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Sample records for rates synergistic interactions

  1. The fluence rate determines the synergistic interaction of UV radiation and heat for mitotic recombination and cell inactivation in yeasts.

    Science.gov (United States)

    Kim, Jin Kyu; Komarova, Ludmila N; Zhurakovskaya, Galina P; Petin, Vladislav G

    2006-01-01

    The significance of the UV fluence rate for the synergistic interaction of UV light (254 nm) and heat was demonstrated for the frequency of mitotic recombination in a wild-type diploid yeast of Saccharomyces cerevisiae (strain T1) and for cell inactivation of two wild-type diploid yeast of S. cerevisiae (strains T1, XS800). It was shown for mitotic recombination that a decrease in the intensity of UV exposure results in the necessity of decreasing the temperature at which UV irradiation occurs to provide the same value of the synergistic enhancement ratio. For cell inactivation, there was a specific temperature maximizing the synergistic effect for any constant fluence rate and the temperature range, synergistically increasing the inactivation effect of UV radiation, should be shifted to lower temperatures with a decrease in the fluence rate. To interpret the results observed, a simple mathematical model of the synergistic interaction was applied. The model suggests that the synergistic interaction of UV light and hyperthermia is expected to result from some additional effective damages arising from the interaction of some sublesions induced by both agents. On the basis of data obtained, it was supposed that the synergistic interaction of these factors might take place at small intensities of UV light and temperatures existing in the biosphere. In other words, for a long duration of interaction, which is important for problems of UV light protection and health effects, one can expect a synergistic interaction of this factor with environmental heat or physiological temperatures and thereby an increase in their inactivating and genetic consequences.

  2. Fluence rate as a determinant of synergistic interaction under simultaneous action of UV light and mild heat in Saccharomyces cerevisiae.

    Science.gov (United States)

    Petin, V G; Zhurakovskaya, G P; Komarova, L N

    1997-04-01

    In experiments with wild-type diploid yeast cells of Saccharomyces cerevisiae, the synergistic lethal action of a simultaneous application of ultraviolet (UV) light (wavelength, 254 nm) and mild heat (45-57.5 degrees C) was studied. It was shown that, at any fixed UV light intensity, the synergistic effect occurred within the given temperature interval. The optimal temperature to achieve the greatest synergistic effect may be shown for every fluence rate examined. The correlation between the optimal temperature that maximized the synergy and UV light intensity was estimated: this temperature shifted towards higher temperature values with an increasing fluence rate. A possible interpretation of this effect is based on the supposition that the mechanism of the synergistic effect is related to additional lethal damage produced by the interaction of sublesions induced by each agent. These sublesions are supposed to be non-lethal when each agent is applied separately.

  3. Synergistic Interactions in Multispecies Biofilms

    DEFF Research Database (Denmark)

    Ren, Dawei

    bacterial species, the study to elucidate the impact of interaction networks on the multispecies biofilms in natural ecosystems, especially in soil, is still at an early stage. The diverse patterns of interactions within the mixed communities as well as the predatorprey relationship between protozoa...... or Paenibacillus amylolyticus as well as in a four-species biofilm. The strongest change in expression profile was observed in the dual-species biofilms of X. retroflexus and P. amylolyticus, while a distinct expression pattern (non-linear response) was detected in the four-species biofilm, indicating...... in integrated communities in multispecies biofilm. However, these conclusions are based on the assumption that this flagellate predator prefers surface attached cells which needs to be confirmed by further studies. Horizontal gene transfer by conjugation occurs more efficiently in biofilms. The connection...

  4. Mathematical description of synergistic interaction of UV light and hyperthermia for yeast cells.

    Science.gov (United States)

    Petin, V G; Kim, J K; Zhurakovskaya, G P; Rassokhina, A V

    2000-03-01

    A new mathematical model for the synergistic interaction of lesions produced by ultraviolet (UV) light and high temperature has been proposed. The model suggests that synergism is expected from the additional lethal lesions arising from the interaction of sublesions induced by both agents. These sublesions are considered noneffective after each agent is taken alone. The model predicts the dependence of the synergistic interaction on the ratio of lethal lesions produced by each agent applied, the greatest value of the synergistic effect as well as the conditions under which it can be achieved, and the dependence of synergistic effect on UV light fluence rate. These predictions of the model have been tested for the simultaneous combined action of UV light (wavelength 254 nm) and heat (45-57.5 degrees C) on two strains of wild-type diploid yeast cells of Saccharomyces cerevisiae. The theory appears to be appropriate and the conclusions valid.

  5. Synergistic interactions between PBDEs and PCBs in human neuroblastoma cells.

    Science.gov (United States)

    Pellacani, C; Tagliaferri, S; Caglieri, A; Goldoni, M; Giordano, G; Mutti, A; Costa, L G

    2014-04-01

    Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunction, and reproductive disorders. Humans and wildlife are generally exposed to a mixture of these environmental pollutants, highlighting the need to evaluate the potential effects of combined exposures. In this study, we investigated the cytotoxic effects of the combined exposure to two PBDEs and two PCBs in a human neuronal cell line. 2,2',4,4'-Tetrabromodiphenyl ether, 2,2',4,4',5-pentabromodiphenyl ether, PCB-126 (3,3',4,4',5-pentachlorobiphenyl; a dioxin-like PCB), and PCB-153 (2,2',4,4',5,5'-hexachlorobiphenyl; a non-dioxin-like PCB) were chosen, because their concentrations are among the highest in human tissues and the environment. The results suggest that the nature of interactions is related to the PCB structure. Mixtures of PCB-153 and both PBDEs had a prevalently synergistic effect. In contrast, mixtures of each PBDE congener with PCB-126 showed additive effects at threshold concentrations, and synergistic effects at higher concentrations. These results emphasize the concept that the toxicity of xenobiotics may be affected by possible interactions, which may be of significance given the common coexposures to multiple contaminants. Copyright © 2012 Wiley Periodicals, Inc.

  6. [Simultaneous action of UV light and hyperthermia on survival and recombination of yeast: effect of intensity of agents on their synergistic interaction].

    Science.gov (United States)

    Rassokhina, A V; Petin, V G; Zhurakovskaia, G P

    2000-01-01

    Synergistic effects of simultaneous application of ultraviolet (UV) light and hyperthermia on survival and recombination of diploid yeast cells were studied. For both test-systems the dependence of the synergistic interaction on UV light fluence rate and exposure temperature was revealed: the temperature range synergistically increasing the action of UV light is shifted towards low temperature values with decreasing of UV light fluence rate. For cell survival, the dependence of the synergistic enhancement ratio on the exposure temperature passes through a maximum. A possible qualitative interpretation of these results is discussed.

  7. Synergistic interactions between cefalexin and kanamycin in Mueller-Hinton broth medium and in milk.

    Science.gov (United States)

    Ganière, J P; Denuault, L

    2009-07-01

    This study investigated the in vitro bactericidal activity of an intramammary drug product by comparing the kill kinetics of cefalexin and kanamycin, alone and in fixed ratio combination, against Streptococcus uberis, Staphylococcus aureus and Escherichia coli strains isolated from field cases of bovine mastitis. The effect of milk as a diluent on the rate of bacterial killing was also assessed. Antibacterial kill kinetics was determined against each bacterial strain in Mueller-Hinton broth (MHB) and in milk. In MHB, the fixed cefalexin : kanamycin combination (1.5 : 1 w/w) exhibited a clear synergistic bactericidal activity against the strains tested. The combination also showed an enhanced killing activity in milk, as compared to either agent alone. The data show the occurrence of synergistic interactions between cefalexin and kanamycin, resulting in a faster and enhanced bactericidal activity against major mastitis pathogens. The study demonstrated that the combination exhibited a larger and faster rate of kill of S. aureus, S. uberis and E. coli compared to either cefalexin or kanamycin alone, while using a lower total amount of antibiotic. Synergistic and additive effects were also observed when milk was used as a medium. The results support the use of this combination of narrow spectrum antibiotics to treat clinical mastitis via the intramammary route and provide data on its killing kinetics.

  8. Synergistic interaction between oncolytic viruses augments tumor killing.

    Science.gov (United States)

    Le Boeuf, Fabrice; Diallo, Jean-Simon; McCart, J Andrea; Thorne, Steve; Falls, Theresa; Stanford, Marianne; Kanji, Femina; Auer, Rebecca; Brown, Christopher W; Lichty, Brian D; Parato, Kelley; Atkins, Harold; Kirn, David; Bell, John C

    2010-05-01

    A major barrier to all oncolytic viruses (OVs) in clinical development is cellular innate immunity, which is variably active in a spectrum of human malignancies. To overcome the heterogeneity of tumor response, we combined complementary OVs that attack cancers in distinct ways to improve therapeutic outcome. Two genetically distinct viruses, vesicular stomatitis virus (VSV) and vaccinia virus (VV), were used to eliminate the risk of recombination. The combination was tested in a variety of tumor types in vitro, in immunodeficient and immunocompetent mouse tumor models, and ex vivo, in a panel of primary human cancer samples. We found that VV synergistically enhanced VSV antitumor activity, dependent in large part on the activity of the VV B18R gene product. A recombinant version of VSV expressing the fusion-associated small-transmembrane (p14FAST) protein also further enhanced the ability of VV to spread through an infected monolayer, resulting in a "ping pong" oncolytic effect wherein each virus enhanced the ability of the other to replicate and/or spread in tumor cells. Our strategy is the first example where OVs are rationally combined to utilize attributes of different OVs to overcome the heterogeneity of malignancies and demonstrates the feasibility of combining complementary OVs to improve therapeutic outcome.

  9. Overview of QTL detection in plants and tests for synergistic epistatic interactions.

    Science.gov (United States)

    Jannink, Jean-Luc; Moreau, Laurence; Charmet, Gilles; Charcosset, Alain

    2009-06-01

    Improvements in the usefulness of QTL analysis arise from better statistical methods applied to the problem, ability to analyze more complex mating designs, and the fitting of less simplified genetic models. Here we review the advantages of different plant mating designs in QTL analysis and conclude that diallel designs have several favorable properties. We then turn to the detection of systematic genome-wide synergistic epistasis. This form of epistasis has important implications from evolutionary (maintenance of sexual reproduction and concealment of cryptic genetic variation) and practical perspectives (response to pyramided favorable alleles). We develop two methods for detecting systematic synergistic epistasis, one based on analyzing interactions between locus effects and predicted individual genotypic values and one based on analyzing pairwise locus interactions. Using the first method we detect synergistic epistasis in a barley and a wheat dataset but not in a maize dataset. We fail to detect synergistic epistasis with the second method. We discuss our results in the light of theoretical questions concerning the mechanisms of synergistic epistasis.

  10. In vivo synergistic interaction of liposome-coencapsulated gentamicin and ceftazidime

    NARCIS (Netherlands)

    R.M. Schiffelers (Raymond); G. Storm (Gert); M.T. ten Kate (Marian); L.E. Stearne-Cullen; J.G. den Hollander (Jan); H.A. Verbrugh (Henri); I.A.J.M. Bakker-Woudenberg (Irma)

    2001-01-01

    textabstractAntimicrobial agents may interact synergistically. But to ensure synergy in vivo, the drugs should both be present at the site of infection at sufficiently high concentrations for an adequate period of time. Coencapsulation of the drugs in a drug carrier may

  11. Synergistic interaction of the cannabinoid and death receptor systems - a potential target for future cancer therapies?

    Science.gov (United States)

    Keresztes, Attila; Streicher, John M

    2017-10-01

    Cannabinoid receptors have been shown to interact with other receptors, including tumor necrosis factor receptor superfamily (TNFRS) members, to induce cancer cell death. When cannabinoids and death-inducing ligands (including TNF-related apoptosis-inducing ligand) are administered together, they have been shown to synergize and demonstrate enhanced antitumor activity in vitro. Certain cannabinoid ligands have been shown to sensitize cancer cells and synergistically interact with members of the TNFRS, thus suggesting that the combination of cannabinoids with death receptor (DR) ligands induces additive or synergistic tumor cell death. This review summarizes recent findings on the interaction of the cannabinoid and DR systems and suggests possible clinical co-application of cannabinoids and DR ligands in the treatment of various malignancies. © 2017 Federation of European Biochemical Societies.

  12. Defaunation and habitat disturbance interact synergistically to alter seedling recruitment.

    Science.gov (United States)

    Granados, Alys; Brodie, Jedediah F; Bernard, Henry; O'Brien, Michael J

    2017-10-01

    Vertebrate granivores destroy plant seeds, but whether animal-induced seed mortality alters plant recruitment varies with habitat context, seed traits, and among granivore species. An incomplete understanding of seed predation makes it difficult to predict how widespread extirpations of vertebrate granivores in tropical forests might affect tree communities, especially in the face of habitat disturbance. Many tropical forests are simultaneously affected by animal loss as well as habitat disturbance, but the consequences of each for forest regeneration are often studied separately or additively, and usually on a single plant demographic stage. The combined impacts of these threats could affect plant recruitment in ways that are not apparent when studied in isolation. We used wire cages to exclude large (elephants), medium, (sambar deer, bearded pigs, muntjac deer), and small (porcupines, chevrotains) ground-dwelling mammalian granivores and herbivores in logged and unlogged forests in Malaysian Borneo. We assessed the interaction between habitat disturbance (selective logging) and experimental defaunation on seed survival, germination, and seedling establishment in five dominant dipterocarp tree species spanning a 21-fold gradient in seed size. Granivore-induced seed mortality was consistently higher in logged forest. Germination of unpredated seeds was reduced in logged forest and in the absence of small to large-bodied mammals. Experimental defaunation increased germination and reduced seed removal but had little effect on seed survival. Seedling recruitment however, was more likely where logging and animal loss occurred together. The interacting effects of logging and hunting could therefore, actually increase seedling establishment, suggesting that the loss of mammals in disturbed forest could have important consequences for forest regeneration and composition. © 2017 by the Ecological Society of America.

  13. Synergistic interaction effect between job control and social support at work on general psychological distress

    Science.gov (United States)

    Östergren, Per-Olof; Canivet, Catarina; Moghadassi, Mahnaz; Lindeberg, Sara; Karasek, Robert; Isacsson, Sven-Olof

    2010-01-01

    Purpose Little is known about the interaction between job control and social support at work on common mental disorders. To examine whether there is a synergistic interaction effect between job control and social support at work on general psychological distress and whether it differs by the level of job demands. Methods About 1,940 male and female workers from the Malmö Shoulder and Neck Study were chosen for this cross-sectional study. Job control, social support at work, and job demands were measured by the Swedish version of the Job Content Questionnaire, and general psychological distress was assessed by the General Health Questionnaire. Results A significant excessive risk increase for general psychological distress was observed when workers had both low job control and low social support at work in both men and women. The synergistic effect was stronger in women, when job demands were low (Rothman’s synergy index was 2.16 vs. 1.51 when job demands were high). However, in male workers, while a strong synergistic effect between job control and social support at work was found when job demands were low (synergy index was 9.25), there was an antagonistic effect when job demands were high (synergy index was 0.52). Conclusions There was a synergistic interaction effect between job control and social support at work on general psychological distress, but the synergistic effect or its effect size differed by the level of job demands and gender. An atomic, additive approach to the risk assessment of the psychosocial work characteristics on common mental disorders could be misleading or lead to a risk underestimation. PMID:20582551

  14. Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells.

    Science.gov (United States)

    Sonnemann, Jürgen; Hüls, Isabel; Sigler, Michael; Palani, Chithra D; Hong, Le Thi Thu; Völker, Uwe; Kroemer, Heyo K; Beck, James F

    2008-07-01

    Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1- and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy.

  15. Synergistic Interaction of the Triple Combination of Amphotericin B, Ciprofloxacin, and Polymorphonuclear Neutrophils against Aspergillus fumigatus▿

    Science.gov (United States)

    Stergiopoulou, Theodouli; Meletiadis, Joseph; Sein, Tin; Papaioannidou, Paraskevi; Walsh, Thomas J.; Roilides, Emmanuel

    2011-01-01

    Aspergillus is damaged by polymorphonuclear neutrophils (PMNs) by means of nonoxidative and oxidative mechanisms, which may be affected by antifungal and antibacterial agents that patients with invasive pulmonary aspergillosis often receive. The pharmacodynamic interactions among deoxycholate amphotericin B (AMB), ciprofloxacin (CIP), and human PMNs against Aspergillus fumigatus growth are unknown. We therefore studied the interactions between 0.032 to 2.0 μg/ml of AMB, 0.1 to 50 μg/ml of CIP at a fixed AMB/CIP ratio of 1:3.125, and PMNs from six donors at an effector-to-target (E:T) ratio of 400:1 against a clinical A. fumigatus isolate using an XTT metabolic assay and the Bliss independence pharmacodynamic-interaction model. CIP exhibited no antifungal activity alone or in combination with PMNs. Synergy was found between AMB and PMNs, with interaction indices (II) of 0.06 to 0.21; the highest interaction of 21% ± 3.6% was observed at 0.22 ± 0.09 μg/ml of AMB. The AMB and CIP (AMB+CIP) combination was synergistic (II = 0.39) at low AMB concentrations and antagonistic (II = 1.39) at high AMB concentrations, with a maximal synergistic interaction of 16% ± 3.7% observed at 0.16 ± 0.08 μg/ml of AMB. The triple combination AMB+CIP+PMNs was synergistic, with interaction indices of 0.05 to 0.20, and a maximal synergistic interaction of 24% ± 4% was observed at 0.20 ± 0.07 μg/ml of AMB. The increased percentage of Bliss synergy of the triple combination AMB+CIP+PMNs (24% ± 4%) was the product of those of the constituent double combinations AMB+PMNs (21% ± 3.6%) and AMB+CIP (16% ± 3.7%). Thus, the antifungal activity of AMB, at clinically relevant concentrations, was enhanced in combination with PMNs and CIP against A. fumigatus growth in a concentration-dependent manner. PMID:21911564

  16. Geminivirus mixed infection on pepper plants: Synergistic interaction between PHYVV and PepGMV

    Directory of Open Access Journals (Sweden)

    Rivera-Bustamante Rafael F

    2011-03-01

    Full Text Available Abstract Background PHYVV and PepGMV are plant viruses reported in Mexico and Southern US as causal agents of an important pepper disease known as "rizado amarillo". Mixed infections with PHYVV and PepGMV have been reported in several hosts over a wide geographic area. Previous work suggested that these viruses might interact at the replication and/or movement level in a complex manner. The aim of present report was to study some aspects of a synergistic interaction between PHYVV and PepGMV in pepper plants. These include analyses of symptom severity, viral DNA concentration and tissue localization of both viruses in single and mixed infections. Results Mixed infections with PepGMV and PHYVV induced symptoms more severe than those observed in single viral infections. Whereas plants infected with either virus (single infection presented a remission stage with a corresponding decrease in viral DNA levels, double-infected plants did not present symptom remission and both viral DNA concentrations dramatically increased. In situ hybridization experiments revealed that both viruses are restricted to the vascular tissue. Interestingly, the amount of viral DNA detected was higher in plants inoculated with PepGMV than that observed in PHYVV-infected plants. During mixed infections, the location of both viruses remained similar to the one observed in single infections, although the number of infected cells increases. Infections with the tripartite mixture PHYVV (A+B + PepGMV A produced a similar synergistic infection to the one observed after inoculation with both full viruses. On the contrary, tripartite mixture PepGMV (A+B + PHYVV A did not produce a synergistic interaction. In an attempt to study the contribution of individual genes to the synergism, several mutants of PHYVV or PepGMV were inoculated in combination with the corresponding wild type, second virus (wt PepGMV or wt PHYVV. All combinations tested resulted in synergistic infections, with

  17. Synergistic interaction between choline and aspirin against acute inflammation induced by carrageenan and lipopolysaccharide.

    Science.gov (United States)

    Pan, Zhi-Yuan; Wang, Hai

    2014-05-01

    The simultaneous use of drugs with different mechanisms of anti-inflammatory action is a strategy for achieving effective control of inflammation while minimizing dose-related side effects. Choline was described to potentiate the antinociceptive action of aspirin at small doses in several inflammatory pain models. However, these findings are only limited to alleviating pain, more associated data are required to confirm the effectiveness of the combined choline and aspirin therapy against inflammatory disorders. Moreover, no report is available regarding the mechanism responsible for their synergism. Here, we first investigated the anti-inflammatory activity and pharmacological mechanisms of co-administration of choline and aspirin in 2 commonly studied inflammation models, carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced sepsis in mice. Isobolographic analysis revealed that combined choline and aspirin administration exhibited a strong synergistic interaction in reducing carrageenan-mediated edema, and the estimated combination index values at 50%, 75%, and 90% effective dose (ED50, ED75, and ED90) were 0.25, 0.32, and 0.44. Drug co-administration also afforded synergistic protection against LPS-induced sepsis and mortality, since aspirin or choline alone was inadequate to improve survival. The effects of choline-aspirin co-administration were blocked by methyllycaconitine, suggesting that activation of alpha 7 nicotinic acetylcholine receptor participates in the interaction between choline and aspirin. Furthermore, co-administration of choline and aspirin was more likely to inhibit the production of pro-inflammatory mediators induced by LPS. Our results indicated that combined choline and aspirin therapy represented a significant synergistic interaction in attenuating acute inflammatory response. This preclinical relevant evidence provides a promising approach to treat inflammation-based diseases such as arthritis and sepsis. Copyright © 2014

  18. Interaction and its induced inhibiting or synergistic effects during co-gasification of coal char and biomass char.

    Science.gov (United States)

    Ding, Liang; Zhang, Yongqi; Wang, Zhiqing; Huang, Jiejie; Fang, Yitian

    2014-12-01

    Co-gasification of coal char and biomass char was conducted to investigate the interactions between them. And random pore model (RPM) and modified random pore model (MRPM) were applied to describe the gasification behaviors of the samples. The results show that inhibiting effect was observed during co-gasification of corn stalk char with Hulunbeier lignite coal char, while synergistic effects were observed during co-gasification of corn stalk char with Shenmu bituminous coal char and Jincheng anthracite coal char. The inhibiting effect was attributed to the intimate contact and comparable gasification rate between biomass char and coal char, and the loss of the active form of potassium caused by the formation of KAlSiO4, which was proved to be inactive during gasification. While the synergistic effect was caused by the high potassium content of biomass char and the significant difference of reaction rate between coal char and biomass char during gasification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Synergistic interaction between UVB radiation and temperature increases susceptibility to parasitic infection in a fish.

    Science.gov (United States)

    Cramp, Rebecca L; Reid, Stefanie; Seebacher, Frank; Franklin, Craig E

    2014-09-01

    Levels of UVB radiation (UVB) and mean temperatures have increased substantially over recent decades in many regions of the world. Both stressors independently can compromise immune function, disease resistance and fitness in fish. The impact of UVB can also be exacerbated by interactions with environmental temperatures. In this paper, we test the hypothesis that UVB and temperature act synergistically to influence patterns of energy consumption and susceptibility to disease. We exposed mosquitofish, Gambusia holbrooki, to a factorial design of low and high UVB levels and low (18°C) and high (25°C) temperatures. The combination of high UVB and high temperature interacted synergistically to suppress metabolism and exacerbate infection intensity by the fish pathogen whitespot (Ichtyhophthirius multifiliis). Given the rapid changes in the thermal environment globally, the interaction between UVB and temperatures on energy use and disease resistance could pose significant problems for aquatic animal health in the context of both pre-existing and emerging diseases. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  20. Response surface analysis of synergistic interactions of morphine and gabapentin in a rat model of postoperative pain

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    on the AIC criterion. Result The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58...... % for the synergistic doses. Conclusions The finding of dose-dependent synergistic interactions might indicate that there is a high potential for gabapentin and morphine to be used in combination in the clinic, in order to optimize postoperative pain management and minimize side effects of morphine. 1. Brennan TJ......, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain [Internet]. 1996 Mar;64(3):493–501. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8783314 2. Greco W, Bravo G, Parsons J. The search for synergy: A critical review from a responce surface perspective. Pharmacol Rev...

  1. Lack of synergistic interaction between the two mechanisms of action of tapentadol in gastrointestinal transit.

    Science.gov (United States)

    Cowan, A; Raffa, R B; Tallarida, C S; Tallarida, R J; Christoph, T; Schröder, W; Tzschentke, T M

    2014-09-01

    A multi-mechanistic approach offers potential enhancement of analgesic efficacy, but therapeutic gain could be offset by an increase in adverse events. The centrally acting analgesic tapentadol [(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride] combines μ-opioid receptor (MOR) agonism and neuronal noradrenaline reuptake inhibition (NRI), both of which contribute to its analgesic effects. Previously, isobolographic analysis of occupation-effect data and a theoretically equivalent methodology determining interactions from the effect scale demonstrated pronounced synergistic interaction between the two mechanisms of action of tapentadol in two models of antinociception (low-intensity tail-flick and spinal nerve ligation). The present study investigated the nature of interaction of the two mechanisms on a surrogate measure for gastrointestinal adverse effect (inhibition of gastrointestinal transit). Dose-response curves were generated in rats for tapentadol alone or in combination with the opioid receptor antagonist, naloxone, or the α2 -adrenoceptor antagonist, yohimbine, to reveal the effect of tapentadol based upon MOR agonism, NRI, and combined mechanisms. The dose-effect curve of tapentadol was shifted to the right by both antagonists, thereby providing data to distinguish between MOR agonism and NRI. Analysis revealed a simple additive interaction between the two mechanisms on this endpoint, in contrast to the synergistic interaction previously demonstrated for antinociception. We believe this is the first published evaluation of mechanistic interaction for a surrogate measure of adverse effect of a single compound with two mechanisms of action, and the results suggest that there is a greater separation between the analgesic and gastrointestinal effects of tapentadol than expected based upon its analgesic efficacy. © 2014 European Pain Federation - EFIC®

  2. Synergistic interactions of biotic and abiotic environmental stressors on gene expression.

    Science.gov (United States)

    Altshuler, Ianina; McLeod, Anne M; Colbourne, John K; Yan, Norman D; Cristescu, Melania E

    2015-03-01

    Understanding the response of organisms to multiple stressors is critical for predicting if populations can adapt to rapid environmental change. Natural and anthropogenic stressors often interact, complicating general predictions. In this study, we examined the interactive and cumulative effects of two common environmental stressors, lowered calcium concentration, an anthropogenic stressor, and predator presence, a natural stressor, on the water flea Daphnia pulex. We analyzed expression changes of five genes involved in calcium homeostasis - cuticle proteins (Cutie, Icp2), calbindin (Calb), and calcium pump and channel (Serca and Ip3R) - using real-time quantitative PCR (RT-qPCR) in a full factorial experiment. We observed strong synergistic interactions between low calcium concentration and predator presence. While the Ip3R gene was not affected by the stressors, the other four genes were affected in their transcriptional levels by the combination of the stressors. Transcriptional patterns of genes that code for cuticle proteins (Cutie and Icp2) and a sarcoplasmic calcium pump (Serca) only responded to the combination of stressors, changing their relative expression levels in a synergistic response, while a calcium-binding protein (Calb) responded to low calcium stress and the combination of both stressors. The expression pattern of these genes (Cutie, Icp2, and Serca) were nonlinear, yet they were dose dependent across the calcium gradient. Multiple stressors can have complex, often unexpected effects on ecosystems. This study demonstrates that the dominant interaction for the set of tested genes appears to be synergism. We argue that gene expression patterns can be used to understand and predict the type of interaction expected when organisms are exposed simultaneously to natural and anthropogenic stressors.

  3. Synergistic Interaction between the Two Mechanisms of Action of Tapentadol in Analgesia

    Science.gov (United States)

    Tzschentke, T. M.; Terlinden, R.; De Vry, J.; Jahnel, U.; Christoph, T.; Tallarida, R. J.

    2011-01-01

    The novel centrally acting analgesic tapentadol [(−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride] combines two mechanisms of action, μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), in a single molecule. Pharmacological antagonism studies have demonstrated that both mechanisms of action contribute to the analgesic effects of tapentadol. This study was designed to investigate the nature of the interaction of the two mechanisms. Dose-response curves were generated in rats for tapentadol alone or in combination with the opioid antagonist naloxone or the α2-adrenoceptor antagonist yohimbine. Two different pain models were used: 1) low-intensity tail-flick and 2) spinal nerve ligation. In each model, we obtained dose-effect relations to reveal the effect of tapentadol based on MOR agonism, NRI, and unblocked tapentadol. Receptor fractional occupation was determined from tapentadol's brain concentration and its dissociation constant for each binding site. Tapentadol produced dose-dependent analgesic effects in both pain models, and its dose-effect curves were shifted to the right by both antagonists, thereby providing data to distinguish between MOR agonism and NRI. Both isobolographic analysis of occupation-effect data and a theoretically equivalent methodology determining interactions from the effect scale demonstrated very pronounced synergistic interaction between the two mechanisms of action of tapentadol. This may explain why tapentadol is only 2- to 3-fold less potent than morphine across a variety of preclinical pain models despite its 50-fold lower affinity for the MOR. This is probably the first demonstration of a synergistic interaction between the occupied receptors for a single compound with two mechanisms of action. PMID:21262850

  4. Antinociceptive synergistic interaction between Achillea millefolium and Origanum vulgare L. extract encapsulated in liposome in rat.

    Science.gov (United States)

    Hassanzadeh-Kiabi, Farshad; Negahdari, Babak

    2017-07-18

    This study aims to evaluate the antinociceptive effect of combined Achillea millefolium and Origanum extract encapsulated in liposome. The effect of Achillea millefolium and Origanum vulgare L. extract, and their liposome-incorporated form was assessed using 3% formalin test in rat. 12 male Wistar rats, 4 in each group, were used in this study, and increasing doses of Achillea millefolium (31.6, 100, 178, and 316 mg/kg) and Origanum vulgare L. extract (5.6, 10, 17.8, and 31.6 mg/kg), and co-administered extract were i.p. administered 10 min before 3% formalin. The mechanisms of action were evaluated for the liposomal encapsulated co-administered extract using N(G)-nitro-l-arginine methyl ester (L-NAME) (3 mg/kg) and naloxone (1 mg/kg). The interaction index and isobolographic analysis revealed a synergistic effect of the extracts. We observed a lower experimental ED30 as compared to the theoretical ED30. Naloxone also reduced the antinociceptive effect of the liposome encapsulated co-administered extract. These data suggest that the Achillea millefolium and Origanum vulgare L. extract encapsulated in liposome gave a synergistic effect.

  5. Anomalous water dynamics at surfaces and interfaces: synergistic effects of confinement and surface interactions.

    Science.gov (United States)

    Biswas, Rajib; Bagchi, Biman

    2018-01-10

    In nature, water is often found in contact with surfaces that are extended on the scale of molecule size but small on a macroscopic scale. Examples include lipid bilayers and reverse micelles as well as biomolecules like proteins, DNA and zeolites, to name a few. While the presence of surfaces and interfaces interrupts the continuous hydrogen bond network of liquid water, confinement on a mesoscopic scale introduces new features. Even when extended on a molecular scale, natural and biological surfaces often have features (like charge, hydrophobicity) that vary on the scale of the molecular diameter of water. As a result, many new and exotic features, which are not seen in the bulk, appear in the dynamics of water close to the surface. These different behaviors bear the signature of both water-surface interactions and of confinement. In other words, the altered properties are the result of the synergistic effects of surface-water interactions and confinement. Ultrafast spectroscopy, theoretical modeling and computer simulations together form powerful synergistic approaches towards an understanding of the properties of confined water in such systems as nanocavities, reverse micelles (RMs), water inside and outside biomolecules like proteins and DNA, and also between two hydrophobic walls. We shall review the experimental results and place them in the context of theory and simulations. For water confined within RMs, we discuss the possible interference effects propagating from opposite surfaces. Similar interference is found to give rise to an effective attractive force between two hydrophobic surfaces immersed and kept fixed at a separation of d, with the force showing an exponential dependence on this distance. For protein and DNA hydration, we shall examine a multitude of timescales that arise from frustration effects due to the inherent heterogeneity of these surfaces. We pay particular attention to the role of orientational correlations and modification of the

  6. Anomalous water dynamics at surfaces and interfaces: synergistic effects of confinement and surface interactions

    Science.gov (United States)

    Biswas, Rajib; Bagchi, Biman

    2018-01-01

    In nature, water is often found in contact with surfaces that are extended on the scale of molecule size but small on a macroscopic scale. Examples include lipid bilayers and reverse micelles as well as biomolecules like proteins, DNA and zeolites, to name a few. While the presence of surfaces and interfaces interrupts the continuous hydrogen bond network of liquid water, confinement on a mesoscopic scale introduces new features. Even when extended on a molecular scale, natural and biological surfaces often have features (like charge, hydrophobicity) that vary on the scale of the molecular diameter of water. As a result, many new and exotic features, which are not seen in the bulk, appear in the dynamics of water close to the surface. These different behaviors bear the signature of both water–surface interactions and of confinement. In other words, the altered properties are the result of the synergistic effects of surface–water interactions and confinement. Ultrafast spectroscopy, theoretical modeling and computer simulations together form powerful synergistic approaches towards an understanding of the properties of confined water in such systems as nanocavities, reverse micelles (RMs), water inside and outside biomolecules like proteins and DNA, and also between two hydrophobic walls. We shall review the experimental results and place them in the context of theory and simulations. For water confined within RMs, we discuss the possible interference effects propagating from opposite surfaces. Similar interference is found to give rise to an effective attractive force between two hydrophobic surfaces immersed and kept fixed at a separation of d, with the force showing an exponential dependence on this distance. For protein and DNA hydration, we shall examine a multitude of timescales that arise from frustration effects due to the inherent heterogeneity of these surfaces. We pay particular attention to the role of orientational correlations and modification of

  7. Theory of synergistic effects: Hill-type response surfaces as 'null-interaction' models for mixtures.

    Science.gov (United States)

    Schindler, Michael

    2017-08-02

    The classification of effects caused by mixtures of agents as synergistic, antagonistic or additive depends critically on the reference model of 'null interaction'. Two main approaches are currently in use, the Additive Dose (ADM) or concentration addition (CA) and the Multiplicative Survival (MSM) or independent action (IA) models. We compare several response surface models to a newly developed Hill response surface, obtained by solving a logistic partial differential equation (PDE). Assuming that a mixture of chemicals with individual Hill-type dose-response curves can be described by an n-dimensional logistic function, Hill's differential equation for pure agents is replaced by a PDE for mixtures whose solution provides Hill surfaces as 'null-interaction' models and relies neither on Bliss independence or Loewe additivity nor uses Chou's unified general theory. An n-dimensional logistic PDE decribing the Hill-type response of n-component mixtures is solved. Appropriate boundary conditions ensure the correct asymptotic behaviour. Mathematica 11 (Wolfram, Mathematica Version 11.0, 2016) is used for the mathematics and graphics presented in this article. The Hill response surface ansatz can be applied to mixtures of compounds with arbitrary Hill parameters. Restrictions which are required when deriving analytical expressions for response surfaces from other principles, are unnecessary. Many approaches based on Loewe additivity turn out be special cases of the Hill approach whose increased flexibility permits a better description of 'null-effect' responses. Missing sham-compliance of Bliss IA, known as Colby's model in agrochemistry, leads to incompatibility with the Hill surface ansatz. Examples of binary and ternary mixtures illustrate the differences between the approaches. For Hill-slopes close to one and doses below the half-maximum effect doses MSM (Colby, Bliss, Finney, Abbott) predicts synergistic effects where the Hill model indicates 'null-interaction

  8. Kinetic study and synergistic interactions on catalytic CO2 gasification of Sudanese lower sulphur petroleum coke and sugar cane bagasse

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    Elbager M.A. Edreis

    2017-04-01

    Full Text Available In this study the effects of iron chloride (FeCl3 on the CO2 gasification kinetics of lower sulphur petroleum coke (PC and sugar cane bagasse (SCB via thermogravimetric analyser (TGA were investigated. The FeCl3 loading effects on the thermal behaviour and reactivity of CO2 gasification of PC were studied. The possible synergistic interaction between the PC and SCB was also examined. Then the homogeneous model or first order chemical reaction (O1 and shrinking core models (SCM or phase boundary controlled reactions (R2 and R3 were employed through Coats–Redfern method in order to detect the optimum mechanisms for the catalytic CO2 gasification, describe the best reaction behaviour and determine the kinetic parameters. The results showed that the thermal behaviour of PC is significantly affected by the FeCl3 loading. Among various catalyst loadings, the addition of 7 wt% FeCl3 to PC leads to improve the PC reactivity up to 39% and decrease the activation energy up to 22%. On the other hand, for char gasification stage of SCB and blend, the addition 5 wt% FeCl3 improved their reactivities to 18.7% and 29.8% and decreased the activation energies to 10% and 17%, respectively. The synergistic interaction between the fuel blend was observed in both reaction stages of the blend and became more significant in the pyrolysis stage. For all samples model R2 shows the lowest values of activation energy (E and the highest reaction rates constant (k. Finally, model R2 was the most suitable to describe the reactions of non-catalytic and catalytic CO2 gasification.

  9. Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

    Science.gov (United States)

    Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

    2010-12-15

    The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

  10. Characterization of the interaction between cadmium and chlorpyrifos with integrative techniques in incurring synergistic hepatoxicity.

    Directory of Open Access Journals (Sweden)

    Liqun Chen

    Full Text Available Mixture toxicity is an important issue for the risk assessment of environmental pollutants, for which an extensive amount of data are necessary in evaluating their potential adverse health effects. However, it is very hard to decipher the interaction between compounds due to limited techniques. Contamination of heavy metals and organophosphoric insecticides under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium (Cd and chlorpyrifos (CPF in environmental medium and food chains, their interaction and potentially synergistic toxicity remain elusive thus far. Here we integrated the approaches of thin-layer chromatography and (1H NMR to study the interaction between Cd(2+ and CPF in inducing hepatoxicity. A novel interaction was identified between Cd(2+ and CPF, which might be the bonding between Cd(2+ and nitrogen atom in the pyridine ring of CPF, or the chelation formation between one Cd(2+ and two CPF molecules. The Cd-CPF complex was conferred with distinct biological fate and toxicological performances from its parental components. We further demonstrated that the joint hepatoxicity of Cd ion and CPF was chiefly due to the Cd-CPF complex-facilitated intracellular transport associated with oxidative stress.

  11. Synergistic interaction between job control and social support at work on depression, burnout, and insomnia among Japanese civil servants.

    Science.gov (United States)

    Saijo, Yasuaki; Chiba, Shigeru; Yoshioka, Eiji; Nakagi, Yoshihiko; Ito, Toshihiro; Kitaoka-Higashiguchi, Kazuyo; Yoshida, Takahiko

    2015-02-01

    To elucidate whether low job control and low social support at work have synergistic interaction on mental health. The synergistic interaction was also analyzed after stratification by high and low job demands. Participants were 2,121 local government employees in Asahikawa city, Japan. The Brief Job Stress Questionnaire was used to assess job demands, job control, and social support. Depression was assessed using the Patient Health Questionnaire-9. The Maslach Burnout Inventory-General Survey was used to assess burnout. Insomnia was assessed using the Athens Insomnia Scale. Possible confounder-adjusted logistic regression analyses were performed to obtain odds ratios for depression, burnout, and insomnia, and synergy indices between job control and social support at work were assessed. The synergy indices among men and women, respectively, were 2.08 (80 % confidence interval: 1.01, 4.27) and 1.98 (0.67, 5.89) for depression, 1.79 (1.28, 2.51) and 2.62 (1.07, 6.40) for burnout, and 1.92 (1.22, 3.02) and 2.77 (0.43, 18.01) for insomnia. Men with high job demands had higher synergistic interaction on depression and burnout, compared to men with low job demands, and women with low job demands had higher synergistic interaction between job control and social support at work on burnout and insomnia, compared to women with high job demands. There were more-than-additive interactions of job control and social support at work on depression, burnout, and insomnia. After stratification by job demands, the synergistic interaction may be different between men and women. To assess job stress, it is necessary to consider the interactive effect of not only job demands and job control but also job control and social support at work.

  12. Interfacial reaction in the synergistic extraction rate of Ni(II) with dithizone and 1,10-phenanthroline.

    Science.gov (United States)

    Watarai, H; Sasaki, K; Takahashi, K; Murakami, J

    1995-11-01

    The kinetic synergistic effect of 1,10-phenanthroline (phen) on the extraction rate of Ni(II) with dithizone (HDz) into chloroform was studied by means of a high-speed stirring method combined with photodiode-array spectrophotometry. The initial extraction rate of the adduct complex NiDz(2)phen depended upon the concentrations of both HDz and phen, suggesting the formation of NiDzphen(+) as the rate-controlling step. When [HDz] < [phen], the initial extraction of NiDz(2)phen competed with the formation of an intermediate complex, which was adsorbed at the interface and assigned most probably to NiDzphen(+)(2). The intermediate complex was gradually converted to NiDz(2)phen at a later stage of the extraction. The rate constants for the formation and consumption of the intermediate were determined, and the kinetic mechanism in the synergistic extraction was discussed.

  13. Home Remodeling and Food Allergy Interact Synergistically to Increase the Risk of Atopic Dermatitis

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    Won Seok Lee

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to investigate the effects of home remodeling and food allergy (FA on the development of atopic dermatitis (AD in children. Methods. The Modified International Study of Asthma and Allergies in Childhood questionnaire was used to survey 4,111 children recruited from 3 kindergartens and 6 elementary schools from Seongnam, Korea. Participants’ parents agreed for them to participate in physical examinations, skin prick tests, and blood tests. Results. Home remodeling in the past 12 months (adjusted odds ratio [aOR] 3.40, P=0.006, lifetime diagnosis of FA (aOR 3.95, P<0.001, parental history of AD (aOR 2.67, P=0.001, and FA (aOR 2.35, P=0.004 were independent risk factors for lifetime diagnosis of AD ever. When history of home remodeling and FA were combined, the risk for moderate-to-severe AD by scoring atopic dermatitis (SCORAD score increased (aOR, 7.19, P=0.011, P for interaction = 0.034. Conclusion. Home remodeling, lifetime diagnosis of FA, parental history of AD, and parental history of FA were independent risk factors for AD. In addition, we observed a synergistic interaction between home remodeling and FA in the risk of moderate-to-severe AD.

  14. Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats.

    Science.gov (United States)

    Beltrán-Villalobos, Karla Lyzet; Déciga-Campos, Myrna; Aguilar-Mariscal, Hidemi; González-Trujano, María Eva; Martínez-Salazar, María Fernanda; Ramírez-Cisneros, María de Los Ángeles; Rios, María Yolanda; López-Muñoz, Francisco Javier

    2017-10-01

    Syzygium aromaticum (L.) Merr. & L.M. Perry (Mirtaceae) and Rosmarinus officinalis L. (Lamiaceae) are both medicinal plants used for centuries to alleviate pain. The aim of the study was to demonstrate the therapeutic potential utility of herb-drug association of S. aromaticum essential oil or R. officinalis ethanolic extract coadministered with ketorolac. Antinociceptive pharmacological interaction was investigated by an isbolographic study using the formalin test in rats. Both alone and in combination with ketorolac; S. aromaticum and R. officinalis produced a dose-dependent antinociceptive response. To plot the isobologram, we used the effective dose 50 of each one component in a fixed 1:1 ratio. The isobolographic analysis showed that, in both combinations, ketorolac plus essential oil S. aromaticum and ketorolac plus ethanolic extract R. officinalis, the experimental value (Zexp) was lower than the theoretical value (Zadd). In addition, this study shows that eugenol, a metabolite present in S. aromaticum, and ursolic acid, a metabolite present in R. officinalis, also synergized the antinociceptive effect of ketorolac. While, the oleanolic acid present in both medicinal species did not show a synergistic antinociceptive effect in combination with ketorolac. No adverse effects were observed with these herb-drug interactions. These findings suggest that essential oil S. aromaticum and ethanolic extract R. officinalis could be useful in combination with ketorolac for the treatment of inflammatory pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Synergistic interaction between diclofenac and pyrilamine on nociception, inflammation, and gastric damage in rats.

    Science.gov (United States)

    Ortiz, Mario I

    2017-01-01

    Experiments using nonsteroidal anti-inflammatory drugs (NSAIDs) alone have produced limited antinociceptive effects in animal models. For this reason, the number of studies involving the administration of NSAIDs along with an adjuvant drug harboring different mechanisms of action has increased enormously. Here, combinations of diclofenac and pyrilamine were used to determine their influence on nociception (formalin test), inflammation (paw inflammation produced by carrageenan), and gastric damage in rodents. Diclofenac, pyrilamine, or combinations of diclofenac and pyrilamine produced antinociceptive and anti-inflammatory effects in the rat. The systemic administration of diclofenac alone and in combination with pyrilamine produced significant gastric damage. Effective dose (ED) values were determined for each individual drug, and isobolograms were prepared. The theoretical ED values for the antinociceptive (systemic, 35.4 mg/kg; local, 343.4 μg/paw) and the anti-inflammatory (37.9 mg/kg) effects differed significantly from the experimental ED values (systemic antinociception, 18.1 mg/kg; local antinociception, 183.3 μg/paw; anti-inflammation, 10.6 mg/kg). Therefore, it was concluded that the interactions between diclofenac and pyrilamine are synergistic. The data suggest that the diclofenac-pyrilamine combinations can interact at the systemic and local peripheral levels, thereby offering a therapeutic alternative for the clinical management of inflammatory pain.

  16. Citral, a monoterpenoid aldehyde interacts synergistically with norfloxacin against methicillin resistant Staphylococcus aureus.

    Science.gov (United States)

    Gupta, Priyanka; Patel, Dinesh Kumar; Gupta, Vivek Kumar; Pal, Anirban; Tandon, Sudeep; Darokar, M P

    2017-10-15

    Staphylococcus aureus (SA), is a major human pathogen causing wide range of clinical infections, which has been further complicated by drug resistance like methicillin resistant S. aureus (MRSA), vancomycin intermediate S. aureus (VISA)/vancomycin resistant S. aureus (VRSA), etc. The present study was aimed at determining anti-staphylococcal potential of citral against drug resistant clinical isolates alone and in combination with antibiotics. To assess the potential of citral in combination with norfloxacin in treating drug resistant infections of SA. In the present study, synergistic interaction of citral and norfloxacin against drug resistant SA strains was evaluated. Further the efficacy and possible mechanism of action of the combination was also evaluated using in vitro and in vivo assays. The anti-staphylococcal activity of each of the monoterpene and the antibiotic was determined in terms of MIC and the effective concentration of both compounds in combination was obtained by checkerboard assay. In vivo efficacy and oral acute toxicity was evaluated in Swiss albino mice model. To understand the mechanism of action, time-kill curve, bacteriolysis, leakage, membrane depolarization, salt tolerance and ethidium bromide efflux assays were performed. Citral was found effective against clinical isolates of SA with MIC values ranging from 75 to 150 µg ml-1 exhibiting bacteriostatic activity. Citral interacted synergistically, reducing MIC of norfloxacin up to 32-folds with FICI ≤ 0.50. Citral did not affect cell wall, but could damage cell membrane, inhibit efflux pump and affect the membrane potential. Citral could reduce the staphylococcal load of spleen and liver tissues in a dose-dependent manner which was further reduced when used in combination with norfloxacin. Citral did not exhibit any mortality or morbidity up to 500 mg kg-1 body weight and found to prolong the post-antibiotic effect of norfloxacin. Based on these observations, citral could be a

  17. Critical nutrient thresholds needed to control eutrophication and synergistic interactions between phosphorus and different nitrogen sources.

    Science.gov (United States)

    Zeng, Qinghui; Qin, Lihuan; Bao, Linlin; Li, Yayong; Li, Xuyong

    2016-10-01

    Eutrophication is one of the greatest threats to global freshwater ecosystems. The phytoplankton responses to nutrient inputs vary in different water bodies, so it is particularly important to determine the nutrient thresholds and synergistic interactions between nutrients in different freshwater ecosystems. Field sampling and bioassay experiments were conducted to determine the thresholds of soluble reactive phosphorus (SRP), nitrate-nitrogen (NO 3 -N), and ammonium-nitrogen (NH 4 -N) in Miyun Reservoir. A separate nutrient addition bioassay was designed to assess the synergistic interactions between these nutrients. Chlorophyll a (Chl a) concentrations were used to estimate phytoplankton biomass. The results showed the following: (1) nutrient threshold bioassay indicated that eutrophication thresholds of SRP, NO 3 -N, and NH 4 -N should be targeted at below 0.04 mg P L -1 , 0.5 mg N L -1 , and 0.3 mg N L -1 , respectively, to limit the growth of phytoplankton. (2) The stimulatory effect of "NH 4 -N plus P" on phytoplankton biomass was greater than "NO 3 -N plus P" at the same N concentration, and "NH 4 -N plus NO 3 -N" did not show such associated stimulatory effect as "NH 4 -N plus P" or "NO 3 -N plus P". (3) The average concentrations of total phosphorus (TP), NO 3 -N, and NH 4 -N in Miyun Reservior were 0.017 mg P L -1 , 0.620 mg N L -1 , and 0.143 mg N L -1 , respectively. The reservoir-wide average Chl a is below 20 μg L -1 on an annual basis. (4) Ammonium was an important factor for the growth of phytoplankton and inputs of both NH 4 -N and NO 3 -N should be reduced to control bloom formation. Our findings imply that although P load reduction is important, appropriate reductions of all forms of N in watershed is recommended in the nutrient management strategy for Miyun Reservoir.

  18. Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test.

    Science.gov (United States)

    Déciga-Campos, Myrna; Ramírez-Marín, Pamela Moncerrat; López-Muñoz, Francisco Javier

    2015-10-15

    Pharmacological synergism has been used to obtain a higher efficacy using drug concentrations at which side effects are minimal. In this study, the pharmacological antinociceptive interaction between N-palmitoylethanolamide (PEA) and tramadol was investigated. The individual concentration-response curves for PEA (0.1-56.2 μg/paw) and tramadol (1-56.2 μg/paw) were evaluated in mice in which nociception was induced by an intraplantar injection of 2% formalin. Isobolographic analysis was used to evaluate the pharmacological interaction between PEA (EC50=23.7±1.6 μg/paw) and tramadol (EC50=26.02±2.96 μg/paw) using the EC50 and a fixed 1:1 ratio combination. The isobologram demonstrated that the combinations investigated in this study produced a synergistic interaction; the experimental values (Zexp=9.5±0.2 μg/paw) were significantly smaller than those calculated theoretically (Zadd=24.8±0.2 μg/paw). The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-α). The sedative effect of the combination of PEA and tramadol was less than that generated by individual treatments. These findings suggest that the PEA and tramadol combination produced enhanced antinociceptive efficacy at concentrations at which side effects are minimal. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Intra- And Inter-Monomer Interactions are Required to Synergistically Facilitate ATP Hydrolysis in HSP90

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, C.N.; Krukenberg, K.A.; Agard, D.A.

    2009-05-12

    Nucleotide-dependent conformational changes of the constitutively dimeric molecular chaperone Hsp90 are integral to its molecular mechanism. Recent full-length crystal structures (Protein Data Bank codes 2IOQ, 2CG9, AND 2IOP) of Hsp90 homologs reveal large scale quaternary domain rearrangements upon the addition of nucleotides. Although previous work has shown the importance of C-terminal domain dimerization for efficient ATP hydrolysis, which should imply cooperativity, other studies suggest that the two ATPases function independently. Using the crystal structures as a guide, we examined the role of intra- and intermonomer interactions in stabilizing the ATPase activity of a single active site within an intact dimer. This was accomplished by creating heterodimers that allow us to differentially mutate each monomer, probing the context in which particular residues are important for ATP hydrolysis. Although the ATPase activity of each monomer can function independently, we found that the activity of one monomer could be inhibited by the mutation of hydrophobic residues on the trans N-terminal domain (opposite monomer). Furthermore, these trans interactions are synergistically mediated by a loop on the cis middle domain. This loop contains hydrophobic residues as well as a critical arginine that provides a direct linkage to the {gamma}-phosphate of bound ATP. Small angle x-ray scattering demonstrates that deleterious mutations block domain closure in the presence of AMPPNP (5{prime}-adenylyl-{beta},{gamma}-imidodiphosphate), providing a direct linkage between structural changes and functional consequences. Together, these data indicate that both the cis monomer and the trans monomer and the intradomain and interdomain interactions cooperatively stabilize the active conformation of each active site and help explain the importance of dimer formation.

  20. Synergistic interaction between the fungus Beauveria bassiana and desiccant dusts applied against poultry red mites (Dermanyssus gallinae).

    Science.gov (United States)

    Steenberg, Tove; Kilpinen, Ole

    2014-04-01

    The poultry red mite, Dermanyssus gallinae, is a major pest in egg production, feeding on laying hens. Widely used non-chemical control methods include desiccant dusts, although their persistence under field conditions is often short. Entomopathogenic fungi may also hold potential for mite control, but these fungi often take several days to kill mites. Laboratory experiments were carried out to study the efficacy of 3 types of desiccant dusts, the fungus Beauveria bassiana and combinations of the two control agents against D. gallinae. There was significant synergistic interaction between each of the desiccant dusts and the fungus, with observed levels of mite mortality significantly higher than those expected for an additive effect (up to 38 % higher). Synergistic interaction between desiccant dust and fungus was found also when different application methods were used for the fungus and at different levels of relative humidity. Although increased levels of mortality were reached due to the synergistic interaction, the speed of lethal action was not influenced by combining the two components. The persistence of the control agents applied separately or in combination did not change over a period of 4 weeks. Overall, combinations of desiccant dusts and fungus conidia seem to hold considerable promise for future non-chemical control of poultry red mites.

  1. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis.

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    Jingyue Xu

    Full Text Available Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects in homozygotes. How OSR1 regulates kidney development and nephron endowment is not well understood, however. In this study, by using the recently developed CRISPR genome editing technology, we genetically labeled the endogenous Osr1 protein and show that Osr1 interacts with Wt1 in the developing kidney. Whereas mice heterozygous for either an Osr1 or Wt1 null allele have normal kidneys at birth, most mice heterozygous for both Osr1 and Wt1 exhibit defects in metanephric kidney development, including unilateral or bilateral kidney agenesis or hypoplasia. The developmental defects in the Osr1+/-Wt1+/- mouse embryos were detected as early as E10.5, during specification of the metanephric mesenchyme, with the Osr1+/-Wt1+/- mouse embryos exhibiting significantly reduced Pax2-positive and Six2-positive nephron progenitor cells. Moreover, expression of Gdnf, the major nephrogenic signal for inducing ureteric bud outgrowth, was significantly reduced in the metanephric mesenchyme in Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- littermates. By E11.5, as the ureteric buds invade the metanephric mesenchyme and initiate branching morphogenesis, kidney morphogenesis was significantly impaired in the Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- embryos. These results indicate that Osr1 and Wt1 act synergistically to regulate nephron endowment by controlling metanephric mesenchyme specification during early nephrogenesis.

  2. Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

    2017-05-01

    Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

  3. Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

    Directory of Open Access Journals (Sweden)

    Stuart J Grice

    2015-03-01

    Full Text Available Autism spectrum disorders (ASDs are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs. These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our

  4. An In Vitro Synergistic Interaction of Combinations of Thymus glabrescens Essential Oil and Its Main Constituents with Chloramphenicol

    Directory of Open Access Journals (Sweden)

    Budimir S. Ilić

    2014-01-01

    Full Text Available The chemical composition and antibacterial activity of Thymus glabrescens Willd. (Lamiaceae essential oil were examined, as well as the association between it and chloramphenicol. The antibacterial activities of geraniol and thymol, the main constituents of T. glabrescens oil, individually and in combination with chloramphenicol, were also determined. The interactions of the essential oil, geraniol, and thymol with chloramphenicol toward five selected strains were evaluated using the microdilution checkerboard assay in combination with chemometric methods. Oxygenated monoterpenes were the most abundant compound class in the oil, with geraniol (22.33% as the major compound. The essential oil exhibited in vitro antibacterial activity against all tested bacterial strains, but the activities were lower than those of the standard antibiotic and thymol. A combination of  T. glabrescens oil and chloramphenicol produced a strong synergistic interaction (FIC indices in the range 0.21–0.87 and a substantial reduction of the MIC value of chloramphenicol, thus minimizing its adverse side effects. The combinations geraniol-chloramphenicol and thymol-chloramphenicol produced synergistic interaction to a greater extent, compared with essential oil-chloramphenicol association, which may indicate that the activity of the thyme oil could be attributed to the presence of significant concentrations of geraniol and thymol.

  5. Synergistic effects of plasma-catalyst interactions for CH4activation.

    Science.gov (United States)

    Kim, Jongsik; Go, David B; Hicks, Jason C

    2017-05-24

    The elucidation of catalyst surface-plasma interactions is a challenging endeavor and therefore requires thorough and rigorous assessment of the reaction dynamics on the catalyst in the plasma environment. The first step in quantifying and defining catalyst-plasma interactions is a detailed kinetic study that can be used to verify appropriate reaction conditions for comparison and to discover any unexpected behavior of plasma-assisted reactions that might prevent direct comparison. In this paper, we provide a kinetic evaluation of CH 4 activation in a dielectric barrier discharge plasma in order to quantify plasma-catalyst interactions via kinetic parameters. The dry reforming of CH 4 with CO 2 was studied as a model reaction using Ni supported on γ-Al 2 O 3 at temperatures of 790-890 K under atmospheric pressure, where the partial pressures of CH 4 (or CO 2 ) were varied over a range of ≤25.3 kPa. Reaction performance was monitored by varying gas hourly space velocity, plasma power, bulk gas temperature, and reactant concentration. After correcting for gas-phase plasma reactions, a linear relationship was observed in the log of the measured rate constant with respect to reciprocal power (1/power). Although thermal catalysis displays typical Arrhenius behavior for this reaction, plasma-assisted catalysis occurs from a complex mixture of sources and shows non-Arrhenius behavior. However, an energy barrier was obtained from the relationship between the reaction rate constant and input power to exhibit ≤∼20 kJ mol -1 (compared to ∼70 kJ mol -1 for thermal catalysis). Of additional importance, the energy barriers measured during plasma-assisted catalysis were relatively consistent with respect to variations in total flow rates, types of diluent, or bulk reaction temperature. These experimental results suggest that plasma-generated vibrationally-excited CH 4 favorably interacts with Ni sites at elevated temperatures, which helps reduce the energy barrier

  6. Electrochemical and theoretical studies on the synergistic interaction and corrosion inhibition of alkyl benzimidazoles and thiosemicarbazide pair on mild steel in hydrochloric acid

    Energy Technology Data Exchange (ETDEWEB)

    Ramya, K.; Mohan, Revathi; Anupama, K.K.; Joseph, Abraham, E-mail: drabrahamj@gmail.com

    2015-01-15

    Synergistic hydrogen bonded interaction of alkyl benzimidazoles and thiosemicarbazide (TSC) and its corrosion protection properties on mild steel in hydrochloric acid at different temperatures have been studied using polarization, EIS, adsorption, surface studies and computational methods. The extent of synergistic interaction increases with temperature. Quantum chemical approach used to calculate some electronic properties of the molecules and to ascertain the synergistic interaction, inhibitive effect and molecular structures. The corrosion inhibition efficiencies and the global chemical reactivity relate to some parameters, such as total energy, E{sub HOMO}, E{sub LUMO} and gap energy (ΔE) thiosemicarbazide (TSC) interacts with benzimidazoles derivatives up to a bond length of approximately 1.99Å. This interaction represents the formation of a hydrogen bond between the thiosemicarbazide (TSC) and benzimidazoles. This synergistic interaction of thiosemicarbazide (TSC) and benzimidazole derivatives offer extended inhibition efficiency towards mild steel in hydrochloric acid. - Highlights: • Synergistic interaction between alkyl benzimidazoles and TSC has been studied. • Mechanism involves combination of physisorption and chemisorption. • The adsorption phenomenon obeys Langmuir isotherm. • Inhibition efficiency increases with temperature.

  7. Synergistic Airframe-Propulsion Interactions and Integrations: A White Paper Prepared by the 1996-1997 Langley Aeronautics Technical Committee

    Science.gov (United States)

    Yaros, Steven F.; Sexstone, Matthew G.; Huebner, Lawrence D.; Lamar, John E.; McKinley, Robert E., Jr.; Torres, Abel O.; Burley, Casey L.; Scott, Robert C.; Small, William J.

    1998-01-01

    This white paper addresses the subject of Synergistic Airframe-Propulsion interactions and integrations (SnAPII). The benefits of SnAPII have not been as extensively explored. This is due primarily to the separateness of design process for airframes and propulsion systems, with only unfavorable interactions addressed. The question 'How to design these two systems in such a way that the airframe needs the propulsion and the propulsion needs the airframe?' is the fundamental issue addressed in this paper. Successful solutions to this issue depend on appropriate technology ideas. This paper first details some ten technologies that have yet to make it to commercial products (with limited exceptions) and that could be utilized in a synergistic manner. Then these technologies, either alone or in combination, are applied to both a conventional twin-engine transonic transport and to an unconventional transport, the Blended Wing Body. Lastly, combinations of these technologies are applied to configuration concepts to assess the possibilities of success relative to five of the ten NASA aeronautics goals. These assessments are subjective, but they point the way in which the applied technologies could work together for some break-through benefits.

  8. Synergistic interaction in simultaneous exposure to Streptomyces californicus and Stachybotrys chartarum

    DEFF Research Database (Denmark)

    Huttunen, K.; Pelkonen, J.; Nielsen, Kristian Fog

    2004-01-01

    and their metabolites, although the cytotoxicity and inflammatory potential of certain individual microbes have been reported. In this study, we investigated the inflammatory responses of mouse RAW264.7 macrophages after exposure to six indoor air microbes (Aspergillus versicolor, Penicillium spinulosum, Stachybotrys...... chartarum, Bacillus cereus, Mycobacterium terrae, and Pseudomonas fluorescens) alone and together with the actinomycete Streptomyces californicus. The production of nitric oxide, levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), and cytotoxicity were......-hydroxytrichodermol. Finally, the synergistic inflammatory response caused by Str. californicus and trichodermin together was studied by analyzing for the presence of nuclear factor-kappaB (NF-kappaB) in nuclear extracts of the exposed cells. The exposure to Str. californicus induced the binding of NF-kappaB proteins...

  9. Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Michele Cea

    Full Text Available Aberrant histone deacetylase (HDAC activity is frequent in human leukemias. However, while classical, NAD(+-independent HDACs are an established therapeutic target, the relevance of NAD(+-dependent HDACs (sirtuins in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527 and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+ levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

  10. Synergistic Interactions between Hepatitis B Virus RNase H Antagonists and Other Inhibitors.

    Science.gov (United States)

    Lomonosova, Elena; Zlotnick, Adam; Tavis, John E

    2017-03-01

    Combination therapies are standard for management of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections; however, no such therapies are established for human hepatitis B virus (HBV). Recently, we identified several promising inhibitors of HBV RNase H (here simply RNase H) activity that have significant activity against viral replication in vitro Here, we investigated the in vitro antiviral efficacy of combinations of two RNase H inhibitors with the current anti-HBV drug nucleoside analog lamivudine, with HAP12, an experimental core protein allosteric modulator, and with each other. Anti-HBV activities of the compounds were tested in a HepG2-derived cell line by monitoring intracellular core particle DNA levels, and cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The antiviral efficiencies of the drug combinations were evaluated using the median-effect equation derived from the mass-action law principle and combination index theorem of Chou and Talalay. We found that combinations of two RNase H inhibitors from different chemical classes were synergistic with lamivudine against HBV DNA synthesis. Significant synergism was also observed for the combination of the two RNase H inhibitors. Combinations of RNase H inhibitors with HAP12 had additive antiviral effects. Enhanced cytotoxicity was not observed in the combination experiments. Because of these synergistic and additive effects, the antiviral activity of combinations of RNase H inhibitors with drugs that act by two different mechanisms and with each other can be achieved by administering the compounds in combination at doses below the respective single drug doses. Copyright © 2017 American Society for Microbiology.

  11. The allosteric AKT inhibitor MK2206 shows a synergistic interaction with chemotherapy and radiotherapy in glioblastoma spheroid cultures.

    Science.gov (United States)

    Narayan, Ravi S; Fedrigo, Carlos A; Brands, Eelke; Dik, Rogier; Stalpers, Lukas J A; Baumert, Brigitta G; Slotman, Ben J; Westerman, Bart A; Peters, Godefridus J; Sminia, Peter

    2017-03-21

    Glioblastoma multiforme (GBM) is the most common, invasive and deadly primary type of malignant brain tumor. The Phosphatidylinositol-3-Kinase/AKT (PI3K/AKT) pathway is highly active in GBM and has been associated with increased survival and resistance to therapy. The aim of this study is to investigate the effects of AKT inhibition in combination with the current standard of care which consists of irradiation and temozolomide (TMZ) on human malignant glioma cells growing adherent and as multicellular spheroids in vitro. The effects of the allosteric inhibitor MK2206 combined with irradiation and TMZ were assessed on glioma cells growing adherent and as multicellular 3D spheroids. The interaction was studied on proliferation, clonogenic cell survival, cell invasion, -migration and on expression of key proteins in the PI3K-AKT pathway by western blot. A differential effect was found at low- (1 μM) and high dose (10 μM) MK2206. At 1 μM, the inhibitor reduced phosphorylation of Thr308 and Ser473 residues of AKT in both adherent cells and spheroids. Low dose MK2206 delayed spheroid growth and sensitized spheroids to both irradiation and TMZ in a synergistic way (Combination index 5 μM). The data show that a 3D spheroid model show different sensitivity to irradiation when combined with AKT inhibition. Thereby we show that MK2206 has potential synergistic efficacy to the current standard of care for glioma patients.

  12. Stability of strong species interactions resist the synergistic effects of local and global pollution in kelp forests.

    Science.gov (United States)

    Falkenberg, Laura J; Russell, Bayden D; Connell, Sean D

    2012-01-01

    Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp) would continue to inhibit a key competitor (turf-forming algae) under moderately increased local (nutrient) and near-future forecasted global pollution (CO(2)). Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO(2)). The positive effects of nutrient and CO(2) enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading) rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities.

  13. Hierarchical Nacre Mimetics with Synergistic Mechanical Properties by Control of Molecular Interactions in Self-Healing Polymers.

    Science.gov (United States)

    Zhu, Baolei; Jasinski, Nils; Benitez, Alejandro; Noack, Manuel; Park, Daesung; Goldmann, Anja S; Barner-Kowollik, Christopher; Walther, Andreas

    2015-07-20

    Designing the reversible interactions of biopolymers remains a grand challenge for an integral mimicry of mechanically superior biological composites. Yet, they are the key to synergistic combinations of stiffness and toughness by providing sacrificial bonds with hidden length scales. To address this challenge, dynamic polymers were designed with low glass-transition temperature T(g) and bonded by quadruple hydrogen-bonding motifs, and subsequently assembled with high-aspect-ratio synthetic nanoclays to generate nacre-mimetic films. The high dynamics and self-healing of the polymers render transparent films with a near-perfectly aligned structure. Varying the polymer composition allows molecular control over the mechanical properties up to very stiff and very strong films (E≈45 GPa, σ(UTS)≈270 MPa). Stable crack propagation and multiple toughening mechanisms occur in situations of balanced dynamics, enabling synergistic combinations of stiffness and toughness. Excellent gas barrier properties complement the multifunctional property profile. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Stability of strong species interactions resist the synergistic effects of local and global pollution in kelp forests.

    Directory of Open Access Journals (Sweden)

    Laura J Falkenberg

    Full Text Available Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp would continue to inhibit a key competitor (turf-forming algae under moderately increased local (nutrient and near-future forecasted global pollution (CO(2. Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO(2. The positive effects of nutrient and CO(2 enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities.

  15. Synergistic interactions of begomoviruses with Sweet potato chlorotic stunt virus (genus Crinivirus) in sweet potato (Ipomoea batatas L.).

    Science.gov (United States)

    Cuellar, Wilmer J; Galvez, Marco; Fuentes, Segundo; Tugume, Joab; Kreuze, Jan

    2015-06-01

    Three hundred and ninety-four sweet potato accessions from Latin America and East Africa were screened by polymerase chain reaction (PCR) for the presence of begomoviruses, and 46 were found to be positive. All were symptomless in sweet potato and generated leaf curling and/or chlorosis in Ipomoea setosa. The five most divergent isolates, based on complete genome sequences, were used to study interactions with Sweet potato chlorotic stunt virus (SPCSV), known to cause synergistic diseases with other viruses. Co-infections led to increased titres of begomoviruses and decreased titres of SPCSV in all cases, although the extent of the changes varied notably between begomovirus isolates. Symptoms of leaf curling only developed temporarily in combination with isolate StV1 and coincided with the presence of the highest begomovirus concentrations in the plant. Small interfering RNA (siRNA) sequence analysis revealed that co-infection of SPCSV with isolate StV1 led to relatively increased siRNA targeting of the central part of the SPCSV genome and a reduction in targeting of the genomic ends, but no changes to the targeting of StV1 relative to single infection of either virus. These changes were not observed in the interaction between SPCSV and the RNA virus Sweet potato feathery mottle virus (genus Potyvirus), implying specific effects of begomoviruses on RNA silencing of SPCSV in dually infected plants. Infection in RNase3-expressing transgenic plants showed that this protein was sufficient to mediate this synergistic interaction with DNA viruses, similar to RNA viruses, but exposed distinct effects on RNA silencing when RNase3 was expressed from its native virus, or constitutively from a transgene, despite a similar pathogenic outcome. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  16. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila.

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    Hsueh-Yen Ku

    2016-01-01

    Full Text Available Piwi proteins associate with piRNAs and functions in epigenetic programming, post-transcriptional regulation, transposon silencing, and germline development. However, it is not known whether the diverse functions of these proteins are molecularly separable. Here we report that Piwi interacts with Tudor-SN (Tudor staphylococcal nuclease, TSN antagonistically in regulating spermatogenesis but synergistically in silencing transposons. However, it is not required for piRNA biogenesis. TSN is known to participate in diverse molecular functions such as RNAi, degradation of hyper-edited miRNAs, and spliceosome assembly. We show that TSN colocalizes with Piwi in primordial germ cells (PGCs and embryonic somatic cells. In adult ovaries and testes, TSN is ubiquitously expressed and enriched in the cytoplasm of both germline and somatic cells. The tsn mutants display a higher mitotic index of spermatogonia, accumulation of spermatocytes, defects in meiotic cytokinesis, a decreased number of spermatids, and eventually reduced male fertility. Germline-specific TSN-expression analysis demonstrates that this function is germline-dependent. Different from other known Piwi interters, TSN represses Piwi expression at both protein and mRNA levels. Furthermore, reducing piwi expression in the germline rescues tsn mutant phenotype in a dosage-dependent manner, demonstrating that Piwi and TSN interact antagonistically in germ cells to regulate spermatogenesis. However, the tsn deficiency has little, if any, impact on piRNA biogenesis but displays a synergistic effect with piwi mutants in transposon de-silencing. Our results reveal the biological function of TSN and its contrasting modes of interaction with Piwi in spermatogenesis, transposon silencing, and piRNA biogenesis.

  17. Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test.

    Science.gov (United States)

    Montiel-Ruiz, Rosa Mariana; González-Trujano, María Eva; Déciga-Campos, Myrna

    2013-11-15

    In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 was investigated in the mouse formalin test. Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B1+B6+B12 by using the ED30 and a fixed 1:1 ratio combination. Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED50=81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K(+) channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED30 values were significantly smaller than those calculated theoretically. These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. THE ANTIBACTERIAL EFFECT OF SOME MEDICINAL PLANTS (INULA VISCOSA, ANACYCLUS VALENTINUS AND THEIR SYNERGISTIC INTERACTION WITH ANTIBIOTIC DRUGS

    Directory of Open Access Journals (Sweden)

    K. Side Larbi

    2016-05-01

    Full Text Available With the emergence of multidrug-resistant organisms, combining medicinal plants with synthetic medicines against resistant bacteria becomes necessary. In this study, Synergism between plant extracts (methanolic extract and essential oils of Inula viscosa and Anacyclus valentinus and two commonly used antibiotics (gentamycin, oxacillin were investigated on three bacterian strains (E. coli, Bacillus subtilis, Staphylococcus aureus. In the first time, the antibacterial effect of extracts alone was tested against 7 strains by disc diffusion and microdilution methods. The minimum inhibitory concentrations of methanolic extracts ranged between 6.25 and 50mg/ml while that of the essential oils varied between 12.5 and 100µL/mL. Interactions extracts /antibiotics and extracts/extracts by checkboard. The results show that the synergistic effect of combinations plant extracts/antibiotics was more important than extracts/extracts.

  19. Effect of Eugenol against Streptococcus agalactiae and Synergistic Interaction with Biologically Produced Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Renata Perugini Biasi-Garbin

    2015-01-01

    Full Text Available Streptococcus agalactiae (group B streptococci (GBS is an important infections agent in newborns associated with maternal vaginal colonization. Intrapartum antibiotic prophylaxis in GBS-colonized pregnant women has led to a significant reduction in the incidence of early neonatal infection in various geographic regions. However, this strategy may lead to resistance selecting among GBS, indicating the need for new alternatives to prevent bacterial transmission and even to treat GBS infections. This study reported for the first time the effect of eugenol on GBS isolated from colonized women, alone and in combination with silver nanoparticles produced by Fusarium oxysporum (AgNPbio. Eugenol showed a bactericidal effect against planktonic cells of all GBS strains, and this effect appeared to be time-dependent as judged by the time-kill curves and viability analysis. Combination of eugenol with AgNPbio resulted in a strong synergistic activity, significantly reducing the minimum inhibitory concentration values of both compounds. Scanning and transmission electron microscopy revealed fragmented cells and changes in bacterial morphology after incubation with eugenol. In addition, eugenol inhibited the viability of sessile cells during biofilm formation and in mature biofilms. These results indicate the potential of eugenol as an alternative for controlling GBS infections.

  20. Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

    Science.gov (United States)

    Oechslin, Frank; Piccardi, Philippe; Mancini, Stefano; Gabard, Jérôme; Moreillon, Philippe; Entenza, José M; Resch, Gregory; Que, Yok-Ai

    2017-03-01

    Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P 6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration.

  1. Silver nanoparticle-algae interactions: oxidative dissolution, reactive oxygen species generation and synergistic toxic effects.

    Science.gov (United States)

    He, Di; Dorantes-Aranda, Juan José; Waite, T David

    2012-08-21

    The short-term toxicity of citrate-stabilized silver nanoparticles (AgNPs) and ionic silver Ag(I) to the ichthyotoxic marine raphidophyte Chattonella marina has been examined using the fluorometric indicator alamarBlue. Aggregation and dissolution of AgNPs occurred after addition to GSe medium while uptake of dissolved Ag(I) occurred in the presence of C. marina. Based on total silver mass, toxicity was much higher for Ag(I) than for AgNPs. Cysteine, a strong Ag(I) ligand, completely removed the inhibitory effects of Ag(I) and AgNPs on the metabolic activity of C. marina, suggesting that the toxicity of AgNPs was due to the release of Ag(I). Synergistic toxic effects of AgNPs/Ag(I) and C. marina to fish gill cells were observed with these effects possibly attributable to enhancement in the generation of reactive oxygen species by C. marina on exposure of the organism to silver.

  2. Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity?

    Science.gov (United States)

    Miller, Neil Z; Goldman, Gary S

    2011-01-01

    The infant mortality rate (IMR) is one of the most important indicators of the socio-economic well-being and public health conditions of a country. The US childhood immunization schedule specifies 26 vaccine doses for infants aged less than 1 year—the most in the world—yet 33 nations have lower IMRs. Using linear regression, the immunization schedules of these 34 nations were examined and a correlation coefficient of r = 0.70 (p infants. Nations were also grouped into five different vaccine dose ranges: 12–14, 15–17, 18–20, 21–23, and 24–26. The mean IMRs of all nations within each group were then calculated. Linear regression analysis of unweighted mean IMRs showed a high statistically significant correlation between increasing number of vaccine doses and increasing infant mortality rates, with r = 0.992 (p = 0.0009). Using the Tukey-Kramer test, statistically significant differences in mean IMRs were found between nations giving 12–14 vaccine doses and those giving 21–23, and 24–26 doses. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRs is essential. PMID:21543527

  3. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists

    Directory of Open Access Journals (Sweden)

    Khan N

    2015-07-01

    Full Text Available Nadia Khan,1,2 Ahsana Dar Farooq,1 Bassem Sadek21Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; 2Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesAbstract: In the present study, the mechanism(s of synergistic interaction of various platelet mediators such as arachidonic acid (AA when combined with 5-hydroxytryptamine (5-HT or adenosine diphosphate (ADP on human platelet aggregation were examined. The results demonstrated that 5-HT had no or negligible effect on aggregation but it did potentiate the aggregation response of AA. Similarly, the combination of subeffective concentrations of ADP and AA exhibited noticeable rise in platelet aggregation. Moreover, the observed synergistic effect of AA with 5-HT on platelets was inhibited by different cyclooxygenase (COX inhibitors, namely ibuprofen and celecoxib, with half maximal inhibitory effect (IC50 values of 18.0±1.8 and 15.6±3.4 µmol/L, respectively. Interestingly, the synergistic effect observed for AA with 5-HT was, also, blocked by the 5-HT receptor blockers cyproheptadine (IC50=22.0±7 µmol/L, ketanserin (IC50=152±23 µmol/L, phospholipase C (PLC inhibitor (U73122; IC50=6.1±0.8 µmol/L, and mitogen activated protein kinase (MAPK inhibitor (PD98059; IC50=3.8±0.5 µmol/L. Likewise, the synergism of AA and ADP was, also, attenuated by COX inhibitors (ibuprofen; IC50=20±4 µmol/L and celecoxib; IC50=24±7 µmol/L, PLC inhibitor (U73122; IC50=3.7±0.3 µmol/L, and MAPK inhibitor (PD98059; IC50=2.8±1.1 µmol/L. Our observed data demonstrate that the combination of subthreshold concentrations of agonists amplifies platelet aggregation and that these synergistic effects largely depend on activation of COX/thromboxane A2, receptor-operated Ca2+ channels, Gq/PLC, and MAPK signaling

  4. Effects of nitrogen application rate, nitrogen synergist and biochar on nitrous oxide emissions from vegetable field in south China.

    Directory of Open Access Journals (Sweden)

    Qiong Yi

    Full Text Available Globally, vegetable fields are the primary source of greenhouse gas emissions. A closed-chamber method together with gas chromatography was used to measure the fluxes of nitrous oxide (N2O emissions in typical vegetable fields planted with four vegetables sequentially over time in the same field: endive, lettuce, cabbage and sweet corn. Results showed that N2O fluxes occurred in pulses with the N2O emission peak varying greatly among the crops. In addition, N2O emissions were linearly associated with the nitrogen (N application rate (r = 0.8878, n = 16. Excessive fertilizer N application resulted in N loss through nitrous oxide gas emitted from the vegetable fields. Compared with a conventional fertilization (N2 treatment, the cumulative N2O emissions decreased significantly in the growing seasons of four plant species from an nitrogen synergist (a nitrification inhibitor, dicyandiamide and biochar treatments by 34.6% and 40.8%, respectively. However, the effects of biochar on reducing N2O emissions became more obvious than that of dicyandiamide over time. The yield-scaled N2O emissions in consecutive growing seasons for four species increased with an increase in the N fertilizer application rate, and with continuous application of N fertilizer. This was especially true for the high N fertilizer treatment that resulted in a risk of yield-scaled N2O emissions. Generally, the additions of dicyandiamide and biochar significantly decreased yield-scaled N2O-N emissions by an average of 45.9% and 45.7%, respectively, compared with N2 treatment from the consecutive four vegetable seasons. The results demonstrated that the addition of dicyandiamide or biochar in combination with application of a rational amount of N could provide the best strategy for the reduction of greenhouse gas emissions in vegetable field in south China.

  5. Effects of nitrogen application rate, nitrogen synergist and biochar on nitrous oxide emissions from vegetable field in south China

    Science.gov (United States)

    Zhang, Mu; Pang, Yuwan; Huang, Xu; Huang, Qiaoyi

    2017-01-01

    Globally, vegetable fields are the primary source of greenhouse gas emissions. A closed-chamber method together with gas chromatography was used to measure the fluxes of nitrous oxide (N2O) emissions in typical vegetable fields planted with four vegetables sequentially over time in the same field: endive, lettuce, cabbage and sweet corn. Results showed that N2O fluxes occurred in pulses with the N2O emission peak varying greatly among the crops. In addition, N2O emissions were linearly associated with the nitrogen (N) application rate (r = 0.8878, n = 16). Excessive fertilizer N application resulted in N loss through nitrous oxide gas emitted from the vegetable fields. Compared with a conventional fertilization (N2) treatment, the cumulative N2O emissions decreased significantly in the growing seasons of four plant species from an nitrogen synergist (a nitrification inhibitor, dicyandiamide and biochar treatments by 34.6% and 40.8%, respectively. However, the effects of biochar on reducing N2O emissions became more obvious than that of dicyandiamide over time. The yield-scaled N2O emissions in consecutive growing seasons for four species increased with an increase in the N fertilizer application rate, and with continuous application of N fertilizer. This was especially true for the high N fertilizer treatment that resulted in a risk of yield-scaled N2O emissions. Generally, the additions of dicyandiamide and biochar significantly decreased yield-scaled N2O-N emissions by an average of 45.9% and 45.7%, respectively, compared with N2 treatment from the consecutive four vegetable seasons. The results demonstrated that the addition of dicyandiamide or biochar in combination with application of a rational amount of N could provide the best strategy for the reduction of greenhouse gas emissions in vegetable field in south China. PMID:28419127

  6. Synergistic interaction of sumac and raspberry mixtures in their antioxidant capacities and selective cytotoxicity against cancerous cells.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan; Marcone, Massimo F

    2015-03-01

    Previous works on staghorn sumac (Rhus hirta) were mostly dedicated to its phytochemical profiles, antioxidant properties, and antidiabetic potentials. This study explored the potential of staghorn-sumac-derived functional ingredients for food and pharmacological applications. Sumac may have other biological functions, such as inhibitory effect on cancerous cells independent of its antioxidant properties. We characterized sumac and raspberry interactions, and their antioxidant capacities (ACs) and their inhibitory effect on both normal and cancerous cells. Mixing sumac and raspberry extracts yielded significantly higher ACs than the sum of sumac and raspberry as evaluated by three in vitro AC assays. However, the potential use of staghorn sumac as a natural source of dietary antioxidant supplement for oxidative-stress-related disorders might be challenged by its cytotoxicity in culturing normal cells. Remarkably, mixing sumac and raspberry showed maximal inhibition of the growth of both rat colon and human breast cancer cells with relatively low cytotoxicity toward normal rat colon and human breast epithelial cells, as compared with sumac or raspberry treatment alone. Sumac-derived products and their synergistic interactions with other food ingredients have great promise as functional food or nutraceutical products that would target cancer cells with minimal toxic effects to normal cells.

  7. Hyperglycemia Interacts with Ischemia in a Synergistic Way on Wound Repair and Myofibroblast Differentiation.

    Science.gov (United States)

    Tobalem, Mickaël; Lévigne, Dominik; Modarressi, Ali; Atashi, Fatemeh; Villard, Frederic; Hinz, Boris; Pittet-Cuénod, Brigitte

    2015-07-01

    Hyperglycemia is known to adversely affect the outcome of ischemic insults, but its interaction with ischemia has not been investigated in wound repair yet. In this study, we develop a new animal model allowing to investigate the interaction between hyperglycemia and ischemia during the wound repair process. We focus on myofibroblast differentiation, a key element of wound repair. Ischemia was inflicted in Wistar rats by resection of the femoral to popliteal arteries on the left side, whereas arteries were dissected without resection on the right side. Full-thickness skin wounds (1 cm(2)) were created on both feet. Hyperglycemia was induced by injection of streptozotocin. Normoglycemic animals served as control (n = 23/group). Blood flow, wound closure, and myofibroblast expression were measured. Wound closure was significantly delayed in ischemic compared with nonischemic wounds in all rats. This delay was almost 5-fold exacerbated in hyperglycemic rats compared with normoglycemic rats, while hyperglycemia alone showed only a slight effect on wound repair. Delayed wound repair was associated with impaired wound contraction and myofibroblast differentiation. Our model allows to specifically quantify the effect of hyperglycemia and ischemia alone or in combination on wound repair. We show that hyperglycemia amplifies the inhibitory effect of ischemia on wound repair and myofibroblast expression. Our data reveal for the first time the synergic aspect of this interaction and therefore stress the importance of a strict glycemic control in the management of ischemic wounds.

  8. Synergistic Interaction Between Alcoholism and Polypharmacy on the Risk of Falls in the Elderly

    OpenAIRE

    Lin, Hsien-Feng; Lai, Shih-Wei; Liao, Kuan-Fu; Muo, Chih-Hsin; Hsientang Hsieh, Dennis Paul

    2013-01-01

    The aim of this study was to explore the interaction between alcoholism and polypharmacy on the risk of falls in the elderly in Taiwan. A data set of 1 million randomly sampled National Health Insurance claims in Taiwan was used in our analysis, from which 3482 new cases of falls in 2000–2008 and 13928 randomly selected controls without falls, both aged ≥ 65 years, were identified for a case-control study. Polypharmacy was defined as the average daily use of five or more prescribed drugs. Rel...

  9. Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats

    Science.gov (United States)

    Ortiz, Mario I

    2013-01-01

    BACKGROUND There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA) in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA. OBJECTIVE: To determine whether metformin-sulfonylurea combinations affect DIA during the formalin test. METHODS: Rats received the appropriate vehicle or diclofenac before 1% formaldehyde was injected into the paw. Rats were also pretreated with vehicle, glibenclamide, glipizide, metformin or glibenclamide/metformin and glipizide/metformin combinations before the diclofenac and formaldehyde injections, and the effect on antinociception was assessed. Isobolograms of the combinations were constructed to test for a synergistic interaction. RESULTS: Systemic injection of diclofenac resulted in antinociception during the second phase of the test. Systemic pretreatment with the combinations of glibenclamide (0.56 mg/kg to 10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) and glipizide (0.56 mg/kg to10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) blocked DIA. The derived theoretical effective doses for 50% of subjects (ED50) for the glibenclamide/metformin and glipizide/metformin combinations were 32.52 mg/kg and 32.42 mg/kg, respectively, and were significantly higher than the actual observed experimental ED50 values (7.57 mg/kg and 8.43 mg/kg, respectively). CONCLUSION: Pretreatment with glibenclamide, glipizide or metformin blocked DIA in a dose-dependent manner, and combining either sulfonylurea with metformin produced even greater effects. The observed ED50s for the combinations were approximately fourfold lower than the calculated additive effects. These data indicate that sulfonylureas interact to produce antagonism of DIA. Combination therapy is a common second-line treatment for patients with diabetes and metabolic syndrome, a group that experiences pain from multiple sources. The results suggest that at least some anti-inflammatory agents may not be

  10. Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA.

    Science.gov (United States)

    de Vera, Ian Mitchelle S; Zheng, Jie; Novick, Scott; Shang, Jinsai; Hughes, Travis S; Brust, Richard; Munoz-Tello, Paola; Gardner, William J; Marciano, David P; Kong, Xiangming; Griffin, Patrick R; Kojetin, Douglas J

    2017-10-03

    Nuclear receptor (NR) transcription factors bind various coreceptors, small-molecule ligands, DNA response element sequences, and transcriptional coregulator proteins to affect gene transcription. Small-molecule ligands and DNA are known to influence receptor structure, coregulator protein interaction, and function; however, little is known on the mechanism of synergy between ligand and DNA. Using quantitative biochemical, biophysical, and solution structural methods, including 13C-detected nuclear magnetic resonance and hydrogen/deuterium exchange (HDX) mass spectrometry, we show that ligand and DNA cooperatively recruit the intrinsically disordered steroid receptor coactivator-2 (SRC-2/TIF2/GRIP1/NCoA-2) receptor interaction domain to peroxisome proliferator-activated receptor gamma-retinoid X receptor alpha (PPARγ-RXRα) heterodimer and reveal the binding determinants of the complex. Our data reveal a thermodynamic mechanism by which DNA binding propagates a conformational change in PPARγ-RXRα, stabilizes the receptor ligand binding domain dimer interface, and impacts ligand potency and cooperativity in NR coactivator recruitment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Synergistic Interaction Between Alcoholism and Polypharmacy on the Risk of Falls in the Elderly

    Directory of Open Access Journals (Sweden)

    Hsien-Feng Lin

    2013-06-01

    Full Text Available The aim of this study was to explore the interaction between alcoholism and polypharmacy on the risk of falls in the elderly in Taiwan. A data set of 1 million randomly sampled National Health Insurance claims in Taiwan was used in our analysis, from which 3482 new cases of falls in 2000–2008 and 13928 randomly selected controls without falls, both aged ≥ 65 years, were identified for a case-control study. Polypharmacy was defined as the average daily use of five or more prescribed drugs. Relative risks were estimated by adjusted odds ratio (OR and 95% confidence interval (CI using a multivariate logistic regression analysis.In comparison with participants using one or no drugs without alcoholism, the OR increased from 1.15 (95% CI 1.01–1.32 for those using two to four drugs without alcoholism, to 1.27 (95% CI 1.10–1.47 for those using five or more drugs without alcoholism, up to 5.32 (95% CI 1.58–18.0 for those using two to four drugs with alcoholism, and as high as to 6.29 (95% CI 2.22–17.8 for those using five or more drugs with alcoholism. We conclude that polypharmacy may interact with alcoholism and further increases the risk of falls in the elderly.

  12. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    Science.gov (United States)

    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

  13. Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila.

    Science.gov (United States)

    Wangler, Michael F; Reiter, Lawrence T; Zimm, Georgianna; Trimble-Morgan, Jennifer; Wu, Jane; Bier, Ethan

    2011-07-01

    Alzheimer's disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer's disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer's pathogenesis.

  14. The Daughterless N-terminus directly mediates synergistic interactions with Notch transcription complexes via the SPS+A DNA transcription code

    Directory of Open Access Journals (Sweden)

    Xia Li

    2009-04-01

    Full Text Available Abstract Background Cell-specific expression of a subset of Enhancer of split (E(spl-C genes in proneural clusters is mediated by synergistic interactions between bHLH A (basic Helix-Loop-Helix Activator and Notch-signalling transcription complex (NTC proteins. For a some of these E(spl-C genes, such as m8, these synergistic interactions are programmed by an "SPS+A" transcription code in the cis-regulatory regions. However, the molecular mechanisms underlying this synergistic interaction between NTCs and proneural bHLH A proteins are not fully understood. Findings Using cell transcription assays, we show that the N-terminal region of the Daughterless (Da bHLH A protein is critical for synergistic interactions with NTCs that activate the E(spl-C m8 promoter. These assays also show that this interaction is dependent on the specific inverted repeat architecture of Suppressor of Hairless (Su(H binding sites in the SPS+A transcription code. Using protein-protein interaction assays, we show that two distinct regions within the Da N-terminus make a direct physical interaction with the NTC protein Su(H. Deletion of these interaction domains in Da creates a dominant negative protein that eliminates NTC-bHLH A transcriptional synergy on the m8 promoter. In addition, over-expression of this dominant negative Da protein disrupts Notch-mediated lateral inhibition during mechanosensory bristle neurogenesis in vivo. Conclusion These findings indicate that direct physical interactions between Da-N and Su(H are critical for the transcriptional synergy between NTC and bHLH A proteins on the m8 promoter. Our results also indicate that the orientation of the Su(H binding sites in the SPS+A transcription code are critical for programming the interaction between Da-N and Su(H proteins. Together, these findings provide insight into the molecular mechanisms by which the NTC synergistically interacts with bHLH A proteins to mediate Notch target gene expression in

  15. Observations on the Synergistic Interactions of Aqueous Oxidizers and Ultraviolet Radiation for Decontamination Applications

    Science.gov (United States)

    1986-05-20

    constants in Table 4 indicate that, to a first approxi- mation, malathion reacted with hydrogen peroxide and sodium perborate at the same rate, with or...Peroxydisulfate, Na2S 2 0 8 238.0 0.076 Alfa Sodium Perborate , NaBO 3 .4H 2O 153.8 0.047• Alfa Sodium Percarbonate, 2Na 2 CO3 -3H2 0 2 314.0 0.083 Burlington...conditions were adjusted ýo pH -8.6 with aqueous sodium hydroxide as needed. Furthermore, the fluorescence of quinine sulfate solutions is pH dependent

  16. Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

    Directory of Open Access Journals (Sweden)

    Francesco Nazzi

    Full Text Available The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV, transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

  17. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer.

    Science.gov (United States)

    Yang, Chunhua; Gundala, Sushma Reddy; Mukkavilli, Rao; Vangala, Subrahmanyam; Reid, Michelle D; Aneja, Ritu

    2015-06-01

    Phytochemical complexity of plant extracts may offer health-promoting benefits including chemotherapeutic and chemopreventive effects. Isolation of 'most-active fraction' or single constituents from whole extracts may not only compromise the therapeutic efficacy but also render toxicity, thus emphasizing the importance of preserving the natural composition of whole extracts. The leaves of Annona muricata, commonly known as Graviola, are known to be rich in flavonoids, isoquinoline alkaloids and annonaceous acetogenins. Here, we demonstrate phytochemical synergy among the constituents of Graviola leaf extract (GLE) compared to its flavonoid-enriched (FEF) and acetogenin-enriched (AEF) fractions. Comparative quantitation of flavonoids revealed enrichment of rutin (~7-fold) and quercetin-3-glucoside (Q-3-G, ~3-fold) in FEF compared to GLE. In vivo pharmacokinetics and in vitro absorption kinetics of flavonoids revealed enhanced bioavailability of rutin in FEF compared to GLE. However, GLE was more effective in inhibiting in vitro prostate cancer proliferation, viability and clonogenic capacity compared to FEF. Oral administration of 100mg/kg bw GLE showed ~1.2-fold higher tumor growth-inhibitory efficacy than FEF in human prostate tumor xenografts although the concentration of rutin and Q-3-G was more in FEF. Contrarily, AEF, despite its superior in vitro and in vivo efficacy, resulted in death of the mice due to toxicity. Our data indicate that despite lower absorption and bioavailability of rutin, maximum efficacy was achieved in the case of GLE, which also comprises of other phytochemical groups including acetogenins that make up its natural complex environment. Hence, our study emphasizes on evaluating the nature of interactions among Graviola leaf phytochemcials for developing favorable dose regimen for prostate cancer management to achieve optimal therapeutic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions

  18. Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53.

    Science.gov (United States)

    Terranova-Barberio, Manuela; Pecori, Biagio; Roca, Maria Serena; Imbimbo, Serena; Bruzzese, Francesca; Leone, Alessandra; Muto, Paolo; Delrio, Paolo; Avallone, Antonio; Budillon, Alfredo; Di Gennaro, Elena

    2017-12-06

    Recurrence with distant metastases has become the predominant pattern of failure in locally advanced rectal cancer (LARC), thus the integration of new antineoplastic agents into preoperative fluoropyrimidine-based chemo-radiotherapy represents a clinical challenge to implement an intensified therapeutic strategy. The present study examined the combination of the histone deacetylase inhibitor (HDACi) valproic acid (VPA) with fluoropyrimidine-based chemo-radiotherapy on colorectal cancer (CRC) cells. HCT-116 (p53-wild type), HCT-116 p53-/- (p53-null), SW620 and HT29 (p53-mutant) CRC cell lines were used to assess the antitumor interaction between VPA and capecitabine metabolite 5'-deoxy-5-fluorouridine (5'-DFUR) in combination with radiotherapy and to evaluate the role of p53 in the combination treatment. Effects on proliferation, clonogenicity and apoptosis were evaluated, along with γH2AX foci formation as an indicator for DNA damage. Combined treatment with equipotent doses of VPA and 5'-DFUR resulted in synergistic effects in CRC lines expressing p53 (wild-type or mutant). In HCT-116 p53-/- cells we observed antagonist effects. Radiotherapy further potentiated the antiproliferative, pro-apoptotic and DNA damage effects induced by 5'-DFUR/VPA combination in p53 expressing cells. These results highlighted the role of VPA as valuable candidate to be added to preoperative chemo-radiotherapy in LARC. On these bases we launched the ongoing phase I/II study of VPA and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer (V-shoRT-R3).

  19. Synergistic effect of interaction between perceived health and social activity on depressive symptoms in the middle-aged and elderly: a population-based longitudinal study.

    Science.gov (United States)

    Chun, Sung-Youn; Han, Kyu-Tae; Lee, Seo Yoon; Kim, Chan Ok; Park, Eun-Cheol

    2015-03-13

    To examine the synergistic effect of interaction between perceived health and social activity on depressive symptoms. We investigated whether the interaction between perceived health and social activity has a synergistic effect on depressive symptoms in the middle-aged and elderly using data from 6590 respondents aged 45 and older in the Korean Longitudinal Study on Aging (KLoSA), 2006-2012. A generalised linear mixed-effects model was used to investigate the association in a longitudinal data form. Depressive symptoms were measured using the Center for Epidemiological Studies Depression 10 Scale (CES-D10). Perceived health and level of social activity were categorical variables with three values. Participation in six social activities was assessed. Interactions between perceived health status and social activity were statistically significant for almost all social activity/perceived health combinations. Addition of the interaction term significantly decreased CES-D10 scores, confirming the synergistic effect of the interaction between perceived health status and social activity ('normal×moderate', β=-0.1826; 'poor×moderate', β=-0.5739; 'poor×active', β=-0.8935). In addition, we performed stratified analyses by region: urban or rural. In urban respondents, the additional effect of the interaction term decreased CES-D10 scores and all social activity/perceived health combinations were statistically significant ('normal×moderate', β=-0.2578; 'normal×active', β=-0.3945; 'poor×moderate', β=-0.5739; 'poor×active', β=-0.8935). In rural respondents, only one social activity/perceived health combination was statistically significant, and the additional effect of the interaction term showed no consistent trend on CES-D10 scores. The interaction between perceived health and social activity has a synergistic effect on depressive symptoms; the additional effect of the interaction term significantly decreased CES-D10 scores in our models. Published by the BMJ

  20. Synergistic interaction of catecholamine hormones and Mycobacterium avium results in the induction of interleukin-10 mRNA expression by murine peritoneal macrophages.

    Science.gov (United States)

    Chen, L; Boomershine, C; Wang, T; Lafuse, W P; Zwilling, B S

    1999-01-01

    The results of this investigation provides evidence that catecholamine hormones interact with macrophages that are infected with Mycobacterium avium resulting in the induction of IL-10 mRNA and protein. The effect of catecholamine hormones was prevented by treating the cells with the beta-adrenergic receptor antagonist propranolol but not by alpha-adrenergic antagonist phentolamine. The effect of catecholamine stimulation was mimicked by the addition of beta-2 adrenergic agonists and by the addition of cAMP to the infected macrophage cultures. These observations suggest that sympathetic nervous system activation together with microbial infection results in a synergistic interaction that could result in the control of inflammatory processes.

  1. Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

    Science.gov (United States)

    Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

    2008-12-01

    Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

  2. Synergistic interaction between the fungus Beauveria bassiana and desiccant dusts applied against poultry red mites (Dermanyssus gallinae)

    DEFF Research Database (Denmark)

    Steenberg, Tove; Kilpinen, Ole Østerlund

    2014-01-01

    The poultry red mite, Dermanyssus gallinae, is a major pest in egg production, feeding on laying hens. Widely used non-chemical control methods include desiccant dusts, although their persistence under field conditions is often short. Entomopathogenic fungi may also hold potential for mite control......, but these fungi often take several days to kill mites. Laboratory experiments were carried out to study the efficacy of 3 types of desiccant dusts, the fungus Beauveria bassiana and combinations of the two control agents against D. gallinae. There was significant synergistic interaction between each...

  3. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Directory of Open Access Journals (Sweden)

    Mahin Khatami

    2014-01-01

    Full Text Available Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates is heavy investment on numerous genetic mutations (molecular false-flags in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance. Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs demonstrated at least three stages of interactions between resident (host and recruited immune cells: (a, acute phase; activation of mast cells (MCs, IgE Abs, histamine and prostaglandin synthesis; (b, intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos infiltrations into epithelia and goblet cells (GCs, tissue hypertrophy and neovascularization; and (c, chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mfs, increased (irregular size B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth and/or thinning (necrosis and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  4. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Energy Technology Data Exchange (ETDEWEB)

    Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

    2014-01-27

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  5. Lower alert rates by clustering of related drug interaction alerts

    NARCIS (Netherlands)

    Heringa, M.; Siderius, H.; Floor-Schreudering, A.; Smet, P.A.G.M. de; Bouvy, M.L.

    2017-01-01

    OBJECTIVE: We aimed to investigate to what extent clustering of related drug interaction alerts (drug-drug and drug-disease interaction alerts) would decrease the alert rate in clinical decision support systems (CDSSs). METHODS: We conducted a retrospective analysis of drug interaction alerts

  6. Lower alert rates by clustering of related drug interaction alerts

    NARCIS (Netherlands)

    Heringa, M.; Siderius, Hidde; Schreudering, A.; De Smet, Peter Agm; Bouvy, M.L.

    OBJECTIVE: We aimed to investigate to what extent clustering of related drug interaction alerts (drug-drug and drug-disease interaction alerts) would decrease the alert rate in clinical decision support systems (CDSSs). METHODS: We conducted a retrospective analysis of drug interaction alerts

  7. Investigating the synergistic interaction of diabetes, tobacco smoking, alcohol consumption, and hypercholesterolemia on the risk of pancreatic cancer: a case-control study in Italy.

    Science.gov (United States)

    La Torre, Giuseppe; Sferrazza, Antonella; Gualano, Maria Rosaria; de Waure, Chiara; Clemente, Gennaro; De Rose, Agostino Maria; Nicolotti, Nicola; Nuzzo, Gennaro; Siliquini, Roberta; Boccia, Antonio; Ricciardi, Walter

    2014-01-01

    The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods).

  8. Investigating the Synergistic Interaction of Diabetes, Tobacco Smoking, Alcohol Consumption, and Hypercholesterolemia on the Risk of Pancreatic Cancer: A Case-Control Study in Italy

    Directory of Open Access Journals (Sweden)

    Giuseppe La Torre

    2014-01-01

    Full Text Available The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls was conducted at the Teaching Hospital “Agostino Gemelli” in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR and 95% confidence intervals (95% CI. We also investigated the possible interactions between risk factors and calculated the synergism index (SI. The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94–8.66; OR: 2.25, 95% CI: 1.30–3.89, resp.. Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61 as well as alcohol consumption and diabetes (SI = 17.77. In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods.

  9. Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model

    Science.gov (United States)

    Burkhardt, Melanie A.; Waser, Jasmin; Milleret, Vincent; Gerber, Isabel; Emmert, Maximilian Y.; Foolen, Jasper; Hoerstrup, Simon P.; Schlottig, Falko; Vogel, Viola

    2016-02-01

    Low correlations of cell culture data with clinical outcomes pose major medical challenges with costly consequences. While the majority of biomaterials are tested using in vitro cell monocultures, the importance of synergistic interactions between different cell types on paracrine signalling has recently been highlighted. In this proof-of-concept study, we asked whether the first contact of surfaces with whole human blood could steer the tissue healing response. This hypothesis was tested using alkali-treatment of rough titanium (Ti) surfaces since they have clinically been shown to improve early implant integration and stability, yet blood-free in vitro cell cultures poorly correlated with in vivo tissue healing. We show that alkali-treatment, compared to native Ti surfaces, increased blood clot thickness, including platelet adhesion. Strikingly, blood clots with entrapped blood cells in synergistic interactions with fibroblasts, but not fibroblasts alone, upregulated the secretion of major factors associated with fast healing. This includes matrix metalloproteinases (MMPs) to break down extracellular matrix and the growth factor VEGF, known for its angiogenic potential. Consequently, in vitro test platforms, which consider whole blood-implant interactions, might be superior in predicting wound healing in response to biomaterial properties.

  10. Sensory information and encounter rates of interacting species.

    Directory of Open Access Journals (Sweden)

    Andrew M Hein

    Full Text Available Most motile organisms use sensory cues when searching for resources, mates, or prey. The searcher measures sensory data and adjusts its search behavior based on those data. Yet, classical models of species encounter rates assume that searchers move independently of their targets. This assumption leads to the familiar mass action-like encounter rate kinetics typically used in modeling species interactions. Here we show that this common approach can mischaracterize encounter rate kinetics if searchers use sensory information to search actively for targets. We use the example of predator-prey interactions to illustrate that predators capable of long-distance directional sensing can encounter prey at a rate proportional to prey density to the [Formula: see text] power (where [Formula: see text] is the dimension of the environment when prey density is low. Similar anomalous encounter rate functions emerge even when predators pursue prey using only noisy, directionless signals. Thus, in both the high-information extreme of long-distance directional sensing, and the low-information extreme of noisy non-directional sensing, encounter rate kinetics differ qualitatively from those derived by classic theory of species interactions. Using a standard model of predator-prey population dynamics, we show that the new encounter rate kinetics derived here can change the outcome of species interactions. Our results demonstrate how the use of sensory information can alter the rates and outcomes of physical interactions in biological systems.

  11. Predicting rates of interspecific interaction from phylogenetic trees.

    Science.gov (United States)

    Nuismer, Scott L; Harmon, Luke J

    2015-01-01

    Integrating phylogenetic information can potentially improve our ability to explain species' traits, patterns of community assembly, the network structure of communities, and ecosystem function. In this study, we use mathematical models to explore the ecological and evolutionary factors that modulate the explanatory power of phylogenetic information for communities of species that interact within a single trophic level. We find that phylogenetic relationships among species can influence trait evolution and rates of interaction among species, but only under particular models of species interaction. For example, when interactions within communities are mediated by a mechanism of phenotype matching, phylogenetic trees make specific predictions about trait evolution and rates of interaction. In contrast, if interactions within a community depend on a mechanism of phenotype differences, phylogenetic information has little, if any, predictive power for trait evolution and interaction rate. Together, these results make clear and testable predictions for when and how evolutionary history is expected to influence contemporary rates of species interaction. © 2014 John Wiley & Sons Ltd/CNRS.

  12. Synergistic interaction of glycoalkaloids alpha-chaconine and alpha-solanine on developmental toxicity in Xenopus embryos.

    Science.gov (United States)

    Rayburn, J R; Friedman, M; Bantle, J A

    1995-12-01

    The embryo toxicities of two major potato glycoalkaloids, alpha-chaconine and alpha-solanine, were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus. Calculations of toxic units (TUs) were used to assess possible antagonism, synergism or response addition of several mixtures ranging from approximately 3:1 to 1:20 TUs of alpha-chaconine to alpha-solanine. Some combinations exhibited strong synergism in the following measures of developmental toxicity: (a) 96-hr LC50, defined as the median concentration causing 50% embryo lethality; (b) 96-hr EC50 (malformation), defined as the concentration causing 50% malformation of the surviving embryos; and (c) teratogenic index which is equal to LC50/EC50 (malformation). The results indicated that each of the mixtures caused synergistic mortality or malformation. Furthermore, these studies suggested that the synergism observed for a specific mixture cannot be used to predict possible synergism of other mixtures with different ratios of the two glycoalkaloids; toxicities observed for individual glycoalkaloids may not be able to predict toxicities of mixtures; and specific combinations found in different potato varieties need to be tested to assess the safety of a particular cultivar.

  13. Perfectly Wetting Mixtures of Surfactants from Renewable Resources: The Interaction and Synergistic Effects on Adsorption and Micellization.

    Science.gov (United States)

    Szumała, Patrycja; Mówińska, Alicja

    This paper presents a study of the surface properties of mixtures of surfactants originating from renewable sources, i.e., alkylpolyglucoside (APG), ethoxylated fatty alcohol (AE), and sodium soap (Na soap). The main objective was to optimize the surfactant ratio which produces the highest wetting properties during the analysis of the solution of the individual surfactants, two- and three-component mixtures, and at different pH values. The results showed the existence of a synergistic effect in lowering the interfacial tension, critical micelle concentration and the formation of mixed micelles in selected solutions. We found that best wetting properties were measured for the binary AE:APG mixtures. It has been demonstrated that slightly lower contact angles values were observed on Teflon and glass surfaces for the AE:APG:soap mixtures but the results were obtained for higher concentration of the components. In addition, all studied solutions have very good surface properties in acidic, basic and neural media. However, the AE:soap (molar ratio of 1:2), AE:APG (2:1) and AE:APG:soap (1:1:1) compositions improved their wetting power at pH 7 on the aluminium and glass surfaces, as compared to solutions at other pH values tested (selected Θ values close to zero-perfectly wetting liquids). All described effects detected would allow less surfactant to be used to achieve the maximum capacity of washing, wetting or solubilizing while minimizing costs and demonstrating environmental care.

  14. Synergistic interactions between temporal coupling of complex light and magnetic pulses upon melanoma cell proliferation and planarian regeneration.

    Science.gov (United States)

    Murugan, Nirosha J; Karbowski, Lukasz M; Persinger, Michael A

    2017-01-01

    Synergisms between a physiologically patterned magnetic field that is known to enhance planarian growth and suppress proliferation of malignant cells in culture and three light emitting diode (LED) generated visible wavelengths (blue, green, red) upon planarian regeneration and melanoma cell numbers were discerned. Five days of hourly exposures to either a physiologically patterned (2.5-5.0 μT) magnetic field, one of three wavelengths (3 kLux) or both treatments simultaneously indicated that red light (680 nm), blue light (470 nm) or the magnetic field significantly facilitated regeneration of planarian compared to sham field exposed planarian. Presentation of both light and magnetic field conditions enhanced the effect. Whereas the blue and red light diminished the growth of malignant (melanoma) cells, the effect was not as large as that produced by the magnetic field. Only the paired presentation of the blue light and magnetic field enhanced the suppression. On the other hand, the changes following green light (540 nm) exposure did not differ from the control condition and green light presented with the magnetic field eliminated its effects for both the planarian and melanoma cells. These results indicate specific colors affect positive adaptation that is similar to weak, physiologically patterned frequency modulated (8-24 Hz) magnetic fields and that the two forms of energy can synergistically summate or cancel.

  15. Effect of Hydrodynamic Interactions on Reaction Rates in Membranes.

    Science.gov (United States)

    Oppenheimer, Naomi; Stone, Howard A

    2017-07-25

    The Brownian motion of two particles in three dimensions serves as a model for predicting the diffusion-limited reaction rate, as first discussed by von Smoluchowski. Deutch and Felderhof extended the calculation to account for hydrodynamic interactions between the particles and the target, which results in a reduction of the rate coefficient by about half. Many chemical reactions take place in quasi-two-dimensional systems, such as on the membrane or surface of a cell. We perform a Smoluchowski-like calculation in a quasi-two-dimensional geometry, i.e., a membrane surrounded by fluid, and account for hydrodynamic interactions between the particles. We show that rate coefficients are reduced relative to the case of no interactions. The reduction is more pronounced than the three-dimensional case due to the long-range nature of two-dimensional flows. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. The ERECTA, CLAVATA and class III HD-ZIP Pathways Display Synergistic Interactions in Regulating Floral Meristem Activities.

    Directory of Open Access Journals (Sweden)

    Udi Landau

    Full Text Available In angiosperms, the production of flowers marks the beginning of the reproductive phase. At the emergence of flower primordia on the flanks of the inflorescence meristem, the WUSCHEL (WUS gene, which encodes a homeodomain transcription factor starts to be expressed and establishes de novo stem cell population, founder of the floral meristem (FM. Similarly to the shoot apical meristem a precise spatial and temporal expression pattern of WUS is required and maintained through strict regulation by multiple regulatory inputs to maintain stem cell homeostasis. However, following the formation of a genetically determined fixed number of floral organs, this homeostasis is shifted towards organogenesis and the FM is terminated. In here we performed a genetic study to test how a reduction in ERECTA, CLAVATA and class III HD-ZIP pathways affects floral meristem activity and flower development. We revealed strong synergistic phenotypes of extra flower number, supernumerary whorls, total loss of determinacy and extreme enlargement of the meristem as compared to any double mutant combination indicating that the three pathways, CLV3, ER and HD-ZIPIII distinctively regulate meristem activity and that they act in parallel. Our findings yield several new insights into stem cell-driven development. We demonstrate the crucial requirement for coupling floral meristem termination with carpel formation to ensure successful reproduction in plants. We also show how regulation of meristem size and alternation in spatial structure of the meristem serve as a mechanism to determine flower organogenesis. We propose that the loss of FM determinacy due to the reduction in CLV3, ER and HD-ZIPIII activity is genetically separable from the AGAMOUS core mechanism of meristem termination.

  17. Synergistic formation and stabilization of oil-in-water emulsions by a weakly interacting mixture of zwitterionic surfactant and silica nanoparticles.

    Science.gov (United States)

    Worthen, Andrew J; Foster, Lynn M; Dong, Jiannan; Bollinger, Jonathan A; Peterman, Adam H; Pastora, Lucinda E; Bryant, Steven L; Truskett, Thomas M; Bielawski, Christopher W; Johnston, Keith P

    2014-02-04

    Oil-in-water emulsions were formed and stabilized at low amphiphile concentrations by combining hydrophilic nanoparticles (NPs) (i.e., bare colloidal silica) with a weakly interacting zwitterionic surfactant, caprylamidopropyl betaine, to generate a high hydrophilic-lipophilic balance. The weak interaction of the NPs with surfactant was quantified with contact angle measurements. Emulsions were characterized by static light scattering to determine the droplet size distributions, optical photography to quantify phase separation due to creaming, and both optical and electron microscopy to determine emulsion microstructure. The NPs and surfactant acted synergistically to produce finer emulsions with a greater stability to coalescence relative to the behavior with either NPs or surfactant alone. As a consequence of the weak adsorption of the highly hydrophilic surfactant on the anionic NPs along with the high critical micelle concentration, an unusually large surfactant concentration was available to adsorb at the oil-water interface and lower the interfacial tension. The synergy for emulsion formation and stabilization for the two amphiphiles was even greater in the case of a high-salinity synthetic seawater aqueous phase. Here, higher NP adsorption at the oil-water interface was caused by electrostatic screening of interactions between (1) NPs and the anionic oil-water interface and (2) between the NPs. This greater adsorption as well as partial flocculation of the NPs provided a more efficient barrier to droplet coalescence.

  18. Mussel byssus-inspired engineering of synergistic nanointerfacial interactions as sacrificial bonds into carbon nanotube-reinforced soy protein/nanofibrillated cellulose nanocomposites: Versatile mechanical enhancement

    Science.gov (United States)

    Wang, Zhong; Zhao, Shujun; Kang, Haijiao; Zhang, Wei; Zhang, Shifeng; Li, Jianzhang

    2018-03-01

    Achieving flexible and stretchable biobased nanocomposites combining high strength and toughness is still a very challenging endeavor. Herein, we described a novel and versatile biomimetic design for tough and high-performance TEMPO-oxidized nanofibrillated cellulose (TONFC)/soy protein isolate (SPI) nanocomposites, which are triggered by catechol-mimetic carbon nanotubes (PCT) and iron ions (Fe(III)) to yield a strong yet sacrificial metal-ligand motifs into a chemically cross-linked architecture network. Taking advantage of self-polymerization of catechol-inspired natural tannic acid, PCT nanohybrid was prepared through adhering reactive poly-(tannic acid) (PTA) layer onto surfaces of carbon nanotubes via a simple dip-coating process. The high-functionality PCT induced the formation of the metal-ligand bonds through the ionic coordinates between the catechol groups in PCT and -COOH groups of TONFC skeleton with Fe(III) mediation that mimicked mussel byssus. Upon stretching, this tailored TONFC-Fe(III)-catechol coordination bonds served as sacrificial bonds that preferentially detach prior to the covalent network, which gave rise to efficient energy dissipation that the nanocomposites integrity was survived. As a result of these kind of synergistic interfacial interactions (sacrificial and covalent bonding), the optimal nanocomposite films processed high tensile strength (ca. 11.5 MPa), large elongation (ca. 79.3%), remarkable toughness (ca. 6.9 MJ m-3), and favorable water resistance as well as electrical conductivity. The proposed bioinspired strategy for designing plant protein-based materials enables control over their mechanical performance through the synergistic engineering of sacrificial bonds into the composite interface.

  19. Behavioral Ratings of Health Professionals' Interactions with the Geriatric Patient.

    Science.gov (United States)

    Adelson, R.; And Others

    1982-01-01

    Reports the reliability and validity of the Health Professional-Geriatric Patient Interaction Behavior Rating Code, an observational instrument that is used to quantify the interpersonal behaviors of health professionals in the care of the geriatric patient. Condensed 15 behavioral factors into 10 operationally defined behavioral categories.…

  20. Lower alert rates by clustering of related drug interaction alerts.

    Science.gov (United States)

    Heringa, Mette; Siderius, Hidde; Floor-Schreudering, Annemieke; de Smet, Peter A G M; Bouvy, Marcel L

    2017-01-01

    We aimed to investigate to what extent clustering of related drug interaction alerts (drug-drug and drug-disease interaction alerts) would decrease the alert rate in clinical decision support systems (CDSSs). We conducted a retrospective analysis of drug interaction alerts generated by CDSSs in community pharmacies. Frequently generated combinations of alerts were analyzed for associations in a 5% random data sample (dataset 1). Alert combinations with similar management recommendations were defined as clusters. The alert rate was assessed by simulating a CDSS generating 1 alert per cluster per patient instead of separate alerts. The simulation was performed in dataset 1 and replicated in another 5% data sample (dataset 2). Data were extracted from the CDSSs of 123 community pharmacies. Dataset 1 consisted of 841 572 dispensed prescriptions and 298 261 drug interaction alerts. Dataset 2 was comparable. Twenty-two frequently occurring alert combinations were identified. Analysis of these associated alert combinations for similar management recommendations resulted in 3 clusters (related to renal function, electrolytes, diabetes, and cardiovascular diseases). Using the clusters in alert generation reduced the alert rate within these clusters by 53-70%. The overall number of drug interaction alerts was reduced by 11% in dataset 1 and by 12% in dataset 2. This corresponds to a decrease of 21 alerts per pharmacy per day. Using clusters of drug interaction alerts with similar management recommendations in CDSSs can substantially decrease the overall alert rate. Further research is needed to establish the applicability of this concept in daily practice. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Competitive interactions modify the temperature dependence of damselfly growth rates.

    Science.gov (United States)

    Nilsson-Ortman, Viktor; Stoks, Robby; Johansson, Frank

    2014-05-01

    Individual growth rates and survival are major determinants of individual fitness, population size structure, and community dynamics. The relationships between growth rate, survival, and temperature may thus be important for predicting biological responses to climate change. Although it is well known that growth rates and survival are affected by competition and predation in addition to temperature, the combined effect of these factors on growth rates, survival, and size structure has rarely been investigated simultaneously in the same ecological system. To address this question, we conducted experiments on the larvae of two species of damselflies and determined the temperature dependence of growth rate, survival, and cohort size structure under three scenarios of increasing ecological complexity: no competition, intraspecific competition, and interspecific competition. In one species, the relationship between growth rate and temperature became steeper in the presence of competitors, whereas that of survival remained unchanged. In the other species, the relationship between growth rate and temperature was unaffected by competitive interactions, but survival was greatly reduced at high temperatures in the presence of interspecific competitors. The combined effect of competitive interactions and temperature on cohort size structure differed from the effects of these factors in isolation. Together, these findings suggest that it will be challenging to scale up information from single-species laboratory studies to the population and community level.

  2. Fuel, fasting, fear: routine metabolic rate and food deprivation exert synergistic effects on risk-taking in individual juvenile European sea bass.

    Science.gov (United States)

    Killen, Shaun S; Marras, Stefano; McKenzie, David J

    2011-09-01

    1. Individuals of the same species often exhibit consistent differences in metabolic rate, but the effects of such differences on ecologically important behaviours remain largely unknown. In particular, it is unclear whether there is a cause-and-effect relationship between metabolic rate and the tendency to take risks while foraging. Individuals with higher metabolic rates may need to take greater risks while foraging to obtain the additional food required to satisfy their energy requirements. Such a relationship could be exacerbated by food deprivation if a higher metabolic demand also causes greater mass loss and hunger. 2. We investigated relationships among metabolic rate, risk-taking and tolerance of food deprivation in juvenile European sea bass. Individual fish were tested for risk-taking behaviours following a simulated predator attack, both before and after a 7-day period of food deprivation. The results were then related to their routine metabolic rate (RMR), which was measured throughout the period of food deprivation. 3. The amount of risk displayed by individual fish before food deprivation showed no relationship with RMR. After food deprivation, however, the amount of risk among individuals was positively correlated with RMR. In general, most fish showed an increase in risk-taking after food deprivation, and the magnitude of the increase in risk-taking was correlated with the rate of individual mass loss during food deprivation, which was itself strongly correlated with RMR. 4. The observation that RMR was related to risk-taking behaviour after food deprivation, but not before, suggests that although RMR can influence risk-taking, the strength of the relationship is flexible and context dependent. The effects of RMR on risk-taking may be subtle or non-existent in regularly feeding animals, but may lead to variability in risk-taking among individuals when food is scarce or supply is unpredictable. This synergistic relationship between RMR and food

  3. Multiple-stressor interactions influence embryo development rate in the American horseshoe crab, Limulus polyphemus.

    Science.gov (United States)

    Vasquez, M Christina; Murillo, Andrea; Brockmann, H Jane; Julian, David

    2015-08-01

    Fertilized eggs of the American horseshoe crab, Limulus polyphemus, are buried in shallow nests above the high tide line, where they are exposed to variations in abiotic conditions during early development. Using a multiple-stressors approach, we examined whether the rate of embryonic development is affected by exposure to combinations of three factors: temperature (25, 30 and 35°C), salinity (5, 15 and 34 ppt) and ambient O2 (5%, 13% and 21% O2). Newly fertilized eggs were incubated under 27 fully factorial stressor combinations for 14 days, then allowed to recover in control conditions (30°C, 34 ppt, 21% O2) for an additional 14 days. Growth rate was measured every 2 days throughout the experiment (N=1289). We found that the effect of isolated stressors (high temperature, low salinity or low O2) reduced developmental success by up to 72% (low salinity), and that stressor combinations showed stronger effects and evidence of complex interactions. For example, low O2 had little effect individually but was lethal in combination with high temperature, and low temperature in isolation slightly decreased the rate of development but reduced the negative effects of low salinity and low O2. Development was delayed under exposure to low O2 but resumed upon return to control conditions after a 10 day lag. These data demonstrate that complex, synergistic interactions among abiotic stressors can substantially alter the development of a coastal invertebrate in ways that may not be predicted from the effects of the stressors in isolation. © 2015. Published by The Company of Biologists Ltd.

  4. Gene × environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict

    Directory of Open Access Journals (Sweden)

    Jernigan Katherine

    2010-04-01

    Full Text Available Abstract Background Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD; prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR on liability for ADHD. Method 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution was genotyped and participants were assigned as having high (La/La N = 78, intermediate (La/Lg, La/short, N = 137, or low (Lg/Lg, Lg/short, short/short, N = 89 serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Results Hierarchical linear regression analyses indicated significant 5HTTLPR × self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Conclusion Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to

  5. Gene x environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict.

    Science.gov (United States)

    Nikolas, Molly; Friderici, Karen; Waldman, Irwin; Jernigan, Katherine; Nigg, Joel T

    2010-04-16

    Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Hierarchical linear regression analyses indicated significant 5HTTLPR x self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to

  6. Gene × environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict

    Science.gov (United States)

    2010-01-01

    Background Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD. Method 304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures. Results Hierarchical linear regression analyses indicated significant 5HTTLPR × self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes. Conclusion Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict

  7. ORA59 and EIN3 interaction couples jasmonate-ethylene synergistic action to antagonistic salicylic acid regulation of PDF expression.

    Science.gov (United States)

    He, Xiang; Jiang, Jishan; Wang, Chang-Quan; Dehesh, Katayoon

    2017-04-01

    Hormonal crosstalk is central for tailoring plant responses to the nature of challenges encountered. The role of antagonism between the two major defense hormones, salicylic acid (SA) and jasmonic acid (JA), and modulation of this interplay by ethylene (ET) in favor of JA signaling pathway in plant stress responses is well recognized, but the underlying mechanism is not fully understood. Here, we show the opposing function of two transcription factors, ethylene insensitive3 (EIN3) and EIN3-Like1 (EIL1), in SA-mediated suppression and JA-mediated activation of PLANT DEFENSIN1.2 (PDF1.2). This functional duality is mediated via their effect on protein, not transcript levels of the PDF1.2 transcriptional activator octadecanoid-responsive Arabidopsis59 (ORA59). Specifically, JA induces ORA59 protein levels independently of EIN3/EIL1, whereas SA reduces the protein levels dependently of EIN3/EIL1. Co-infiltration assays revealed nuclear co-localization of ORA59 and EIN3, and split-luciferase together with yeast-two-hybrid assays established their physical interaction. The functional ramification of the physical interaction is EIN3-dependent degradation of ORA59 by the 26S proteasome. These findings allude to SA-responsive reduction of ORA59 levels mediated by EIN3 binding to and targeting of ORA59 for degradation, thus nominating ORA59 pool as a coordination node for the antagonistic function of ET/JA and SA. © 2017 Institute of Botany, Chinese Academy of Sciences.

  8. Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Daniela Massihnia

    2017-01-01

    Full Text Available Abstract Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC, associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs with specimens tissue from radically-resected patients (n = 100. Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their Akt1 mRNA and phospho-Akt/Akt levels by quantitative-RT-PCR and immunocytochemistry. Growth inhibitory effects of Akt inhibitors and gemcitabine were evaluated by SRB assay, whereas modulation of Akt and phospho-Akt was investigated by Western blotting and ELISA. Cell cycle perturbation, apoptosis-induction, and anti-migratory behaviors were studied by flow cytometry, AnnexinV, membrane potential, and migration assay, while pharmacological interaction with gemcitabine was determined with combination index (CI method. Results Immunohistochemistry of TMAs revealed a correlation between phospho-Akt expression and worse outcome, particularly in patients with the highest phospho-Akt levels, who had significantly shorter overall and progression-free-survival. Similar expression levels were detected in LPC028 primary cells, while LPC006 were characterized by low phospho-Akt. Remarkably, Akt inhibitors reduced cancer cell growth in monolayers and spheroids and synergistically enhanced the antiproliferative activity of gemcitabine in LPC028, while this combination was antagonistic in LPC006 cells. The synergistic effect was paralleled by a reduced expression of ribonucleotide reductase, potentially facilitating gemcitabine cytotoxicity. Inhibition of Akt

  9. Synergistic interaction of Rhizobium leguminosarum bv. viciae and arbuscular mycorrhizal fungi as a plant growth promoting biofertilizers for faba bean (Vicia faba L.) in alkaline soil.

    Science.gov (United States)

    Abd-Alla, Mohamed Hemida; El-Enany, Abdel-Wahab Elsadek; Nafady, Nivien Allam; Khalaf, David Mamdouh; Morsy, Fatthy Mohamed

    2014-01-20

    Egyptian soils are generally characterized by slightly alkaline to alkaline pH values (7.5-8.7) which are mainly due to its dry environment. In arid and semi-arid regions, salts are less concentrated and sodium dominates in carbonate and bicarbonate forms, which enhance the formation of alkaline soils. Alkaline soils have fertility problems due to poor physical properties which adversely affect the growth and the yield of crops. Therefore, this study was devoted to investigating the synergistic interaction of Rhizobium and arbuscular mycorrhizal fungi for improving growth of faba bean grown in alkaline soil. A total of 20 rhizobial isolates and 4 species of arbuscular mycorrhizal fungi (AMF) were isolated. The rhizobial isolates were investigated for their ability to grow under alkaline stress. Out of 20 isolates 3 isolates were selected as tolerant isolates. These 3 rhizobial isolates were identified on the bases of the sequences of the gene encoding 16S rRNA and designated as Rhizobium sp. Egypt 16 (HM622137), Rhizobium sp. Egypt 27 (HM622138) and Rhizobium leguminosarum bv. viciae STDF-Egypt 19 (HM587713). The best alkaline tolerant was R. leguminosarum bv. viciae STDF-Egypt 19 (HM587713). The effect of R. leguminosarum bv. viciae STDF-Egypt 19 and mixture of AMF (Acaulospora laevis, Glomus geosporum, Glomus mosseae and Scutellospora armeniaca) both individually and in combination on nodulation, nitrogen fixation and growth of Vicia faba under alkalinity stress were assessed. A significant increase over control in number and mass of nodules, nitrogenase activity, leghaemoglobin content of nodule, mycorrhizal colonization, dry mass of root and shoot was recorded in dual inoculated plants than plants with individual inoculation. The enhancement of nitrogen fixation of faba bean could be attributed to AMF facilitating the mobilization of certain elements such as P, Fe, K and other minerals that involve in synthesis of nitrogenase and leghaemoglobin. Thus it is

  10. Solvation of apolar compounds in protic ionic liquids: the non-synergistic effect of electrostatic interactions and hydrogen bonds.

    Science.gov (United States)

    Sedov, I A; Magsumov, T I; Salikov, T M; Solomonov, B N

    2017-09-27

    The solvation properties of protic ionic liquids such as alkylammonium salts are still virtually uncharacterized. Both electrostatic interactions between charged particles and hydrogen bond networks in a solvent are known to hinder the solubility of apolar species. Protic ionic liquids can be a priori expected to dissolve hydrocarbons worse than aprotic ionic liquids which do not form hydrogen bonds between the ions. We measured the limiting activity coefficients of several alkanes and alkylbenzenes in propylammonium and butylammonium nitrates at 298 K. Surprisingly, we observed the tendency of higher solubility than for the same compounds in aprotic ionic liquids with a similar molar volume. The calculations of the excess Gibbs free energies using test particle insertions into the snapshots of molecular dynamics trajectories reproduced lower values in protic rather than in aprotic ionic liquids for both methane molecules and hard sphere solutes. This can be explained by the favorable solvation of apolar species in the apolar domain of nanostructured PILs. For the first time, we point out at the essential difference between the solvation properties of two types of ionic liquids and prove that it arises from the cavity formation term.

  11. Enhanced 3-sulfanylhexan-1-ol production in sequential mixed fermentation with Torulaspora delbrueckii/Saccharomyces cerevisiae reveals a situation of synergistic interaction between two industrial strains

    Directory of Open Access Journals (Sweden)

    Philippe eRenault

    2016-03-01

    Full Text Available The aim of this work was to study the volatile thiol productions of 2 industrial strains of Torulaspora delbrueckii and Saccharomyces cerevisiae during alcoholic fermentation (AF of Sauvignon Blanc must. In order to evaluate the influence of the inoculation procedure, sequential and simultaneous mixed cultures were carried out and compared to pure cultures of T. delbrueckii and S. cerevisiae. The results confirmed the inability of T. delbrueckii to release 4-methyl-4-sulfanylpentan-2-one (4MSP and its low capacity to produce 3-sulfanylhexyl acetate (3SHA, as already reported in previous studies. A synergistic interaction was observed between the two species, resulting in higher levels of 3SH (3-sulfanylhexan-1-ol and its acetate when S. cerevisiae was inoculated 24 hours after T. delbrueckii, compared to the pure cultures. To elucidate the nature of the interactions between these 2 species, the yeast population kinetics were examined and monitored, as well as the production of 3SH, its acetate and their related non-odorous precursors: Glut-3SH (glutathionylated conjugate precursor and Cys-3SH (cysteinylated conjugate precursor. For the first time, it was suggested that, unlike, S. cerevisiae, which is able to metabolize the two precursor forms, T. delbrueckii was only able to metabolize the glutathionylated precursor. Consequently, the presence of T. delbrueckii during mixed fermentation led to an increase in Glut-3SH degradation and Cys-3SH production. This overproduction was dependent on the T. delbrueckii biomass. In sequential culture, thus favouring T. delbrueckii development, the higher availability of Cys-3SH throughout AF (alcoholic fermentation resulted in more abundant 3SH and 3SHA production by S. cerevisiae

  12. In-vitro antimicrobial activity and synergistic/antagonistic effect of interactions between antibiotics and some spice essential oils.

    Science.gov (United States)

    Toroglu, Sevil

    2011-01-01

    Spices and herbs have been used for many years by different cultures. The aim of the present study is (1) to investigate in-vitro antimicrobial effects of different spices and herbs (5 species: Rosmarinus officinalis (Rosemary), Coriandrum sativum (coriander), Micromeria fruticosa (L.) Druce subsp. Brachycalyx P.H. Davis (White micromeria), Cumium cyminum (cumin), Mentha piperita (Peppermint) against different bacteria and fungi species, and (2) to discuss the in-vitro possible effects between the plants and antibiotics. The microorganisms used were Micrococcus luteus LA 2971, Bacillus megaterium NRS, Bacillus brevis FMC 3, Enterococcus faecalis ATCC 15753, Pseudomonas pyocyaneus DC 127, Mycobacterium smegmatis CCM 2067, Escherichia coil DM, Aeromonas hydrophila ATCC 7966, Yersinia enterocolitica AU 19, Staphylococcus aureus Cowan 1, Streptococcus faecalis DC 74 bacteria, and Saccharomyces cerevisiae WET 136, Kluvyeromyces fragilis DC 98 fungi in this study. The results indicated that essential oils of Rosmarinus officinalis, Coriandrum sativum L., Micromeria fruticosa (L.) Druce subsp. brachycalyx P.H. Davis, Cumium cyminum L., Mentha piperita L. were shown antimicrobial activity in the range of 7-60 mm 2 microl(-1) inhibition zone to the microorganisms tested, using disc diffusion method. Standard antibiotic such as Gentamicin (10 microg), Cephalothin (30 microg), Ceftriaxone (10 microg), Nystatin (10 U) discs were used for comparison with the antimicrobial activities of essential oils of these plants. In addition, antibacterial activity of essential oils of these plants was researched by effects when it was used together with these standard antibiotics in vitro. However, antibacterial activity changed also by in vitro interactions between these standard antibiotics and essential oils of these plants. Synergic, additive or antagonist effects were observed in antibacterial activity.

  13. Interactive-rate Motion Planning for Concentric Tube Robots.

    Science.gov (United States)

    Torres, Luis G; Baykal, Cenk; Alterovitz, Ron

    2014-05-01

    Concentric tube robots may enable new, safer minimally invasive surgical procedures by moving along curved paths to reach difficult-to-reach sites in a patient's anatomy. Operating these devices is challenging due to their complex, unintuitive kinematics and the need to avoid sensitive structures in the anatomy. In this paper, we present a motion planning method that computes collision-free motion plans for concentric tube robots at interactive rates. Our method's high speed enables a user to continuously and freely move the robot's tip while the motion planner ensures that the robot's shaft does not collide with any anatomical obstacles. Our approach uses a highly accurate mechanical model of tube interactions, which is important since small movements of the tip position may require large changes in the shape of the device's shaft. Our motion planner achieves its high speed and accuracy by combining offline precomputation of a collision-free roadmap with online position control. We demonstrate our interactive planner in a simulated neurosurgical scenario where a user guides the robot's tip through the environment while the robot automatically avoids collisions with the anatomical obstacles.

  14. Interactive-rate Motion Planning for Concentric Tube Robots

    Science.gov (United States)

    Torres, Luis G.; Baykal, Cenk; Alterovitz, Ron

    2014-01-01

    Concentric tube robots may enable new, safer minimally invasive surgical procedures by moving along curved paths to reach difficult-to-reach sites in a patient’s anatomy. Operating these devices is challenging due to their complex, unintuitive kinematics and the need to avoid sensitive structures in the anatomy. In this paper, we present a motion planning method that computes collision-free motion plans for concentric tube robots at interactive rates. Our method’s high speed enables a user to continuously and freely move the robot’s tip while the motion planner ensures that the robot’s shaft does not collide with any anatomical obstacles. Our approach uses a highly accurate mechanical model of tube interactions, which is important since small movements of the tip position may require large changes in the shape of the device’s shaft. Our motion planner achieves its high speed and accuracy by combining offline precomputation of a collision-free roadmap with online position control. We demonstrate our interactive planner in a simulated neurosurgical scenario where a user guides the robot’s tip through the environment while the robot automatically avoids collisions with the anatomical obstacles. PMID:25436176

  15. Relativistic collision rate calculations for electron-air interactions

    Energy Technology Data Exchange (ETDEWEB)

    Graham, G. [EG and G Energy Measurements, Inc., Los Alamos, NM (United States); Roussel-Dupre, R. [Los Alamos National Lab., NM (United States)

    1993-12-01

    The most recent data available on differential cross sections for electron-air interactions are used to calculate the avalanche, momentum transfer, and energy loss rates that enter into the fluid equations. Data for the important elastic, inelastic, and ionizing processes are generally available out to electron energies of 1--10 keV. Prescriptions for extending these cross sections to the relativistic regime are presented. The angular dependence of the cross sections is included where data are available as is the doubly differential cross section for ionizing collisions. The collision rates are computed by taking moments of the Boltzmann collision integrals with the assumption that the electron momentum distribution function is given by the Juettner distribution function which satisfies the relativistic H- theorem and which reduces to the familiar Maxwellian velocity distribution in the nonrelativistic regime. The distribution function is parameterized in terms of the electron density, mean momentum, and thermal energy and the rates are therefore computed on a two dimensional grid as a function of mean kinetic energy and thermal energy.

  16. Synergistic Man: Outcome Model for Counselors

    Science.gov (United States)

    Rousseve, Ronald J.

    1973-01-01

    Drawing on the insights of Ruth Benedict and Abraham Maslow in their search for an ethical gauge by which to rate personal-social health, this article proposes synergistic man'' as the desired outcome model for counselors. (Author)

  17. Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli.

    Science.gov (United States)

    Sanhueza, Loreto; Melo, Ricardo; Montero, Ruth; Maisey, Kevin; Mendoza, Leonora; Wilkens, Marcela

    2017-01-01

    Synergy could be an effective strategy to potentiate and recover antibiotics nowadays useless in clinical treatments against multi-resistant bacteria. In this study, synergic interactions between antibiotics and grape pomace extract that contains high concentration of phenolic compounds were evaluated by the checkerboard method in clinical isolates of Staphylococcus aureus and Escherichia coli. To define which component of the extract is responsible for the synergic effect, phenolic compounds were identified by RP-HPLC and their relative abundance was determined. Combinations of extract with pure compounds identified there in were also evaluated. Results showed that the grape pomace extract combined with representatives of different classes of antibiotics as β-lactam, quinolone, fluoroquinolone, tetracycline and amphenicol act in synergy in all S. aureus and E. coli strains tested with FICI values varying from 0.031 to 0.155. The minimal inhibitory concentration (MIC) was reduced 4 to 75 times. The most abundant phenolic compounds identified in the extract were quercetin, gallic acid, protocatechuic acid and luteolin with relative abundance of 26.3, 24.4, 16.7 and 11.4%, respectively. All combinations of the extract with the components also showed synergy with FICI values varying from 0.031 to 0.5 and MIC reductions of 4 to 125 times with both bacteria strains. The relative abundance of phenolic compounds has no correlation with the obtained synergic effect, suggesting that the mechanism by which the synergic effect occurs is by a multi-objective action. It was also shown that combinations of grape pomace extract with antibiotics are not toxic for the HeLa cell line at concentrations in which the synergistic effect was observed (47 μg/mL of extract and 0.6-375 μg/mL antibiotics). Therefore, these combinations are good candidates for testing in animal models in order to enhance the effect of antibiotics of different classes and thus restore the currently unused

  18. Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Loreto Sanhueza

    Full Text Available Synergy could be an effective strategy to potentiate and recover antibiotics nowadays useless in clinical treatments against multi-resistant bacteria. In this study, synergic interactions between antibiotics and grape pomace extract that contains high concentration of phenolic compounds were evaluated by the checkerboard method in clinical isolates of Staphylococcus aureus and Escherichia coli. To define which component of the extract is responsible for the synergic effect, phenolic compounds were identified by RP-HPLC and their relative abundance was determined. Combinations of extract with pure compounds identified there in were also evaluated. Results showed that the grape pomace extract combined with representatives of different classes of antibiotics as β-lactam, quinolone, fluoroquinolone, tetracycline and amphenicol act in synergy in all S. aureus and E. coli strains tested with FICI values varying from 0.031 to 0.155. The minimal inhibitory concentration (MIC was reduced 4 to 75 times. The most abundant phenolic compounds identified in the extract were quercetin, gallic acid, protocatechuic acid and luteolin with relative abundance of 26.3, 24.4, 16.7 and 11.4%, respectively. All combinations of the extract with the components also showed synergy with FICI values varying from 0.031 to 0.5 and MIC reductions of 4 to 125 times with both bacteria strains. The relative abundance of phenolic compounds has no correlation with the obtained synergic effect, suggesting that the mechanism by which the synergic effect occurs is by a multi-objective action. It was also shown that combinations of grape pomace extract with antibiotics are not toxic for the HeLa cell line at concentrations in which the synergistic effect was observed (47 μg/mL of extract and 0.6-375 μg/mL antibiotics. Therefore, these combinations are good candidates for testing in animal models in order to enhance the effect of antibiotics of different classes and thus restore the

  19. Exploring synergistic interactions and catalysts in complex interventions: longitudinal, mixed methods case studies of an optimised multi-level suicide prevention intervention in four european countries (Ospi-Europe

    Directory of Open Access Journals (Sweden)

    Fiona M. Harris

    2016-03-01

    Full Text Available Abstract Background The Medical Research Council (MRC Framework for complex interventions highlights the need to explore interactions between components of complex interventions, but this has not yet been fully explored within complex, non-pharmacological interventions. This paper draws on the process evaluation data of a suicide prevention programme implemented in four European countries to illustrate the synergistic interactions between intervention levels in a complex programme, and to present our method for exploring these. Methods A realist evaluation approach informed the process evaluation, which drew on mixed methods, longitudinal case studies. Data collection consisted of 47 semi-structured interviews, 12 focus groups, one workshop, fieldnoted observations of six programme meetings and 20 questionnaires (delivered at six month intervals to each of the four intervention sites. Analysis drew on the framework approach, facilitated by the use of QSR NVivo (v10. Our qualitative approach to exploring synergistic interactions (QuaSIC also developed a matrix of hypothesised synergies that were explored within one workshop and two waves of data collection. Results All four implementation countries provided examples of synergistic interactions that added value beyond the sum of individual intervention levels or components in isolation. For instance, the launch ceremony of the public health campaign (a level 3 intervention in Ireland had an impact on the community-based professional training, increasing uptake and visibility of training for journalists in particular. In turn, this led to increased media reporting of OSPI activities (monitored as part of the public health campaign and also led to wider dissemination of editorial guidelines for responsible reporting of suicidal acts. Analysis of the total process evaluation dataset also revealed the new phenomenon of the OSPI programme acting as a catalyst for externally generated (and funded

  20. Exploring synergistic interactions and catalysts in complex interventions: longitudinal, mixed methods case studies of an optimised multi-level suicide prevention intervention in four european countries (Ospi-Europe).

    Science.gov (United States)

    Harris, Fiona M; Maxwell, Margaret; O'Connor, Rory; Coyne, James C; Arensman, Ella; Coffey, Claire; Koburger, Nicole; Gusmão, Ricardo; Costa, Susana; Székely, András; Cserhati, Zoltan; McDaid, David; van Audenhove, Chantal; Hegerl, Ulrich

    2016-03-15

    The Medical Research Council (MRC) Framework for complex interventions highlights the need to explore interactions between components of complex interventions, but this has not yet been fully explored within complex, non-pharmacological interventions. This paper draws on the process evaluation data of a suicide prevention programme implemented in four European countries to illustrate the synergistic interactions between intervention levels in a complex programme, and to present our method for exploring these. A realist evaluation approach informed the process evaluation, which drew on mixed methods, longitudinal case studies. Data collection consisted of 47 semi-structured interviews, 12 focus groups, one workshop, fieldnoted observations of six programme meetings and 20 questionnaires (delivered at six month intervals to each of the four intervention sites). Analysis drew on the framework approach, facilitated by the use of QSR NVivo (v10). Our qualitative approach to exploring synergistic interactions (QuaSIC) also developed a matrix of hypothesised synergies that were explored within one workshop and two waves of data collection. All four implementation countries provided examples of synergistic interactions that added value beyond the sum of individual intervention levels or components in isolation. For instance, the launch ceremony of the public health campaign (a level 3 intervention) in Ireland had an impact on the community-based professional training, increasing uptake and visibility of training for journalists in particular. In turn, this led to increased media reporting of OSPI activities (monitored as part of the public health campaign) and also led to wider dissemination of editorial guidelines for responsible reporting of suicidal acts. Analysis of the total process evaluation dataset also revealed the new phenomenon of the OSPI programme acting as a catalyst for externally generated (and funded) activity that shared the goals of suicide prevention

  1. Azole Fungicides as Synergists in the Aquatic Environment

    DEFF Research Database (Denmark)

    Bjergager, Maj-Britt Andersen

    hazard.This PhD thesis evaluates the role of the so called azole fungicides as synergists in the aquaticenvironment through an assessment of the effect of sorption, time and azole concentration on theoccurrence and magnitude of synergistic interactions with pyrethroid insecticides towards...... ofsynergistically acting azoles in the environment. As a consequence of sorbents acting as vectors andpotential accumulation within exposed organisms, aquatic organisms may experience larger exposureconcentrations, leading to greater synergistic effects, than expected based on single azole concentrationsmeasured...

  2. Determining lower threshold concentrations for synergistic effects

    DEFF Research Database (Denmark)

    Bjergager, Maj-Britt Andersen; Dalhoff, Kristoffer; Kretschmann, Andreas

    2017-01-01

    on synergistic interactions between the pyrethroid insecticide, alpha-cypermethrin, and one of the three azole fungicides prochloraz, propiconazole or epoxiconazole measured on Daphnia magna immobilization. Three different experimental setups were applied: A standard 48h acute toxicity test, an adapted 48h test...... of immobile organisms increased more than two-fold above what was predicted by independent action (vertical assessment). All three tests confirmed the hypothesis of the existence of a lower azole threshold concentration below which no synergistic interaction was observed. The lower threshold concentration...

  3. Repeated Interaction and Rating Inflation: A Model of Double Reputation

    OpenAIRE

    Sivan Frenkel

    2015-01-01

    Credit rating agencies have an incentive to maintain a public reputation for credibility among investors but also have an incentive to develop a second, private reputation for leniency among issuers. We show that in markets with few issuers, such as markets for structured assets, these incentives may lead rating agencies to inflate ratings as a strategic tool to form a "double reputation". The model extends the existing literature on "cheap-talk" reputation to the case of two audiences. Our r...

  4. EMU, Monetary Policy Interactions and Exchange Rate Stability

    NARCIS (Netherlands)

    P.A.D. Cavelaars

    2003-01-01

    textabstractThis memorandum discusses the possible impact of a monetary union in Europe on transatlantic exchange rate stability. EMU leads to the elimination of coordination failures within the euro area. Whether this translates into more stable exchange rates, depends on the origin of the shock.

  5. Entertainment Capture through Heart Rate Activity in Physical Interactive Playgrounds

    DEFF Research Database (Denmark)

    Yannakakis, Georgios; Hallam, John; Lund, Henrik Hautop

    2008-01-01

    An approach for capturing and modeling individual entertainment (“fun”) preferences is applied to users of the innovative Playware playground, an interactive physical playground inspired by computer games, in this study. The goal is to construct, using representative statistics computed from...... that predict reported entertainment preferences given HR features. These models are expressed as artificial neural networks and are demonstrated and evaluated on two Playware games and two control tasks requiring physical activity. The best network is able to correctly match expressed preferences in 64...

  6. Interaction between Total Cost and Fill Rate: A Case Study

    Directory of Open Access Journals (Sweden)

    Liljana Ferbar Tratar

    2016-09-01

    Full Text Available Forecasting plays a central role in the efficient operation of a supply chain – i.e., the total costs and fill rate. As forecasts of demand are required on a regular basis for a very large number of products, the methods developed should be fast, flexible, user-friendly, and able to produce results that are reliable and easy to interpret by a manager. In this paper we show that the supply chain costs cannot be optimal if the forecasting method is treated separately from the inventory model. We analyse the performance of the joint optimization of the modified Holt-Winters forecasting method and a stock control policy and investigate the effect of different penalties for unsatisfied demand on the total cost and fill rate of the supply chain. From the results obtained with 1,428 real time series from M3-Competition we show that an essential reduction of supply chain costs and an increase of fill rate can be achieved if we use the joint model with the modified Holt-Winters method.

  7. Evaluation of irradiation hardening and microstructure evolution under the synergistic interaction of He and subsequent Fe ions irradiation in CLAM steel

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Y.P.; Liu, P.P.; Zhu, Y.M.; Wang, Z.Q.; Wan, F.R.; Zhan, Q., E-mail: qzhan@mater.ustb.edu.cn

    2016-08-15

    Sequential dual-ion irradiation is a useful technique for experimental exploration on the synergistic effects of ion accumulation and cascade damage. In this research, the helium-ion accumulation concomitant with displacement damage induced by helium and iron ions irradiation in China low active martensitic (CLAM) steel was studied by ion-irradiation, transmission electron microscopy and nano-indentation technique. The helium bubbles formed under continuous implantation of helium ions at room temperature and the helium dose forming observed bubbles resolved by TEM clearly in CLAM steel is around 0.7 × 10{sup 17}–1.0 × 10{sup 17} He{sup +}/cm{sup 2} under single 100 keV He{sup +} irradiation. Significant irradiation hardening was observed in the samples with various ion- and dose-irradiations. Positive correlation between the hardening increment and the helium-ion dose has been established in single helium-ion irradiated samples. On the other hand, the subsequent Fe-ion irradiation greatly promoted the formation and growth of helium bubbles as well as dislocation loops in sequential dual-ion irradiated samples. No significant contribution of the subsequent Fe-ion irradiation on the hardness increment was found for the sequential dual-ion irradiated samples. It is suggested that the defects recombination, the combination effects of size and density of defects contribute to the degree of irradiation hardening. The calculated hardness increment based on dispersion strengthening model and the experimental microstructure analysis followed the same trend as the experimental nano-indentation data. - Highlights: • Sequential dual-ion irradiation was used to study the synergistic effects of helium accumulation and cascade damage. • The critical helium dose for notable growth of bubbles is around 1.0 × 10{sup 17} He{sup +}/cm{sup 2}. • Bubbles and dislocation loops grew greatly after subsequent Fe-ions irradiation. • The tested and calculated hardness increments

  8. Mud, Macrofauna and Microbes: An ode to benthic organism-abiotic interactions at varying scales

    Science.gov (United States)

    Benthic environments are dynamic habitats, subject to variable sources and rates of sediment delivery, reworking from the abiotic and biotic processes, and complex biogeochemistry. These activities do not occur in a vacuum, and interact synergistically to influence food webs, bi...

  9. The interactive effects of microcystin-LR and cylindrospermopsin on the growth rate of the freshwater algae Chlorella vulgaris.

    Science.gov (United States)

    Pinheiro, Carlos; Azevedo, Joana; Campos, Alexandre; Vasconcelos, Vítor; Loureiro, Susana

    2016-05-01

    Microcystin-LR (MC-LR) and cylindrospermopsin (CYN) are the most representative cyanobacterial cyanotoxins. They have been simultaneously detected in aquatic systems, but their combined ecotoxicological effects to aquatic organisms, especially microalgae, is unknown. In this study, we examined the effects of these cyanotoxins individually and as a binary mixture on the growth rate of the freshwater algae Chlorella vulgaris. Using the MIXTOX tool, the reference model concentration addition (CA) was selected to evaluate the combined effects of MC-LR and CYN on the growth of the freshwater green algae due to its conservative prediction of mixture effect for putative similar or dissimilar acting chemicals. Deviations from the CA model such as synergism/antagonism, dose-ratio and dose-level dependency were also assessed. In single exposures, our results demonstrated that MC-LR and CYN had different impacts on the growth rates of C. vulgaris at the highest tested concentrations, being CYN the most toxic. In the mixture exposure trial, MC-LR and CYN showed a synergistic deviation from the conceptual model CA as the best descriptive model. MC-LR individually was not toxic even at high concentrations (37 mg L(-1)); however, the presence of MC-LR at much lower concentrations (0.4-16.7 mg L(-1)) increased the CYN toxicity. From these results, the combined exposure of MC-LR and CYN should be considered for risk assessment of mixtures as the toxicity may be underestimated when looking only at the single cyanotoxins and not their combination. This study also represents an important step to understand the interactions among MC-LR and CYN detected previously in aquatic systems.

  10. Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole.

    NARCIS (Netherlands)

    Afeltra, J.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

    2004-01-01

    To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds--amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF),

  11. Heart rate variability during adolescent and adult social interactions: a meta-analysis.

    Science.gov (United States)

    Shahrestani, Sara; Stewart, Elizabeth M; Quintana, Daniel S; Hickie, Ian B; Guastella, Adam J

    2015-02-01

    Social interaction skill is important for psychological wellbeing, stress regulation, protection from disability and overall life satisfaction. Increase in activity of the vagus nerve, measured by heart rate variability (HRV), is associated with social interaction skill and decreased stress. In this meta-analysis we collated statistics from thirteen studies consisting of 787 participants who were participating in social interactions while HRV was simultaneously collected. Results revealed that while dyadic social interactions do not increase HRV generally from a baseline state, negative dyadic social interactions decrease HRV in a manner similar to the Trier Social Stress Task. Further, participants with psychopathology do not show cardiac autonomic flexibility during social interactions as indicated by reductions under stress and increases with subsequently positive social interactions. The role of age, gender and HRV index were also examined as potential moderators of HRV. Implications for health and wellbeing resulting from exposure to negative social interactions are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. A simple dependence between protein evolution rate and the number of protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Hirsh Aaron E

    2003-05-01

    Full Text Available Abstract Background It has been shown for an evolutionarily distant genomic comparison that the number of protein-protein interactions a protein has correlates negatively with their rates of evolution. However, the generality of this observation has recently been challenged. Here we examine the problem using protein-protein interaction data from the yeast Saccharomyces cerevisiae and genome sequences from two other yeast species. Results In contrast to a previous study that used an incomplete set of protein-protein interactions, we observed a highly significant correlation between number of interactions and evolutionary distance to either Candida albicans or Schizosaccharomyces pombe. This study differs from the previous one in that it includes all known protein interactions from S. cerevisiae, and a larger set of protein evolutionary rates. In both evolutionary comparisons, a simple monotonic relationship was found across the entire range of the number of protein-protein interactions. In agreement with our earlier findings, this relationship cannot be explained by the fact that proteins with many interactions tend to be important to yeast. The generality of these correlations in other kingdoms of life unfortunately cannot be addressed at this time, due to the incompleteness of protein-protein interaction data from organisms other than S. cerevisiae. Conclusions Protein-protein interactions tend to slow the rate at which proteins evolve. This may be due to structural constraints that must be met to maintain interactions, but more work is needed to definitively establish the mechanism(s behind the correlations we have observed.

  13. Drug interaction alert override rates in the Meaningful Use era: no evidence of progress.

    Science.gov (United States)

    Bryant, A D; Fletcher, G S; Payne, T H

    2014-01-01

    Interruptive drug interaction alerts may reduce adverse drug events and are required for Stage I Meaningful Use attestation. For the last decade override rates have been very high. Despite their widespread use in commercial EHR systems, previously described interventions to improve alert frequency and acceptance have not been well studied. (1) To measure override rates of inpatient medication alerts within a commercial clinical decision support system, and assess the impact of local customization efforts. (2) To compare override rates between drug-drug interaction and drug-allergy interaction alerts, between attending and resident physicians, and between public and academic hospitals. (3) To measure the correlation between physicians' individual alert quantities and override rates as an indicator of potential alert fatigue. We retrospectively analyzed physician responses to drug-drug and drug-allergy interaction alerts, as generated by a common decision support product in a large teaching hospital system. (1) Over four days, 461 different physicians entered 18,354 medication orders, resulting in 2,455 visible alerts; 2,280 alerts (93%) were overridden. (2) The drug-drug alert override rate was 95.1%, statistically higher than the rate for drug-allergy alerts (90.9%) (p drug interaction alert system and to reduce alerting, override rates remain as high as reported over a decade ago. Alert fatigue does not seem to contribute. The results suggest the need to fundamentally question the premises of drug interaction alert systems.

  14. Interactions between rates of temperature change and acclimation affect latitudinal patterns of warming tolerance.

    Science.gov (United States)

    Allen, Jessica L; Chown, Steven L; Janion-Scheepers, Charlene; Clusella-Trullas, Susana

    2016-01-01

    Critical thermal limits form an increasing component of the estimation of impacts of global change on ectotherms. Whether any consistent patterns exist in the interactive effects of rates of temperature change (or experimental ramping rates) and acclimation on critical thermal limits and warming tolerance (one way of assessing sensitivity to climate change) is, however, far from clear. Here, we examine the interacting effects of ramping rate and acclimation on the critical thermal maxima (CTmax) and minima (CTmin) and warming tolerance of six species of springtails from sub-tropical, temperate and polar regions. We also provide microhabitat temperatures from 26 sites spanning 5 years in order to benchmark environmentally relevant rates of temperature change. Ramping rate has larger effects than acclimation on CTmax, but the converse is true for CTmin. Responses to rate and acclimation effects are more consistent among species for CTmax than for CTmin. In the latter case, interactions among ramping rate and acclimation are typical of polar species, less marked for temperate ones, and reduced in species from the sub-tropics. Ramping rate and acclimation have substantial effects on estimates of warming tolerance, with the former being more marked. At the fastest ramping rates (>1.0°C/min), tropical species have estimated warming tolerances similar to their temperate counterparts, whereas at slow ramping rates (warming tolerance is much reduced in tropical species. Rates of temperate change in microhabitats relevant to the springtails are typically warming tolerance approach.

  15. GLOBAL STAR FORMATION RATES AND DUST EMISSION OVER THE GALAXY INTERACTION SEQUENCE

    Energy Technology Data Exchange (ETDEWEB)

    Lanz, Lauranne; Zezas, Andreas; Smith, Howard A.; Ashby, Matthew L. N.; Fazio, Giovanni G.; Hernquist, Lars [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Brassington, Nicola [School of Physics, Astronomy and Mathematics, University of Hertfordshire, College Lane, Hatfield, AL10 9AB (United Kingdom); Da Cunha, Elisabete [Max Planck Institute for Astronomy (MPIA), Koenigstuhl 17, D-69117, Heidelberg (Germany); Hayward, Christopher C. [Heidelberger Institut fuer Theoretische Studien, Schloss-Wolfsbrunnenweg 35, D-69118, Heidelberg (Germany); Jonsson, Patrik, E-mail: llanz@head.cfa.harvard.edu [Space Exploration Technologies, 1 Rocket Road, Hawthorne, CA 90250 (United States)

    2013-05-01

    We measured and modeled spectral energy distributions (SEDs) in 28 bands from the ultraviolet to the far-infrared (FIR) for 31 interacting galaxies in 14 systems. The sample is drawn from the Spitzer Interacting Galaxy Survey, which probes a range of galaxy interaction parameters at multiple wavelengths with an emphasis on the infrared bands. The subset presented in this paper consists of all galaxies for which FIR Herschel SPIRE observations are publicly available. Our SEDs combine the Herschel photometry with multi-wavelength data from Spitzer, GALEX, Swift UVOT, and 2MASS. While the shapes of the SEDs are broadly similar across our sample, strongly interacting galaxies typically have more mid-infrared emission relative to their near-infrared and FIR emission than weakly or moderately interacting galaxies. We modeled the full SEDs to derive host galaxy star formation rates (SFRs), specific star formation rates (sSFRs), stellar masses, dust temperatures, dust luminosities, and dust masses. We find increases in the dust luminosity and mass, SFR, and cold (15-25 K) dust temperature as the interaction progresses from moderately to strongly interacting and between non-interacting and strongly interacting galaxies. We also find increases in the SFR between weakly and strongly interacting galaxies. In contrast, the sSFR remains unchanged across all the interaction stages. The ultraviolet photometry is crucial for constraining the age of the stellar population and the SFR, while dust mass is primarily determined by SPIRE photometry. The SFR derived from the SED modeling agrees well with rates estimated by proportionality relations that depend on infrared emission.

  16. Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats.

    Science.gov (United States)

    Ortiz, Mario I; Fernández-Martínez, Eduardo; Soria-Jasso, Luis Enrique; Lucas-Gómez, Isaac; Villagómez-Ibarra, Roberto; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

    2016-03-01

    Chamomile (Matricaria chamomilla L., Asteraceae) is a medicinal plant widely used as remedy for pain and gastric disorders. The association of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase its antinociceptive activity, permit the use of lower doses and limit side effects. The aim was to isolate and identify the main chemical constituents of Matricaria chamomilla ethanolic extract (MCE) as well as to explore their activity as cyclooxygenase (COX) inhibitors in silico; besides, to examine the interaction between MCE and diclofenac on nociception in the formalin test by isobolographic analysis, and to determine the level of gastric injury in rats. Three terpenoids, α-bisabolol, bisabolol oxide A, and guaiazulene, were isolated and identified by (1)H NMR. Docking simulation predicted COX inhibitory activity for those terpenoids. Diclofenac, MCE, or their combinations produced an antinociceptive effect. The sole administration of diclofenac and the highest combined dose diclofenac-MCE produced significant a gastric damage, but that effect was not seen with MCE alone. An isobologram was constructed and the derived theoretical ED35 for the antinociceptive effect was significantly different from the experimental ED35; hence, the interaction between diclofenac and MCE that mediates the antinociceptive effect is synergist. The MCE contains three major terpenoids with plausible COX inhibitory activity in silico, but α-bisabolol showed the highest affinity. Data suggest that the diclofenac-MCE combination can interact at the systemic level in a synergic manner and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Synergistic impacts of habitat loss and fragmentation on model ecosystems

    OpenAIRE

    Bartlett, Lewis J.; Newbold, Tim; Purves, Drew W.; Tittensor, Derek P.; Harfoot, Michael B. J.

    2016-01-01

    Habitat loss and fragmentation are major threats to biodiversity, yet separating their effects is challenging. We use a multi-trophic, trait-based, and spatially explicit general ecosystem model to examine the independent and synergistic effects of these processes on ecosystem structure. We manipulated habitat by removing plant biomass in varying spatial extents, intensities, and configurations. We found that emergent synergistic interactions of loss and fragmentation are major determinants o...

  18. Hunter-gatherer inter-band interaction rates: implications for cumulative culture.

    Directory of Open Access Journals (Sweden)

    Kim R Hill

    Full Text Available Our species exhibits spectacular success due to cumulative culture. While cognitive evolution of social learning mechanisms may be partially responsible for adaptive human culture, features of early human social structure may also play a role by increasing the number potential models from which to learn innovations. We present interview data on interactions between same-sex adult dyads of Ache and Hadza hunter-gatherers living in multiple distinct residential bands (20 Ache bands; 42 Hadza bands; 1201 dyads throughout a tribal home range. Results show high probabilities (5%-29% per year of cultural and cooperative interactions between randomly chosen adults. Multiple regression suggests that ritual relationships increase interaction rates more than kinship, and that affinal kin interact more often than dyads with no relationship. These may be important features of human sociality. Finally, yearly interaction rates along with survival data allow us to estimate expected lifetime partners for a variety of social activities, and compare those to chimpanzees. Hadza and Ache men are estimated to observe over 300 men making tools in a lifetime, whereas male chimpanzees interact with only about 20 other males in a lifetime. High intergroup interaction rates in ancestral humans may have promoted the evolution of cumulative culture.

  19. Growth rate and resource imbalance interactively control biomass stoichiometry and elemental quotas of aquatic bacteria.

    Science.gov (United States)

    Godwin, Casey M; Whitaker, Emily A; Cotner, James B

    2017-03-01

    The effects of resource stoichiometry and growth rate on the elemental composition of biomass have been examined in a wide variety of organisms, but the interaction among these effects is often overlooked. To determine how growth rate and resource imbalance affect bacterial carbon (C): nitrogen (N): phosphorus (P) stoichiometry and elemental content, we cultured two strains of aquatic heterotrophic bacteria in chemostats at a range of dilution rates and P supply levels (C:P of 100:1 to 10,000:1). When growing below 50% of their maximum growth rate, P availability and dilution rate had strong interactive effects on biomass C:N:P, elemental quotas, cell size, respiration rate, and growth efficiency. In contrast, at faster growth rates, biomass stoichiometry was strongly homeostatic in both strains (C:N:P of 70:13:1 and 73:14:1) and elemental quotas of C, N, and P were tightly coupled (but not constant). Respiration and cell size increased with both growth rate and P limitation, and P limitation induced C accumulation and excess respiration. These results show that bacterial biomass stoichiometry is relatively constrained when all resources are abundant and growth rates are high, but at low growth rates resource imbalance is relatively more important than growth rate in controlling bacterial biomass composition. © 2016 by the Ecological Society of America.

  20. Cross-correlated relaxation rates between protein backbone H–X dipolar interactions

    Energy Technology Data Exchange (ETDEWEB)

    Vögeli, Beat, E-mail: beat.vogeli@ucdenver.edu [University of Colorado Denver, Department of Biochemistry and Molecular Genetics (United States)

    2017-03-15

    The relaxation interference between dipole–dipole interactions of two separate spin pairs carries structural and dynamics information. In particular, when compared to individual dynamic behavior of those spin pairs, such cross-correlated relaxation (CCR) rates report on the correlation between the spin pairs. We have recently mapped out correlated motion along the backbone of the protein GB3, using CCR rates among and between consecutive H{sup N}–N and H{sup α}–C{sup α} dipole–dipole interactions. Here, we provide a detailed account of the measurement of the four types of CCR rates. All rates were obtained from at least two different pulse sequences, of which the yet unpublished ones are presented. Detailed comparisons between the different methods and corrections for unwanted pathways demonstrate that the averaged CCR rates are highly accurate and precise with errors of 1.5–3% of the entire value ranges.

  1. Fluorescence Quenching of a Conjugated Polymer by Synergistic Amine-Carboxylic Acid and π-π Interactions for Selective Detection of Aromatic Amines in Aqueous Solution.

    Science.gov (United States)

    Zhao, Yi-Jia; Miao, Kesong; Zhu, Zhengtao; Fan, Li-Juan

    2017-06-23

    Fluorescence sensing of amine in aqueous solution is challenging. The various basicity and chemical structures of amines may lead to poor selectivity in aqueous solution, and selective fluorescence detection of primary aromatic amine is rarely reported. This paper presents design and synthesis of a fluorescent conjugated polymer for rapid and selective sensing of aromatic amines in aqueous solution. The fluorescent conjugated polymer, poly[fluorenyl-alt-p-phenyleneethynylene] with pendant carboxylic acid groups and long alky chains, is synthesized via palladium-catalyzed Sonogashira coupling reaction. The fluorescence of the polymer is selectively quenched by the aromatic amines in aqueous solution, whereas the aliphatic amines enhance the fluorescence of the polymer. The high selectivity to the aromatic amines, particularly to the environmentally important p-phenylenediamine, likely originates from the amplified π-π fluorescence quenching synergized by amine and carboxylic acid interaction. Our results demonstrate an effective material design strategy that may be extended to fluorescence sensing of other aromatic compounds.

  2. A green and efficient technology for the degradation of cellulosic materials: structure changes and enhanced enzymatic hydrolysis of natural cellulose pretreated by synergistic interaction of mechanical activation and metal salt.

    Science.gov (United States)

    Zhang, Yanjuan; Li, Qian; Su, Jianmei; Lin, Ye; Huang, Zuqiang; Lu, Yinghua; Sun, Guosong; Yang, Mei; Huang, Aimin; Hu, Huayu; Zhu, Yuanqin

    2015-02-01

    A new technology for the pretreatment of natural cellulose was developed, which combined mechanical activation (MA) and metal salt treatments in a stirring ball mill. Different valent metal nitrates were used to investigate the changes in degree of polymerization (DP) and crystallinity index (CrI) of cellulose after MA+metal salt (MAMS) pretreatment, and Al(NO3)3 showed better pretreatment effect than NaNO3 and Zn(NO3)2. The destruction of morphological structure of cellulose was mainly resulted from intense ball milling, and the comparative studies on the changes of DP and crystal structure of MA and MA+Al(NO3)3 pretreated cellulose samples showed a synergistic interaction of MA and Al(NO3)3 treatments with more effective changes of structural characteristics of MA+Al(NO3)3 pretreated cellulose and substantial increase of reducing sugar yield in enzymatic hydrolysis of cellulose. In addition, the results indicated that the presence of Al(NO3)3 had significant enhancement for the enzymatic hydrolysis of cellulose. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Synergistic effects in mixed Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Reisner, A.; Holler, B.M.; Molin, Søren

    2006-01-01

    the pathways governing development of more complex heterogeneous communities. In this study, we established a laboratory model where biofilm-stimulating effects due to interactions between genetically diverse strains of Escherichia coli were monitored. Synergistic induction of biofilm formation resulting from...... the cocultivation of 403 undomesticated E. coli strains with a characterized E. coli K-12 strain was detected at a significant frequency. The survey suggests that different mechanisms underlie the observed stimulation, yet synergistic development of biofilm within the subset of E. coli isolates (n = 56) exhibiting...... the strongest effects was most often linked to conjugative transmission of natural plasmids carried by the E. coli isolates (70%). Thus, the capacity of an isolate to promote the biofilm through cocultivation was (i) transferable to the K-12 strain, (ii) was linked with the acquisition of conjugation genes...

  4. Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild-type ILV1 promoter and interacts synergistically with Reb1p

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Remacle, J E; Kielland-Brandt, Morten

    1998-01-01

    synergistically to control ILV1 expression and that the synergistic effect is distance dependent. We demonstrate that (i) datin (Dat1p), the only known poly (dA:dT)-binding protein in yeast, specifically binds to the ILV1 poly(dA:dT) element in vitro; (ii) Dat1p functions as a trans-activating factor in the ILV1...

  5. Flow rate through microfilters: Influence of the pore size distribution, hydrodynamic interactions, wall slip, and inertia

    DEFF Research Database (Denmark)

    Jensen, Kaare Hartvig; Valente, Andre X. C. N.; Stone, Howard A.

    2014-01-01

    to obtain an analytical formula for the pressure drop across the microfilter versus the flow rate that accounts for the non-uniform distribution of pore sizes, the hydrodynamic interactions between the pores given their layout pattern, and wall slip. Further, we discuss inertial effects and their order...

  6. Heart Rate Variability during Social Interactions in Children with and without Psychopathology: A Meta-Analysis

    Science.gov (United States)

    Shahrestani, Sara; Stewart, Elizabeth M.; Quintana, Daniel S.; Hickie, Ian B.; Guastella, Adam J.

    2014-01-01

    Background: The inability to regulate autonomic activity during social interactions is believed to contribute to social and emotional dysregulation in children. Research has employed heart rate variability (HRV) during both socially engaging and socially disengaging dyadic tasks between children and adults to assess this. Methods: We conducted a…

  7. Genotype X Season interaction effects on the mortality rates of the ...

    African Journals Online (AJOL)

    Genotype X Season interaction effects on the mortality rates of the Nigerian local chicken and its crosses with the barred Plymouth rocks. FUC Mmerole, I Bratte, SI Omeje. Abstract. No Abstract. International Journal of Agriculture and Rural Development Vol. 7(1) 2006: 19-24. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT

  8. The novel interaction between Phytophthora ramorum and wildfire elicits elevated ambrosia beetle landing rates on tanoak

    Science.gov (United States)

    Maia M. Beh; Margaret Metz; Steven J. Seybold; David Rizzo

    2013-01-01

    Beh, Maia M.; Metz, Margaret; Seybold, Steven J.; Rizzo, David. 2013. The novel interaction between Phytophthora ramorum and wildfire elicits elevated ambrosia beetle landing rates on tanoak. In: Frankel, S.J.; Kliejunas, J.T.; Palmieri, K.M.; Alexander, J.M. tech. coords. Proceedings of the sudden oak death fifth science symposium. Gen. Tech. Rep...

  9. Effects of smoking on heart rate, anxiety, and feelings of success during social interaction.

    Science.gov (United States)

    Gilbert, D G; Spielberger, C D

    1987-12-01

    The effects of smoking on heart rate (HR) and emotional processes during social interactions were assessed in 12 smokers. Smoking was associated with less anxiety and with enhanced feelings of being successful both in changing the opinions of others and in expressing one's own point of view. These findings are consistent with others in the literature. The increase in HR during social interactions in which the participants smoked was similar in magnitude to the HR increase associated with speaking versus listening during conversation. The effects of smoking and social interaction on HR appeared to be additive. Smoking during the social interaction increased HR only about half as much as is typically reported for smokers seated quietly in nonsocial situations.

  10. Synergistic Synthetic Biology: Units In Concert

    Directory of Open Access Journals (Sweden)

    Jean-Yves eTrosset

    2013-10-01

    Full Text Available Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancellation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multidrug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  11. Silica ecosystem for synergistic biotransformation

    Science.gov (United States)

    Mutlu, Baris R.; Sakkos, Jonathan K.; Yeom, Sujin; Wackett, Lawrence P.; Aksan, Alptekin

    2016-06-01

    Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues, we designed and produced a synthetic ecosystem by co-encapsulation in a silica gel matrix, which enabled precise control of the microbial populations and their microenvironment. As a case study, two greatly different microorganisms: Pseudomonas sp. NCIB 9816 and Synechococcus elongatus PCC 7942 were encapsulated. NCIB 9816 can aerobically biotransform over 100 aromatic hydrocarbons, a feat useful for synthesis of higher value commodity chemicals or environmental remediation. In our system, NCIB 9816 was used for biotransformation of naphthalene (a model substrate) into CO2 and the cyanobacterium PCC 7942 was used to provide the necessary oxygen for the biotransformation reactions via photosynthesis. A mathematical model was constructed to determine the critical cell density parameter to maximize oxygen production, and was then used to maximize the biotransformation rate of the system.

  12. Does replication groups scoring reduce false positive rate in SNP interaction discovery?

    Directory of Open Access Journals (Sweden)

    Demsar Janez

    2010-01-01

    Full Text Available Abstract Background Computational methods that infer single nucleotide polymorphism (SNP interactions from phenotype data may uncover new biological mechanisms in non-Mendelian diseases. However, practical aspects of such analysis face many problems. Present experimental studies typically use SNP arrays with hundreds of thousands of SNPs but record only hundreds of samples. Candidate SNP pairs inferred by interaction analysis may include a high proportion of false positives. Recently, Gayan et al. (2008 proposed to reduce the number of false positives by combining results of interaction analysis performed on subsets of data (replication groups, rather than analyzing the entire data set directly. If performing as hypothesized, replication groups scoring could improve interaction analysis and also any type of feature ranking and selection procedure in systems biology. Because Gayan et al. do not compare their approach to the standard interaction analysis techniques, we here investigate if replication groups indeed reduce the number of reported false positive interactions. Results A set of simulated and false interaction-imputed experimental SNP data sets were used to compare the inference of SNP-SNP interactions by means of replication groups to the standard approach where the entire data set was directly used to score all candidate SNP pairs. In all our experiments, the inference of interactions from the entire data set (e.g. without using the replication groups reported fewer false positives. Conclusions With respect to the direct scoring approach the utility of replication groups does not reduce false positive rates, and may, depending on the data set, often perform worse.

  13. Ant Larval Demand Reduces Aphid Colony Growth Rates in an Ant-Aphid Interaction

    Directory of Open Access Journals (Sweden)

    James M. Cook

    2012-02-01

    Full Text Available Ants often form mutualistic interactions with aphids, soliciting honeydew in return for protective services. Under certain circumstances, however, ants will prey upon aphids. In addition, in the presence of ants aphids may increase the quantity or quality of honeydew produced, which is costly. Through these mechanisms, ant attendance can reduce aphid colony growth rates. However, it is unknown whether demand from within the ant colony can affect the ant-aphid interaction. In a factorial experiment, we tested whether the presence of larvae in Lasius niger ant colonies affected the growth rate of Aphis fabae colonies. Other explanatory variables tested were the origin of ant colonies (two separate colonies were used and previous diet (sugar only or sugar and protein. We found that the presence of larvae in the ant colony significantly reduced the growth rate of aphid colonies. Previous diet and colony origin did not affect aphid colony growth rates. Our results suggest that ant colonies balance the flow of two separate resources from aphid colonies- renewable sugars or a protein-rich meal, depending on demand from ant larvae within the nest. Aphid payoffs from the ant-aphid interaction may change on a seasonal basis, as the demand from larvae within the ant colony waxes and wanes.

  14. Specific absorption rate benefits of including measured electric field interactions in parallel excitation pulse design.

    Science.gov (United States)

    Deniz, Cem Murat; Alon, Leeor; Brown, Ryan; Sodickson, Daniel K; Zhu, Yudong

    2012-01-01

    Specific absorption rate management and excitation fidelity are key aspects of radiofrequency pulse design for parallel transmission at ultra-high magnetic field strength. The design of radiofrequency pulses for multiple channels is often based on the solution of regularized least-squares optimization problems for which a regularization term is typically selected to control the integrated or peak pulse waveform amplitude. Unlike single-channel transmission, the specific absorption rate of parallel transmission is significantly influenced by interferences between the electric fields associated with the individual transmission elements, which a conventional regularization term does not take into account. This work explores the effects upon specific absorption rate of incorporating experimentally measurable electric field interactions into parallel transmission pulse design. Results of numerical simulations and phantom experiments show that the global specific absorption rate during parallel transmission decreases when electric field interactions are incorporated into pulse design optimization. The results also show that knowledge of electric field interactions enables robust prediction of the net power delivered to the sample or subject by parallel radiofrequency pulses before they are played out on a scanner. Copyright © 2011 Wiley-Liss, Inc.

  15. Analyzing Reaction Rates with the Distortion/Interaction-Activation Strain Model.

    Science.gov (United States)

    Bickelhaupt, F Matthias; Houk, Kendall N

    2017-08-14

    The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, the activation energies are the sum of the energies to distort the reactants into geometries they have in transition states plus the interaction energies between the two distorted molecules. The energy required to distort the molecules is called the activation strain or distortion energy. This energy is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by the stabilizing interaction energy. Following the changes in these energies along the reaction coordinate gives insights into the factors controlling reactivity. This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  16. On the stream-accretion disk interaction - Response to increased mass transfer rate

    Science.gov (United States)

    Dgani, Ruth; Livio, Mario; Soker, Noam

    1989-01-01

    The time-dependent interaction between the stream of mass from the inner Lagrangian point and the accretion disk, resulting from an increasing mass transfer rate is calculated. The calculation is fully three-dimensional, using a pseudoparticle description of the hydrodynamics. It is demonstrated that the results of such calculations, when combined with specific observations, have the potential of both determining essential parameters, such as the viscosity parameter alpha, and can distinguish between different models of dwarf nova eruptions.

  17. Cerberus Fossae and Elysium Planitia Lavas, Mars: Source Vents, Flow Rates, Edifice Styles and Water Interactions

    Science.gov (United States)

    Sakimoto, S. E. H.; Gregg, T. K. P.

    2004-01-01

    The Cerberus Fossae and Elysium Planitia regions have been suggested as some of the youngest martian surfaces since the Viking mission, although there was doubt whether the origins were predominantly volcanic or fluvial. The Mars Global Surveyor and Mars Odyssey Missions have shown that the region is certainly young in terms of the topographic preservation and the youthful crater counts (e.g. in the tens to a few hundred million yrs.). Numerous authors have shown that fluvial and volcanic features share common flow paths and vent systems, and that there is evidence for some interaction between the lava flows and underlying volatiles as well as the use by lavas and water of the same vent system. Given the youthful age and possible water-volcanism interaction environment, we'd like constraints on water and volcanic flux rates and interactions. Here, we model ranges of volcanic flow rates where we can well-constrain them, and consider the modest flow rate results results in context with local eruption styles, and track vent locations, edifice volumes, and flow sources and data.

  18. Interactions among temperature, moisture, and oxygen concentrations in controlling decomposition rates in a boreal forest soil

    Science.gov (United States)

    Sierra, Carlos A.; Malghani, Saadatullah; Loescher, Henry W.

    2017-02-01

    Determining environmental controls on soil organic matter decomposition is of importance for developing models that predict the effects of environmental change on global soil carbon stocks. There is uncertainty about the environmental controls on decomposition rates at temperature and moisture extremes, particularly at high water content levels and high temperatures. It is uncertain whether observed declines in decomposition rates at high temperatures are due to declines in the heat capacity of extracellular enzymes as predicted by thermodynamic theory, or due to simultaneous declines in soil moisture. It is also uncertain whether oxygen limits decomposition rates at high water contents. Here we present the results of a full factorial experiment using organic soils from a boreal forest incubated at high temperatures (25 and 35 °C), a wide range of water-filled pore space (WFPS; 15, 30, 60, 90 %), and contrasting oxygen concentrations (1 and 20 %). We found support for the hypothesis that decomposition rates are high at high temperatures, provided that enough moisture and oxygen are available for decomposition. Furthermore, we found that decomposition rates are mostly limited by oxygen concentrations at high moisture levels; even at 90 % WFPS, decomposition proceeded at high rates in the presence of oxygen. Our results suggest an important degree of interaction among temperature, moisture, and oxygen in determining decomposition rates at the soil core scale.

  19. Consequences of complex environments: Temperature and energy intake interact to influence growth and metabolic rate.

    Science.gov (United States)

    Stahlschmidt, Zachary R; Jodrey, Alicia D; Luoma, Rachel L

    2015-09-01

    The field of comparative physiology has a rich history of elegantly examining the effects of individual environmental factors on performance traits linked to fitness (e.g., thermal performance curves for locomotion). However, animals live in complex environments wherein multiple environmental factors co-vary. Thus, we investigated the independent and interactive effects of temperature and energy intake on the growth and metabolic rate of juvenile corn snakes (Pantherophis guttatus) in the context of shifts in complex environments. Unlike previous studies that imposed constant or fluctuating temperature regimes, we manipulated the availability of preferred thermal microclimates (control vs. relatively warm regimes) for eight weeks and allowed snakes to behaviorally thermoregulate among microclimates. By also controlling for energy intake, we demonstrate an interactive effect of temperature and energy on growth-relevant temperature shifts had no effect on snakes' growth when energy intake was low and a positive effect on growth when energy intake was high. Thus, acclimation to relatively warm thermal options can result in increased rates of growth when food is abundant in a taxon in which body size confers fitness advantages. Temperature and energy also interactively influenced metabolic rate-snakes in the warmer temperature regime exhibited reduced metabolic rate (O2 consumption rate at 25 °C and 30 °C) if they had relatively high energy intake. Although we advocate for continued investigation into the effects of complex environments on other traits, our results indicate that warming may actually benefit important life history traits in some taxa and that metabolic shifts may underlie thermal acclimation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Furry picture transition rates in the intense fields at a lepton collider interaction point

    Directory of Open Access Journals (Sweden)

    A. Hartin

    2015-04-01

    Full Text Available The effect on particle physics processes by intense electromagnetic fields in the charge bunch collisions at future lepton colliders is considered. Since the charge bunch fields are tied to massive sources (the e+e− charges, a reference frame is chosen in which the fields appear to be co-propagating. Solutions of the Dirac equation minimally coupled to the electromagnetic fields reasonably associated with two intense overlapping charge bunches are obtained and found to be a Volkov solution with respect to a null 4-vector whose 3-vector part lies in the common propagation direction. These solutions are used within the Furry interaction picture to calculate the beamstrahlung transition rate for electron radiation due to interaction with the electromagnetic fields of two colliding charge bunches. New analytic expressions are obtained and compared numerically with the beamstrahlung in the electromagnetic field of one charge bunch. The techniques developed will be applied to other collider physics processes in due course.

  1. Synergistic In Vitro Antimalarial Activity of Omeprazole and Quinine

    OpenAIRE

    Skinner-Adams, T.; Davis, T. M. E.

    1999-01-01

    Previous studies have shown that the proton pump inhibitor omeprazole has antimalarial activity in vitro. The interactions of omeprazole with commonly used antimalarial drugs were assessed in vitro. Omeprazole and quinine combinations were synergistic; however, chloroquine and omeprazole combinations were antagonistic. Artemisinin drugs had additive antimalarial activities with omeprazole.

  2. Test and analysis of hadronic interaction models with KASCADE event rates

    Energy Technology Data Exchange (ETDEWEB)

    Risse, M. E-mail: risse@ik1.fzk.de; Antoni, T.; Apel, W.D.; Badea, F.; Bekk, K.; Bernloehr, K.; Bluemer, H.; Bollmann, E.; Bozdog, H.; Brancus, I.M.; Buettner, C.; Chilingarian, A.; Daumiller, K.; Doll, P.; Engler, J.; Fessler, F.; Gils, H.J.; Glasstetter, R.; Haeusler, R.; Hafemann, W.; Haungs, A.; Heck, D.; Hoerandel, J.R.; Holst, T.; Kampert, K.-H.; Kempa, J.; Klages, H.O.; Knapp, J.; Martello, D.; Mathes, H.J.; Matussek, P.; Mayer, H.J.; Milke, J.; Muehlenberg, D.; Oehlschlaeger, J.; Petcu, M.; Rebel, H.; Roth, M.; Schatz, G.; Thouw, T.; Ulrich, H.; Vardanyan, A.; Vulpescu, B.; Weber, J.H.; Wentz, J.; Wiegert, T.; Wochele, J.; Zabierowski, J.; Zagromski, S

    2001-04-01

    Based on the KASCADE multi-detector system with its large hadron calorimeter and using the CORSIKA simulation program with the implemented high-energy hadronic interaction models QGSJET, VENUS, DPMJET, SIBYLL, and HDPM, a method for the test of models by comparing event rates is described. Preliminary results show differences of the model predictions both among each other and when confronted with measurements. The rates are strongly influenced by the inelastic cross sections and the elasticity, especially by the contribution of diffractive dissociation. The discrepancy to measurements at primary energies below {approx_equal} 3 {center_dot} 10{sup 13} eV can be reduced by increasing the non-diffractive inelastic cross section.

  3. Statistical analysis of interaction between lake seepage rates and groundwater and lake levels

    Science.gov (United States)

    Ala-aho, P.; Rossi, P. M.; Klöve, B.

    2012-04-01

    In Finland, the main sources of groundwater are the esker deposits from the last ice age. Small lakes imbedded in the aquifer with no outlets or inlets are typically found in eskers. Some lakes at Rokua esker, in Northern Finland, have been suffering from changes in water stage and quality. A possible permanent decline of water level has raised considerable concern as the area is also used for recreation and tourism. Rare biotypes supported by the oligotrophic lakes can also be endangered by the level decline. Drainage of peatlands located in the discharge zone of the aquifer is a possible threat for the lakes and the whole aquifer. Drainage can potentially lower the aquifer water table which can have an effect on the groundwater-lake interaction. The aim of this study was to understand in more detail the interaction of the aquifer and the lake systems so potential causes for the lake level variations could be better understood and managed. In-depth understanding of hydrogeological system provides foundation to study the nutrient input to lakes affecting lake ecosystems. A small lake imbedded the Rokua esker aquifer was studied in detail. Direct measurements of seepage rate between the lake and the aquifer were carried out using seepage meters. Seepage was measured from six locations for eight times during May 2010 - November 2010. Precipitation was recorded with a tipping bucket rain gauge adjacent to the lake. Lake stage and groundwater levels from three piezometers were registered on an hourly interval using pressure probes. Statistical methods were applied to examine relationship between seepage measurements and levels of lake and groundwater and amount of precipitation. Distinct areas of inseepage and outseepage of the lake were distinguished with seepage meter measurements. Seepage rates showed only little variation within individual measurement locations. Nevertheless analysis revealed statistically significant correlation of seepage rate variation in four

  4. Synergistic effect on co-pyrolysis of capsicum stalks and coal | Niu ...

    African Journals Online (AJOL)

    Synergistic effect on co-pyrolysis of capsicum stalks and coal. ... Results show that the thermal degradation temperature range of capsicum stalks was 290 to 387°C, while that of Baoji coal was 416 to 586°C. According to the comparison of ... Keywords: Pyrolysis, capsicum stalks, mixing rate, kinetics, synergistic effect ...

  5. Low-Grade Inflammation and Ambulatory Cortisol in Adolescents: Interaction Between Interviewer-Rated Versus Self-Rated Acute Stress and Chronic Stress.

    Science.gov (United States)

    Schreier, Hannah M C; Chen, Edith

    To determine whether the association between self-rated or interviewer-rated recent acute stress exposures and low-grade inflammation and daily cortisol production in adolescents is moderated by chronic stress ratings. Acute and chronic stress exposures were assessed in 261 adolescents aged 13 to 16 years using a semistructured life stress interview. The negative impact of acute stressors was independently rated by both adolescents (self-rated) and interviewers (interviewer-rated). Markers of inflammation (interleukin (IL)-6, IL-1ra, C-reactive protein) were measured from peripheral blood samples obtained via antecubital venipuncture. Participants collected 4 saliva samples at home on each of 6 consecutive days for the analysis of diurnal salivary cortisol profiles. There were no main effects of acute stressors (self- and interviewer-rated) and chronic family or peer stress on adolescent inflammation markers and cortisol (p values > .10). However, the interaction between interviewer-rated acute stress and chronic family stress was significantly associated with adolescent inflammation markers (IL-6, IL-1ra). Specifically, as chronic family stress increased, the association between acute stressor impact (interviewer-rated) and inflammation markers became more positive (IL-6 (B = .054, SE = .023, p = .022); IL-1ra (B = .030, SE = .014, p = .034)). Interactions between self-rated acute stress and chronic family stress were not associated with any biological measures (p values > .10). Interactions between acute stressor impact (both self- and interviewer-rated) and chronic peer stress were also not significantly associated with any biological measures (p values > .05). Among adolescents, interviewer-based ratings of acute stressor impact may allow for better prediction of health-relevant inflammation markers than adolescents' own ratings.

  6. Synergistic efficacy in human ovarian cancer cells by histone deacetylase inhibitor TSA and proteasome inhibitor PS-341.

    Science.gov (United States)

    Fang, Yong; Hu, Yi; Wu, Peng; Wang, Beibei; Tian, Yuan; Xia, Xi; Zhang, Qinghua; Chen, Tong; Jiang, Xuefeng; Ma, Quanfu; Xu, Gang; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding; Meng, Li

    2011-05-01

    Histone deacetylase inhibitors and proteasome inhibitor are all emerging as new classes of anticancer agents. We chose TSA and PS-341 to identify whether they have a synergistic efficacy on human ovarian cancer cells. After incubated with 500 nM TSA or/and 40 nM PS-341, we found that combined groups resulted in a striking increase of apoptosis and G2/M blocking rates, no matter in A2780, cisplatin-sensitive ovarian cancer cell line OV2008 or its resistant variant C13*. This demonstrated that TSA interacted synergistically with PS-341, which raised the possibility that combined the two drugs may represent a novel strategy in ovarian cancer.

  7. Evidence for synergistic activity of plant-derived essential oils against fungal pathogens of food.

    Science.gov (United States)

    Hossain, Farah; Follett, Peter; Dang Vu, Khang; Harich, Mehdi; Salmieri, Stephane; Lacroix, Monique

    2016-02-01

    The antifungal activities of eight essential oils (EOs) namely basil, cinnamon, eucalyptus, mandarin, oregano, peppermint, tea tree and thyme were evaluated for their ability to inhibit growth of Aspergillus niger, Aspergillus flavus, Aspergillus parasiticus and Penicillium chrysogenum. The antifungal activity of the EOs was assessed by the minimum inhibitory concentration (MIC) using 96-well microplate analysis. The interactions between different EO combinations were done by the checkerboard technique. The highest antifungal activity was exhibited by oregano and thyme which showed lower MIC values amongst all the tested fungi. The antifungal activity of the other EOs could be appropriately ranked in a descending sequence of cinnamon, peppermint, tea tree and basil. Eucalyptus and mandarin showed the least efficiency as they could not inhibit any of the fungal growth at 10,000 ppm. The interaction between these two EOs also showed no interaction on the tested species. A combined formulation of oregano and thyme resulted in a synergistic effect, showing enhanced efficiency against A. flavus and A. parasiticus and P. chrysogenum. Mixtures of peppermint and tea tree produced synergistic effect against A. niger. Application of a modified Gompertz model considering fungal growth parameters like maximum colony diameter, maximum growth rate and lag time periods, under the various EO treatment scenarios, showed that the model could adequately describe and predict the growth of the tested fungi under these conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Wood source and pyrolysis temperature interact to control PyOM degradation rates

    Science.gov (United States)

    Bird, J. A.; Hatton, P. J.; Filley, T. R.; Chatterjee, S.; Auclerc, A.; Gormley, M.; Dastmalchi, K.; Stark, R. E.; Nadelhoffer, K. J.

    2015-12-01

    Surprisingly little is known about how shifts in tree species composition and increased forest fire frequency and intensity will affect one of the most stable pools of soil organic matter, i.e. the pyrogenic organic matter (PyOM or char). In a previous study, we showed that wood source and pyrolysis temperature interact to control PyOM structure and potential reactivity for two tree species common in high-latitude forests, jack pine (JP) and red maple (RM). Here, we investigate whether these differences affect PyOM turnover by examining the fates of 13C/15N-enriched JP wood and PyOM pyrolyzed at 300 (JP300) and 450 °C (JP450) and RM pyrolyzed at 450 °C (RM450). The substrates were applied 1-3 cm below the O/A interface of a well-drained Spodosol in a long-term forest fire study located at the University of Michigan Biological Station (Pellston, MI, USA). 13C-CO2effluxes from the first 996 days of decay showed a significant wood source by pyrolysis temperature interaction on PyOM field mineralisation rates, with RM450 mineralising twice faster than JP450 during the first 90 days. Increasing pyrolysis temperature substantially decreased field mineralization rates during the first 996 days, with mineralisation rates 24 and 80 times slower for JP300 and JP450 compared with JP wood. After 1 year, (i) bacterial groups were large sinks for PyOM-derived C as pyrolysis temperature increased and as substrate use efficiency decreased; (ii) potential phenol oxidase and net peroxidase activities were unaffected by the PyOM addition, although net peroxidase activities measured tended to lesser for soils amended with JP450 and RM450; and (iii) Collembola detritivores appeared less likely to be found for soils amended with JP450 and RM450. PyOM-derived C and N recoveries did not differ after 1 year; we will present 3-y recovery data. Our results suggest that the composition of angiosperms (e.g. RM) and gymnosperms (e.g. JP) in high-latitude forests is an underappreciated but

  9. The utility of ICF for describing interaction in non-speaking children with disabilities--caregiver ratings and perceptions.

    Science.gov (United States)

    Ibragimova, Nina; Lillvist, Anne; Pless, Mia; Granlund, Mats

    2007-11-30

    The purpose of the study is to explore the utility of the International Classification of Functioning, Disability and Health (ICF) when assessing caregivers' perceptions of interaction and factors related to interaction in non-speaking children with disability. A questionnaire with focus on interaction and related factors was constructed by linking questions in existing instruments to ICF and was completed by 208 professionals and parents of 195 non-speaking children with disabilities in Russia. Caregivers' descriptions of interaction in open-ended questions were qualitatively analysed and compared to selected caregivers' ratings of children's functioning and environment in the questionnaire based on ICF. In the open-ended questions about interaction the caregivers described modes of communication children used, situations in which interactions took place, positive and negative aspects of interactions. Thirty eight respondents described interaction with children negatively, 66 neutrally, and 76 positively. Statistical analyses revealed significant differences among the three groups of respondents concerning their ratings of children's functioning and environment in the ICF-based questionnaire. The ICF-related items in the questionnaire corresponded to caregivers' perceptions of interaction, which shows their relevance for the description of interactions. ICF is feasible in describing of interaction and interaction-related factors in non-speaking children with disabilities in Russia.

  10. Synergistic activity of biocides and antibiotics on resistant bacteria from organically produced foods.

    Science.gov (United States)

    Fernández Fuentes, Miguel Angel; Abriouel, Hikmate; Gadea, Rebeca; Pérez Pulido, Rubén; Gálvez, Antonio; Ortega, Elena

    2014-10-01

    Synergism between biocides and antibiotics was investigated in 20 biocide and antibiotic-resistant bacterial strains that were previously isolated from organically produced foods, according to their antimicrobial resistance profiles. Most of the antibiotic/biocide combinations yielded synergistic interactions, reducing the inhibitory concentrations of biocides and antibiotics by 4- to 16-fold. Among enterococci, synergism with biocides was detected for amoxicillin (AM), cefuroxime (CX), erythromycin (EM), ciprofloxacin (CP), and trimethoprim/sulphametoxazol (T/S). Among staphylococci, interactions were synergistic (AM) and either synergistic or indifferent (CX and EM, depending on biocide). Among the three methicillin-resistant Staphylococcus aureus clinical strains included in the study, the combinations of methicillin and triclosan or hexachlorophene acted synergistically in all strains, but interactions were either synergistic or indifferent for the other biocides, depending on the strain. All combinations tested were synergistic for Lactobacillus (AM, CX, EM, and CP) and Micrococcus (AM, EM). In Salmonella, interactions were indifferent (AM, CX, EM, and CP) or synergistic (T/S). Synergism with biocides was also detected in Klebsiella isolates (AM, CX, and T/S), Enterobacter sp. (AM, CX, EM, and T/S), Pantoea (AM, CX, EM, CP, and T/S), and Chryseobacterium sp. (EM). These results suggest that combinations of biocides and antibiotics may open new possibilities to combat antimicrobial resistance.

  11. Temperature dependence of the rate constant of hydrogen isotope interactions with a lithium capillary-porous system under reactor irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tazhibayeva, Irina, E-mail: tazhibayeva@ntsc.kz [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Kulsartov, Timur; Gordienko, Yuri [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Mukanova, Aliya [Al’ Farabi Kazakh National University, Almaty (Kazakhstan); Ponkratov, Yuri; Barsukov, Nikolay; Tulubaev, Evgeniy [Institute of Atomic Energy NNC RK, Kurchatov (Kazakhstan); Platacis, Erik [University of Latvia (IPUL), Riga (Latvia); Kenzhin, Ergazy [Shakarim Semey State University, Semey (Kazakhstan)

    2013-10-15

    Highlights: • The experiments with Li CPS sample were carried out at reactor IVG-1.M. • The gas absorption technique was used to study hydrogen isotope interaction with lithium CPS. • The temperature dependence of constants of interaction rate was obtained for various power rates of the reactor. • Determination of the activation energies, and pre-exponents of Arrhenius dependence. • The effect of increase of the rate constant under reaction irradiation. -- Abstract: Experiments with a sample of a lithium capillary-porous system (CPS) were performed at the reactor IVG-1.M of the Institute of Atomic Energy NNC RK to study the effects of neutron irradiation on the parameters of hydrogen isotope interactions with a lithium CPS. The absorption technique was used during the experiments, and this technique allowed the temperature dependences of the hydrogen isotope interaction rate constants with the lithium CPS to be obtained under various reactor powers. The obtained dependencies were used to determine the main interaction parameters: the activation energies and the pre-exponents of the Arrhenius dependence of the hydrogen interaction rate constants with lithium and the lithium CPS. An increase of the hydrogen isotope interaction rate with the lithium CPS was observed under reactor irradiation.

  12. Relationship between interaction parent-child with addictability rate and heterosexual orientation in students

    Directory of Open Access Journals (Sweden)

    Abbas Ali Hosseinkhanzadeh

    2014-02-01

    Full Text Available Objective: the purpose of this study was to study relationship between interaction parent-child with addictability rate and heterosexual orientation in students. Method: The statistical population consisted of all students of Guilan University in 2012-2013 academic year, which among them a sample of 200 students were selected by random cluster sampling method and they completed preparation to addiction scale relationship between parent–child scale and attitude and heterosexual orientation before marriage. Findings: Correlation analysis indicated a significant negative correlation between addictability in female students and male students with relationship with father, and positive affect, interlace and communication subscales. The relationship between female students’ addictability with relationship with mother and positive affect, hurt and confusion and communication subscales was observed significant negative correlation, also there is a significant negative relationship between male students’ addictability with the relationship with mother. There is significant negative relationship between heterosexual orientations in male students with relation with father, positive affects and interlace. Results of regression analysis showed that relationship with father and relationship with mother can anticipate addict ability in female and male students. Conclusion: If parents cannot establish an appropriate and constructive interaction with their child cause child face with affection and emotional deprivation and this poor emotional and affection deprivation may cause he or she bring to the addict ability and heterosexual orientation.

  13. Understanding the effect of response rate and class size interaction on students evaluation of teaching in a higher education

    National Research Council Canada - National Science Library

    Al Kuwaiti, Ahmed; AlQuraan, Mahmoud; Subbarayalu, Arun Vijay

    2016-01-01

    Objective: This study aims to investigate the interaction between response rate and class size and its effects on students' evaluation of instructors and the courses offered at a higher education Institution in Saudi Arabia. Study Design...

  14. Synergistic drug combinations from electronic health records and gene expression.

    Science.gov (United States)

    Low, Yen S; Daugherty, Aaron C; Schroeder, Elizabeth A; Chen, William; Seto, Tina; Weber, Susan; Lim, Michael; Hastie, Trevor; Mathur, Maya; Desai, Manisha; Farrington, Carl; Radin, Andrew A; Sirota, Marina; Kenkare, Pragati; Thompson, Caroline A; Yu, Peter P; Gomez, Scarlett L; Sledge, George W; Kurian, Allison W; Shah, Nigam H

    2017-05-01

    Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding. We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis. From EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence. This is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing.

  15. Evaluation of Finite-Rate Gas/Surface Interaction Models for a Carbon Based Ablator

    Science.gov (United States)

    Chen, Yih-Kanq; Goekcen, Tahir

    2015-01-01

    Two sets of finite-rate gas-surface interaction model between air and the carbon surface are studied. The first set is an engineering model with one-way chemical reactions, and the second set is a more detailed model with two-way chemical reactions. These two proposed models intend to cover the carbon surface ablation conditions including the low temperature rate-controlled oxidation, the mid-temperature diffusion-controlled oxidation, and the high temperature sublimation. The prediction of carbon surface recession is achieved by coupling a material thermal response code and a Navier-Stokes flow code. The material thermal response code used in this study is the Two-dimensional Implicit Thermal-response and Ablation Program, which predicts charring material thermal response and shape change on hypersonic space vehicles. The flow code solves the reacting full Navier-Stokes equations using Data Parallel Line Relaxation method. Recession analyses of stagnation tests conducted in NASA Ames Research Center arc-jet facilities with heat fluxes ranging from 45 to 1100 wcm2 are performed and compared with data for model validation. The ablating material used in these arc-jet tests is Phenolic Impregnated Carbon Ablator. Additionally, computational predictions of surface recession and shape change are in good agreement with measurement for arc-jet conditions of Small Probe Reentry Investigation for Thermal Protection System Engineering.

  16. Interactions Between Temperature and Intercellular CO2 Concentration in Controlling Leaf Isoprene Emission Rates

    Science.gov (United States)

    Monson, Russell K.; Neice, Amberly A.; Trahan, Nicole A.; Shiach, Ian; McCorkel, Joel T.; Moore, David J. P.

    2016-01-01

    Plant isoprene emissions have been linked to several reaction pathways involved in atmospheric photochemistry. Evidence exists from a limited set of past observations that isoprene emission rate (I(sub s)) decreases as a function of increasing atmospheric CO2 concentration, and that increased temperature suppresses the CO2 effect. We studied interactions between intercellular CO2 concentration (C(sub I)) and temperature as they affect I(sub s) in field-grown hybrid poplar trees in one of the warmest climates on earth - the Sonoran Desert of the southwestern United States. We observed an unexpected midsummer down regulation of I(sub s) despite the persistence of relatively high temperatures. High temperature suppression of the I(sub s):C(sub I) relation occurred at all times during the growing season, but sensitivity of I(sub s) to increased C(sub I) was greatest during the midsummer period when I(subs) was lowest. We interpret the seasonal down regulation of I(sub s) and increased sensitivity of I(sub s) to C(sub I) as being caused by weather changes associated with the onset of a regional monsoon system. Our observations on the temperature suppression of the I(sub s):C(sub I) relation are best explained by the existence of a small pool of chloroplastic inorganic phosphate, balanced by several large, connected metabolic fluxes, which together, determine the C(sub I) and temperature dependencies of phosphoenolpyruvate import into the chloroplast.

  17. The conceptual cueing database: Rated items for the study of the interaction between language and attention.

    Science.gov (United States)

    Goodhew, Stephanie C; Kidd, Evan

    2016-09-01

    Humans appear to rely on spatial mappings to describe and represent concepts. In particular, conceptual cueing refers to the effect whereby after reading or hearing a particular word, the location of observers' visual attention in space can be systematically shifted in a particular direction. For example, words such as "sun" and "happy" orient attention upwards, whereas words such as "basement" and "bitter" orient attention downwards. This area of research has garnered much interest, particularly within the embodied cognition framework, for its potential to enhance our understanding of the interaction between abstract cognitive processes such as language and basic visual processes such as attention and stimulus processing. To date, however, this area has relied on subjective classification criteria to determine whether words ought to be classified as having a meaning that implies "up" or "down." The present study, therefore, provides a set of 498 items that have each been systematically rated by over 90 participants, providing refined, continuous measures of the extent to which people associate given words with particular spatial dimensions. The resulting database provides an objective means to aid item-selection for future research in this area.

  18. High Textbook Reading Rates When Using an Interactive Textbook for a Material and Energy Balances Course

    Science.gov (United States)

    Liberatore, Matthew

    2017-01-01

    Textbooks are experiencing a 21st century makeover. The author has created a web-based electronic textbook, Material and Energy Balances zyBook, that records students' interactions. Animations and question sets create interactive and scaffolded content. The interactive format is adopted successfully in other engineering disciplines and is now…

  19. Investigating the interaction between heart rate variability and sleep EEG using nonlinear algorithms.

    Science.gov (United States)

    Yeh, Jia-Rong; Peng, Chung-Kang; Lo, Men-Tzung; Yeh, Chien-Hung; Chen, Shih-Ching; Wang, Cheng-Yen; Lee, Po-Lei; Kang, Jiunn-Horng

    2013-10-15

    The multi-mode modulation is a key feature of sleep EEG. And the short-term fractal property reflects the sympathovagal modulation of heart rate variability (HRV). The properties of EEG and HRV strongly correlated with sleep status and are interesting in clinic diagnosis. 19 healthy female subjects were included for over-night standard polysomnographic study. Hilbert Huang transform (HHT) was used to characterize the temporal features of slow- and fast-wave oscillations decomposed from sleep EEG at different stages. Masking signals were used for solving the mode-mixing problem in HHT. On the other hand, detrended fluctuation analysis (DFA) was used to assess short-term property of HRV denoted as DFA α1, which reflects the temporal activity of autonomic nerve system (ANS). Thus, the dynamic interaction between sleep EEG and HRV can be examined through the relationship between the features of sleep EEG and DFA α1 of HRV. The frequency feature of sleep EEG serves as a good indicator for the depth of sleep during non-rapid eye movement (NREM) sleep, and amplitude feature of fast-wave oscillation is a good index for distinguishing rapid eye movement (REM) from NREM sleep. The relationship between DFA α1 of HRV and the mean amplitude of fast-wave oscillation of sleep EEG affirmed with Pearson correlation coefficient is more significant than the correlation verified by the traditional spectral analysis. The dynamic properties of sleep EEG and HRV derived by EMD and DFA represent important features for cortex and ANS activities during sleep. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Mechanism of the Synergistic Toxicity of Malononitrile and p -Nitrobenzaldehyde with Photobacterium phosphoreum.

    Science.gov (United States)

    Lin, Zhifen; Zhang, Wenhuan; Wang, Liansheng; Yu, Hongxia; Wu, Chunde

    2003-01-01

    In this study the mechanism of synergistic toxicity between malononitrile and p -nitrobenzaldehyde was revealed by examining their toxicodynamic and toxicokinetic interactions. The investigation of the toxicodynamic interactions focused on the interactions among malononitrile, p -nitrobenzaldehyde, and luciferase, and found that malononitrile does not induce luciferase to bind p -nitrobenzaldehyde. This result suggested that the synergistic toxicity does not arise from toxicodynamic interactions. Further research on toxicokinetic interactions compared the amounts of p -nitrobenzaldehyde being transported from the water phase to the biotic phase in two circumstances--in the presence of malononitrile and in its absence. The results of this research indicated that in the presence of malononitrile, more p -nitrobenzaldehyde is transported, and it is the increased amount of p -nitrobenzaldehyde that leads to the synergistic toxicity of malononitrile and p -nitrobenzaldehyde.

  1. Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and their major contributed antioxidant compounds

    OpenAIRE

    Shuqin Mao; Kaidi Wang; Yukun Lei; Shuting Yao; Baiyi Lu; Weisu Huang

    2017-01-01

    The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea were evaluated, and their major antioxidant compounds contributed to the total amount of synergy were determined. The antioxidant compounds in O. fragrans flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The synergistic antioxidant interactions between O. fragrans flowers with green tea and their antioxidant compounds were tested using the Prieto?s model after the simulated digestion. T...

  2. Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system.

    Science.gov (United States)

    Li, Gaowen; Ruan, Lina; Chen, Ruijie; Wang, Renye; Xie, Xupei; Zhang, Meixi; Chen, Lichao; Yan, Qizhi; Reed, Miranda; Chen, Jiechun; Xu, Ying; Pan, Jianchun; Huang, Wu

    2015-12-01

    The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.

  3. Effects of Parental Interaction on Infant Vocalization Rate, Variability and Vocal Type

    Science.gov (United States)

    Franklin, Beau; Warlaumont, Anne S.; Messinger, Daniel; Bene, Edina; Iyer, Suneeti Nathani; Lee, Chia-Chang; Lambert, Brittany; Oller, D. Kimbrough

    2014-01-01

    Examination of infant vocalization patterns across interactive and noninteractive contexts may facilitate better understanding of early communication development. In the current study, with 24 infant-parent dyads, infant volubility increased significantly when parent interaction ceased (presenting a "still face," or SF) after a period of…

  4. Web GIS in practice: an interactive geographical interface to English Primary Care Trust performance ratings for 2003 and 2004

    Directory of Open Access Journals (Sweden)

    Kamel Boulos Maged N

    2004-07-01

    Full Text Available Abstract Background On 21 July 2004, the Healthcare Commission http://www.healthcarecommission.org.uk/ released its annual star ratings of the performance of NHS Primary Care Trusts (PCTs in England for the year ending March 2004. The Healthcare Commission started work on 1 April 2004, taking over all the functions of the former Commission for Health Improvement http://www.chi.nhs.uk/, which had released the corresponding PCT ratings for 2002/2003 in July 2003. Results We produced two Web-based interactive maps of PCT star ratings, one for 2003 and the other for 2004 http://healthcybermap.org/PCT/ratings/, with handy functions like map search (by PCT name or part of it. The maps feature a colour-blind friendly quadri-colour scheme to represent PCT star ratings. Clicking a PCT on any of the maps will display the detailed performance report of that PCT for the corresponding year. Conclusion Using our Web-based interactive maps, users can visually appreciate at a glance the distribution of PCT performance across England. They can visually compare the performance of different PCTs in the same year and also between 2003 and 2004 (by switching between the synchronised 'PCT Ratings 2003' and 'PCT Ratings 2004' themes. The performance of many PCTs has improved in 2004, whereas some PCTs achieved lower ratings in 2004 compared to 2003. Web-based interactive geographical interfaces offer an intuitive way of indexing, accessing, mining, and understanding large healthcare information sets describing geographically differentiated phenomena. By acting as an enhanced alternative or supplement to purely textual online interfaces, interactive Web maps can further empower organisations and decision makers.

  5. Interactions in multispecies biofilms

    DEFF Research Database (Denmark)

    Burmølle, Mette; Ren, Dawei; Bjarnsholt, Thomas

    2014-01-01

    The recent focus on complex bacterial communities has led to the recognition of interactions across species boundaries. This is particularly pronounced in multispecies biofilms, where synergistic interactions impact the bacterial distribution and overall biomass produced. Importantly, in a number...... of settings, the interactions in a multispecies biofilm affect its overall function, physiology, or surroundings, by resulting in enhanced resistance, virulence, or degradation of pollutants, which is of significant importance to human health and activities. The underlying mechanisms causing these synergistic...

  6. Synergistic combination dry powders for inhaled antimicrobial therapy

    Science.gov (United States)

    Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

    2013-06-01

    Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

  7. Understanding the Effect of Response Rate and Class Size Interaction on Students Evaluation of Teaching in a Higher Education

    Science.gov (United States)

    Al Kuwaiti, Ahmed; AlQuraan, Mahmoud; Subbarayalu, Arun Vijay

    2016-01-01

    Objective: This study aims to investigate the interaction between response rate and class size and its effects on students' evaluation of instructors and the courses offered at a higher education Institution in Saudi Arabia. Study Design: A retrospective study design was chosen. Methods: One thousand four hundred and forty four different courses…

  8. Three-body recombination rates near a Feshbach resonance within a two-channel contact interaction model

    DEFF Research Database (Denmark)

    Sørensen, Peder Klokmose; V. Fedorov, D.; S. Jensen, A.

    2011-01-01

    We calculate the three-body recombination rate into a shallow dimer in a gas of cold bosonic atoms near a Feshbach resonance using a two-channel contact interaction model. The two-channel model naturally describes the variation of the scattering length through the Feshbach resonance and has a fin...

  9. Characteristics and synergistic effects of co-pyrolysis of yinning coal and poplar sawdust

    Directory of Open Access Journals (Sweden)

    Zhu Shenghua

    2016-01-01

    Full Text Available Co-process of biomass and coal is perceived as a way to enhance the energy utilization by virtue of the integrated and interactive effects between different types of carbonaceous fuels. The purpose of this study was to investigate the co-pyrolysis characteristics of Yining coal and poplar sawdust, and to determine whether there is any synergistic effect in pyrolytic product yields. The coal was blended with sawdust at a mass fraction of 9:1, 7:3, 5:5, 3:7 and 1:9 respectively. The change of char yields, maximum weight loss rate and the corresponding temperature of different coal/sawdust blends during pyrolysis were compared by thermogravimetric analysis (TG. The total tar yields during separate coal, sawdust as well as their blends pyrolysis were acquired from the low temperature aluminum retort distillation test. By compare the experimental and theoretical value of the char yields from TG and tar yields from carbonization test, it was observed that co-pyrolysis of coal/sawdust blends produced less char and tar than the total amount produced by separate coal and sawdust pyrolysis. The different product distribution suggested that there was synergy effect in gas product yields. The co-pyrolysis of demineralized and devolatilized sawdust with coal indicated that the ash in the sawdust was the main contributor to the synergistic effect.

  10. Experimental study of vorticity-strain rate interaction in turbulent partially premixed jet flames using tomographic particle image velocimetry

    Science.gov (United States)

    Coriton, Bruno; Frank, Jonathan H.

    2016-02-01

    In turbulent flows, the interaction between vorticity, ω, and strain rate, s, is considered a primary mechanism for the transfer of energy from large to small scales through vortex stretching. The ω-s coupling in turbulent jet flames is investigated using tomographic particle image velocimetry (TPIV). TPIV provides a direct measurement of the three-dimensional velocity field from which ω and s are determined. The effects of combustion and mean shear on the ω-s interaction are investigated in turbulent partially premixed methane/air jet flames with high and low probabilities of localized extinction as well as in a non-reacting isothermal air jet with Reynolds number of approximately 13 000. Results show that combustion causes structures of high vorticity and strain rate to agglomerate in highly correlated, elongated layers that span the height of the probe volume. In the non-reacting jet, these structures have a more varied morphology, greater fragmentation, and are not as well correlated. The enhanced spatiotemporal correlation of vorticity and strain rate in the stable flame results in stronger ω-s interaction characterized by increased enstrophy and strain-rate production rates via vortex stretching and straining, respectively. The probability of preferential local alignment between ω and the eigenvector of the intermediate principal strain rate, s2, which is intrinsic to the ω-s coupling in turbulent flows, is larger in the flames and increases with the flame stability. The larger mean shear in the flame imposes a preferential orientation of ω and s2 tangential to the shear layer. The extensive and compressive principal strain rates, s1 and s3, respectively, are preferentially oriented at approximately 45° with respect to the jet axis. The production rates of strain and vorticity tend to be dominated by instances in which ω is parallel to the s1 ¯-s2 ¯ plane and orthogonal to s3 ¯.

  11. Material interactions with the Low Earth Orbital (LEO) environment: Accurate reaction rate measurements

    Science.gov (United States)

    Visentine, James T.; Leger, Lubert J.

    1987-01-01

    To resolve uncertainties in estimated LEO atomic oxygen fluence and provide reaction product composition data for comparison to data obtained in ground-based simulation laboratories, a flight experiment has been proposed for the space shuttle which utilizes an ion-neutral mass spectrometer to obtain in-situ ambient density measurements and identify reaction products from modeled polymers exposed to the atomic oxygen environment. An overview of this experiment is presented and the methodology of calibrating the flight mass spectrometer in a neutral beam facility prior to its use on the space shuttle is established. The experiment, designated EOIM-3 (Evaluation of Oxygen Interactions with Materials, third series), will provide a reliable materials interaction data base for future spacecraft design and will furnish insight into the basic chemical mechanisms leading to atomic oxygen interactions with surfaces.

  12. Dark matter haloes in modified gravity and dark energy: interaction rate, small- and large-scale alignment

    Science.gov (United States)

    L'Huillier, Benjamin; Winther, Hans A.; Mota, David F.; Park, Changbom; Kim, Juhan

    2017-07-01

    We study the properties of dark matter haloes in a wide range of modified gravity models, namely, f(R), DGP and interacting dark energy models. We study the effects of modified gravity and dark energy on the internal properties of haloes, such as the spin and the structural parameters. We find that f(R) gravity enhances the median value of the Bullock spin parameter, but could not detect such effects for DGP and coupled dark energy. f(R) also yields a lower median sphericity and oblateness, while coupled dark energy has the opposite effect. However, these effects are very small. We then study the interaction rate of haloes in different gravity and find that only strongly coupled dark energy models enhance the interaction rate. We then quantify the enhancement of the alignment of the spins of interacting halo pairs by modified gravity. Finally, we study the alignment of the major axes of haloes with the large-scale structures. The alignment of the spins of interacting pairs of haloes in DGP and coupled dark energy models show no discrepancy with GR, while f(R) shows a weaker alignment. Strongly coupled dark energy shows a stronger alignment of the halo shape with the large-scale structures.

  13. Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231

    Directory of Open Access Journals (Sweden)

    Azimahtol Hawariah

    2009-01-01

    Full Text Available Abstract Background It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50 was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study. Results Isobole analysis revealed that substances interaction was synergistic when xanthorrhizol and curcumin were added concurrently to the cultures but merely additive when they were added sequentially. The synergistic combination treatment was then applied to the cultures to investigate the mode of cell death induced by the treatment. Immunofluorescence staining using antibody MitoCapture™ revealed the possibility of altered mitochondrial transmembrane potential, which is one of the hallmark of apoptosis. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to the treatment. Apoptotic cell death was further confirmed by DNA fragmentation assay, where internucleosomal excision of DNA was induced upon treatment with xanthorrhizol-curcumin. Conclusion This is the first time the combined cytotoxic effect of xanthorrhizol and curcumin on MDA-MB-231 cells has been documented and our findings provide experimental support to the hypothesis that combined xanthorrhizol-curcumin showed synergistic growth inhibitory activity on

  14. An Interactive Classroom Activity Demonstrating Reaction Mechanisms and Rate-Determining Steps

    Science.gov (United States)

    Jennings, Laura D.; Keller, Steven W.

    2005-01-01

    An interactive classroom activity that includes two-step reaction of unwrapping and eating chocolate candies is described which brings not only the reaction intermediate, but also the reactants and products into macroscopic view. The qualitative activation barriers of both steps can be adjusted independently.

  15. The interactive effect of leader-member exchange and communication frequency on performance ratings.

    Science.gov (United States)

    Kacmar, K Michele; Witt, L A; Zivnuska, Suzanne; Gully, Stanley M

    2003-08-01

    The authors tested the hypothesis that communication frequency moderates the relationship between leader-member exchange (LMX) and job-performance ratings. In a study of 188 private sector workers, they found that LMX was more strongly related to job-performance ratings among individuals reporting frequent communication with the supervisor than among those reporting infrequent communication. At high levels of LMX, workers reporting frequent communication with the supervisor received more favorable job-performance ratings than did workers reporting infrequent communication. In contrast, at low levels of LMX, workers reporting frequent communication with the supervisor received less favorable job-performance ratings than workers reporting infrequent communication. The authors conducted a 2nd study of 153 public sector workers to provide a constructive replication and found similar results.

  16. A Compilation of Rate Parameters of Water-Mineral Interaction Kinetics for Application to Geochemical Modeling

    National Research Council Canada - National Science Library

    Palandri, James L; Kharaka, Yousif K

    2004-01-01

    .... Modeling of some systems, such as those at low temperature with relatively high hydrologic flow rates, or those perturbed by the subsurface injection of industrial waste such as CO2 or H2S, must...

  17. Interactions between temperature and intercellular CO2 concentration in controlling leaf isoprene emission rates

    National Research Council Canada - National Science Library

    Monson, Russell K; Neice, Amberly A; Trahan, Nicole A; Shiach, Ian; McCorkel, Joel T; Moore, David J.P

    2016-01-01

    .... Evidence exists from a limited set of past observations that isoprene emission rate (I s ) decreases as a function of increasing atmospheric CO 2 concentration, and that increased temperature suppresses the CO 2 effect...

  18. Interactions among temperature, moisture, and oxygen concentrations in controlling decomposition rates in a boreal forest soil

    OpenAIRE

    Sierra, Carlos A.; Malghani, Saadatullah; Henry W Loescher

    2017-01-01

    Determining environmental controls on soil organic matter decomposition is of importance for developing models that predict the effects of environmental change on global soil carbon stocks. There is uncertainty about the environmental controls on decomposition rates at temperature and moisture extremes, particularly at high water content levels and high temperatures. It is uncertain whether observed declines in decomposition rates at high temperatures are due to declines ...

  19. Fluid-Structure Interaction Effects on Mass Flow Rates in Solid Rocket Motors

    Science.gov (United States)

    2015-09-02

    in Solid Rocket Motors 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) William Harrigan 5d. PROJECT NUMBER...Determination of mass flow rate in a solid rocket motor is critical in the design of a new motor due to its effect on the thrust produced. Fluid...mass flow rates. The FSI analyses with two‐way coupling provided a more accurate assessment of solid rocket motor internal ballistics. 15. SUBJECT

  20. Bilateral interactions in disease dynamics - Decreasing epidemic thresholds with facilitated contact rates

    Science.gov (United States)

    Morales Gallardo, Alejandro; Brockmann, Dirk; Geisel, Theo

    2008-03-01

    Compartmental epidemiological models are very successful modeling paradigms in epidemiology. Typically, they are employed for quantitative assessments of key parameters such as the basic reproduction number R0. These models rest on two key assumptions: 1.) a population is well mixed 2.) transmission is triggered by a population averaged contact rate. However, experimental evidence shows that contact rates vary substantially, and it has been hypothesized that this variability can change the dynamics of population relevant disease dynamics. However, for inhomogeneous populations the translation of distributed contact rates into effective disease transmission events is non-trivial. Transmission may either depend only on the contact rate of the transmitting individual alone (unilateral transmission), or on the contact rates of transmitting and receiving individual (bilateral transmission). In the SIS model we show that in either systems the endemic state of a disease can be stable for values of R0<1 unlike homogeneous systems with a critical value R0=1. Furthermore, bilateral contact dynamics entail parameter regimes in which a stable endemic state can cease to exist if the mean contact rate is increased, an unexpected effect absent in homogeneous populations.

  1. Influence of the Chemical Interactions on the Removal Rate of Different Salts in Electrokinetic Desalination Processes

    DEFF Research Database (Denmark)

    Paz-Garcia, Juan Manuel; Johannesson, Björn; Ottosen, Lisbeth M.

    2011-01-01

    Electrokinetic desalination techniques have been successfully applied for the prevention of salt-induced deterioration problems of masonry and other construction materials. A mathematical model for electrochemical desalination treatments is described, based on the Poisson-Nernst-Planck system...... and sculptures. Simulations of the desalination treatment of brick samples contaminated with these target contaminants are shown. The influence of the chemical interactions on the efficiency is highlighted in the results....

  2. Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zhen Hua Wu

    Full Text Available The major challenges we are facing in cancer therapy with paclitaxel (PTX are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ, an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP, an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.

  3. Clarithromycin Synergistically Enhances Thalidomide Cytotoxicity in Myeloma Cells.

    Science.gov (United States)

    Qiu, Xu-Hua; Shao, Jing-Jing; Mei, Jian-Gang; Li, Han-Qing; Cao, Hong-Qin

    2016-01-01

    Clarithromycin (CAM) is a macrolide antibiotic that is widely used in the treatment of respiratory tract infections, sexually transmitted diseases and infections caused by the Helicobacter pylori and Mycobacterium avium complex. Recent studies showed that CAM was highly effective against multiple myeloma (MM) when used in combination with immunomodulatory drugs and dexamethasone. However, the related mechanism is still unknown. As 3 immunomodulatory agents are all effective in the respective regimen, we postulated that CAM might enhance the effect of immunomodulatory drugs. We evaluated the interaction effects of CAM and thalidomide on myeloma cells. Taking into consideration that thalidomide did not affect the proliferation of myeloma cells in vitro, we cocultured myeloma cells with peripheral blood monocytes and evaluated the effects of CAM and thalidomide on the cocultured cell model. Data showed that thalidomide and CAM synergistically inhibited the proliferation of the cells. On this same model, we also found that thalidomide and CAM synergistically decreased the secretion of tumor necrosis factor-α and interleukin-6. This might be caused by the effect of the 2 drugs on inhibiting the activation of ERK1/2 and AKT. These data suggest that the efficacy of CAM against MM was partly due to its synergistic action with the immunomodulatory agents. © 2015 S. Karger AG, Basel.

  4. Synergistic Effects of Heavy Metals and Pesticides in Living Systems

    Directory of Open Access Journals (Sweden)

    Nitika Singh

    2017-10-01

    Full Text Available There is a widespread repeated exposure of the population to the pesticides and heavy metals of occupational and environmental origin. Such population is forced to undergo continuous stress imposed by combined exposure of the heavy metals and different classes of the pesticides used in agricultural as well as health practices. The existing reports from several workers have indicated that heavy metals and pesticides in combination may lead more severe impact on the human health when compared to their individual effects. Such a combination of pesticides and heavy metals may also change or influence the detection of exposure. Several studies in past have shown the synergistic toxic effects of heavy metals and pesticides. Such evaluations have revealed the synergistic interactions of various heavy metals and pesticides in animals as well as humans. The aim of the present article is to provide a synthesis of existing knowledge on the synergistic effects of heavy metal and pesticides in living systems. The information included in this article may be useful for different environment protection agencies and policy makers to consider the combined effects of heavy metals and pesticides on humans while designing strategies toward environmental protection and safety regulations about human health.

  5. Displacement determinations of synergistic motion platform jacks

    Directory of Open Access Journals (Sweden)

    В. В. Кабанячий

    2003-03-01

    Full Text Available Urgency, statement and precise solution of displacement determinations problem of synergistic motion platform jacks depending on construction parameters and desired displacements along degrees of freedom are represented

  6. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    Science.gov (United States)

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.Didecyldimethylammonium chloride [DDAC] was...

  7. Interactions between the Exchange Rates and the Differential of the Stock Returns between Romania and US during the Global Crisis

    Directory of Open Access Journals (Sweden)

    Razvan STEFANESCU

    2011-06-01

    Full Text Available The relation between the foreign exchange markets and the stock markets is still a controversial subject in the specialized literature. Recent studies revealed the changes that occur in this relation during the financial crisis. In this paper we approach the interactions between the exchange rates and the differentials of the stock returns between Romania and the US in the period of the global crisis. We find some significant differences in this relations during the main stages of the crisis.

  8. Synergistic chemopreventive effects of nobiletin and atorvastatin on colon carcinogenesis.

    Science.gov (United States)

    Wu, Xian; Song, Mingyue; Qiu, Peiju; Rakariyatham, Kanyasiri; Li, Fang; Gao, Zili; Cai, Xiaokun; Wang, Minqi; Xu, Fei; Zheng, Jinkai; Xiao, Hang

    2017-04-01

    Different cancer chemopreventive agents may act synergistically and their combination may produce enhanced protective effects against carcinogenesis than each individual agent alone. Herein, we investigated the chemopreventive effects of nobiletin (NBT, a citrus polymethoxyflavone) and atorvastatin (ATST, a lipid-lowering drug) in colon cancer cells/macrophages and an azoxymethane (AOM)-induced colon carcinogenesis rat model. The results demonstrated that co-treatments of NBT/ATST produced enhanced growth inhibitory and anti-inflammatory effects on the colon cancer cells and macrophages, respectively. Isobologram analysis confirmed that these interactions between NBT and ATST were synergistic. NBT/ATST co-treatment also synergistically induced extensive cell cycle arrest and apoptosis in colon cancer cells. Oral administration of NBT (0.1%, w/w in diet) or ATST (0.04%, w/w in diet) significantly decreased colonic tumor incidence and multiplicity in AOM-treated rats. Most importantly, co-treatment of NBT/ATST at their half doses (0.05% NBT + 0.02% ATST, w/w in diet) resulted in even stronger inhibitory effects on colonic tumor incidence and multiplicity than did NBT or ATST alone at higher doses. Statistical analysis confirmed that the enhanced chemopreventive activities against colon carcinogenesis in rats by the NBT/ATST combination were highly synergistic. Our results further demonstrated that NBT/ATST co-treatment profoundly modulated key cellular signaling regulators associated with inflammation, cell proliferation, cell cycle progression, apoptosis, angiogenesis and metastasis in the colon of AOM-treated rats. In conclusion, for the first time, our results demonstrated a strong synergy in inhibiting colon carcinogenesis produced by the co-treatment of NBT and ATST, which provided a scientific basis for using NBT in combination with ATST for colon cancer chemoprevention in humans. © The Author 2017. Published by Oxford University Press. All rights reserved

  9. Social interaction moderates the relationship between depressive mood and heart rate variability: evidence from an ambulatory monitoring study.

    Science.gov (United States)

    Schwerdtfeger, Andreas; Friedrich-Mai, Peter

    2009-07-01

    There is considerable evidence that depressive mood is related to lower parasympathetic control of the heart, thus increasing cardiovascular risk. However, little is known about social factors (e.g., social affiliation) that might moderate this relationship. The authors examined whether cardiac autonomic control in healthy individuals with depressive symptoms could be altered by social interaction. Therefore, the authors conducted a 22-hr ambulatory monitoring study with a sample of 63 adults. Depression was assessed by questionnaire. Heart rate, heart rate variability (HRV), physical activity, and negative affect were recorded throughout one day via portable monitoring devices. Multilevel analyses revealed that depression was related to elevated negative affect and higher heart rate throughout the day. Moreover, there was a tendency toward lower HRV in individuals with higher depression scores. This association, however, was moderated by social context. When depressive participants were alone they evidenced lower HRV and higher negative affect, but not when they were engaged in social interactions with a partner, family members, or friends. These findings suggest that the relation between depression and cardiac autonomic control could be altered by social interaction, thus possibly buffering adverse health effects.

  10. Interacting Effects of Instructions and Presentation Rate on Visual Statistical Learning

    Directory of Open Access Journals (Sweden)

    Julie eBertels

    2015-11-01

    Full Text Available The statistical regularities of a sequence of visual shapes can be learned incidentally. Arciuli et al. (2014 recently argued that intentional instructions only improve learning at slow presentation rates as they favor the use of explicit strategies. The aim of the present study was (1 to test this assumption directly by investigating how instructions (incidental vs. intentional and presentation rate (fast vs. slow affect the acquisition of knowledge and (2 to examine how these factors influence the conscious vs. unconscious nature of the knowledge acquired. To this aim, we exposed participants to four triplets of shapes, presented sequentially in a pseudo-random order, and assessed their degree of learning in a subsequent completion task that integrated confidence judgments. Supporting Arciuli et al.’s claim, participant performance only benefited from intentional instructions at slow presentation rates. Moreover, informing participants beforehand about the existence of statistical regularities increased their explicit knowledge of the sequences, an effect that was not modulated by presentation speed. These results support that, although visual statistical learning can take place incidentally and, to some extent, outside conscious awareness, factors such as presentation rate and prior knowledge can boost learning of these regularities, presumably by favoring the acquisition of explicit knowledge.

  11. Exploring synergistic interactions and catalysts in complex interventions : longitudinal, mixed methods case studies of an optimised multi-level suicide prevention intervention in four european countries (Ospi-Europe)

    NARCIS (Netherlands)

    Harris, Fiona M.; Maxwell, Margaret; O'Connor, Rory; Coyne, James C.; Arensman, Ella; Coffey, Claire; Koburger, Nicole; Gusmao, Ricardo; Costa, Susana; Szekely, Andras; Cserhati, Zoltan; McDaid, David; van Audenhove, Chantal; Hegerl, Ulrich

    2016-01-01

    Background: The Medical Research Council (MRC) Framework for complex interventions highlights the need to explore interactions between components of complex interventions, but this has not yet been fully explored within complex, non-pharmacological interventions. This paper draws on the process

  12. Synergistic and Non-synergistic Associations for Cigarette Smoking and Non-tobacco Risk Factors for Cardiovascular Disease Incidence in the Atherosclerosis Risk In Communities (ARIC) Study.

    Science.gov (United States)

    Lubin, Jay H; Couper, David; Lutsey, Pamela L; Yatsuya, Hiroshi

    2017-07-01

    Cigarette smoking, various metabolic and lipid-related factors and hypertension are well-recognized cardiovascular disease (CVD) risk factors. Since smoking affects many of these factors, use of a single imprecise smoking metric, for example, ever or never smoked, may allow residual confounding and explain inconsistencies in current assessments of interactions. Using a comprehensive model in pack-years and cigarettes/day for the complex smoking-related relative risk (RR) of CVD to reduce residual confounding, we evaluated interactions with non-tobacco risk factors, including additive (non-synergistic) and multiplicative (synergistic) forms. Data were from the prospective Atherosclerosis Risk in Communities (ARIC) Study from four areas of the United States recruited in 1987-1989 with follow-up through 2008. Analyses included 14 127 participants, 207 693 person-years and 2857 CVD events. Analyses revealed distinct interactions with smoking: including statistical consistency with additive (body mass index [BMI], waist to hip ratio [WHR], diabetes mellitus [DM], glucose, insulin, high density lipoproteins [HDL] and HDL(2)); and multiplicative (hypertension, total cholesterol [TC], low density lipoproteins [LDLs], apolipoprotein B [apoB], TC to HDL ratio and HDL(3)) associations, as well as indeterminate (apolipoprotein A-I [apoA-I] and triglycerides) associations. The forms of the interactions were revealing but require confirmation. Improved understanding of joint associations may help clarify the public health burden of smoking for CVD, links between etiologic factors and biological mechanisms, and the consequences of joint exposures, whereby synergistic associations highlight joint effects and non-synergistic associations suggest distinct contributions. Joint associations for cigarette smoking and non-tobacco risk factors were distinct, revealing synergistic/multiplicative (hypertension, TC, LDL, apoB, TC/HDL, HDL(3)), non-synergistic/additive (BMI, WHR, DM, glucose

  13. Working memory performance correlates with prefrontal-hippocampal theta interactions but not with prefrontal neuron firing rates

    Directory of Open Access Journals (Sweden)

    James M Hyman

    2010-03-01

    Full Text Available Performance of memory tasks is impaired by lesions to either the medial prefrontal cortex (mPFC or the hippocampus (HPC; although how these two areas contribute to successful performance is not well understood. mPFC unit activity is temporally affected by hippocampal theta oscillations, with almost half the mPFC population entrained to theta in behaving animals, pointing to theta interactions as the mechanism enabling collaborations between these two areas. mPFC neurons respond to sensory stimuli and responses in working memory tasks, though the function of these correlated firing rate changes remains unclear because similar responses are reported during mPFC dependent and independent tasks. Using a DNMS task we compared error trials vs. correct trials and found almost all mPFC cells fired at similar rates during both error and correct trials (92%, however theta-entrainment of mPFC neurons declined during error performance as only 17% of cells were theta-entrained (during correct trials 46% of the population was theta-entrained. Across the population, error and correct trials did not differ in firing rate, but theta-entrainment was impaired. Periods of theta-entrainment and firing rate changes appeared to be independent variables, and only theta-entrainment was correlated with successful performance, indicating mPFC-HPC theta range interactions are the key to successful DNMS performance.

  14. Stock Prices and Exchange Rates in the EU and the USA: Evidence of their Mutual Interactions

    OpenAIRE

    Stavarek, Daniel

    2004-01-01

    This paper investigates the nature of the causal relationships among stock prices and effective exchange rates in four old EU member countries (Austria, France, Germany, and the UK), four new EU member countries (Czech Republic, Hungary, Poland, and Slovakia), and in the United States. Both the long- and short-term causalities between these variables are explored using monthly data. The paper also endeavors to answer the question of whether the linkages between the analyzed economic variables...

  15. Validation of computer-administered clinical rating scale: Hamilton Depression Rating Scale assessment with Interactive Voice Response technology--Japanese version.

    Science.gov (United States)

    Kunugi, Hiroshi; Koga, Norie; Hashikura, Miyako; Noda, Takamasa; Shimizu, Yu; Kobayashi, Takayuki; Yamanaka, Jun; Kanemoto, Noriaki; Higuchi, Teruhiko

    2013-05-01

    The aim of this study was to examine the reliability and validity of the Interactive Voice Response (IVR) program to rate the 17-item Hamilton Rating Scale for Depression (HAM-D) score in Japanese depressive patients. Depression severity was assessed in 60 patients by a clinician and psychologists using HAM-D. Scoring by the IVR program was conducted on the same and the following days. Test-retest reliability, internal consistency, and concurrent validity for total HAM-D scores were examined by calculating intraclass correlation coefficient, Cronbach's alpha, and Pearson's correlation coefficient. Inter-rater consistency for each HAM-D item was examined by Cohen's kappa. Test-retest reliability of the IVR program was high (intraclass correlation coefficient: 0.93). Internal consistency of each total score obtained by the clinician, psychologists, and IVR program was high (Cronbach's alpha: 0.77, 0.79, 0.78, and 0.83). Regarding concurrent validity, correlation coefficients between total scores obtained by the clinician versus IVR and that by the clinician versus psychologists were high (0.81 and 0.93). The HAM-D total score rated by the clinician was 3 points lower than that of IVR. Inter-rater consistency for each HAM-D item evaluated by the clinician versus IVR was estimated to be fair (Cohen's kappa coefficient: 0.02-0.50). Our results suggest that the Japanese IVR HAM-D program is reliable and valid to assess 17-item HAM-D total score in Japanese depressive patients. However, the current program tends to overestimate depression severity, and the score of each item did not always show high agreement with clinician's rating, which warrants further improvement in the program. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  16. On the convergence rate of the Dirichlet-Neumann iteration for unsteady thermal fluid-structure interaction

    Science.gov (United States)

    Monge, Azahar; Birken, Philipp

    2017-11-01

    We consider the Dirichlet-Neumann iteration for partitioned simulation of thermal fluid-structure interaction, also called conjugate heat transfer. We analyze its convergence rate for two coupled fully discretized 1D linear heat equations with jumps in the material coefficients across the interface. The heat equations are discretized using an implicit Euler scheme in time, whereas a finite element method on one domain and a finite volume method with variable aspect ratio on the other one are used in space. We provide an exact formula for the spectral radius of the iteration matrix. The formula indicates that for large time steps, the convergence rate is the aspect ratio times the quotient of heat conductivities and that decreasing the time step will improve the convergence rate. Numerical results confirm the analysis and show that the 1D formula is a very good estimator in 2D and even for nonlinear thermal FSI applications.

  17. Network target for screening synergistic drug combinations with application to traditional Chinese medicine

    Directory of Open Access Journals (Sweden)

    Zhang Ningbo

    2011-06-01

    Full Text Available Abstract Background Multicomponent therapeutics offer bright prospects for the control of complex diseases in a synergistic manner. However, finding ways to screen the synergistic combinations from numerous pharmacological agents is still an ongoing challenge. Results In this work, we proposed for the first time a “network target”-based paradigm instead of the traditional "single target"-based paradigm for virtual screening and established an algorithm termed NIMS (Network target-based Identification of Multicomponent Synergy to prioritize synergistic agent combinations in a high throughput way. NIMS treats a disease-specific biological network as a therapeutic target and assumes that the relationship among agents can be transferred to network interactions among the molecular level entities (targets or responsive gene products of agents. Then, two parameters in NIMS, Topology Score and Agent Score, are created to evaluate the synergistic relationship between each given agent combinations. Taking the empirical multicomponent system traditional Chinese medicine (TCM as an illustrative case, we applied NIMS to prioritize synergistic agent pairs from 63 agents on a pathological process instanced by angiogenesis. The NIMS outputs can not only recover five known synergistic agent pairs, but also obtain experimental verification for synergistic candidates combined with, for example, a herbal ingredient Sinomenine, which outperforms the meet/min method. The robustness of NIMS was also showed regarding the background networks, agent genes and topological parameters, respectively. Finally, we characterized the potential mechanisms of multicomponent synergy from a network target perspective. Conclusions NIMS is a first-step computational approach towards identification of synergistic drug combinations at the molecular level. The network target-based approaches may adjust current virtual screen mode and provide a systematic paradigm for facilitating the

  18. Synergistic impacts of habitat loss and fragmentation on model ecosystems.

    Science.gov (United States)

    Bartlett, Lewis J; Newbold, Tim; Purves, Drew W; Tittensor, Derek P; Harfoot, Michael B J

    2016-09-28

    Habitat loss and fragmentation are major threats to biodiversity, yet separating their effects is challenging. We use a multi-trophic, trait-based, and spatially explicit general ecosystem model to examine the independent and synergistic effects of these processes on ecosystem structure. We manipulated habitat by removing plant biomass in varying spatial extents, intensities, and configurations. We found that emergent synergistic interactions of loss and fragmentation are major determinants of ecosystem response, including population declines and trophic pyramid shifts. Furthermore, trait-mediated interactions, such as a disproportionate sensitivity of large-sized organisms to fragmentation, produce significant effects in shaping responses. We also show that top-down regulation mitigates the effects of land use on plant biomass loss, suggesting that models lacking these interactions-including most carbon stock models-may not adequately capture land-use change impacts. Our results have important implications for understanding ecosystem responses to environmental change, and assessing the impacts of habitat fragmentation. © 2016 The Authors.

  19. Do inertial wave interactions control the rate of energy dissipation of rotating turbulence?

    Science.gov (United States)

    Cortet, Pierre-Philippe; Campagne, Antoine; Machicoane, Nathanael; Gallet, Basile; Moisy, Frederic

    2015-11-01

    The scaling law of the energy dissipation rate, ɛ ~U3 / L (with U and L the characteristic velocity and lengthscale), is one of the most robust features of fully developed turbulence. How this scaling is affected by a background rotation is still a controversial issue with importance for geo and astrophysical flows. At asymptotically small Rossby numbers Ro = U / ΩL , i.e. in the weakly nonlinear limit, wave-turbulence arguments suggest that ɛ should be reduced by a factor Ro . Such scaling has however never been evidenced directly, neither experimentally nor numerically. We report here direct measurements of the injected power, and therefore of ɛ, in an experiment where a propeller is rotating at a constant rate in a large volume of fluid rotating at Ω. In co-rotation, we find a transition between the wave-turbulence scaling at small Ro and the classical Kolmogorov law at large Ro . The transition between these two regimes is characterized from experiments varying the propeller and tank dimensions. In counter-rotation, the scenario is much richer with the observation of an additional peak of dissipation, similar to the one found in Taylor-Couette experiments.

  20. The dietary biogenic amines tyramine and histamine show synergistic toxicity towards intestinal cells in culture.

    Science.gov (United States)

    Del Rio, Beatriz; Redruello, Begoña; Linares, Daniel M; Ladero, Victor; Fernandez, Maria; Martin, Maria Cruz; Ruas-Madiedo, Patricia; Alvarez, Miguel A

    2017-03-01

    Tyramine and histamine are the biogenic amines (BA) most commonly found at high concentrations in food; they may even appear together at toxic concentrations. The present work examines, via real-time cell analysis, whether histamine and tyramine show synergistic toxicity towards intestinal cell cultures. Employing a constant equipotency ratio, their interaction was examined via the combination index (CI) method of Chou & Talalay. Co-treatment with tyramine and histamine was associated with a stronger cytotoxic effect than was treatment with either BA or on its own. Indeed, a synergistic interaction (CIhistamine, at concentrations below the legal limit, increases the cytotoxicity of tyramine at concentrations frequently reached in some foods. The synergistic cytotoxicity of tyramine and histamine should be taken into account when establishing legal limits designed to ensure consumer safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. COMBINATION OF MORPHINE AND GABAPENTIN LEADS TO SYNERGISTIC EFFECTS IN A RAT MODEL OF POSTOPERATIVE PAIN

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    nervous system might lead to synergistic effects, thus minimizing the necessary morphine dose and correspondingly its side effects. In a blinded, randomized, 16 arms study, the pharmacodynamic interactions of morphine and gabapentin were evaluated. In the plantar incision model in the rat, a series...... of hindpaw withdrawal thresholds, after subcutaneous administration of morphine (0, 1, 3 and 7 mg/kg), gabapentin (0, 10, 30 and 100 mg/kg) or their combination (9 combinations of the above doses) were obtained using an electronic von Frey device. Surface of synergistic interaction (SSI) analysis was used...... doses. Combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. This might indicate that there is a high potential for gabapentin and morphine to be used in the clinic, in order to optimize postoperative pain management...

  2. Synergistic antibacterial activity of Salvia officinalis and Cichorium intybus extracts and antibiotics.

    Science.gov (United States)

    Stefanović, Olgica D; Stanojević, Dragana D; Comić, Ljiljana R

    2012-01-01

    Synergistic activity of Salvia officinalis and Cichorium intybus extracts and commonly used antibiotics, amoxicillin and chloramphenicol, were evaluated. Interactions between plant extracts and antibiotics were tested by checkerboard method and interpreted as FIC index. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and clinical isolates Staphylococcus aureus, Bacillus subtilis, Enterobacter cloacae, Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis were used. Salvia officinalis showed better synergistic capacity than Cichorium intybus. Synergistic interactions were observed between amoxicillin and acetone or ethyl acetate extract of Salvia officinalis and between chloramphenicol and ethyl acetate extract of Salvia officinalis. In the presence of sub-inhibitory concentration (1/4 MIC to 1/32 MIC) of sage extracts, the MIC values of antibiotics were decreased by 2- to 10-fold. Synergism was observed against all test bacteria, except Escherichia coli. The combinations of acetone and ethyl acetate extract from Cichorium intybus and antibiotics resulted in additive and indifferent effects against tested bacteria.

  3. Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

    Directory of Open Access Journals (Sweden)

    Mikael A Kowal

    Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

  4. Gender-age interaction in incidence rates of childhood emotional disorders

    DEFF Research Database (Denmark)

    Wesselhoeft, R; Pedersen, C B; Mortensen, P B

    2014-01-01

    .24-2.43) for boys and 3.77% (95% CI 3.64-3.90) for girls. The pre-pubertal male preponderance was also significant for depressive disorders (F32-F33, p = 0.00144) and anxiety disorders (F40-F42, F93, p separately. CONCLUSIONS: Emotional disorders seem to display a male preponderance before the age of 12......BACKGROUND: The post-pubertal association of female gender with emotional disorder is a robust finding. However, studies exploring the association of gender and emotional disorders before puberty are few and present diverging results. The aim of this study was to present gender-specific incidence...... rates of emotional disorders throughout childhood. METHOD: This is a population-based cohort study of 907 806 Danish 3- to 18-year-olds. The outcome was assignment of an emotional disorder diagnosis based on in-patient and out-patient data from The Danish Psychiatric Central Register. Outcome measures...

  5. Determination of rate constants and equilibrium constants for solution-phase drug-protein interactions by ultrafast affinity extraction.

    Science.gov (United States)

    Zheng, Xiwei; Li, Zhao; Podariu, Maria I; Hage, David S

    2014-07-01

    A method was created on the basis of ultrafast affinity extraction to determine both the dissociation rate constants and equilibrium constants for drug-protein interactions in solution. Human serum albumin (HSA), an important binding agent for many drugs in blood, was used as both a model soluble protein and as an immobilized binding agent in affinity microcolumns for the analysis of free drug fractions. Several drugs were examined that are known to bind to HSA. Various conditions to optimize in the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered, and several approaches for these measurements were examined. The dissociation rate constants obtained for soluble HSA with each drug gave good agreement with previous rate constants reported for the same drugs or other solutes with comparable affinities for HSA. The equilibrium constants that were determined also showed good agreement with the literature. The results demonstrated that ultrafast affinity extraction could be used as a rapid approach to provide information on both the kinetics and thermodynamics of a drug-protein interaction in solution. This approach could be extended to other systems and should be valuable for high-throughput drug screening or biointeraction studies.

  6. Human harvest, climate change and their synergistic effects drove the Chinese Crested Tern to the brink of extinction

    Directory of Open Access Journals (Sweden)

    Shuihua Chen

    2015-07-01

    Full Text Available Synergistic effect refers to simultaneous actions of separate factors which have a greater total effect than the sum of the individual factor effects. However, there has been a limited knowledge on how synergistic effects occur and individual roles of different drivers are not often considered. Therefore, it becomes quite challenging to manage multiple threatening processes simultaneously in order to mitigate biodiversity loss. In this regard, our hypothesis is, if the traits actually play different roles in the synergistic interaction, conservation efforts could be made more effectively. To understand the synergistic effect and test our hypothesis, we examined the processes associated with the endangerment of critically endangered Chinese Crested Tern (Thalasseus bernsteini, whose total population number was estimated no more than 50. Through monitoring of breeding colonies and investigations into causative factors, combined with other data on human activities, we found that widespread human harvest of seabird eggs and increasing frequency of typhoons are the major factors that threatened the Chinese Crested Tern. Furthermore, 28 percent of breeding failures were due to the synergistic effects in which egg harvest-induced renestings suffered the higher frequent typhoons. In such combined interactions, the egg harvest has clearly served as a proximal factor for the population decline, and the superimposition of enhanced typhoon activity further accelerated the species toward imminent extinction. Our findings suggest that species endangerment, on one hand, should be treated as a synergistic process, while conservation efforts, on the other hand, should focus principally on combatting the threat that triggers synergistic effects.

  7. Interaction between calcium and potassium modulates elongation rate in cotton fiber cells.

    Science.gov (United States)

    Guo, Kai; Tu, Lili; He, Yonghui; Deng, Jinwu; Wang, Maojun; Huang, Hui; Li, Zhonghua; Zhang, Xianlong

    2017-11-02

    Calcium (Ca2+) is necessary for fiber cell development in cotton (Gossypium hirsutum), both as a cell wall structural component and for environmental signaling responses. It is also known that potassium (K+) plays a critical role in cotton fiber cell elongation. However, it is unclear whether Ca2+ integrates its activities with K+ to regulate fiber elongation. Here, we report the novel discovery that Ca2+ deficiency, when integrated with K+ signaling, promotes fiber elongation. Using inductively coupled plasma-mass spectrometry (ICP-MS), we determined dynamic profiles of the ionome in ovules and fibers at different developmental stages, and found that a high accumulation of macro-elements, but not Ca2+, was associated with longer fibers. Using an in vitro ovule culture system, we found that under Ca2+-deficient conditions, sufficient K+ (52 mM) rapidly induced ovule and fiber browning, while reduced K+ (2 or 27 mM) not only suppressed tissue browning but also altered fiber elongation. Reduced K+ also enhanced reactive oxygen species scavenging ability and maintained abscisic acid and jasmonic acid levels, which in turn compensated for Ca2+ deficiency. Ca2+ deficiency combined with reduced K+ (0 mM Ca2+ and 27 mM K+) produced longer fibers in cultured ovules, due to cell wall loosening by phytosulfokine (PSK), expansin (EXP), and xyloglucan endotransglycosylase/hydrolase (XTH), and an increase of the K+ content of fiber cells. Using transgenic cotton, we showed that the CBL-INTERACTING PROTEIN KINASE 6 (GhCIPK6) gene mediates the uptake of K+ under Ca2+-deficient conditions. This study establishes a new link between Ca2+, K+, and fiber elongation. © Society for Experimental Biology 2017.

  8. Rate of non-linearity in DMS aerosol-cloud-climate interactions

    Directory of Open Access Journals (Sweden)

    M. A. Thomas

    2011-11-01

    Full Text Available The degree of non-linearity in DMS-cloud-climate interactions is assessed using the ECHAM5-HAMMOZ model by taking into account end-to-end aerosol chemistry-cloud microphysics link. The evaluation is made over the Southern oceans in austral summer, a region of minimal anthropogenic influence. In this study, we compare the DMS-derived changes in the aerosol and cloud microphysical properties between a baseline simulation with the ocean DMS emissions from a prescribed climatology, and a scenario where the DMS emissions are doubled. Our results show that doubling the DMS emissions in the current climate results in a non-linear response in atmospheric DMS burden and subsequently, in SO2 and H2SO4 burdens due to inadequate OH oxidation. The aerosol optical depth increases by only ~20 % in the 30° S–75° S belt in the SH summer months. This increases the vertically integrated cloud droplet number concentrations (CDNC by 25 %. Since the vertically integrated liquid water vapor is constant in our model simulations, an increase in CDNC leads to a reduction in cloud droplet radius of 3.4 % over the Southern oceans in summer. The equivalent increase in cloud liquid water path is 10.7 %. The above changes in cloud microphysical properties result in a change in global annual mean radiative forcing at the TOA of −1.4 W m−2. The results suggest that the DMS-cloud microphysics link is highly non-linear. This has implications for future studies investigating the DMS-cloud climate feedbacks in a warming world and for studies evaluating geoengineering options to counteract warming by modulating low level marine clouds.

  9. A synergistic effect of albumin and H₂O₂ accelerates corrosion of Ti6Al4V.

    Science.gov (United States)

    Yu, Fei; Addison, Owen; Davenport, Alison J

    2015-10-01

    The synergistic effect of albumin and H2O2 on corrosion of titanium alloy Ti6Al4V in physiological saline was investigated with long-term immersion tests and electrochemical methods. It was found that in the presence of both albumin and H2O2, the rate of metal release in immersion tests was far higher than in the presence of either species alone. Electrochemical polarisation curves and potentiostatic tests showed that H2O2 increased both the rates of the anodic and cathodic reactions, whilst albumin significantly decreased the rate of the cathodic reaction and slightly decreased the rate of the anodic reaction. The synergistic effect of albumin and H2O2 during immersion tests was attributed to the effect of adsorption of albumin in lowering the rate of the cathodic reaction and thus lowering the open circuit potential into the active region of titanium where complexation by H2O2 increased the corrosion rate. The corrosion attack was found to be greater in the β-phase of the alloy. The findings suggest that current standard tests in physiological or phosphate-buffered saline may underestimate the rate of corrosion in the peri-implant environment, in which albumin is the predominant protein, and reactive oxygen species such as H2O2 can occur as a result of inflammatory reactions in response to surgery, infection, or implant corrosion products. Corrosion of many biomedical implant materials occurs in the body leading to adverse biological responses. Several components of the environment into which a metal implant is placed including proteins and products of cellular physiology, been shown to modify corrosion resistance. Previously all studies on such components including the common protein albumin and the inflammatory product H2O2 have considered the effects of these species in isolation. For the first time we report a synergistic interaction between albumin and H2O2 significantly accelerating corrosion of Ti6Al4V at physiological pH and temperature. This is

  10. Synergistic effects of Chinese herbal medicine: a comprehensive review of methodology and current research

    Directory of Open Access Journals (Sweden)

    Xian Zhou

    2016-07-01

    Full Text Available Traditional Chinese medicine is an important part of primary health care in Asian countries that has utilised complex herbal formulations (consisting 2 or more medicinal herbs for treating diseases over thousands of years. There seems to be a general assumption that the synergistic therapeutic effects of Chinese herbal medicine derive from the complex interactions between the multiple bioactive components within the herbs and/or herbal formulations. However, evidence to support these synergistic effects remains weak and controversial due to several reasons, including the very complex nature of Chinese herbal medicine, misconceptions about synergy, methodological challenges to study design. In this review, we clarify the definition of synergy, identify common errors in synergy research and describe current methodological approaches to test for synergistic interaction. We discuss the strengthen and weakness of these models in the context of Chinese herbal medicine and summarise the current status of synergy research in CHM. Despite the availability of some scientific data to support the synergistic effects of multi-herbal and/or herb-drug combinations, the level of evidence remains low and the clinical relevancy of most of these findings is undetermined. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations.

  11. Interactions between long and synoptic-scale waves. I - Instability of a nonzonal flow. II - Growth rate of long waves

    Science.gov (United States)

    Ebisuzaki, Wesley

    1989-01-01

    The interactions between synoptic-scale and long waves were investigated analytically. First, the influence of the long wave on the synoptic-scale wave is examined. The structure of a synoptic-scale wave growing on a wavy basic scale was analyzed under an assumption that the synoptic-scale waves have the structure of the most unstable normal modes. The derived analytical solution, which is simple and is amenable to physical interpretation, can be understood in terms of eddies and their local growth rate. The analytical solution is then used to examine growth of a long wave in the presence of parameterized synoptic-scale waves. Two possibly unstable solutions were found; one is a modification of the linear long wave, and the other a strongly nonlinear solution. In both cases, the synoptic-scale wave increases the growth rate of the long wave.

  12. Non-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure

    Directory of Open Access Journals (Sweden)

    Ajay K. Verma

    2017-10-01

    Full Text Available Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP from 0 to −40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27 during each LBNP stage, from which heart rate (represented by RR interval, systolic blood pressure (SBP, diastolic blood pressure (DBP, and mean arterial pressure (MAP were derived. The heart rate and blood pressure causal interaction (RR↔SBP and RR↔MAP was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR→SBP and RR→MAP showed a significantly (p < 0.001 higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP→RR and MAP→RR. In response to moderate category hemorrhage (−30 mmHg LBNP, no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10 along with the RR→SBP (p = 0.76, RR→MAP (p = 0.60, and SBP→RR (p = 0.07 causality compared to the resting stage. Contrarily, a significant elevation in the MAP→RR (p = 0.004 causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP→RR of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from

  13. Success rates in smoking cessation: Psychological preparation plays a critical role and interacts with other factors such as psychoactive substances.

    Science.gov (United States)

    Joly, Bertrand; Perriot, Jean; d'Athis, Philippe; Chazard, Emmanuel; Brousse, Georges; Quantin, Catherine

    2017-01-01

    The aim of this study was to identify factors associated with the results of smoking cessation attempts. Data were collected in Clermont-Ferrand from a smoking cessation clinic between 1999 and 2009 (1,361 patients). Smoking cessation was considered a success when patients were abstinent 6 months after the beginning of cessation. Multivariate logistic regression was used to investigate the association between abstinence and different factors. The significant factors were a history of depression (ORadjusted = 0.57, p = 0.003), state of depression at the initial consultation (ORa = 0.64, p = 0.005), other psychoactive substances (ORa = 0.52, psuccess was four times higher). A high score in the Richmond test had a greater impact on success with increasing age (significant interaction: p = 0.01). In exclusive smokers, the contemplation level in the Prochaska algorithm was enough to obtain a satisfactory abstinence rate (65.5%) whereas among consumers of other psychoactive substances, it was necessary to reach the preparation level in the Prochaska algorithm to achieve a success rate greater than 50% (significant interaction: p = 0.02). The psychological preparation of the smoker plays a critical role. The management of smoking cessation must be personalized, especially for consumers of other psychoactive substances and/or smokers with a history of depression.

  14. β-Elemene and taxanes synergistically induce cytotoxicity and inhibit proliferation in ovarian cancer and other tumor cells.

    Science.gov (United States)

    Zou, Baobo; Li, Q Quentin; Zhao, Jinshun; Li, Jueli M; Cuff, Christopher F; Reed, Eddie

    2013-03-01

    β-Elemene, originally derived from plants, has been recently investigated as a new anticancer agent. The purpose of this study was to explore the efficacy and mechanisms of action of the combined use of β-elemene plus a taxane as an antitumor therapeutic strategy for ovarian cancer and other carcinomas. The interaction of β-elemene with paclitaxel or docetaxel produced additive to moderately synergistic effects against the platinum-resistant ovarian cancer cell line A2780/CP70 and its parental cell line A2780, and showed moderately synergistic activity against PC-3 prostate cancer cells. In addition, the co-administration of β-elemene and a taxane at low-micromolar concentrations dramatically increased the rate of micronucleus formation and the percentage of mitotic arrest in both ovarian cancer cell lines, as compared with treatment with either agent alone. The highest synergy towards the ovarian cancer cells was observed with β-elemene plus docetaxel. Consistent with these data, treatment of A2780/CP70 cells with β-elemene plus a taxane strikingly reduced cell viability and increased cell apoptosis, as assessed by annexin V binding. Moreover, β-elemene plus docetaxel induced elevated levels of caspase-9 and p53 proteins in A2780/CP70 cells, and the combination of β-elemene plus a taxane caused marked cell-cycle arrest at the G2/M phase in these cells. One possible mechanism to account for the enhanced cytotoxic efficacy of this combination treatment is a β-elemene-induced increase in taxane influx into cancer cells. These observations indicate that combination therapy with β-elemene and taxanes has synergistic antitumor activity against ovarian and prostate carcinomas in vitro. This promising new therapeutic combination warrants further pre-clinical exploration for the treatment of chemoresistant ovarian cancer and other types of tumors.

  15. Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation.

    Science.gov (United States)

    Ikeda, T; Nishikawa, A; Son, H Y; Nakamura, H; Miyauchi, M; Imazawa, T; Kimura, S; Hirose, M

    2001-04-01

    The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses.

  16. Synergistic effects of iron powder on intumescent flame retardant polypropylene system

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available The effects of iron powder as a synergistic agent on the flame retardancy of intumescent flame retardant polypropylene composites (IFR-PP were studied. The thermogravimetric analysis (TGA and cone calorimeter (CONE were used to evaluate the synergistic effects of iron powder (Fe. The TGA data showed that Fe could enhance the thermal stability of the IFR-PP systems at high temperature and effectively increase the char residue formation. The CONE results revealed that Fe and IFR could clearly change the decomposition behavior of PP and form a char layer on the surface of the composites, consequently resulting in efficient reduction of the flammability parameters, such as heat release rate (HRR, mass loss (ML, Mass loss rate (MLR, total heat release (THR, carbon monoxide and so on. Thus, a suitable amount of Fe plays a synergistic effect in the flame retardancy of IFR composites.

  17. Synergistic effects of some essential oils against fungal spoilage on pear fruit.

    Science.gov (United States)

    Nikkhah, Mehdi; Hashemi, Maryam; Habibi Najafi, Mohammad B; Farhoosh, Reza

    2017-09-18

    The development of natural protective agents as alternatives to chemical fungicides is currently in the spotlight. In the present investigation, chemical composition and antifungal activities of thyme, cinnamon, rosemary and marjoram essential oils (EO), as well as synergism of their possible double and triple combinations were investigated. The compositions of the oils were determined by GC/MS. For determination of antifungal activity against Penicillium expansum and Botrytis cinerea, a broth microdilution method was used. The possible interactions of some essential oil combinations were performed by the two and three-dimensional checkerboard assay and isobologram construction. An in vivo antifungal assay was performed by artificial wounding of pear fruits. The maximum antifungal activity was demonstrated by thyme and cinnamon oils which displayed lower MIC values whereas rosemary and marjoram oils with MIC range between 2500 and 10,000μg/mL exhibited weak antifungal activities against tested fungi. In synergy testing, some double combinations (thyme/cinnamon, thyme/rosemary, cinnamon/rosemary) were found to be synergistic (FICi≤0.5). The triple combination of thyme, cinnamon and rosemary was synergistic for B. cinerea and P. expansum (FICi values of 0.5 and 0.375, respectively); while combination of cinnamon, marjoram and thyme exhibited additive and synergistic effect against P. expansum (FIC=0.625) and B. cinerea (FIC=0.375) respectively. The usage of a mathematical Gompertz model in relation to fungal kinetics, showed that the model could be used to predict growth curves (R 2 =0.993±0.05). For B. cinerea, Gompertz parameters for double and triple combination treatments showed significant increase in lag phase (1.92 and 2.92days, respectively) compared to single treatments. Increase lag time up to 2.82days (P<0.05) also observed in P. expansum treated by triple combination of EOs. Base on the results, the lowest maximum growth rate (0.37mm/day) was observed

  18. Synergistic effect of Glomus fasciculatum and Trichoderma ...

    African Journals Online (AJOL)

    The effect of two soil amendments of tannery sludge (10% and 20%) on growth and metal uptake of Helianthus annuus L. was studied under three treatments of ... and mycorrhizal (F+M) treatment showed the maximum uptake of metals and thus the synergistic effect of these fungi can be exploited in decontamination of ...

  19. Synergistic Antimicrobial Activities Of Phytoestrogens In Crude ...

    African Journals Online (AJOL)

    Intensive studies on extracts and biologically active compounds isolated from medicinal plants have doubled in the last decade worldwide. However, as a result of paucity of knowledge and folkloric claim on the effectiveness of sesame leaves in infectious disease treatments, we aimed to determine the synergistic ...

  20. Modelling synergistic effects of appetite regulating hormones

    DEFF Research Database (Denmark)

    Schmidt, Julie Berg; Ritz, Christian

    2016-01-01

    We briefly reviewed one definition of dose addition, which is applicable within the framework of generalized linear models. We established how this definition of dose addition corresponds to effect addition in case only two doses per compound are considered for evaluating synergistic effects. The....... The link between definitions was exemplified for an appetite study where two appetite hormones were studied....

  1. antioxidant, antimicrobial and synergistic activities of tea ...

    African Journals Online (AJOL)

    ACSS

    Microbial resistance to antibiotics has become an increasing global problem and there is a need to find out novel potent antimicrobial agents with alternative modes of action as accessories to antibiotic therapy. This study investigated the antioxidant, antimicrobial and synergistic properties of tea polyphenols. The tea ...

  2. Protein Interacting with C Kinase 1 (PICK1) Reduces Reinsertion Rates of Interaction Partners Sorted to Rab11-dependent Slow Recycling Pathway*

    Science.gov (United States)

    Madsen, Kenneth L.; Thorsen, Thor S.; Rahbek-Clemmensen, Troels; Eriksen, Jacob; Gether, Ulrik

    2012-01-01

    The scaffolding protein PICK1 (protein interacting with C kinase 1) contains an N-terminal PSD-95/Discs large/ZO-1 (PDZ) domain and a central lipid-binding Bin/amphiphysin/Rvs (BAR) domain. PICK1 is thought to regulate trafficking of its PDZ binding partners but different and even opposing functions have been suggested. Here, we apply ELISA-based assays and confocal microscopy in HEK293 cells with inducible PICK1 expression to assess in an isolated system the ability of PICK1 to regulate trafficking of natural and engineered PDZ binding partners. The dopamine transporter (DAT), which primarily sorts to degradation upon internalization, did not form perinuclear clusters with PICK1, and PICK1 did not affect DAT internalization/recycling. However, transfer of the PICK1-binding DAT C terminus to the β2-adrenergic receptor, which sorts to recycling upon internalization, led to formation of PICK1 co-clusters in Rab11-positive compartments. Furthermore, PICK1 inhibited Rab11-mediated recycling of the receptor in a BAR and PDZ domain-dependent manner. In contrast, transfer of the DAT C terminus to the δ-opioid receptor, which sorts to degradation, did not result in PICK1 co-clusters or any change in internalization/recycling. Further support for a role of PICK1 determined by its PDZ cargo was obtained for the PICK1 interaction partner prolactin-releasing peptide receptor (GPR10). GPR10 co-localized with Rab11 and clustered with PICK1 upon constitutive internalization but co-localized with the late endosomal marker Rab7 and did not cluster with PICK1 upon agonist-induced internalization. Our data suggest a selective role of PICK1 in clustering and reducing the recycling rates of PDZ domain binding partners sorted to the Rab11-dependent recycling pathway. PMID:22303009

  3. Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

    Directory of Open Access Journals (Sweden)

    Sinjan Choudhary

    Full Text Available We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

  4. Synergistic effects of sepiolite on intumescent flame retardant polypropylene

    Directory of Open Access Journals (Sweden)

    2010-12-01

    Full Text Available In this paper, the effects of sepiolite as a synergistic agent on the flame retardancy of intumescent flame retardant polypropylene (PP/IFR were studied using the limiting oxygen index (LOI, the UL-94 test, thermogravimetric analysis (TGA, laser Raman spectroscopy (LRS, cone calorimeter test (CCT and scanning electron microscopy (SEM, and the IFR system mainly consisted of the ammonium polyphosphate modified with γ-aminopropyltriethoxysilane coupling agent, melamine and dipentaerythritol. The results from the LOI and UL 94 tests show that sepiolite added to the PP/IFR system has a synergistic flame retardant effects with the IFR system. The TGA results reveal that sepiolite enhances the thermal stability of the PP/IFR composite and increases the char residue formation. The cone calorimeter results indicate that the heat release rate, mass loss rate, total heat release and average specific extinction area of the PP/IFR/sepiolite composite decrease in comparison with the PP/IFR composite. The LRS measurements provide useful information on the carbonaceous microstructures. The morphological structures observed by SEM have demonstrated that sepiolite promote the formation of the reinforced and homogeneous char barrier on the surface of the composites. Simultaneously, the Young’s modulus and flexural modulus of the PP/IFR composites are also much better improved with the increase of sepiolite added.

  5. Interaction of rare gas metastable atoms. [Differential and total cross sections, elastic scattering, ionization, potential scattering, phase shifts, rate constants

    Energy Technology Data Exchange (ETDEWEB)

    Wang, A.Z.F.

    1977-11-01

    The physical and chemical properties of metastable rare gas atoms are discussed and summarized. This is followed by a detailed examination of the various possible pathways whereby the metastable's excess electronic energy can be dissipated. The phenomenon of chemi-ionization is given special emphasis, and a theoretical treatment based on the use of complex (optical) potential is presented. This is followed by a discussion on the unique advantages offered by elastic differential cross section measurements in the apprehension of the fundamental forces governing the ionization process. The methodology generally adopted to extract information about the interaction potential for scattering data is also systematically outlined. Two widely studied chemi-ionization systems are then closely examined in the light of accurate differential cross section measurements obtained in this work. The first system is He(2/sup 3/S) + Ar for which one can obtain an interaction potential which is in good harmony with the experimental results of other investigators. The validity of using the first-order semiclassical approximation for the phase shifts calculation in the presence of significant opacities is also discussed. The second reaction studied is He*+D/sub 2/ for which measurements were made on both spin states of the metastable helium. A self-consistent interaction potential is obtained for the triplet system, and reasons are given for not being able to do likewise for the singlet system. The anomalous hump proposed by a number of laboratories is analyzed. Total elastic and ionization cross sections as well as rate constants are calculated for the triplet case. Good agreement with experimental data is found. Finally, the construction and operation of a high power repetitively pulsed nitrogen laser pumped dye laser system is described in great details. Details for the construction and operation of a flashlamp pumped dye laser are likewise given.

  6. Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells.

    Science.gov (United States)

    van Haaften, Caroline; Boot, Arnoud; Corver, Willem E; van Eendenburg, Jaap D H; Trimbos, Baptist J M Z; van Wezel, Tom

    2015-04-25

    Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed. Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit. In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G2/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis. Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

  7. In Vitro Antifungal Activity of Sertraline and Synergistic Effects in Combination with Antifungal Drugs against Planktonic Forms and Biofilms of Clinical Trichosporon asahii Isolates.

    Science.gov (United States)

    Cong, Lin; Liao, Yong; Yang, Suteng; Yang, Rongya

    2016-01-01

    Trichosporon asahii (T. asahii) is the major pathogen of invasive trichosporonosis which occurred mostly in immunocompromised patients. The biofilms formation ability of T. asahii may account for resistance to antifungal drugs and results a high mortality rate. Sertraline, a commonly prescribed antidepressant, has been demonstrated to show in vitro and in vivo antifungal activities against many kinds of pathogenic fungi, especially Cryptococcus species. In the present study, the in vitro activities of sertraline alone or combined with fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B against planktonic forms and biofilms of 21 clinical T. asahii isolates were evaluated using broth microdilution checkerboard method and XTT reduction assay, respectively. The fractional inhibitory concentration index (FICI) was used to interpret drug interactions. Sertraline alone exhibited antifungal activities against both T. asahii planktonic cells (MICs, 4-8 μg/ml) and T. asahii biofilms (SMICs, 16-32 μg/ml). Furthermore, SRT exhibited synergistic effects against T. asahii planktonic cells in combination with amphotericin B, caspofungin or fluconazole (FICI≤0.5) and exhibited synergistic effects against T. asahii biofilms in combination with amphotericin B (FICI≤0.5). SRT exhibited mostly indifferent interactions against T. asahii biofilms in combination with three azoles in this study. Sertraline-amphotericin B combination showed the highest percentage of synergistic effects against both T. asahii planktonic cells (90.5%) and T. asahii biofilms (81.0%). No antagonistic interaction was observed. Our study suggests the therapeutic potential of sertraline against invasive T. asahii infection, especially catheter-related T. asahii infection. Further in vivo studies are needed to validate our findings.

  8. Can Mindful Parenting Be Observed? Relations between Observational Ratings of Mother-Youth Interactions and Mothers’ Self-Report Mindful Parenting

    OpenAIRE

    Duncan, Larissa G.; Coatsworth, J. Douglas; Gayles, Jochebed G.; Geier, Mary H.; Greenberg, Mark T

    2015-01-01

    Research on mindful parenting, an extension of mindfulness to the interpersonal domain of parent-child relationships, has been limited by its reliance on self-report assessment. The current study is the first to examine whether observational indices of parent-youth interactions differentiate between high and low levels of self-reported mindful parenting. The Iowa Family Interaction Rating Scales (IFIRS) were used to code interactions between mothers and their 7th grade youth. Mothers drawn fr...

  9. Solid state interaction of raloxifene HCl with different hydrophilic carriers during co-grinding and its effect on dissolution rate.

    Science.gov (United States)

    Garg, Anuj; Singh, S; Rao, V U; Bindu, K; Balasubramaniam, J

    2009-04-01

    This study investigated the effects of different classes of hydrophilic carriers (poly vinyl pyrrolidones [PVPs] [Plasdone K-25 and Plasdone S-630], cellulosic polymers [hydroxypropyl methyl cellulose and hydroxy propyl cellulose], and Sodium Alginate) on the solid state and dissolution rate of Raloxifene hydrochloride (R-HCl). Solid state characterizations of co-ground mixtures and physical mixtures in 1:1 and 1:2 ratios of drug to polymer were performed by employing laser diffractometer for particle size and differential scanning calorimetry (DSC) for solid state interactions. The results of particle size studies showed that only co-grinding with PVPs was more effective in the reduction of particle size than the milling of drug alone. DSC study indicated that the crystalline nature of the drug was reduced after co-grinding with PVPs when compared with their corresponding physical mixtures. The hydrophilic carriers other than PVPs did not reduce the crystalline nature of the drug significantly. X-ray diffraction and scanning electron microscopy were carried out for selected batches to confirm DSC results. Significant enhancement in dissolution rate and extent was observed with co-ground mixtures of drug and PVPs. Plasdone S-630 was found to be a better carrier for R-HCl in terms of achieving improvement in dissolution. In vitro dissolution data can be described by Hixson-Crowell model, indicating the drug release mechanism predominated by erosion.

  10. Synergistic Induction of Eotaxin and VCAM-1 Expression in Human Corneal Fibroblasts by Staphylococcal Peptidoglycan and Either IL-4 or IL-13

    Directory of Open Access Journals (Sweden)

    Ken Fukuda

    2011-01-01

    Conclusions: Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy.

  11. Interactions among cluster-root investment, leaf phosphorus concentration, and relative growth rate in two Lupinus species.

    Science.gov (United States)

    Wang, Xing; Veneklaas, Erik J; Pearse, Stuart J; Lambers, Hans

    2015-09-01

    Cluster-root (CR) formation is a desirable trait to improve phosphorus (P) acquisition as global P resources are dwindling. CRs in some lupine species are suppressed at higher P status. Whether increased growth rate enhances CR formation due to a "dilution" of leaf P concentration is unknown. We investigated interactive effects of leaf P status and relative growth rate (RGR) on CR formation in two Lupinus species, which differ in their CR biomass investment. Variation in RGR was imposed by varying day length. Lupinus albus and L. pilosus were grown hydroponically with KH2PO4 at a day length of 6, 10, or 14 h. We used a slightly higher P supply at longer day lengths to avoid a decline in leaf P concentration, which would induce CRs. Cluster-root percentage, leaf P concentrations, and RGR were determined at 22, 38, and 52 d after sowing. Lupinus species grown at similar root P availability, but with a faster growth rate, as dependent on day length, showed a greater CR percentage. Because our aim to achieve exactly the same leaf P concentrations at different day lengths was only partially achieved, we carried out a multiple regression analysis. This analysis showed the CR percentage was strongly and negatively correlated with plant P status and only marginally and positively correlated with RGR. The two Lupinus species invariably formed fewer cluster roots at higher leaf P status, irrespective of RGR. Differences in RGR or leaf P concentration cannot explain the species-specific variation in cluster-root investment. © 2015 Botanical Society of America.

  12. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...... including puppetry and dance. However, the aesthetics of these traditions vary across cultures and carry different associative and interpretive meanings. Puppetry offers a useful frame for understanding the relationship between abstract and imitative gestures and behavior, and instantiates the complex...

  13. Synergistic Interactions of Neuroprotective and Neurotrophic Factors Against Sleep Deprivation

    Science.gov (United States)

    2017-03-30

    treatment with ADNP-8 or CNTF-11 restored glutathione peroxidase activity in frontal lobe . Furthermore, immunohistochemistry analysis performed...response…………………………….……36 4.2. Endoplasmic reticulum molecular chaperones response…………….……39 4.3. Neuronal cell death in frontal lobe , thalamus and...deprivation…...25 Figure 10: Blood serum corticosterone concentration after 96h sleep deprivation….25 Figure 11: Neuronal cell death in frontal lobe

  14. Synergistic interactions between plant extracts, some antibiotics and ...

    African Journals Online (AJOL)

    user

    rutin solution by methanol, using the spectrophotometer. Determinations were carried out and absorbance was plotted versus concentration. Method: 1 g of defatted air-dried powdered plants was accurately weighed and extracted with methanol (till exhaustion). The methanolic extract was transferred to a measuring flask of ...

  15. Carbon Dioxide and Nisin Act Synergistically on Listeria monocytogenes

    Science.gov (United States)

    Nilsson, Lilian; Chen, Yuhuan; Chikindas, Michael L.; Huss, Hans Henrik; Gram, Lone; Montville, Thomas J.

    2000-01-01

    This paper examines the synergistic action of carbon dioxide and nisin on Listeria monocytogenes Scott A wild-type and nisin-resistant (Nisr) cells grown in broth at 4°C. Carbon dioxide extended the lag phase and decreased the specific growth rate of both strains, but to a greater degree in the Nisr cells. Wild-type cells grown in 100% CO2 were two to five times longer than cells grown in air. Nisin (2.5 μg/ml) did not decrease the viability of Nisr cells but for wild-type cells caused an immediate 2-log reduction of viability when they were grown in air and a 4-log reduction when they were grown in 100% CO2. There was a quantifiable synergistic action between nisin and CO2 in the wild-type strain. The MIC of nisin for the wild-type strain grown in the presence of 2.5 μg of nisin per ml increased from 3.1 to 12.5 μg/ml over 35 days, but this increase was markedly delayed for cultures in CO2. This synergism between nisin and CO2 was examined mechanistically by following the leakage of carboxyfluorescein (CF) from listerial liposomes. Carbon dioxide enhanced nisin-induced CF leakage, indicating that the synergistic action of CO2 and nisin occurs at the cytoplasmic membrane. Liposomes made from cells grown in a CO2 atmosphere were even more sensitive to nisin action. Liposomes made from cells grown at 4°C were dramatically more nisin sensitive than were liposomes derived from cells grown at 30°C. Cells grown in the presence of 100% CO2 and those grown at 4°C had a greater proportion of short-chain fatty acids. The synergistic action of nisin and CO2 is consistent with a model where membrane fluidity plays a role in the efficiency of nisin action. PMID:10653749

  16. No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2003-01-01

    Full Text Available Abstract Background It has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function. In agreement with this hypothesis, recent work has shown a negative correlation between evolutionary rates and the number of protein-protein interactions. However, the extent to which the number of protein-protein interactions influences evolutionary rates remains unclear. Here, we address this question at several different levels of evolutionary relatedness. Results Manually curated data on the number of protein-protein interactions among Saccharomyces cerevisiae proteins was examined for possible correlation with evolutionary rates between S. cerevisiae and Schizosaccharomyces pombe orthologs. Only a very weak negative correlation between the number of interactions and evolutionary rate of a protein was observed. Furthermore, no relationship was found between a more general measure of the evolutionary conservation of S. cerevisiae proteins, based on the taxonomic distribution of their homologs, and the number of protein-protein interactions. However, when the proteins from yeast were assorted into discrete bins according to the number of interactions, it turned out that 6.5% of the proteins with the greatest number of interactions evolved, on average, significantly slower than the rest of the proteins. Comparisons were also performed using protein-protein interaction data obtained with high-throughput analysis of Helicobacter pylori proteins. No convincing relationship between the number of protein-protein interactions and evolutionary rates was detected, either for comparisons of orthologs from two completely sequenced H. pylori strains or for comparisons of H. pylori and Campylobacter jejuni orthologs, even when the proteins were classified into bins by the number of interactions. Conclusion The currently available comparative-genomic data do not

  17. Effect of plasma density on diffusion rates due to wave particle interactions with chorus and plasmaspheric hiss: extreme event analysis

    Directory of Open Access Journals (Sweden)

    A. Sicard-Piet

    2014-08-01

    Full Text Available Wave particle interactions play an important role in controlling the dynamics of the radiation belts. The purpose of this study is to estimate how variations in the plasma density can affect diffusion rates resulting from interactions between chorus waves and plasmaspheric hiss with energetic particles and the resulting evolution of the energetic electron population. We perform a statistical analysis of the electron density derived from the plasma wave experiment on the CRRES satellite for two magnetic local time sectors corresponding to near midnight and near noon. We present the cumulative probability distribution of the electron plasma density for three levels of magnetic activity as measured by Kp. The largest densities are seen near L* = 2.5 while the smallest occur near L* = 6. The broadest distribution, corresponding to the greatest variability, occurs near L* = 4. We calculate diffusion coefficients for plasmaspheric hiss and whistler mode chorus for extreme values of the electron density and estimate the effects on the radiation belts using the Salammbô model. At L* = 4 and L* = 6, in the low density case, using the density from the 5th percentile of the cumulative distribution function, electron energy diffusion by chorus waves is strongest at 2 MeV and increases the flux by up to 3 orders of magnitude over a period of 24 h. In contrast, in the high density case, using the density from the 95th percentile, there is little acceleration at energies above 800 keV at L* = 6, and virtually no acceleration at L* = 4. In this case the strongest energy diffusion occurs at lower energies around 400 keV where the flux at L* = 6 increases 3 orders of magnitude.

  18. Effect of plasma density on diffusion rates due to wave particle interactions with chorus and plasmaspheric hiss: extreme event analysis

    Science.gov (United States)

    Sicard-Piet, A.; Boscher, D.; Horne, R. B.; Meredith, N. P.; Maget, V.

    2014-08-01

    Wave particle interactions play an important role in controlling the dynamics of the radiation belts. The purpose of this study is to estimate how variations in the plasma density can affect diffusion rates resulting from interactions between chorus waves and plasmaspheric hiss with energetic particles and the resulting evolution of the energetic electron population. We perform a statistical analysis of the electron density derived from the plasma wave experiment on the CRRES satellite for two magnetic local time sectors corresponding to near midnight and near noon. We present the cumulative probability distribution of the electron plasma density for three levels of magnetic activity as measured by Kp. The largest densities are seen near L* = 2.5 while the smallest occur near L* = 6. The broadest distribution, corresponding to the greatest variability, occurs near L* = 4. We calculate diffusion coefficients for plasmaspheric hiss and whistler mode chorus for extreme values of the electron density and estimate the effects on the radiation belts using the Salammbô model. At L* = 4 and L* = 6, in the low density case, using the density from the 5th percentile of the cumulative distribution function, electron energy diffusion by chorus waves is strongest at 2 MeV and increases the flux by up to 3 orders of magnitude over a period of 24 h. In contrast, in the high density case, using the density from the 95th percentile, there is little acceleration at energies above 800 keV at L* = 6, and virtually no acceleration at L* = 4. In this case the strongest energy diffusion occurs at lower energies around 400 keV where the flux at L* = 6 increases 3 orders of magnitude.

  19. Synergistic antinociceptive effects of alfentanil and propofol in the formalin test.

    Science.gov (United States)

    Jia, Na; Zuo, Xiaochun; Guo, Chao; Li, Yuwen; Cui, Jia; Zhao, Chao; Cao, Shanshan; Wang, Chao; Li, Ruili; Wu, Yin; Wen, Aidong

    2017-04-01

    The present study was conducted to determine the combined analgesic effect of alfentanil and propofol in the formalin test. Diluted formalin was injected into the dorsal surface of the right hind paw in rats. Nociceptive behavior was determined by counting the number of flinches of the injected paw for 1 h after injection; a reduction in formalin‑induced flinching was interpreted as an antinociceptive effect. Isobolographic analysis was used to determine the type of antinociceptive interaction (additivity, antagonism or synergism). Extracellular signal‑regulated kinase (ERK) and c‑fos protein levels were also detected by western blot analysis to determine the potential mechanisms of the synergistic effect. Alfentanil, propofol or an alfentanil‑propofol combination had an antinociceptive effect in the formalin test. The median effective dose (ED50), value of the individual drug was also obtained. The derived theoretical ED50 for the antinociceptive effect (4.36 mg/kg) was different from the observed experimental ED50 value (2.51 mg/kg). The interaction between alfentanil and propofol that produced the antinociceptive effect was synergistic according to isobolographic analysis. Furthermore, the combination of alfentanil and propofol treatments may produce synergistically antinociceptive effects by inhibiting the phosphorylation of ERK1/2 and decreasing the expression of c‑fos in the spinal cord. These results demonstrated that combined treatment, with alfentanil and propofol, produced synergistic antinociceptive effects in the formalin test and may have therapeutic potential for the treatment of acute pain.

  20. Panobinostat synergistically enhances the cytotoxic effects of cisplatin, doxorubicin or etoposide on high-risk neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Guan Wang

    Full Text Available High-risk neuroblastoma remains a therapeutic challenge with a long-term survival rate of less than 40%. Therefore, new agents are urgently needed to overcome chemotherapy resistance so as to improve the treatment outcome of this deadly disease. Histone deacetylase (HDAC inhibitors (HDACIs represent a novel class of anticancer drugs. Recent studies demonstrated that HDACIs can down-regulate the CHK1 pathway by which cancer cells can develop resistance to conventional chemotherapy drugs. This prompted our hypothesis that combining HDACIs with DNA damaging chemotherapeutic drugs for treating neuroblastoma would result in enhanced anti-tumor activities of these drugs. Treatment of high-risk neuroblastoma cell lines with a novel pan-HDACI, panobinostat (LBH589, resulted in dose-dependent growth arrest and apoptosis in 4 high-risk neuroblastoma cell lines. Further, the combination of panobinostat with cisplatin, doxorubicin, or etoposide resulted in highly synergistic antitumor interactions in the high-risk neuroblastoma cell lines, independent of the sequence of drug administration. This was accompanied by cooperative induction of apoptosis. Furthermore, panobinostat treatment resulted in substantial down-regulation of CHK1 and its downstream pathway and abrogation of the G2 cell cycle checkpoint. Synergistic antitumor interactions were also observed when the DNA damaging agents were combined with a CHK1-specific inhibitor, LY2603618. Contrary to panobinostat treatment, LY2603618 treatments neither resulted in abrogation of the G2 cell cycle checkpoint nor enhanced cisplatin, doxorubicin, or etoposide-induced apoptosis in the high-risk neuroblastoma cells. Surprisingly, LY2603618 treatments caused substantial down-regulation of total CDK1. Despite this discrepancy between panobinostat and LY2603618, our results indicate that suppression of the CHK1 pathway by panobinostat is at least partially responsible for the synergistic antitumor interactions

  1. Synergistic effects in threshold models on networks

    Science.gov (United States)

    Juul, Jonas S.; Porter, Mason A.

    2018-01-01

    Network structure can have a significant impact on the propagation of diseases, memes, and information on social networks. Different types of spreading processes (and other dynamical processes) are affected by network architecture in different ways, and it is important to develop tractable models of spreading processes on networks to explore such issues. In this paper, we incorporate the idea of synergy into a two-state ("active" or "passive") threshold model of social influence on networks. Our model's update rule is deterministic, and the influence of each meme-carrying (i.e., active) neighbor can—depending on a parameter—either be enhanced or inhibited by an amount that depends on the number of active neighbors of a node. Such a synergistic system models social behavior in which the willingness to adopt either accelerates or saturates in a way that depends on the number of neighbors who have adopted that behavior. We illustrate that our model's synergy parameter has a crucial effect on system dynamics, as it determines whether degree-k nodes are possible or impossible to activate. We simulate synergistic meme spreading on both random-graph models and networks constructed from empirical data. Using a heterogeneous mean-field approximation, which we derive under the assumption that a network is locally tree-like, we are able to determine which synergy-parameter values allow degree-k nodes to be activated for many networks and for a broad family of synergistic models.

  2. Synergistic effect of repulsive inhibition in synchronization of excitatory networks

    Science.gov (United States)

    Belykh, Igor; Reimbayev, Reimbay; Zhao, Kun

    2015-06-01

    We show that the addition of pairwise repulsive inhibition to excitatory networks of bursting neurons induces synchrony, in contrast to one's expectations. Through stability analysis, we reveal the mechanism underlying this purely synergistic phenomenon and demonstrate that it originates from the transition between different types of bursting, caused by excitatory-inhibitory synaptic coupling. This effect is generic and observed in different models of bursting neurons and fast synaptic interactions. We also find a universal scaling law for the synchronization stability condition for large networks in terms of the number of excitatory and inhibitory inputs each neuron receives, regardless of the network size and topology. This general law is in sharp contrast with linearly coupled networks with positive (attractive) and negative (repulsive) coupling where the placement and structure of negative connections heavily affect synchronization.

  3. Locating the rate-limiting step for the interaction of hydrogen with Mg(0001) using density-functional theory calculations and rate theory

    DEFF Research Database (Denmark)

    Vegge, Tejs

    2004-01-01

    the nudged elastic band method, and rates of the activated processes are calculated within the harmonic approximation to transition state rate theory, using both classical and quantum partition functions based atomic vibrational frequencies calculated by DFT. The dissociation/recombination of H2 is found......The dissociation of molecular hydrogen on a Mgs0001d surface and the subsequent diffusion of atomic hydrogen into the magnesium substrate is investigated using Density Functional Theory (DFT) calculations and rate theory. The minimum energy path and corresponding transition states are located using...... to be rate-limiting for the ab- and desorption of hydrogen, respectively. Zero-point energy contributions are found to be substantial for the diffusion of atomic hydrogen, but classical rates are still found to be within an order of magnitude at room temperature....

  4. The influence of microbial synergistic and antagonistic effects on the performance of refinery wastewater microbial fuel cells

    Science.gov (United States)

    Guo, Xuan; Zhan, Yali; Chen, Chunmao; Zhao, Lijie; Guo, Shaohui

    2014-04-01

    This study provides a preliminary investigation of the synergistic and antagonistic effects of different microbial strains and their influence on electricity generation and wastewater treatment performances in microbial fuel cells (MFCs). Microbial metabolic characteristics of petroleum hydrocarbon pollutants are studied simultaneously to provide further insight into how microbial synergistic and antagonistic effects influence MFCs. We observed a synergistic effect between Paenibacillus sp. and Deinococcus sp. and an antagonistic effect between Microbacterium sp. and Paenibacillus sp. and Deinococcus sp. The microbial synergistic and antagonistic effects significantly influenced MFC performance directly. The best MFC performance was observed with Paenibacillus sp. + Deinococcus sp. due to their synergistic effect, where the power density output reached 102.93 mW m-3, and the oil removal rate was 85.56 ± 1.10%. However, the performances of MFCs inoculated with Microbacterium sp. were considerably poorer because of its antagonistic effect on the other microbial strains, where the lowest power density output was 24.93 mW m-3, and the oil removal rate was 65.88 ± 1.10%. The degradation characteristics of petroleum hydrocarbons differ between microbial strains; thus, the relative results can provide further insight into how microbial synergistic and antagonistic effects influence MFCs.

  5. Improving Rates of Outpatient Influenza Vaccination Through EHR Portal Messages and Interactive Automated Calls: A Randomized Controlled Trial.

    Science.gov (United States)

    Cutrona, Sarah L; Golden, Jessica G; Goff, Sarah L; Ogarek, Jessica; Barton, Bruce; Fisher, Lloyd; Preusse, Peggy; Sundaresan, Devi; Garber, Lawrence; Mazor, Kathleen M

    2018-01-30

    Patient reminders for influenza vaccination, delivered via electronic health record (EHR) patient portal messages and interactive voice response (IVR) calls, offer an innovative approach to improving patient care. To test the effectiveness of portal and IVR outreach in improving rates of influenza vaccination. Randomized controlled trial of EHR portal messages and IVR calls promoting influenza vaccination. Adults with no documented influenza vaccination 2 months after the start of influenza season (2014-2015). Using a factorial design, we assigned 20,000 patients who were active portal users to one of four study arms: (a) receipt of a portal message promoting influenza vaccines, (b) receipt of IVR call with similar content, (c) both a and b, or (d) neither (usual care). We randomized 10,000 non-portal users to receipt of IVR call or usual care. In all intervention arms, information on pneumococcal vaccination was included if the targeted patient was overdue for pneumococcal vaccine. EHR-documented influenza vaccination during the 2014-2015 influenza season, measured April 2015. Among portal users, 14.0% (702) of those receiving both portal messages and calls, 13.4% (669) of message recipients, 12.8% (642) of call recipients, and 11.6% (582) of those with usual care received vaccines. On multivariable analysis of portal users, those receiving portal messages alone (OR 1.20, 95% CI 1.06-1.35) or IVR calls alone (OR 1.15 95% CI 1.02-1.30) were more likely than usual care recipients to be vaccinated. Those receiving both messages and calls were also more likely than the usual care group to be vaccinated (ad hoc analysis, using a Bonferroni correction: OR 1.29, 97.5% CI 1.13, 1.48). Among non-portal users, 8.5% of call recipients and 8.6% of usual care recipients received influenza vaccines (p = NS). Pneumococcal vaccination rates showed no significant improvement. Our outreach achieved a small but significant improvement in influenza vaccination rates. Registration

  6. Looming signals reveal synergistic principles of multisensory integration.

    Science.gov (United States)

    Cappe, Céline; Thelen, Antonia; Romei, Vincenzo; Thut, Gregor; Murray, Micah M

    2012-01-25

    Multisensory interactions are a fundamental feature of brain organization. Principles governing multisensory processing have been established by varying stimulus location, timing and efficacy independently. Determining whether and how such principles operate when stimuli vary dynamically in their perceived distance (as when looming/receding) provides an assay for synergy among the above principles and also means for linking multisensory interactions between rudimentary stimuli with higher-order signals used for communication and motor planning. Human participants indicated movement of looming or receding versus static stimuli that were visual, auditory, or multisensory combinations while 160-channel EEG was recorded. Multivariate EEG analyses and distributed source estimations were performed. Nonlinear interactions between looming signals were observed at early poststimulus latencies (∼75 ms) in analyses of voltage waveforms, global field power, and source estimations. These looming-specific interactions positively correlated with reaction time facilitation, providing direct links between neural and performance metrics of multisensory integration. Statistical analyses of source estimations identified looming-specific interactions within the right claustrum/insula extending inferiorly into the amygdala and also within the bilateral cuneus extending into the inferior and lateral occipital cortices. Multisensory effects common to all conditions, regardless of perceived distance and congruity, followed (∼115 ms) and manifested as faster transition between temporally stable brain networks (vs summed responses to unisensory conditions). We demonstrate the early-latency, synergistic interplay between existing principles of multisensory interactions. Such findings change the manner in which to model multisensory interactions at neural and behavioral/perceptual levels. We also provide neurophysiologic backing for the notion that looming signals receive preferential

  7. Investigating the synergistic antioxidant effects of some flavonoid and phenolic compounds

    Directory of Open Access Journals (Sweden)

    H. Hajimehdipoor

    2014-04-01

    Full Text Available Phenolic and flavonoid compounds are secondary metabolites of plants which possess various activities such as anti-inflammatory, analgesic, anti-diabetes and anticancer effects. It has been established that these compounds can scavenge free radicals produced in the body. Because of this ability, not only the plants containing phenolic and flavonoid compounds but also, the pure compounds are used in medicinal products for prevention and treatment of many disorders. Considering that the golden aim of the pharmaceutical industries is using the most effective compounds with lower concentrations, determination of the best combination of the compounds with synergistic effects is important. In the present study, synergistic antioxidant effects of four phenolic compounds including caffeic acid, gallic acid, rosmarinic acid, chlorogenic acid and two flavonoids,  rutin and quercetin, have been investigated by FRAP (Ferric Reducing Antioxidant Power method. The synergistic effect was assessed by comparing the experimental antioxidant activity of the mixtures with calculated theoretical values and the interactions of the compounds were determined. The results showed that combination of gallic acid and caffeic acid demonstrated considerable synergistic effects (137.8% while other combinations were less potent. Among examined substances, rutin was the only one which had no effect on the other compounds. The results of ternary combinations of compounds demonstrated antagonistic effects in some cases. This was more considerable in mixture of rutin, caffeic acid, rosmarinic acid (-21.8%, chlorogenic acid, caffeic acid, rosmarinic acid (-20%, rutin, rosmarinic acid, gallic acid (-18.5% and rutin, chlorogenic acid, caffeic acid (-15.8%, while, combination of quercetin, gallic acid, caffeic acid (59.4% and quercetin, gallic acid, rutin (55.2% showed the most synergistic effects. It was concluded that binary and ternary combination of quercetin, rutin, caffeic acid

  8. Synergistic effect of carbon nanotube and clay for improving the flame retardancy of ABS resin

    Energy Technology Data Exchange (ETDEWEB)

    Ma Haiyun [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China); Tong Lifang [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China); Xu Zhongbin [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China); Fang Zhengping [Institute of Polymer Composites, Key Laboratory of Macromolecular Synthesis and Functionalization, Zhejiang University, Hangzhou 310027 (China)

    2007-09-19

    Synergistic effect between multi-walled carbon nanotubes (MWNTs) and clay on improving the flame retardancy of acrylonitrile-butadiene-styrene (ABS) resin was studied. Flammability properties measured by a cone calorimeter revealed that incorporation of clay and MWNTs into ABS resin significantly reduced the peak heat release rate (PHRR) and slowed down the whole combustion process compared to the individually filled system based on clay or MWNTs. The flame retardancy of the ABS/clay/MWNTs nanocomposites was strongly affected by the formation of a network structure. Linear viscoelastic properties of the ABS nanocomposites showed that the coexistence of clay and MWNTs can enhance the network structure which can hinder the movement of polymer chains and improve flame retardancy. From transmission electron microscope analysis, MWNTs were shortened after combustion and there was no significant change in their diameters. For chars of ABS/clay/MWNTs nanocomposites, some MWNTs ran across between clay layers, indicating a strong interaction existed between clay and MWNTs. The existence of clay enhanced the graphitization degree of MWNTs during combustion. Clay can assist the elimination of dislocations and defects and the rearrangement of crystallites. Al{sub 2}O{sub 3}, one of the components of clay, acts as the catalyst of graphitization.

  9. Organisational downsizing and work stress: testing synergistic health effects in employed men and women

    Science.gov (United States)

    Dragano, N.; Verde, P. E.; Siegrist, J.

    2005-01-01

    Study objective: To systematically study the separate and combined effects of organisational downsizing and work related stress on a measure of health in "survivors of layoffs". Design: Using Rothman's approach, separate and combined effects of the two exposures in estimating the risk of poor self rated health (work related symptoms) are analysed in a large sample of male and female employees. Setting: 0.1% cross sectional sample of the German working population. Participants: 12 240 men and 10 319 women, aged 16 to 59 years, surveyed in 1998–1999. Main results: Compared with the reference group, the group of participants who were simultaneously exposed to downsizing and work related stress (effort-reward imbalance) exhibited odds ratios (OR) of three or more work related symptoms that were by far higher (OR 4.41 in men and OR 5.37 in women) than those associated with single exposures. Altogether 21% (men) and 31% (women) of the effect size of the combined exposure was attributable to synergistic interaction. Conclusion: Although reduced health associated with organisational downsizing is partly attributable to an increase in work related stress these findings show an additional synergy effect produced by the combined exposure to both conditions. PMID:16020648

  10. High salinity and UVR synergistically reduce the photosynthetic performance of an intertidal benthic diatom.

    Science.gov (United States)

    Wu, Yaping; Zhu, Yanchen; Xu, Juntian

    2017-09-01

    The intertidal flat is an important intermediate ecosystem characterized by abrupt fluctuations of some environmental factors. As a major contributor to coastal primary productivity, benthic diatoms have to cope up with these fluctuating conditions, such as variations in salinity and light. In this study, we used a typical benthic diatom, Nitzschia sp., to investigate how the photosynthetic performance of a benthic species responded to coupled stresses of high salinity and simulated sunlight. Results showed that their responses were largely dependent on the spectra of light they received. Further, ultraviolet radiation (UVR) interacted with high salinity more effectively than photosynthetically active radiation (PAR), which synergistically reduced the photochemical performance of photosystem II (PSII). The different responses to PAR and UVR were mainly attributed to the repair processes of PSII. Under high salinity, particularly for cells exposed to UVR, the repair rate was significantly lower than those under the control treatment. The present work suggests that UVR, rather than PAR, could be more important in influencing the benthic diatom under high salinity conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates

    Directory of Open Access Journals (Sweden)

    Laura Bedin Denardi

    2015-03-01

    Full Text Available In vitro interaction between tacrolimus (FK506 and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%, followed by that of the combination with ketoconazole (37%, against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%, itraconazole (73%, voriconazole (63% and fluconazole (60%. The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

  12. Synergistic effects of dietary nano selenium and vitamin C on growth, feeding, and physiological parameters of mahseer fish (Tor putitora

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Khan

    2017-02-01

    Full Text Available The current study was conducted to determine the synergistic effects of dietary nano selenium (Nano Se and vitamin C on growth, feeding, and physiological parameters of juvenile mahseer, Tor putitora. L-ascorbyl-2-polyphosphate (APP was used as a source of vitamin C. Four semi-purified experimental diets were prepared. A basal diet kept without the supplementation of any micronutrient and the other three diets were formulated such that three different levels of APP (100, 200, and 300 mg kg−1 were used in combination with a pre-determined dose of Nano Se (0.68 mg kg−1. The results showed that both the micronutrients positively synergized the effects of each other. APP at the rate of 300 mg kg−1 showed strong interaction with Nano Se. The APP300 + Nano Se0.68 mg kg−1 diet supplemented diet significantly decreased (P< 0.05 the feed conversion ratio (FCR while significantly increased (P< 0.05 the weight gain percentage (WG%, feed conversion efficiency (FCE%, specific growth rate (SGR, and serum growth hormone (GH concentration. Similarly, the physiological parameters such as red blood cells count (RBCs, hemoglobin level (Hb, hematocrit value (Hct, and serum lysozyme activity were also significantly increased in group of fish fed diet supplemented with APP100 mg kg−1 in combination with Nano Se0.68 mg kg−1 as compared to the control group. The present results clearly indicated the beneficent synergistic effects of Nano Se and APP in mahseer fish. Moreover, the current finding also supported our hypothesis that Nano Se and APP potentiate positively the effect of each other when both the micronutrients are supplemented together in the same fish feed.

  13. Characteristics and mechanism of the synergistic effect between erosion and corrosion

    Science.gov (United States)

    Xie, Jianhui (Jeffrey)

    The characteristics and mechanism of synergistic effect between the erosion and corrosion were investigated by means of erosion and corrosion testing, electrochemical measurements and microstrain measurement by XRD broadening. The investigations were carried out on heat-treated (as-received, annealed, quenched and tempered) AISI 52100 and AISI 1020 steels eroded with varying amounts of erodent (10g, 50g and 100g SiC particles) and/or at varying erosion angles (30°, 45° and 60°). The variation of selected electrochemical parameters i.e. open-circuit potential, linear polarization and polarization curves, corrosion potential, polarization resistance and calculated corrosion rate, was measured as a function of the amount of erodent, erosion angle and heat treatment. A synergistic effect was shown to exist between erosion and corrosion, i.e. the material loss due to the combined erosion-corrosion is much greater than the summation of those components due to erosion and corrosion separately. Synergistic effect between erosion and corrosion for AISI 52100 steel contributes 80% of the total material loss whereas that for AISI 1020 steel contributes 60% of the total material loss. The synergistic effect is a result of the accelerated corrosion rate, whereby erosion both thermodynamically and kinetically facilitates the corrosion reaction. As a result of the impacting erodent, the open-circuit potential and corrosion potential decreased negatively, the polarization resistance increased positively, and thus the corrosion rate is correspondingly increased. In addition to the effect of the amount of erodent, the erosion angle also affects the electrochemical behavior. There is a minimum negative open-circuit potential and corrosion potential, a minimum polarization resistance and a maximum corrosion rate at an erosion angle of 45°. The microstrain induced in the steels due to impact was determined using XRD peak broadening. The microstrain increases with increasing amount

  14. High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

    Directory of Open Access Journals (Sweden)

    Morgan A Wambaugh

    2017-06-01

    Full Text Available Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M. O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT. We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional

  15. High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

    Science.gov (United States)

    Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

    2017-06-01

    Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that

  16. Investigating the Synergistic Effects of Combined Modified Alginates on Macrophage Phenotype

    OpenAIRE

    Hannah C. Bygd; Bratlie, Kaitlin M.

    2016-01-01

    Understanding macrophage responses to biomaterials is crucial to the success of implanted medical devices, tissue engineering scaffolds, and drug delivery vehicles. Cellular responses to materials may depend synergistically on multiple surface chemistries, due to the polyvalent nature of cell–ligand interactions. Previous work in our lab found that different surface functionalities of chemically modified alginate could sway macrophage phenotype toward either the pro-inflammatory or pro-angiog...

  17. Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination

    OpenAIRE

    Anwesa Bag; Rabi Ranjan Chattopadhyay

    2015-01-01

    The present study was carried out to evaluate the possible synergistic interactions on antibacterial and antioxidant efficacy of essential oils of some selected spices and herbs [bay leaf, black pepper, coriander (seed and leaf), cumin, garlic, ginger, mustard, onion and turmeric] in combination. Antibacterial combination effect was evaluated against six important food-borne bacteria (Bacillus cereus, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Salm...

  18. Synergistic effect of pasireotide and teriflunomide in carcinoids in vitro.

    Science.gov (United States)

    Somnay, Yash; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2013-01-01

    Somatostatin (SST) analogs are mainstay for controlling tumor proliferation and hormone secretion in carcinoid patients. Recent data suggest that extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation may potentiate the anti-tumor effects of SST analogs in carcinoids. Additionally, ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in carcinoids. Thus, Raf-1/MEK/ERK1/2 pathway activating drugs may be synergistic with SST analogs such as pasireotide (SOM230), which may be more effective than others in its class given its elevated receptor affinity and broader binding spectrum. Here, we investigate the effects of SOM230 in combination with teriflunomide (TFN), a Raf-1 activator, in a human carcinoid cell line. Human pancreatic carcinoid cells (BON) were incubated in TFN, SOM230 or a combination. Cell proliferation was measured using a rapid colorimetric assay. Western analysis was performed to analyze expression levels of achaete-scute complex-like 1 (ASCL1), chromogranin A (CgA), phosphorylated and total ERK1/2, and markers for apoptosis. Combination treatment with SOM230 and TFN reduced cell growth beyond the additive effect of either drug alone. Combination indices (CI) fell below 1, thus quantifiably verifying synergy between both drugs as per the Chou-Talalay CI scale. Combined treatment also reduced ASCL1 and CgA expression beyond the additive effect of either drug alone. Furthermore, it increased levels of phosphorylated ERK1/2, cleaved poly(ADP)-ribose polymerase and caspase-3, and reduced levels of anti-apoptotic biomarkers. Elevated phosphorylated ERK1/2 expression following combination therapy may underlie the synergistic interaction between the two drugs. Since efficacy is achieved at lower doses, combination therapy may palliate symptoms at low toxicity levels. Because each drug has already been evaluated in clinical trials, combinatorial drug trials are warranted. Copyright © 2012 S. Karger AG, Basel.

  19. Growth rate variation among passerine species in tropical and temperate sites: an antagonistic interaction between parental food provisioning and nest predation risk

    Science.gov (United States)

    Martin, Thomas E.; Llyod, Penn; Bosque, Carlos; Barton, Daniel C.; Biancucci, Atilio L.; Cheng, Yi-Ru; Ton, Riccardo

    2011-01-01

    Causes of interspecific variation in growth rates within and among geographic regions remain poorly understood. Passerine birds represent an intriguing case because differing theories yield the possibility of an antagonistic interaction between nest predation risk and food delivery rates on evolution of growth rates. We test this possibility among 64 Passerine species studied on three continents, including tropical and north and south temperate latitudes. Growth rates increased strongly with nestling predation rates within, but not between, sites. The importance of nest predation was further emphasized by revealing hidden allometric scaling effects. Nestling predation risk also was associated with reduced total feeding rates and per-nestling feeding rates within each site. Consequently, faster growth rates were associated with decreased per-nestling food delivery rates across species, both within and among regions. These relationships suggest that Passerines can evolve growth strategies in response to predation risk whereby food resources are not the primary limit on growth rate differences among species. In contrast, reaction norms of growth rate relative to brood size suggest that food may limit growth rates within species in temperate, but not tropical, regions. Results here provide new insight into evolution of growth strategies relative to predation risk and food within and among species.

  20. Protein interacting with C kinase 1 (PICK1) reduces reinsertion rates of interaction partners sorted to Rab11-dependent slow recycling pathway

    DEFF Research Database (Denmark)

    Madsen, Kenneth Lindegaard; Thorsen, Thor Seneca; Rahbek-Clemmensen, Troels

    2012-01-01

    The scaffolding protein PICK1 (protein interacting with C kinase 1) contains an N-terminal PSD-95/Discs large/ZO-1 (PDZ) domain and a central lipid-binding Bin/amphiphysin/Rvs (BAR) domain. PICK1 is thought to regulate trafficking of its PDZ binding partners but different and even opposing...

  1. Culture and neuroscience: additive or synergistic?

    Science.gov (United States)

    Dapretto, Mirella; Iacoboni, Marco

    2010-01-01

    The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cognitive neuroscience inform the investigation of the role of cultural experience in shaping the brain. Drawing on well-established methodologies from cross-cultural psychology and cognitive neuroscience, we outline a set of guidelines for CN, evaluate 17 CN studies in terms of these guidelines, and provide a summary table of our results. We conclude that the combination of culture and neuroscience is both additive and synergistic; while some CN methodologies and findings will represent the direct union of information from parent fields, CN studies employing the methodological rigor required by this logistically challenging new field have the potential to transform existing methodologies and produce unique findings. PMID:20083533

  2. Hemolytic interactions of Dermatophilus congolensis.

    Science.gov (United States)

    Skalka, B; Pospísil, L

    1992-03-01

    The strains of Dermatophilus congolensis grew on blood agar with washed sheep erythrocytes with marked total hemolysis. In testing for hemolytic interactions they gave a significant synergistic effect of a characteristic shape with Rhodococcus equi and Streptococcus agalactiae, whereas with Staphylococcus aureus producing beta hemolysin and with Staphylococcus aureus producing delta hemolysin a simultaneous synergistic as well as antagonistic effect were observed. First of all a conspicuous inhibition of in the beta hemolysin zone began and then the hemolytic effect of D. congolensis was enhanced. A similar double reaction was also observed with Listeria ivanovii. With delta hemolysin there was an inhibition of the hemolytic effect of D. congolensis and at the same time a synergistic effect could be observed. Also D. congolensis gave a weak synergistic effect with Micrococcus lylae and Listeria monocytogenes, and a further weak antagonistic effect with alpha hemolysin of Staphylococcus aureus, Staphylococcus hyicus, Staphylococcus chromogenes and Micrococcus luteus. No interaction of D. congolensis was established with Corynebacterium pseudotuberculosis.

  3. Gene-environment interaction in teacher-rated internalizing and externalizing problem behavior in 7- to 12-year-old twins.

    Science.gov (United States)

    Lamb, Diane J; Middeldorp, Christel M; Van Beijsterveldt, Catarina E M; Boomsma, Dorret I

    2012-08-01

    Internalizing and externalizing problem behavior at school can have major consequences for a child and is predictive for disorders later in life. Teacher ratings are important to assess internalizing and externalizing problems at school. Genetic epidemiological studies on teacher-rated problem behavior are relatively scarce and the reported heritability estimates differ widely. A unique feature of teacher ratings of twins is that some pairs are rated by different and others are rated by the same teacher. This offers the opportunity to assess gene-environment interaction. Teacher ratings of 3,502 7-year-old, 3,134 10-year-old and 2,193 12-year-old twin pairs were analyzed with structural equation modeling. About 60% of the twin pairs were rated by the same teacher. Twin correlations and the heritability of internalizing and externalizing behavior were estimated, separately for pairs rated by the same and different teachers. Socioeconomic status and externalizing behavior at age 3 were included as covariates. Twin correlations and heritability estimates were higher when twin pairs were in the same class and rated by the same teacher than when pairs were rated by different teachers. These differences could not be explained by twin confusion or rater bias. When twins were rated by the same teacher, heritability estimates were about 70% for internalizing problems and around 80% in boys and 70% in girls for externalizing problems. When twins were rated by different teachers, heritability estimates for internalizing problems were around 30% and for externalizing problems around 50%. Exposure to different teachers during childhood may affect the heritability of internalizing and externalizing behavior at school. This finding points to gene-environment interaction and is important for the understanding of childhood problem behavior. In addition, it could imply an opportunity for interventions at school. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012

  4. Incidence rate and pattern of clinically relevant potential drug-drug interactions in a large outpatient population of a developing country

    NARCIS (Netherlands)

    Nabovati, Ehsan; Vakili-Arki, Hasan; Taherzadeh, Zhila; Saberi, Mohammad Reza; Abu-Hanna, Ameen; Eslami, Saeid

    2016-01-01

    The objective of this study was to determine incidence rate, type, and pattern of clinically relevant potential drug-drug interactions (pDDIs) in a large outpatient population of a developing country. A retrospective, descriptive cross-sectional study was conducted on outpatients' prescriptions in

  5. Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 π0 detector

    Science.gov (United States)

    Abe, K.; Adam, J.; Aihara, H.; Andreopoulos, C.; Aoki, S.; Ariga, A.; Assylbekov, S.; Autiero, D.; Barbi, M.; Barker, G. J.; Barr, G.; Bartet-Friburg, P.; Bass, M.; Batkiewicz, M.; Bay, F.; Berardi, V.; Berger, B. E.; Berkman, S.; Bhadra, S.; Blaszczyk, F. d. M.; Blondel, A.; Bolognesi, S.; Bordoni, S.; Boyd, S. B.; Brailsford, D.; Bravar, A.; Bronner, C.; Buchanan, N.; Calland, R. G.; Caravaca Rodríguez, J.; Cartwright, S. L.; Castillo, R.; Catanesi, M. G.; Cervera, A.; Cherdack, D.; Chikuma, N.; Christodoulou, G.; Clifton, A.; Coleman, J.; Coleman, S. J.; Collazuol, G.; Connolly, K.; Cremonesi, L.; Dabrowska, A.; Das, R.; Davis, S.; de Perio, P.; De Rosa, G.; Dealtry, T.; Dennis, S. R.; Densham, C.; Dewhurst, D.; Di Lodovico, F.; Di Luise, S.; Dolan, S.; Drapier, O.; Duffy, K.; Dumarchez, J.; Dytman, S.; Dziewiecki, M.; Emery-Schrenk, S.; Ereditato, A.; Escudero, L.; Feusels, T.; Finch, A. J.; Fiorentini, G. A.; Friend, M.; Fujii, Y.; Fukuda, Y.; Furmanski, A. P.; Galymov, V.; Garcia, A.; Giffin, S.; Giganti, C.; Gilje, K.; Goeldi, D.; Golan, T.; Gonin, M.; Grant, N.; Gudin, D.; Hadley, D. R.; Haegel, L.; Haesler, A.; Haigh, M. D.; Hamilton, P.; Hansen, D.; Hara, T.; Hartz, M.; Hasegawa, T.; Hastings, N. C.; Hayashino, T.; Hayato, Y.; Helmer, R. L.; Hierholzer, M.; Hignight, J.; Hillairet, A.; Himmel, A.; Hiraki, T.; Hirota, S.; Holeczek, J.; Horikawa, S.; Hosomi, F.; Huang, K.; Ichikawa, A. K.; Ieki, K.; Ieva, M.; Ikeda, M.; Imber, J.; Insler, J.; Irvine, T. J.; Ishida, T.; Ishii, T.; Iwai, E.; Iwamoto, K.; Iyogi, K.; Izmaylov, A.; Jacob, A.; Jamieson, B.; Jiang, M.; Johnson, S.; Jo, J. H.; Jonsson, P.; Jung, C. K.; Kabirnezhad, M.; Kaboth, A. C.; Kajita, T.; Kakuno, H.; Kameda, J.; Kanazawa, Y.; Karlen, D.; Karpikov, I.; Katori, T.; Kearns, E.; Khabibullin, M.; Khotjantsev, A.; Kielczewska, D.; Kikawa, T.; Kilinski, A.; Kim, J.; King, S.; Kisiel, J.; Kitching, P.; Kobayashi, T.; Koch, L.; Koga, T.; Kolaceke, A.; Konaka, A.; Kopylov, A.; Kormos, L. L.; Korzenev, A.; Koshio, Y.; Kropp, W.; Kubo, H.; Kudenko, Y.; Kurjata, R.; Kutter, T.; Lagoda, J.; Lamont, I.; Larkin, E.; Laveder, M.; Lawe, M.; Lazos, M.; Lindner, T.; Lister, C.; Litchfield, R. P.; Longhin, A.; Lopez, J. P.; Ludovici, L.; Magaletti, L.; Mahn, K.; Malek, M.; Manly, S.; Marino, A. D.; Marteau, J.; Martin, J. F.; Martins, P.; Martynenko, S.; Maruyama, T.; Matveev, V.; Mavrokoridis, K.; Mazzucato, E.; McCarthy, M.; McCauley, N.; McFarland, K. S.; McGrew, C.; Mefodiev, A.; Metelko, C.; Mezzetto, M.; Mijakowski, P.; Miller, C. A.; Minamino, A.; Mineev, O.; Mine, S.; Missert, A.; Miura, M.; Moriyama, S.; Mueller, Th. A.; Murakami, A.; Murdoch, M.; Murphy, S.; Myslik, J.; Nakadaira, T.; Nakahata, M.; Nakamura, K. G.; Nakamura, K.; Nakayama, S.; Nakaya, T.; Nakayoshi, K.; Nantais, C.; Nielsen, C.; Nirkko, M.; Nishikawa, K.; Nishimura, Y.; Nowak, J.; O'Keeffe, H. M.; Ohta, R.; Okumura, K.; Okusawa, T.; Oryszczak, W.; Oser, S. M.; Ovsyannikova, T.; Owen, R. A.; Oyama, Y.; Palladino, V.; Palomino, J. L.; Paolone, V.; Payne, D.; Perevozchikov, O.; Perkin, J. D.; Petrov, Y.; Pickard, L.; Pinzon Guerra, E. S.; Pistillo, C.; Plonski, P.; Poplawska, E.; Popov, B.; Posiadala-Zezula, M.; Poutissou, J.-M.; Poutissou, R.; Przewlocki, P.; Quilain, B.; Radicioni, E.; Ratoff, P. N.; Ravonel, M.; Rayner, M. A. M.; Redij, A.; Reeves, M.; Reinherz-Aronis, E.; Riccio, C.; Rodrigues, P. A.; Rojas, P.; Rondio, E.; Roth, S.; Rubbia, A.; Ruterbories, D.; Rychter, A.; Sacco, R.; Sakashita, K.; Sánchez, F.; Sato, F.; Scantamburlo, E.; Scholberg, K.; Schoppmann, S.; Schwehr, J. D.; Scott, M.; Seiya, Y.; Sekiguchi, T.; Sekiya, H.; Sgalaberna, D.; Shah, R.; Shaikhiev, A.; Shaker, F.; Shaw, D.; Shiozawa, M.; Short, S.; Shustrov, Y.; Sinclair, P.; Smith, B.; Smy, M.; Sobczyk, J. T.; Sobel, H.; Sorel, M.; Southwell, L.; Stamoulis, P.; Steinmann, J.; Suda, Y.; Suzuki, A.; Suzuki, K.; Suzuki, S. Y.; Suzuki, Y.; Tacik, R.; Tada, M.; Takahashi, S.; Takeda, A.; Takeuchi, Y.; Tanaka, H. K.; Tanaka, H. A.; Tanaka, M. M.; Terhorst, D.; Terri, R.; Thompson, L. F.; Thorley, A.; Tobayama, S.; Toki, W.; Tomura, T.; Touramanis, C.; Tsukamoto, T.; Tzanov, M.; Uchida, Y.; Vacheret, A.; Vagins, M.; Vasseur, G.; Wachala, T.; Wakamatsu, K.; Walter, C. W.; Wark, D.; Warzycha, W.; Wascko, M. O.; Weber, A.; Wendell, R.; Wilkes, R. J.; Wilking, M. J.; Wilkinson, C.; Williamson, Z.; Wilson, J. R.; Wilson, R. J.; Wongjirad, T.; Yamada, Y.; Yamamoto, K.; Yanagisawa, C.; Yano, T.; Yen, S.; Yershov, N.; Yokoyama, M.; Yoo, J.; Yoshida, K.; Yuan, T.; Yu, M.; Zalewska, A.; Zalipska, J.; Zambelli, L.; Zaremba, K.; Ziembicki, M.; Zimmerman, E. D.; Zito, M.; Żmuda, J.; T2K Collaboration

    2015-06-01

    This paper presents a measurement of the charged current interaction rate of the electron neutrino beam component of the beam above 1.5 GeV using the large fiducial mass of the T2K π0 detector. The predominant portion of the νe flux (˜85 % ) at these energies comes from kaon decays. The measured ratio of the observed beam interaction rate to the predicted rate in the detector with water targets filled is 0.89 ±0.08 (stat)±0.11 (sys) , and with the water targets emptied is 0.90 ±0.09 (stat)±0.13 (sys) . The ratio obtained for the interactions on water only from an event subtraction method is 0.87 ±0.33 (stat)±0.21 (sys) . This is the first measurement of the interaction rate of electron neutrinos on water, which is particularly of interest to experiments with water Cherenkov detectors.

  6. Synergistic effects of amides from two piper species on generalist and specialist herbivores.

    Science.gov (United States)

    Richards, Lora A; Dyer, Lee A; Smilanich, Angela M; Dodson, Craig D

    2010-10-01

    Plants use a diverse mix of defenses against herbivores, including multiple secondary metabolites, which often affect herbivores synergistically. Chemical defenses also can affect natural enemies of herbivores via limiting herbivore populations or by affecting herbivore resistance to parasitoids. In this study, we performed feeding experiments to examine the synergistic effects of imides and amides (hereafter "amides") from Piper cenocladum and P. imperiale on specialist (Eois nympha, Geometridae) and generalist (Spodoptera frugiperda, Noctuidae) lepidopteran larvae. Each Piper species has three unique amides, and in each experiment, larvae were fed diets containing different concentrations of single amides or combinations of the three. The amides from P. imperiale had negative synergistic effects on generalist survival and specialist pupal mass, but had no effect on specialist survival. Piper cenocladum amides also acted synergistically to increase mortality caused by parasitoids, and the direct negative effects of mixtures on parasitoid resistance and pupal mass were stronger than indirect effects via changes in growth rate and approximate digestibility. Our results are consistent with plant defense theory that predicts different effects of plant chemistry on generalist versus adapted specialist herbivores. The toxicity of Piper amide mixtures to generalist herbivores are standard bottom-up effects, while specialists experienced the top-down mediated effect of mixtures causing reduced parasitoid resistance and associated decreases in pupal mass.

  7. Relating trait self-control and forgiveness among prosocials and proselfs: A test of compensatory and synergistic models

    NARCIS (Netherlands)

    Balliet, D.P.; Li, N.P.; Joireman, J.A.

    2011-01-01

    The present research tested 2 competing models specifying how 2 traits (concern with the well-being of others and self-control) interact to predict forgiveness. According to the compensatory model, forgiveness requires being high on either trait; according to the synergistic model, forgiveness

  8. Rhinovirus-bacteria coexposure synergistically induces CCL20 production from human bronchial epithelial cells.

    Science.gov (United States)

    Maciejewski, Barbara A; Jamieson, Kyla C; Arnason, Jason W; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L; Leigh, Richard; Proud, David

    2017-05-01

    Exacerbations of chronic obstructive pulmonary disease are triggered by viral or bacterial pathogens, with human rhinovirus (HRV) and nontypeable Hemophilus influenzae (NTHI) among the most commonly detected pathogens. Patients who suffer from concomitant viral and bacterial infection have more severe exacerbations. The airway epithelial cell is the initial site of viral and bacterial interactions, and CCL20 is an epithelial chemokine that attracts immature dendritic cells to the airways and can act as an antimicrobial. As such, it contributes to innate and adaptive immune responses to infection. We used primary cultures of human bronchial epithelial cells and the BEAS-2B cell line to examine the effects of bacterial-viral coexposure, as well as each stimulus alone, on epithelial expression of CXCL8 and, in particular, CCL20. HRV-bacterial coexposure induced synergistic production of CXCL8 and CCL20 compared with the sum of each stimulus alone. Synergistic induction of CCL20 did not require viral replication and occurred with two different HRV serotypes that use different viral receptors. Synergy was also seen with either NTHI or Pseudomonas aeruginosa Synergistic induction of CCL20 was transcriptionally regulated. Although NF-κB was required for transcription, it did not regulate synergy, but NF-IL-6 did appear to contribute. Among MAPK inhibitors studied, neither SB203580 nor PD98059 had any effect on synergy, whereas U0126 prevented synergistic induction of CCL20 by HRV and bacteria, apparently via "off-target" effects. Thus bacterial-viral coexposure synergistically increases innate immune responses compared with individual infections. We speculate that this increased inflammatory response leads to worse clinical outcomes. Copyright © 2017 the American Physiological Society.

  9. Synergistic Effects of Reserve and Adaptive Personality in Multiple Sclerosis.

    Science.gov (United States)

    Roy, Shumita; Schwartz, Carolyn E; Duberstein, Paul; Dwyer, Michael G; Zivadinov, Robert; Bergsland, Niels; Powell, Victoria; Weinstock-Guttman, Bianca; Benedict, Ralph H B

    2016-10-01

    Cognitive reserve moderates the effects of gray matter (GM) atrophy on cognitive function in neurological disease. Broadly speaking, Reserve explains how persons maintain function in the face of cerebral injury in cognitive and other functional domains (e.g., physical, social). Personality, as operationalized by the Five Factor Model (FFM), is also implicated as a moderator of this relationship. It is conceivable that these protective mechanisms are related. Prior studies suggest links between Reserve and personality, but the degree to which these constructs overlap and buffer the clinical effects of neuropathology is unclear. We evaluated Reserve and FFM traits-Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness-in a cohort of 67 multiple sclerosis (MS) patients. We also examined the extent to which FFM traits and aspects of Reserve interact in predicting cognitive processing speed. Retrospectively reported educational/occupational achievement was associated with higher Openness, and childhood social engagement was associated with higher Extraversion, Agreeableness, and Conscientiousness. Current involvement in exercise activities and social activities was associated with Extraversion, current involvement in hobbies was associated with Neuroticism, and current receptive behaviors were associated with Agreeableness and Conscientiousness. When tested as predictors, Conscientiousness and childhood enrichment activities interacted in predicting cognitive processing speed after accounting for age, disease duration, disability, and GM volume. Childhood enrichment activities and Conscientiousness have a synergistic effect on cognitive processing speed. Current findings have implications for using psychological interventions to foster both Reserve and adaptive personality characteristics to stave off clinical symptoms in MS. (JINS, 2016, 22, 920-927).

  10. Synergistic effects of IL-7 and IL-12 on human T cell activation.

    Science.gov (United States)

    Mehrotra, P T; Grant, A J; Siegel, J P

    1995-05-15

    We have previously demonstrated that human rIL-12 alone can augment the development of cytotoxic activity in stimulated CD8+ T cells. The present study was undertaken to examine the interactions of rIL-7 and rIL-12 on human peripheral blood T cell activation and CTL differentiation. Purified T lymphocytes were pulsed overnight with immobilized alpha-CD3 and then cultured for 3 additional days with IL-7 and/or IL-12. The combination of IL-7 and IL-12 synergistically enhanced the proliferation of either fresh CD3+ T cells or an IL-2-dependent CD4+ T cell line, Kit-225-K6. This synergy was seen on both subsets of T cells; however, CD8+ T cells were usually more responsive to IL-7 and IL-12 at lower concentrations than were CD4+ T cells. Furthermore, these cytokines additively/synergistically augmented the cytotoxic activity of CD8+ T cells. Abs to IL-2 and IL-2R alpha blocked the synergistic effect on proliferation of CD4+ T cells, but had a minimal effect on the synergistic response of the proliferative and cytotoxic activity of CD8+ T cells. Examination of the effects of IL-7 and IL-12 on the expression of IL-12 receptor on T cells revealed an increase in the subunit of IL-12R by IL-7 as determined by flow cytometric analysis. We analyzed the effects on IFN-gamma production by CD8+ T cells and found that IL-7 alone did not induce detectable levels of IFN-gamma production but together with IL-12 it synergistically enhanced the production of IFN-gamma. We also found that IFN-gamma was probably not required for enhanced CTL activity of CD8+ T cells, because Ab to human IFN-gamma did not block additive/synergistic effects of either cytokine. The synergistic stimulatory activity of IL-7 and IL-12 may be of significance in vivo and may provide an alternative mechanism of stimulating T cells for use in immunotherapy.

  11. Supervising Staff in Student Affairs: Exploration of the Synergistic Approach.

    Science.gov (United States)

    Saunders, Sue A.; Cooper, Diane L.; Winston, Roger B., Jr.; Chernow, Erin

    2000-01-01

    Describes the development andexplores the validity of the Synergistic Supervision Scale (SSS), which measures the extent to which staff perceive that their supervisor focuses on the advancement of the institutional mission and the personal and professional advancement of staff. Results indicate that synergistic supervision seems to be a valid…

  12. Synergistic effects of sodium lauroyl sarcosinate and glutamic acid in inhibition assembly against copper corrosion in acidic solution

    Science.gov (United States)

    Yu, Yinzhe; Zhang, Daquan; Zeng, Huijing; Xie, Bin; Gao, Lixin; Lin, Tong

    2015-11-01

    A self-assembled multilayer (SAM) from sodium lauroyl sarcosinate (SLS) and glutamic acid (GLU) is formed on copper surface. Its inhibition ability against copper corrosion is examined by electrochemical analysis and weight loss test. In comparison to SAM formed by just SLS or GLU, a synergistic effect is observed when the coexistence of SLS and GLU in SAM. The SLS/GLU SAM has an acicular multilayer structure, and SAM prepared under the condition of 5 mM SLS and 1 mM GLU shows the best protection efficiency. PM6 calculation reveals that the synergistic effect stems from interactions between SLS, GLU and cupric ions.

  13. Separation and recovery of heavy metals from waste water using synergistic solvent extraction

    Science.gov (United States)

    Li, Yan; Yang, Limei; Xu, Zheng; Sun, Qi

    2017-01-01

    Heavy metal wastewater pollution is one of the three major water pollutions in the world. The zinc hydrometallurgy smelting process usually discharge large quantities of heavy metal wastewater into the environment. In this paper, a synergistic solvent extraction process has been developed to recover copper, nickel, zinc and cadmium respectively from calcium and magnesium. The synergistic organic system contained 0.50 M Versatic 10 and 0.5 M Mextral 984H in DT100. Adjusting pH to 2.0 at 40 °C, the copper will be extracted preferentially with the extraction rate more than 99%. Continuing to adjust pH to 4.2 at 40 °C, the nickel will be extracted secondly with an extraction rate more than 98%; the zinc and cadmium in raffinate could be extracted separately while pH is about 6.5.

  14. Interaction of heat production, strain rate and stress power in a plastically deforming body under tensile test

    Science.gov (United States)

    Paglietti, A.

    1982-01-01

    At high strain rates the heat produced by plastic deformation can give rise to a rate dependent response even if the material has rate independent constitutive equations. This effect has to be evaluated when interpreting a material test, or else it could erroneously be ascribed to viscosity. A general thermodynamic theory of tensile testing of elastic-plastic materials is given in this paper; it is valid for large strain at finite strain rates. It enables discovery of the parameters governing the thermodynamic strain rate effect, provides a method for proper interpretation of the results of the tests of dynamic plasticity, and suggests a way of planning experiments in order to detect the real contribution of viscosity.

  15. A drop in the pond: the effect of rapid mass-loss on the dynamics and interaction rate of collisionless particles

    Science.gov (United States)

    Penoyre, Zephyr; Haiman, Zoltán

    2018-01-01

    In symmetric gravitating systems experiencing rapid mass-loss, particle orbits change almost instantaneously, which can lead to the development of a sharply contoured density profile, including singular caustics for collisionless systems. This framework can be used to model a variety of dynamical systems, such as accretion discs following a massive black hole merger and dwarf galaxies following violent early star formation feedback. Particle interactions in the high-density peaks seem a promising source of observable signatures of these mass-loss events (i.e. a possible EM counterpart for black hole mergers or strong gamma-ray emission from dark matter annihilation around young galaxies), because the interaction rate depends on the square of the density. We study post-mass-loss density profiles, both analytic and numerical, in idealized cases and present arguments and methods to extend to any general system. An analytic derivation is presented for particles on Keplerian orbits responding to a drop in the central mass. We argue that this case, with initially circular orbits, gives the most sharply contoured profile possible. We find that despite the presence of a set of singular caustics, the total particle interaction rate is reduced compared to the unperturbed system; this is a result of the overall expansion of the system dominating over the steep caustics. Finally, we argue that this result holds more generally, and the loss of central mass decreases the particle interaction rate in any physical system.

  16. Can mindful parenting be observed? Relations between observational ratings of mother-youth interactions and mothers' self-report of mindful parenting.

    Science.gov (United States)

    Duncan, Larissa G; Coatsworth, J Douglas; Gayles, Jochebed G; Geier, Mary H; Greenberg, Mark T

    2015-04-01

    Research on mindful parenting, an extension of mindfulness to the interpersonal domain of parent-child relationships, has been limited by its reliance on self-report assessment. The current study is the first to examine whether observational indices of parent-youth interactions differentiate between high and low levels of self-reported mindful parenting. The Iowa Family Interaction Rating Scales (IFIRS) were used to code interactions between mothers and their 7th grade youth. Mothers drawn from the top and bottom quartiles (n = 375) of a larger distribution of self-reported interpersonal mindfulness in parenting (N = 804) represented clearly defined high- and low-mindful parenting groups. Discriminant function analysis (DFA) was used to analyze how well 6 composite IFIRS observational rating variables (e.g., parental warmth, consistent discipline) discriminated between high and low self-reports of mindful parenting. DFA results were cross-validated, with statistically significant canonical correlations found for both subsamples (p mindful parenting and the observational ratings was also provided through hierarchical regression analyses conducted with a continuous predictor of mindful parenting using the full sample. Thus, the present study provides preliminary evidence for a link between self-reported mindful parenting and observed interactions between parents and youth. (c) 2015 APA, all rights reserved).

  17. Can Mindful Parenting Be Observed? Relations between Observational Ratings of Mother-Youth Interactions and Mothers’ Self-Report Mindful Parenting

    Science.gov (United States)

    Duncan, Larissa G.; Coatsworth, J. Douglas; Gayles, Jochebed G.; Geier, Mary H.; Greenberg, Mark T.

    2015-01-01

    Research on mindful parenting, an extension of mindfulness to the interpersonal domain of parent-child relationships, has been limited by its reliance on self-report assessment. The current study is the first to examine whether observational indices of parent-youth interactions differentiate between high and low levels of self-reported mindful parenting. The Iowa Family Interaction Rating Scales (IFIRS) were used to code interactions between mothers and their 7th grade youth. Mothers drawn from the top and bottom quartiles (n = 375) of a larger distribution of self-reported interpersonal mindfulness in parenting (N = 804) represented clearly defined high and low mindful parenting groups. Discriminant function analysis (DFA) was used to analyze how well six composite IFIRS observational rating variables (e.g., parental warmth, consistent discipline) discriminated between high and low self-reports of mindful parenting. DFA results were cross-validated, with statistically significant canonical correlations found for both subsamples (p parenting and the observational ratings was also provided through hierarchical regression analyses conducted with a continuous predictor of mindful parenting using the full sample. Thus, the present study provides preliminary evidence for a link between self-reported mindful parenting and observed interactions between parents and youth. PMID:25844494

  18. Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine

    OpenAIRE

    Michael Du; Linna Zhang; Scorsone, Kathleen A.; Woodfield, Sarah E.; Zage, Peter E.

    2016-01-01

    Children with aggressive neural tumors have poor survival rates and novel therapies are needed. Previous studies have identified nifurtimox and buthionine sulfoximine (BSO) as effective agents in children with neuroblastoma and medulloblastoma. We hypothesized that nifurtimox would be effective against other neural tumor cells and would be synergistic with BSO. We determined neural tumor cell viability before and after treatment with nifurtimox using MTT assays. Assays for DNA ladder formatio...

  19. A coarse-grained model for synergistic action of multiple enzymes on cellulose

    Directory of Open Access Journals (Sweden)

    Asztalos Andrea

    2012-08-01

    Full Text Available Abstract Background Degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates. Results We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose. Conclusions Our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures

  20. Interactions between plant size and canopy openness influence vital rates and life-history tradeoffs in two neotropical understory herbs.

    Science.gov (United States)

    Westerband, Andrea C; Horvitz, Carol C

    2015-08-01

    • For tropical forest understory plants, the ability to grow, survive, and reproduce is limited by the availability of light. The extent to which reproduction incurs a survival or growth cost may change with light availability, plant size, and adaptation to shade, and may vary among similar species.• We estimated size-specific rates of growth, survival, and reproduction (vital rates), for two neotropical understory herbs (order Zingiberales) in a premontane tropical rainforest in Costa Rica. During three annual censuses we monitored 1278 plants, measuring leaf area, number of inflorescences, and canopy openness. We fit regression models of all vital rates and evaluated them over a range of light levels. The best fitting models were selected using Akaike's Information Criterion.• All vital rates were significantly influenced by size in both species, but not always by light. Increasing light resulted in higher growth and a higher probability of reproduction in both species, but lower survival in one species. Both species grew at small sizes but shrank at larger sizes. The size at which shrinkage began differed among species and light environments. Vital rates of large individuals were more sensitive to changes in light than small individuals.• Increasing light does not always positively influence vital rates; the extent to which light affects vital rates depends on plant size. Differences among species in their abilities to thrive under different light conditions and thus occupy distinct niches may contribute to the maintenance of species diversity. © 2015 Botanical Society of America, Inc.

  1. Changes in Children's Peer Interactions Following a Natural Disaster: How Predisaster Bullying and Victimization Rates Changed Following Hurricane Katrina

    Science.gov (United States)

    Terranova, Andrew M.; Boxer, Paul; Morris, Amanda Sheffield

    2009-01-01

    Youth exposed to disasters experience stress and adjustment difficulties, which likely influence their interactions with peers. In this study, we examined changes in bullying and peer victimization in two cohorts of children. Youth from an area affected by Hurricane Katrina were assessed pre- and postdisaster (n = 96, mean [M] = 10.9 years old,…

  2. The novel interaction between Phytophthora ramorum and wildfire elicits elevated ambrosia beetle landing rates on tanoak, Notholithocarpus densiflorus

    Science.gov (United States)

    Maia M. Beh; Margaret R. Metz; Steven J. Seybold; David M. Rizzo

    2014-01-01

    The 2008 wildfires in the Big Sur region of California’s central coast—the first to occur in forests impacted by Phytophthora ramorum, the non-native, invasive pathogen that causes sudden oak death—provided the rare opportunity to study the response of scolytid and other subcortical beetles to this novel disturbance interaction...

  3. Synergistic action of fatty acids, sulphides and stilbene against acaricide-resistant Rhipicephalus microplus ticks.

    Science.gov (United States)

    Arceo-Medina, G N; Rosado-Aguilar, J A; Rodríguez-Vivas, R I; Borges-Argaez, R

    2016-09-15

    Six compounds in a methanolic extract of Petiveria alliacea stem (cis-stilbene; benzyl disulphide; benzyl trisulphide; and methyl esters of hexadecanoic acid, octadecadienoic acid and octadecenoic acid) are known to exercise acaricide activity against cattle tick Rhipicephalus microplus larvae and adults. The synergistic effect of 57 combinations of these six compounds on acaricide activity against R. microplus was evaluated. Larvae immersion tests produced the lethal concentrations needed to kill 50% (LC50) and 99% (LC99) of the population. Adult immersion tests produced rates (%) for mortality, oviposition inhibition and eclosion inhibition. Individually, none of the compounds (1% concentration) exhibited acaricide activity (mortality ≤2.3%). When combined, however, nine mixtures exhibited a synergistic increase in activity, with high mortality rates (≥92%) in larvae. Values for LC50 ranged from 0.07 to 0.51% and those for LC99 from 0.66 to 5.16%. Thirty six compound mixtures had no significant activity (mortality ≤30%) against larvae. Two mixtures exhibited synergism against adults, with high rates (≥92%) of oviposition inhibition. The mixtures based on the benzyl disulphide+benzyl trisulphide pairing produced a synergistic effect against acaricide-resistant R. microplus larva and adults, and are therefore the most promising combination for controlling this ubiquitous ectoparasite. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Synergistic Processing of Biphenyl and Benzoate: Carbon Flow Through the Bacterial Community in Polychlorinated-Biphenyl-Contaminated Soil

    Science.gov (United States)

    Leewis, Mary-Cathrine; Uhlik, Ondrej; Leigh, Mary Beth

    2016-02-01

    Aerobic mineralization of PCBs, which are toxic and persistent organic pollutants, involves the upper (biphenyl, BP) and lower (benzoate, BZ) degradation pathways. The activity of different members of the soil microbial community in performing one or both pathways, and their synergistic interactions during PCB biodegradation, are not well understood. This study investigates BP and BZ biodegradation and subsequent carbon flow through the microbial community in PCB-contaminated soil. DNA stable isotope probing (SIP) was used to identify the bacterial guilds involved in utilizing 13C-biphenyl (unchlorinated analogue of PCBs) and/or 13C-benzoate (product/intermediate of BP degradation and analogue of chlorobenzoates). By performing SIP with two substrates in parallel, we reveal microbes performing the upper (BP) and/or lower (BZ) degradation pathways, and heterotrophic bacteria involved indirectly in processing carbon derived from these substrates (i.e. through crossfeeding). Substrate mineralization rates and shifts in relative abundance of labeled taxa suggest that BP and BZ biotransformations were performed by microorganisms with different growth strategies: BZ-associated bacteria were fast growing, potentially copiotrophic organisms, while microbes that transform BP were oligotrophic, slower growing, organisms. Our findings provide novel insight into the functional interactions of soil bacteria active in processing biphenyl and related aromatic compounds in soil, revealing how carbon flows through a bacterial community.

  5. A multiunit catalyst with synergistic stability and reactivity: a polyoxometalate-metal organic framework for aerobic decontamination.

    Science.gov (United States)

    Song, Jie; Luo, Zhen; Britt, David K; Furukawa, Hiroyasu; Yaghi, Omar M; Hardcastle, Kenneth I; Hill, Craig L

    2011-10-26

    A combination of polyanion size and charge allows the Keggin-type polyoxometalate (POM), [CuPW(11)O(39)](5-), a catalyst for some air-based organic oxidations, to fit snuggly in the pores of MOF-199 (HKUST-1), a metal-organic framework (MOF) with the POM countercations residing in alternative pores. This close matching of POM diameter and MOF pore size in this POM-MOF material, [Cu(3)(C(9)H(3)O(6))(2)](4)[{(CH(3))(4)N}(4)CuPW(11)O(39)H] (1), results in a substantial synergistic stabilization of both the MOF and the POM. In addition, this heretofore undocumented POM-MOF interaction results in a dramatic increase in the catalytic turnover rate of the POM for air-based oxidations. While 1 catalyzes the rapid chemo- and shape-selective oxidation of thiols to disulfides and, more significantly, the rapid and sustained removal of toxic H(2)S via H(2)S + 1/2 O(2) → 1/8 S(8) + H(2)O (4000 turnovers in MOF alone is catalytically slow or inactive. Three arguments are consistent with the catalytic reactions taking place inside the pores. POM activation by encapsulation in the MOF likely involves electrostatic interactions between the two components resulting in a higher reduction potential of the POM.

  6. Synergistic enhancement of in vitro irradiation by concomitant cisplatinum

    Energy Technology Data Exchange (ETDEWEB)

    Kigawa, Junzo; Kanamori, Yasunobu; Morishita, Kaichiro; Ishihara, Hiroshi; Minagawa, Yukihisa (Tottori Univ., Yonago (Japan). School of Medicine)

    1991-06-01

    The purpose of this study was to obtain information concerning combination therapy using irradiation with CDDP. The SKGIIIb strain of uterine cervical squamous cell carcinoma origin was used in this study. In cells exposed to CDDP, the ratio in the G{sub 1} G{sub 0} phase decreased until 48 hours after administration. Seventy two hours after administration, that in G{sub 1} G{sub 0} phase increased and that in S phase slightly decreased. Labeling indices increased particularly 48 hours after CDDP administration. The survival fraction rate at 24 hours after irradiation revealed a synergistic effect in those cells exposed to more than 0.2 Gy gamma rays 24, 48 and 72 hours after administration of CDDP. There were no significant differences in survival fraction rates among the three intervals prior to gamma-ray. SEM findings suggested that cell damage substantially increased with combined therapy. The results of the present study suggested that cell accumulation in S and G{sub 2}M phases, which were sensitive to irradiation, was induced by CDDP. The present report indicates therefore that combination therapy with radiation and CDDP will be useful in cancer treatment. (author).

  7. Measurement of the Electron Neutrino Charged-current Interaction Rate on Water with the T2K ND280 pi-zero Detector

    CERN Document Server

    Abe, K; Aihara, H; Andreopoulos, C; Aoki, S; Ariga, A; Assylbekov, S; Autiero, D; Barbi, M; Barker, G J; Barr, G; Bartet-Friburg, P; Bass, M; Batkiewicz, M; Bay, F; Berardi, V; Berger, B E; Berkman, S; Bhadra, S; Blaszczyk, F d M; Blondel, A; Bolognesi, S; Bordoni, S; Boyd, S B; Brailsford, D; Bravar, A; Bronner, C; Buchanan, N; Calland, R G; Caravaca, J; Cartwright, S L; Castillo, R; Catanesi, M G; Cervera, A; Cherdack, D; Christodoulou, G; Clifton, A; Coleman, J; Coleman, S J; Collazuol, G; Connolly, K; Cremonesi, L; Dabrowska, A; Das, R; Davis, S; de, P; De, G; Dealtry, T; Dennis, S R; Densham, C; Dewhurst, D; Di, F; Di, S; Dolan, S; Drapier, O; Duffy, K; Dumarchez, J; Dytman, S; Dziewiecki, M; Emery-Schrenk, S; Ereditato, A; Escudero, L; Feusels, T; Finch, A J; Fiorentini, G A; Friend, M; Fujii, Y; Fukuda, Y; Furmanski, A P; Galymov, V; Garcia, A; Giffin, S; Giganti, C; Gilje, K; Goeldi, D; Golan, T; Gonin, M; Grant, N; Gudin, D; Hadley, D R; Haegel, L; Haesler, A; Haigh, M D; Hamilton, P; Hansen, D; Hara, T; Hartz, M; Hasegawa, T; Hastings, N C; Hayashino, T; Hayato, Y; Helmer, R L; Hierholzer, M; Hignight, J; Hillairet, A; Himmel, A; Hiraki, T; Hirota, S; Holeczek, J; Horikawa, S; Huang, K; Ichikawa, A K; Ieki, K; Ieva, M; Ikeda, M; Imber, J; Insler, J; Irvine, T J; Ishida, T; Ishii, T; Iwai, E; Iwamoto, K; Iyogi, K; Izmaylov, A; Jacob, A; Jamieson, B; Jiang, M; Johnson, S; Jo, J H; Jonsson, P; Jung, C K; Kabirnezhad, M; Kaboth, A C; Kajita, T; Kakuno, H; Kameda, J; Kanazawa, Y; Karlen, D; Karpikov, I; Katori, T; Kearns, E; Khabibullin, M; Khotjantsev, A; Kielczewska, D; Kikawa, T; Kilinski, A; Kim, J; King, S; Kisiel, J; Kitching, P; Kobayashi, T; Koch, L; Koga, T; Kolaceke, A; Konaka, A; Kormos, L L; Korzenev, A; Koshio, Y; Kropp, W; Kubo, H; Kudenko, Y; Kurjata, R; Kutter, T; Lagoda, J; Lamont, I; Larkin, E; Laveder, M; Lawe, M; Lazos, M; Lindner, T; Lister, C; Litchfield, R P; Longhin, A; Lopez, J P; Ludovici, L; Magaletti, L; Mahn, K; Malek, M; Manly, S; Marino, A D; Marteau, J; Martin, J F; Martins, P; Martynenko, S; Maruyama, T; Matveev, V; Mavrokoridis, K; Mazzucato, E; McCarthy, M; McCauley, N; McFarland, K S; McGrew, C; Mefodiev, A; Metelko, C; Mezzetto, M; Mijakowski, P; Miller, C A; Minamino, A; Mineev, O; Missert, A; Miura, M; Moriyama, S; Mueller, Th A; Murakami, A; Murdoch, M; Murphy, S; Myslik, J; Nakadaira, T; Nakahata, M; Nakamura, K G; Nakamura, K; Nakayama, S; Nakaya, T; Nakayoshi, K; Nantais, C; Nielsen, C; Nirkko, M; Nishikawa, K; Nishimura, Y; Nowak, J; O'Keeffe, H M; Ohta, R; Okumura, K; Okusawa, T; Oryszczak, W; Oser, S M; Ovsyannikova, T; Owen, R A; Oyama, Y; Palladino, V; Palomino, J L; Paolone, V; Payne, D; Perevozchikov, O; Perkin, J D; Petrov, Y; Pickard, L; Pinzon, E S; Pistillo, C; Plonski, P; Poplawska, E; Popov, B; Posiadala-Zezula, M; Poutissou, J -M; Poutissou, R; Przewlocki, P; Quilain, B; Radicioni, E; Ratoff, P N; Ravonel, M; Rayner, M A M; Redij, A; Reeves, M; Reinherz-Aronis, E; Riccio, C; Rodrigues, P A; Rojas, P; Rondio, E; Roth, S; Rubbia, A; Ruterbories, D; Rychter, A; Sacco, R; Sakashita, K; S, F; Sato, F; Scantamburlo, E; Scholberg, K; Schoppmann, S; Schwehr, J; Scott, M; Seiya, Y; Sekiguchi, T; Sekiya, H; Sgalaberna, D; Shah, R; Shaker, F; Shaw, D; Shiozawa, M; Short, S; Shustrov, Y; Sinclair, P; Smith, B; Smy, M; Sobczyk, J T; Sobel, H; Sorel, M; Southwell, L; Stamoulis, P; Steinmann, J; Suda, Y; Suzuki, A; Suzuki, K; Suzuki, S Y; Suzuki, Y; Tacik, R; Tada, M; Takahashi, S; Takeda, A; Takeuchi, Y; Tanaka, H K; Tanaka, H A; Tanaka, M M; Terhorst, D; Terri, R; Thompson, L F; Thorley, A; Tobayama, S; Toki, W; Tomura, T; Totsuka, Y; Touramanis, C; Tsukamoto, T; Tzanov, M; Uchida, Y; Vacheret, A; Vagins, M; Vasseur, G; Wachala, T; Wakamatsu, K; Walter, C W; Wark, D; Warzycha, W; Wascko, M O; Weber, A; Wendell, R; Wilkes, R J; Wilking, M J; Wilkinson, C; Williamson, Z; Wilson, J R; Wilson, R J; Wongjirad, T; Yamada, Y; Yamamoto, K; Yanagisawa, C; Yano, T; Yen, S; Yershov, N; Yokoyama, M; Yoshida, K; Yuan, T; Yu, M; Zalewska, A; Zalipska, J; Zambelli, L; Zaremba, K; Ziembicki, M; Zimmerman, E D; Zito, M; Zmuda, J

    2015-01-01

    The first direct observation of the appearance of electron neutrinos in a muon neutrino beam through neutrino oscillation was recently reported by the T2K experiment. The main background in this observation was the presence of the electron neutrino component of the beam, which accounts for 1.2 % of the beam below the 1.2 GeV threshold. This paper presents a measurement of the charged current interaction rate of the electron neutrino beam component using the large fiducial mass of the T2K $\\pi^0$ detector. The measured ratio of the observed beam interaction rate to the predicted rate in the detector with water targets filled is 0.89 $\\pm$ 0.08 (stat.) $\\pm$ 0.11 (sys.), and with the water targets emptied is 0.90 $\\pm$ 0.09 (stat.) $\\pm$ 0.13 (sys.). The ratio obtained for the interactions on water only from an event subtraction method is 0.87 $\\pm$ 0.33 (stat.) $\\pm$ 0.21 (sys.). These are pioneering measurements of the $\

  8. The reflex control of heart rate and cardiac output in the rainbow trout: interactive influences of hypoxia, haemorrhage, and systemic vasomotor tone.

    Science.gov (United States)

    Wood, C M; Shelton, G

    1980-08-01

    In cannulated trout there was no cholinergic vagal tone as revealed by atropine blockade during normal heart rates. Reductions in heart rate occasionally occurred under normoxia without apparent external stimuli ('spontaneous' bradycardia) and always occurred under environmental hypoxia (hypoxic bradycardia) due to the imposition of significant vagal tone. Direct measurements of cardiac output (Q) during these bradycardias showed that increases in cardiac stroke volume compensated for the falls in heart rate so that total Q remained unchanged or increased slightly. Sudden experimental reductions in arterial blood pressure via blockade of systemic vasomotor tone with yohimbine or via haemorrhage had no effect on heart rate during normal rates, but caused cardioacceleration during both types of bradycardia. These increases in heart rate never exceeded the point of zero vagal tone (normal heart rate) and were largely or wholly due to reductions in endogenous vagal tone. These cardioaccelerations were temporary; spontaneous bradycardia could re-occur at any time, while hypoxic bradycardia always re-occurred if the hypoxic stimulus were maintained. The results are interpreted in terms of a central interaction between the baroreceptor and chemoreceptor reflexes.

  9. Synergistic Catalysis: A Powerful Synthetic Strategy for New Reaction Development

    Science.gov (United States)

    Allen, Anna E.; MacMillan, David W. C.

    2012-01-01

    Synergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature. PMID:22518271

  10. Synergistic neurotrophic effects of piracetam and thiotriazoline

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available The paper considers the synergy between the nootropic drug piracetam and the metabolic agent thiotriazoline that maintains energy metabolism and survival of neurons and other types of cells. Piracetam, a nootropic drug, a chemical pyrrolidone derivative, is used in neurological, psychiatric, and narcological practice. There is evidence on the positive effect of piracetam in elderly and senile patients with coronary heart disease. This drug is supposed to stimulate redox processes, to enhance glucose utilization, and to improve regional blood flow in the ischemic brain regions. Due to its action, the drug activates glycolytic processes and elevates ATP concentrations in brain tissue. Thiotriazoline is a compound that has antioxidant, anti-ischemic properties. The co-administration of piracetam and thiothriazoline is an innovation area in the treatment of stroke and other brain damages, especially in insulin resistance and high blood glucose levels. The paper considers the neurobiological properties of thiotriazoline and piracetam, which synergistically exert neuroprotective and neurotrophic effects.

  11. Synergistic Smart Fuel For Microstructure Mediated Measurements

    Energy Technology Data Exchange (ETDEWEB)

    James A. Smith; Dale K. Kotter; Steven L. Garrett; Randall A. Ali

    2013-07-01

    Advancing the Nuclear Fuel Cycle and Next Generation Nuclear Power Plants requires enhancing our basic understanding of fuel and materials behavior under irradiation. The two most significant issues limiting the effectiveness and lifespan of the fuel are the loss of thermal conductivity of the fuel and the mechanical strength of both fuel and cladding. The core of a nuclear reactor presents an extremely harsh and challenging environment for both sensors and telemetry due to elevated temperatures and large fluxes of energetic and ionizing particles from radioactive decay processes. The majority of measurements are made in reactors using “radiation hardened” sensors and materials. A different approach has been pursued in this research that exploits high temperatures and materials that are robust with respect to ionizing radiation. This synergistically designed thermoacoustic sensor will be self-powered, wireless, and provide telemetry. The novel sensor will be able to provide reactor process information even if external electrical power and communication are unavailable. In addition, the form-factor for the sensor is identical to the existing fuel rods within reactors and contains no moving parts. Results from initial proof of concept experiments designed to characterize porosity, surface properties and monitor gas composition will be discussed.

  12. Synergistic smart fuel for microstructure mediated measurements

    Energy Technology Data Exchange (ETDEWEB)

    Smith, James A.; Kotter, Dale K. [Idaho National Laboratory, Fuel Performance and Design, P.O. Box 1625, Idaho Falls, Idaho, 83415-6188 (United States); Ali, Randall A. [Graduate Program in Acoustics and Applied Research Laboratory, Penn State University, P. . Box 30, M/S 3520D, State College, PA 16804-0030 (United States); Garrett, Steven L. [Graduate Program in Acoustics and Applied Research Laboratory, Penn State University, P.O. Box 30, M/S 3520D, State College, PA 16804-0030 (United States)

    2014-02-18

    Advancing the Nuclear Fuel Cycle and Next Generation Nuclear Power Plants requires enhancing our basic understanding of fuel and materials behavior under irradiation. The two most significant issues limiting the effectiveness and lifespan of the fuel are the loss of thermal conductivity of the fuel and the mechanical strength of both fuel and cladding. The core of a nuclear reactor presents an extremely harsh and challenging environment for both sensors and telemetry due to elevated temperatures and large fluxes of energetic and ionizing particles from radioactive decay processes. The majority of measurements are made in reactors using 'radiation hardened' sensors and materials. A different approach has been pursued in this research that exploits high temperatures and materials that are robust with respect to ionizing radiation. This synergistically designed thermoacoustic sensor will be self-powered, wireless, and provide telemetry. The novel sensor will be able to provide reactor process information even if external electrical power and communication are unavailable. In addition, the form-factor for the sensor is identical to the existing fuel rods within reactors and contains no moving parts. Results from initial proof of concept experiments designed to characterize porosity, surface properties and monitor gas composition will be discussed.

  13. Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin

    Energy Technology Data Exchange (ETDEWEB)

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Crettaz, Pierre [Federal Office of Public Health, Division Chemical Products, 3003 Bern (Switzerland); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); ETH Zürich, Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, Universitätsstrasse 16, CH-8092 Zürich (Switzerland)

    2014-09-15

    Objective: Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. Methods: The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose–response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. Results: The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC{sub 25} and EC{sub 50}. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Conclusion: Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Practice: Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Implications: Our evaluation provides an appropriate “proof of concept”, but whether it equally translates to in vivo effects should further be investigated. - Highlights: • Humans are exposed to pesticide mixtures such as pyrethroids and azole fungicides. • We assessed the antiandrogenicity of

  14. Metabolic and protein interaction sub-networks controlling the proliferation rate of cancer cells and their impact on patient survival.

    Science.gov (United States)

    Feizi, Amir; Bordel, Sergio

    2013-10-24

    Cancer cells can have a broad scope of proliferation rates. Here we aim to identify the molecular mechanisms that allow some cancer cell lines to grow up to 4 times faster than other cell lines. The correlation of gene expression profiles with the growth rate in 60 different cell lines has been analyzed using several genome-scale biological networks and new algorithms. New possible regulatory feedback loops have been suggested and the known roles of several cell cycle related transcription factors have been confirmed. Over 100 growth-correlated metabolic sub-networks have been identified, suggesting a key role of simultaneous lipid synthesis and degradation in the energy supply of the cancer cells growth. Many metabolic sub-networks involved in cell line proliferation appeared also to correlate negatively with the survival expectancy of colon cancer patients.

  15. Trophic interactions and consumption rates of subyearling Chinook Salmon and nonnative juvenile American Shad in Columbia River reservoirs

    Science.gov (United States)

    Haskell, Craig A.; Beauchamp, David A.; Bollins, Stephen M

    2017-01-01

    We used a large lampara seine coupled with nonlethal gastric lavage to examine the diets and estimate consumption rates of subyearling Chinook Salmon Oncorhynchus tshawytscha during July and August 2013. During August we also examined the diet and consumption rates of juvenile American Shad Alosa sapidissima, a potential competitor of subyearling Chinook Salmon. Subyearling Chinook Salmon consumed Daphnia in July but switched to feeding on smaller juvenile American Shad in August. We captured no juvenile American Shad in July, but in August juvenile American Shad consumed cyclopoid and calanoid copepods. Stomach evacuation rates for subyearling Chinook Salmon were high during both sample periods (0.58 h−1 in July, 0.51 h−1 in August), and daily ration estimates were slightly higher than values reported in the literature for other subyearlings. By switching from planktivory to piscivory, subyearling Chinook Salmon gained greater growth opportunity. While past studies have shown that juvenile American Shad reduce zooplankton availability for Chinook Salmon subyearlings, our work indicates that they also become important prey after Daphnia abundance declines. The diet and consumption data here can be used in future bioenergetics modeling to estimate the growth of subyearling Chinook Salmon in lower Columbia River reservoirs.

  16. Nutrients interaction investigation to improve Monascus purpureus FTC5391 growth rate using Response Surface Methodology and Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Mohamad, R.

    2013-01-01

    Full Text Available Aims: Two vital factors, certain environmental conditions and nutrients as a source of energy are entailed for successful growth and reproduction of microorganisms. Manipulation of nutritional requirement is the simplest and most effectual strategy to stimulate and enhance the activity of microorganisms. Methodology and Results: In this study, response surface methodology (RSM and artificial neural network (ANN were employed to optimize the carbon and nitrogen sources in order to improve growth rate of Monascus purpureus FTC5391,a new local isolate. The best models for optimization of growth rate were a multilayer full feed-forward incremental back propagation network, and a modified response surface model using backward elimination. The optimum condition for cell mass production was: sucrose 2.5%, yeast extract 0.045%, casamino acid 0.275%, sodium nitrate 0.48%, potato starch 0.045%, dextrose 1%, potassium nitrate 0.57%. The experimental cell mass production using this optimal condition was 21 mg/plate/12days, which was 2.2-fold higher than the standard condition (sucrose 5%, yeast extract 0.15%, casamino acid 0.25%, sodium nitrate 0.3%, potato starch 0.2%, dextrose 1%, potassium nitrate 0.3%. Conclusion, significance and impact of study: The results of RSM and ANN showed that all carbon and nitrogen sources tested had significant effect on growth rate (P-value < 0.05. In addition the use of RSM and ANN alongside each other provided a proper growth prediction model.

  17. Synergistic activity of doped zinc oxide nanoparticles with antibiotics: ciprofloxacin, ampicillin, fluconazole and amphotericin B against pathogenic microorganisms

    Directory of Open Access Journals (Sweden)

    NEHA SHARMA

    Full Text Available ABSTRACT Combination therapy of antibiotics and nanoparticles can be used against multi drug resistant microorganisms. Nanoparticles (NPs have been reported to show antimicrobial activity. The antimicrobial activities of doped ZnO nanoparticles (ZnO NPs were studied against fungi, gram-positive and gram-negative bacteria using the standard microdilution method. The interaction between the nanoparticle and the antibiotic was estimated by calculating the fractional inhibitory concentration (FIC index of the combination through checkerboard assay. Experimental results demonstrated that 10% doped zinc oxide nanoparticles (ZnO NPs exhibited the maximum antimicrobial effect in contrast with that of the 1% loading and pure ZnO nanoparticles. The enhancement in antimicrobial effect was seen when combined with antibiotic. Synergistic and additive effects were found. No antagonistic effect was found. More synergistic effect was observed when combined with ciprofloxacin than ampicillin. Fungus showed only additive effect. The results are quite in terms with MIC clearly depicting that high doping agent is most suitable for combined therapy. 100% synergistic interaction was observed in higher doping with both ciprofloxacin and ampicillin. This study provides a preliminary report of the synergistic activity of nanoparticles with antibiotics against different pathogenic strains. This provides groundwork for further studies on the combination therapy of nanoparticles with antibiotics.

  18. In-situ characterization of laser-powder interaction and cooling rates through high-speed imaging of powder bed fusion additive manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Scipioni Bertoli, Umberto; Guss, Gabe; Wu, Sheldon; Matthews, Manyalibo J.; Schoenung, Julie M.

    2017-12-01

    Detailed understanding of the complex melt pool physics plays a vital role in predicting optimal processing regimes in laser powder bed fusion additive manufacturing. In this work, we use high framerate video recording of Selective Laser Melting (SLM) to provide useful insight on the laser-powder interaction and melt pool evolution of 316 L powder layers, while also serving as a novel instrument to quantify cooling rates of the melt pool. The experiment was performed using two powder types – one gas- and one water-atomized – to further clarify how morphological and chemical differences between these two feedstock materials influence the laser melting process. Finally, experimentally determined cooling rates are compared with values obtained through computer simulation, and the relationship between cooling rate and grain cell size is compared with data previously published in the literature.

  19. Genotype x environmental interaction for mature size and rate of maturing for Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte infected fescue.

    Science.gov (United States)

    Sandelin, B A; Brown, A H; Brown, M A; Johnson, Z B; Kellogg, D W; Stelzleni, A M

    2002-12-01

    Mature weight and rate of maturing were estimated in 177 Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte-infected tall fescue over a 4-yr period to evaluate genotype x environment interactions. Data were collected every 28 d until cows were approximately 18 mo of age and then at prebreeding, postcalving, and weaning of calf. All cows with weight data to at least 42 mo of age were included in the analysis. Mature weight and rate of maturing were estimated using the three-parameter growth curve model described by Brody (1945). Data were pooled over year and analyzed by the general linear model procedure of SAS. Included in the models for mature weight and rate of maturing were the independent variables of genotype, environment, and genotype x environment interaction. There was a genotype x environment interaction (P pastures had greater (P < 0.01) mean mature BW than Angus x Brahman cows grazing bermudagrass (611 +/- 17 vs 546 +/- 16 kg). Angus x Brahman cows grazing bermudagrass had lower (P < 0.05) mean mature BW than Brahman x Angus cows grazing bermudagrass or endophyte-infected fescue and Brahman cows grazing bermudagrass (546 +/- 16 vs 624 +/- 19, 614 +/- 22 and 598 +/- 20 kg, respectively). Brahman cows grazing endophyte-infected fescue had smaller (P < 0.05) mean mature BW than all genotype x forage combinations except for Angus x Brahman cows grazing bermudagrass. Angus cows had a smaller (P < 0.05) mean rate of maturing than Angus x Brahman and Brahman x Angus cows (0.039 +/- 0.002 vs 0.054 +/- 0.002 and 0.049 +/- 0.002%/mo, respectively), respectively, and Angus x Brahman cows had a larger (P < 0.05) mean rate of maturing than Brahman x Angus and Brahman cows (0.054 +/- 0.002 vs 0.049 +/- 0.002 and 0.041 +/- 0.002 %/mo, respectively). There was a direct breed x forage interaction (P < 0.05) for mature BW. These data suggest that the choice of breed type is important in maintaining a crossbreeding program, in that mature BW and

  20. Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.

    Directory of Open Access Journals (Sweden)

    Janina K Hellmann

    Full Text Available BACKGROUND: Most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. However, little is known about synergistic effects between such potential drug candidates and adjuvants. To probe for such effects, we tested the green tea compound epigallocatechin gallate (EGCG and the membrane permeabilising digitonin on Plasmodium sporozoite motility and viability. METHODOLOGY/PRINCIPAL FINDINGS: Green fluorescent P. berghei sporozoites were imaged using a recently developed visual screening methodology. Motility and viability parameters were automatically analyzed and IC50 values were calculated, and the synergism of drug and adjuvant was assessed by the fractional inhibitory concentration index. Validating our visual screening procedure, we showed that sporozoite motility and liver cell infection is inhibited by EGCG at nontoxic concentrations. Digitonin synergistically increases the cytotoxicity of EGCG on sporozoite survival, but shows an additive effect on sporozoite motility. CONCLUSIONS/SIGNIFICANCE: We proved the feasibility of performing highly reliable visual screens for compounds against Plasmodium sporozoites. We thereby could show an advantage of administering mixtures of plant metabolites on inhibition of cell motility and survival. Although the effective concentration of both drugs is too high for use in malaria prophylaxis, the demonstration of a synergistic effect between two plant compounds could lead to new avenues in drug discovery.

  1. Room temperature phosphorescence of five PAHs in a synergistic mesoporous silica nanoparticle-deoxycholate substrate

    Science.gov (United States)

    Qin, Jun; Li, Xiaomei; Feng, Feng; Pan, Qiliang; Bai, Yunfeng; Zhao, Jianguo

    2017-05-01

    A synergistic mesoporous silica nanoparticle-sodium deoxycholate (mPS-NaDC) substrate was developed for room temperature phosphorimetry. The synergistic substrate exhibited rapid and strong RTP-inducing ability against temperature variation. NaDC might adsorb on the inner surface of mPS pore by possible hydrogen bonding and protected the triplet state of polycyclic aromatic hydrocarbons (PAHs) with different molecular sizes. Two mPSs named LPMS1 and LPMS2 with pore size of 3.05 and 3.83 nm were synthesized and optimized in inducing RTP, and the latter, LPMS2, was selected as an ideal substrate because of its stronger protection ability to the triplet and good stability. Dibromopropane and cyclohexane were also used as assistant phosphorescence-inducers. All results demonstrated the feasibility and application potential of synergistic mPS-NaDC substrate in phosphorimetry. The interaction detail of NaDC and inner surface of selected mPS still needs to be explored in future.

  2. Improved inhaled air quality at reduced ventilation rate by control of airflow interaction at the breathing zone with lobed jets

    DEFF Research Database (Denmark)

    Bolashikov, Zhecho Dimitrov; Melikov, Arsen Krikor; Spilak, Michal

    2014-01-01

    Inhaled air quality at a reduced supply of clean air was studied by controlling the airflow interaction at the breathing zone of a person using lobed jets as part of personalized ventilation (PV). Experiments were performed in a full-scale test room at 23°C (73.4°F) with a breathing thermal manikin......) equivalent diameter. The nozzles were positioned frontally at the face within the boundary layer and centered to the mouth. The enhancement of inhaled air quality by changing the initial velocity (0.2-0.6 m/s, 0.66-1.97 fps) and the distance from the mouth (0.02-0.06 m, 0.07-0.20 ft) was studied. The control....... The other lobed nozzle, the six-edged star, performed similarly to the circular nozzle. © 2014 Taylor and Francis Group, LLC....

  3. Detailed Analysis of Configuration Interaction and Calculation of Radiative Transition Rates in Seven Times Ionized Tungsten (W VIII

    Directory of Open Access Journals (Sweden)

    Jérôme Deprince

    2015-06-01

    Full Text Available A new set of oscillator strengths and transition probabilities for EUV spectral lines of seven times ionized tungsten (W VIII is reported in the present paper. These results have been obtained using the pseudo-relativistic Hartree-Fock (HFR method combined with a semi-empirical optimization of the radial parameters minimizing the discrepancies between computed energy levels and available experimental data. The final physical model considered in the calculations has been chosen further to a detailed investigation of the configuration interaction in this atomic system characterized by complex configurations of the type 4f145s25p5, 4f145s25p4nl, 4f145s5p6, 4f135s25p6, 4f135s25p5nl and 4f125s25p6nl (nl = 5d, 6s.

  4. New insights into saline water evaporation from porous media: Complex interaction between evaporation rates, precipitation, and surface temperature

    Science.gov (United States)

    Shokri-Kuehni, Salomé M. S.; Vetter, Thomas; Webb, Colin; Shokri, Nima

    2017-06-01

    Understanding salt transport and deposition patterns during evaporation from porous media is important in many engineering and hydrological processes such as soil salinization, ecosystem functioning, and land-atmosphere interaction. As evaporation proceeds, salt concentration increases until it exceeds solubility limits, locally, and crystals precipitate. The interplay between transport processes, crystallization, and evaporation influences where crystallization occurs. During early stages, the precipitated salt creates an evolving porous structure affecting the evaporation kinetics. We conducted a comprehensive series of experiments to investigate how the salt concentration and precipitation influence evaporation dynamics. Our results illustrate the contribution of the evolving salt crust to the evaporative mass losses. High-resolution thermal imaging enabled us to investigate the complex temperature dynamics at the surface of precipitated salt, providing further confirmation of salt crust contribution to the evaporation. We identify different phases of saline water evaporation from porous media with the corresponding dominant mechanisms in each phase and extend the physical understanding of such processes.

  5. Distinct gene expression profile of Xanthomonas retroflexus engaged in synergistic multispecies biofilm formation.

    Science.gov (United States)

    Hansen, Lea Benedicte Skov; Ren, Dawei; Burmølle, Mette; Sørensen, Søren J

    2017-01-01

    It is well known that bacteria often exist in naturally formed multispecies biofilms. Within these biofilms, interspecies interactions seem to have an important role in ecological processes. Little is known about the effects of interspecies interactions on gene expression in these multispecies biofilms. This study presents a comparative gene expression analysis of the Xanthomonas retroflexus transcriptome when grown in a single-species biofilm and in dual- and four-species consortia with Stenotrophomonas rhizophila, Microbacterium oxydans and Paenibacillus amylolyticus. The results revealed complex interdependent interaction patterns in the multispecies biofilms. Many of the regulated functions are related to interactions with the external environment and suggest a high phenotypic plasticity in response to coexistence with other species. Furthermore, the changed expression of genes involved in aromatic and branched-chain amino acid biosynthesis suggests nutrient cross feeding as a contributing factor for the observed synergistic biofilm production when these four species coexists in a biofilm.

  6. Synergistic effect of PEGylated resveratrol on delivery of anticancer drugs.

    Science.gov (United States)

    Wang, Wenlong; Zhang, Liang; Le, Yuan; Chen, Jian-Feng; Wang, Jiexin; Yun, Jimmy

    2016-02-10

    Resveratrol (RES) is a natural polyphenol which can be considered as a nutraceutical because of its benefits such as anticancer and antioxidant activity. In this paper, we designed polymer-RES conjugates as anticancer drug carrier for synergistic therapeutic effect in cancer treatment. Bicalutamide (BIC) was used as a model drug to investigate the drug release behaviors and in vitro anticancer performance. PEG-RES and PEG-Glycine-RES nanoparticles were prepared and characterized. The size of the prepared particles was around 50 nm with RES content of 17.2 and 16.3 wt% for PEG-RES and PEG-Glycine-RES, respectively, and BIC loading efficiency were of 81.6% and 84.5%, separately. Release rate of RES from conjugates depended on the stability of ester group against hydrolysis. BIC release was much faster than RES release. The anticancer activity of BIC loaded PEGylated RES nanoparticles was much better than that of free BIC, indicating the conjugates provided a synergetic cytotoxicity to cancer cells. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that PEGylated RES conjugates were more efficiently internalized into cells, released drug into cytoplasm. These results suggest that PEGylated RES conjugates show great potential for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Basal metabolic rate, maximum thermogenic capacity and aerobic scope in rodents: interaction between environmental temperature and torpor use

    OpenAIRE

    Careau, Vincent

    2013-01-01

    When torpid animals arouse and warm up to restore normal body temperature (Tb), they produce heat at levels that can reach up to 10 times basal metabolic rate (BMR), close to the cold-induced summit metabolism (VO2-sum). Because torpor is an adaptation aimed at conserving energy over periods of low ambient temperature (Ta) and food availability, selective forces that have led to the evolution of torpor may have simultaneously favoured high thermogenic capacity (i.e. VO2-sum) relative to the m...

  8. Interaction of hydrated electron with dietary flavonoids and phenolic acids. Rate constants and transient spectra studied by pulse radiolysis

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Zhongli; Li, Xifeng; Katsumura, Yosuke [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab

    2000-03-01

    The reaction rate constants and transient spectra of 11 flavonoids and 4 phenolic acids reacting with e{sub aq}{sup -} at neutral pH were measured. The results suggest that C{sub 4} keto group is the active site for e{sub aq}{sup -} to attack on flavonoids and phenolic acids, while the o-dihydroxy structure in B-ring, the C{sub 2,3} double bond, the C{sub 3}-OH group and glycosylation have little effects on the e{sub aq}{sup -} scavenging activities. (author)

  9. Guest–Host Interactions Investigated by Time-Resolved X-ray Spectroscopies and Scattering at MHz Rates

    DEFF Research Database (Denmark)

    Haldrup, Martin Kristoffer; Vanko, G.; Gawelda, W.

    2012-01-01

    We have studied the photoinduced low spin (LS) to high spin (HS) conversion of [Fe(bipy)3]2+ in aqueous solution. In a laser pump/X-ray probe synchrotron setup permitting simultaneous, time-resolved X-ray diffuse scattering (XDS) and X-ray spectroscopic measurements at a 3.26 MHz repetition rate,...... of the caging solvent, in particular, a decrease in the number of water molecules in the first solvation shell is inferred, as predicted by recent theoretical work....

  10. Synergistic Antimicrobial Combinations Inhibit and Inactivate Listeria monocytogenes in Neutral and Acidic Broth Systems.

    Science.gov (United States)

    Kozak, Sarah M; Margison, Kyle M; D'amico, Dennis J

    2017-08-01

    The use of antimicrobial compounds can be an effective approach to control Listeria monocytogenes in ready-to-eat foods, but it can also be limited by cost, restrictions on concentrations in foods, and potential changes to organoleptic properties. Combinatorial approaches that produce additive or synergistic effects allow for reductions in individual antimicrobial concentrations while achieving the same level of control. The present study determined the MIC and MBC of an antimicrobial compound when used alone or in binary combinations against L. monocytogenes in growth media adjusted to pH values 7.4 and 5.5 and characterized interactions as synergistic, additive, or antagonistic. Inhibitory and bactericidal concentrations were defined as changes in L. monocytogenes counts of ≤1.0 or ≥3.0 log CFU/mL compared with the starting inoculum, respectively. Individually, lauric arginate (LAE), hydrogen peroxide (HP), and ε-polylysine (EPL) inhibited L. monocytogenes growth at the lowest concentrations when applied alone in broth adjusted to pH 7.4. Similarly, LAE, EPL, and HP had the lowest MBCs in broth adjusted to both pH levels. The inhibitory efficacy of both caprylic acid and sodium caprylate (SC) increased at the lower pH, with reductions in MICs of >98%. In total, 35 and 19 additive or synergistic inhibitory and bactericidal combinations were identified at pH values 7.4 and 5.5, respectively. Combinations of acidified calcium sulfate with lactic acid (ACSL) and SC were among the most synergistic inhibitory groupings at both pH levels, whereas EPL+LAE were the most effective bactericides at pH 7.4. Combinations of SC with EPL or ACSL were also among the most effective bactericides at pH 5.5. These data serve as a foundation for developing more effective antimicrobial approaches for the control of L. monocytogenes in foods with different pH levels.

  11. Interactions of Nitrogen Source and Rate and Weed Removal Timing Relative to Nitrogen Content in Corn and Weeds and Corn Grain Yield.

    Science.gov (United States)

    Knight, Alexandra M; Everman, Wesley J; Jordan, David L; Heiniger, Ronnie W; Smyth, T Jot

    2017-01-01

    Adequate fertility combined with effective weed management is important in maximizing corn (Zea mays L.) grain yield. Corn uptake of nitrogen (N) is dependent upon many factors including weed species and density and the rate and formulation of applied N fertilizer. Understanding interactions among corn, applied N, and weeds is important in developing management strategies. Field studies were conducted in North Carolina to compare corn and weed responses to urea ammonium nitrate (UAN), sulfur-coated urea (SCU), and composted poultry litter (CPL) when a mixture of Palmer amaranth (Amaranthus palmeri S. Wats.) and large crabgrass (Digitaria sanguinalis L.) was removed with herbicides at heights of 8 or 16 cm. These respective removal timings corresponded with 22 and 28 days after corn planting or V2 and V3 stages of growth, respectively. Differences in N content in above-ground biomass of corn were noted early in the season due to weed interference but did not translate into differences in corn grain yield. Interactions of N source and N rate were noted for corn grain yield but these factors did not interact with timing of weed control. These results underscore that timely implementation of control tactics regardless of N fertility management is important to protect corn grain yield.

  12. Interactions of Nitrogen Source and Rate and Weed Removal Timing Relative to Nitrogen Content in Corn and Weeds and Corn Grain Yield

    Directory of Open Access Journals (Sweden)

    Alexandra M. Knight

    2017-01-01

    Full Text Available Adequate fertility combined with effective weed management is important in maximizing corn (Zea mays L. grain yield. Corn uptake of nitrogen (N is dependent upon many factors including weed species and density and the rate and formulation of applied N fertilizer. Understanding interactions among corn, applied N, and weeds is important in developing management strategies. Field studies were conducted in North Carolina to compare corn and weed responses to urea ammonium nitrate (UAN, sulfur-coated urea (SCU, and composted poultry litter (CPL when a mixture of Palmer amaranth (Amaranthus palmeri S. Wats. and large crabgrass (Digitaria sanguinalis L. was removed with herbicides at heights of 8 or 16 cm. These respective removal timings corresponded with 22 and 28 days after corn planting or V2 and V3 stages of growth, respectively. Differences in N content in above-ground biomass of corn were noted early in the season due to weed interference but did not translate into differences in corn grain yield. Interactions of N source and N rate were noted for corn grain yield but these factors did not interact with timing of weed control. These results underscore that timely implementation of control tactics regardless of N fertility management is important to protect corn grain yield.

  13. Interactive effects of nitrogen and light on growth rates and RUBISCO content of small and large centric diatoms.

    Science.gov (United States)

    Li, Gang; Campbell, Douglas A

    2017-01-01

    Among marine phytoplankton groups, diatoms span the widest range of cell size, with resulting effects upon their nitrogen uptake, photosynthesis and growth responses to light. We grew two strains of marine centric diatoms differing by ~4 orders of magnitude in cell biovolume in high (enriched artificial seawater with ~500 µmol L(-1) µmol L(-1) NO3(-)) and lower-nitrogen (enriched artificial seawater with Nitrogen and total protein per cell decreased with increasing growth light in both species when grown under the lower-nitrogen media. Cells growing under lower-nitrogen media increased their cellular allocation to RUBISCO and their rate of electron transport away from PSII, for the smaller diatom under low growth light and for the larger diatom across the range of growth lights. The smaller coastal diatom Thalassiosira pseudonana is able to exploit high nitrogen in growth media by up-regulating growth rate, but the same high-nitrogen growth media inhibits growth of the larger diatom species.

  14. Synergistic Adsorption and Flotation of New Mixed Cationic/Nonionic Collectors on Muscovite

    Directory of Open Access Journals (Sweden)

    Hao Jiang

    2017-05-01

    Full Text Available The mixed cationic collector cetyltrimethylammonium chloride (CTAC and nonionic collector octanol (OCT was found to exhibit a synergistic effect on the flotation and adsorption of muscovite. To understand the underlying synergistic mechanism, flotation, contact angle, surface tension, and adsorption measurements were carried out. The results obtained from flotation measurements indicated that the mixed CTAC/OCT exhibits a better collecting ability than CTAC or OCT. The recovery of muscovite with CTAC only rapidly decreased from 97.25% at pH 2.64 to 75.26% at pH 5.82, followed by a flat horizontal at a pH is higher than 6. In contrast, a high recovery of greater than 85% muscovite was observed using mixed CTAC/OCT at α CTAC = 0.67 (the mole ratio of CTAC:OCT = 2:1 over the investigated pH range. From the surface activity parameters (CMC, γ CMC, Γmax, Amin estimated from surface measurements and interaction parameters (βm, βσ, in addition to the micellar and interfacial compositions ( x 1 m , x 1 σ obtained from the theory of regular solutions, a synergistic effect is evident in the mixed micelle and at the water/air interface. Moreover, the mixed CTAC/OCT at α CTAC = 0.67 exhibited the maximum synergistic interaction. The results obtained from surface tension measurements indicated that the mixed CTAC/OCT exhibits considerably higher surface activities compared to single CTAC or OCT. The contact angle results confirmed that the mixed CTAC/OCT is a better collector than the individual CTAC or OCT for the flotation of muscovite. According to the results obtained from adsorption experiments, compared with that of individual CTAC or OCT, the amounts of CTAC and OCT adsorbed on the muscovite surface are considerably increase in the mixed systems because of co-adsorption. Based on these results, the mixed CTAC/OCT exhibits a remarkable synergistic effect during the flotation and adsorption of muscovite.

  15. Cell-cell interactions impacts on the rate of swarm expansion and the edge shape of a colony swarming Pseudomonas aeruginosa

    Science.gov (United States)

    Amiri, Aboutaleb; Tierra, Giordano; Xu, Zhiliang; Shrout, Joshua; Alber, Mark

    Collective motion has been observed by several bacterial species including the pathogenic bacterium P. aeruginosa. A flagellum at the pole is known to generate a self-propulsion motion. However, the role of type IV pili (TFP), distributed on the cell membrane, during swarming needs to be investigated in more details. In this work we introduce a model that combines the hydrodynamic and biophysical interactions in order to study the impact of the TFP interactions on swarming behavior of the colony. The model describes the motion and interactions of rod-shaped self propelled bacteria inside a thin liquid film. It also includes the equations describing the production and diffusion of surfactant rhamnolipids that is responsible for extraction of water from substrate, and Marangoni driven expansion of the thin liquid film by altering the surface tension. We show that TFP interactions are responsible for slower expansion rate of colonies of TFP deficient mutants compared to wild type. Experimental observations were used to calibrate the model and verify the model assumptions and predictions.

  16. Acquaintance ratings of the Big Five personality traits: incremental validity beyond and interactive effects with self-reports in the prediction of workplace deviance.

    Science.gov (United States)

    Kluemper, Donald H; McLarty, Benjamin D; Bing, Mark N

    2015-01-01

    It is widely established that the Big Five personality traits of conscientiousness, agreeableness, and emotional stability are antecedents to workplace deviance (Berry, Ones, & Sackett, 2007). However, these meta-analytic findings are based on self-reported personality traits. A recent meta-analysis by Oh, Wang, and Mount (2011) identified the value of acquaintance-reported personality in the prediction of job performance. The current investigation extends prior work by comparing the validities of self- and acquaintance-reported personality in the prediction of workplace deviance across 2 studies. We also hypothesized and tested an interactive, value-added integration of self- with acquaintance-reported personality using socioanalytic personality theory (R. T. Hogan, 1991). Both studies assessed self- and acquaintance-rated Big Five traits, along with supervisor-rated workplace deviance. However, the studies varied the measures of workplace deviance, and the 2nd study also included a self-rated workplace deviance criterion for additional comparison. Across both studies, the traits of conscientiousness and agreeableness were strong predictors of workplace deviance, and acquaintance-reported personality provided incremental validity beyond self-reports. Additionally, acquaintance-reported conscientiousness and agreeableness moderated the prediction of workplace deviance by interacting with the corresponding self-reported traits. Implications for personality theory and measurement are discussed along with applications for practice. (c) 2015 APA, all rights reserved.

  17. Factorial design for the evaluation of the interaction effect between particle size and heating rate in the kinetic energy of coal combustion

    Energy Technology Data Exchange (ETDEWEB)

    Avila, Ivonete; Silva, Eugenio A.G.; Mortari, Daniela A.; Crnkovic, Paula M.; Milioli, Fernando E. [University of Sao Paulo (EESC/USP), Sao Carlos, SP (Brazil). Engineering School. Group of Thermal and Fluids Engineering], Emails: iavila@sc.usp.br, eugenio.silva@usp.br, paulam@sc.usp.br, milioli@sc.usp.br

    2010-07-01

    This paper evaluates the behavior of kinetic energy for different heating rates ({alpha}) and particle sizes of the material in the study of the coal combustion process. It aims to obtain a response surface in a large range of particle size, using heating rates between the minimum and maximum values allowed by the equipment. Therefore it searches for a model to evaluate the interaction effect between particle size and the heating rate and to predict the activation energy of the process studied. The activation energy of the process was determined using the isoconversional model Model Free Kinetics. In this model, the activation energy (E{sub {alpha}}) is obtained as a function of the reaction extent ({alpha}). The subscript in E{sub {alpha}} designates the values related to a given value of conversion ({alpha}). All experiments were conducted in thermogravimetric balance using samples of a Brazilian coal (EC4500) witch average particle size between 163 to 650 {mu}m and heating rates between 10 and 40 deg C min{sup -1} in dynamic atmosphere of air. A central rotatable composite design was applied for the 2{sup 2} factorial design including 4 tests under the axial conditions and 3 repetitions in the central point. As expected, the results show that both the particle size and the heating rate affected significantly the values of activation energy of the coal combustion process obtained by the model used. (author)

  18. The effect of consultant-led interactive pre-clinic case note review on follow-up rates of an otology outpatient clinic.

    Science.gov (United States)

    Lo, S; Eze, N; Jonathan, D A

    2005-02-01

    The effect of pre-clinic consultant-led interactive case note discussion on the follow-up rate of an otology outpatient clinic was assessed. The clinic was divided into two groups. In one group, all cases were delegated by the consultant at the beginning of clinic without discussion. In the other group, before the start of clinic, the team reviewed all case notes and formed a management plan for each patient. Overall, lower follow-up rates were observed in cases which were discussed prior to the start of clinic (53.2-45.7%; p = 0.02). This was found in all doctor grades, although statistically significant only for middle grade (consultant: 48.3-41.6%, p = 0.10; middle grade: 58.5-45.5%, p = 0.05 and senior house officer: 60.2-57.8%, p = 0.73). Junior doctor's follow-up rates were much higher than the consultant's rates (p < 0.01). In conclusion, pre-clinic consultant-led case note review reduced otology outpatient follow-up rate.

  19. Influence of pH and ionic strength on electrostatic properties of ferredoxin, FNR, and hydrogenase and the rate constants of their interaction

    Science.gov (United States)

    Diakonova, A. N.; Khrushchev, S. S.; Kovalenko, I. B.; Riznichenko, G. Yu; Rubin, A. B.

    2016-10-01

    Ferredoxin (Fd) protein transfers electrons from photosystem I (PSI) to ferredoxin:NADP+-reductase (FNR) in the photosynthetic electron transport chain, as well as other metabolic pathways. In some photosynthetic organisms including cyanobacteria and green unicellular algae under anaerobic conditions Fd transfers electrons not only to FNR but also to hydrogenase—an enzyme which catalyzes reduction of atomic hydrogen to H2. One of the questions posed by this competitive relationship between proteins is which characteristics of thylakoid stroma media allow switching of the electron flow between the linear path PSI-Fd-FNR-NADP+ and the path PSI-Fd-hydrogenase-H2. The study was conducted using direct multiparticle simulation approach. In this method protein molecules are considered as individual objects that experience Brownian motion and electrostatic interaction with the surrounding media and each other. Using the model we studied the effects of pH and ionic strength (I) upon complex formation between ferredoxin and FNR and ferredoxin and hydrogenase. We showed that the rate constant of Fd-FNR complex formation is constant in a wide range of physiologically significant pH values. Therefore it can be argued that regulation of FNR activity doesn’t involve pH changes in stroma. On the other hand, in the model rate constant of Fd-hydrogenase interaction dramatically depends upon pH: in the range 7-9 it increases threefold. It may seem that because hydrogenase reduces protons it should be more active when pH is acidic. Apparently, regulation of hydrogenase’s affinity to both her reaction partners (H+ and Fd) is carried out by changes in its electrostatic properties. In the dark, the protein is inactive and in the light it is activated and starts to interact with both Fd and H+. Therefore, we can conclude that in chloroplasts the rate of hydrogen production is regulated by pH through the changes in the affinity between hydrogenase and ferredoxin.

  20. Synergistic effects of fire and elephants on arboreal animals in an African savanna.

    Science.gov (United States)

    Pringle, Robert M; Kimuyu, Duncan M; Sensenig, Ryan L; Palmer, Todd M; Riginos, Corinna; Veblen, Kari E; Young, Truman P

    2015-11-01

    Disturbance is a crucial determinant of animal abundance, distribution and community structure in many ecosystems, but the ways in which multiple disturbance types interact remain poorly understood. The effects of multiple-disturbance interactions can be additive, subadditive or super-additive (synergistic). Synergistic effects in particular can accelerate ecological change; thus, characterizing such synergies, the conditions under which they arise, and how long they persist has been identified as a major goal of ecology. We factorially manipulated two principal sources of disturbance in African savannas, fire and elephants, and measured their independent and interactive effects on the numerically dominant vertebrate (the arboreal gekkonid lizard Lygodactylus keniensis) and invertebrate (a guild of symbiotic Acacia ants) animal species in a semi-arid Kenyan savanna. Elephant exclusion alone (minus fire) had negligible effects on gecko density. Fire alone (minus elephants) had negligible effects on gecko density after 4 months, but increased gecko density twofold after 16 months, likely because the decay of fire-damaged woody biomass created refuges and nest sites for geckos. In the presence of elephants, fire increased gecko density nearly threefold within 4 months of the experimental burn; this occurred because fire increased the incidence of elephant damage to trees, which in turn improved microhabitat quality for geckos. However, this synergistic positive effect of fire and elephants attenuated over the ensuing year, such that only the main effect of fire was evident after 16 months. Fire also altered the structure of symbiotic plant-ant assemblages occupying the dominant tree species (Acacia drepanolobium); this influenced gecko habitat selection but did not explain the synergistic effect of fire and elephants. However, fire-driven shifts in plant-ant occupancy may have indirectly mediated this effect by increasing trees' susceptibility to elephant damage. Our

  1. Synergistic Polaron Formation in the Hubbard-Holstein Model at Small Doping

    Energy Technology Data Exchange (ETDEWEB)

    Macridin, Alexandru [University of Cincinnati; Moritz, Brian [University of Waterloo, Canada; Jarrell, Mark [University of Cincinnati; Maier, Thomas A [ORNL

    2006-01-01

    We study the effect of dynamical Holstein phonons on the physics of the Hubbard model at small doping using the dynamical cluster approximation. Non-local antiferromagnetic correlations are found to significantly enhance the electron-phonon coupling, resulting in polaron formation for moderate coupling strengths. At finite doping, the electron-phonon coupling is found to strongly enhance the non-local spin correlations, indicating a synergistic interplay between the electron- phonon coupling and antiferromagnetic correlations. Although it enhances the pairing interaction, the electron-phonon coupling is found to decrease the superconducting transition temperature, due to the reduction in the quasiparticle fraction.

  2. Lichenysin-geminal amino acid-based surfactants: Synergistic action of an unconventional antimicrobial mixture.

    Science.gov (United States)

    Coronel-León, Jonathan; Pinazo, Aurora; Pérez, Lourdes; Espuny, Mª José; Marqués, Ana Mª; Manresa, Angeles

    2017-01-01

    Recently it has been demonstrated that catanionic mixtures of oppositely charged surfactants have improved physicochemical-biological properties compared to the individual components. Isotherms of mixtures of an anionic biosurfactant (lichenysin) and a cationic aminoacid surfactant (C3(LA)2) indicate a strong interaction suggesting the formation of a new "pseudo-surfactant". The antimicrobial properties of the mixture lichenysin and C3(LA)2 M80:20, indicate a synergistic effect of the components. The mechanism of action on the bacterial envelope was assessed by flow cytometry and Transmission Electron Microscopy. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Stroke from Vasospasm due to Marijuana Use: Can Cannabis Synergistically with Other Medications Trigger Cerebral Vasospasm?

    Directory of Open Access Journals (Sweden)

    Marium Jamil

    2016-01-01

    Full Text Available We present a case of imaging proven cerebral vasospasm causing ischemic stroke in a young patient chronically on buprenorphine-naloxone for heroin remission who started smoking cannabis on a daily basis. With cannabis legalization spreading across the states in the USA, it is important for physicians not only to be aware of cannabis reported association with cerebral vasospasm in some patients but also to be on the lookout for possible interacting medications that can synergistically affect cerebral vessels causing debilitating strokes.

  4. Fatal kernicterus in a girl deficient in glucose-6-phosphate dehydrogenase: a paradigm of synergistic heterozygosity.

    Science.gov (United States)

    Zangen, Shmuel; Kidron, Devorah; Gelbart, Terri; Roy-Chowdhury, Namita; Wang, Xia; Kaplan, Michael

    2009-04-01

    A 6-day-old female newborn, readmitted for extreme hyperbilirubinemia with bilirubin encephalopathy, died despite 2 double-volume exchange transfusions. On autopsy examination the basal ganglia and hippocampus were selectively stained deep yellow. The infant was heterozygous for both the glucose-6-phosphate dehydrogenase Mediterranean mutation and for the (TA)(6)/(TA)(7) promoter polymorphism for the gene encoding the bilirubin conjugating enzyme uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1*28, associated with Gilbert syndrome). No additional mutations of the UGT1A1 were detected. Seemingly innocuous, heterozygotic mutations may interact synergistically to result in serious and even fatal outcomes.

  5. Synergistic Effect of Fullerene-Capped Gold Nanoparticles on Graphene Electrochemical Supercapacitors

    OpenAIRE

    Yong, Virginia; Hahn, H. Thomas

    2013-01-01

    We report the synthesis of graphene/fullerene-capped gold nanoparticle nanocomposite film which was used to construct supercapacitor electrodes. The fullerene-based self-assembled monolayers on gold nanoparticles (AuNPs) were attained via the fullerene(C60)-gold interaction. The fullerene-capped AuNPs effectively separated the graphene sheets preventing aggregation. A synergistic effect was observed—the specific capacitance of graphene/fullerene-capped AuNP electrode is 197 F/g, which is high...

  6. Basal metabolic rate, maximum thermogenic capacity and aerobic scope in rodents: interaction between environmental temperature and torpor use.

    Science.gov (United States)

    Careau, Vincent

    2013-04-23

    When torpid animals arouse and warm up to restore normal body temperature (T(b)), they produce heat at levels that can reach up to 10 times basal metabolic rate (BMR), close to the cold-induced summit metabolism (VO(2)-sum). Because torpor is an adaptation aimed at conserving energy over periods of low ambient temperature (T(a)) and food availability, selective forces that have led to the evolution of torpor may have simultaneously favoured high thermogenic capacity (i.e. VO(2)-sum) relative to the maintenance costs (i.e. BMR), hence a higher factorial aerobic scope (FAS; the ratio of VO(2)-sum to BMR). My objective was to test this adaptive hypothesis using a phylogenetically informed comparative approach with data on BMR and VO(2)-sum in rodents. I found a strong negative correlation between FAS and the average of the daily minimum T(a) (T(min)) in species using torpor, which was due to differential effects of T(a) on BMR (but not VO(2)-sum) in species that use torpor compared with species that do not. In addition, FAS was negatively correlated with the lowest torpid T(b) in a subset of nine species. These results suggest that in species using torpor, selective forces may have acted to maximize the efficiency of thermogenic capacity (VO(2)-sum) relative to maintenance costs (BMR), resulting in an increasing FAS with decreasing T(a).

  7. Driving factors of interactions between the exchange rate market and the commodity market: A wavelet-based complex network perspective

    Science.gov (United States)

    Wen, Shaobo; An, Haizhong; Chen, Zhihua; Liu, Xueyong

    2017-08-01

    In traditional econometrics, a time series must be in a stationary sequence. However, it usually shows time-varying fluctuations, and it remains a challenge to execute a multiscale analysis of the data and discover the topological characteristics of conduction in different scales. Wavelet analysis and complex networks in physical statistics have special advantages in solving these problems. We select the exchange rate variable from the Chinese market and the commodity price index variable from the world market as the time series of our study. We explore the driving factors behind the behavior of the two markets and their topological characteristics in three steps. First, we use the Kalman filter to find the optimal estimation of the relationship between the two markets. Second, wavelet analysis is used to extract the scales of the relationship that are driven by different frequency wavelets. Meanwhile, we search for the actual economic variables corresponding to different frequency wavelets. Finally, a complex network is used to search for the transfer characteristics of the combination of states driven by different frequency wavelets. The results show that statistical physics have a unique advantage over traditional econometrics. The Chinese market has time-varying impacts on the world market: it has greater influence when the world economy is stable and less influence in times of turmoil. The process of forming the state combination is random. Transitions between state combinations have a clustering feature. Based on these characteristics, we can effectively reduce the information burden on investors and correctly respond to the government's policy mix.

  8. Heart-rate variability and blood-lactate threshold interaction during progressive resistance exercise in healthy older men.

    Science.gov (United States)

    Simões, Rodrigo P; Mendes, Renata G; Castello, Viviane; Machado, Heloísa G; Almeida, Larissa B; Baldissera, Vilmar; Catai, Aparecida M; Arena, Ross; Borghi-Silva, Audrey

    2010-05-01

    The objective of this study was to (a) evaluate the impact of the leg press, at variable percentages of 1 repetition maximum (1RM), on heart rate variability (HRV) and blood lactate and (b) determine the relationship between HRV with blood lactate in a healthy elderly cohort. Ten healthy men (64 +/- 4 years) participated in a progressive leg-press protocol to maximal exertion. Initially, 1RM for the leg press was determined for all subjects. The protocol then began at 10% of 1RM, with subsequent increases of 10% until 30% of 1RM, followed by incremental adjustments of 5% until exhaustion. The measurement of instantaneous R-R interval variability from Poincare plots (SD1 and SD2) and time domain indexes (RMSSD and RMSM), blood pressure, and blood lactate were obtained at rest and all leg-press loads. Significant alterations of HRV and blood lactate were observed from 30% of 1RM leg press (p measure obtained at a relatively low cost may be used to identify neural and metabolic alterations during RE in older subjects.

  9. Gas flow rate dependence of the discharge characteristics of a helium atmospheric pressure plasma jet interacting with a substrate

    Science.gov (United States)

    Yan, Wen; Economou, Demetre J.

    2017-10-01

    A 2D (axisymmetric) computational study of the discharge characteristics of an atmospheric pressure plasma jet as a function of gas flow rate was performed. The helium jet emerged from a dielectric tube, with an average gas flow velocity in the range 2.5-20 m s-1 (1 atm, 300 K) in a nitrogen ambient, and impinged on a substrate a short distance dowstream. The effect of the substrate conductivity (conductror versus insulator) was also studied. Whenever possible, simulation predictions were compared with published experimental observations. Discharge ignition and propagation in the dielectric tube were hardly affected by the He gas flow velocity. Most properties of the plasma jet, however, depended sensitively on the He gas flow velocity, which determined the concentration distributions of helium and nitrogen in the mixing layer forming in the gap between the tube exit and the substrate. At low gas flow velocity, the plasma jet evolved from a hollow (donut-shaped) feature to one where the maximum of electron density was on axis. When the gas flow velocity was high, the plasma jet maintained its hollow structure until it struck the substrate. For a conductive substrate, the radial ion fluxes to the surface were relatively uniform over a radius of ~0.4-0.8 mm, and the dominant ion flux was that of He+. For a dielectric substrate, the radial ion fluxes to the surface peaked on the symmetry axis at low He gas flow velocity, but a hollow ion flux distribution was observed at high gas flow velocity. At the same time, the main ion flux switched from N2+ to He2+ as the He gas flow velocity increased from a low to a high value. The diameter of the plasma ‘footprint’ on the substrate first increased with increasing He gas flow velocity, and eventually saturated with further increases in velocity.

  10. Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum.

    Science.gov (United States)

    Anju, S; Kumar, Nishanth S; Krishnakumar, B; Kumar, B S Dileep

    2015-01-01

    Superficial mycoses caused by dermatophytic fungi such as Trichophyton rubrum represent the most common type of worldwide human infection affecting various keratinized tissues in our body such as the skin, hair, and nails, etc. The dermatophytic infection is a significant public health threat due to its persistent nature and high recurrence rates, and thus alternative treatments to cure this fungal infection are urgently required. The present study mainly focused on the synergistic activity of violacein with four azole drugs (ketoconazole, fluconazole, clotrimazole, and itraconazole) against T. rubrum. The synergistic antifungal activities of violacein and azoles were measured by checkerboard microdilution and time-kill assays. In our study, combinations of violacein and azoles predominantly recorded synergistic effect (FIC index rubrum was significantly arrested after 4-12 h of treatment. The combination of violacein and azoles leads to the enhanced inhibition of mycelial growth and conidial germination. Moreover combination enhanced the rate of release of intracellular materials. Morphological changes by SEM analysis were also prominent with the combination. A normal human cell line [Foreskin (FS) normal fibroblast] was used to check the cytotoxicity of violacein. Interestingly violacein recorded no cytotoxicity up to 100 μg/ml. The in vitro synergistic effect of violacein and azoles against clinically relevant fungi, T. rubrum, is reported here for the first time. Finally, our findings support the potential use of the violacein as an antifungal agent especially against dermatophytic fungi T. rubrum.

  11. Mesoporous polydopamine nanoparticles with co-delivery function for overcoming multidrug resistance via synergistic chemo-photothermal therapy.

    Science.gov (United States)

    Xing, Yuxin; Zhang, Jixi; Chen, Feng; Liu, Junjie; Cai, Kaiyong

    2017-06-29

    Theranostic agents for combined chemo-photothermal therapy have attracted intensive interest in the treatment of multi-drug resistance (MDR) in cancer therapy. However, the development of simple theranostic agents as dual hosts for both heat and a high payload of chemotherapeutic agents remains a big challenge. Herein, mesoporous polydopamine nanoparticles (MPDA) were successfully developed with properties of a high payload of DOX (up to 2000 μg mg(-1)) and the drug efflux inhibitor TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate), as well as strong near-infrared absorption. Particularly, DOX and TPGS were sequentially loaded in the pore space and on the external particle surface of MPDA via π-π stacking and hydrophobic interactions, resulting in a MPDA-DOX@TPGS complex. The DOX release observably relies on the pH value and glutathione (GSH). Furthermore, it is possible to accelerate the rate of drug release by NIR irradiation. Importantly, the MPDA-DOX@TPGS complex was found to escape from endosomes after cellular uptake and release the loaded drugs into the cytosol. By TPGS mediated MDR reversal, the delivered DOX induced significant cytotoxicity to MCF-7/ADR cells. Besides, MPDA can absorb the NIR light and convert it into fatal heat to kill the cancer cells. As a consequence, the combined therapy in our system yields a synergistic effect with high therapeutic efficacy.

  12. Synergistic estrogenic effects of Fusarium and Alternaria mycotoxins in vitro.

    Science.gov (United States)

    Vejdovszky, Katharina; Hahn, Kathrin; Braun, Dominik; Warth, Benedikt; Marko, Doris

    2017-03-01

    Mycotoxins are toxic secondary metabolites formed by various fungal species that are found as natural contaminants in food. This very heterogeneous group of compounds triggers multiple toxic mechanisms, including endocrine disruptive potential. Current risk assessment of mycotoxins, as for most chemical substances, is based on the effects of single compounds. However, concern on a potential enhancement of risks by interactions of single substances in naturally occurring mixtures has greatly increased recently. In this study, the combinatory effects of three mycoestrogens were investigated in detail. This includes the endocrine disruptors zearalenone (ZEN) and α-zearalenol (α-ZEL) produced by Fusarium fungi and alternariol (AOH), a cytotoxic and estrogenic mycotoxin formed by Alternaria species. For evaluation of effects, estrogen-dependent activation of alkaline phosphatase (AlP) and cell proliferation were tested in the adenocarcinoma cell line Ishikawa. The estrogenic potential varied among the single substances. Half maximum effect concentrations (EC50) for AlP activation were evaluated for α-ZEL, ZEN and AOH as 37 pM, 562 pM and 995 nM, respectively. All three mycotoxins were found to act as partial agonists. The majority of binary combinations, even at very low concentrations in the case of α-ZEL, showed strong synergism in the AlP assay. These potentiating phenomena of mycotoxin mixtures highlight the urgent need to incorporate combinatory effects into future risk assessment, especially when endocrine disruptors are involved. To the best of our knowledge, this study presents the first investigation on synergistic effects of mycoestrogens.

  13. Resveratrol Radical Repair by Vitamin C at the Micelle-Water Interface: Unexpected Reaction Rates Explained by Ion-Dipole Interactions.

    Science.gov (United States)

    Kerzig, Christoph; Hoffmann, Matthias; Goez, Martin

    2018-02-26

    Repair reactions of lipophilic phenoxy radicals by hydrophilic co-antioxidants at model membranes are important for understanding the factors that govern the interactions between radical scavengers in biological systems. By using near-UV photoionization, we have selectively generated the phenoxy radical of the famous antioxidant resveratrol inside anionic (SDS), cationic (DTAC), or neutral (TX-100) micelles, as well as in homogeneous aqueous solution, and have compared its repairs in these media by the water-soluble co-antioxidants ascorbic acid and ascorbate monoanion. With all surfactants, these reactions are dynamic processes at the micelle-water interface. Whereas for the combinations ascorbate monoanion/ ionic micelle the repair rates can be rationalized by the Coulombic interactions, unexpected effects were observed with the neutral ascorbic acid and the charged micelles: for the anionic micelles, this repair is three times faster than in homogeneous solution, and two orders of magnitude faster than for the cationic micelles. Given that the repair by a concerted proton-electron transfer demands a coplanar arrangement of the resveratrol phenoxy centre sticking out into the Stern layer and the co-antioxidant hydroxy moiety approaching from the aqueous bulk, we explain these results by ion-dipole interactions: only at a negatively charged micellar surface does the direction of the large dipole moment of ascorbic acid lead to an orientation favourable for the repair. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. A tool for rapid screening of direct DNA agents using reaction rates and relative interaction potency: towards screening environmental contaminants for hazard.

    Science.gov (United States)

    Gavina, Jennilee M A; Rubab, Mamoona; Zhang, Huijuan; Zhu, Jiping; Nong, Andy; Feng, Yong-Lai

    2011-11-01

    DNA damage represents a potential biomarker for determining the exposure risk to chemicals and may provide early warning data for identifying chemical hazards to human health. Here, we have demonstrated a simple chromatography-based method that can be used to rapidly screen for the presence of chemical hazards as well as to determine parameters relevant to hazard assessment. In this proof-of-principle study, a simple in vitro system was used to determine the interaction of pollutants and probable carcinogens, phenyl glycidyl ether (PGE), tetrachlorohydroquinone (Cl(4)HQ), methylmethane sulfonate (MMS), styrene-7,8-oxide (SO), and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), a metabolite of benzo[a]pyrene (B[a]P), with single- and double-stranded DNA probes. Differences in potency and reaction kinetics were studied for chemical and DNA type. A relative interaction potency equivalency (PEQ) of a chemical was determined by ratio of interaction potency of a chemical to BPDE as the reference chemical in the reaction with single- and double-stranded oligodeoxynucleotides. PEQs were found to be BPDE > PGE > SO > MMS > Cl(4)HQ for single-stranded oligodeoxynucleotides while they were found to be BPDE > PGE > Cl(4)HQ > MMS > SO for double-stranded oligodeoxynucleotides. Kinetics evaluation revealed that BPDE reacted with both DNA probes at a significantly faster rate, as compared to the remaining test chemicals. Equilibrium was reached within an hour for BPDE, but required a minimum of 48 h for the remaining chemicals. First-order rate constants were (1.61 ± 0.2) × 10(-3) s(-1) and (3.18 ± 0.4) × 10(-4) s(-1) for reaction of BPDE with double- and single-stranded DNA, respectively. The remaining chemicals possessed rate constants from 2 to 13 × 10(-6) s(-1) with a relative kinetic order for reaction with DNA of BPDE ≫ MMS > SO > PGE > Cl(4)HQ for ds-DNA and BPDE ≫ SO ≈ Cl(4)HQ ≈ MMS > PGE for ss-DNA. We further found that the reaction potency, defined by

  15. Interactive Voice Response and Text-based Self-report Versions of the Electronic Columbia-Suicide Severity Rating Scale Are Equivalent.

    Science.gov (United States)

    Gwaltney, Chad; Mundt, James C; Greist, John H; Paty, Jean; Tiplady, Brian

    2017-01-01

    Objectives: Our study objective was to compare the equivalence of a new version of the electronic Columbia-Suicide Severity Rating Scale that was administered on a tablet device with the existing interactive voice response version in order to support the prospective monitoring of suicidal ideation and behavior in clinical trials and clinical practice. Design: This was a randomized, crossover-equivalence study with no treatment intervention. Setting: The study setting was a psychiatric hospital. Participants: Fifty-eight recently admitted psychiatric inpatients and 28 employees of the hospital site were included in the study. Mean age was 41.0 years (standard deviation=12.5), and 59 percent were female. Measurements: Participants completed both tablet and interactive voice response versions in randomized order, with a 25-minute break between administrations. Finally, participants completed a second administration of the first administered version. Intraclass correlation coefficients (ICCs) and Kappa coefficients were used to evaluate agreement across modalities. Results: High levels of agreement were observed for most severe lifetime (ICC=0.88) and recent (ICC=0.79) ideation, occurrence of actual lifetime (Kappa=0.81) and recent (Kappa=0.73) suicide attempts, and occurrence of lifetime interrupted attempts (Kappa=0.78), aborted attempts (Kappa=0.54), and preparatory behaviors (Kappa=0.77), as well as non-suicidal self-injurious behavior (Kappa=0.73). Scores from both modes significantly differentiated psychiatric patients and hospital employee controls, and the test-retest reliability of both modes was excellent. Conclusions: These results support the validity and reliability of the new tablet-based electronic Columbia-Suicide Severity Rating Scale. This will allow the inclusion of the electronic Columbia-Suicide Severity Rating Scale in a wider range of clinical studies, particularly where a tablet is also being used to collect other study data.

  16. Examining flow-flame interaction and the characteristic stretch rate in vortex-driven combustion dynamics using PIV and numerical simulation

    KAUST Repository

    Hong, Seunghyuck

    2013-08-01

    In this paper, we experimentally investigate the combustion dynamics in lean premixed flames in a laboratory scale backward-facing step combustor in which flame-vortex driven dynamics are observed. A series of tests was conducted using propane/hydrogen/air mixtures for various mixture compositions at the inlet temperature ranging from 300K to 500K and at atmospheric pressure. Pressure measurements and high speed particle image velocimetry (PIV) are used to generate pressure response curves and phase-averaged vorticity and streamlines as well as the instantaneous flame front, respectively, which describe unsteady flame and flow dynamics in each operating regime. This work was motivated in part by our earlier study where we showed that the strained flame consumption speed Sc can be used to collapse the pressure response curves over a wide range of operating conditions. In previous studies, the stretch rate at which Sc was computed was determined by trial and error. In this study, flame stretch is estimated using the instantaneous flame front and velocity field from the PIV measurement. Independently, we also use computed strained flame speed and the experimental data to determine the characteristic values of stretch rate near the mode transition points at which the flame configuration changes. We show that a common value of the characteristic stretch rate exists across all the flame configurations. The consumption speed computed at the characteristic stretch rate captures the impact of different operating parameters on the combustor dynamics. These results suggest that the unsteady interactions between the turbulent flow and the flame dynamics can be encapsulated in the characteristic stretch rate, which governs the critical flame speed at the mode transitions and thereby plays an important role in determining the stability characteristics of the combustor. © 2013 The Combustion Institute.

  17. Microbial Reverse Electrodialysis Cells for Synergistically Enhanced Power Production

    KAUST Repository

    Kim, Younggy

    2011-07-01

    A new type of bioelectrochemical system for producing electrical power, called a microbial reverse-electrodialysis cell (MRC), was developed to increase voltages and power densities compared to those generated individually by microbial fuel cells (MFCs) or reverse electrodialysis (RED) systems. In RED systems, electrode overpotentials create significant energy losses due to thermodynamically unfavorable electrode reactions, and therefore a large number of stacked cells must be used to have significant energy recovery. This results in high capital costs for the large number of membranes, and increases energy losses from pumping water through a large number of cells. In an MRC, high overpotentials are avoided through oxidation of organic matter by exoelectrogenic bacteria on the anode and oxygen reduction on the cathode. An MRC containing only five pairs of RED cells, fed solutions typical of seawater (600 mM NaCl) and river water (12 mM NaCl) at 0.85 mL/min, produced up to 3.6 W/m2 (cathode surface area) and 1.2-1.3 V with acetate as a substrate. Pumping accounted for <2% of the produced power. A higher flow rate (1.55 mL/min) increased power densities up to 4.3 W/m2. COD removal was 98% with a Coulombic efficiency of 64%. Power production by the individual components was substantially lower with 0.7 W/m2 without salinity driven energy, and <0.015 W/m2 with reduced exoelectrogenic activity due to substrate depletion. These results show that the combination of an MFC and a RED stack synergistically increases performance relative to the individual systems, producing a new type of system that can be used to more efficiently capture salinity driven energy from seawater and river water. © 2011 American Chemical Society.

  18. Mitotic recombination and inactivation in Saccharomyces cerevisiae induced by UV-radiation (254 nm) and hyperthermia depend on UV fluence rate.

    Science.gov (United States)

    Petin, V G; Kim, J K; Rassokhina, A V; Zhurakovskaya, G P

    2001-07-01

    In experiments with wild-type diploid yeast cells of Saccharomyces cerevisiae, the synergistic interaction of ultraviolet (UV) light (wavelength, 254 nm) and heat (45--60 degrees C) was studied both for mutagenic and inactivation effects. Simultaneous hyperthermia and UV light treatments increase the frequency of UV-induced mitotic intergenic recombination (crossing-over) and cell inactivation. The enhancing effect was a function of UV light fluence rate. It is concluded that the effect of hyperthermia on low fluence UV or high fluence UV irradiation results in comparable effects on survival and mitotic recombination suggesting similar modulation by hyperthermia of the effects induced by UV at different fluence rates. The interpretation of the data obtained was carried out within the widely accepted point of view considering the synergistic effects as a result of repair ability damage.

  19. Prognostic relevance of the interaction between short-term, metronome-paced heart rate variability, and inflammation: results from the population-based CARLA cohort study.

    Science.gov (United States)

    Medenwald, Daniel; Swenne, Cees A; Loppnow, Harald; Kors, Jan A; Pietzner, Diana; Tiller, Daniel; Thiery, Joachim; Nuding, Sebastian; Greiser, Karin H; Haerting, Johannes; Werdan, Karl; Kluttig, Alexander

    2017-01-01

    To determine the interaction between HRV and inflammation and their association with cardiovascular/all-cause mortality in the general population. Subjects of the CARLA study (n = 1671; 778 women, 893 men, 45-83 years of age) were observed for an average follow-up period of 8.8 years (226 deaths, 70 cardiovascular deaths). Heart rate variability parameters were calculated from 5-min segments of 20-min resting electrocardiograms. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and soluble tumour necrosis factor-alpha receptor type 1 (sTNF-R1) were measured as inflammation parameters. The HRV parameters determined included the standard deviation of normal-to-normal intervals (SDNN), the root-mean-square of successive normal-interval differences (RMSSD), the low- and high-frequency (HF) power, the ratio of both, and non-linear parameters [Poincaré plot (SD1, SD2, SD1/SD2), short-term detrended fluctuation analysis]. We estimated hazard ratios by using covariate-adjusted Cox regression for cardiovascular and all-cause mortality incorporating an interaction term of HRV/inflammation parameters. Relative excess risk due to interactions (RERIs) were computed. We found an interaction effect of sTNF-R1 with SDNN (RERI: 0.5; 99% confidence interval (CI): 0.1-1.0), and a weaker effect with RMSSD (RERI: 0.4; 99% CI: 0.0-0.9) and HF (RERI: 0.4; 99% CI: 0.0-0.9) with respect to cardiovascular mortality on an additive scale after covariate adjustment. Neither IL-6 nor hsCRP showed a significant interaction with the HRV parameters. A change in TNF-α levels or the autonomic nervous system influences the mortality risk through both entities simultaneously. Thus, TNF-α and HRV need to be considered when predicating mortality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  20. MicroRNAs tend to synergistically control expression of genes encoding extensively-expressed proteins in humans

    Directory of Open Access Journals (Sweden)

    Xue Chen

    2017-08-01

    Full Text Available Considering complicated microRNA (miRNA biogenesis and action mechanisms, it was thought so high energy-consuming for a cell to afford simultaneous over-expression of many miRNAs. Thus it prompts that an alternative miRNA regulation pattern on protein-encoding genes must exist, which has characteristics of energy-saving and precise protein output. In this study, expression tendency of proteins encoded by miRNAs’ target genes was evaluated in human organ scale, followed by quantitative assessment of miRNA synergism. Expression tendency analysis suggests that universally expressed proteins (UEPs tend to physically interact in clusters and participate in fundamental biological activities whereas disorderly expressed proteins (DEPs are inclined to relatively independently execute organ-specific functions. Consistent with this, miRNAs that mainly target UEP-encoding mRNAs, such as miR-21, tend to collaboratively or even synergistically act with other miRNAs in fine-tuning protein output. Synergistic gene regulation may maximize miRNAs’ efficiency with less dependence on miRNAs’ abundance and overcome the deficiency that targeting plenty of genes by single miRNA makes miRNA-mediated regulation high-throughput but insufficient due to target gene dilution effect. Furthermore, our in vitro experiment verified that merely 25 nM transfection of miR-21 be sufficient to influence the overall state of various human cells. Thus miR-21 was identified as a hub in synergistic miRNA–miRNA interaction network. Our findings suggest that synergistic miRNA–miRNA interaction is an important endogenous miRNA regulation mode, which ensures adequate potency of miRNAs at low abundance, especially those implicated in fundamental biological regulation.

  1. Effect of interactions with humans on behaviour, mucosal immunity and upper respiratory disease of shelter cats rated as contented on arrival.

    Science.gov (United States)

    Gourkow, Nadine; Phillips, Clive J C

    2015-10-01

    Sustained positive affect may decrease vulnerability to upper respiratory infections in cats admitted to a shelter. Incidence of upper respiratory infections was examined in cats rated as Content upon admission to an animal shelter when provided with or without treatment to sustain contentment. Ninety-six cats rated as Content upon admission were provided with either human interaction, including petting, playing, and grooming, in four 10min sessions/d for 10 days or were exposed to a control treatment of a human standing in front of the cage with eyes averted for the same period. Changes in emotional state and mucosal immune responses were measured daily in treated and control groups. Infectious status was determined upon admission and on days 4 and 10 using combined conjunctival and oropharyngeal swab specimens tested by quantitative real-time PCR for feline herpes virus type 1, feline calicivirus, Mycoplasma felis, Chlamydophila felis, and Bordetella bronchiseptica. The onset of upper respiratory disease (URD) was determined by veterinary staff based on clinical signs, including ocular or nasal discharge. Treated cats were more likely to remain Content (Incident Rate Ratio [IRR]:1.13, Confidence Interval: 0.98-1.30, P <0.0001) and less likely to be rated as Anxious or Frustrated than Control cats over a 10 day period (IRR: 0.61, 95% CI: 0.42-0.88, P =0.007). Feline secretory IgA (S-IgA) quantified in faeces by ELISA techniques, was greater for Treated than Control cats (1451 Vs 846μg/g). Within the Treatment group, S-IgA was greater for cats that sustained Contentment throughout the study period compared to cats that became Anxious or Frustrated (1846 Vs 1394μg/g). An increasing proportion of Control than Treated cats shed pathogens over time (Control 22%, 36%, 61%; Treated 35%, 26%, 32% on d 1, 4 and 10, respectively; P =0.006). Control cats were more likely to develop URD than Treated cats (HR 2.9, CI: 1.30-6.67, P =0.01). Cats that responded positively to

  2. Determination of correlation times from selective and non-selective spin-lattice relaxation rates and their use in drug-drug and drug-albumin interaction studies

    Directory of Open Access Journals (Sweden)

    Tinoco Luzineide Wanderley

    1999-01-01

    Full Text Available The effects of the changes in sample concentration on the NMR chemical shifts and on the selective and non-selective spin-lattice relaxation rates (R1S and R1NS of the three isomers of nitrobenzaldeyde guanyl hydrazone (NBGH pure and with bovine serum albumin (BSA were measured in solution. The results wereused to determine the correlation times (tauc, showing that the degree of intermolecular drug-drug association varies with the nitro group position on the ring and that this degree of association interferes with the interaction of these drugs with BSA. The results suggest that the degree of drug-drug and drug-BSA association are related to the in vitro anti-Trypanosoma cruzi activity of these compounds.

  3. Intersystem-crossing and phosphorescence rates in fac-Ir{sup III}(ppy){sub 3}: A theoretical study involving multi-reference configuration interaction wavefunctions

    Energy Technology Data Exchange (ETDEWEB)

    Kleinschmidt, Martin; Marian, Christel M., E-mail: Christel.Marian@hhu.de [Institute of Theoretical and Computational Chemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf (Germany); Wüllen, Christoph van [Fachbereich Chemie and Forschungszentrum OPTIMAS, Technical University of Kaiserslautern, Erwin-Schrödinger-Straße 52, 67663 Kaiserslautern (Germany)

    2015-03-07

    We have employed combined density functional theory and multi-reference configuration interaction methods including spin–orbit coupling (SOC) effects to investigate the photophysics of the green phosphorescent emitter fac-tris-(2-phenylpyridine)iridium (fac-Ir(ppy){sub 3}). A critical evaluation of our quantum chemical approaches shows that a perturbational treatment of SOC is the method of choice for computing the UV/Vis spectrum of this heavy transition metal complex while multi-reference spin–orbit configuration interaction is preferable for calculating the phosphorescence rates. The particular choice of the spin–orbit interaction operator is found to be of minor importance. Intersystem crossing (ISC) rates have been determined by Fourier transformation of the time correlation function of the transition including Dushinsky rotations. In the electronic ground state, fac-Ir(ppy){sub 3} is C{sub 3} symmetric. The calculated UV/Vis spectrum is in excellent agreement with experiment. The effect of SOC is particularly pronounced for the metal-to-ligand charge transfer (MLCT) band in the visible region of the absorption spectrum which does not only extend its spectral onset towards longer wavelengths but also experiences a blue shift of its maximum. Pseudo-Jahn-Teller interaction leads to asymmetric coordinate displacements in the lowest MLCT states. Substantial electronic SOC and a small energy gap make ISC an ultrafast process in fac-Ir(ppy){sub 3}. For the S{sub 1}↝T{sub 1} non-radiative transition, we compute a rate constant of k{sub ISC} = 6.9 × 10{sup 12} s{sup −1} which exceeds the rate constant of radiative decay to the electronic ground state by more than six orders of magnitude, in agreement with the experimental observation of a subpicosecond ISC process and a triplet quantum yield close to unity. As a consequence of the geometric distortion in the T{sub 1} state, the T{sub 1} → S{sub 0} transition densities are localized on one of the

  4. Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Johnathan Cooper-Knock

    2017-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs. We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18. Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033. We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025. Our data are

  5. Research on the relationship of institutional innovation, organizational learning and synergistic effect: An empirical study of chineses university spin-offs

    Directory of Open Access Journals (Sweden)

    Zhang Hao

    2014-06-01

    also as enterprise. This result of study pointed that. “Institutions” and “organizations” are the two important factors in synergistic innovation, so the synergy mechanism design should be followed by the interaction relationship between these two above. Originality/value: Synergistic innovation is the guidance theory which leads the development trend of university-industrial cooperation in China. In this paper, the "institution" and "organization", as the two primary elements, are introduced to analyze the process of synergistic innovation. Then, the authors discussed the role of the "institutional innovation" and "organizational learning" in the process of synergistic innovation, aimed at study on the operational mechanism of the influence factors.

  6. Negative cognitive style and looming cognitive style synergistically predict stress generation.

    Science.gov (United States)

    Kleiman, Evan M; Riskind, John H

    2014-05-01

    There is a growing body of evidence that suggests that cognitive vulnerabilities to depression or anxiety may lead individuals to generate negative interpersonal life events. However, there has been no study to date that examines the effects of co-occurring vulnerabilities to depression and anxiety. In a sample of 304 participants, we examined the potential interaction of co-occurring negative cognitive style, a vulnerability to depression and looming cognitive style, vulnerability to anxiety. Results indicate that co-occurring cognitive vulnerabilities synergistically predict higher levels of negative interpersonal life events six weeks later, even when controlling for initial levels of stressful life events and symptoms of depression and anxiety. Thus, co-occurring vulnerabilities may have stronger stress generating effects than would be expected from the additive effects of each vulnerability considered separately. This finding highlights the importance of examining cognitive vulnerabilities as interactive effects rather than as individual vulnerabilities.

  7. Synergistic effect of photocatalysis and adsorption of nano-TiO2self-assembled onto sulfanyl/activated carbon composite.

    Science.gov (United States)

    Sun, Zhenya; He, Xiaojun; Du, Jianhua; Gong, Wenqi

    2016-11-01

    We report a significant synergistic effect of photocatalysis and adsorption by depositing 3-6 nm TiO 2 particles onto sulfanyl (HS)/activated carbon composite using molecular self-assemble method in low-temperature aqueous system. The synergistic effect was studied by comparing pure TiO 2 and TiO 2 /sulfanyl/activated carbon composite to photocatalytic degrade methylene blue (MB) in a quartz glass reactor. The results showed that the photocatalytic activity of the TiO 2 /HS/AC composite compared to pure TiO 2 has been greatly enhanced calculated from a simulated first-order kinetics model. The synergistic enhancement at low MB concentration was significantly stronger than that at high concentration, and the synergistic effect calculated from the model at initial concentration of 1 mg/L was approximately 64 times than at initial concentration of 15 mg/L. This is because when the adsorption rate was much faster than the photocatalytic degradation rate, strong adsorption of MB molecules may inhibit subsequent photocatalytic degradation reaction. The enhancement was found mainly due to the strong synergistic effect of the adsorption of MB of sulfanyl/activated carbon substrate and the photocatalysis of TiO 2 nanoparticles.

  8. Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies.

    Science.gov (United States)

    Tilahun, Mulualem E; Rajagopalan, Govindarajan; Shah-Mahoney, Nalini; Lawlor, Rebecca G; Tilahun, Ashenafi Y; Xie, Chen; Natarajan, Kannan; Margulies, David H; Ratner, David I; Osborne, Barbara A; Goldsby, Richard A

    2010-06-01

    Staphylococcal enterotoxin B (SEB), a shock-inducing exotoxin synthesized by Staphylococcus aureus, is an important cause of food poisoning and is a class B bioterrorism agent. SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen. We derived and searched a set of monoclonal mouse anti-SEB antibodies to identify neutralizing anti-SEB antibodies that bind to different sites on the toxin. A pair of non-cross-reactive, neutralizing anti-SEB monoclonal antibodies (MAbs) was found, and a combination of these antibodies inhibited SEB-induced T-cell proliferation in a synergistic rather than merely additive manner. In order to engineer antibodies more suitable than mouse MAbs for use in humans, the genes encoding the VL and VH gene segments of a synergistically acting pair of mouse MAbs were grafted, respectively, onto genes encoding the constant regions of human Igkappa and human IgG1, transfected into mammalian cells, and used to generate chimeric versions of these antibodies that had affinity and neutralization profiles essentially identical to their mouse counterparts. When tested in cultures of human peripheral blood mononuclear cells or splenocytes derived from HLA-DR3 transgenic mice, the chimeric human-mouse antibodies synergistically neutralized SEB-induced T-cell activation and cytokine production.

  9. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, Clement; Fernandez, Manuel [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Requardt, Herwig [European Synchrotron Radiation Facility, Grenoble (France); Wion, Didier [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Vial, Jean-Claude [Université Joseph Fourier, Grenoble (France); Laboratoire Interdisciplinaire de Physique, St Martin d’Hères (France); Segebarth, Christoph; Sanden, Boudewijn van der, E-mail: boudewijn.vandersanden@ujf-grenoble.fr [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France)

    2013-09-01

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

  10. Rising CO2 interacts with growth light and growth rate to alter photosystem II photoinactivation of the coastal diatom Thalassiosira pseudonana.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available We studied the interactive effects of pCO(2 and growth light on the coastal marine diatom Thalassiosira pseudonana CCMP 1335 growing under ambient and expected end-of-the-century pCO(2 (750 ppmv, and a range of growth light from 30 to 380 µmol photons·m(-2·s(-1. Elevated pCO(2 significantly stimulated the growth of T. pseudonana under sub-saturating growth light, but not under saturating to super-saturating growth light. Under ambient pCO(2 susceptibility to photoinactivation of photosystem II (σ(i increased with increasing growth rate, but cells growing under elevated pCO(2 showed no dependence between growth rate and σ(i, so under high growth light cells under elevated pCO(2 were less susceptible to photoinactivation of photosystem II, and thus incurred a lower running cost to maintain photosystem II function. Growth light altered the contents of RbcL (RUBISCO and PsaC (PSI protein subunits, and the ratios among the subunits, but there were only limited effects on these and other protein pools between cells grown under ambient and elevated pCO(2.

  11. Characterisation of the interactions between substrate, copper(II) complex and DNA and their role in rate acceleration in DNA-based asymmetric catalysis.

    Science.gov (United States)

    Draksharapu, Apparao; Boersma, Arnold J; Browne, Wesley R; Roelfes, Gerard

    2015-02-28

    Interactions of the azachalcone derived substrate Aza with copper(II) complexes in the presence and absence of st-DNA were studied in detail by UV/Vis absorption, EPR and Raman and (UV and vis) resonance Raman spectroscopies. The binding of Aza to the Lewis acidic copper(II) complexes, which results in activation of the substrate, was established spectroscopically. It was shown that the binding of Aza differs between Cu(II)dmbpy and Cu(II)terpy, consistent with the observed differences in catalytic asymmetric Diels-Alder reactions with regard to both the rate and enantiomeric preference. Finally, it was shown that DNA has a major beneficial effect on the binding of Aza to the copper(II) complex due to the fact that both bind to the DNA. The result is a high effective molarity of both the copper complexes and the Aza substrate, which leads to a significant increase in binding of Aza to the copper(II) complex. This effect is a key reason for the observed rate acceleration in the catalyzed reactions brought about by the presence of DNA.

  12. Efficacy of cinnamon bark oil and cinnamaldehyde on anti-multidrug resistant Pseudomonas aeruginosa and the synergistic effects in combination with other antimicrobial agents.

    Science.gov (United States)

    Utchariyakiat, Itsaraporn; Surassmo, Suvimol; Jaturanpinyo, Montree; Khuntayaporn, Piyatip; Chomnawang, Mullika Traidej

    2016-06-01

    The emergence of drug resistant pathogens becomes a crucial problem for infectious diseases worldwide. Among these bacteria, Pseudomonas aeruginosa is one of which highly resists to many currently used drugs and becomes a major concern in public health. Up till now, the search for potential antimicrobial agents has been still a challenge for researchers. Broth microdilution assay was used to determine minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the essential oils and antibiotics against P. aeruginosa. Inhibition activity of the essential oils under vapor condition was examined to obtain the minimum inhibitory dose (MID). Time-kill assay included in this study was performed according to CLSI guideline. Bioautographic assay was used to detect active components of the essential oil. Synergistic effect with currently used antibiotics was further examined by checkerboard assay. In this study, a variety of essential oils were examined for anti-multidrug resistant P. aeruginosa (MDR-PA) activity, of which cinnamon bark oil showed the strongest antimicrobial activity against all clinical-isolated MDR-PA strains with MIC of 0.0562-0.225 % v/v and MBC of 0.1125-1.8 % v/v. Bioautographic results demonstrated that the active compounds of cinnamon bark oil were cinnamaldehyde and eugenol which showed strong inhibitory effect against P. aeruginosa. Interestingly, cinnamaldehyde, a major constituent of cinnamon bark oil, possessed stronger antimicrobial effect to P. aeruginosa than eugenol. Under gaseous condition, cinnamon bark oil and cinnamaldehyde showed antibacterial activity against MDR-PA strains with MID of 0.5-1 mg/L. Moreover, combination of cinnamon bark oil or cinnamaldehyde with currently used antibiotics was further studied by checkerboard assay to examine synergistic interactions on clinically isolated MDR-PA strains. Cinnamon bark oil and cinnamaldehyde combined with colistin demonstrated synergistic rates at 16

  13. Mice perceive synergistic umami mixtures as tasting sweet.

    Science.gov (United States)

    Saites, Louis N; Goldsmith, Zachary; Densky, Jaron; Guedes, Vivian A; Boughter, John D

    2015-06-01

    Previous electrophysiological investigation shows that combinations of compounds classified by humans as umami-tasting, such as glutamate salts and 5'-ribonucleotides, elicit synergistic responses in neurons throughout the rodent taste system and produce a pattern that resembles responses to sweet compounds. The current study tested the hypothesis that a synergistic mixture of monopotassium glutamate (MPG) and inositol monophosphate (IMP) possesses perceptual similarity to sucrose in mice. We estimated behavioral similarity among these tastants and the individual umami compounds using a series of conditioned taste aversion (CTA) tests, a procedure that measures whether a CTA formed to one stimulus generalizes to another. Our primary finding was that a CTA to a synergistic mixture of MPG + IMP generalizes to sucrose, and vice-versa. This indicates umami synergistic mixtures are perceived as having a sweet, or at least sucrose-like, taste to mice. Considering other recent studies, our data argue strongly in favor of multiple receptor mechanisms for umami detection, and complexity in taste perception models for rodents. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Quantifying Synergistic Information Using Intermediate Stochastic Variables †

    Directory of Open Access Journals (Sweden)

    Rick Quax

    2017-02-01

    Full Text Available Quantifying synergy among stochastic variables is an important open problem in information theory. Information synergy occurs when multiple sources together predict an outcome variable better than the sum of single-source predictions. It is an essential phenomenon in biology such as in neuronal networks and cellular regulatory processes, where different information flows integrate to produce a single response, but also in social cooperation processes as well as in statistical inference tasks in machine learning. Here we propose a metric of synergistic entropy and synergistic information from first principles. The proposed measure relies on so-called synergistic random variables (SRVs which are constructed to have zero mutual information about individual source variables but non-zero mutual information about the complete set of source variables. We prove several basic and desired properties of our measure, including bounds and additivity properties. In addition, we prove several important consequences of our measure, including the fact that different types of synergistic information may co-exist between the same sets of variables. A numerical implementation is provided, which we use to demonstrate that synergy is associated with resilience to noise. Our measure may be a marked step forward in the study of multivariate information theory and its numerous applications.

  15. Synergistic Effect of Trehalose and Saccharose Pretreatment on ...

    African Journals Online (AJOL)

    Purpose: To investigate the synergistic effect of trehalose and saccharose pretreatment on maintenance of lyophilized human red blood cell (RBC) quality. Methods: RBCs were pre-treated with trehalose and saccharose, and then lyophilized and re-hydrated. Prior to lyophilization and after re hydration, RBC parameters, ...

  16. Antioxidant, antimicrobial and synergistic activities of tea polyphenols

    African Journals Online (AJOL)

    Microbial resistance to antibiotics has become an increasing global problem and there is a need to find out novel potent antimicrobial agents with alternative modes of action as accessories to antibiotic therapy. This study investigated the antioxidant, antimicrobial and synergistic properties of tea polyphenols. The tea ...

  17. Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

  18. A Synergistic Model to Enhance Multicultural Competence in Supervision

    Science.gov (United States)

    Ober, Anne M.; Granello, Darcy Haag; Henfield, Malik S.

    2009-01-01

    The Synergistic Model of Multicultural Supervision is an integration of 3 existing models to provide concrete and practical guidance for supervisors wishing to enhance supervisee multicultural competence in personally meaningful and developmentally appropriate ways. The model attends to both content and process within the supervisory session and…

  19. Synergistic antibacterial effect of stem bark extracts of Faidherbia ...

    African Journals Online (AJOL)

    The study was aimed at screening the stem bark extracts of Faidherbia albida and Psidium guajava for synergistic antibacterial effect against methicillin resistant Staphylococcus aureus (MRSA). The powdered plant materials were extracted with methanol using cold maceration technique and the extracts were screened for ...

  20. Synergistic effects of squalene and polyunsaturated fatty acid ...

    African Journals Online (AJOL)

    We have studied the synergistic effects of squalene and polyunsaturated fatty acids (PUFA concentrate) on isoprenaline-induced infarction in rats with respect to changes in the levels of plasma diagnostic marker enzymes and myocardial antioxidant defense system. Intraperitoneal injection of isoprenaline caused a ...

  1. Synergistic Curriculum Development: An Idea Whose Time Has Come.

    Science.gov (United States)

    Chopra, Raj K.

    1989-01-01

    Describes a Kansas public school district's efforts to develop a synergistic curriculum plan combining the most positive elements of a standardized curriculum with those of a school-based curriculum. Encouraging staff commitment demands mutuality of expectations, dependence, trust, respect, communication, and vision. (MLH)

  2. Movement Organizations, Synergistic Tactics and Environmental Public Policy

    Science.gov (United States)

    Johnson, Erik W.; Agnone, Jon; McCarthy, John D.

    2010-01-01

    This study builds on political mediation and movement infrastructure models to highlight contingent and synergistic ways in which social movements may impinge upon the U.S. national policy-making process. Analyses employ a variety of datasets to examine the role of environmental movement organizational capacity, protest and institutional activity…

  3. Carbon dioxide and nisin act synergistically on Listeria monocytogenes

    DEFF Research Database (Denmark)

    Nilsson, Lilian; Chen, Y.H.; Chikindas, M.L.

    2000-01-01

    for cultures in CO2. This synergism between nisin and CO2 was examined mechanistically by following the leakage of carboxyfluorescein (CF) from listerial liposomes. Carbon dioxide enhanced nisin-induced CF leakage, indicating that the synergistic action of CO2 and nisin occurs at the cytoplasmic membrane...

  4. Synergistic therapy of enalapril and Cordyceps sinensis in the ...

    African Journals Online (AJOL)

    Chronic allograft nephropathy (CAN) still remains an important factor that affects the long-term survival of renal recipients. The aim of the study was to investigate synergistic effect of enalapril (an angiotensin converting enzyme inhibitor, ACEI) and Cordyceps sinensis (Bailing capsule, fermented agent of C. sinensis) on ...

  5. Chemotherapeutic Impact Of Natural Antioxidant Flavonoids Gallic Acid Rutin Quercetin And Mannitol On Pathogenic Microbes And Their Synergistic Effect

    Directory of Open Access Journals (Sweden)

    Ganesh Ghosh

    2015-08-01

    Full Text Available Several studies suggest that natural flavonoids with antioxidants and can influence the response to chemotherapy as well as the development of adverse side effects that results from treatment with antineoplastic agents and Its prevalence over Multi drug resistant bacterial strain revived interest on Flavonoids. Synergistic effect is defined as passive interaction arises when two agents combine and together they exert an inhibitory effect that is greater than the sum of individual effect The new Synergistic therapy so that antioxidant are more effective in combination on multi drug resistant bacterial strain. Interaction between natural antioxidants and topoisomerase enzyme can be seen through Quercetin as a potent antimicrobial compound alone and in combination with other natural antioxidant like rutin. MICMBC result show antibacterial activity of the flavonoids were enhanced when used in combination against Staphylococcus aureus Bacillus cereus Bacillus subtilis Klebsiella pneumonae Escherichia coli as the test bacteria. The combination of rutin and quercetin rutin and gallic acid mannitol and gallic acid were much more effective than either flavonoid alone. Furthermore Its gave a good relation between these antioxidant compound and antimicrobial activity. Flavonoids as a chemotherapeutic agent and its Synergistic effect can be solution for various microbial disease conditions.

  6. A comparison of the geochemical signatures of water-rock interaction and erosion rates between developed and undeveloped watersheds, St. John, US Virgin Islands

    Science.gov (United States)

    Gudino, N.; Kretzschmar, T.; Gray, S. C.

    2012-12-01

    Human activities such as deforestation, agriculture, and the building of dirt roads may increase soil erosion and the delivery of land-based sediment into coastal waters from steep sub-tropical islands. These changes may also affect water-rock interaction, which alters the geochemistry of storm waters and the clay mineralogy of eroded sediments. In the US Virgin Islands, land-based sedimentation is thought to be a major cause of the decline of near-shore coral reefs. The objective of this study was to 1) evaluate whether chemical erosion (water-rock interaction) during storms affected the major-element chemistry of storm-water and the clay mineralogy of eroded sediments; and 2) determine if enhanced erosion associated with human activities may impact these parameters. Our approach was to compare storm-water and sediment geochemistry and modeled erosion rates between developed (Coral Bay) and undeveloped (Lameshur) watersheds on St. John, USVI. Terrestrial and marine sediment samples and runoff samples from three storm events, including Hurricane Otto (Oct. 7-9th), were collected during the 2010 hurricane season in Coral Bay and Lameshur watersheds and bays. Major elements in storm waters were measured using ICP-AES. The mineral saturation index was calculated using "The Geochemist's Workbench" (GWB), supported by X-Ray Diffraction analysis on clay minerals. The Revised and Modified Universal Soil Loss Equations were used to estimate both annual mean (2010, RUSLE) and storm-event (Hurricane Otto, MUSLE) based erosion rates. In addition, rates of marine terrigenous sediment accumulation were estimated by Loss On Ignition (LOI) analysis of marine sediment collected using submarine sediment trap arrays. Spatial variations in calcium, magnesium, sodium and potassium concentrations in storm water samples were measured and only calcium was statistical different (p<0.05) between the developed and undeveloped study sites during Hurricane Otto. Event specific differences in

  7. A simulation environment for validating ultrasonic blood flow and vessel wall imaging based on fluid-structure interaction simulations: ultrasonic assessment of arterial distension and wall shear rate.

    Science.gov (United States)

    Swillens, Abigail; Degroote, Joris; Vierendeels, Jan; Lovstakken, Lasse; Segers, Patrick

    2010-08-01

    Ultrasound (US) is a commonly used vascular imaging tool when screening for patients at high cardiovascular risk. However, current blood flow and vessel wall imaging methods are hampered by several limitations. When optimizing and developing new ultrasound modalities, proper validation is required before clinical implementation. Therefore, the authors present a simulation environment integrating ultrasound and fluid-structure interaction (FSI) simulations, allowing construction of synthetic ultrasound images based on physiologically realistic behavior of an artery. To demonstrate the potential of the model for vascular ultrasound research, the authors studied clinically relevant imaging modalities of arterial function related to both vessel wall deformation and arterial hemodynamics: Arterial distension (related to arterial stiffness) and wall shear rate (related to the development of atherosclerosis) imaging. An in-house code ("TANGO") was developed to strongly couple the flow solver FLUENT and structural solver ABAQUS using an interface quasi-Newton technique. FIELD II was used to model realistic transducer and scan settings. The input to the FSI-US model is a scatterer phantom on which the US waves reflect, with the scatterer displacement derived from the FSI flow and displacement fields. The authors applied the simulation tool to a 3D straight tube, representative of the common carotid artery (length: 5 cm; and inner and outer radius: 3 and 4 mm). A mass flow inlet boundary condition, based on flow measured in a healthy subject, was applied. A downstream pressure condition, based on a noninvasively measured pressure waveform, was chosen and scaled to simulate three different degrees of arterial distension (1%, 4%, and 9%). The RF data from the FSI-US coupling were further processed for arterial wall and flow imaging. Using an available wall tracking algorithm, arterial distensibility was assessed. Using an autocorrelation estimator, blood velocity and shear

  8. Identification of a novel acetate-utilizing bacterium belonging to Synergistes group 4 in anaerobic digester sludge

    Science.gov (United States)

    Ito, Tsukasa; Yoshiguchi, Kazumi; Ariesyady, Herto Dwi; Okabe, Satoshi

    2011-01-01

    Major acetate-utilizing bacterial and archaeal populations in methanogenic anaerobic digester sludge were identified and quantified by radioisotope- and stable-isotope-based functional analyses, microautoradiography-fluorescence in situ hybridization (MAR-FISH) and stable-isotope probing of 16S rRNA (RNA-SIP) that can directly link 16S rRNA phylogeny with in situ metabolic function. First, MAR-FISH with 14C-acetate indicated the significant utilization of acetate by only two major groups, unidentified bacterial cells and Methanosaeta-like filamentous archaeal cells, in the digester sludge. To identify the acetate-utilizing unidentified bacteria, RNA-SIP was conducted with 13C6-glucose and 13C3-propionate as sole carbon source, which were followed by phylogenetic analysis of 16S rRNA. We found that bacteria belonging to Synergistes group 4 were commonly detected in both 16S rRNA clone libraries derived from the sludge incubated with 13C-glucose and 13C-propionate. To confirm that this bacterial group can utilize acetate, specific FISH probe targeting for Synergistes group 4 was newly designed and applied to the sludge incubated with 14C-acetate for MAR-FISH. The MAR-FISH result showed that bacteria belonging to Synergistes group 4 significantly took up acetate and their active population size was comparable to that of Methanosaeta in this sludge. In addition, as bacteria belonging to Synergistes group 4 had high Km for acetate and maximum utilization rate, they are more competitive for acetate over Methanosaeta at high acetate concentrations (2.5–10 m). To our knowledge, it is the first time to report the acetate-utilizing activity of uncultured bacteria belonging to Synergistes group 4 and its competitive significance to acetoclastic methanogen, Methanosaeta. PMID:21562600

  9. Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

    NARCIS (Netherlands)

    Nijholt, W.; Jager-Wittenaar, H.; Visser, M.; Van der Schans, C. P.; Hobbelen, J. S. M.

    Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being

  10. Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

    NARCIS (Netherlands)

    Dr. C.P. van der Schans; MSc Willemke Nijholt; M. Visser; Dr Harriët Jager-Wittenaar; dr. Hans Hobbelen

    2015-01-01

    Objectives: Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and

  11. In Situ Growth of Prussian Blue Nanostructures at Reduced Graphene Oxide as a Modified Platinum Electrode for Synergistic Methanol Oxidation.

    Science.gov (United States)

    Manivannan, Shanmugam; Kang, Inhak; Kim, Kyuwon

    2016-02-23

    Herein, we report a facile synthetic strategy for the in situ growth of Prussian blue nanostructures (PB NSs) at the amine-functionalized silicate sol-gel matrix (TPDT)-RGO composite via the electrostatic interaction. Subsequently, Pt nanostructures are electrodeposited onto the preformed ITO/TPDT-RGO-PB electrode to prepare the RGO/PB/Pt catalyst. The significance of the present method is that the PB NSs are in situ grown by interconnecting the RGO layers, leading to 3D cage-like porous nanostructure. The modified electrodes are characterized by FESEM, EDAX, XRD, XPS, and electrochemical techniques. The RGO/PB/Pt catalyst exhibits synergistic electrocatalytic activity and high stability toward methanol oxidation. The porous nature of the TPDT and PB and unique electron-transfer mediating behavior of PB integrated with RGO in the presence of Pt nanostructures facilitated synergistic electrocatalytic activity for methanol oxidation.

  12. Effect of NaNO2 and C6H15NO3 Synergistic Admixtures on Steel-Rebar Corrosion in Concrete Immersed in Aggressive Environments

    Directory of Open Access Journals (Sweden)

    Joshua Olusegun Okeniyi

    2015-01-01

    Full Text Available This paper studies effect of different combinations of NaNO2 (sodium nitrite and C6H15NO3 (triethanolamine (TEA, as synergistic admixtures in concrete immersed in NaCl and in H2SO4 test environments, on the corrosion of the concrete reinforcing steel (rebar. Although statistically analysed electrochemical test results confirmed NaNO2 effectiveness, synergistic combinations of 4 g NaNO2 + 4 g C6H15NO3 in NaCl medium and of 2 g NaNO2 + 6 g C6H15NO3 in H2SO4 medium were also highly effective at inhibiting rebar corrosion. Synergistic parameter analyses showed that the effective synergistic admixtures that inhibited concrete steel-rebar corrosion in their respective medium were the NaNO2 and C6H15NO3 combinations that exhibited synergistic interactions of cooperative adsorption on steel-rebar. These support the suitability of requisite concentration of triethanolamine as additive admixture with sodium nitrite for steel-rebar corrosion mitigation, which is potent with reduced environmental effects, in concrete immersed in NaCl and in H2SO4 corrosive media.

  13. Improving Efficacy of Beauveria bassiana against Stored Grain Beetles with a Synergistic Co-Formulant

    Directory of Open Access Journals (Sweden)

    Clare Storm

    2016-08-01

    Full Text Available The potential of a dry powder co-formulant, kaolin, to improve the control of storage beetles by the entomopathogenic fungus Beauveria bassiana, isolate IMI389521, was investigated. The response of Oryzaephilus surinamensis adults to the fungus when applied to wheat at 1 × 1010 conidia per kg with and without kaolin at 1.74 g per kg wheat was assessed. Addition of kaolin increased control from 46% to 88% at day 7 and from 81% to 99% at day 14 post-treatment. Following this the dose response of O. surinamensis and Tribolium confusum to both kaolin and the fungus was investigated. Synergistic effects were evident against O. surinamensis at ≥0.96 g of kaolin per kg of wheat when combined with the fungus at all concentrations tested. For T. confusum, adult mortality did not exceed 55%, however, the larvae were extremely susceptible with almost complete suppression of adult emergence at the lowest fungal rate tested even without the addition of kaolin. Finally, the dose response of Sitophilus granarius to the fungus at 15 and 25 °C, with and without kaolin at 1 g per kg of wheat, was examined. Improvements in efficacy were achieved by including kaolin at every fungal rate tested and by increasing the temperature. Kaolin by itself was not effective, only when combined with the fungus was an effect observed, indicating that kaolin was having a synergistic effect on the fungus.

  14. Use of nanoclay as an environmentally friendly flame retardant synergist in polyamide-6.

    Science.gov (United States)

    Kaynak, Cevdet; Gunduz, Huseyin Ozgur; Isitman, Nihat Ali

    2010-11-01

    Due to their very high levels of flame retardancy, chlorinated and brominated flame retardants had been the most widely used flame retardant additives in plastics industry. However, these flame retardants lead to formation of very toxic volatiles and by-products during fire. Therefore, the recent trend is to replace all of them with non-halogenated flame retardants. In this respect, the use of nanoclays as a synergist flame retardant is becoming more and more important. Thus, the main aim of this work was to investigate the synergistic flame retardant effect of nanoclays with phosphorous compounds in polyamide-6 composites. For this purpose, exfoliated clay nanocomposites of flame retarded/glass fiber reinforced polyamide-6 were prepared by melt compounding. A flame retardant based on phosphorus compounds was used at various levels in glass fiber reinforced polyamide-6 and nanocomposites. Flammability and fire behaviors were evaluated by limiting oxygen index, UL94 and cone calorimeter tests. Substitution of a certain fraction of the flame retardant with nanoclays was found to significantly reduce the peak heat release rate and delay the ignition in cone calorimeter. Moreover, remarkable improvements were obtained in limiting oxygen index along with maintained UL94 ratings.

  15. Synergistic flame retardant effects between sepiolite and magnesium hydroxide in ethylene-vinyl acetate (EVA matrix

    Directory of Open Access Journals (Sweden)

    2010-04-01

    Full Text Available Some customers are reluctant to change, because the halogen-free solutions may have higher cost. This is one of the reasons that the synergistic effect is always the subject for researchers to pursue. The synergy between sepiolite and magnesium hydroxide (MH in halogen-free flame retardant ethylene-vinyl acetate (EVA copolymer was investigated in the paper through some common facilities, such as limiting oxygen index (LOI, UL-94 test, thermogravimetric analysis (TGA, differential thermal analysis (DTA and cone calorimeter test (CCT. In the wake of the positive results from the LOI and UL-94 tests, the CCT data indicated not only the reduction of heat release rate (HRR and mass loss rates (MLR, but also prolonged ignition time (TTI and depressed smoke release (SR were observed during combustion. Simultaneously, the tensile strength and Young’s modulus of the system were also much better improved with the increase of sepiolite added due to the hydrogen bonds between silanol groups attached to the sepiolite molecules and the ester groups of EVA. The synergistic mechanism has been discussed in the paper in terms of the barrier mechanism in the condensed phase.

  16. Abdominal and internal intercostal motoneurones are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs

    DEFF Research Database (Denmark)

    Ford, Tim W; Meehan, Claire Francesca; Kirkwood, Peter

    2014-01-01

    Internal intercostal and abdomininal motoneurones are strongly co-activated during expiration (Saywell et al. 2007; Road et al. 2013). We investigated whether that synergy was paralleled by synergistic Group I reflex excitation. Intracellular recordings were made from motoneurones of the internal...

  17. Are a Healthy Diet and Physical Activity Synergistically Associated with Cognitive Functioning in Older Adults?

    Science.gov (United States)

    Nijholt, W; Jager-Wittenaar, H; Visser, M; van der Schans, C P; Hobbelen, J S M

    2016-01-01

    associated with good cognitive functioning (p=.017). No interaction among sufficient physical activity, healthy diet adherence and good cognitive functioning was observed (crude: p=.401, adjusted: p=.216). The results of this cross-sectional study indicate that adherence to a healthy diet is inde-pendently related to cognitive functioning. Being physically active does not modify this association. Furthermore, these two lifestyle factors do not synergistically relate to cognitive functioning.

  18. Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion.

    Science.gov (United States)

    Haridas, Parvathi; Penington, Catherine J; McGovern, Jacqui A; McElwain, D L Sean; Simpson, Matthew J

    2017-06-21

    Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro. We perform a suite of circular barrier assays that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast cells. Using immunostaining, detailed cell density histograms are constructed to illustrate how the two subpopulations of cells are spatially arranged within the spreading heterogeneous population. Calibrating the solution of a continuum partial differential equation to the experimental results from the monoculture assays allows us to estimate the cell diffusivity and the cell proliferation rate for the melanoma and the fibroblast cells, separately. Using the parameter estimates from the monoculture assays, we then make a prediction of the spatial spreading in the co-culture assays. Results show that the parameter estimates obtained from the monoculture assays lead to a reasonably accurate prediction of the spatial arrangement of the two subpopulations in the co-culture assays. Overall, the spatial pattern of spreading of the melanoma cells and the fibroblast cells is very similar in monoculture and co-culture conditions. Therefore, we find no clear evidence of any interactions other than cell-to-cell contact and crowding effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. One pathogen two stones: are Australian tree frog antimicrobial peptides synergistic against human pathogens?

    Science.gov (United States)

    Sani, Marc-Antoine; Carne, Siobhan; Overall, Sarah A; Poulhazan, Alexandre; Separovic, Frances

    2017-10-01

    Antimicrobial peptides (AMPs) may act by targeting the lipid membranes and disrupting the bilayer structure. In this study, three AMPs from the skin of Australian tree frogs, aurein 1.2, maculatin 1.1 and caerin 1.1, were investigated against Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and vesicles that mimic their lipid compositions. Furthermore, equimolar mixtures of the peptides were tested to identify any synergistic interactions in antimicrobial activity. Minimum inhibition concentration and minimum bactericidal concentration assays showed significant activity against S. aureus but not against E. coli. Aurein was the least active while maculatin was the most active peptide and some synergistic effects were observed against S. aureus. Circular dichroism experiments showed that, in the presence of phospholipid vesicles, the peptides transitioned from an unstructured to a predominantly helical conformation (>50%), with greater helicity for POPG/TOCL compared to POPE/POPG vesicles. The helical content, however, was less in the presence of live E. coli and S. aureus, 25 and 5%, respectively. Equimolar concentrations of the peptides did not appear to form greater supramolecular structures. Dye release assays showed that aurein required greater concentration than caerin and maculatin to disrupt the lipid bilayers, and mixtures of the peptides did not cooperate to enhance their lytic activity. Overall, aurein, maculatin, and caerin showed moderate synergy in antimicrobial activity against S. aureus without becoming more structured or enhancement of their membrane-disrupting activity in phospholipid vesicles.

  20. Synergistic mechanism between SDBS and oleic acid in anionic flotation of rhodochrosite

    Science.gov (United States)

    Bu, Yong-jie; Liu, Run-qing; Sun, Wei; Hu, Yue-hua

    2015-05-01

    Pure mineral flotation experiments, zeta potential testing, and infrared spectroscopy were employed to investigate the interfacial reactions of oleic acid (collector), sodium dodecyl benzene sulfonate (SDBS, synergist), and rhodochrosite in an anionic system. The pure mineral test shows that oleic acid has a strong ability to collect products on rhodochrosite. Under neutral to moderately alkaline conditions, low temperature (e.g., 10°C) adversely affects the flotation performance of oleic acid; the addition of SDBS significantly improves the dispersion and solubility of oleic acid, enhancing its collecting ability and flotation recovery. The zeta potential test shows that rhodochrosite interacts with oleic acid and SDBS, resulting in a more negative zeta potential and the co-adsorption of the collector and synergist at the mineral surface. Infrared spectroscopy demonstrated that when oleic acid and SDBS are used as a mixed collector, oleates along with -COO- and -COOH functional groups are formed on the mineral surface, indicating chemical adsorption on rhodochrosite. The results demonstrate that oleic acid and SDBS co-adsorb chemically on the surface of rhodochrosite, thereby improving the flotation performance of the collector.

  1. The Goldilocks contract: The synergistic benefits of combining structure and autonomy for persistence, creativity, and cooperation.

    Science.gov (United States)

    Chou, Eileen Y; Halevy, Nir; Galinsky, Adam D; Murnighan, J Keith

    2017-09-01

    Contracts are commonly used to regulate a wide range of interactions and relationships. Yet relying on contracts as a mechanism of control often comes at a cost to motivation. Integrating theoretical perspectives from psychology, economics, and organizational theory, we explore this control-motivation dilemma inherent in contracts and present the Contract-Autonomy-Motivation-Performance-Structure (CAMPS) model, which highlights the synergistic benefits of combining structure and autonomy. The model proposes that subtle reductions in the specificity of a contract's language can boost autonomy, which increases intrinsic motivation and improves a range of desirable behaviors. Nine field and laboratory experiments found that less specific contracts increased task persistence, creativity, and cooperation, both immediately and longitudinally, because they boosted autonomy and intrinsic motivation. These positive effects, however, only occurred when contracts provided sufficient structure. Furthermore, the effects were limited to control-oriented clauses (i.e., legal clauses), and did not extend to coordination-oriented clauses (i.e., technical clauses). That is, there were synergistic benefits when a contract served as a scaffold that combined structure with general clauses. Overall, the current model and experiments identify a low-cost solution to the common problem of regulating social relationships: finding the right amount of contract specificity promotes desirable outcomes, including behaviors that are notoriously difficult to contract. The CAMPS model and the current set of empirical findings explain why, when, and how contracts can be used as an effective motivational tool. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Synergistic performance of lecithin and glycerol monostearate in oil/water emulsions.

    Science.gov (United States)

    Moran-Valero, María I; Ruiz-Henestrosa, Víctor M Pizones; Pilosof, Ana M R

    2017-03-01

    The effects of the combination of two low-molecular weight emulsifiers (lecithin and glycerol-monostearate (GMS)) on the stability, the dynamic interfacial properties and rheology of emulsions have been studied. Different lecithin/GMS ratios were tested in order to assess their impact in the formation and stabilization of oil in water emulsions. The combination of the two surfactants showed a synergistic behaviour, mainly when combined at the same ratio. The dynamic film properties and ζ-potential showed that lecithin dominated the surface of oil droplets, providing stability to the emulsions against flocculation and coalescence, while allowing the formation of small oil droplets. At long times of adsorption, all of the mixtures showed similar interfacial activity. However, higher values of interfacial pressure at the initial times were reached when lecithin and GMS were at the same ratio. Interfacial viscoelasticity and viscosity of mixed films were also similar to that of lecithin alone. On the other hand, emulsions viscosity was dominated by GMS. The synergistic performance of lecithin-GMS blends as stabilizers of oil/water emulsions is attributed to their interaction both in the bulk and at the interface. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Temperature rise and parasitic infection interact to increase the impact of an invasive species.

    Science.gov (United States)

    Laverty, Ciaran; Brenner, David; McIlwaine, Christopher; Lennon, Jack J; Dick, Jaimie T A; Lucy, Frances E; Christian, Keith A

    2017-04-01

    Invasive species often detrimentally impact native biota, e.g. through predation, but predicting such impacts is difficult due to multiple and perhaps interacting abiotic and biotic context dependencies. Higher mean and peak temperatures, together with parasites, might influence the impact of predatory invasive host species additively, synergistically or antagonistically. Here, we apply the comparative functional response methodology (relationship between resource consumption rate and resource supply) in one experiment and conduct a second scaled-up mesocosm experiment to assess any differential predatory impacts of the freshwater invasive amphipod Gammarus pulex, when uninfected and infected with the acanthocephalan Echinorhynchus truttae, at three temperatures representative of current and future climate. Individual G. pulex showed Type II predatory functional responses. In both experiments, infection was associated with higher maximum feeding rates, which also increased with increasing temperatures. Additionally, infection interacted with higher temperatures to synergistically elevate functional responses and feeding rates. Parasitic infection also generally increased Q10 values. We thus suggest that the differential metabolic responses of the host and parasite to increasing temperatures drives the synergy between infection and temperature, elevating feeding rates and thus enhancing the ecological impact of the invader. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  4. Individually and Synergistic Degradation of Hydrocarbons by Biosurfactant Producing Bacteria

    Directory of Open Access Journals (Sweden)

    Amirarsalan Kavyanifard

    2016-02-01

    Full Text Available Background: Increasing worldwide contamination with hydrocarbons has urged environmental remediation using biological agents such as bacteria. Our goal here was to study the phylogenetic relationship of two crude oil degrader bacteria and investigation of their ability to degrade hydrocarbons. Materials and Methods: Phylogenetic relationship of isolates was determined using morphological and biochemical characteristics and 16S rDNA gene sequencing. Optimum conditions of each isolate for crude oil degradation were investigated using one factor in time method. The rate of crude oil degradation by individual and consortium bacteria was assayed via Gas chromatography–mass spectrometry (GC-MS analysis. Biosurfactant production was measured by Du Noüy ring method using Krüss-K6 tensiometer. Results: The isolates were identified as Dietzia cinnamea KA1 and Dietzia cinnamea AP and clustered separately, while both are closely related to each other and with other isolates of Dietzia cinnamea. The optimal conditions for D. cinnamea KA1 were 35°C, pH9.0, 510 mM NaCl, and minimal requirement of 46.5 mM NH4Cl and 2.10 mM NaH2PO4. In the case of D. cinnamea AP, the values were 30°C, pH8.0, 170 mM NaCl, and minimal requirement of 55.8 mM NH4Cl and 2.10 mM NaH2PO4, respectively. Gas chromatography – Mass Spectroscopy (GC-MS analysis showed that both isolates were able to utilize various crude oil compounds, but D. cinnamea KA1 was more efficient individually and consortium of isolates was the most. The isolates were able to grow and produce biosurfactant when cultured in MSM supplemented with crude oil and optimization of MSM conditions lead to increase in biosurfactant production. Conclusion: To the best of our knowledge this is the first report of synergistic relationship between two strains of D. cinnamea in biodegradation of crude oil components, including poisonous and carcinogenic compound in a short time.

  5. The coordination structure of the extracted copper(II) complex with a synergistic mixture containing dinonylnaphthalene sulfonic acid and n-hexyl 3-pyridinecarboxylate ester

    Science.gov (United States)

    Zhu, Shan; Hu, Huiping; Hu, Jiugang; Li, Jiyuan; Hu, Fang; Wang, Yongxi

    2017-09-01

    In continuation of our interest in the coordination structure of the nickel(II) complex with dinonylnaphthalene sulfonic acid (HDNNS) and 2-ethylhexyl 4-pyridinecarboxylate ester (4PC), it was observed that the coordination sphere was completed by the coordination of two N atoms of pyridine rings in ligands 4PC and four water molecules while no direct interaction between Ni(II) and deprotonated HDNNS was observed. To investigate whether the coordination structure of nickel(II) with the synergistic mixture containing HDNNS and 4PC predominates or not in the copper(II) complex with the synergistic mixtures containing HDNNS and pyridinecarboxylate esters, a copper(II) synergist complex with n-hexyl 3-pyridinecarboxylate ester (L) and naphthalene-2-sulfonic acid (HNS, the short chain analogue of HDNNS), was prepared and studied by X-ray single crystal diffraction, elemental analyses and thermo gravimetric analysis (TGA), respectively. It was shown that the composition of the copper(II) synergist complex was [Cu(H2O)2(L)2(NS)2] and formed a trans-form distorted octahedral coordination structure. Two oxygen atoms of the two coordinated water molecules and two N atoms of the pyridine rings in the ligands L defined the basal plane while two O atoms from two sulfonate anions of the deprotonated HNS ligands occupied the apical positions by direct coordination with Cu(II), which was distinguished from the coordination structure of the nickel(II) synergist complex as reported in our previous work. In the crystal lattice, neighboring molecules [Cu(H2O)2L2(NS)2] were linked through the intermolecular hydrogen bonds between the hydrogen atoms of the coordinated water molecules and the oxygen atoms of the sulfonate anions in the copper(II) synergist complex to form a 2D plane. In order to bridge the gap between the solid state structure of the copper(II) synergist complex and the solution structure of the extracted copper(II) complex with the actual synergistic mixture containing

  6. Calculations with spectroscopic accuracy for energies, transition rates, hyperfine interaction constants, and Landé gJ-factors in nitrogen-like Kr XXX

    Science.gov (United States)

    Wang, K.; Li, S.; Jönsson, P.; Fu, N.; Dang, W.; Guo, X. L.; Chen, C. Y.; Yan, J.; Chen, Z. B.; Si, R.

    2017-01-01

    Extensive self-consistent multi-configuration Dirac-Fock (MCDF) calculations and second-order many-body perturbation theory (MBPT) calculations are performed for the lowest 272 states belonging to the 2s22p3, 2s2p4, 2p5, 2s22p23l, and 2s2p33l (l=s, p, d) configurations of N-like Kr XXX. Complete and consistent data sets of level energies, wavelengths, line strengths, oscillator strengths, lifetimes, AJ, BJ hyperfine interaction constants, Landé gJ-factors, and electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), magnetic quadrupole (M2) transition rates among all these levels are given. The present MCDF and MBPT results are compared with each other and with other available experimental and theoretical results. The mean relative difference between our two sets of level energies is only about 0.003% for these 272 levels. The accuracy of the present calculations are high enough to facilitate identification of many observed spectral lines. These accurate data can be served as benchmark for other calculations and can be useful for fusion plasma research and astrophysical applications.

  7. Synergistic effects of zinc borate and aluminium trihydroxide on flammability behaviour of aerospace epoxy system

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available The flame retardancy of mono-component epoxy resin (RTM6, widely used for aerospace composites, treated with zinc borate (ZB, aluminium trihydroxide (ATH and their mixtures at different concentrations have been investigated by morphological and thermal characterization. Cone calorimeter data reveal that combustion behaviour, heat release rate peak (PHRR and heat release rate average (HRR Average of RTM6 resin decrease substantially when synergistic effects of zinc borate and aluminium trihydroxide intervene. Thermogravimetric (TGA results and analysis of the residue show that addition higher than 20% w/w of ZB, ATH, and their mixture greatly promotes RTM6 char formation acting as a barrier layer for the fire development. Depending upon the different used flame additives, SEM micrographs indicate that the morphology of residual char could vary from a compact amalgam-like structure, for the RTM6+ZB system, to a granular structure, characterized by very small particles of degraded resin and additive for the ATH.

  8. New Mechanism on Synergistic Effect of Nitrite and Triethanolamine Addition on the Corrosion of Ductile Cast Iron

    Directory of Open Access Journals (Sweden)

    K. T. Kim

    2016-01-01

    Full Text Available In general, we compared the different inhibition mechanisms of organic inhibitor with that of anodic inhibitor. When triethanolamine or nitrite was added separately to tap water for inhibiting the corrosion of ductile cast iron, large amounts of inhibitor were needed. This is because the corrosion inhibitors had to overcome the galvanic corrosion that occurs between graphite and matrix. In this work, we investigated the corrosion of ductile cast iron in tap water with/without inhibitors. The corrosion rate was measured using chemical immersion test and electrochemical methods, including anodic polarization test. The inhibited surface was analyzed using EPMA and XPS. Test solutions were analyzed by performing FT-IR measurement. When triethanolamine and nitrite coexisted in tap water, synergistic effect built up, and the inhibition effect was ca. 30 times more effective than witnessed with single addition. This work focused on the synergistic effect brought about by nitrite and triethanolamine and its novel mechanism was also proposed.

  9. Copyrolysis of Biomass and Coal: A Review of Effects of Copyrolysis Parameters, Product Properties, and Synergistic Mechanisms.

    Science.gov (United States)

    Quan, Cui; Gao, Ningbo

    2016-01-01

    Concerns in the last few decades regarding the environmental and socioeconomic impacts of the dependence on fossil fuels have resulted in calls for more renewable and alternative energy sources. This has led to recent interest in copyrolysis of biomass and coal. Numerous reviews have been found related to individual pyrolysis of coal and biomass. This review deals mainly with the copyrolysis of coal and biomass and then compares their results with those obtained using coal and biomass pyrolysis in detail. It is controversial whether there are synergistic or additive behaviours when coal and biomass are blended during copyrolysis. In this review, the effects of reaction parameters such as feedstock types, blending ratio, heating rate, temperature, and reactor types on the occurrence of synergy are discussed. Also, the main properties of the copyrolytic products are pointed out. Some possible synergistic mechanisms are also suggested. Additionally, several outlooks based on studies in the literature are also presented in this paper.

  10. Regeneration of Aplysia Bag Cell Neurons is Synergistically Enhanced by Substrate-Bound Hemolymph Proteins and Laminin

    Science.gov (United States)

    Hyland, Callen; Dufrense, Eric R.; Forscher, Paul

    2014-04-01

    We have investigated Aplysia hemolymph as a source of endogenous factors to promote regeneration of bag cell neurons. We describe a novel synergistic effect between substrate-bound hemolymph proteins and laminin. This combination increased outgrowth and branching relative to either laminin or hemolymph alone. Notably, the addition of hemolymph to laminin substrates accelerated growth cone migration rate over ten-fold. Our results indicate that the active factor is either a high molecular weight protein or protein complex and is not the respiratory protein hemocyanin. Substrate-bound factor(s) from central nervous system-conditioned media also had a synergistic effect with laminin, suggesting a possible cooperation between humoral proteins and nervous system extracellular matrix. Further molecular characterization of active factors and their cellular targets is warranted on account of the magnitude of the effects reported here and their potential relevance for nervous system repair.

  11. Copyrolysis of Biomass and Coal: A Review of Effects of Copyrolysis Parameters, Product Properties, and Synergistic Mechanisms

    Directory of Open Access Journals (Sweden)

    Cui Quan

    2016-01-01

    Full Text Available Concerns in the last few decades regarding the environmental and socioeconomic impacts of the dependence on fossil fuels have resulted in calls for more renewable and alternative energy sources. This has led to recent interest in copyrolysis of biomass and coal. Numerous reviews have been found related to individual pyrolysis of coal and biomass. This review deals mainly with the copyrolysis of coal and biomass and then compares their results with those obtained using coal and biomass pyrolysis in detail. It is controversial whether there are synergistic or additive behaviours when coal and biomass are blended during copyrolysis. In this review, the effects of reaction parameters such as feedstock types, blending ratio, heating rate, temperature, and reactor types on the occurrence of synergy are discussed. Also, the main properties of the copyrolytic products are pointed out. Some possible synergistic mechanisms are also suggested. Additionally, several outlooks based on studies in the literature are also presented in this paper.

  12. Copyrolysis of Biomass and Coal: A Review of Effects of Copyrolysis Parameters, Product Properties, and Synergistic Mechanisms

    Science.gov (United States)

    2016-01-01

    Concerns in the last few decades regarding the environmental and socioeconomic impacts of the dependence on fossil fuels have resulted in calls for more renewable and alternative energy sources. This has led to recent interest in copyrolysis of biomass and coal. Numerous reviews have been found related to individual pyrolysis of coal and biomass. This review deals mainly with the copyrolysis of coal and biomass and then compares their results with those obtained using coal and biomass pyrolysis in detail. It is controversial whether there are synergistic or additive behaviours when coal and biomass are blended during copyrolysis. In this review, the effects of reaction parameters such as feedstock types, blending ratio, heating rate, temperature, and reactor types on the occurrence of synergy are discussed. Also, the main properties of the copyrolytic products are pointed out. Some possible synergistic mechanisms are also suggested. Additionally, several outlooks based on studies in the literature are also presented in this paper. PMID:27722171

  13. Interaction of Benzimidazoles and Benzotriazole: Its Corrosion Protection Properties on Mild Steel in Hydrochloric Acid

    Science.gov (United States)

    Ramya, K.; Mohan, Revathi; Joseph, Abraham

    2014-11-01

    Synergistic hydrogen-bonded interaction of alkyl benzimidazoles and 1,2,3-benzotrizole and its corrosion protection properties on mild steel in hydrochloric acid at different temperatures have been studied using polarization, EIS, adsorption, surface studies, and computational methods. The extent of synergistic interaction increases with temperature. Quantum chemical approach is used to calculate some electronic properties of the molecules and to ascertain the synergistic interaction, inhibitive effect, and molecular structures. The corrosion inhibition efficiencies and the global chemical reactivity relate to some parameters, such as total energy, E HOMO, E LUMO, and gap energy (Δ E). 1,2,3-Benzotrizole interacts with benzimidazoles derivatives up to a bond length of approximately 1.99 Å. This interaction represents the formation of a hydrogen bond between the 1,2,3-benzotrizole and benzimidazoles. This synergistic interaction of 1,2,3-benzotrizole and benzimidazole derivatives offers extended inhibition efficiency toward mild steel in hydrochloric acid.

  14. Effects of immune synergist of Chinese medicinal herbs on the ...

    African Journals Online (AJOL)

    Two-month-old piglets were fed with 1, 1.5 and 2% immune synergist of Chinese medicinal herbs together with vaccination against classic swine fever. Serum IgG and IgM levels increased more than the control group on day 30 (P<0.05). B and T lymphocyte proliferation in piglets fed with 1.5 and 2% herbal immune ...

  15. Effects of immune synergist of Chinese medicinal herbs on the ...

    African Journals Online (AJOL)

    AJL

    2012-01-19

    Jan 19, 2012 ... Two-month-old piglets were fed with 1, 1.5 and 2% immune synergist of Chinese medicinal herbs together with vaccination against classic swine fever. Serum IgG and IgM levels increased more than the control group on day. 30 (P<0.05). B and T lymphocyte proliferation in piglets fed with 1.5 and 2% ...

  16. Inhibition of homologous recombination with vorinostat synergistically enhances ganciclovir cytotoxicity.

    Science.gov (United States)

    Ladd, Brendon; Ackroyd, Jeffrey J; Hicks, J Kevin; Canman, Christine E; Flanagan, Sheryl A; Shewach, Donna S

    2013-12-01

    The nucleoside analog ganciclovir (GCV) elicits cytotoxicity in tumor cells via a novel mechanism in which drug incorporation into DNA produces minimal disruption of replication, but numerous DNA double strand breaks occur during the second S-phase after drug exposure. We propose that homologous recombination (HR), a major repair pathway for DNA double strand breaks, can prevent GCV-induced DNA damage, and that inhibition of HR will enhance cytotoxicity with GCV. Survival after GCV treatment in cells expressing a herpes simplex virus thymidine kinase was strongly dependent on HR (>14-fold decrease in IC50 in HR-deficient vs. HR-proficient CHO cells). In a homologous recombination reporter assay, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA; vorinostat), decreased HR repair events up to 85%. SAHA plus GCV produced synergistic cytotoxicity in U251tk human glioblastoma cells. Elucidation of the synergistic mechanism demonstrated that SAHA produced a concentration-dependent decrease in the HR proteins Rad51 and CtIP. GCV alone produced numerous Rad51 foci, demonstrating activation of HR. However, the addition of SAHA blocked GCV-induced Rad51 foci formation completely and increased γH2AX, a marker of DNA double strand breaks. SAHA plus GCV also produced synergistic cytotoxicity in HR-proficient CHO cells, but the combination was antagonistic or additive in HR-deficient CHO cells. Collectively, these data demonstrate that HR promotes survival with GCV and compromise of HR by SAHA results in synergistic cytotoxicity, revealing a new mechanism for enhancing anticancer activity with GCV. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Synergistic capture mechanisms for alkali and sulfur species from combustion

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, T.W.; Shadman, F.; Wendt, J.O.L.; Olsen, E.

    1992-01-10

    An aerosol reactor system has been designed and constructed for the systematic study of the mechanisms governing the possible synergistic capture of sulfur oxide and alkalis with aluminosilicates and lime (CaO). Actual particle dynamics found in coal combustor systems can be simulated, mass balances can be closed, and the system conditions are well controlled. The collection of hot reactive aerosol flows is performed utilizing an isokinetic probe.

  18. A synergistic effect of artocarpanone fromArtocarpus heterophyllusL. (Moraceae) on the antibacterial activity of selected antibiotics and cell membrane permeability.

    Science.gov (United States)

    Septama, Abdi Wira; Xiao, Jianbo; Panichayupakaranant, Pharkphoom

    2017-01-01

    Artocarpanone isolated from Artocarpus heterophyllus L. (Moraceae) exhibits antibacterial activity. The present study investigated synergistic activity between artocarpanone and tetracycline, ampicillin, and norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Escherichia coli . A broth microdilution method was used for evaluating antibacterial susceptibility. Synergistic effects were identified using a checkerboard method, and a bacterial cell membrane disruption was investigated by assay of released 260 nm absorbing materials following bacteriolysis. Artocarpanone exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum inhibitory concentrations values of 125 and 500 μg/mL, respectively. However, the compound showed strong antibacterial activity against E. coli (7.8 μg/mL). The interaction between artocarpanone and all tested antibiotics revealed indifference and additive effects against P. aeruginosa and E. coli (fractional inhibitory concentration index [FICI] values of 0.75-1.25). The combination of artocarpanone (31.2 μg/mL) and norfloxacin (3.9 μg/mL) resulted in synergistic antibacterial activity against MRSA, with an FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, the combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. These findings suggest that artocarpanone may be used to enhance the antibacterial activity of norfloxacin against MRSA.

  19. Synergistic Flame Retardancy of Aluminium Dipropylphosphinate and Melamine in Polyamide 6

    Directory of Open Access Journals (Sweden)

    Linsheng Tang

    2013-01-01

    Full Text Available The synergistic flame retardancy of aluminium dipropylphosphinate (ADPP and melamine (ME in polyamide 6 (PA6 was studied by the limiting oxygen index (LOI measurement, the vertical burning test, and the cone calorimeter test, and the mechanism was also discussed by thermogravimetric and residual analyses. The experimental results indicated that there was obvious synergistic flame retardancy between ADPP and ME under their appropriate weight ratios. The thermogravimetric results and the analysis of the residues obtained in cone calorimeter test showed that ADPP and ADPP/ME played the role of flame retardance by gaseous- and condensed-phase mechanisms, where, on one hand, they were decomposed into nonvolatile aluminum phosphate and promoted the carbonization of PA6, and the formed intumescent layer resulted in flame retardancy by the barrier effect on heat, air, and decomposition products, and on the other hand, they were decomposed into volatile phosphorus compounds which bring about flame retardancy by flame inhibition. Using a combination of ADPP and ME improved charring of PA6 and raised the residual rate of P and Al, thus, improving the barrier effect in the condensed phase.

  20. Synergistic cytotoxic effect of tetrachlorocatechol and sodium azide in Escherichia coli: toxicity, metabolism, and mechanistic aspects.

    Science.gov (United States)

    Levy, Smadar; Chevion, Mordechai

    2009-07-01

    Pentachlorophenol (PCP) is used in industrial and domestic applications, including as a biocide and a wood preservative. Metabolism of PCP undergoes oxidative dechlorination, forming tetrachlorocatechol (TCC) and tetrachlorohydroquinone (TCHQ). Both sodium azide (NaN(3)) and TCC appear naturally in soil. None of them are cytotoxic by themselves or facilitate autooxidation. Here, we show that their combination leads to synergistic cytotoxicity (>6 log bacterial killing) to Escherichia coli. The rate of oxygen consumption in a cell-free system showed that NaN(3) increases TCC oxidation by 520-fold. The synergism coefficient to cells was calculated as 96 or greater, and we have shown the formation of a new compound. It is suggested that the intermediate species, o-tetrachlorosemiquinine, and an unknown, nitrogen-centered free radical, both visualized by electron-spin resonance, are harmful species responsible for the synergistic cytotoxicity of TCC/NaN(3), rather than the endproduct formed during the reaction. Desferrioxamine and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide offered nearly complete protection, but through radical scavenging rather than through chelating properties. The mechanism of damage for TCC compared to its analogue, TCHQ, were investigated, and whereas the cellular damage of TCHQ/NaN(3) is through a site-specific mechanism, in the case of TCC/NaN(3) it is through the accumulation of the component(s) in the bacterial cell membrane, eventually leading to dysfunction, as evidenced by electron microscopy.

  1. Negative cognitive styles synergistically predict suicidal ideation in bipolar spectrum disorders: a 3-year prospective study.

    Science.gov (United States)

    Stange, Jonathan P; Hamilton, Jessica L; Burke, Taylor A; Kleiman, Evan M; O'Garro-Moore, Jared K; Seligman, Nicole D; Abramson, Lyn Y; Alloy, Lauren B

    2015-03-30

    Rates of suicidal ideation and behavior are extremely high in bipolar spectrum disorders (BSDs). However, relatively little work has evaluated potentially synergistic relationships between cognitive and emotion-regulatory processes proposed by theoretical models of suicidality in BSDs. The present study evaluated whether negative cognitive style and subtypes of rumination would exacerbate the impact of self-criticism on suicidal ideation in a prospective study of individuals with BSDs. Seventy-two young adults with BSDs (bipolar II, bipolar NOS, or cyclothymia) completed diagnostic interviews and trait measures of self-criticism, negative cognitive style, and brooding and reflective rumination at a baseline assessment. The occurrence of suicidal ideation was assessed as part of diagnostic interviews completed every 4 months for an average of 3 years of follow-up. Negative cognitive style and reflective rumination strengthened the association between self-criticism and the prospective occurrence of suicidal ideation across follow-up. Individuals with high levels of self-criticism in conjunction with negative cognitive style or reflective rumination were most likely to experience the onset of suicidal ideation. Self-criticism may work synergistically with negative cognitive style and rumination to confer risk for suicidal ideation in bipolar spectrum disorders. These results support theoretical models of suicidality in BSDs and indicate that evaluating and understanding negative cognitive styles may help to identify individuals who are at risk of suicide. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Green synthesis and synergistic catalytic effect ofAg/reduced graphene oxide nanocomposite.

    Science.gov (United States)

    Hsu, Kai-Chih; Chen, Dong-Hwang

    2014-01-01

    A nanocomposite of silver nanoparticles and reduced graphene oxide (Ag/rGO) has been developed as a catalyst for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with sodium borohydride, owing to the larger specific surface area and synergistic effect of rGO. A facile and rapid microwave-assisted green route has been used for the uniform deposition of Ag nanoparticles and the reduction of graphene oxide simultaneously with l-arginine as the reducing agent. The resulting Ag/rGO nanocomposite contained about 51 wt% of Ag, and the Ag nanoparticles deposited on the surface of rGO had a mean diameter of 8.6 ± 3.5 nm. Also, the Ag/rGO nanocomposite exhibited excellent catalytic activity and stability toward the reduction of 4-NP to 4-AP with sodium borohydride. The reduction reaction obeyed the pseudo-first-order kinetics. The rate constants increased not only with the increase of temperature and catalyst amount but also with the increase of initial 4-NP concentration, revealing that the support rGO could enhance the catalytic activity via a synergistic effect. A mechanism for the catalytic reduction of 4-NP with NaBH4 by Ag/rGO nanocomposite via both the liquid-phase and solid-phase routes has been suggested.

  3. Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine.

    Science.gov (United States)

    Du, Michael; Zhang, Linna; Scorsone, Kathleen A; Woodfield, Sarah E; Zage, Peter E

    2016-06-10

    Children with aggressive neural tumors have poor survival rates and novel therapies are needed. Previous studies have identified nifurtimox and buthionine sulfoximine (BSO) as effective agents in children with neuroblastoma and medulloblastoma. We hypothesized that nifurtimox would be effective against other neural tumor cells and would be synergistic with BSO. We determined neural tumor cell viability before and after treatment with nifurtimox using MTT assays. Assays for DNA ladder formation and poly-ADP ribose polymerase (PARP) cleavage were performed to measure the induction of apoptosis after nifurtimox treatment. Inhibition of intracellular signaling was measured by Western blot analysis of treated and untreated cells. Tumor cells were then treated with combinations of nifurtimox and BSO and evaluated for viability using MTT assays. All neural tumor cell lines were sensitive to nifurtimox, and IC50 values ranged from approximately 20 to 210 μM. Nifurtimox treatment inhibited ERK phosphorylation and induced apoptosis in tumor cells. Furthermore, the combination of nifurtimox and BSO demonstrated significant synergistic efficacy in all tested cell lines. Additional preclinical and clinical studies of the combination of nifurtimox and BSO in patients with neural tumors are warranted.

  4. Synergistic effects of hollow structure and surface fluorination on the photocatalytic activity of titania

    Energy Technology Data Exchange (ETDEWEB)

    Lv Kangle, E-mail: lvkangle@mail.scuec.edu.cn [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, South-Central University for Nationalities, Wuhan 430074 (China); State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Yu Jiaguo, E-mail: jiaguoyu@yahoo.com [State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Deng Kejian; Sun Jie; Zhao Yanxi; Du Dongyun; Li Mei [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, South-Central University for Nationalities, Wuhan 430074 (China)

    2010-01-15

    To study the synergistic effects of hollow structure and surface fluorination on the photoactivity of TiO{sub 2}, TiO{sub 2} hollow microspheres were synthesized by a hydrolysis-precipitate method using sulfonated polystyrene (PS) as templates and tetrabutylorthotitanate (TBOT) as precursor, and then calcined at 500 {sup o}C for 2 h. The calcined samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and N{sub 2} sorption. Photocatalytic activity was evaluated using reactive brilliant red X3B, an anionic organic dye, as a model pollutant in water. The results show that the photocatalytic activity of TiO{sub 2} hollow microspheres is significantly higher than that of TiO{sub 2} nanoparticles prepared in the same experimental conditions. At pH 7 and 3, the apparent rate constants of the former exceed that of the latter by a factor of 3.38 and 3.15, respectively. After surface fluorination at pH 3, the photoactivity of hollow microspheres and nanoparticles further increases for another 1.61 and 2.19 times, respectively. The synergistic effect of surface fluorination and hollow structure can also be used to prepare other highly efficient photocatalyst.

  5. Identification of pheromone synergists for Rhynchophorus ferrugineus trapping systems from Phoenix canariensis palm volatiles.

    Science.gov (United States)

    Vacas, Sandra; Abad-Payá, María; Primo, Jaime; Navarro-Llopis, Vicente

    2014-07-02

    Trapping systems for the red palm weevil, Rhynchophorus ferrugineus Olivier, rely on the use of natural plant odor sources to boost the attractiveness of the aggregation pheromone. The identification of the key odorants involved in attraction is essential in the development of a synthetic pheromone synergist to replace the nonstandardized use of plant material in traps. Canary Islands date palms (Phoenix canariensis) have become preferred hosts for R. ferrugineus in Europe; thus, the volatile profile of different P. canariensis plant materials, including healthy and infested tissues, is investigated in the present work by means of solid phase microextraction (SPME-GC-MS), aimed to identify pheromone synergists. The electroantennography (EAG) response of the compounds identified was recorded, as well as the preliminary field response of several EAG-active compounds. The so-called "palm esters" (ethyl acetate, ethyl propionate, ethyl butyrate, and propyl butyrate) elicit the strongest EAG responses but performed poorly in the field. Mixtures of esters and alcohols give evidence of better performance, but release rates need further optimization.

  6. Thermodynamic Description of Synergy in Solvent Extraction: II Thermodynamic Balance of Driving Forces Implied in Synergistic Extraction.

    Science.gov (United States)

    Rey, J; Bley, M; Dufrêche, J-F; Gourdin, S; Pellet-Rostaing, S; Zemb, T; Dourdain, S

    2017-11-21

    In the second part of this study, we analyze the free energy of transfer in the case of synergistic solvent extraction. This free energy of the transfer of an ion in dynamic equilibrium between two coexisting phases is decomposed into four driving forces combining long-range interactions with the classical complexation free energy associated with the nearest neighbors. We demonstrate how the organometallic complexation is counterbalanced by the cost in free energy related to structural change on the colloidal scale in the solvent phase. These molecular forces of synergistic extraction are driven not only by the entropic term associated with the tight packing of electrolytes in the solvent and by the free energy cost of coextracting water toward the hydrophilic core of the reverse aggregates present but also by the entropic costs in the formation of the reverse aggregate and by the interfacial bending energy of the extractant molecules packed around the extracted species. Considering the sum of the terms, we can rationalize the synergy observed, which cannot be explained by classical extraction modeling. We show an industrial synergistic mixture combining an amide and a phosphate complexing site, where the most efficient/selective mixture is observed for a minimal bending energy and maximal complexation energy.

  7. Synergistic Effect of the Flavonoid Catechin, Quercetin, or Epigallocatechin Gallate with Fluconazole Induces Apoptosis in Candida tropicalis Resistant to Fluconazole

    Science.gov (United States)

    da Silva, Cecília Rocha; de Andrade Neto, João Batista; de Sousa Campos, Rosana; Figueiredo, Narjara Silvestre; Sampaio, Letícia Serpa; Magalhães, Hemerson Iury Ferreira; Cavalcanti, Bruno Coêlho; Gaspar, Danielle Macêdo; de Andrade, Geanne Matos; Lima, Iri Sandro Pampolha; de Barros Viana, Glauce Socorro; de Moraes, Manoel Odorico; Lobo, Marina Duarte Pinto; Grangeiro, Thalles Barbosa

    2014-01-01

    Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the in vitro interactions of flavonoids with fluconazole against Candida tropicalis strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (−)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of C. tropicalis resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation. PMID:24366745

  8. Synergistic combinations of five single drugs from Centella asiatica for neuronal differentiation.

    Science.gov (United States)

    Lin, Jinjin; Jiang, Hui; Ding, Xianting

    2017-01-01

    To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression. According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.

  9. SUMOylation of Rad52-Rad59 synergistically change the outcome of mitotic recombination

    DEFF Research Database (Denmark)

    Silva, Sonia; Altmannova, Veronika; Eckert-Boulet, Nadine

    2016-01-01

    for survival after genotoxic stress, it affects the outcome of recombination to promote conservative DNA repair. In some genetic assays, Rad52 and Rad59 SUMOylation act synergistically. Collectively, our data indicate that the described SUMO modifications affect the balance between conservative and non......Homologous recombination (HR) is essential for maintenance of genome stability through double-strand break (DSB) repair, but at the same time HR can lead to loss of heterozygosity and uncontrolled recombination can be genotoxic. The post-translational modification by SUMO (small ubiquitin......-like modifier) has been shown to modulate recombination, but the exact mechanism of this regulation remains unclear. Here we show that SUMOylation stabilizes the interaction between the recombination mediator Rad52 and its paralogue Rad59 in Saccharomyces cerevisiae. Although Rad59 SUMOylation is not required...

  10. Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination.

    Directory of Open Access Journals (Sweden)

    Anwesa Bag

    Full Text Available The present study was carried out to evaluate the possible synergistic interactions on antibacterial and antioxidant efficacy of essential oils of some selected spices and herbs [bay leaf, black pepper, coriander (seed and leaf, cumin, garlic, ginger, mustard, onion and turmeric] in combination. Antibacterial combination effect was evaluated against six important food-borne bacteria (Bacillus cereus, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium using microbroth dilution, checkerboard titration and time-kill methods. Antioxidant combination effect was assessed by DPPH free radical scavenging method. Total phenolic content was measured by Folin-Ciocalteu method. Bioactivity -guided fractionation of active essential oils for isolation of bioactive compounds was done using TLC-bioautography assay and chemical characterization (qualitative and quantitative of bioactive compounds was performed using DART-MS and HPLC analyses. Cytotoxic potential was evaluated by brine shrimp lethality assay as well as MTT assay using human normal colon cell line. Results showed that among the possible combinations tested only coriander/cumin seed oil combination showed synergistic interactions both in antibacterial (FICI : 0.25-0.50 and antioxidant (CI : 0.79 activities. A high positive correlation between total phenolic content and antibacterial activity against most of the studied bacteria (R2 = 0.688 - 0.917 as well as antioxidant capacity (R2 = 0.828 was also observed. TLC-bioautography-guided screening and subsequent combination studies revealed that two compounds corresponding to Rf values 0.35 from coriander seed oil and 0.53 from cumin seed oil exhibited both synergistic antibacterial and antioxidant activities. The bioactive compound corresponding to Rf 0.35 from coriander seed oil was identified as linalool (68.69% and the bioactive compound corresponding to Rf 0.53 from cumin seed oil was

  11. Evaluation of Synergistic Antibacterial and Antioxidant Efficacy of Essential Oils of Spices and Herbs in Combination.

    Science.gov (United States)

    Bag, Anwesa; Chattopadhyay, Rabi Ranjan

    2015-01-01

    The present study was carried out to evaluate the possible synergistic interactions on antibacterial and antioxidant efficacy of essential oils of some selected spices and herbs [bay leaf, black pepper, coriander (seed and leaf), cumin, garlic, ginger, mustard, onion and turmeric] in combination. Antibacterial combination effect was evaluated against six important food-borne bacteria (Bacillus cereus, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium) using microbroth dilution, checkerboard titration and time-kill methods. Antioxidant combination effect was assessed by DPPH free radical scavenging method. Total phenolic content was measured by Folin-Ciocalteu method. Bioactivity -guided fractionation of active essential oils for isolation of bioactive compounds was done using TLC-bioautography assay and chemical characterization (qualitative and quantitative) of bioactive compounds was performed using DART-MS and HPLC analyses. Cytotoxic potential was evaluated by brine shrimp lethality assay as well as MTT assay using human normal colon cell line. Results showed that among the possible combinations tested only coriander/cumin seed oil combination showed synergistic interactions both in antibacterial (FICI : 0.25-0.50) and antioxidant (CI : 0.79) activities. A high positive correlation between total phenolic content and antibacterial activity against most of the studied bacteria (R2 = 0.688 - 0.917) as well as antioxidant capacity (R2 = 0.828) was also observed. TLC-bioautography-guided screening and subsequent combination studies revealed that two compounds corresponding to Rf values 0.35 from coriander seed oil and 0.53 from cumin seed oil exhibited both synergistic antibacterial and antioxidant activities. The bioactive compound corresponding to Rf 0.35 from coriander seed oil was identified as linalool (68.69%) and the bioactive compound corresponding to Rf 0.53 from cumin seed oil was identified as p

  12. Synergistic associations of depression and apolipoprotein E genotype with incidence of dementia.

    Science.gov (United States)

    Kim, Jae-Min; Stewart, Robert; Kim, Seon-Young; Kim, Sung-Wan; Bae, Kyung-Yeol; Yang, Su-Jin; Shin, Il-Seon; Yoon, Jin-Sang

    2011-09-01

    A cohort study of Japanese-American men suggested interactive effects of depression and apolipoprotein E (APOE) e4 allele on risk of incident dementia. In another sample of East Asian origin, we sought to replicate the findings and to explore individual depressive symptoms where this interaction was most evident. Of 625 Korean community elders without dementia at baseline, 518 (83%) were followed over a 2.4-year period and were clinically assessed for incident dementia. Depression was identified by the Geriatric Mental State Schedule (GMS), and nine individual depressive symptoms relevant to DSM-IV major depressive episode criteria were extracted. APOE genotype was ascertained. Covariates included age, gender, education, and disability. There were synergistic interactions between depression and APOE e4 on incident dementia independent of covariates. This interaction was particularly strong for four depressive symptoms: depressed mood, worthlessness, concentration difficulty, and suicidal ideation. We were able to replicate the previous study, finding that, at least in East Asian origin populations, the APOE e4 allele is a stronger predictor of incident dementia in the presence of depressive syndrome, and particular depressive symptoms. Copyright © 2010 John Wiley & Sons, Ltd.

  13. Pre-clinical drug prioritization via prognosis-guided genetic interaction networks.

    Directory of Open Access Journals (Sweden)

    Jianghui Xiong

    Full Text Available The high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Patient population heterogeneity and unpredictable physiology complicate pre-clinical cancer modeling efforts. We hypothesize that gene networks associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. Here we propose a novel in vivo genetic interaction which we call 'synergistic outcome determination' (SOD, a concept similar to 'Synthetic Lethality'. SOD is defined as the synergy of a gene pair with respect to cancer patients' outcome, whose correlation with outcome is due to cooperative, rather than independent, contributions of genes. The method combines microarray gene expression data with cancer prognostic information to identify synergistic gene-gene interactions that are then used to construct interaction networks based on gene modules (a group of genes which share similar function. In this way, we identified a cluster of important epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to the cancer-specific inter-module network, we defined a perturbation index for each drug based upon its characteristic perturbation pattern on the inter-module network. Finally, by calculating this index for compounds in the NCI Standard Agent Database, we significantly discriminated successful drugs from a broad set of test compounds, and further revealed the mechanisms of drug combinations. Thus, prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies.

  14. Promoting synergistic research and education in genomics and bioinformatics

    Science.gov (United States)

    2008-01-01

    scientific achievements by bridging these two very important disciplines into an interactive and attractive forum. Keeping this objective in mind, Biocomp 2007 aims to promote interdisciplinary and multidisciplinary education and research. 25 high quality peer-reviewed papers were selected from 400+ submissions for this supplementary issue of BMC Genomics. Those papers contributed to a wide-range of important research fields including gene expression data analysis and applications, high-throughput genome mapping, sequence analysis, gene regulation, protein structure prediction, disease prediction by machine learning techniques, systems biology, database and biological software development. We always encourage participants submitting proposals for genomics sessions, special interest research sessions, workshops and tutorials to Professor Hamid R. Arabnia (hra@cs.uga.edu) in order to ensure that Biocomp continuously plays the leadership role in promoting inter/multidisciplinary research and education in the fields. Biocomp received top conference ranking with a high score of 0.95/1.00. Biocomp is academically co-sponsored by the International Society of Intelligent Biological Medicine and the Research Laboratories and Centers of Harvard University – Massachusetts Institute of Technology, Indiana University - Purdue University, Georgia Tech – Emory University, UIUC, UCLA, Columbia University, University of Texas at Austin and University of Iowa etc. Biocomp - Worldcomp brings leading scientists together across the nation and all over the world and aims to promote synergistic components such as keynote lectures, special interest sessions, workshops and tutorials in response to the advances of cutting-edge research. PMID:18366597

  15. Promoting synergistic research and education in genomics and bioinformatics.

    Science.gov (United States)

    Yang, Jack Y; Yang, Mary Qu; Zhu, Mengxia Michelle; Arabnia, Hamid R; Deng, Youping

    2008-01-01

    scientific achievements by bridging these two very important disciplines into an interactive and attractive forum. Keeping this objective in mind, Biocomp 2007 aims to promote interdisciplinary and multidisciplinary education and research. 25 high quality peer-reviewed papers were selected from 400+ submissions for this supplementary issue of BMC Genomics. Those papers contributed to a wide-range of important research fields including gene expression data analysis and applications, high-throughput genome mapping, sequence analysis, gene regulation, protein structure prediction, disease prediction by machine learning techniques, systems biology, database and biological software development. We always encourage participants submitting proposals for genomics sessions, special interest research sessions, workshops and tutorials to Professor Hamid R. Arabnia (hra@cs.uga.edu) in order to ensure that Biocomp continuously plays the leadership role in promoting inter/multidisciplinary research and education in the fields. Biocomp received top conference ranking with a high score of 0.95/1.00. Biocomp is academically co-sponsored by the International Society of Intelligent Biological Medicine and the Research Laboratories and Centers of Harvard University--Massachusetts Institute of Technology, Indiana University--Purdue University, Georgia Tech--Emory University, UIUC, UCLA, Columbia University, University of Texas at Austin and University of Iowa etc. Biocomp--Worldcomp brings leading scientists together across the nation and all over the world and aims to promote synergistic components such as keynote lectures, special interest sessions, workshops and tutorials in response to the advances of cutting-edge research.

  16. Exploring interaction effects in small samples increases rates of false-positive and false-negative findings: Results from a systematic review and simulation study

    NARCIS (Netherlands)

    Schmidt, Amand F.; Groenwold, Rolf H.H.; Knol, Mirjam J.; Hoes, Arno W.; Nielen, Mirjam; Roes, Kit C.B.; De Boer, Anthonius; Klungel, Olaf H.

    2014-01-01

    Objective To give a comprehensive comparison of the performance of commonly applied interaction tests. Methods A literature review and simulation study was performed evaluating interaction tests on the odds ratio (OR) or the risk difference (RD) scales: Cochran Q (Q), Breslow-Day (BD), Tarone,

  17. Synergistic antibacterial and antibiofilm efficacy of nisin in combination with p-coumaric acid against food-borne bacteria Bacillus cereus and Salmonella typhimurium.

    Science.gov (United States)

    Bag, A; Chattopadhyay, R R

    2017-11-01

    The aim of the study was to evaluate possible antibacterial and antibiofilm efficacy of a bacteriocin, nisin with two essential oil components linalool and p-coumaric acid in combination against food-borne bacteria Bacillus cereus and Salmonella typhimurium. Their inhibition effects on planktonic cells and preformed biofilms were evaluated using microbroth dilution and checkerboard titration methods. Nisin/p-coumaric acid combination showed synergistic effects against planktonic cells of both the studied bacteria, whereas nisin/linalool combination showed synergistic activity against B. cereus and additive effect against S. typhimurium. In preformed biofilms, nisin by itself failed to show >50% antibiofilm efficacy against both the studied bacteria, but in combination with linalool and p-coumaric acid, it exerted >50% antibiofilm efficacy. On the basis of fractional inhibitory concentration indices values, nisin/p-coumaric acid combination exhibited synergistic antibiofilm activity, whereas nisin/linalool combination showed additive effects against preformed biofilms of studied bacteria. The results provide evidence that p-coumaric acid due to its synergistic interactions with nisin against planktonic cells and biofilms of both Gram-positive and Gram-negative food-borne bacteria enhanced the antibacterial spectrum of nisin, which subsequently may facilitate their use in the food industry. In the present work, synergistic interactions between a bacteriocin, nisin and essential oil component p-coumaric acid on planktonic cells as well as on biofilms of Gram-positive and Gram-negative food-borne bacteria have been reported. The results of this study provide evidence that nisin/p-coumaric acid combination can be considered as a promising source for development of more potent broad spectrum antimicrobial blend for food preservation, which subsequently may facilitate their use in the food industry. To the best of our knowledge, this is the first report of the

  18. Synergistic effects of anaerobic co-digestion of whey, manure and fish ensilage.

    Science.gov (United States)

    Vivekanand, Vivekanand; Mulat, Daniel Girma; Eijsink, Vincent G H; Horn, Svein J

    2017-09-27

    Biogas production potential of the three feedstocks fish ensilage, manure and whey was evaluated using biochemical methane potential (BMP) tests. Since anaerobic digestion of single substrates may be inefficient due to imbalances in the carbon-nitrogen ratio, degree of biodegradability and/or due to lack of nutrients needed by the microbial community, co-digestion of these substrates was also assessed, revealing synergistic effects and a particularly good effect of combining manure with fish ensilage. In this latter case, methane yields were up to 84% higher than the weighted average of the methane yields obtained with the individual substrates. The type of substrate was the dominating cause of variation in methane production rates and yields. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. In situ hydrothermal synthesis of a novel hierarchically porous TS-1/modified-diatomite composite for methylene blue (MB) removal by the synergistic effect of adsorption and photocatalysis.

    Science.gov (United States)

    Yuan, Weiwei; Yuan, Peng; Liu, Dong; Yu, Wenbin; Laipan, Minwang; Deng, Liangliang; Chen, Fanrong

    2016-01-15

    Hierarchically porous TS-1/modified-diatomite composites with high removal efficiency for methylene blue (MB) were prepared via a facile in situ hydrothermal route. The surface charge state of the diatomite was modified to enhance the electrostatic interactions, followed by in situ hydrothermal coating with TS-1 nanoparticles. The zeolite loading amount in the composites could be adjusted by changing the hydrothermal time. The highest specific surface area and micropore volume of the obtained composites were 521.3m(2)/g and 0.254cm(3)/g, respectively, with an optimized zeolite loading amount of 96.8%. Based on the synergistic effect of efficient adsorption and photocatalysis resulting from the newly formed hierarchically porous structure and improved dispersion of TS-1 nanoparticles onto diatomite, the composites' removal efficiency for MB reached 99.1% after 2h of photocatalytic reaction, even higher than that observed using pure TS-1 nanoparticles. Moreover, the superior MB removal kinetics of the composites were well represented by a pseudo-first-order model, with a rate constant (5.28×10(-2)min(-1)) more than twice as high as that of pure TS-1 nanoparticles (2.43×10(-2)min(-1)). The significant dye removal performance of this novel TS-1/modified-diatomite composite indicates that it is a promising candidate for use in waste water treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Synergistic exacerbation of mitochondrial and synaptic dysfunction and resultant learning and memory deficit in a mouse model of diabetic Alzheimer's disease.

    Science.gov (United States)

    Wang, Yongfu; Wu, Long; Li, Jianping; Fang, Du; Zhong, Changjia; Chen, John Xi; Yan, Shirley ShiDu

    2015-01-01

    Diabetes is considered to be a risk factor in Alzheimer's disease (AD) pathogenesis. Although recent evidence indicates that diabetes exaggerates pathologic features of AD, the underlying mechanisms are not well understood. To determine whether mitochondrial perturbation is associated with the contribution of diabetes to AD progression, we characterized mouse models of streptozotocin (STZ)-induced type 1 diabetes and transgenic AD mouse models with diabetes. Brains from mice with STZ-induced diabetes revealed a significant increase of cyclophilin D (CypD) expression, reduced respiratory function, and decreased hippocampal long-term potentiation (LTP); these animals had impaired spatial learning and memory. Hyperglycemia exacerbated the upregulation of CypD, mitochondrial defects, synaptic injury, and cognitive dysfunction in the brains of transgenic AD mice overexpressing amyloid-β as shown by decreased mitochondrial respiratory complex I and IV enzyme activity and greatly decreased mitochondrial respiratory rate. Concomitantly, hippocampal LTP reduction and spatial learning and memory decline, two early pathologic indicators of AD, were enhanced in the brains of diabetic AD mice. Our results suggest that the synergistic interaction between effects of diabetes and AD on mitochondria may be responsible for brain dysfunction that is in common in both diabetes and AD.

  1. Synergistic Exacerbation of Mitochondrial and Synaptic Dysfunction and Resultant Learning and Memory Deficit in a Mouse Model of Diabetic Alzheimer’s Disease

    Science.gov (United States)

    Wang, Yongfu; Wu, Long; Li, Jianping; Fang, Du; Zhong, Changjia; Chen, John Xi; Yan, Shirley ShiDu

    2015-01-01

    Diabetes is considered to be a risk factor in Alzheimer’s disease (AD) pathogenesis. Although recent evidence indicates that diabetes exaggerates pathologic features of AD, the underlying mechanisms are not well understood. To determine whether mitochondrial perturbation is associated with the contribution of diabetes to AD progression, we characterized mouse models of streptozotocin (STZ)-induced type 1 diabetes and transgenic AD mouse models with diabetes. Brains from mice with STZ-induced diabetes revealed a significant increase of cyclophilin D (CypD) expression, reduced respiratory function, and decreased hippocampal long-term potentiation (LTP); these animals had impaired spatial learning and memory. Hyperglycemia exacerbated the upregulation of CypD, mitochondrial defects, synaptic injury, and cognitive dysfunction in the brains of transgenic AD mice overexpressing amyloid-β as shown by decreased mitochondrial respiratory complex I and IV enzyme activity and greatly decreased mitochondrial respiratory rate. Concomitantly, hippocampal LTP reduction and spatial learning and memory decline, two early pathologic indicators of AD, were enhanced in the brains of diabetic AD mice. Our results suggest that the synergistic interaction between effects of diabetes and AD on mitochondria may be responsible for brain dysfunction that is in common in both diabetes and AD. PMID:25096625

  2. Searching for Drug Synergy in Complex Dose-Response Landscapes Using an Interaction Potency Model.

    Science.gov (United States)

    Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero; Tang, Jing

    2015-01-01

    Rational design of multi-targeted drug combinations is a promising strategy to tackle the drug resistance problem for many complex disorders. A drug combination is usually classified as synergistic or antagonistic, depending on the deviation of the observed combination response from the expected effect calculated based on a reference model of non-interaction. The existing reference models were proposed originally for low-throughput drug combination experiments, which make the model assumptions often incompatible with the complex drug interaction patterns across various dose pairs that are typically observed in large-scale dose-response matrix experiments. To address these limitations, we proposed a novel reference model, named zero interaction potency (ZIP), which captures the drug interaction relationships by comparing the change in the potency of the dose-response curves between individual drugs and their combinations. We utilized a delta score to quantify the deviation from the expectation of zero interaction, and proved that a delta score value of zero implies both probabilistic independence and dose additivity. Using data from a large-scale anticancer drug combination experiment, we demonstrated empirically how the ZIP scoring approach captures the experimentally confirmed drug synergy while keeping the false positive rate at a low level. Further, rather than relying on a single parameter to assess drug interaction, we proposed the use of an interaction landscape over the full dose-response matrix to identify and quantify synergistic and antagonistic dose regions. The interaction landscape offers an increased power to differentiate between various classes of drug combinations, and may therefore provide an improved means for understanding their mechanisms of action toward clinical translation.

  3. Searching for Drug Synergy in Complex Dose–Response Landscapes Using an Interaction Potency Model

    Science.gov (United States)

    Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero; Tang, Jing

    2015-01-01

    Rational design of multi-targeted drug combinations is a promising strategy to tackle the drug resistance problem for many complex disorders. A drug combination is usually classified as synergistic or antagonistic, depending on the deviation of the observed combination response from the expected effect calculated based on a reference model of non-interaction. The existing reference models were proposed originally for low-throughput drug combination experiments, which make the model assumptions often incompatible with the complex drug interaction patterns across various dose pairs that are typically observed in large-scale dose–response matrix experiments. To address these limitations, we proposed a novel reference model, named zero interaction potency (ZIP), which captures the drug interaction relationships by comparing the change in the potency of the dose–response curves between individual drugs and their combinations. We utilized a delta score to quantify the deviation from the expectation of zero interaction, and proved that a delta score value of zero implies both probabilistic independence and dose additivity. Using data from a large-scale anticancer drug combination experiment, we demonstrated empirically how the ZIP scoring approach captures the experimentally confirmed drug synergy while keeping the false positive rate at a low level. Further, rather than relying on a single parameter to assess drug interaction, we proposed the use of an interaction landscape over the full dose–response matrix to identify and quantify synergistic and antagonistic dose regions. The interaction landscape offers an increased power to differentiate between various classes of drug combinations, and may therefore provide an improved means for understanding their mechanisms of action toward clinical translation. PMID:26949479

  4. Synergistic Anticancer Action of Lysosomal Membrane Permeabilization and Glycolysis Inhibition.

    Science.gov (United States)

    Kosic, Milica; Arsikin-Csordas, Katarina; Paunovic, Verica; Firestone, Raymond A; Ristic, Biljana; Mircic, Aleksandar; Petricevic, Sasa; Bosnjak, Mihajlo; Zogovic, Nevena; Mandic, Milos; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2016-10-28

    We investigated the in vitro and in vivo anticancer effect of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-d-glucose (2DG). NDI-triggered LMP and 2DG-mediated glycolysis block synergized in inducing rapid ATP depletion, mitochondrial damage, and reactive oxygen species production, eventually leading to necrotic death of U251 glioma cells but not primary astrocytes. NDI/2DG-induced death of glioma cells was partly prevented by lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol, suggesting the involvement of LMP and oxidative stress in the observed cytotoxicity. LMP-inducing agent chloroquine also displayed a synergistic anticancer effect with 2DG, whereas glucose deprivation or glycolytic inhibitors iodoacetate and sodium fluoride synergistically cooperated with NDI, thus further indicating that the anticancer effect of NDI/2DG combination was indeed due to LMP and glycolysis block. The two agents synergistically induced ATP depletion, mitochondrial depolarization, oxidative stress, and necrotic death also in B16 mouse melanoma cells. Moreover, the combined oral administration of NDI and 2DG reduced in vivo melanoma growth in C57BL/6 mice by inducing necrotic death of tumor cells, without causing liver, spleen, or kidney toxicity. Based on these results, we propose that NDI-triggered LMP causes initial mitochondrial damage that is further increased by 2DG due to the lack of glycolytic ATP required to maintain mitochondrial health. This leads to a positive feedback cycle of mitochondrial dysfunction, ATP loss, and reactive oxygen species production, culminating in necrotic cell death. Therefore, the combination of LMP-inducing agents and glycolysis inhibitors seems worthy of further exploration as an anticancer strategy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Engineered microenvironments for synergistic VEGF - Integrin signalling during vascularization.

    Science.gov (United States)

    Moulisová, Vladimíra; Gonzalez-García, Cristina; Cantini, Marco; Rodrigo-Navarro, Aleixandre; Weaver, Jessica; Costell, Mercedes; Sabater I Serra, Roser; Dalby, Matthew J; García, Andrés J; Salmerón-Sánchez, Manuel

    2017-05-01

    We have engineered polymer-based microenvironments that promote vasculogenesis both in vitro and in vivo through synergistic integrin-growth factor receptor signalling. Poly(ethyl acrylate) (PEA) triggers spontaneous organization of fibronectin (FN) into nanonetworks which provide availability of critical binding domains. Importantly, the growth factor binding (FNIII12-14) and integrin binding (FNIII9-10) regions are simultaneously available on FN fibrils assembled on PEA. This material platform promotes synergistic integrin/VEGF signalling which is highly effective for vascularization events in vitro with low concentrations of VEGF. VEGF specifically binds to FN fibrils on PEA compared to control polymers (poly(methyl acrylate), PMA) where FN remains in a globular conformation and integrin/GF binding domains are not simultaneously available. The vasculogenic response of human endothelial cells seeded on these synergistic interfaces (VEGF bound to FN assembled on PEA) was significantly improved compared to soluble administration of VEGF at higher doses. Early onset of VEGF signalling (PLCγ1 phosphorylation) and both integrin and VEGF signalling (ERK1/2 phosphorylation) were increased only when VEGF was bound to FN nanonetworks on PEA, while soluble VEGF did not influence early signalling. Experiments with mutant FN molecules with impaired integrin binding site (FN-RGE) confirmed the role of the integrin binding site of FN on the vasculogenic response via combined integrin/VEGF signalling. In vivo experiments using 3D scaffolds coated with FN and VEGF implanted in the murine fat pad demonstrated pro-vascularization signalling by enhanced formation of new tissue inside scaffold pores. PEA-driven organization of FN promotes efficient presentation of VEGF to promote vascularization in regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. A Synergistic Approach of Desirability Functions and Metaheuristic Strategy to Solve Multiple Response Optimization Problems

    Science.gov (United States)

    Bera, Sasadhar; Mukherjee, Indrajit

    2010-10-01

    Ensuring quality of a product is rarely based on observations of a single quality characteristic. Generally, it is based on observations of family of properties, so-called `multiple responses'. These multiple responses are often interacting and are measured in variety of units. Due to presence of interaction(s), overall optimal conditions for all the responses rarely result from isolated optimal condition of individual response. Conventional optimization techniques, such as design of experiment, linear and nonlinear programmings are generally recommended for single response optimization problems. Applying any of these techniques for multiple response optimization problem may lead to unnecessary simplification of the real problem with several restrictive model assumptions. In addition, engineering judgements or subjective ways of decision making may play an important role to apply some of these conventional techniques. In this context, a synergistic approach of desirability functions and metaheuristic technique is a viable alternative to handle multiple response optimization problems. Metaheuristics, such as simulated annealing (SA) and particle swarm optimization (PSO), have shown immense success to solve various discrete and continuous single response optimization problems. Instigated by those successful applications, this chapter assesses the potential of a Nelder-Mead simplex-based SA (SIMSA) and PSO to resolve varied multiple response optimization problems. The computational results clearly indicate the superiority of PSO over SIMSA for the selected problems.

  7. Interactive effects of a bacterial parasite and the insecticide carbaryl to life-history and physiology of two Daphnia magna clones differing in carbaryl sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    De Coninck, Dieter I.M., E-mail: Dieter.DeConinck@UGent.be [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium); De Schamphelaere, Karel A.C. [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium); Jansen, Mieke; De Meester, Luc [Laboratory of Aquatic Ecology, Evolution and Conservation, University of Leuven, Ch. Deberiotstraat 32, B-3000 Leuven (Belgium); Janssen, Colin R. [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium)

    2013-04-15

    Highlights: ► Interactive effects between a bacterial parasite and an insecticide in Daphnia magna. ► Two D. magna clones differing strongly in their sensitivity to the insecticide. ► Effects studied on various life-history and physiological endpoints. ► Genetic differences in strength and direction of interaction effects. -- Abstract: Natural and chemical stressors occur simultaneously in the aquatic environment. Their combined effects on biota are usually difficult to predict from their individual effects due to interactions between the different stressors. Several recent studies have suggested that synergistic effects of multiple stressors on organisms may be more common at high compared to low overall levels of stress. In this study, we used a three-way full factorial design to investigate whether interactive effects between a natural stressor, the bacterial parasite Pasteuria ramosa, and a chemical stressor, the insecticide carbaryl, were different between two genetically distinct clones of Daphnia magna that strongly differ in their sensitivity to carbaryl. Interactive effects on various life-history and physiological endpoints were assessed as significant deviations from the reference Independent Action (IA) model, which was implemented by testing the significance of the two-way carbaryl × parasite interaction term in two-way ANOVA's on log-transformed observational data for each clone separately. Interactive effects (and thus significant deviations from IA) were detected in both the carbaryl-sensitive clone (on survival, early reproduction and growth) and in the non-sensitive clone (on growth, electron transport activity and prophenoloxidase activity). No interactions were found for maturation rate, filtration rate, and energy reserve fractions (carbohydrate, protein, lipid). Furthermore, only antagonistic interactions were detected in the non-sensitive clone, while only synergistic interactions were observed in the carbaryl sensitive clone

  8. The synergistic effect of functional status and comorbidity burden on mortality: a 16-year survival analysis.

    Directory of Open Access Journals (Sweden)

    Cynthia Chen

    Full Text Available The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty.National data were retrospectively extracted from medical records of community hospital.There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011.Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality.During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%. The mean age was 73.0 (standard deviation: 11.5 years. Independent risk factors of mortality were higher comorbidity (p<0.001, severity of disability at discharge (p<0.001, being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25-1.53, low socioeconomic status (aHR:1.40, 95%CI:1.29-1.53, discharge to nursing home (aHR:1.14, 95%CI:1.05-1.22 and re-admission into acute care (aHR:1.54, 95%CI:1.45-1.65. In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13-2.72 whereas those with total disability had an aHR = 2.28 (95%CI:2.12-2.46. In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001 where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15-8.37.Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk.

  9. Ionic Liquids: The Synergistic Catalytic Effect in the Synthesis of Cyclic Carbonates

    Directory of Open Access Journals (Sweden)

    Flora T.T. Ng

    2013-10-01

    Full Text Available This review presents the synergistic effect in the catalytic system of ionic liquids (ILs for the synthesis of cyclic carbonate from carbon dioxide and epoxide. The emphasis of this review is on three aspects: the catalytic system of metal-based ionic liquids, the catalytic system of hydrogen bond-promoted ionic liquids and supported ionic liquids. Metal and ionic liquids show a synergistic effect on the cycloaddition reactions of epoxides. The cations and anions of ionic liquids show a synergistic effect on the cycloaddition reactions. The functional groups in cations or supports combined with the anions have a synergistic effect on the cycloaddition reactions. Synergistic catalytic effects of ILs play an important role of promoting the cycloaddition reactions of epoxides. The design of catalytic system of ionic liquids will be possible if the synergistic effect on a molecular level is understood.

  10. Control of anthracnose caused by Colletotrichum species in guava, mango and papaya using synergistic combinations of chitosan and Cymbopogon citratus (D.C. ex Nees) Stapf. essential oil.

    Science.gov (United States)

    Lima Oliveira, Priscila Dinah; de Oliveira, Kataryne Árabe Rimá; Vieira, Willie Anderson Dos Santos; Câmara, Marcos Paz Saraiva; de Souza, Evandro Leite

    2018-02-02

    This study assessed the efficacy of chitosan (Chi) and Cymbopogon citratus (D.C. ex Nees) Stapf. essential oil (CCEO) combinations to control the mycelial growth of five pathogenic Colletotrichum species (C. asianum, C. siamense, C. fructicola, C. tropicale and C. karstii) in vitro, as well as the anthracnose development in guava (Psidium guajava L.) cv. Paluma, mango (Mangifera indica L.) cv. Tommy Atkins and papaya (Carica papaya L.) cv. Papaya artificially inoculated with these species. Combinations of Chi (2.5, 5 or 7.5mg/mL) and CCEO (0.15, 0.3, 0.6 or 1.25μL/mL) inhibited the mycelial growth of all tested fungal species in vitro. Examined Chi-CCEO combinations showed additive or synergistic interactions to inhibit the target Colletotrichum species based on the Abbott index. Coatings formed by synergistic Chi (5mg/mL) and CCEO (0.15, 0.3 or 0.6μL/mL) combinations decreased anthracnose lesion development in guava, mango and papaya inoculated with any of the tested Colleotrichum species during storage. Overall, anthracnose lesion development inhibition in fruit coated with synergistic Chi-CCEO combinations was higher than that observed in fruit treated with synthetic fungicides. These results show that the application of coatings formed by Chi-CCEO synergistic combinations could be effective to control postharvest anthracnose development in fruit. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Pesticide Interactions: Mechanisms, Benefits, and Risks.

    Science.gov (United States)

    Casida, John E

    2017-06-14

    Interactions between pesticides at common molecular targets and detoxification systems often determine their effectiveness and safety. Compounds with the same mode of action or target are candidates for cross resistance and restrictions in their recommended uses. Discovery research is therefore focused on new mechanisms and modes of action. Interactions in detoxification systems also provide cross resistance and synergist and safener mechanisms illustrated with serine hydrolases and inhibitors, cytochrome P450 and insecticide synergists, and glutathione S-transferases and herbicide safeners. Secondary targets are also considered for inhibitors of serine hydrolases, aldehyde dehydrogenases, and transporters. Emphasis is given to the mechanistic aspects of interactions, not the incidence, which depends on potency, exposure, ratios, and timing. The benefits of pesticide interactions are the additional levels of chemical control to achieve desired organismal effects. The risks are the unpredictable interactions of complex interconnected biological systems. However, with care, two can be better than one.

  12. Synergistic atmospheric retrievals: Using OMEGA and PFS to retrieve martian CO

    Science.gov (United States)

    Robert, S.; Aoki, S.; Piccialli, A.; Audouard, J.; Montmessin, F.; Ferron, S.; Altieri, F.; Bellucci, G.; Geminale, A.; Giuranna, M.; Sindoni, G.; Vandaele, A. C.

    2017-09-01

    Recently, a theoretical study was published showing how science return can benefit from synergistic retrievals [Robert et al., 2017]. The same approach is here applied to experimental data. OMEGA and PFS instruments, both on Mars Express spacecraft, have collected high-quality data enabling us to retrieve CO volume mixing ratio, among others. The synergy between OMEGA and PFS channels will be presented and the benefits of the synergy will be described by comparing synergistic spectral retrievals and non-synergistic ones.

  13. Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2005-02-01

    Full Text Available Abstract Background Recent studies have shown that gamma interferon (IFN-γ synergizes with the innate IFNs (IFN-α and IFN-β to inhibit herpes simplex virus type 1 (HSV-1 replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV replication. Results We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE genes (IE1 and IE2 revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. Conclusion These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo.

  14. The Synergistic Effect of Pasireotide and Teriflunomide in Carcinoids in vitro

    Science.gov (United States)

    Somnay, Yash; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2012-01-01

    Background/Aim Somatostatin analogs are mainstay for controlling tumor proliferation and hormone secretion in carcinoid patients. Recent data suggest that ERK1/2 phosphorylation may potentiate the anti-tumor effects of somatostatin analogs in carcinoids. Additionally, ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in carcinoids. Thus, Raf-1/MEK/ERK1/2 pathway activating drugs may be synergistic with somatostatin analogs such as Pasireotide (SOM230), which may be more effective than others in its class given its elevated receptor affinity and broader binding spectrum. Here, we investigate the effects of SOM230 in combination with Teriflunomide (TFN), a Raf-1 activator, in a human carcinoid cell line. Methods Human pancreatic carcinoid cells (BON) were incubated in TFN, SOM230 or a combination. Cell proliferation was measured using a rapid colorimetric assay. Western analysis was performed to analyze expression levels of achaete-scute complex-like1 (ASCL1), Chromogranin A (CgA), phosphorylated and total ERK1/2, and markers for apoptosis. Results Combination treatment with SOM230 and TFN reduced cell growth beyond the additive effect of either drug alone. Combination indices (CI) fell below 1, thus quantifiably verifying synergy between both drugs as per the Chou-Talalay CI scale. Combined treatment also reduced ASCL1 and CgA expression beyond the additive effect of either drug alone. Furthermore, it increased levels of phosphorylated ERK1/2, cleaved PARP and caspase-3, and reduced levels of anti-apoptotic biomarkers. Elevated phosphorylated ERK1/2 expression following combination therapy may underlie the synergistic interaction between the two drugs. Conclusion Since efficacy is achieved at lower doses, combination therapy may palliate symptoms at low toxicity levels. Because each drug has already been evaluated in clinical trials, combinatorial drug trials are warranted. PMID:22965070

  15. Anti-leukemic action of the novel agent MGI 114 (HMAF) and synergistic action with topotecan.

    Science.gov (United States)

    Kelner, M J; McMorris, T C; Estes, L; Samson, K M; Trani, N A; MacDonald, J R

    2000-01-01

    The illudin derivative MGI 114 (6-hydroxymethylacylfulvene or HMAF) is currently in phase II chemotherapeutic clinical trials for a variety of solid tumors. The illudins were originally thought to be potentially useful agents for myeloid leukemias, because hematopoietic tumor cells were markedly sensitive whereas normal bone marrow progenitors were relatively resistant to the cytotoxic effects of illudins. Due to the marked preclinical efficacy of MGI 114 against a variety of solid tumor xenografts, the current phase II human trials are restricted to solid tumor (breast, lung, colon, ovarian, pancreas, prostate, etc) malignancies. The present studies were undertaken to evaluate the efficacy of MGI 114 in the HL60/MRI myeloid leukemia xenograft. In addition, because of the reported synergistic cytotoxic activity between MGI 114 and the topoisomerase I inhibitor topotecan towards pediatric human tumor cell lines, we tested the activity of MGI 114 and topotecan combinations against HL60 cells in vitro and the HL60/MRI myelocytic xenograft. Our results indicate that MGI 114 at maximum tolerated doses (MTD) of 7 mg/kg, five times per week for 3 weeks does display anti-myeloid leukemic properties in the HL60/MRI xenograft model which exceeds activity noted with other conventional agents (TGI > 70%). A marked therapeutic synergistic action was observed with MGI 114 and topotecan combinations of (1/2) MTD of each agent producing complete tumor remission in 50% of animals, without development of excessive or additive toxicity in animals. These results support further in vitro and clinical investigation into both the anti-myeloid leukemic activity of MGI-114, and the cooperative pharmacologic interaction noted between MGI-114 and topoisomerase I inhibitors. Leukemia (2000) 14, 136-141.

  16. Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling.

    Science.gov (United States)

    Pansters, N A; Langen, R C; Wouters, E F; Schols, A M

    2013-05-01

    Muscle wasting is associated with poor prognosis in chronic obstructive pulmonary disease (COPD). Exercise stimulates muscle recovery, but its efficacy is variable, depending on the clinical condition and medical treatment. Systemic glucocorticoids, commonly administered in high doses during acute disease exacerbations or as maintenance treatment in end-stage disease, are known to contribute to muscle wasting. As muscle mass recovery involves insulin-like growth factor (IGF)-I signaling, which can be stimulated by anabolic steroids, the impact of glucocorticoids and the effect of simultaneous IGF-I stimulation by anabolic steroids on muscle recovery and growth were investigated. The effects of, and interactions between, glucocorticoid and IGF-I signaling on skeletal muscle growth were assessed in differentiating C2C12 myocytes. As proof of principle, we performed a post hoc analysis stratifying patients by glucocorticoid use of a clinical trial investigating the efficacy of anabolic steroid supplementation on muscle recovery in muscle-wasted patients with COPD. Glucocorticoids strongly impaired protein synthesis signaling, myotube formation, and muscle-specific protein expression. In contrast, in the presence of glucocorticoids, IGF-I synergistically stimulated myotube fusion and myofibrillar protein expression, which corresponded with restored protein synthesis signaling by IGF-I and increased transcriptional activation of muscle-specific genes by glucocorticoids. In COPD patients on maintenance glucocorticoid treatment, the clinical trial also revealed an enhanced effect of anabolic steroids on muscle mass and respiratory muscle strength. In conclusion, synergistic effects of anabolic steroids and glucocorticoids on muscle recovery may be caused by relief of the glucocorticoid-imposed blockade on protein synthesis signaling, allowing effective translation of glucocorticoid-induced accumulation of muscle-specific gene transcripts.

  17. Synergistic antibaterial activity of medicinal plants essential oils with biogenic silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Fatemeh Oroojalian

    2017-10-01

    Full Text Available Objective(s: Development of a nanobiosystem by using plant essential oils with green synthesized silver nanoparticles that present synergistic antibacterial activity for overcoming antibiotic resistance in pathogenic bacteria. Material and Methods: Essential oils (EOs of Kelussia odoratissima and Teucrium polium extracted by hydrodistillation were analyzed by gas chromatography-mass spectrometry (GC-MS. Then leaf aqueous extract of K. odoratissima prepared and used for green synthesise of silver nanoparticles (SNPs.  The oils, and the colloidal preparations of silver nanoparticles, were then subjected to microdilution technique using ELISA reader to determine their minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC on Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Escherichia coli O157: H7, Salmonella enterica and Pseudomonas aeruginosa. The type of interaction between EO and SNPs was also determined by calculating the fractional inhibitory concentration index and isibologram type. Results: GC-MS analysis of K. odoratissima EO showed (Z-ligustilide, (Z-3-butylidene-phthalide,  limonene and β-phellandren as main constiuents, while T. polium EO has β-caryophylene, germacrene D, γ-cadinene, (Z-nerolidol, camphor, β-pinene, α- camphene, linalool and α-humulene. T. polium EO has more potent antibacterial property at MIC of 0.16-1.25 mg/ml compared to K. odoratissima (MIC of 0.3-2.5 mg/ml. Silver nanoparticles showed a potent antibacterial property (MIC of 0.006-0.025 mg/ml, and its colloidal suspension with plant EOs revealed a pathogen-dependent synergistic and additive effect based on calculated fractional inhibitory concentration index (FICi.

  18. Nonlinear Synergistic Emergence and Predictability in Complex Systems: Theory and Hydro-Climatic Applications

    Science.gov (United States)

    Perdigão, Rui A. P.; Hall, Julia; Pires, Carlos A. L.; Blöschl, Günter

    2017-04-01

    Classical and stochastic dynamical system theories assume structural coherence and dynamic recurrence with invariants of motion that are not necessarily so. These are grounded on the unproven assumption of universality in the dynamic laws derived from statistical kinematic evaluation of non-representative empirical records. As a consequence, the associated formulations revolve around a restrictive set of configurations and intermittencies e.g. in an ergodic setting, beyond which any predictability is essentially elusive. Moreover, dynamical systems are fundamentally framed around dynamic codependence among intervening processes, i.e. entail essentially redundant interactions such as couplings and feedbacks. That precludes synergistic cooperation among processes that, whilst independent from each other, jointly produce emerging dynamic behaviour not present in any of the intervening parties. In order to overcome these fundamental limitations, we introduce a broad class of non-recursive dynamical systems that formulate dynamic emergence of unprecedented states in a fundamental synergistic manner, with fundamental principles in mind. The overall theory enables innovations to be predicted from the internal system dynamics before any a priori information is provided about the associated dynamical properties. The theory is then illustrated to anticipate, from non-emergent records, the spatiotemporal emergence of multiscale hyper chaotic regimes, critical transitions and structural coevolutionary changes in synthetic and real-world complex systems. Example applications are provided within the hydro-climatic context, formulating and dynamically forecasting evolving hydro-climatic distributions, including the emergence of extreme precipitation and flooding in a structurally changing hydro-climate system. Validation is then conducted with a posteriori verification of the simulated dynamics against observational records. Agreement between simulations and observations is

  19. Concomitant epigenetic targeting of LSD1 and HDAC synergistically induces mitochondrial apoptosis in rhabdomyosarcoma cells.

    Science.gov (United States)

    Haydn, Tinka; Metzger, Eric; Schuele, Roland; Fulda, Simone

    2017-06-15

    The lysine-specific demethylase 1 (LSD1) is overexpressed in several cancers including rhabdomyosarcoma (RMS). However, little is yet known about whether or not LSD1 may serve as therapeutic target in RMS. We therefore investigated the potential of LSD1 inhibitors alone or in combination with other epigenetic modifiers such as histone deacetylase (HDAC) inhibitors. Here, we identify a synergistic interaction of LSD1 inhibitors (i.e., GSK690, Ex917) and HDAC inhibitors (i.e., JNJ-26481585, SAHA) to induce cell death in RMS cells. By comparison, LSD1 inhibitors as single agents exhibit little cytotoxicity against RMS cells. Mechanistically, GSK690 acts in concert with JNJ-26481585 to upregulate mRNA levels of the proapoptotic BH3-only proteins BMF, PUMA, BIM and NOXA. This increase in mRNA levels is accompanied by a corresponding upregulation of BMF, PUMA, BIM and NOXA protein levels. Importantly, individual knockdown of either BMF, BIM or NOXA significantly reduces GSK690/JNJ-26481585-mediated cell death. Similarly, genetic silencing of BAK significantly rescues cell death upon GSK690/JNJ-26481585 cotreatment. Also, overexpression of antiapoptotic BCL-2 or MCL-1 significantly protects RMS cells from GSK690/JNJ-26481585-induced cell death. Furthermore, GSK690 acts in concert with JNJ-26481585 to increase activation of caspase-9 and -3. Consistently, addition of the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) significantly reduces GSK690/JNJ-26481585-mediated cell death. In conclusion, concomitant LSD1 and HDAC inhibition synergistically induces cell death in RMS cells by shifting the ratio of pro- and antiapoptotic BCL-2 proteins in favor of apoptosis, thereby engaging the intrinsic apoptotic pathway. This indicates that combined treatment with LSD1 and HDAC inhibitors is a promising new therapeutic approach in RMS.

  20. OSU-2S/sorafenib synergistic antitumor combination against hepatocellular carcinoma: The role of PKCδ/p53

    Directory of Open Access Journals (Sweden)

    Hany A Omar

    2016-11-01

    Full Text Available Background: Sorafenib (Nexavar® is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC. However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. The synergistic interactions were determined by Calcusyn analysis. PKCδ knockdown was used to elucidate the role of PKCδ activation as a mechanism for the synergy. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices < 1. This effect was accompanied by parallel increases in caspase 3/7 activity, PARP cleavage, PKCδ activation and HCC cell migration/invasion. In addition, PKCδ knockdown abolished the synergy between sorafenib and OSU-2S. Furthermore, p53 restoration in Hep3B cells through the over-expression rendered them more sensitive to both agents while p53 knockdown from HepG2 cells increased their resistance to both agents. Conclusions: OSU-2S augments the anti-proliferative effect of sorafenib in HCC cell lines, in part, through the activation of PKCδ. The p53 status in HCC cells predicts their sensitivity towards both sorafenib and OSU-2S. The proposed combination represents a therapeutically relevant approach that can lead to a new HCC therapeutic protocol.

  1. Hazards and Benefits of Drug Interaction

    Science.gov (United States)

    Labianca, Dominick A.

    1978-01-01

    Most cases of drug toxicity are direct consequences of drug misuse--either intentional or inadvertent. Discusses two types of drug interaction--synergistic and antagonistic. The former produces a combined effect greater than the sum of the effects of the individual drugs concerned; the latter is produced when the desired action of one drug is…

  2. INSECT AND MYCOFLORA INTERACTIONS IN MAIZE FLOUR ...

    African Journals Online (AJOL)

    Ten species isolated from maize flour with T. castaneum were A. pullulans, Auxarthron spp., C. herbarum, Eurotium sp., Phoma glomerata, Neosauorya spp., Scopulariopsis brevicaulis, Rhizopus oryzae, R. stolonifer and Wallemia sebi. These results suggest an association and a synergistic interaction between important ...

  3. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions.

    Science.gov (United States)

    Lansky, Ephraim P; Jiang, Wenguo; Mo, Huanbiao; Bravo, Lou; Froom, Paul; Yu, Weiping; Harris, Neil M; Neeman, Ishak; Campbell, Moray J

    2005-01-01

    We investigated whether dissimilar biochemical fractions originating in anatomically discrete sections of the pomegranate (Punica granatum) fruit might act synergistically against proliferation, metastatic potential, and phosholipase A2 (PLA2) expression of human prostate cancer cells in vitro . Proliferation of DU 145 human prostate cancer cells was measured following treatment with a range of therapeutically active doses of fermented pomegranate juice polyphenols (W) and sub-therapeutic doses of either pomegranate pericarp (peel) polyphenols (P) or pomegranate seed oil (Oil). Invasion across Matrigel by PC-3 human prostate cancer cells was measured following treatment with combinations of W, P and Oil such that the total gross weight of pomegranate extract was held constant. Expression of PLA2, associated with invasive potential, was measured in the PC-3 cells after treatment with the same dosage combinations as per invasion. Supra-additive, complementary and synergistic effects were proven in all models by the Kruskal-Wallis non-parametric H test at p < 0.001 for the proliferation tests, p < 0.01 for invasion, and p < 0.05 for PLA2 expression. Proliferation effects were additionally evaluated with CompuSyn software median effect analysis and showed a concentration index CI < 1, confirming synergy. The results suggest vertical as well as the usual horizontal strategies for discovering pharmacological actives in plants.

  4. Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies.

    Science.gov (United States)

    Nimako, George K; Wintrob, Zachary A P; Sulik, Dmitriy A; Donato, Jennifer L; Ceacareanu, Alice C

    2017-04-01

    To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM). We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards. Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer-related benefits. Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.

  5. Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

  6. Synergistic extraction of vanadium (V, IV) with dithizone

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    Akaiwa, H.; Kawamoto, H.; Hiyamuta, E. (Gunma Univ., Kiryu (Japa