antimicrobial, antioxidant and cytotoxic potential of selected medicinal plants from India, which indicates that these plants might be valuable source for human and animal health.

  15. Metabolic changes associated with metformin potentiates Bcl-2 inhibitor, Venetoclax, and CDK9 inhibitor, BAY1143572 and reduces viability of lymphoma cells.

    PubMed

    Chukkapalli, Vineela; Gordon, Leo I; Venugopal, Parameswaran; Borgia, Jeffrey A; Karmali, Reem

    2018-04-20

    Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines. We demonstrated that metformin as a single agent, especially at high concentrations produced significant reductions in viability and proliferation only in Daudi and SUDHL-4 cell lines with associated alterations in mitochondrial oxidative and glycolytic metabolism. As bcl-2 proteins, cyclin dependent kinases (CDK) and phosphoinositol-3- kinase (PI3K) also influence mitochondrial physiology and metabolism with clear relevance to the pathogenesis of lymphoma, we investigated the potentiating effects of metformin when combined with novel agents Venetoclax (bcl-2 inhibitor), BAY-1143572 (CDK9 inhibitor) and Idelalisib (p110δ- PI3K inhibitor). Co-treating KPUM-UH1 and SUDHL-4 cells with 10 mM of metformin resulted in 1.4 fold and 8.8 fold decreases, respectively, in IC-50 values of Venetoclax. By contrast, 3-fold and 10 fold reduction in IC-50 values of BAY-1143572 in Daudi and Jeko-1 cells respectively was seen in the presence of 10 mM of metformin. No change in IC-50 value for Idelalisib was observed across cell lines. These data suggest that although metformin is not a potent single agent, targeting cancer metabolism with similar but more effective drugs in novel combination with either bcl-2 or CDK9 inhibitors warrants further exploration.

  16. Evaluation of Phenolic Content Variability along with Antioxidant, Antimicrobial, and Cytotoxic Potential of Selected Traditional Medicinal Plants from India

    PubMed Central

    Singh, Garima; Passsari, Ajit K.; Leo, Vincent V.; Mishra, Vineet K.; Subbarayan, Sarathbabu; Singh, Bhim P.; Kumar, Brijesh; Kumar, Sunil; Gupta, Vijai K.; Lalhlenmawia, Hauzel; Nachimuthu, Senthil K.

    2016-01-01

    Plants have been used since ancient times as an important source of biologically active substances. The aim of the present study was to investigate the phytochemical constituents (flavonoids and phenolics), antioxidant potential, cytotoxicity against HepG2 (human hepato carcinoma) cancer cell lines, and the antimicrobial activity of the methanol extract of selected traditional medicinal plants collected from Mizoram, India. A number of phenolic compounds were detected using HPLC-DAD-ESI-TOF-MS, mainly Luteolin, Kaempferol, Myricetin, Gallic Acid, Quercetin and Rutin, some of which have been described for the first time in the selected plants. The total phenolic and flavonoid contents showed high variation ranging from 4.44 to 181.91 μg of Gallic Acid equivalent per milligram DW (GAE/mg DW) and 3.17 to 102.2 μg of Quercetin/mg, respectively. The antioxidant capacity was determined by DPPH (IC50 values ranges from 34.22 to 131.4 μg/mL), ABTS (IC50 values ranges from 24.08 to 513.4 μg/mL), and reducing power assays. Antimicrobial activity was assayed against gram positive (Staphylococcus aureus), gram negative (Escherichia coli, Pseudomonas aeruginosa), and yeast (Candida albicans) demonstrating that the methanol extracts of some plants were efficacious antimicrobial agents. Additionally, cytotoxicity was assessed on human hepato carcinoma (HepG2) cancer cell lines and found that the extracts of Albizia lebbeck, Dillenia indica, and Bombax ceiba significantly decreased the cell viability at low concentrations with IC50 values of 24.03, 25.09, and 29.66 μg/mL, respectively. This is the first report of detection of phenolic compounds along with antimicrobial, antioxidant and cytotoxic potential of selected medicinal plants from India, which indicates that these plants might be valuable source for human and animal health. PMID:27066046

  17. (-)-Kusunokinin and piperloguminine from Piper nigrum: An alternative option to treat breast cancer.

    PubMed

    Sriwiriyajan, Somchai; Sukpondma, Yaowapa; Srisawat, Theera; Madla, Siribhorn; Graidist, Potchanapond

    2017-08-01

    Several studies have reported that active compounds isolated from Piper nigrum possess anticancer properties. However, there are no data on anticancer activity of (-)-kusunokinin and piperlonguminine. The purposes of this study were to isolate active compounds from P. nigrum and identify the molecular mechanisms underlying growth and apoptosis pathway in breast cancer cells. Two bioactive compounds, (-)-kusunokinin and piperlonguminine, were isolated from P. nigrum. Cytotoxicity and the molecular mechanism were measured by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and Western blot analysis. We found that the active compounds, which effect cancer cell lines were (-)-kusunokinin and piperlonguminine. These compounds have potent cytotoxic effects on breast cancer cells (MCF-7 and MDA-MB-468) and colorectal cells (SW-620). (-)-Kusunokinin demonstrated a cytotoxic effect on MCF-7 and MDA-MB-468 with IC 50 values of 1.18 and 1.62μg/mL, respectively. Piperlonguminine had a cytotoxic effect on MCF-7 and MDA-MB-468 with IC 50 values of 1.63 and 2.19μg/mL, respectively. Both compounds demonstrated lower cytotoxicity against normal breast cell lines with IC 50 values higher than 11μg/mL. Cell cycle and apoptotic analysis using flow cytometry, showed that the (-)-kusunokinin and piperlonguminine induced cell undergoing apoptosis and drove cells towards the G2/M phase. Moreover, both compounds decreased topoisomerase II and bcl-2. The increasing of p53 levels further increased p21, bax, cytochrome c, caspase-8, -7 and -3 activities, except caspase-9. These results suggest that the (-)-kusunokinin and piperlonguminine have been shown to have potent anticancer activities through extrinsic pathway and G2/M phase arrest. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Impact of the International Continence Society (ICS) report on the standardisation of terminology in nocturia on the quality of reports on nocturia and nocturnal polyuria: a systematic review.

    PubMed

    Hofmeester, Ilse; Kollen, Boudewijn J; Steffens, Martijn G; Bosch, J L H Ruud; Drake, Marcus J; Weiss, Jeffrey P; Blanker, Marco H

    2015-04-01

    To systematically review and evaluate the impact of the International Continence Society (ICS)-2002 report on standardisation of terminology in nocturia, on publications reporting on nocturia and nocturnal polyuria (NP). In 2002, the ICS defined NP as a Nocturnal Polyuria Index (nocturnal urine volume/total 24-h urine volume) of >0.2-0.33, depending on age. In April 2013 the PubMed and Embase databases were searched for studies (in English, German, French or Dutch) based on original data and adult participants, investigating the relationship between nocturia and NP. A methodological quality assessment was performed, including scores on external validity, internal validity and informativeness. Quality scores of items were compared between studies published before and after the ICS-2002 report. The search yielded 78 publications based on 66 studies. Quality scores of studies were generally high for internal validity (median 5, interquartile range [IQR] 4-6) but low for external validity. After publication of the ICS-2002 report, external validity showed a significant change from 1 (IQR 1-2) to 2 (IQR 1-2.5; P = 0.019). Nocturia remained undefined in 12 studies. In all, 19 different definitions were used for NP, most often being the ICS (or similar) definition: this covered 52% (n = 11) of studies before and 66% (n = 27) after the ICS-2002 report. Clear definitions of both nocturia and NP were identified in 67% and 76% before, and in 88% and 88% of the studies after the ICS-2002 report, respectively. The ICS-2002 report on standardisation of terminology in nocturia appears to have had a beneficial impact on reporting definitions of nocturia and NP, enabling better interpretation of results and comparisons between research projects. Because the external validity of most of the 66 studies is considered a problem, the results of these studies may not be validly extrapolated to other populations. The ICS definition of NP is used most often. However, its discriminative

  19. Differential modulation of microglia superoxide anion and thromboxane B2 generation by the marine manzamines

    PubMed Central

    Mayer, Alejandro MS; Hall, Mary L; Lynch, Sean M; Gunasekera, Sarath P; Sennett, Susan H; Pomponi, Shirley A

    2005-01-01

    Background Thromboxane B2 (TXB2) and superoxide anion (O2-) are neuroinflammatory mediators that appear to be involved in the pathogenesis of several neurodegenerative diseases. Because activated-microglia are the main source of TXB2 and O2- in these disorders, modulation of their synthesis has been hypothesized as a potential therapeutic approach for neuroinflammatory disorders. Marine natural products have become a source of novel agents that modulate eicosanoids and O2- generation from activated murine and human leukocytes. With the exception of manzamine C, all other manzamines tested are characterized by a complex pentacyclic diamine linked to C-1 of the β-carboline moiety. These marine-derived alkaloids have been reported to possess a diverse range of bioactivities including anticancer, immunostimulatory, insecticidal, antibacterial, antimalarial and antituberculosis activities. The purpose of this investigation was to conduct a structure-activity relationship study with manzamines (MZ) A, B, C, D, E and F on agonist-stimulated release of TXB2 and O2- from E. coli LPS-activated rat neonatal microglia in vitro. Results The manzamines differentially attenuated PMA (phorbol 12-myristate 13-acetate)-stimulated TXB2 generation in the following order of decreasing potency: MZA (IC50 <0.016 μM) >MZD (IC50 = 0.23 μM) >MZB (IC50 = 1.6 μM) >MZC (IC50 = 2.98 μM) >MZE and F (IC50 >10 μM). In contrast, there was less effect on OPZ (opsonized zymosan)-stimulated TXB2 generation: MZB (IC50 = 1.44 μM) >MZA (IC50 = 3.16 μM) >MZC (IC50 = 3.34 μM) >MZD, MZE and MZF (IC50 >10 μM). Similarly, PMA-stimulated O2- generation was affected differentially as follows: MZD (apparent IC50<0.1 μM) >MZA (IC50 = 0.1 μM) >MZB (IC50 = 3.16 μM) >MZC (IC50 = 3.43 μM) >MZE and MZF (IC50 >10 μM). In contrast, OPZ-stimulated O2- generation was minimally affected: MZB (IC50 = 4.17 μM) >MZC (IC50 = 9.3 μM) >MZA, MZD, MZE and MZF (IC50 > 10 μM). From the structure

  20. Cytotoxicity evaluation of a new set of 2-aminobenzo[de]iso-quinoline-1,3-diones.

    PubMed

    Al-Salahi, Rashad; Alswaidan, Ibrahim; Marzouk, Mohamed

    2014-12-04

    A new series of 2-amino-benzo[de]isoquinoline-1,3-diones was synthesized and fully characterized in our previous paper. Here, their cytotoxic effects have been evaluated in vitro in relation to colon HCT-116, hepatocellular Hep-G2 and breast MCF-7 cancer cell lines, using a crystal violet viability assay. The IC50-values of the target compounds are reported in µg/mL, using doxorubicin as a reference drug. The findings revealed that compounds 14, 15, 16, 21 and 22 had significant cytotoxic effects against HCT-116, MCF-7 and Hep-G2 cell lines. Their IC50 values ranged between 1.3 and 8.3 μg/mL in relation to doxorubicin (IC50 ≈ 0.45-0.89 μg/mL). Therefore, these compounds could be used as templates for furthering the development and design of more potent antitumor agents through structural modification.

  1. Analog/digital pH meter system I.C.

    NASA Technical Reports Server (NTRS)

    Vincent, Paul; Park, Jea

    1992-01-01

    The project utilizes design automation software tools to design, simulate, and fabricate a pH meter integrated circuit (IC) system including a successive approximation type seven-bit analog to digital converter circuits using a 1.25 micron N-Well CMOS MOSIS process. The input voltage ranges from 0.5 to 1.0 V derived from a special type pH sensor, and the output is a three-digit decimal number display of pH with one decimal point.

  2. Model Checking with Multi-Threaded IC3 Portfolios

    DTIC Science & Technology

    2015-01-15

    different runs varies randomly depending on the thread interleaving. The use of a portfolio of solvers to maximize the likelihood of a quick solution is...empirically show (cf. Sec. 5.2) that the predictions based on this formula have high accuracy. Note that each solver in the portfolio potentially searches...speedup of over 300. We also show that widening the proof search of ic3 by randomizing its SAT solver is not as effective as paral- lelization

  3. In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4.

    PubMed

    Lv, Qiao-Li; Wang, Gui-Hua; Chen, Shu-Hui; Hu, Lei; Zhang, Xue; Ying, Guo; Qin, Chong-Zhen; Zhou, Hong-Hao

    2015-12-25

    Glycyrrhetinic acid (GA) has been used clinically in the treatment of patients with chronic hepatitis. This study evaluated the effect of GA on the activity of five P450(CYP450) cytochrome enzymes: CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, in human liver microsomes (HLMs) and recombinant cDNA-expressed enzyme systems using a HPLC-MS/MS CYP-specific probe substrate assay. With midazolam as the probe substrate, GA greatly decreased CYP3A4 activity with IC50 values of 8.195 μM in HLMs and 7.498 μM in the recombinant cDNA-expressed CYP3A4 enzyme system, respectively. It significantly decreased CYP3A4 activity in a dose- but not time-dependent manner. Results from Lineweaver-Burk plots showed that GA could inhibit CYP3A4 activity competitively, with a Ki value of 1.57 μM in HLMs. Moreover, CYP2C9 and CYP2C19 could also be inhibited significantly by GA with IC50 of 42.89 and 40.26 μM in HLMs, respectively. Other CYP450 isoforms were not markedly affected by GA. The inhibition was also confirmed by an in vivo study of mice. In addition, it was observed that mRNA expressions of the Cyps2c and 3a family decreased significantly in the livers of mice treated with GA. In conclusion, this study indicates that GA may exert herb-drug interactions by competitively inhibiting CYP3A4.

  4. Parsec-scale Variations in the 7Li I/6Li I Isotope Ratio Toward IC 348 and the Perseus OB 2 Association

    NASA Astrophysics Data System (ADS)

    Knauth, D. C.; Taylor, C. J.; Ritchey, A. M.; Federman, S. R.; Lambert, D. L.

    2017-01-01

    Measurements of the lithium isotopic ratio in the diffuse interstellar medium from high-resolution spectra of the Li I λ6708 resonance doublet have now been reported for a number of lines of sight. The majority of the results for the 7Li/6Li ratio are similar to the solar system ratio of 12.2, but the line of sight toward o Per, a star near the star-forming region IC 348, gave a ratio of about two, the expected value for gas exposed to spallation and fusion reactions driven by cosmic rays. To examine the association of IC 348 with cosmic rays more closely, we measured the lithium isotopic ratio for lines of sight to three stars within a few parsecs of o Per. One star, HD 281159, has 7Li/6Li ≃ 2 confirming production by cosmic rays. The lithium isotopic ratio toward o Per and HD 281159 together with published analyses of the chemistry of interstellar diatomic molecules suggest that the superbubble surrounding IC 348 is the source of the cosmic rays. Based on observations obtained with the Hobby-Eberly Telescope, which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Ludwig-Maximilians-Universität München, and Georg-August-Universität Göttingen.

  5. Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis.

    PubMed

    Paulino, Niraldo; Teixeira, Cristiane; Martins, Regiane; Scremin, Amarilis; Dirsch, Verena M; Vollmar, Angelika M; Abreu, Sheila R; de Castro, Solange L; Marcucci, Maria Cristina

    2006-08-01

    Phamacological activities of a standard ethanol extract G1 from Brazilian green propolis, typified as BRP1, was evaluated in mouse models of pain and inflammation. Intraperitoneal injection ( I. P.) of G1 inhibited acetic acid-induced abdominal constrictions with an ID (50) = 0.75 +/- 0.05 mg/kg, and in the formalin test the ID (50) values were 0.85 +/- 0.07 mg/kg and 13.88 +/- 1.12 mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema, G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered I. P. and of 36 % after 15 min by the oral route ( O. R.). When the inflammatory agent was complete Freund's adjuvant, inhibition of paw edema was also observed after administration of the extract by both routes. In the capsaicin-induced ear edema the ID (50) values were 1.09 +/- 0.08 mg/kg ( I. P.) and 10.00 +/- 0.90 mg/kg ( O. R.). In the acute carrageenan-induced inflammatory reaction induced by carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with IC (50) values of 0.72 +/- 0.08 mg/kg and 4.17 +/- 0.50 mg/kg, by I. P. or O. R. administration, with a preferential migration of polymorphonuclear neutrophils. IN VITRO, G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells (IC (50) = 41.60 microg/mL), and also the luciferase activity in TNF-alpha-stimulated HEK 293 cells transfected with NF-kappaB-luciferase reporter gene driven by the nuclear factor kappaB (NF-kappaB) (IC (50) = 200 microg/mL). This extract, which at low concentrations induces anti-inflammatory and analgesic effects in mouse models, presents a high content of flavonoids, known to inhibit inducible NOS (iNOS) activity. These data taken together led us to reinforce the hypothesis in the literature that the anti-inflammatory effect of propolis may be a due to inhibition of iNOS gene expression, through interference with NF-kappaB sites in the i

  6. Inhibition of the acetoclastic methanogenic activity by phenol and alkyl phenols.

    PubMed

    Olguin-Lora, P; Puig-Grajales, L; Razo-Flores, E

    2003-08-01

    Chemical and petrochemical industries are important sources of aromatic pollutants. Petrochemical processes like caustic washing of middle distillates produce the spent caustic liquors highly concentrated in phenol and alkyl phenols. The anaerobic technology is considered a feasible strategy for petrochemical wastewater pre-treatment although high concentrations of phenol could limit its efficiency. The goal of this work was to determine the toxicity of both selected alkyl phenols and a synthetic "spent-caustic phenols mixture" on the acetoclastic Specific Methanogenic Activity (SMA) of unadapted and phenol-adapted granular sludge. Alkyl phenols were responsible for 50% (IC50) and 100% (IC100) inhibition of the SMA at concentrations ranging from 1.6 to 5.0 mM and from 4.1 to 27.5 mM, respectively, for un-adapted granular sludge. In the case of phenol-adapted granular sludge, the inhibitory concentrations ranged from 1.7 to 14.9 mM and from 4.0 to 83.0 for IC50 and IC100, respectively, highlighting the impact of sludge acclimation. The inhibition produced by 2-ethylphenol was more acute compared to phenol and was not reduced by the phenol acclimation process. The IC50 and IC100 values obtained for the synthetic "spent-caustic phenols mixture" were 9.5 mM and 88.4 mM, respectively. The inhibitory concentrations of phenol compounds were closely correlated with compound apolarity (log P), indicating that the lipophilic character of the tested compounds was responsible for their methanogenic toxicity. An inhibition model is confirmed to estimate the IC50 and IC100.

  7. In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity.

    PubMed

    Pan, Yan; Tiong, Kai Hung; Abd-Rashid, Badrul Amini; Ismail, Zakiah; Ismail, Rusli; Mak, Joon Wah; Ong, Chin Eng

    2014-10-15

    This study was designed to investigate eight herbal active constituents (andrographolide, asiaticoside, asiatic acid, madecassic acid, eupatorin, sinensetin, caffeic acid, and rosmarinic acid) on their potential inhibitory effects on human cytochrome P450 1A2 (CYP1A2) activity. A fluorescence-based enzyme assay was performed by co-incubating human cDNA-expressed CYP1A2 with its selective probe substrate, 3-cyano-7-ethoxycoumarin (CEC), in the absence or presence of various concentrations of herbal active constituents. The metabolite (cyano-hydroxycoumarin) formed was subsequently measured in order to obtain IC50 values. The results indicated that only eupatorin and sinensetin moderately inhibited CYP1A2 with IC50 values of 50.8 and 40.2 μM, while the other active compounds did not significantly affect CYP1A2 activity with IC50 values more than 100 μM. Ki values further determined for eupatorin and sinensetin were 46.4 and 35.2 μM, respectively. Our data indicated that most of the investigated herbal constituents have negligible CYP1A2 inhibitory effect. In vivo studies however may be warranted to ascertain the inhibitory effect of eupatorin and sinensetin on CYP1A2 activity in clinical situations. Copyright © 2014 Elsevier GmbH. All rights reserved.

  8. The size and structure of the spheroid of IC 1613

    NASA Astrophysics Data System (ADS)

    Battinelli, P.; Demers, S.; Artigau, É.

    2007-05-01

    Context: Nearby galaxies, spirals as well as irregulars, have been found to be much larger than previously believed. The structure of the huge spheroid surrounding dwarf galaxies could give clues to their past gravitational history. Thanks to wide field imagers, nearby galaxies with diameter of dozens of arcmin can be effectively surveyed. Aims: We obtain, from the CFHT archives, a series of i' and g' MegaCam images of IC 1613 in order to determine the stellar surface density of the field and determine the shape of its spheroid. Methods: From the colour magnitude diagram we select some 36 000 stars, in the first three magnitudes of the red giant branch. The spatial distribution of these stars is used to establish the structure of the spheroid. Results: The position angle of the major axis of the stellar spheroid is found to be ≈90°, some 30° from the major axis of the HI cloud surrounding IC 1613. The surface density profile of the spheroid is not exponential over all the length of the major axis. A King profile, with a core radius of 4.5' and a tidal radius of 24' fits the data. The tidal truncation of the spheroid suggests that IC 1613 is indeed a satellite of M 31. Based on observations obtained with MegaPrime/MegaCam, a joint project of CFHT and CEA/DAPNIA, at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council (NRC) of Canada, the Institute National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii.

  9. A Pilot Study of the Kinematics of the Open Cluster IC 4756.

    NASA Astrophysics Data System (ADS)

    Upgren, A. R.; Lee, J. T.; Weis, E. W.

    1998-12-01

    In 1982 a working group of I.A.U. Commission 24 was established in order to provide parallax standard fields (IAU Transactions, XVIIIB,127 1982). Three of these fields for regular trigonometric parallax observation are centered on open clusters; the Pleiades, Praesepe and IC4756. Very few studies on IC4756 have been made; one is by Herzog and Sanders (AAPS, 19, 211 1975). The Van Vleck Observatory began normal parallax observations of IC4756 with its 0.5m astrometric refractor in 1980. A few observations were also obtained in 1963. Using Yale PDS machine, Lee has measured two of these early plates and two from 1997-98. The proper motion differences among the stars from different plate pair solutions are about 0.0008"/yr, and the mean proper motion of member stars is about 0.003"/yr, with respect to the mean motion of the field stars. The epoch difference of 34 years appears sufficient for accurate measures of the internal motion of the member stars. This cluster has also been observed with the 1.5m reflector of the U.S. Naval Observatory and the 0.65m McCormick Observatory refractor. These observations may also become available for the motion study.

  10. Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation.

    PubMed

    Ponnam, Devendar; Shilpi, Singh; Srinivas, K V N S; Suiab, Luqman; Alam, Sarfaraz; Amtul, Zehra; Arigari, Niranjan Kumar; Jonnala, Kotesh Kumar; Siddiqui, Lubna; Dubey, Vijaya; Tiwari, Ashok Kumar; Balasubramanian, Sridhar; Khan, Feroz

    2014-11-24

    A new series of 1,9-acetals of forskolin were synthesized by treating with aromatic and aliphatic aldehydes using Ceric ammonium nitrate as catalyst and evaluated for anticancer and α-glucosidase inhibition activities. Among the synthesized compounds 2a, 2b and 3a showed potential cytotoxic activity towards human cancer cell lines MCF-7 (Human Breast Adenocarcinoma), MDA-MB (Human Breast Carcinoma), HeLa (Human Cervix Adenocarcinoma), A498 (Human Kidney Carcinoma), K562 (Human Erythromyeloblastoid leukemia), SH-SY5Y (Human Neuroblastoma), Hek293 (Human Embryonic Kidney) and WRL68 (Human Hepatic) with IC50 values ranging between 0.95 and 47.96 μg/ml. Osmotic fragility test revealed compound 3a as non-toxic to human erythrocytes at the tested concentrations of 50 and 100 μg/ml. Compounds 1g (IC50 value 0.76 μg/ml) and 1p (IC50 value 0.74 μg/ml) significantly inhibited α-glucosidase in in vitro system. In silico based docking, ADME and toxicity risk assessment studies also showed discernible α-glucosidase activity for compounds 1g, 1p compared to standard acarbose. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Inhibition properties of propolis extracts to some clinically important enzymes.

    PubMed

    Baltas, Nimet; Yildiz, Oktay; Kolayli, Sevgi

    2016-01-01

    The present study was conducted to envisage inhibition effects of propolis on the crucial enzymes, urease, xanthine oxidase (XO) and acetylcholinesterase (AChE). Some of the antioxidant properties of the propolis samples were determined using the total phenolic content (TPE) and total flavonoids in the eight different ethanolic propolis extracts (EPE) samples. Inhibition values of the enzymes were expressed as inhibition concentration (IC 50 ; mg/mL or μg/mL) causing 50% inhibition of the enzymes with donepezil, acetohydroxamic acid and allopurinol as reference inhibitors. All the propolis extracts exhibited variable inhibition effects on these enzymes, but the higher the phenolic contents the lower the inhibitions values (IC 50 = 0.074 to 1.560 mg/mL). IC 50 values of the P5 propolis sample having the highest TPE, obtained from Zonguldak, for AChE, urease and XO were 0.081 ± 0.009, 0.080 ± 0.006 and 0.074 ± 0.011 μg/mL, respectively. The EPE proved to be a good source of inhibitor agents that can be used as natural inhibitors to serve human health.

  12. Capsofulvesins A-C, cholinesterase inhibitors from Capsosiphon fulvescens.

    PubMed

    Fang, Zhe; Yang Jeong, Su; Ah Jung, Hyun; Sue Choi, Jae; Sun Min, Byung; Hee Woo, Mi

    2012-01-01

    Activity-directed isolation of the n-hexane and dichloromethane fractions of Capsosiphon fulvescens resulted in the identification of four new glycolipids (1-3): (2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-O-(4Z,7Z,10Z,13Z-hexadecatetraenoyl)-3-O-β-D-galactopyranosyl glycerol (1, capsofulvesin A), (2S)-l-O-(9Z,12Z,15Z-octadecatrienoyl)-2-O-(10Z,13Z-hexadecadienoyl)-3-O-β-D-galactopyranosyl glycerol (2, capsofulvesin B), (2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-3-O-β-D-galacatopyranosyl glycerol (3, capsofulvesin C). Compounds 1-6 exhibited acetylcholinesterase (AChE) inhibitory activities with IC(50) values ranging from 50.90 to 82.83 µM, whereas 2-6 showed butyrylcholinesterase (BChE) inhibitory activities with IC(50) values of 114.75-185.55 µM. Although most of the compounds isolated lacked scavenging activity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and peroxynitrite (ONOO(-)), compound 8 showed ONOO(-) scavenging activity with an IC(50) value of 26.23 µg/mL.

  13. Protective effects of a standard extract of Mangifera indica L. (VIMANG) against mouse ear edemas and its inhibition of eicosanoid production in J774 murine macrophages.

    PubMed

    Garrido, G; González, D; Lemus, Y; Delporte, C; Delgado, R

    2006-06-01

    A standard aqueous extract of Mangifera indica L., used in Cuba as antioxidant under the brand name VIMANG, was tested in vivo for its anti-inflammatory activity, using commonly accepted assays. The standard extract of M. indica, administered orally (50-200mg/kg body wt.), reduced ear edema induced by arachidonic acid (AA) and phorbol myristate acetate (PMA) in mice. In the PMA model, M. indica extract also reduced myeloperoxidase (MPO) activity. In vitro studies were performed using macrophage cell line J774 stimulated with pro-inflammatory stimuli lipopolysaccharide-interferon gamma (LPS-IFNgamma) or calcium ionophore A23187 to determine prostaglandin PGE(2) or leukotriene LTB(4) release, respectively. The extract inhibited the induction of PGE(2) and LTB(4) with IC(50) values of 21.7 and 26.0microg/ml, respectively. Mangiferin (a glucosylxanthone isolated from the extract) also inhibited these AA metabolites (PGE(2), IC(50) value=17.2microg/ml and LTB(4), IC(50) value=2.1microg/ml). These results represent an important contribution to the elucidation of the mechanism involved in the anti-inflammatory and anti-nociceptive effects reported for the standard extract of M. indica VIMANG.

  14. Large scale screening of commonly used Iranian traditional medicinal plants against urease activity

    PubMed Central

    2012-01-01

    Background and purpose of the study H. pylori infection is an important etiologic impetus usually leading to gastric disease and urease enzyme is the most crucial role is to protect the bacteria in the acidic environment of the stomach. Then urease inhibitors would increase sensitivity of the bacteria in acidic medium. Methods 137 Iranian traditional medicinal plants were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 50% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. Results 37 plants out of the 137 crude extracts revealed strong urease inhibitory activity (more than 70% inhibition against urease activity at 10 mg/ml concentration). Nine of the whole studied plants crude extracts were found as the most effective with IC50 values less than 500 μg/ml including; Rheum ribes, Sambucus ebulus, Pistachia lentiscus, Myrtus communis, Areca catechu, Citrus aurantifolia, Myristica fragrans, Cinnamomum zeylanicum and Nicotiana tabacum. Conclusions The most potent urease inhibitory was observed for Sambucus ebulus and Rheum ribes extracts with IC50 values of 57 and 92 μg/ml, respectively. PMID:23351780

  15. Assessing the organizational context for EBP implementation: the development and validity testing of the Implementation Climate Scale (ICS).

    PubMed

    Ehrhart, Mark G; Aarons, Gregory A; Farahnak, Lauren R

    2014-10-23

    Although the importance of the organizational environment for implementing evidence-based practices (EBP) has been widely recognized, there are limited options for measuring implementation climate in public sector health settings. The goal of this research was to develop and test a measure of EBP implementation climate that would both capture a broad range of issues important for effective EBP implementation and be of practical use to researchers and managers seeking to understand and improve the implementation of EBPs. Participants were 630 clinicians working in 128 work groups in 32 US-based mental health agencies. Items to measure climate for EBP implementation were developed based on past literature on implementation climate and other strategic climates and in consultation with experts on the implementation of EBPs in mental health settings. The sample was randomly split at the work group level of analysis; half of the sample was used for exploratory factor analysis (EFA), and the other half was used for confirmatory factor analysis (CFA). The entire sample was utilized for additional analyses assessing the reliability, support for level of aggregation, and construct-based evidence of validity. The EFA resulted in a final factor structure of six dimensions for the Implementation Climate Scale (ICS): 1) focus on EBP, 2) educational support for EBP, 3) recognition for EBP, 4) rewards for EBP, 5) selection for EBP, and 6) selection for openness. This structure was supported in the other half of the sample using CFA. Additional analyses supported the reliability and construct-based evidence of validity for the ICS, as well as the aggregation of the measure to the work group level. The ICS is a very brief (18 item) and pragmatic measure of a strategic climate for EBP implementation. It captures six dimensions of the organizational context that indicate to employees the extent to which their organization prioritizes and values the successful implementation of EBPs

  16. The optical design of 3D ICs for smartphone and optro-electronics sensing module

    NASA Astrophysics Data System (ADS)

    Huang, Jiun-Woei

    2018-03-01

    Smartphone require limit space for image system, current lens, used in smartphones are refractive type, the effective focal length is limited the thickness of phone physical size. Other, such as optro-electronics sensing chips, proximity optical sensors, and UV indexer chips are integrated into smart phone with limit space. Due to the requirement of multiple lens in smartphone, proximity optical sensors, UV indexer and other optro-electronics sensing chips in a limited space of CPU board in future smart phone, optro-electronics 3D IC's integrated with optical lens or components may be a key technology for 3 C products. A design for reflective lens is fitted to CMOS, proximity optical sensors, UV indexer and other optro-electronics sensing chips based on 3-D IC. The reflective lens can be threes times of effective focal lens, and be able to resolve small object. The system will be assembled and integrated in one 3-D IC more easily.

  17. Comparison of ion chromatographic methods based on conductivity detection, post-column-reaction and on-line-coupling IC-ICP-MS for the determination of bromate.

    PubMed

    Schminke, G; Seubert, A

    2000-02-01

    An established method for the determination of the disinfection by-product bromate is ion chromatography (IC). This paper presents a comparison of three IC methods based on either conductivity detection (IC-CD), a post-column-reaction (IC-PCR-VIS) or the on-line-coupling with inductively coupled plasma mass spectrometry (IC-ICP-MS). Main characteristics of the methods such as method detection limits (MDL), time of analysis and sample pretreatment are compared and applicability for routine analysis is critically discussed. The most sensitive and rugged method is IC-ICP-MS, followed by IC-PCR-VIS. The photometric detection is subject to a minor interference in real world samples, presumably caused by carbonate. The lowest sensitivity is shown by the IC-CD method as slowest method compared, which, in addition, requires a sample pretreatment. The highest amount of information is delivered by IC-PCR-VIS, which allows the simultaneous determination of the seven standard anions and bromate.

  18. Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

    PubMed

    Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

    2016-02-26

    Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

  19. Bioactive compounds from Stuhlmannia moavi from the Madagascar dry forest.

    PubMed

    Liu, Yixi; Harinantenaina, Liva; Brodie, Peggy J; Bowman, Jessica D; Cassera, Maria B; Slebodnick, Carla; Callmander, Martin W; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Applequist, Wendy; Birkinshaw, Chris; Lewis, Gwilym P; Kingston, David G I

    2013-12-15

    Bioassay-directed fractionation of the leaf and root extracts of the antiproliferative Madagascar plant Stuhlmannia moavi afforded 6-acetyl-5,8-dihydroxy-2-methoxy-7-methyl-1,4-naphthoquinone (stuhlmoavin, 1) as the most active compound, with an IC50 value of 8.1 μM against the A2780 human ovarian cancer cell line, as well as the known homoisoflavonoid bonducellin (2) and the stilbenoids 3,4,5'-trihydroxy-3'-methoxy-trans-stilbene (3), piceatannol (4), resveratrol (5), rhapontigenin (6), and isorhapontigenin (7). The structure elucidation of all compounds was based on NMR and mass spectroscopic data, and the structure of 1 was confirmed by a single crystal X-ray analysis. Compounds 2-5 showed weak A2780 activities, with IC50 values of 10.6, 54.0, 41.0, and 74.0 μM, respectively. Compounds 1-3 also showed weak antimalarial activity against Plasmodium falciparum with IC50 values of 23, 26, and 27 μM, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

    PubMed Central

    Kondratyuk, Tamara P.; Park, Eun-Jung; Yu, Rui; van Breemen, Richard B.; Asolkar, Ratnakar N.; Murphy, Brian T.; Fenical, William; Pezzuto, John M.

    2012-01-01

    Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects. PMID:22412812