Science.gov

Sample records for pa-824 kills nonreplicating

  1. Selective killing of nonreplicating mycobacteria.

    PubMed

    Bryk, Ruslana; Gold, Benjamin; Venugopal, Aditya; Singh, Jasbir; Samy, Raghu; Pupek, Krzysztof; Cao, Hua; Popescu, Carmen; Gurney, Mark; Hotha, Srinivas; Cherian, Joseph; Rhee, Kyu; Ly, Lan; Converse, Paul J; Ehrt, Sabine; Vandal, Omar; Jiang, Xiuju; Schneider, Jean; Lin, Gang; Nathan, Carl

    2008-03-13

    Antibiotics are typically more effective against replicating rather than nonreplicating bacteria. However, a major need in global health is to eradicate persistent or nonreplicating subpopulations of bacteria such as Mycobacterium tuberculosis (Mtb). Hence, identifying chemical inhibitors that selectively kill bacteria that are not replicating is of practical importance. To address this, we screened for inhibitors of dihydrolipoamide acyltransferase (DlaT), an enzyme required by Mtb to cause tuberculosis in guinea pigs and used by the bacterium to resist nitric oxide-derived reactive nitrogen intermediates, a stress encountered in the host. Chemical screening for inhibitors of Mtb DlaT identified select rhodanines as compounds that almost exclusively kill nonreplicating mycobacteria in synergy with products of host immunity, such as nitric oxide and hypoxia, and are effective on bacteria within macrophages, a cellular reservoir for latent Mtb. Compounds that kill nonreplicating pathogens in cooperation with host immunity could complement the conventional chemotherapy of infectious disease.

  2. Evaluation of Pharmacokinetic Interaction between PA-824 and Midazolam in Healthy Adult Subjects

    PubMed Central

    Winter, Helen; Egizi, Erica; Erondu, Ngozi; Ginsberg, Ann; Rouse, Doris J.; Severynse-Stevens, Diana; Pauli, Elliott

    2013-01-01

    This study assessed the safety, tolerability, and pharmacokinetic interaction between PA-824, a novel antitubercular nitroimidazo-oxazine, and midazolam, a CYP3A4 substrate, in 14 healthy adult male and female subjects. The study followed up on observations in vitro that PA-824 caused weak and time-dependent inhibition of CYP3A4. Subjects received a single oral dose of midazolam (2 mg), followed by a 2-day washout. After the washout, all subjects received PA-824 (400 mg) once daily for 14 consecutive days. On day 14, all subjects received the final PA-824 dose coadministered with a 2-mg oral dose of midazolam. The pharmacokinetic endpoints AUC0–t, AUC0–∞, and Cmax for midazolam and 1-hydroxy midazolam were compared between midazolam administered alone versus midazolam coadministered with PA-824. Statistical analysis demonstrated that the mean midazolam values of Cmax, AUC0–t, and AUC0–∞ parameters were reduced by ca. 16, 15, and 15%, respectively, when PA-824 was coadministered with midazolam. The total exposure (AUC) of 1-hydroxy midazolam was 13 to 14% greater when coadministered with PA-824 compared to midazolam administered alone. The Cmax of 1-hydroxy midazolam was similar between treatments. Based on these results, PA-824 does not inhibit or induce CYP3A4 to a clinically meaningful extent and is not likely to markedly affect the pharmacokinetics of CYP3A4 metabolized drugs. PMID:23689718

  3. Discovery of a capuramycin analog that kills nonreplicating Mycobacterium tuberculosis and its synergistic effects with translocase I inhibitors.

    PubMed

    Siricilla, Shajila; Mitachi, Katsuhiko; Wan, Bajoie; Franzblau, Scott G; Kurosu, Michio

    2015-04-01

    Capuramycin (1) and its analogs are strong translocase I (MurX/MraY) inhibitors. In our structure-activity relationship studies of capuramycin analogs against Mycobacterium tuberculosis (Mtb), we observed for the first time that a capuramycin analog, UT-01320 (3) killed nonreplicating (dormant) Mtb at low concentrations under low oxygen conditions, whereas selective MurX inhibitors killed only replicating Mtb under aerobic conditions. Interestingly, 3 did not exhibit MurX enzyme inhibitory activity even at high concentrations, however, 3 inhibited bacterial RNA polymerases with the IC50 values of 100-150 nM range. A new RNA polymerase inhibitor 3 displayed strong synergistic effects with a MurX inhibitor SQ 641 (2), a promising preclinical tuberculosis drug.

  4. Discovery of a capuramycin analog that kills non-replicating Mycobacterium tuberculosis and its synergistic effects with translocase I inhibitors

    PubMed Central

    Siricilla, Shajila; Mitachi, Katsuhiko; Wan, Bajoie; Franzblau, Scott G.; Kurosu, Michio

    2014-01-01

    Capuramycin (1) and its analogs are strong translocase I (MurX/MraY) inhibitors. In our SAR studies of capuramycin analogs against M. tuberculosis (Mtb), we observed for the first time that a capuramycin analog, UT-01320 (3) killed non-replicating (dormant) Mtb at low concentrations under low-oxygen conditions, whereas selective MurX inhibitors killed only replicating Mtb under aerobic conditions. Interestingly, 3 did not exhibit MurX enzyme inhibitory activity even at high concentrations, however, 3 inhibited bacterial RNA polymerases with the IC50 values of 100-150 nM range. A new RNA polymerase inhibitor 3 displayed strong synergistic effects with a MurX inhibitor SQ 641 (2), a promising preclinical TB drug. PMID:25269459

  5. The effect of 5-substitution on the electrochemical behavior and antitubercular activity of PA-824

    PubMed Central

    Bollo, Soledad; Núñez-Vergara, Luis J.; Kang, Sunhee; Zhang, Liang; Boshoff, Helena I.; Barry, Clifton E.; Squella, Juan A.; Dowd, Cynthia S.

    2011-01-01

    Nitroimidazole PA-824 is part of an exciting new class of compounds currently undergoing clinical evaluation as novel TB therapeutics. The recently elucidated mechanism of action of PA-824 involves reduction of the nitroimidazole ring and subsequent nitric oxide release. The importance of this compound and its unique activity prompted us to explore how substitution of the nitroimidazole ring would affect electrochemical reduction and antitubercular activity. We prepared analogs of PA-824 with bromo, chloro, cyano, and amino substituents in the 5-position of the aromatic ring. We found that substitution of the imidazole ring greatly influences reduction and the stability of the corresponding nitro radical anion. Further, the antitubercular activities of the bromo and chloro analogs may indicate that an alternate nitroreductase pathway within Mycobacterium tuberculosis exists. PMID:21168331

  6. The effect of 5-substitution on the electrochemical behavior and antitubercular activity of PA-824.

    PubMed

    Bollo, Soledad; Núñez-Vergara, Luis J; Kang, Sunhee; Zhang, Liang; Boshoff, Helena I; Barry, Clifton E; Squella, Juan A; Dowd, Cynthia S

    2011-01-15

    Nitroimidazole PA-824 is part of an exciting new class of compounds currently undergoing clinical evaluation as novel TB therapeutics. The recently elucidated mechanism of action of PA-824 involves reduction of the nitroimidazole ring and subsequent nitric oxide release. The importance of this compound and its unique activity prompted us to explore how substitution of the nitroimidazole ring would affect electrochemical reduction and antitubercular activity. We prepared analogs of PA-824 with bromo, chloro, cyano, and amino substituents in the 5-position of the aromatic ring. We found that substitution of the imidazole ring greatly influences reduction and the stability of the corresponding nitro radical anion. Further, the antitubercular activities of the bromo and chloro analogs may indicate that an alternate nitroreductase pathway within Mycobacterium tuberculosis exists. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Mycobacterium tuberculosis Is Selectively Killed by Rifampin and Rifapentine in Hypoxia at Neutral pH.

    PubMed

    Iacobino, Angelo; Piccaro, Giovanni; Giannoni, Federico; Mustazzolu, Alessandro; Fattorini, Lanfranco

    2017-03-01

    The activities of rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide, isoniazid, amikacin, moxifloxacin, niclosamide, thioridazine, and pyrazinamide were tested against nonreplicating (dormant) Mycobacterium tuberculosis H37Rv under conditions of hypoxia at pHs 5.8 and 7.3, mimicking environments of cellular granulomas and caseous granulomas, respectively. At pH 5.8, several drugs killed dormant bacilli, with the best being rifampin and rifapentine. At pH 7.3, only rifampin and rifapentine efficiently killed dormant bacilli, while all other drugs showed little activity.

  8. Impact of fgd1 and ddn Diversity in Mycobacterium tuberculosis Complex on In Vitro Susceptibility to PA-824 ▿ ‡

    PubMed Central

    Feuerriegel, Silke; Köser, Claudio U.; Baù, Davide; Rüsch-Gerdes, Sabine; Summers, David K.; Archer, John A. C.; Marti-Renom, Marc A.; Niemann, Stefan

    2011-01-01

    PA-824 is a promising drug candidate for the treatment of tuberculosis (TB). It is in phase II clinical trials as part of the first newly designed regimen containing multiple novel antituberculosis drugs (PA-824 in combination with moxifloxacin and pyrazinamide). However, given that the genes involved in resistance against PA-824 are not fully conserved in the Mycobacterium tuberculosis complex (MTBC), this regimen might not be equally effective against different MTBC genotypes. To investigate this question, we sequenced two PA-824 resistance genes (fgd1 [Rv0407] and ddn [Rv3547]) in 65 MTBC strains representing major phylogenetic lineages. The MICs of representative strains were determined using the modified proportion method in the Bactec MGIT 960 system. Our analysis revealed single-nucleotide polymorphisms in both genes that were specific either for several genotypes or for individual strains, yet none of these mutations significantly affected the PA-824 MICs (≤0.25 μg/ml). These results were supported by in silico modeling of the mutations identified in Fgd1. In contrast, “Mycobacterium canettii” strains displayed a higher MIC of 8 μg/ml. In conclusion, we found a large genetic diversity in PA-824 resistance genes that did not lead to elevated PA-824 MICs. In contrast, M. canettii strains had MICs that were above the plasma concentrations of PA-824 documented so far in clinical trials. As M. canettii is also intrinsically resistant against pyrazinamide, new regimens containing PA-824 and pyrazinamide might not be effective in treating M. canettii infections. This finding has implications for the design of multiple ongoing clinical trials. PMID:21930879

  9. Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease.

    PubMed

    Li, D G; Ren, Z X

    2017-08-07

    PA-824 is a novel bicyclic nitroimidazole anti-tuberculosis (TB) drug. Cordyceps sinensis (Berk.) Sacc. (CS) was proven to be a good immunomodulatory compound. This research aimed to investigate the effect of CS on PA-824 in Mycobacterium tuberculosis (M.tb) infected mice (female CBA/J mice, 6 to 8 weeks of age and 20±2 g of weight). Mice were randomly assigned to 4 groups: PA-824, CS, PA-824+CS, and control. To verify the effect of PA-824 and CS on M.tb, after drug administration, mice lungs were harvested and bacterial colony formations were measured. Cells were isolated from infected lungs and spleens to analyze the percentage of CD4+ T cells (CD11a positive). Lung cells were cultured to detect the secretion of interferon-γ (IFN-γ) and interleukin-10 (IL-10) by ELISA. IFN-γ and IL-10 double-positive CD4+ cells in peripheral blood were measured by flow cytometry. The expression levels of IL-2 and IL-10 in mice lungs were analyzed by real-time PCR and western blot. Results showed that PA-824 combined with CS led to the lowest lung colony-forming units (CFU) counts among treated groups. Furthermore, this beneficial outcome might be associated with the decreased CD11a on CD4+ cells in mice lungs and spleens. Moreover, the suppressed secretion of IFN-γ and IL-10, and IL-10 expressions, as well as the decreased IFN-γ and IL-10 double-positive CD4+ cells in blood, could also be associated with the positive effect. However, no significant effect on IL-2 production was found. The combination of PA-824 and CS had more effective bacteriostatic and immunomodulatory effects on M.tb infected mice than PA-824 alone. In conclusion, CS has the potential to be an effective adjuvant in TB treatment.

  10. Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease

    PubMed Central

    Li, D.G.; Ren, Z.X.

    2017-01-01

    PA-824 is a novel bicyclic nitroimidazole anti-tuberculosis (TB) drug. Cordyceps sinensis (Berk.) Sacc. (CS) was proven to be a good immunomodulatory compound. This research aimed to investigate the effect of CS on PA-824 in Mycobacterium tuberculosis (M.tb) infected mice (female CBA/J mice, 6 to 8 weeks of age and 20±2 g of weight). Mice were randomly assigned to 4 groups: PA-824, CS, PA-824+CS, and control. To verify the effect of PA-824 and CS on M.tb, after drug administration, mice lungs were harvested and bacterial colony formations were measured. Cells were isolated from infected lungs and spleens to analyze the percentage of CD4+ T cells (CD11a positive). Lung cells were cultured to detect the secretion of interferon-γ (IFN-γ) and interleukin-10 (IL-10) by ELISA. IFN-γ and IL-10 double-positive CD4+ cells in peripheral blood were measured by flow cytometry. The expression levels of IL-2 and IL-10 in mice lungs were analyzed by real-time PCR and western blot. Results showed that PA-824 combined with CS led to the lowest lung colony-forming units (CFU) counts among treated groups. Furthermore, this beneficial outcome might be associated with the decreased CD11a on CD4+ cells in mice lungs and spleens. Moreover, the suppressed secretion of IFN-γ and IL-10, and IL-10 expressions, as well as the decreased IFN-γ and IL-10 double-positive CD4+ cells in blood, could also be associated with the positive effect. However, no significant effect on IL-2 production was found. The combination of PA-824 and CS had more effective bacteriostatic and immunomodulatory effects on M.tb infected mice than PA-824 alone. In conclusion, CS has the potential to be an effective adjuvant in TB treatment. PMID:28793052

  11. Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.

    PubMed

    Dooley, Kelly E; Luetkemeyer, Anne F; Park, Jeong-Gun; Allen, Reena; Cramer, Yoninah; Murray, Stephen; Sutherland, Deborah; Aweeka, Francesca; Koletar, Susan L; Marzan, Florence; Bao, Jing; Savic, Rada; Haas, David W

    2014-09-01

    There is an urgent need for new antituberculosis (anti-TB) drugs, including agents that are safe and effective with concomitant antiretrovirals (ARV) and first-line TB drugs. PA-824 is a novel antituberculosis nitroimidazole in late-phase clinical development. Cytochrome P450 (CYP) 3A, which can be induced or inhibited by ARV and antituberculosis drugs, is a minor (∼20%) metabolic pathway for PA-824. In a phase I clinical trial, we characterized interactions between PA-824 and efavirenz (arm 1), lopinavir/ritonavir (arm 2), and rifampin (arm 3) in healthy, HIV-uninfected volunteers without TB disease. Participants in arms 1 and 2 were randomized to receive drugs via sequence 1 (PA-824 alone, washout, ARV, and ARV plus PA-824) or sequence 2 (ARV, ARV with PA-824, washout, and PA-824 alone). In arm 3, participants received PA-824 and then rifampin and then both. Pharmacokinetic sampling occurred at the end of each dosing period. Fifty-two individuals participated. Compared to PA-824 alone, plasma PA-824 values (based on geometric mean ratios) for maximum concentration (Cmax), area under the concentration-time curve from 0 to 24 h (AUC0-24), and trough concentration (Cmin) were reduced 28%, 35%, and 46% with efavirenz, 13%, 17%, and 21% with lopinavir-ritonavir (lopinavir/r) and 53%, 66%, and 85% with rifampin, respectively. Medications were well tolerated. In conclusion, lopinavir/r had minimal effect on PA-824 exposures, supporting PA-824 use with lopinavir/r without dose adjustment. PA-824 exposures, though, were reduced more than expected when given with efavirenz or rifampin. The clinical implications of these reductions will depend upon data from current clinical trials defining PA-824 concentration-effect relationships. (This study has been registered at ClinicalTrials.gov under registration no. NCT01571414.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    Roberts, Julia; Ling, Yan; Quezada, Landys Lopez; Glasheen, Jou; Ballinger, Elaine; Somersan-Karakaya, Selin; Warrier, Thulasi; Warren, J. David; Nathan, Carl

    2015-01-01

    The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days—about 2 weeks sooner than required to count CFU—fluorometry reveals whether M. tuberculosis bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log10 CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic. PMID:26239979

  13. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models.

    PubMed

    Lenaerts, Anne J; Gruppo, Veronica; Marietta, Karen S; Johnson, Christine M; Driscoll, Diane K; Tompkins, Nicholas M; Rose, Jerry D; Reynolds, Robert C; Orme, Ian M

    2005-06-01

    This study extends earlier reports regarding the in vitro and in vivo efficacies of the nitroimidazopyran PA-824 against Mycobacterium tuberculosis. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC<1 microg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 microg/ml, similar to that of metronidazole, in a dose-dependent manner. In a short-course mouse infection model, the efficacy of PA-824 at 50, 100, and 300 mg/kg of body weight formulated in methylcellulose or cyclodextrin/lecithin after nine oral treatments was compared with those of isoniazid, rifampin, and moxifloxacin. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. No significant differences in activity between PA-824 and the other single drug treatments tested (isoniazid at 25 mg/kg, rifampin at 10 mg/kg, gatifloxacin at 100 mg/kg, and moxifloxacin at 100 mg/kg) could be observed. In summary, its good activity in in vivo models, as well as its activity against multidrug-resistant M. tuberculosis and against M. tuberculosis isolates in a potentially latent state, makes PA-824 an attractive drug candidate for the therapy of tuberculosis. These data indicate that there is significant potential for effective oral delivery of PA-824 for the treatment of tuberculosis.

  14. In vitro and in vivo activities of rifampin, streptomycin, amikacin, moxifloxacin, R207910, linezolid, and PA-824 against Mycobacterium ulcerans.

    PubMed

    Ji, Baohong; Lefrançois, Sébastien; Robert, Jerome; Chauffour, Aurélie; Truffot, Chantal; Jarlier, Vincent

    2006-06-01

    Seven antimicrobials were tested in vitro against 29 clinical isolates of Mycobacterium ulcerans. R207910 demonstrated the lowest MIC(50) and MIC(90), followed by moxifloxacin (MXF), streptomycin (STR), rifampin (RIF), amikacin (AMK), linezolid (LZD), and PA-824. All but PA-824 demonstrated an MIC(90) significantly less than the clinically achievable peak serum level. Administered as monotherapy to mice, RIF, STR, AMK, MXF, R207910, and LZD demonstrated some degree of bactericidal activity, whereas PA-824 failed to prevent mortality and to reduce the mean number of CFU in the footpads. Because 4 or 8 weeks of treatment by the combinations RIF-MXF, RIF-R207910, and RIF-LZD displayed bactericidal effects similar to those of RIF-STR and RIF-AMK, these three combinations might be considered as orally administered combined regimens for treatment of Buruli ulcer. Taking into account the cost, potential toxicity, and availability, the combination RIF-MXF appears more feasible for application in the field; additional experiments with mice are warranted to define further its activity against M. ulcerans. In addition, a pilot clinical trial is proposed to test the efficacy of RIF-MXF for treatment of Buruli ulcer.

  15. Crystal Structures of An F420-Dependent Glucose-6-Phosphate Dehydrogenase Fgd1 Involved in the Activation of the Anti-Tb Drug Candidate Pa-824 Reveal the Basis of Coenzyme And Substrate Binding

    SciTech Connect

    Bashiri, G.; Squire, C.J.; Moreland, N.J.; Baker, E.N.

    2009-05-11

    The modified flavin coenzyme F{sub 420} is found in a restricted number of microorganisms. It is widely distributed in mycobacteria, however, where it is important in energy metabolism, and in Mycobacterium tuberculosis (Mtb) is implicated in redox processes related to non-replicating persistence. In Mtb, the F{sub 420}-dependent glucose-6-phosphate dehydrogenase FGD1 provides reduced F{sub 420} for the in vivo activation of the nitroimidazopyran prodrug PA-824, currently being developed for anti-tuberculosis therapy against both replicating and persistent bacteria. The structure of M. tuberculosis FGD1 has been determined by x-ray crystallography both in its apo state and in complex with F{sub 420} and citrate at resolutions of 1.90 and 1.95{angstrom}, respectively. The structure reveals a highly specific F{sub 420} binding mode, which is shared with several other F{sub 420}-dependent enzymes. Citrate occupies the substrate binding pocket adjacent to F{sub 420} and is shown to be a competitive inhibitor (IC{sub 50} 43 {micro}m). Modeling of the binding of the glucose 6-phosphate (G6P) substrate identifies a positively charged phosphate binding pocket and shows that G6P, like citrate, packs against the isoalloxazine moiety of F{sub 420} and helps promote a butterfly bend conformation that facilitates F{sub 420} reduction and catalysis.

  16. Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide.

    PubMed

    Wallis, Robert S; Jakubiec, Wesley; Mitton-Fry, Mark; Ladutko, Lynn; Campbell, Sheldon; Paige, Darcy; Silvia, Annette; Miller, Paul F

    2012-01-01

    There presently is no rapid method to assess the bactericidal activity of new regimens for tuberculosis. This study examined PNU-100480, TMC207, PA-824, SQ109, and pyrazinamide, singly and in various combinations, against intracellular M. tuberculosis, using whole blood culture (WBA). The addition of 1,25-dihydroxy vitamin D facilitated detection of the activity of TMC207 in the 3-day cultures. Pyrazinamide failed to show significant activity against a PZA-resistant strain (M. bovis BCG), and was not further considered. Low, mid, and high therapeutic concentrations of each remaining drug were tested individually and in a paired checkerboard fashion. Observed bactericidal activity was compared to that predicted by the sum of the effects of individual drugs. Combinations of PNU-100480, TMC207, and SQ109 were fully additive, whereas those including PA-824 were less than additive or antagonistic. The cumulative activities of 2, 3, and 4 drug combinations were predicted based on the observed concentration-activity relationship, published pharmacokinetic data, and, for PNU-100480, published WBA data after oral dosing. The most active regimens, including PNU-100480, TMC207, and SQ109, were predicted to have cumulative activity comparable to standard TB therapy. Further testing of regimens including these compounds is warranted. Measurement of whole blood bactericidal activity can accelerate the development of novel TB regimens.

  17. Ribosome Rescue Inhibitors Kill Actively Growing and Nonreplicating Persister Mycobacterium tuberculosis Cells

    PubMed Central

    2017-01-01

    The emergence of Mycobacterium tuberculosis (MTB) strains that are resistant to most or all available antibiotics has created a severe problem for treating tuberculosis and has spurred a quest for new antibiotic targets. Here, we demonstrate that trans-translation is essential for growth of MTB and is a viable target for development of antituberculosis drugs. We also show that an inhibitor of trans-translation, KKL-35, is bactericidal against MTB under both aerobic and anoxic conditions. Biochemical experiments show that this compound targets helix 89 of the 23S rRNA. In silico molecular docking predicts a binding pocket for KKL-35 adjacent to the peptidyl-transfer center in a region not targeted by conventional antibiotics. Computational solvent mapping suggests that this pocket is a druggable hot spot for small molecule binding. Collectively, our findings reveal a new target for antituberculosis drug development and provide critical insight on the mechanism of antibacterial action for KKL-35 and related 1,3,4-oxadiazole benzamides. PMID:28762275

  18. Targeting tumors with nonreplicating Toxoplasma gondii uracil auxotroph vaccines

    PubMed Central

    Fox, Barbara A.; Sanders, Kiah L.; Chen, Shan; Bzik, David J.

    2013-01-01

    Toxoplasma gondii is an intracellular parasite that has evolved to actively control its invaded host cells. Toxoplasma triggers then actively regulates host innate IL-12 and interferon-γ responses that elicit T cell control of infection. A live, nonreplicating avirulent uracil auxotroph vaccine strain (cps) of Toxoplasma triggers novel innate immune responses that stimulate amplified CD8+ T cell responses and life-long immunity in vaccinated mice. Here, we review recent reports showing that intratumoral treatment with cps activated immune-mediated regression of established solid tumors in mice. We speculate that a better understanding of host-parasite interaction at the molecular level and applying improved genetic models based on Δku80 Toxoplasma strains will stimulate development of highly effective immunotherapeutic cancer vaccine strategies using engineered uracil auxotrophs. PMID:23928100

  19. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis.

    PubMed

    Dawson, Rodney; Diacon, Andreas H; Everitt, Daniel; van Niekerk, Christo; Donald, Peter R; Burger, Divan A; Schall, Robert; Spigelman, Melvin; Conradie, Almari; Eisenach, Kathleen; Venter, Amour; Ive, Prudence; Page-Shipp, Liesl; Variava, Ebrahim; Reither, Klaus; Ntinginya, Nyanda E; Pym, Alexander; von Groote-Bidlingmaier, Florian; Mendel, Carl M

    2015-05-02

    New antituberculosis regimens are urgently needed to shorten tuberculosis treatment. Following on from favourable assessment in a 2 week study, we investigated a novel regimen for efficacy and safety in drug-susceptible and multidrug-resistant (MDR) tuberculosis during the first 8 weeks of treatment. We did this phase 2b study of bactericidal activity--defined as the decrease in colony forming units (CFUs) of Mycobacterium tuberculosis in the sputum of patients with microscopy smear-positive pulmonary tuberculosis-at eight sites in South Africa and Tanzania. We enrolled treatment-naive patients with drug-susceptible, pulmonary tuberculosis, who were randomly assigned by computer-generated sequences to receive either 8 weeks of moxifloxacin, 100 mg pretomanid (formerly known as PA-824), and pyrazinamide (MPa100Z regimen); moxifloxacin, 200 mg pretomanid, and pyrazinamide (MPa200Z regimen); or the current standard care for drug-susceptible pulmonary tuberculosis, isoniazid, rifampicin, PZA, and ethambutol (HRZE regimen). A group of patients with MDR tuberculosis received MPa200Z (DRMPa200Z group). The primary outcome was bactericidal activity measured by the mean daily rate of reduction in M tuberculosis CFUs per mL overnight sputum collected once a week, with joint Bayesian non-linear mixed-effects regression modelling. We also assessed safety and tolerability by monitoring adverse events. This study is registered with ClinicalTrials.gov, number NCT01498419. Between March 24, 2012, and July 26, 2013 we enrolled 207 patients and randomly assigned them to treatment groups; we assigned 60 patients to the MPa100Z regimen, 62 to the MPa200Z regimen, and 59 to the HRZE regimen. We non-randomly assigned 26 patients with drug-resistant tuberculosis to the DRMPa200Z regimen. In patients with drug-susceptible tuberculosis, the bactericidal activity of MPa200Z (n=54) on days 0-56 (0·155, 95% Bayesian credibility interval 0·133-0·178) was significantly greater than for HRZE

  20. Non-replicating expression vectors: applications in vaccine development and gene therapy

    PubMed Central

    Limbach, K. J.; Paoletti, E.

    1996-01-01

    This review presents experimental, preclinical and clinical data illustrating the multiple uses of recombinant non-replicating virus vectors in the fields of immunoprophylaxis and gene therapy. PMID:8666067

  1. In Vitro and In Vivo Efficacy of β-Lactams against Replicating and Slowly Growing/Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    Dinesh, Neela; Shandil, Radha; Ramachandran, Vasanthi; Sharma, Sreevalli; Bhattacharjee, Deepa; Ganguly, Samit; Reddy, Jitendar; Ahuja, Vijaykamal; Panduga, Vijender; Parab, Manish; Vishwas, K. G.; Kumar, Naveen; Balganesh, Meenakshi; Balasubramanian, V.

    2013-01-01

    Beta-lactams, in combination with beta-lactamase inhibitors, are reported to have activity against Mycobacterium tuberculosis bacteria growing in broth, as well as inside the human macrophage. We tested representative beta-lactams belonging to 3 different classes for activity against replicating M. tuberculosis in broth and nonreplicating M. tuberculosis under hypoxia, as well as against streptomycin-starved M. tuberculosis strain 18b (ss18b) in the presence or absence of clavulanate. Most of the combinations showed bactericidal activity against replicating M. tuberculosis, with up to 200-fold improvement in potency in the presence of clavulanate. None of the combinations, including those containing meropenem, imipenem, and faropenem, killed M. tuberculosis under hypoxia. However, faropenem- and meropenem-containing combinations killed strain ss18b moderately. We tested the bactericidal activities of meropenem-clavulanate and amoxicillin-clavulanate combinations in the acute and chronic aerosol infection models of tuberculosis in BALB/c mice. Based on pharmacokinetic/pharmacodynamic indexes reported for beta-lactams against other bacterial pathogens, a cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%TMIC) of 20 to 40% was achieved in mice using a suitable dosing regimen. Both combinations showed marginal reduction in lung CFU compared to the late controls in the acute model, whereas both were inactive in the chronic model. PMID:23507276

  2. In vitro and in vivo efficacy of β-lactams against replicating and slowly growing/nonreplicating Mycobacterium tuberculosis.

    PubMed

    Solapure, Suresh; Dinesh, Neela; Shandil, Radha; Ramachandran, Vasanthi; Sharma, Sreevalli; Bhattacharjee, Deepa; Ganguly, Samit; Reddy, Jitendar; Ahuja, Vijaykamal; Panduga, Vijender; Parab, Manish; Vishwas, K G; Kumar, Naveen; Balganesh, Meenakshi; Balasubramanian, V

    2013-06-01

    Beta-lactams, in combination with beta-lactamase inhibitors, are reported to have activity against Mycobacterium tuberculosis bacteria growing in broth, as well as inside the human macrophage. We tested representative beta-lactams belonging to 3 different classes for activity against replicating M. tuberculosis in broth and nonreplicating M. tuberculosis under hypoxia, as well as against streptomycin-starved M. tuberculosis strain 18b (ss18b) in the presence or absence of clavulanate. Most of the combinations showed bactericidal activity against replicating M. tuberculosis, with up to 200-fold improvement in potency in the presence of clavulanate. None of the combinations, including those containing meropenem, imipenem, and faropenem, killed M. tuberculosis under hypoxia. However, faropenem- and meropenem-containing combinations killed strain ss18b moderately. We tested the bactericidal activities of meropenem-clavulanate and amoxicillin-clavulanate combinations in the acute and chronic aerosol infection models of tuberculosis in BALB/c mice. Based on pharmacokinetic/pharmacodynamic indexes reported for beta-lactams against other bacterial pathogens, a cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%TMIC) of 20 to 40% was achieved in mice using a suitable dosing regimen. Both combinations showed marginal reduction in lung CFU compared to the late controls in the acute model, whereas both were inactive in the chronic model.

  3. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    2016-01-01

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells. PMID:27144688

  4. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis.

    PubMed

    Gold, Ben; Smith, Robert; Nguyen, Quyen; Roberts, Julia; Ling, Yan; Lopez Quezada, Landys; Somersan, Selin; Warrier, Thulasi; Little, David; Pingle, Maneesh; Zhang, David; Ballinger, Elaine; Zimmerman, Matthew; Dartois, Véronique; Hanson, Paul; Mitscher, Lester A; Porubsky, Patrick; Rogers, Steven; Schoenen, Frank J; Nathan, Carl; Aubé, Jeffrey

    2016-07-14

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells.

  5. Killing Coyotes.

    ERIC Educational Resources Information Center

    Beasley, Conger, Jr.

    1993-01-01

    Presents different viewpoints concerning the federal government's Animal Damage Control (ADC) Program cited as responsible for killing millions of predators. Critics provide evidence of outdated and inhumane methods exemplified in the coyote killings. The ADC emphasizes new, nonlethal methods of controlling animals cited as "noxious."…

  6. Targeted Killings

    DTIC Science & Technology

    2013-03-01

    American territory in history. Two aircraft torpedoed into the Twin Towers in New York City at speeds of over 490mph killing 2,595 people . Shortly...bomb exploded in the World Trade Center in New York City, killing a half-dozen people and wounding over a thousand. Over the next three years Al...executed his most incredible attack killing close to 3,000 people . President Bush announced to the world that, “U.S. troops will hunt down terrorists and

  7. Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors.

    PubMed Central

    Raju, R; Subramaniam, S V; Hajjou, M

    1995-01-01

    Genetically engineered RNA transcripts coding for various Sindbis virus (SIN) genes were used to study structure and sequence requirements of RNA recombination in BHK cells. Three different groups of RNA transcripts were made: (i) RNAs which retain the ability to replicate and which carry sequences coding for either viral polymerase or viral structural proteins; (ii) RNAs which lack the complete 3' end of the SIN genome and thus are incapable of replicating; and (iii) RNAs which lack the complete 5' end of the SIN genome and also are incapable of replicating. BHK cells were transfected with specific combinations of these precursor RNAs, and virus production and RNA synthetic abilities of the released virus were determined. We demonstrate in vivo generation of infectious SIN by fusion of (i) replicative RNAs to nonreplicative RNAs and (ii) two nonreplicative RNA precursors. Both homologous and nonhomologous types of recombinations were observed. In the homologous type of recombination, a 694-nucleotide overlap at the crossover region of the first pair of precursors resulted in the addition of an A residue converting the UAG stop codon of nonstructural protein P4 to a UAA stop codon. In the nonhomologous type of recombination, the crossover sites contained deletion of up to 76 nucleotides from one of the precursors and complete preservation of junction sequence from the other precursor. This is also the first report that a cytoplasmic RNA virus can be generated from biologically nonreplicative RNA precursors. These results have implications for initiation of viral RNA synthesis and recombination between RNA viral genomes in general. We favor template switching as a mechanism for the fusion events described here and suggest inclusion of polymerase scanning of diverse nonreplicative RNAs as an inherent feature of the copy choice model of RNA recombination. Very importantly, the facile nature of RNA recombination occurring between nonreplicative RNA precursors should

  8. Serum neopterin levels in patients with replicative and nonreplicative HBV carriers

    PubMed Central

    Kaleli, Ilknur; Demir, Melek; Cevahir, Nural; Yılmaz, Mustafa; Demir, Suleyman

    2006-01-01

    Background Infection by hepatitis B virus (HBV) causes complicated biochemical, immunological and histological changes in host immune response against the virus which can be specific or non-specific. Recent attention has focused on neopterin as a marker for the activation of cell mediated immunity. The aim of this study was to define the pattern of neopterin levels in replicative and nonreplicative HBV carriers. Methods Thirty HBV replicative carriers and 25 nonreplicative HBV carriers and 30 healthy adult patients were included this study. Hepatitis markers were determined by commercial kit based on chemilumminesans assay. HBV DNA was quantified by hybrid capture system. Serum neopterin levels were measured by the method of competitive enzyme-linked immunosorbent assay. Results were expressed as mean ± SD and ranges. Results In the nonreplicative group, except for one patient, all the patients' HBeAg were negative and anti-HBe were positive. That particular patient was HBeAg positive and anti-HBe negative. In the replicative group, 23 out of 30 patients have positive HBeAg and negative anti-HBe; 7 out of 30 patients have negative HBeAg and positive anti-HBe. Serum neopterin concentrations were 14.5 ± 10.0 (4.2–41) nmol/L in replicative HBV carriers, 8.9 ± 4.3 (2.1–22) nmol/L in nonreplicative HBV carriers and 7.1 ± 2.2 (4.0–12) nmol/L in the control group. Serum neopterin levels and the rates of abnormal serum neopterin levels in the replicative group were higher than the control group (P < 0.01 and P < 0.05). In the nonreplicative group, serum neopterin levels were not different from those of the control. There was a difference between replicative and nonreplicative groups in the respect of neopterin levels. Conclusion In the hepatitis B infected carriers, elevated neopterin levels may be an indicator of the presence of replication. PMID:17076882

  9. Killing Range

    PubMed Central

    Asal, Victor; Rethemeyer, R. Karl; Horgan, John

    2015-01-01

    This paper presents an analysis of the Provisional Irish Republican Army's (PIRA) brigade level behavior during the Northern Ireland Conflict (1970-1998) and identifies the organizational factors that impact a brigade's lethality as measured via terrorist attacks. Key independent variables include levels of technical expertise, cadre age, counter-terrorism policies experienced, brigade size, and IED components and delivery methods. We find that technical expertise within a brigade allows for careful IED usage, which significantly minimizes civilian casualties (a specific strategic goal of PIRA) while increasing the ability to kill more high value targets with IEDs. Lethal counter-terrorism events also significantly affect a brigade's likelihood of killing both civilians and high-value targets but in different ways. Killing PIRA members significantly decreases IED fatalities but also significantly decreases the possibility of zero civilian IED-related deaths in a given year. Killing innocent Catholics in a Brigade's county significantly increases total and civilian IED fatalities. Together the results suggest the necessity to analyze dynamic situational variables that impact terrorist group behavior at the sub-unit level. PMID:25838603

  10. Killing fetuses and killing newborns.

    PubMed

    Di Nucci, Ezio

    2013-05-01

    The argument for the moral permissibility of killing newborns is a challenge to liberal positions on abortion because it can be considered a reductio of their defence of abortion. Here I defend the liberal stance on abortion by arguing that the argument for the moral permissibility of killing newborns on ground of the social, psychological and economic burden on the parents recently put forward by Giubilini and Minerva is not valid; this is because they fail to show that newborns cannot be harmed and because there are morally relevant differences between fetuses and newborns.

  11. Beyond killing

    PubMed Central

    Vale, Pedro F.; McNally, Luke; Doeschl-Wilson, Andrea; King, Kayla C.; Popat, Roman; Domingo-Sananes, Maria R.; Allen, Judith E.; Soares, Miguel P.; Kümmerli, Rolf

    2016-01-01

    The antibiotic pipeline is running dry and infectious disease remains a major threat to public health. An efficient strategy to stay ahead of rapidly adapting pathogens should include approaches that replace, complement or enhance the effect of both current and novel antimicrobial compounds. In recent years, a number of innovative approaches to manage disease without the aid of traditional antibiotics and without eliminating the pathogens directly have emerged. These include disabling pathogen virulence-factors, increasing host tissue damage control or altering the microbiota to provide colonization resistance, immune resistance or disease tolerance against pathogens. We discuss the therapeutic potential of these approaches and examine their possible consequences for pathogen evolution. To guarantee a longer half-life of these alternatives to directly killing pathogens, and to gain a full understanding of their population-level consequences, we encourage future work to incorporate evolutionary perspectives into the development of these treatments. PMID:27016341

  12. Nonreplicating protocells.

    PubMed

    Del Bianco, Cristina; Mansy, Sheref S

    2012-12-18

    Prebiotic soup experiments have shown that the molecular building blocks of life can be built under prebiotically plausible conditions. From this starting point, researchers have launched continued studies of polymerization and explorations of the breadth of RNA function. Recently, effort has intensified to examine experimentally another stage of the origins of life: the assembly of the molecular parts into model protocells intended to represent the first primitive, cell-like systems to emerge on Earth. Although it may not be possible to recreate the precise sequence of events that led to cellular life, laboratory experiments have begun to show what was and was not possible. Prebiotically plausible lipid vesicles form easily and have many properties that are conducive to cellular function. In addition to protecting nascent replicating genetic systems from parasitic sequences, vesicles facilitate evolution. The data thus far suggest that prebiotically plausible vesicles could have grown, divided, and promoted competition between distinct chemical systems. Most protocellular studies to date have probed the role of self-replication, one feature of extant life in the emergence of the first cellular system. Undoubtedly replicating systems were crucial for protocellular evolution, but other features of life must have been important as well. For example, life does not exist in isolation. A living system must cope with and adapt to environmental fluctuations to survive. The protocell must have generated some of these fluctuations because cellular activity necessarily modifies its surroundings by selectively absorbing nutrients and releasing unwanted molecules. It seems likely that life would have faced this challenge early and either emerged in dynamic locales that continuously regenerated conditions conducive to life or exploited mechanisms to physically move to new areas not depleted in resources. Further studies that explore non-replication-based aspects of the origins of life could reveal a more complete picture of the transition from prebiotic chemistry to early life.

  13. Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence

    PubMed Central

    Giffin, Michelle M.; Shi, Lanbo; Gennaro, Maria L.; Sohaskey, Charles D.

    2016-01-01

    Mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. Among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of NADH to NAD. It is involved in the metabolic remodeling of M. tuberculosis through its possible interactions with both the glyoxylate and methylcitrate cycle. Both mRNA levels and enzymatic activities of isocitrate lyase, the first enzyme of the glyoxylate cycle, and alanine dehydrogenase increased during entry into nonreplicating persistence, while the gene and activity for the second enzyme of the glyoxylate cycle, malate synthase were not. This could suggest a shift in carbon flow away from the glyoxylate cycle and instead through alanine dehydrogenase. Expression of ald was also induced in vitro by other persistence-inducing stresses such as nitric oxide, and was expressed at high levels in vivo during the initial lung infection in mice. Enzyme activity was maintained during extended hypoxia even after transcription levels decreased. An ald knockout mutant of M. tuberculosis showed no reduction in anaerobic survival in vitro, but resulted in a significant lag in the resumption of growth after reoxygenation. During reactivation the ald mutant had an altered NADH/NAD ratio, and alanine dehydrogenase is proposed to maintain the optimal NADH/NAD ratio during anaerobiosis in preparation of eventual regrowth, and during the initial response during reoxygenation. PMID:27203084

  14. Transcriptional and Physiological Changes during Mycobacterium tuberculosis Reactivation from Non-replicating Persistence

    PubMed Central

    Du, Peicheng; Sohaskey, Charles D.; Shi, Lanbo

    2016-01-01

    Mycobacterium tuberculosis can persist for years in the hostile environment of the host in a non-replicating or slowly replicating state. While active disease predominantly results from reactivation of a latent infection, the molecular mechanisms of M. tuberculosis reactivation are still poorly understood. We characterized the physiology and global transcriptomic profiles of M. tuberculosis during reactivation from hypoxia-induced non-replicating persistence. We found that M. tuberculosis reactivation upon reaeration was associated with a lag phase, in which the recovery of cellular physiological and metabolic functions preceded the resumption of cell replication. Enrichment analysis of the transcriptomic dynamics revealed changes to many metabolic pathways and transcription regulons/subnetworks that orchestrated the metabolic and physiological transformation in preparation for cell division. In particular, we found that M. tuberculosis reaeration lag phase is associated with down-regulation of persistence-associated regulons/subnetworks, including DosR, MprA, SigH, SigE, and ClgR, as well as metabolic pathways including those involved in the uptake of lipids and their catabolism. More importantly, we identified a number of up-regulated transcription regulons and metabolic pathways, including those involved in metal transport and remobilization, second messenger-mediated responses, DNA repair and recombination, and synthesis of major cell wall components. We also found that inactivation of the major alternative sigma factors SigE or SigH disrupted exit from persistence, underscoring the importance of the global transcriptional reprogramming during M. tuberculosis reactivation. Our observations suggest that M. tuberculosis lag phase is associated with a global gene expression reprogramming that defines the initiation of a reactivation process. PMID:27630619

  15. Protection Against Dengue Virus by Non-Replicating and Live Attenuated Vaccines Used Together in a Prime Boost Vaccination Strategy

    DTIC Science & Technology

    2010-01-01

    Protection against dengue virus by non-replicating and live attenuated vaccines used together in a prime boost vaccination strategy Monika Simmons a...Dengue DNA Punfied inacdvared virus Uvc artenuatcd virus Jlnmc boost A new vaccination strategy for dengue virus (DENV) was eval uated in rhesus...region (TDNA) then boosting 2 months l,ltcr with a tetravalent live aucnuated virus (TLAV) vaccine . Both vaccine combinations elicited virus

  16. Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines

    PubMed Central

    Fox, Helen; Minor, Philip D.

    2017-01-01

    While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models. PMID:28103317

  17. Planning a dynamic kill

    SciTech Connect

    Abel, L.W.

    1996-05-01

    This article discusses the methodology, design philosophy, and guidelines for planning a dynamic-kill operation for a wild well. The topics covered are two methods of computer analysis for designing dynamic-kill requirements, the design process, determining the pumping spread, and the pitfalls that a designer faces in planning a dynamic kill.

  18. Quantitative Proteomic Analysis of Replicative and Nonreplicative Forms Reveals Important Insights into Chromatin Biology of Trypanosoma cruzi.

    PubMed

    Leandro de Jesus, Teresa Cristina; Calderano, Simone Guedes; Vitorino, Francisca Nathalia de Luna; Llanos, Ricardo Pariona; Lopes, Mariana de Camargo; de Araújo, Christiane Bezerra; Thiemann, Otavio Henrique; Reis, Marcelo da Silva; Elias, Maria Carolina; Chagas da Cunha, Julia Pinheiro

    2017-01-01

    Chromatin associated proteins are key regulators of many important processes in the cell. Trypanosoma cruzi, a protozoa flagellate that causes Chagas disease, alternates between replicative and nonreplicative forms accompanied by a shift on global transcription levels and by changes in its chromatin architecture. Here, we investigated the T. cruzi chromatin proteome using three different protocols and compared it between replicative (epimastigote) and nonreplicative (trypomastigote) forms by high-resolution mass spectrometry. More than 2000 proteins were identified and quantified both in chromatin and nonchromatin extracts. Besides histones and other known nuclear proteins, trypanosomes chromatin also contains metabolic (mainly from carbohydrate pathway), cytoskeleton and many other proteins with unknown functions. Strikingly, the two parasite forms differ greatly regarding their chromatin-associated factors composition and amount. Although the nucleosome content is the same for both life forms (as seen by MNase digestion), the remaining proteins were much less detected in nonreplicative forms, suggesting that they have a naked chromatin. Proteins associated to DNA proliferation, such as PCNA, RPA, and DNA topoisomerases were exclusively found in the chromatin of replicative stages. On the other hand, the nonreplicative stages have an enrichment of a histone H2B variant. Furthermore, almost 20% of replicative stages chromatin-associated proteins are expressed in nonreplicative forms, but located at nonchromatin space. We identified different classes of proteins including phosphatases and a Ran-binding protein, that may shuttle between chromatin and nonchromatin space during differentiation. Seven proteins, including those with unknown functions, were selected for further validation. We confirmed their location in chromatin and their differential expression, using Western blotting assays and chromatin immunoprecipitation (ChIP). Our results indicate that the

  19. Null Killing vectors

    NASA Astrophysics Data System (ADS)

    Lukács, B.; Perjés, Z.; Sebestyén, Á.

    1981-06-01

    Space-times admitting a null Killing vector are studied, using the Newman-Penrose spin coefficient formalism. The properties of the eigenrays (principal null curves of the Killing bivector) are shown to be related to the twist of the null Killing vector. Among the electrovacs, the ones containing a null Maxwell field turn out to belong to the twist-free class. An electrovac solution is obtained for which the null Killing vector is twisting and has geodesic and shear-free eigenrays. This solution is parameterless and appears to be the field of a zero-mass, spinning, and charged source.

  20. Ion-kill dosimetry

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Fromm, M.; Chambaudet, A.

    2001-01-01

    Unanticipated late effects in neutron and heavy ion therapy, not attributable to overdose, imply a qualitative difference between low and high LET therapy. We identify that difference as 'ion kill', associated with the spectrum of z/beta in the radiation field, whose measurement we label 'ion-kill dosimetry'.

  1. Killing tensors on tori

    NASA Astrophysics Data System (ADS)

    Heil, Konstantin; Moroianu, Andrei; Semmelmann, Uwe

    2017-07-01

    We show that Killing tensors on conformally flat n-dimensional tori whose conformal factor only depends on one variable, are polynomials in the metric and in the Killing vector fields. In other words, every first integral of the geodesic flow polynomial in the momenta on the sphere bundle of such a torus is linear in the momenta.

  2. Ion-kill dosimetry

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Fromm, M.; Chambaudet, A.

    2001-01-01

    Unanticipated late effects in neutron and heavy ion therapy, not attributable to overdose, imply a qualitative difference between low and high LET therapy. We identify that difference as 'ion kill', associated with the spectrum of z/beta in the radiation field, whose measurement we label 'ion-kill dosimetry'.

  3. Cloning, killing, and identity.

    PubMed Central

    McMahan, J

    1999-01-01

    One potentially valuable use of cloning is to provide a source of tissues or organs for transplantation. The most important objection to this use of cloning is that a human clone would be the sort of entity that it would be seriously wrong to kill. I argue that entities of the sort that you and I essentially are do not begin to exist until around the seventh month of fetal gestation. Therefore to kill a clone prior to that would not be to kill someone like you or me but would be only to prevent one of us from existing. And even after one of us begins to exist, the objections to killing it remain comparatively weak until its psychological capacities reach a certain level of maturation. These claims support the permissibility of killing a clone during the early stages of its development in order to use its organs for transplantation. PMID:10226909

  4. Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non-replicating persistence.

    PubMed

    Dhiman, Rakesh K; Mahapatra, Sebabrata; Slayden, Richard A; Boyne, Melissa E; Lenaerts, Anne; Hinshaw, Jerald C; Angala, Shiva K; Chatterjee, Delphi; Biswas, Kallolmay; Narayanasamy, Prabagaran; Kurosu, Michio; Crick, Dean C

    2009-04-01

    Understanding the basis of bacterial persistence in latent infections is critical for eradication of tuberculosis. Analysis of Mycobacterium tuberculosis mRNA expression in an in vitro model of non-replicating persistence indicated that the bacilli require electron transport chain components and ATP synthesis for survival. Additionally, low microM concentrations of aminoalkoxydiphenylmethane derivatives inhibited both the aerobic growth and survival of non-replicating, persistent M. tuberculosis. Metabolic labelling studies and quantification of cellular menaquinone levels suggested that menaquinone synthesis, and consequently electron transport, is the target of the aminoalkoxydiphenylmethane derivatives. This hypothesis is strongly supported by the observations that treatment with these compounds inhibits oxygen consumption and that supplementation of growth medium with exogenous menaquinone rescued both growth and oxygen consumption of treated bacilli. In vitro assays indicate that the aminoalkoxydiphenylmethane derivatives specifically inhibit MenA, an enzyme involved in the synthesis of menaquinone. Thus, the results provide insight into the physiology of mycobacterial persistence and a basis for the development of novel drugs that enhance eradication of persistent bacilli and latent tuberculosis.

  5. Discovery and Optimization of Benzotriazine Di-N-Oxides Targeting Replicating and Non-replicating Mycobacterium tuberculosis

    PubMed Central

    Chopra, Sidharth; Koolpe, Gary A.; Tambo-ong, Arlyn A.; Matsuyama, Karen N.; Ryan, Kenneth J.; Tran, Tran B.; Doppalapudi, Rupa S.; Riccio, Edward S.; Iyer, Lalitha V.; Green, Carol E.; Wan, Baojie; Franzblau, Scott G.; Madrid, Peter B.

    2012-01-01

    Compounds bactericidal against both replicating and non-replicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and non-replicating Mtb. Medicinal chemistry optimization, guided by semi-empirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC50) against Vero cells of 25 μg/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs. PMID:22691154

  6. Repair of nonreplicating UV-irradiated DNA: cooperative dark repair by Escherichia coli uvr and phr functions

    SciTech Connect

    Hays, J.B.; Martin, S.J.; Bhatia, K.

    1985-02-01

    The system previously used to study recombination of nonreplicating UV-irradiated phage lambda DNA was adapted to study UV repair. Irradiated phages infected undamaged homoimmune lysogens. Pyrimidine dimer content (by treatment with Micrococcus luteus UV endonuclease and alkaline sucrose sedimentation) and a biological activity endpoint (infectivity in transfection of uvrB recA recB spheroplasts) were followed. Unless room light was excluded during DNA extraction procedures, photoreactivation (Phr function) was significant. In uvr ..delta..phr bacteria, repair, by both assays, was very low but not zero. Even when light was totally excluded, Phr function appeared to play a role in Uvr-mediated excision repair: both dimer removal and restoration of infectivity were two to five times as efficient in uvr/sup +/ phr/sup +/ bacteria as in uvr/sup +/ ..delta..phr bacteria. Similarly, UV-irradiated phages plated with higher efficiencies on phr/sup +/ than ..delta..phr bacteria even under totally dark conditions. In uvr phr/sup +/ repressed infections, removal of dimers from nonreplicating DNA did not increase infectivity as much as in uvr2= infections, suggesting a requirement for repair of nondimer photoproducts by the uvrABC system.

  7. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

    PubMed

    Schäfer, Birgit; Holzer, Georg W; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A; Kreil, Thomas R; Barrett, P Noel; Falkner, Falko G

    2011-01-01

    Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

  8. Evolution of coalitionary killing.

    PubMed

    Wrangham, R W

    1999-01-01

    Warfare has traditionally been considered unique to humans. It has, therefore, often been explained as deriving from features that are unique to humans, such as the possession of weapons or the adoption of a patriarchal ideology. Mounting evidence suggests, however, that coalitional killing of adults in neighboring groups also occurs regularly in other species, including wolves and chimpanzees. This implies that selection can favor components of intergroup aggression important to human warfare, including lethal raiding. Here I present the principal adaptive hypothesis for explaining the species distribution of intergroup coalitional killing. This is the "imbalance-of-power hypothesis," which suggests that coalitional killing is the expression of a drive for dominance over neighbors. Two conditions are proposed to be both necessary and sufficient to account for coalitional killing of neighbors: (1) a state of intergroup hostility; (2) sufficient imbalances of power between parties that one party can attack the other with impunity. Under these conditions, it is suggested, selection favors the tendency to hunt and kill rivals when the costs are sufficiently low. The imbalance-of-power hypothesis has been criticized on a variety of empirical and theoretical grounds which are discussed. To be further tested, studies of the proximate determinants of aggression are needed. However, current evidence supports the hypothesis that selection has favored a hunt-and-kill propensity in chimpanzees and humans, and that coalitional killing has a long history in the evolution of both species.

  9. Report Bee Kills

    EPA Pesticide Factsheets

    EPA uses incident report data to help inform our pesticide regulatory decisions. Information from these reports helps us identify patterns of bee kills associated with the use of specific pesticides or active ingredients. Here's how to report incidents.

  10. Rv2744c Is a PspA Ortholog That Regulates Lipid Droplet Homeostasis and Nonreplicating Persistence in Mycobacterium tuberculosis

    PubMed Central

    Armstrong, Richard M.; Adams, Katherine L.; Zilisch, Joseph E.; Bretl, Daniel J.; Sato, Hiromi; Anderson, David M.

    2016-01-01

    ABSTRACT Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant cause of morbidity and mortality worldwide, despite the availability of a live attenuated vaccine and anti-TB antibiotics. The vast majority of individuals infected with M. tuberculosis develop an asymptomatic latent infection in which the bacterium survives within host-generated granulomatous lesions in a physiologically altered metabolic state of nonreplicating persistence. The granuloma represents an adverse environment, as M. tuberculosis is exposed to various stressors capable of disrupting the essential constituents of the bacterium. In Gram-negative and Gram-positive bacteria, resistance to cell envelope stressors that perturb the plasma membrane is mediated in part by proteins comprising the phage shock protein (Psp) system. PspA is an important component of the Psp system; in the presence of envelope stress, PspA localizes to the inner face of the plasma membrane, homo-oligomerizes to form a large scaffold-like complex, and helps maintain plasma membrane integrity to prevent a loss of proton motive force. M. tuberculosis and other members of the Mycobacterium genus are thought to encode a minimal functional unit of the Psp system, including an ortholog of PspA. Here, we show that Rv2744c possesses structural and physical characteristics that are consistent with its designation as a PspA family member. However, although Rv2744c is upregulated under conditions of cell envelope stress, loss of Rv2744c does not alter resistance to cell envelope stressors. Furthermore, Rv2744c localizes to the surface of lipid droplets in Mycobacterium spp. and regulates lipid droplet number, size, and M. tuberculosis persistence during anaerobically induced dormancy. Collectively, our results indicate that Rv2744c is a bona fide ortholog of PspA that may function in a novel role to regulate lipid droplet homeostasis and nonreplicating persistence (NRP) in M. tuberculosis

  11. Illegitimate integration of non-replicative vectors in the genome of Rhodococcus fascians upon electrotransformation as an insertional mutagenesis system.

    PubMed

    Desomer, J; Crespi, M; Van Montagu, M

    1991-09-01

    Electrotransformation of Rhodococcus fascians by non-replicating plasmids containing a suitable resistance marker resulted in stable transformants by integration of these constructs at various sites in the genome, thereby generating different mutations. Tagged genes could be isolated in Escherichia coli owing to the presence of a CoIE1 replicon and an ampicillin resistance gene in the inserted sequences. Southern analysis and nucleotide sequencing revealed that recombination can occur at defined locations in the plasmid, while no site preference for target sequences could be detected. Low homology between the recombining sequences indicates illegitimate recombination. The specificity of the plasmid sites could be explained by assuming a linear recombination intermediate, generated by cleavage of the transformed plasmid.

  12. Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins.

    PubMed

    Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann; Becher, Paul

    2017-04-01

    RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5' terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins

    PubMed Central

    Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann

    2017-01-01

    RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5′ terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. PMID:28338950

  14. Killing vectors and anisotropy

    SciTech Connect

    Krisch, J. P.; Glass, E. N.

    2009-08-15

    We consider an action that can generate fluids with three unequal stresses for metrics with a spacelike Killing vector. The parameters in the action are directly related to the stress anisotropies. The field equations following from the action are applied to an anisotropic cosmological expansion and an extension of the Gott-Hiscock cosmic string.

  15. Children Who Kill.

    ERIC Educational Resources Information Center

    Natale, Jo Anna

    1999-01-01

    Two recent books, "When Good Kids Kill," by Michael D. Kelleher, and "Lost Boys," by James Garbarino, explore how children become killers and suggest ways to reduce our high-pressure society's epidemic levels of youth violence. Physically or psychologically distant parents and unaffirmative media messages are negative…

  16. Children Who Kill.

    ERIC Educational Resources Information Center

    Natale, Jo Anna

    1999-01-01

    Two recent books, "When Good Kids Kill," by Michael D. Kelleher, and "Lost Boys," by James Garbarino, explore how children become killers and suggest ways to reduce our high-pressure society's epidemic levels of youth violence. Physically or psychologically distant parents and unaffirmative media messages are negative…

  17. Older women and mercy killing.

    PubMed

    Canetto, S S; Hollenshead, J D

    Mercy killing is usually defined as intentional killing, often by family members or friends, with the stated intent to end perceived suffering. International evidence suggests that mercy killing typically involves an older man killing his ailing wife. In this study, we examined U.S. cases of mercy killing recorded by The Hemlock Society for the period 1960-1993. We found that the typical case involved an older woman being killed by a man, often her husband, with her poor health as the justification for the killing. A firearm was often used in these incidents. These patterns of mercy killing are consistent with patterns of homicide-suicide among older adults. Future research should seek to understand why women are typically the targets, and men the agents of mercy killing.

  18. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines

    PubMed Central

    Gasper, David J.; Neldner, Brandon; Plisch, Erin H.; Rustom, Hani; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M.

    2016-01-01

    CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the

  19. Synergistic effects of deleting multiple nonessential elements in nonreplicative HSV-1 BAC genomic vectors play a critical role in their viability.

    PubMed

    Ventosa, M; Ortiz-Temprano, A; Khalique, H; Lim, F

    2017-07-01

    Nonreplicative Herpes simplex virus type-1 (HSV-1) genomic vectors have already entered into clinical trials for neurological gene therapy thanks to their scalable growth in permissive cells. However, the small transgene capacity of this type of HSV-1 vectors currently used in the clinic represents an important limiting factor as a gene delivery system. To develop high-capacity nonreplicative genomic HSV-1 vectors, in this study we have characterized a series of multiply deleted mutants which we have constructed in bacterial artificial chromosomes (BACs), removing up to 24 kb of unstable or dispensable genomic sequences to allow insertion of transgenes up to this size. We show that synergistic effects of deletions of: the HSV-1 replication origins oriS and oriL, the HSV-1 internal repeat region, the remaining ICP4 gene copy and the genes encoding for ICP27, UL56, UL55, can severely reduce the growth of these HSV-1 vectors. Given that several of these elements have been characterized as 'non-essential' for viral growth in cell culture by single-deletion experiments of wild-type HSV-1, our study highlights the need to re-evaluate their functional contribution in the context of multiply deleted nonreplicative HSV-1 genomic vectors. Our BAC mutants described here can serve as useful starting platforms to accelerate HSV-1 vector development.

  20. Structure-activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis.

    PubMed

    Lilienkampf, Annamaria; Mao, Jialin; Wan, Baojie; Wang, Yuehong; Franzblau, Scott G; Kozikowski, Alan P

    2009-04-09

    Tuberculosis (TB) remains as a global pandemic that is aggravated by a lack of health care, the spread of HIV, and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. New anti-TB drugs are urgently required to shorten the long 6-12 month treatment regimen and to battle drug-resistant Mtb strains. We have identified several potent quinoline-based anti-TB compounds, bearing an isoxazole containing side-chain. The most potent compounds, 7g and 13, exhibited submicromolar activity against the replicating bacteria (R-TB), with minimum inhibitory concentrations (MICs) of 0.77 and 0.95 microM, respectively. In general, these compounds also had micromolar activity against the nonreplicating persistent bacteria (NRP-TB) and did not show toxicity on Vero cells up to 128 microM concentration. Compounds 7g and 13 were shown to retain their anti-TB activity against rifampin, isoniazid, and streptomycin resistant Mtb strains. The results suggest that quinoline-isoxazole-based anti-TB compounds are promising leads for new TB drug development.

  1. Derivatives of 3-isoxazolecarboxylic acid esters: a potent and selective compound class against replicating and nonreplicating Mycobacterium tuberculosis.

    PubMed

    Lilienkampf, Annamaria; Pieroni, Marco; Franzblau, Scott G; Bishai, William R; Kozikowski, Alan P

    2012-01-01

    New antituberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains and to shorten the long treatment regimen. A series of isoxazole-based compounds, bearing a carboxy moiety at the C3 position, are highly potent and versatile anti-TB agents. Several members of this compound class exhibit submicromolar in vitro activity against replicating Mtb (R-TB) and thus comparable activity to the current first-line anti-TB drugs. Remarkably, certain compounds also show low micromolar activity in a model for nonreplicating Mtb (NRP-TB) phenotype, which is considered a key to shortening the current long treatment protocol. The series shows excellent selectivity towards Mtb and, in general, shows no cytotoxicity on Vero cells (IC50's > 128 μM). Selected compounds retain their activity against isoniazid (INH), rifampin (RMP), and streptomycin (SM) resistant Mtb strains. The foregoing facts make derivatives of 3- isoxazolecarboxylic acid esters a promising anti-TB chemotype, and as such present attractive lead compounds for TB drug development.

  2. Charged conformal Killing spinors

    SciTech Connect

    Lischewski, Andree

    2015-01-15

    We study the twistor equation on pseudo-Riemannian Spin{sup c}-manifolds whose solutions we call charged conformal Killing spinors (CCKSs). We derive several integrability conditions for the existence of CCKS and study their relations to spinor bilinears. A construction principle for Lorentzian manifolds admitting CCKS with nontrivial charge starting from CR-geometry is presented. We obtain a partial classification result in the Lorentzian case under the additional assumption that the associated Dirac current is normal conformal and complete the classification of manifolds admitting CCKS in all dimensions and signatures ≤5 which has recently been initiated in the study of supersymmetric field theories on curved space.

  3. Medicalized killing in Auschwitz.

    PubMed

    Lifton, R J

    1982-11-01

    Since late 1977 I have been conducting a psychological study of medical behavior in Auschwitz, and of Nazi doctors in general. I have been especially interested in the relationship of doctors, SS doctors in particular, to the killing process--in the transformation from healer to killer. I am concerned with the importance of the medicalized pattern for the overall Nazi project of mass murder and have therefore tried to examine the interaction of biomedical ideology, political ideology, and individual behavior. Finally, the work raises questions of more general significance: for doctors and medicine elsewhere; for scientists, other professionals, and institutions of all kinds; for approaches to "triage" and control over life and death; and for our understanding of human nature and human values. After describing how I did the study, I will discuss what I call the Nazi "biomedical vision" and its relationship to the killing of mental patients as well as to Auschwitz. Next I will suggest features of the Auschwitz atmosphere, particularly in regard to the psychological factors, or mechanisms, that enabled the Nazi doctors to do what they did. Finally, I will turn very briefly to the more general problems raised by the study.

  4. Secretion of Rhoptry and Dense Granule Effector Proteins by Nonreplicating Toxoplasma gondii Uracil Auxotrophs Controls the Development of Antitumor Immunity.

    PubMed

    Fox, Barbara A; Sanders, Kiah L; Rommereim, Leah M; Guevara, Rebekah B; Bzik, David J

    2016-07-01

    Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP) and dense granule (GRA) proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α+ dendritic cells, the IL-12/interferon-gamma (IFN-γ) TH1 axis, as well as CD4+ and CD8+ T cells. Deletion of parasitophorous vacuole membrane (PVM) associated proteins ROP5, ROP17, ROP18, ROP35 or ROP38, intravacuolar network associated dense granule proteins GRA2 or GRA12, and GRA24 which traffics past the PVM to the host cell nucleus severely abrogated the antitumor response. In contrast, deletion of other secreted effector molecules such as GRA15, GRA16, or ROP16 that manipulate host cell signaling and transcriptional pathways, or deletion of PVM associated ROP21 or GRA3 molecules did not affect the antitumor activity. Association of ROP18 with the PVM was found to be essential for the development of the antitumor responses. Surprisingly, the ROP18 kinase activity required for resistance to IFN-γ activated host innate immunity related GTPases and virulence was not essential for the antitumor response. These data show that PVM functions of parasite secreted effector molecules, including ROP18, manipulate host cell responses through ROP18 kinase virulence independent mechanisms to activate potent antitumor responses. Our results demonstrate that PVM associated rhoptry effector proteins secreted prior to host cell invasion and dense granule effector proteins localized to the intravacuolar network and host nucleus that are secreted after host cell invasion coordinately control the

  5. Proliferating cell nuclear antigen (PCNA) is required for cell cycle-regulated silent chromatin on replicated and nonreplicated genes.

    PubMed

    Miller, Andrew; Chen, Jiji; Takasuka, Taichi E; Jacobi, Jennifer L; Kaufman, Paul D; Irudayaraj, Joseph M K; Kirchmaier, Ann L

    2010-11-05

    In Saccharomyces cerevisiae, silent chromatin is formed at HMR upon the passage through S phase, yet neither the initiation of DNA replication at silencers nor the passage of a replication fork through HMR is required for silencing. Paradoxically, mutations in the DNA replication processivity factor, POL30, disrupt silencing despite this lack of requirement for DNA replication in the establishment of silencing. We tested whether pol30 mutants could establish silencing at either replicated or non-replicated HMR loci during S phase and found that pol30 mutants were defective in establishing silencing at HMR regardless of its replication status. Although previous studies tie the silencing defect of pol30 mutants to the chromatin assembly factors Asf1p and CAF-1, we found pol30 mutants did not exhibit a gross defect in packaging HMR into chromatin. Rather, the pol30 mutants exhibited defects in histone modifications linked to ASF1 and CAF-1-dependent pathways, including SAS-I- and Rtt109p-dependent acetylation events at H4-K16 and H3-K9 (plus H3-K56; Miller, A., Yang, B., Foster, T., and Kirchmaier, A. L. (2008) Genetics 179, 793-809). Additional experiments using FLIM-FRET revealed that Pol30p interacted with SAS-I and Rtt109p in the nuclei of living cells. However, these interactions were disrupted in pol30 mutants with defects linked to ASF1- and CAF-1-dependent pathways. Together, these results imply that Pol30p affects epigenetic processes by influencing the composition of chromosomal histone modifications.

  6. Secretion of Rhoptry and Dense Granule Effector Proteins by Nonreplicating Toxoplasma gondii Uracil Auxotrophs Controls the Development of Antitumor Immunity

    PubMed Central

    Fox, Barbara A.; Sanders, Kiah L.; Rommereim, Leah M.; Bzik, David J.

    2016-01-01

    Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP) and dense granule (GRA) proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α+ dendritic cells, the IL-12/interferon-gamma (IFN-γ) TH1 axis, as well as CD4+ and CD8+ T cells. Deletion of parasitophorous vacuole membrane (PVM) associated proteins ROP5, ROP17, ROP18, ROP35 or ROP38, intravacuolar network associated dense granule proteins GRA2 or GRA12, and GRA24 which traffics past the PVM to the host cell nucleus severely abrogated the antitumor response. In contrast, deletion of other secreted effector molecules such as GRA15, GRA16, or ROP16 that manipulate host cell signaling and transcriptional pathways, or deletion of PVM associated ROP21 or GRA3 molecules did not affect the antitumor activity. Association of ROP18 with the PVM was found to be essential for the development of the antitumor responses. Surprisingly, the ROP18 kinase activity required for resistance to IFN-γ activated host innate immunity related GTPases and virulence was not essential for the antitumor response. These data show that PVM functions of parasite secreted effector molecules, including ROP18, manipulate host cell responses through ROP18 kinase virulence independent mechanisms to activate potent antitumor responses. Our results demonstrate that PVM associated rhoptry effector proteins secreted prior to host cell invasion and dense granule effector proteins localized to the intravacuolar network and host nucleus that are secreted after host cell invasion coordinately control the

  7. How to kill creativity.

    PubMed

    Amabile, T M

    1998-01-01

    In today's knowledge economy, creativity is more important than ever. But many companies unwittingly employ managerial practices that kill it. How? By crushing their employees' intrinsic motivation--the strong internal desire to do something based on interests and passions. Managers don't kill creativity on purpose. Yet in the pursuit of productivity, efficiency, and control--all worthy business imperatives--they undermine creativity. It doesn't have to be that way, says Teresa Amabile. Business imperatives can comfortably coexist with creativity. But managers will have to change their thinking first. Specifically, managers will need to understand that creativity has three parts: expertise, the ability to think flexibly and imaginatively, and motivation. Managers can influence the first two, but doing so is costly and slow. It would be far more effective to increase employees' intrinsic motivation. To that end, managers have five levers to pull: the amount of challenge they give employees, the degree of freedom they grant around process, the way they design work groups, the level of encouragement they give, and the nature of organizational support. Take challenge as an example. Intrinsic motivation is high when employees feel challenged but not overwhelmed by their work. The task for managers, therefore, becomes matching people to the right assignments. Consider also freedom. Intrinsic motivation--and thus creativity--soars when managers let people decide how to achieve goals, not what goals to achieve. Managers can make a difference when it comes to employee creativity. The result can be truly innovative companies in which creativity doesn't just survive but actually thrives.

  8. Kill operation requires thorough analysis

    SciTech Connect

    Abel, L.W.

    1995-05-15

    Full control of a blowout well requires a properly designed post-capping kill operation because failures in regaining well control usually occur during the kill operation, not during capping. Capping (the installation of pressure control or diverter equipment on the wellhead) is generally very reliable in gaining control of a blowout well. The following techniques are some of the viable means of killing blowout wells once the capping assemblies are in place: direct shut in of the flow; bullheading; momentum kill; volumetric control for migration of fluids or lubrication after migration ceases; and dynamic kills (friction-based dynamic kills or mass flow rate kills) The objective of most post-capping operations is to stop the flow and put the well under hydrostatic control. The means of killing a blowout once capping assemblies are in place should be chosen with care to avoid problems such as cratering, equipment failure, and underground blowouts. The particular circumstances and well integrity will dictate which kill method will be the most viable. Each of these five methods are explained.

  9. Does smoking really kill anybody?

    PubMed

    Eysenck, H J

    1995-12-01

    Statements that so many people are killed by smoking use the term "kill" in a very unusual manner which is easily misunderstood by people not expert in epidemiology. In addition, the usual calculations leave out of account the fact that smoking interacts synergistically with other risk factors, so that it is a combination of risk factors rather than any specific one that is likely to have a causal influence on mortality. Strictly speaking it is quite inappropriate to state that smoking kills anybody, if we use the term "kill" in a meaningful fashion.

  10. Asymptotic symmetries on Killing horizons

    NASA Astrophysics Data System (ADS)

    Koga, Jun-Ichirou

    2001-12-01

    We investigate asymptotic symmetries regularly defined on spherically symmetric Killing horizons in Einstein theory with or without the cosmological constant. These asymptotic symmetries are described by asymptotic Killing vectors, along which the Lie derivatives of perturbed metrics vanish on a Killing horizon. We derive the general form of the asymptotic Killing vectors and find that the group of asymptotic symmetries consists of rigid O(3) rotations of a horizon two-sphere and supertranslations along the null direction on the horizon, which depend arbitrarily on the null coordinate as well as the angular coordinates. By introducing the notion of asymptotic Killing horizons, we also show that local properties of Killing horizons are preserved not only under diffeomorphisms but also under nontrivial transformations generated by the asymptotic symmetry group. Although the asymptotic symmetry group contains the Diff(S1) subgroup, which results from supertranslations dependent only on the null coordinate, it is shown that the Poisson brackets algebra of the conserved charges conjugate to asymptotic Killing vectors does not acquire nontrivial central charges. Finally, by considering extended symmetries, we discuss the fact that unnatural reduction of the symmetry group is necessary in order to obtain the Virasoro algebra with nontrivial central charges, which is not justified when we respect the spherical symmetry of Killing horizons.

  11. How honey kills bacteria.

    PubMed

    Kwakman, Paulus H S; te Velde, Anje A; de Boer, Leonie; Speijer, Dave; Vandenbroucke-Grauls, Christina M J E; Zaat, Sebastian A J

    2010-07-01

    With the rise in prevalence of antibiotic-resistant bacteria, honey is increasingly valued for its antibacterial activity. To characterize all bactericidal factors in a medical-grade honey, we used a novel approach of successive neutralization of individual honey bactericidal factors. All bacteria tested, including Bacillus subtilis, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli, ciprofloxacin-resistant Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecium, were killed by 10-20% (v/v) honey, whereas > or = 40% (v/v) of a honey-equivalent sugar solution was required for similar activity. Honey accumulated up to 5.62 +/- 0.54 mM H(2)O(2) and contained 0.25 +/- 0.01 mM methylglyoxal (MGO). After enzymatic neutralization of these two compounds, honey retained substantial activity. Using B. subtilis for activity-guided isolation of the additional antimicrobial factors, we discovered bee defensin-1 in honey. After combined neutralization of H(2)O(2), MGO, and bee defensin-1, 20% honey had only minimal activity left, and subsequent adjustment of the pH of this honey from 3.3 to 7.0 reduced the activity to that of sugar alone. Activity against all other bacteria tested depended on sugar, H(2)O(2), MGO, and bee defensin-1. Thus, we fully characterized the antibacterial activity of medical-grade honey.

  12. How electroshock weapons kill!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2010-03-01

    Growing numbers of law enforcement officers now carry an electroshock weapon (ESW). Over 500 U.S. deaths have followed ESW use in the past 26 years; over 450 of these deaths followed use of an electromuscular disruptor in the past 9 years. Most training courses teach that ESWs are safe; that they can kill only by the direct effect of electric current on the heart; and that a death following use of an ESW always has some other cause. All these teachings are false! The last was disproved by Lundquist.^1 Williams^2 ruled out direct electrical effects as a cause of almost all the 213 deaths he studied, leaving disruption of normal physiological processes as the only alternative explanation. Careful study of all such deaths identifies 4 different ways that death has or could have been brought about by the ESW: kidney failure following rhabdomyolysis [rare]; cardiac arrest from hyperkalemia following rhabdomyolysis [undocumented]; lactic acid-induced ventricular fibrillation [conclusive proof impossible]; and [most common] anoxia from so much lactic acid in the circulating blood that it acts as an oxygen scavenger, continuously depleting the blood of oxygen until most of the lactate has been metabolized. ^1M. Lundquist, BAPS 54(1) K1.270(2009). ^2Howard E. Williams, Taser Electronic Control Devices and Sudden In-Custody Death, 2008.

  13. Killing, letting die and euthanasia.

    PubMed Central

    Husak, D N

    1979-01-01

    Medical ethicists debate whether or not the moral assessment of cases of euthanasia should depend on whether the patient is 'killed' or 'allowed to die'. The usual presupposition is that a clear distinction between killing and letting die can be drawn so that this substantive question is not begged. I contend that the categorisation of cases of instances of killing rather than as instances of letting die depends in part on a prior moral assessment of the case. Hence is it trivially rather than substantively true that the distinction has moral significance. But even if a morally neutral (ie non-question begging) distinction could be drawn, its application to the euthanasia controversy is problematic. I illustrate the difficulties of employing this distinction to reach moral conclusions by critically discussing Philippa Foot's recent treatment of euthanasia. I conclude that even if an act of euthanasia is an instance of killing, and there exists a prima facie moral duty not to kill, and no more stringent duty overrides this duty, one still cannot determine such an act to be morally impermissible. PMID:541821

  14. Killing, letting die and euthanasia.

    PubMed

    Husak, D N

    1979-12-01

    Medical ethicists debate whether or not the moral assessment of cases of euthanasia should depend on whether the patient is 'killed' or 'allowed to die'. The usual presupposition is that a clear distinction between killing and letting die can be drawn so that this substantive question is not begged. I contend that the categorisation of cases of instances of killing rather than as instances of letting die depends in part on a prior moral assessment of the case. Hence is it trivially rather than substantively true that the distinction has moral significance. But even if a morally neutral (ie non-question begging) distinction could be drawn, its application to the euthanasia controversy is problematic. I illustrate the difficulties of employing this distinction to reach moral conclusions by critically discussing Philippa Foot's recent treatment of euthanasia. I conclude that even if an act of euthanasia is an instance of killing, and there exists a prima facie moral duty not to kill, and no more stringent duty overrides this duty, one still cannot determine such an act to be morally impermissible.

  15. Immunogenicity, Protective Efficacy, and Non-Replicative Status of the HSV-2 Vaccine Candidate HSV529 in Mice and Guinea Pigs

    PubMed Central

    Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

    2015-01-01

    HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine

  16. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    PubMed

    Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

    2015-01-01

    HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.

  17. Killing symmetries as Hamiltonian constraints

    NASA Astrophysics Data System (ADS)

    Lusanna, Luca

    2016-02-01

    The existence of a Killing symmetry in a gauge theory is equivalent to the addition of extra Hamiltonian constraints in its phase space formulation, which imply restrictions both on the Dirac observables (the gauge invariant physical degrees of freedom) and on the gauge freedom. When there is a time-like Killing vector field only pure gauge electromagnetic fields survive in Maxwell theory in Minkowski space-time, while in ADM canonical gravity in asymptotically Minkowskian space-times only inertial effects without gravitational waves survive.

  18. 33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements apply to all bridges across Newtown Creek, Dutch Kills, English Kills, and their tributaries: (1) The...

  19. Farm Education at Stony Kill.

    ERIC Educational Resources Information Center

    Parisio, Richard

    1986-01-01

    Describes typical winter farm lessons for students visiting Stony Kill Farm Environmental Education Center located 70 miles north of New York City: butter and corncake making, soil erosion experiments, dissecting and growing seeds. Emphasizes major theme of conservation of farmland from destructive farming practices and careless development. (NEC)

  20. Does Assessment Kill Student Creativity?

    ERIC Educational Resources Information Center

    Beghetto, Ronald A.

    2005-01-01

    Does assessment kill creativity? In this article, creativity is defined and discussed and an overview of creativity and motivational research is provided to describe how assessment practices can influence students' creativity. Recommendations for protecting creativity when assessing students also are provided.

  1. Farm Education at Stony Kill.

    ERIC Educational Resources Information Center

    Parisio, Richard

    1986-01-01

    Describes typical winter farm lessons for students visiting Stony Kill Farm Environmental Education Center located 70 miles north of New York City: butter and corncake making, soil erosion experiments, dissecting and growing seeds. Emphasizes major theme of conservation of farmland from destructive farming practices and careless development. (NEC)

  2. Beetle Kill Wall at NREL

    ScienceCinema

    None

    2016-07-12

    When it comes to designing an interior decorative feature for one of the most energy efficient office buildings in the world, very few would consider bringing in a beetle to do the job. But thats what happened at the U.S. Department of Energy's (DOE) Research Support Facility (RSF) located on the National Renewable Energy Laboratory (NREL) campus.In June, the RSF will become home to more than 800 workers from DOE and NREL and building visitors will be greeted with a soaring, two-story high wall entirely covered with wood harvested from the bark beetle infestation that has killed millions of pine trees in the Western U.S. But, the use of beetle kill wood is just one example of the resources being leveraged to make the RSF a model for sustainability and one more step toward NRELs goal to be a net zero energy campus.

  3. Beetle Kill Wall at NREL

    SciTech Connect

    2010-01-01

    When it comes to designing an interior decorative feature for one of the most energy efficient office buildings in the world, very few would consider bringing in a beetle to do the job. But thats what happened at the U.S. Department of Energy's (DOE) Research Support Facility (RSF) located on the National Renewable Energy Laboratory (NREL) campus.In June, the RSF will become home to more than 800 workers from DOE and NREL and building visitors will be greeted with a soaring, two-story high wall entirely covered with wood harvested from the bark beetle infestation that has killed millions of pine trees in the Western U.S. But, the use of beetle kill wood is just one example of the resources being leveraged to make the RSF a model for sustainability and one more step toward NRELs goal to be a net zero energy campus.

  4. Women who kill their mates.

    PubMed

    Bourget, Dominique; Gagné, Pierre

    2012-01-01

    Spousal homicide perpetrators are much more likely to be men than women. Accordingly, little research has focused on delineating characteristics of women who have committed spousal homicide. A retrospective clinical review of coroners' files containing all cases of spousal homicide occurring in Quebec over a 20-year period was carried out. A total of 276 spousal homicides occurred between 1991 and 2010, with 42 homicides by female spouses and 234 homicides by male spouses. Differences between homicides committed by female offenders and male offenders are discussed, and findings on spousal homicide committed by women are compared with those of previous studies. Findings regarding offenses perpetrated by females in the context of mental illness, domestic violence, and homicide-suicide are explored. The finding that only 28% of the female offenders in the Quebec sample had previously been subjected to violence by their victim is in contrast to the popular belief and reports that indicate that most female-perpetrated spousal homicide occurs in self-defense or in reaction to long-term abuse. In fact, women rarely gave a warning before killing their mates. Most did not suffer from a mental illness, although one-fifth were acutely intoxicated at the time of the killing. In the vast majority of cases of women who killed their mates, there were very few indicators that might have signaled the risk and helped predict the violent lethal behavior. Copyright © 2012 John Wiley & Sons, Ltd.

  5. 33 CFR 117.702 - Arthur Kill.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Arthur Kill. 117.702 Section 117... OPERATION REGULATIONS Specific Requirements New Jersey § 117.702 Arthur Kill. (a) The draw of the Arthur Kill (AK) Railroad Bridge shall be maintained in the full open position for navigation at all...

  6. 33 CFR 117.702 - Arthur Kill.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Arthur Kill. 117.702 Section 117... OPERATION REGULATIONS Specific Requirements New Jersey § 117.702 Arthur Kill. (a) The draw of the Arthur Kill (AK) Railroad Bridge shall be maintained in the full open position for navigation at all...

  7. 33 CFR 117.702 - Arthur Kill.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Arthur Kill. 117.702 Section 117... OPERATION REGULATIONS Specific Requirements New Jersey § 117.702 Arthur Kill. (a) The draw of the Arthur Kill (AK) Railroad Bridge shall be maintained in the full open position for navigation at all...

  8. 33 CFR 117.702 - Arthur Kill.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Arthur Kill. 117.702 Section 117... OPERATION REGULATIONS Specific Requirements New Jersey § 117.702 Arthur Kill. (a) The draw of the Arthur Kill (AK) Railroad Bridge shall be maintained in the full open position for navigation at all...

  9. A new antituberculosis drug that selectively kills nonmultiplying Mycobacterium tuberculosis.

    PubMed

    Mitchison, Denis A

    2008-03-13

    An important report by Bryk et al. in this issue of Cell Host & Microbe describes the properties of a rhodanine prodrug active against nonmultiplying Mycobacterium tuberculosis (Mtb). Considering the tolerance of nonreplicating Mtb to most currently available agents, such a drug could be a major addition to our antituberculosis arsenal and would greatly benefit control of the disease.

  10. 33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following...

  11. 33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following...

  12. 33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following...

  13. 33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Newtown Creek, Dutch Kills, English Kills and their tributaries. 117.801 Section 117.801 Navigation and Navigable Waters COAST GUARD....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following...

  14. Localization of Low Copy Number Plasmid pRC4 in Replicating Rod and Non-Replicating Cocci Cells of Rhodococcus erythropolis PR4

    PubMed Central

    Singhi, Divya; Jain, Aayushi; Srivastava, Preeti

    2016-01-01

    Rhodococcus are gram-positive bacteria, which can exist in two different shapes rod and cocci. A number of studies have been done in the past on replication and stability of small plasmids in this bacterium; however, there are no reports on spatial localization and segregation of these plasmids. In the present study, a low copy number plasmid pDS3 containing pRC4 replicon was visualized in growing cells of Rhodococcus erythropolis PR4 (NBRC100887) using P1 parS-ParB-GFP system. Cells were initially cocci and then became rod shaped in exponential phase. Cocci cells were found to be non-replicating as evident by the presence of single fluorescence focus corresponding to the plasmid and diffuse fluorescence of DnaB-GFP. Rod shaped cells contained plasmid either present as one fluorescent focus observed at the cell center or two foci localized at quarter positions. The results suggest that the plasmid is replicated at the cell center and then it goes to quarter position. In order to observe the localization of plasmid with respect to nucleoid, plasmid segregation was also studied in filaments where it was found to be replicated at the cell center in a nucleoid free region. To the best of our knowledge, this is the first report on segregation of small plasmids in R. erythropolis. PMID:27935968

  15. Recombinant parvovirus-like particles as an antigen carrier: A novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells

    PubMed Central

    Sedlik, C.; Saron, M.-F.; Sarraseca, J.; Casal, I.; Leclerc, C.

    1997-01-01

    To develop a strategy that promotes efficient antiviral immunity, hybrid virus-like particles (VLP) were prepared by self-assembly of the modified porcine parvovirus VP2 capsid protein carrying a CD8+ T cell epitope from the lymphocytic choriomeningitis virus nucleoprotein. Immunization of mice with these hybrid pseudoparticles, without adjuvant, induced strong cytotoxic T lymphocyte (CTL) responses against both peptide-coated- or virus-infected-target cells. This CD8+ class I-restricted cytotoxic activity persisted in vivo for at least 9 months. Furthermore, the hybrid parvovirus-like particles were able to induce a complete protection of mice against a lethal lymphocytic choriomeningitis virus infection. To our knowledge, this study represents the first demonstration that hybrid nonreplicative VLP carrying a single viral CTL epitope can induce protection against a viral lethal challenge, in the absence of any adjuvant. These recombinant particles containing a single type of protein are easily produced by the baculovirus expression system and, therefore, represent a promising and safe strategy to induce strong CTL responses for the elimination of virus-infected cells. PMID:9207121

  16. Killing(-Yano) tensors in string theory

    NASA Astrophysics Data System (ADS)

    Chervonyi, Yuri; Lunin, Oleg

    2015-09-01

    We construct the Killing(-Yano) tensors for a large class of charged black holes in higher dimensions and study general properties of such tensors, in particular, their behavior under string dualities. Killing(-Yano) tensors encode the symmetries beyond isometries, which lead to insights into dynamics of particles and fields on a given geometry by providing a set of conserved quantities. By analyzing the eigenvalues of the Killing tensor, we provide a prescription for constructing several conserved quantities starting from a single object, and we demonstrate that Killing tensors in higher dimensions are always associated with ellipsoidal coordinates. We also determine the transformations of the Killing(-Yano) tensors under string dualities, and find the unique modification of the Killing-Yano equation consistent with these symmetries. These results are used to construct the explicit form of the Killing(-Yano) tensors for the Myers-Perry black hole in arbitrary number of dimensions and for its charged version.

  17. Fish kill from underwater explosions

    USGS Publications Warehouse

    Stuart, David J.

    1962-01-01

    The U.S. Geological Survey has used 23 different shotpoints during two seasons of field work in our seismic study of crustal structure in western United States. Without exception, it has been found that under-water shotpoints result in a more efficient conversion of explosive energy into seismic energy than do drilled-hole shotpoints. This experience, together with elimination of drilling costs, has led to the use of underwater shotpoints wherever possible. Three of the 23 shotpoints were in the Pacific Ocean, and for these we have no detailed information on the fish kill. Another six shotpoints were located in inland bodies of water. These are: * Soda Lake near Fallon, Nevada * Mono Lake near Lee Vining, California * Lake Mead near Boulder City, Nevada * Shasta Lake near Redding, California * C.J. Strike Reservoir near Bruneau, Idaho * Lucky Peak Reservoir near Boise, Idaho The 22 high-explosive charges, weighing a total of 95,100 pounds, that were fired in lakes containing fish life resulted in the known death of 2,413 game fish with a total weight of 759 pounds. The average mortality was 110 game fish or 34.5 pounds of game fish killed per average shot of 4,325 pounds of high-explosives.

  18. Letting die and mercy killing.

    PubMed

    Narbekovas, Andrius; Meilius, Kazimieras

    2003-01-01

    We are all called to make moral decisions, not only about preserving life and health, but also about accepting our death and dying. There are situations, when it is morally right, and indeed obligatory, to allow a dying person to die in peace and dignity. But there is a world of difference between allowing a peaceful death, and deliberately setting out to bring death of the person either by acts of commission (s.c. 'active euthanasia'), or by acts of omission (s.c. 'passive euthanasia'). The word "killing" seems proper for euthanasia, because "to kill" does mean " to intentionally cause the death of someone." It can be morally acceptable to withhold or withdraw a treatment precisely because it is reasonably judged as inefficacious (futile), or excessively burdensome for the patient. One's reason for withholding such treatment must not be a judgement about the desirability of putting an end to the patient's life, but a judgement about the desirability of putting an end to the treatment, which is futile or burdensome.

  19. Euthanasia: killing as due care?

    PubMed

    Oduncu, Fuat S

    2003-01-01

    On 10 April 2001, the Netherlands was the first country to pass a law on the killing of patients at their request (euthanasia), which took effect on 1 April 2002. Belgium followed and passed a euthanasia law on 16 May 2002, which took effect on 23 September 2002 and is even more liberal than the Dutch one. Physicians will be exempted from criminal liability provided they satisfy the so-called 'due care criteria'. However, in medical history euthanasia has never been part of the medical duty of care. Instead, the goals of medicine have always been the relief of pain and suffering. The current article provides insights into the Dutch, Belgian and Oregon euthanasia and physician-assisted suicide practices and reflects upon some central medical and legal documents on the regulation of euthanasia and the provision of palliative care. Modern palliative care includes both the delivery of competent palliative skills and a virtuous attitude of compassionate caring about the terminally ill patient as an autonomous person. Here, the author rejects killing as due care and proposes a novel concept of 'RAHME' (Aramaic: compassion, love, mercy), which calls for a holistically oriented concept where physicians act as companions to the terminally ill and dying patients.

  20. Sublingual immunization with nonreplicating antigens induces antibody-forming cells and cytotoxic T cells in the female genital tract mucosa and protects against genital papillomavirus infection.

    PubMed

    Cuburu, Nicolas; Kweon, Mi-Na; Hervouet, Catherine; Cha, Hye-Ran; Pang, Yuk-Ying S; Holmgren, Jan; Stadler, Konrad; Schiller, John T; Anjuère, Fabienne; Czerkinsky, Cecil

    2009-12-15

    We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8(+) cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT) as an adjuvant. Sublingual administration of OVA and CT induced Ag-specific IgA and IgG Abs in blood and in cervicovaginal secretions. These responses were associated with large numbers of IgA Ab-secreting cells (ASCs) in the genital mucosa. Genital ASC responses were similar in magnitude and isotype distribution after s.l., intranasal, or vaginal immunization and were superior to those seen after intragastric immunization. Genital, but not blood or spleen, IgA ASC responses were inhibited by treatment with anti-CCL28 Abs, suggesting that the chemokine CCL28 plays a major role in the migration of IgA ASC progenitors to the reproductive tract mucosa. Furthermore, s.l. immunization with OVA induced OVA-specific effector CD8(+) cytolytic T cells in the genital mucosa, and these responses required coadministration of the CT adjuvant. Furthermore, s.l. administration of human papillomavirus virus-like particles with or without the CT adjuvant conferred protection against genital challenge with human papillomavirus pseudovirions. Taken together, these findings underscore the potential of s.l. immunization as an efficient vaccination strategy for inducing genital immune responses and should impact on the development of vaccines against sexually transmitted diseases.

  1. Timelike Killing spinors in seven dimensions

    SciTech Connect

    Cariglia, Marco; Conamhna, Oisin A.P. Mac

    2004-12-15

    We employ the G-structure formalism to study supersymmetric solutions of minimal and SU(2) gauged supergravities in seven dimensions admitting Killing spinors with an associated timelike Killing vector. The most general such Killing spinor defines a SU(3) structure. We deduce necessary and sufficient conditions for the existence of a timelike Killing spinor on the bosonic fields of the theories, and find that such configurations generically preserve one out of 16 supersymmetries. Using our general supersymmetric ansatz we obtain numerous new solutions, including squashed or deformed anti-de Sitter solutions of the gauged theory, and a large class of Goedel-like solutions with closed timelike curves.

  2. A kill curve for Phanerozoic marine species

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1991-01-01

    A kill curve for Phanerozoic species is developed from an analysis of the stratigraphic ranges of 17,621 genera, as compiled by Sepkoski. The kill curve shows that a typical species' risk of extinction varies greatly, with most time intervals being characterized by very low risk. The mean extinction rate of 0.25/m.y. is thus a mixture of long periods of negligible extinction and occasional pulses of much higher rate. Because the kill curve is merely a description of the fossil record, it does not speak directly to the causes of extinction. The kill curve may be useful, however, to li inverted question markmit choices of extinction mechanisms.

  3. A kill curve for Phanerozoic marine species

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1991-01-01

    A kill curve for Phanerozoic species is developed from an analysis of the stratigraphic ranges of 17,621 genera, as compiled by Sepkoski. The kill curve shows that a typical species' risk of extinction varies greatly, with most time intervals being characterized by very low risk. The mean extinction rate of 0.25/m.y. is thus a mixture of long periods of negligible extinction and occasional pulses of much higher rate. Because the kill curve is merely a description of the fossil record, it does not speak directly to the causes of extinction. The kill curve may be useful, however, to li inverted question markmit choices of extinction mechanisms.

  4. Serum factors responsible for killing of Shigella

    PubMed Central

    Reed, W. P.; Albright, Elizabeth L.

    1974-01-01

    Eight strains of Shigella were tested for susceptibility to killing by seven normal human sera. Although there was a wide range of susceptibility between strains of bacteria, there was surprisingly little difference in the killing activity of individual sera and no relationship between antibody titres and killing capacity. Bacteriolysis required small amounts of antibody, but as little as 0.02 mg of a 19S fraction from normal serum restored full killing capacity to 1 ml of antibody depleted serum. Neither 11S IgA nor Cohn fraction II restored the bacteriolytic ability. Both the early reacting complement sequence and the alternate C3 activating pathway appeared to participate in killing as indicated by the roles of C2 and C3PA. Killing occurred, but with reduced efficiency, when either of the two substances was missing. However, serum lacking both C2 and C3PA could no longer kill Shigella. Killing also required the presence of C3, and presumably some of the later components of complement are subsequently involved. PMID:4846468

  5. Bull heading to kill live gas wells

    SciTech Connect

    Oudeman, P.; Avest, D. ter; Grodal, E.O.; Asheim, H.A.; Meissner, R.J.H.

    1994-12-31

    To kill a live closed-in gas well by bull heading down the tubing, the selected pump rate should be high enough to ensure efficient displacement of the gas into the formation (i.e., to avoid the kill fluid bypassing the gas). On the other hand, the pressures that develop during bull heading at high rate must not exceed wellhead pressure rating, tubing or casing burst pressures or the formation breakdown gradient, since this will lead, at best, to a very inefficient kill job. Given these constraints, the optimum kill rate, requited hydraulic horsepower, density and type of kill fluids have to be selected. For this purpose a numerical simulator has been developed, which predicts the sequence of events during bull heading. Pressures and flow rates in the well during the kill job are calculated, taking to account slip between the gas and kill fluid, hydrostatic and friction pressure drop, wellbore gas compression and leak-off to the formation. Comparison with the results of a dedicated field test demonstrates that these parameters can be estimated accurately. Example calculations will be presented to show how the simulator can be used to identify an optimum kill scenario.

  6. Puzzling cases about killing and letting die.

    PubMed

    Favor, C D

    1996-01-01

    Discussions of euthanasia often appeal to the distinction between killing people and letting them die. Favor asks whether this distinction is morally important--in particular, whether killing is worse than merely letting someone die, even when the motivations and consequences are the same. She explores our moral intuitions via a discussion of various subtly different hypothetical examples.

  7. Killing and letting die: a defensible distinction.

    PubMed

    Cartwright, W

    1996-04-01

    The distinction between killing and letting die is investigated and clarified. It is then argued that in most cases, though not in all, it is worse to kill than to let die. In euthanasia the significance of the distinction is diminished, but still important.

  8. Momentum kill procedure can quickly control blowouts

    SciTech Connect

    Watson, W.D. ); Moore, P. )

    1993-08-30

    The momentum kill method can help in quickly regaining control of a blowing well, providing the blowing well rate and fluid properties can be estimated reasonably. The momentum of the kill fluid counteracts and overcomes the flowing momentum of formation fluids. In other words, sufficient mud density pumped at a sufficient rate is directed into the flow stream to force the escaping fluid column back into the well bore. Sufficient kill fluid hydrostatic pressure must be stacked'' in the hole so that the well remains dead after the operation. The momentum kill is not a panacea for all blowouts. An assessment must be made of the potential problems unique to this method, and certain requirements must be met if the technique is to be successful. The paper discusses some of the considerations for evaluating the use of the momentum kill method.

  9. Killing, letting die, and simple conflicts.

    PubMed

    Malm, H M

    1989-01-01

    Proponents of the moral equivalence of killing and letting die argue that in cases of simple conflict, where one agent must either perform a positive act and kill one person, or not perform that act and allow another person to die, the agent's alternatives are clearly morally equivalent. Malm rejects this view in a three part essay. He argues that in cases of simple conflict, the acts of killing and letting die are morally different, and that killing is not in itself worse than letting die. Malm considers and rejects the suggestion that the agent should decide randomly between the two alternatives. He concludes that while simple conflict cases require us to recognize a morally significant difference between killing and letting die, they do not require us to recognize a morally significant difference between acting and refraining.

  10. Antibacterial surface design - Contact kill

    NASA Astrophysics Data System (ADS)

    Kaur, Rajbir; Liu, Song

    2016-08-01

    Designing antibacterial surfaces has become extremely important to minimize Healthcare Associated Infections which are a major cause of mortality worldwide. A previous biocide-releasing approach is based on leaching of encapsulated biocides such as silver and triclosan which exerts negative impacts on the environment and potentially contributes to the development of bacterial resistance. This drawback of leachable compounds led to the shift of interest towards a more sustainable and environmentally friendly approach: contact-killing surfaces. Biocides that can be bound onto surfaces to give the substrates contact-active antibacterial activity include quaternary ammonium compounds (QACs), quaternary phosphoniums (QPs), carbon nanotubes, antibacterial peptides, and N-chloramines. Among the above, QACs and N-chloramines are the most researched contact-active biocides. We review the engineering of contact-active surfaces using QACs or N-chloramines, the modes of actions as well as the test methods. The charge-density threshold of cationic surfaces for desired antibacterial efficacy and attempts to combine various biocides for the generation of new contact-active surfaces are discussed in detail. Surface positive charge density is identified as a key parameter to define antibacterial efficacy. We expect that this research field will continue to attract more research interest in view of the potential impact of self-disinfective surfaces on healthcare-associated infections, food safety and corrosion/fouling resistance required on industrial surfaces such as oil pipes and ship hulls.

  11. Choke and kill control system

    SciTech Connect

    Pringle, R.E.

    1988-08-02

    A control system is described for a choke and kill safety valve for use in a well conduit, in which the valve indicates a housing having a bore therethrough, a sleeve telescopically movable in the housing about the bore, a valve closure member positioned in the housing and connected to the sleeve and movable between open and closed positions in the bore, a flow tube longitudinally movable in the housing for controlling the movement of the valve closure member, means between the sleeve and the flow tube for biasing the flow tube in a direction for causing the valve closure member to move the closed position, releasable latch means between the sleeve and the flow tube initially holding the flow tube in position holding the valve closure member in the open position, a biased piston and cylinder assembly initially engaging the releasable latch and holding the latch engaged, the assembly being exposed on one side to pressure in the housing, and the housing and the sleeve including openings which when aligned by movement of the sleeve by well pressure allows fluid to be inserted into the bore from the outside of the housing.

  12. Spacetime encodings. III. Second order Killing tensors

    SciTech Connect

    Brink, Jeandrew

    2010-01-15

    This paper explores the Petrov type D, stationary axisymmetric vacuum (SAV) spacetimes that were found by Carter to have separable Hamilton-Jacobi equations, and thus admit a second-order Killing tensor. The derivation of the spacetimes presented in this paper borrows from ideas about dynamical systems, and illustrates concepts that can be generalized to higher-order Killing tensors. The relationship between the components of the Killing equations and metric functions are given explicitly. The origin of the four separable coordinate systems found by Carter is explained and classified in terms of the analytic structure associated with the Killing equations. A geometric picture of what the orbital invariants may represent is built. Requiring that a SAV spacetime admits a second-order Killing tensor is very restrictive, selecting very few candidates from the group of all possible SAV spacetimes. This restriction arises due to the fact that the consistency conditions associated with the Killing equations require that the field variables obey a second-order differential equation, as opposed to a fourth-order differential equation that imposes the weaker condition that the spacetime be SAV. This paper introduces ideas that could lead to the explicit computation of more general orbital invariants in the form of higher-order Killing tensors.

  13. Histone deacetylase inhibitors interact with melanoma differentiation associated-7/interleukin-24 to kill primary human glioblastoma cells.

    PubMed

    Hamed, Hossein A; Yacoub, Adly; Park, Margaret A; Archer, Kellie; Das, Swadesh K; Sarkar, Devanand; Grant, Steven; Fisher, Paul B; Dent, Paul

    2013-08-01

    We presently demonstrate that histone deacetylase inhibitors (HDACIs) enhance toxicity of melanoma differentiation-associated gene-7/interleukin 24 (mda-7/IL-24) in invasive primary human glioblastoma multiforme (GBM) cells. Additionally, a method is described to augment the efficacy of adenoviral delivery of mda-7/IL-24 in these cells. HDACIs synergized with melanoma differentiation-associated (MDA)-7/IL-24 killing GBM cells. Enhanced lethality correlated with increased autophagy that was dependent on the expression of ceramide synthase 6. HDACIs interacted with MDA-7/IL-24 prolonging generation of reactive oxygen species and Ca(2+). Quenching of reactive oxygen species and Ca(2+) blocked HDACI and MDA-7/IL-24 killing. In vivo MDA-7/IL-24 prolonged the survival of animals carrying orthotopic tumors, and HDACIs enhanced survival further. A serotype 5/3 adenovirus more effectively delivers mda-7/IL-24 to GBM tumors than a serotype 5 virus. Hence, we constructed a serotype 5/3 adenovirus that conditionally replicates in tumor cells expressing MDA-7/IL-24, in which the adenoviral early region 1A (E1A) gene was driven by the cancer-specific promoter progression elevated gene-3 [Ad.5/3 (INGN 241)-PEG-E1A-mda-7; also called Ad.5/3-CTV (cancer terminator virus)]. Ad.5/3-CTV increased the survival of mice carrying GBM tumors to a significantly greater extent than did a nonreplicative virus Ad.5/3-mda-7. Ad.5/3-CTV exhibited no toxicity in the brains of Syrian hamsters. Collectively our data demonstrate that HDACIs enhance MDA-7/IL-24 lethality, and adenoviral delivery of mda-7/IL-24 combined with tumor-specific viral replication is an effective preclinical GBM therapeutic.

  14. Killing Initial Data on spacelike conformal boundaries

    NASA Astrophysics Data System (ADS)

    Paetz, Tim-Torben

    2016-08-01

    We analyze Killing Initial Data on Cauchy surfaces in conformally rescaled vacuum space-times satisfying Friedrich's conformal field equations. As an application, we derive the KID equations on a spacelike ℐ-.

  15. Acts and omissions, killing and letting die.

    PubMed

    Gillon, R

    1986-01-11

    Gillon asks what, if any, moral importance resides in the distinction between killing and letting die in the context of medical care. He considers and rejects the acts and omissions doctrine, which claims that actions (killing) resulting in some undesirable end are in general morally worse than failures to act (allowing to die) that have the same result. He also refutes the argument that the moral distinction between killing and letting die is one of harming versus benefitting, and that a physician has a responsibility not to harm (kill) a patient but no duty to help (keep alive). Gillon concludes by discussing the moral claims upon which the Roman Catholic rejection of the acts and omissions doctrine is based, which are the subjects of his next British Medical Journal article on medical ethics.

  16. Killing vector fields and harmonic superfield theories

    SciTech Connect

    Groeger, Josua

    2014-09-15

    The harmonic action functional allows a natural generalisation to semi-Riemannian supergeometry, also referred to as harmonic, which resembles the supersymmetric sigma models studied in high energy physics. We show that Killing vector fields are infinitesimal supersymmetries of this harmonic action and prove three different Noether theorems in this context. En passant, we provide a homogeneous treatment of five characterisations of Killing vector fields on semi-Riemannian supermanifolds, thus filling a gap in the literature.

  17. Killing vector fields and harmonic superfield theories

    NASA Astrophysics Data System (ADS)

    Groeger, Josua

    2014-09-01

    The harmonic action functional allows a natural generalisation to semi-Riemannian supergeometry, also referred to as harmonic, which resembles the supersymmetric sigma models studied in high energy physics. We show that Killing vector fields are infinitesimal supersymmetries of this harmonic action and prove three different Noether theorems in this context. En passant, we provide a homogeneous treatment of five characterisations of Killing vector fields on semi-Riemannian supermanifolds, thus filling a gap in the literature.

  18. Is killing no worse than letting die?

    PubMed

    Nesbitt, W

    1995-01-01

    Those who wish to refute the view that it is worse to kill than to let die sometimes produce examples of cases in which an agent lets someone die but would be generally agreed to be no less reprehensible than if he had killed. It is argued that the examples produced typically possess a feature which makes their use in this context illegitimate, and that when modified to remove this feature, they provide support for the view which they were designed to undermine.

  19. Killing and letting die: hidden value assumptions.

    PubMed

    Atkinson, G

    1983-01-01

    In this paper I argue for several related theses: first, that the distinction between killing and letting die, as it is drawn by ordinary persons in ordinary contexts, is more complex than is generally understood; second, that the key feature of this complexity lies in the presence of a hidden normative component in what appears to be a straightforwardly descriptive distinction; and, third, that this complexity renders the killing/letting die distinction an inadequate and hazardous guide for moral reasoning.

  20. Lie algebra of conformal Killing-Yano forms

    NASA Astrophysics Data System (ADS)

    Ertem, Ümit

    2016-06-01

    We provide a generalization of the Lie algebra of conformal Killing vector fields to conformal Killing-Yano forms. A new Lie bracket for conformal Killing-Yano forms that corresponds to slightly modified Schouten-Nijenhuis bracket of differential forms is proposed. We show that conformal Killing-Yano forms satisfy a graded Lie algebra in constant curvature manifolds. It is also proven that normal conformal Killing-Yano forms in Einstein manifolds also satisfy a graded Lie algebra. The constructed graded Lie algebras reduce to the graded Lie algebra of Killing-Yano forms and the Lie algebras of conformal Killing and Killing vector fields in special cases.

  1. Hazardous materials in Fresh Kills landfill

    SciTech Connect

    Hirschhorn, J.S.

    1997-12-31

    No environmental monitoring and corrective action programs can pinpoint multiple locations of hazardous materials the total amount of them in a large landfill. Yet the consequences of hazardous materials in MSW landfills are considerable, in terms of public health concerns, environmental damage, and cleanup costs. In this paper a rough estimation is made of how much hazardous material may have been disposed in Fresh Kills landfill in Staten Island, New York. The logic and methods could be used for other MSW landfills. Fresh Kills has frequently been described as the world`s largest MSW landfill. While records of hazardous waste disposal at Fresh Kills over nearly 50 years of operation certainly do not exist, no reasonable person would argue with the conclusion that large quantities of hazardous waste surely have been disposed at Fresh Kills, both legally and illegally. This study found that at least 2 million tons of hazardous wastes and substances have been disposed at Fresh Kills since 1948. Major sources are: household hazardous waste, commercial RCRA hazardous waste, incinerator ash, and commercial non-RCRA hazardous waste, governmental RCRA hazardous waste. Illegal disposal of hazardous waste surely has contributed even more. This is a sufficient amount to cause serious environmental contamination and releases, especially from such a landfill without an engineered liner system, for example. This figure is roughly 1% of the total amount of waste disposed in Fresh Kills since 1948, probably at least 200 million tons.

  2. Killing of Actinobacillus actinomycetemcomitans by human lactoferrin.

    PubMed Central

    Kalmar, J R; Arnold, R R

    1988-01-01

    Actinobacillus actinomycetemcomitans is a fastidious, facultative gram-negative rod associated with endocarditis, certain forms of periodontal disease, and other focal infections. Human neutrophils have demonstrated bactericidal activity against A. actinomycetemcomitans, and much of the oxygen-dependent killing has been attributed to the myeloperoxidase-H2O2-halide system. However, the contribution of other neutrophil components to killing activity is obscure. Lactoferrin, an iron-binding glycoprotein, is a major constituent of neutrophil-specific granules and is also found in mucosal secretions. In this report, we show that human lactoferrin is bactericidal for A. actinomycetemcomitans. Killing activity required an unsaturated (iron- and anion-free) molecule that produced a 2-log decrease in viability within 120 min at 37 degrees C at a concentration of 1.9 microM. Besides exhibiting concentration dependence, killing kinetics were affected by minor variations in temperature and pH. Magnesium, a divalent cation thought to stabilize lipopolysaccharide interactions on the surface of gram-negative organisms, enhanced lactoferrin killing of A. actinomycetemcomitans, while other cations, such as potassium and calcium, had no effect. Our data suggest that lactoferrin contributes to killing of A. actinomycetemcomitans by human neutrophils and that it may also play a significant role in innate secretory defense against this potential periodontopathogen. PMID:3417349

  3. On the killing of mycobacteria by macrophages.

    PubMed

    Jordao, Luisa; Bleck, Christopher K E; Mayorga, Luis; Griffiths, Gareth; Anes, Elsa

    2008-02-01

    Both pathogenic and non-pathogenic mycobacteria are internalized into macrophage phagosomes. Whereas the non-pathogenic types are invariably killed by all macrophages, the pathogens generally survive and grow. Here, we addressed the survival, production of nitrogen intermediates (RNI) and intracellular trafficking of the non-pathogenic Mycobacterium smegmatis, the pathogen-like, BCG and the pathogenic M. bovis in different mouse, human and bovine macrophages. The bacteriocidal effects of RNI were restricted for all bacterial species to the early stages of infection. EM analysis showed clearly that all the mycobacteria remained within phagosomes even at late times of infection. The fraction of BCG and M. bovis found in mature phagolysosomes rarely exceeded 10% of total, irrespective of whether bacteria were growing, latent or being killed, with little correlation between the extent of phagosome maturation and the degree of killing. Theoretical modelling of our data identified two different potential sets of explanations that are consistent with our results. The model we favour is one in which a small but significant fraction of BCG is killed in an early phagosome, then maturation of a small fraction of phagosomes with both live and killed bacteria, followed by extremely rapid killing and digestion of the bacteria in phago-lysosomes.

  4. Female serial killing: review and case report.

    PubMed

    Frei, Andreas; Völlm, Birgit; Graf, Marc; Dittmann, Volker

    2006-01-01

    Single homicide committed by women is rare. Serial killing is very infrequent, and the perpetrators are usually white, intelligent males with sadistic tendencies. Serial killing by women has, however, also been described. To conduct a review of published literature on female serial killers and consider its usefulness in assessing a presenting case. A literature review was conducted, after searching EMBASE, MEDLINE and PsycINFO. The presenting clinical case is described in detail in the context of the literature findings. Results The literature search revealed few relevant publications. Attempts to categorize the phenomenon of female serial killing according to patterns of and motives for the homicides have been made by some authors. The most common motive identified was material gain or similar extrinsic gratification while the 'hedonistic' sadistic or sexual serial killer seems to be extremely rare in women. There is no consistent theory of serial killing by women, but psychopathic personality traits and abusive childhood experiences have consistently been observed. The authors' case did not fit the description of a 'typical' female serial killer. In such unusual circumstances as serial killing by a woman, detailed individual case formulation is required to make sense of the psychopathology in each case. Publication of cases in scientific journals should be encouraged to advance our understanding of this phenomenon. Copyright (c) 2006 John Wiley & Sons, Ltd.

  5. Kill fluid for oil field operations

    SciTech Connect

    Sydansk, R.D.

    1990-08-14

    This patent describes a process employing a kill fluid to substantially reduce the volumetric flow of formation fluid into a wellbore penetrating a formation containing the formation fluid below an earthen surface. It comprises: admixing components of a continuous flowing gel at the surface comprising of water-soluble carboxylate-containing polymer, a complex capable of crosslinking the polymer and formed of at least one electropositive chromium III species and at least one electronegative carboxylatespecies, and an aqueous solvent for the polymer and the complex; crosslinking the polymer and the complex to form the gel, wherein the kill fluid comprises the gel; placing a volume of the kill fluid in the wellbore sufficient to create a hydrostatic head which exerts a kill fluid pressure against the formation fluid substantially equal to or greater than the formation fluid pressure and thereby substantially reduces the volumetric flow of the formation fluid into the wellbore; performing an oil field operation after placing the volume of the kill fluid in the wellbore; and removing the gel from the wellbore to substantially restore the volumetric flow of the formation fluid into the wellbore.

  6. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be prepared...

  7. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be prepared...

  8. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be prepared...

  9. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be prepared...

  10. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be prepared...

  11. 'Total disability' and the wrongness of killing.

    PubMed

    Omelianchuk, Adam

    2015-08-01

    Walter Sinnott-Armstrong and Franklin G Miller recently argued that the wrongness of killing is best explained by the harm that comes to the victim, and that 'total disability' best explains the nature of this harm. Hence, killing patients who are already totally disabled is not wrong. I maintain that their notion of total disability is ambiguous and that they beg the question with respect to whether there are abilities left over that remain relevant for the goods of personhood and human worth. If these goods remain, then something more is lost in death than in 'total disability,' and their explanation of what makes killing wrong comes up short. But if total disability is equivalent with death, then their argument is an interesting one.

  12. Extracellular killing of inhaled pneumococci in rats

    SciTech Connect

    Coonrod, J.D.; Marple, S.; Holmes, G.P.; Rehm, S.R.

    1987-12-01

    Early clearance of inhaled Staphylococcus aureus is believed to be caused by phagocytosis by alveolar macrophages. In murine models inhaled pneumococci are cleared even more rapidly than S. aureus. Conventional opsonins appear to play no role in this clearance, and recently it has been shown that murine alveolar lining material contains free fatty acids and other soluble factors that are directly bactericidal for pneumococci. To determine whether non-phagocytic factors are involved in pneumococcal clearance, we compared the site of killing of inhaled pneumococci and S. aureus in rats using histologic methods and bronchoalveolar lavage. Spontaneous lysis of pneumococci was prevented by use of autolysin-defective pneumococci or by substitution of ethanolamine for choline in the cell wall. Histologic studies showed that the percent of inhaled staphylococci associated with alveolar macrophages always exceeded the percent of staphylococci cleared, whereas there was little association of pneumococci with macrophages during clearance. Analysis of the intracellular or extracellular location of iron 59 in bronchoalveolar lavage fluid of rats that had inhaled aerosols of /sup 59/Fe-labeled bacteria suggested that staphylococci were killed predominantly in macrophages and pneumococci in the extracellular space. When /sup 59/Fe-labeled pneumococci or staphylococci were ingested and killed by macrophages in vitro, the /sup 59/Fe remained with the macrophages, suggesting that the extracellular location of /sup 59/Fe during pneumococcal killing in vivo was not caused by rapid turnover of /sup 59/Fe in macrophages. Studies of the site of killing of inhaled type 25 pneumococci labeled exclusively in the cell wall with carbon 14-ethanolamine confirmed the results obtained with /sup 59/Fe-labeled pneumococci. Thus, early killing of inhaled pneumococci, unlike staphylococci, appears to take place outside of macrophages.

  13. HIV transcription is induced with cell killing

    SciTech Connect

    Woloschak, G.E.; Schreck, S.; Chang-Liu, Chin-Mei; Panozzo, J.; Libertin, C.R.

    1993-11-01

    In this report, we demonstrate that this induction of HIV-LTR transcription occurs when stably transfected HeLa cells are exposed to agents which mediate cell killing, such as UV radiation, electroporation of sucrose buffer, prolonged heating, and low and high pH. Cells cultured following UV exposure demonstrated a peak in CAT expression that is evident in viable (but not necessarily cell division-competent) cells 24 h after exposure; this inductive response continued until at least 72 h after exposure. HIV-LTR induction was dose-dependent, and the amount of CAT transcription induced was correlated with the amount of cell killing that occurred in the culture.

  14. Cytotoxic Killing and Immune Evasion by Repair

    NASA Astrophysics Data System (ADS)

    Chan, Cliburn; George, Andrew J. T.; Stark, Jaroslav

    2007-07-01

    The interaction between the immune system and pathogens is a complex one, with pathogens constantly developing new ways of evading destruction by the immune system. The immune system's task is made even harder when the pathogen in question is an intra-cellular one (such as a virus or certain bacteria) and it is necessary to kill the infected host cell in order to eliminate the pathogen. This causes damage to the host, and such killing therefore needs to be carefully controlled, particularly in tissues with poor regenerative potential, or those involved in the immune response itself. Host cells therefore possess repair mechanisms which can counteract killing by immune cells. These in turn can be subverted by pathogens which up-regulate the resistance of infected cells to killing. In this paper, we explore the hypothesis that this repair process plays an important role in determining the efficacy of evasion and escape from immune control. We model a situation where cytotoxic T lymphocytes (CTL) and natural killer (NK) cells kill pathogen-infected and tumour cells by directed secretion of preformed granules containing perforin and granzymes. Resistance to such killing can be conferred by the expression of serine protease inhibitors (serpins). These are utilized by several virally infected and tumour cells, as well as playing a role in the protection of host bystander, immune and immuneprivileged cells. We build a simple stochastic model of cytotoxic killing, where serpins can neutralize granzymes stoichiometrically by forming an irreversible complex, and the survival of the cell is determined by the balance between serpin depletion and replenishment, which in its simplest form is equivalent to the well known shot noise process. We use existing analytical results for this process, and additional simulations to analyse the effects of repair on cytotoxic killing. We then extend the model to the case of a replicating target cell population, which gives a branching process

  15. Ambiguities in 'killing' and 'letting die'.

    PubMed

    Atkinson, G M

    1983-05-01

    In a recent article Carla Kary (1980) attempts to show that there can be a significant moral difference between instances of killing and letting die. I shall maintain in Section I that Kary's argument is somewhat weakened by her failure to note an important ambiguity in the notion of killing a person. I shall also argue in Section II that a similar ambiguity affects the notion of letting someone die, and that failure to note this latter ambiguity also weakens the position developed by Robert Coburn (1980) with regard to defective newborns.

  16. Microbial killing activity of peracetic acid.

    PubMed

    Thamlikitkul, V; Trakulsomboon, S; Louisirirotchanakul, S; Chaiprasert, A; Foongladda, S; Thipsuvan, K; Arjratanakool, W; Kunyok, R; Wasi, C; Santiprasitkul, S; Danchaivijitr, S

    2001-10-01

    In vitro killing activity of peracetic acid (Perasafe) at a concentration of 0.26 per cent w/v was tested against Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Salmonella paratyphi A, Acinetobacter baumannii, Sternotrophomonas maltophilia, Enterococcus faecium, Enterococcus faecalis, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis spore, Mycobacterium tuberculosis and human immuno-deficiency virus type I. Exposure to Peracetic acid (0.26% w/v) for 10 minutes resulted in massive killing of all the aforementioned organisms and spore.

  17. Can Vet Schools Teach without Killing Animals?

    ERIC Educational Resources Information Center

    Mangan, Katherine S.

    2000-01-01

    Discusses a protest by students at the University of Illinois (Urbana) College of Veterinary Medicine over the killing of animals that led to temporary curtailing of lethal animal experiments. Examines the conflict between animal rights groups and some faculty who are openly skeptical about the effectiveness of alternatives to the hands-on…

  18. Mass killings and detection of impacts

    NASA Technical Reports Server (NTRS)

    Mclaren, Digby J.

    1988-01-01

    Highly energetic bolide impacts occur and their flux is known. For larger bodies the energy release is greater than for any other short-term global phenomenon. Such impacts produce or release a large variety of shock induced changes including major atmospheric, sedimentologic, seismic and volcanic events. These events must necessarily leave a variety of records in the stratigraphic column, including mass killings resulting in major changes in population density and reduction or extinction of many taxonomic groups, followed by characteristic patterns of faunal and flora replacement. Of these effects, mass killings, marked by large-scale loss of biomass, are the most easily detected evidence in the field but must be manifest on a near-global scale. Such mass killings that appear to be approximately synchronous and involve disappearance of biomass at a bedding plane in many sedimentologically independent sections globally suggest a common cause and probable synchroneity. Mass killings identify an horizon which may be examined for evidence of cause. Geochemical markers may be ephemeral and absence may not be significant. There appears to be no reason why ongoing phenomena such as climate and sea-level changes are primary causes of anomolous episodic events.

  19. School Shootings; Standards Kill Students and Society

    ERIC Educational Resources Information Center

    Angert, Betsy L.

    2008-01-01

    School shootings have been in the news of late. People ponder what occurs in classrooms today. Why would a young person wish to take a life? Within educational institutions, the killings are a concern. In our dire attempt to teach the children and ensure student success, it seems many of our offspring are lost. Some students feel separate from…

  20. Can Vet Schools Teach without Killing Animals?

    ERIC Educational Resources Information Center

    Mangan, Katherine S.

    2000-01-01

    Discusses a protest by students at the University of Illinois (Urbana) College of Veterinary Medicine over the killing of animals that led to temporary curtailing of lethal animal experiments. Examines the conflict between animal rights groups and some faculty who are openly skeptical about the effectiveness of alternatives to the hands-on…

  1. Nonlinear symmetries on spaces admitting Killing tensors

    NASA Astrophysics Data System (ADS)

    Visinescu, Mihai

    2010-04-01

    Nonlinear symmetries corresponding to Killing tensors are investigated. The intimate relation between Killing-Yano tensors and non-standard supersymmetries is pointed out. The gravitational anomalies are absent if the hidden symmetry is associated with a Killing-Yano tensor. In the case of the nonlinear symmetries the dynamical algebras of the Dirac-type operators is more involved and could be organized as infinite dimensional algebras or superalgebras. The general results are applied to some concrete spaces involved in theories of modern physics. As a first example it is considered the 4-dimensional Euclidean Taub-NUT space and its generalizations introduced by Iwai and Katayama. One presents the infinite dimensional superalgebra of Dirac type operators on Taub-NUT space that could be seen as a graded loop superalgebra of the Kac-Moody type. The axial anomaly, interpreted as the index of the Dirac operator, is computed for the generalized Taub-NUT metrics. Finally the existence of the conformal Killing-Yano tensors is investigated for some spaces with mixed Sasakian structures.

  2. Killing Hitler: A Writer's Journey and Angst.

    ERIC Educational Resources Information Center

    Thaler, Paul

    2002-01-01

    Describes the author's experiences in preparing a talk that "evokes the specter" of Adolf Hitler and in writing an historical account of a British plot to kill Hitler. Address the question of why the British allowed him to live that final year of the war. Muses on why scholars write, and the impact of violence and terrorism. (SG)

  3. Peanut Roaster Temperatures Relative to Salmonella Kill

    USDA-ARS?s Scientific Manuscript database

    ARS, Market Quality and Handling Research Unit, Raleigh NC 27695 In response to the limited peanut butter contamination incident of 2006/7, studies were initiated to examine the effect of various time and temperature protocols on log kill levels for Salmonella on peanuts. The objective of the work ...

  4. The evolution of reduced microbial killing.

    PubMed

    Vriezen, Jan A C; Valliere, Michael; Riley, Margaret A

    2009-10-20

    Bacteria engage in a never-ending arms race in which they compete for limited resources and niche space. The outcome of this intense interaction is the evolution of a powerful arsenal of biological weapons. Perhaps the most studied of these are colicins, plasmid-based toxins produced by and active against Escherichia coli. The present study was designed to explore the molecular responses of a colicin-producing strain during serial transfer evolution. What evolutionary changes occur when colicins are produced with no target present? Can killing ability be maintained in the absence of a target? To address these, and other, questions, colicinogenic strains and a noncolicinogenic ancestor were evolved for 253 generations. Samples were taken throughout the experiment and tested for killing ability. By the 38th transfer, a decreased killing ability and an increase in fitness were observed in the colicin-producing strains. Surprisingly, DNA sequence determination of the colicin plasmids revealed no changes in plasmid sequences. However, a set of chromosomally encoded loci experienced changes in gene expression that were positively associated with the reduction in killing. The most significant expression changes were observed in DNA repair genes (which were downregulated in the evolved strains), Mg ion uptake genes (which were upregulated), and late prophage genes (which were upregulated). These results indicate a fine-tuned response to the evolutionary pressures of colicin production, with far more genes involved than had been anticipated.

  5. Integrating Poetry and "To Kill a Mockingbird."

    ERIC Educational Resources Information Center

    Jolley, Susan Arpajian

    2002-01-01

    Outlines a method of teaching "To Kill a Mockingbird" along with the study of poetry. Notes that this method allows students to consider the themes of courage and developing compassion. Concludes that teaching such a multigenre unit allows students to look for connections among fact and fiction, the past and present, their own lives and…

  6. Killing symmetry on the Finsler manifold

    NASA Astrophysics Data System (ADS)

    Ootsuka, Takayoshi; Yahagi, Ryoko; Ishida, Muneyuki

    2017-05-01

    Symmetry and conservation law are discussed on the Finsler manifold M. We adopt the point Finsler approach, where we consider the geometry on a point manifold M not on TM. Generalized vector fields are defined on oriented curves on M, and Finsler non-linear connections are considered on M, not on the tangent space TM. Killing vector fields K are defined as generalized vector fields as {{L}K}F=\\text{d}B , and the Killing symmetry is also reformulated simply as S{{K}\\flat}=0 by using the Killing 1-form {{K}\\flat} and the spray operator S defined by using the non-linear connection. {{K}\\flat} is related to the generalization of Killing tensors on the Finsler manifold, and our ansatz of {{K}\\flat} and S{{K}\\flat}=0 give an analytical method of finding higher derivative conserved quantities, which may be called hidden conserved quantities. We show two examples: the Carter constant on Kerr spacetime and the Runge-Lentz vectors in Newtonian gravity.

  7. A moral dilemma: killing and letting die.

    PubMed

    Johnson, K

    Most health care professionals believe that there is a clear difference between killing and letting die, i.e. between active and passive euthanasia. Philosophers, however, have repeatedly attacked the moral validity of their argument. This article explores various related issues and theoretical approaches to the distinction between acts and omissions.

  8. A moral dilemma: killing and letting die.

    PubMed

    Johnson, Kath

    1993-06-24

    Most health care professionals believe that there is a clear difference between killing and letting die, i.e. between active and passive euthanasia. Philosophers, however, have repeatedly attacked the moral validity of their argument. This article explores various related issues and theoretical approaches to the distinction between acts and omissions.

  9. Killing Hitler: A Writer's Journey and Angst.

    ERIC Educational Resources Information Center

    Thaler, Paul

    2002-01-01

    Describes the author's experiences in preparing a talk that "evokes the specter" of Adolf Hitler and in writing an historical account of a British plot to kill Hitler. Address the question of why the British allowed him to live that final year of the war. Muses on why scholars write, and the impact of violence and terrorism. (SG)

  10. Contagion in Mass Killings and School Shootings.

    PubMed

    Towers, Sherry; Gomez-Lievano, Andres; Khan, Maryam; Mubayi, Anuj; Castillo-Chavez, Carlos

    2015-01-01

    Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at-risk individuals to commit similar acts. Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed). We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event. We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015). We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001). All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings.

  11. Contagion in Mass Killings and School Shootings

    PubMed Central

    Towers, Sherry; Gomez-Lievano, Andres; Khan, Maryam; Mubayi, Anuj; Castillo-Chavez, Carlos

    2015-01-01

    Background Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at-risk individuals to commit similar acts. Methods Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed). We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event. Conclusions We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015). We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001). All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings. PMID:26135941

  12. Bovine polymorphonuclear leukocyte killing of Tritrichomonas foetus.

    PubMed

    Aydintug, M K; Widders, P R; Leid, R W

    1993-07-01

    The role of bovine antibody and complement in bovine neutrophil-mediated killing of Tritrichomonas foetus was investigated. No neutrophil-mediated trichomonacidal activity was detected when Hanks' balanced salt solution, a widely utilized and weakly buffered medium, was used. This lack of neutrophil activity was evident even in the presence of specific bovine antibody and bovine complement. Moreover, the pH of the weakly buffered Hanks' balanced salt solution was observed to fall from pH 7.0 to 5.8 in 4 h at 37 degrees C in the presence of T. foetus. The pH of 5.8 inhibited the bactericidal activity of bovine neutrophils for Staphylococcus epidermidis by 53.2% and may have contributed to the lack of neutrophil-mediated trichomonacidal activity in the weakly buffered salt solution. However, T. foetus was susceptible to bovine neutrophil-mediated destruction when a HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered Hanks' balanced salt solution was used (21.8% killing by neutrophils alone). Neither specific bovine immune serum nor purified immune bovine immunoglobulin G2 alone enhanced bovine neutrophil-mediated killing. When complement-sensitized trichomonads were incubated with bovine neutrophils, killing of T. foetus was observed, a result which represented the additive effects of each treatment. Significant (P < 0.05) killing of trichomonads was observed when antibody- and complement-opsonized trichomonads were exposed to bovine neutrophils (> 70% parasite destruction), an effect which reflected the additive nature of each treatment.

  13. 75 FR 30299 - Drawbridge Operation Regulations; Newtown Creek, Dutch Kills, English Kills, and Their...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ... Kills, and Their Tributaries, NY, Maintenance AGENCY: Coast Guard, DHS. ACTION: Notice of temporary... closures to facilitate bridge rehabilitation maintenance. DATES: This deviation is effective from July 5... regulations to facilitate scheduled bridge rehabilitation maintenance. Under this temporary deviation the...

  14. The Combination of Rifampin plus Moxifloxacin Is Synergistic for Suppression of Resistance but Antagonistic for Cell Kill of Mycobacterium tuberculosis as Determined in a Hollow-Fiber Infection Model

    PubMed Central

    Drusano, G. L.; Sgambati, Nicole; Eichas, Adam; Brown, David L.; Kulawy, Robert; Louie, Arnold

    2010-01-01

    Moxifloxacin is under development for expanded use against Mycobacterium tuberculosis. Rifampin is a mainstay of therapy. We examined the interaction of moxifloxacin plus rifampin for log-phase and nonreplicating persister (NRP) organisms. For this evaluation, we employed our hollow-fiber infection model, in which organisms are exposed to clinically relevant drug concentration-time profiles and the impact on bacterial cell kill and resistant subpopulation amplification is determined. In log phase, resistance emergence was observed in all monotherapy regimens and in no combination therapy regimen. No difference was seen in time to a 3-log reduction in the bacterial burden; there was a significant difference in time to resistance emergence (P = 0.0006). In the NRP experiment, no resistance emergence was seen. There was a significant difference between the monotherapy and combination therapy regimens in time to a 3-log reduction in the bacterial burden (P = 0.042). The combination is efficacious for suppressing resistant organisms but is antagonistic for cell kill. PMID:20802826

  15. Conformal killing tensors and covariant Hamiltonian dynamics

    SciTech Connect

    Cariglia, M.; Gibbons, G. W.; Holten, J.-W. van; Horvathy, P. A.; Zhang, P.-M.

    2014-12-15

    A covariant algorithm for deriving the conserved quantities for natural Hamiltonian systems is combined with the non-relativistic framework of Eisenhart, and of Duval, in which the classical trajectories arise as geodesics in a higher dimensional space-time, realized by Brinkmann manifolds. Conserved quantities which are polynomial in the momenta can be built using time-dependent conformal Killing tensors with flux. The latter are associated with terms proportional to the Hamiltonian in the lower dimensional theory and with spectrum generating algebras for higher dimensional quantities of order 1 and 2 in the momenta. Illustrations of the general theory include the Runge-Lenz vector for planetary motion with a time-dependent gravitational constant G(t), motion in a time-dependent electromagnetic field of a certain form, quantum dots, the Hénon-Heiles and Holt systems, respectively, providing us with Killing tensors of rank that ranges from one to six.

  16. Deprivations, futures and the wrongness of killing.

    PubMed

    Marquis, D

    2001-12-01

    In my essay, Why abortion is immoral, I criticised discussions of the morality of abortion in which the crucial issue is whether fetuses are human beings or whether fetuses are persons. Both argument strategies are inadequate because they rely on indefensible assumptions. Why should being a human being or being a person make a moral difference? I argued that the correct account of the morality of abortion should be based upon a defensible account of why killing children and adults is wrong. I claimed that what makes killing us wrong is that our premature deaths deprive us of our futures of value, that is, the goods of life we would have experienced had we survived. This account of the wrongness of killing explains why killing is one of the worst of crimes and how killing greatly harms the victim. It coheres with the attitudes of those with cancer or HIV facing premature death. It explains why we believe it is wrong to kill infants (as personhood theories do not). It does not entail that it wrongs a human being to end her life if she is in persistent vegetative state or if her future must consist only of unbearable physical suffering and she wants to die (as sanctity of human life theories do not). This account of the wrongness of killing implies (with some defensible additional assumptions) that abortion is immoral because we were fetuses once and we know those fetuses had futures of value. Mark Brown claims that this potential future of value account is unsound because it implies that we have welfare rights to what we need to stay alive that most people would reject. I argue that Brown is incorrect in two ways: a welfare right to what we need to stay alive is not directly implied by my account and, in addition, most of us do believe that dependent human beings have substantial welfare rights to what they need to stay alive. Brown argues that depriving us of a future of value of which we have mental representations both is a better explanation of the wrongness of

  17. Parricide: Children Who Kill Their Parents

    DTIC Science & Technology

    1988-01-01

    adolescents who kill their parents. The research centers on who is the offender, why he or she has used parricide as a solution to an unresolvable problem...parricide. Conclusions Reached Based on the results of the literature review three conclusions were reached. First, adolescents who commit parricide have been...at the hands of their abuser. Secondly, the treatment of these adolescents by the criminal justice system varies greatly depending on the willingness

  18. 11. GENERAL INTERIOR VIEW OF KILLING FLOOR ON LEVEL 4; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. GENERAL INTERIOR VIEW OF KILLING FLOOR ON LEVEL 4; LOOKING SOUTHWEST TOWARD SPLITTERS' PLATFORMS - Rath Packing Company, Beef Killing Building, Sycamore Street between Elm & Eighteenth Streets, Waterloo, Black Hawk County, IA

  19. GOETHALS BRIDGE FROM NORTH SIDE OVER ARTHUR KILL. RAILROAD BRIDGE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GOETHALS BRIDGE FROM NORTH SIDE OVER ARTHUR KILL. RAILROAD BRIDGE IN FOREGROUND - Goethals Bridge, Spanning Arthur Kill from New Jersey to Staten Island, Staten Island (subdivision), Richmond County, NY

  20. HIV transcription is induced with cell killing

    SciTech Connect

    Woloschak, G.E.; Schreck, S.; Chang-Liu, Chin Mei; Panozzo, J.; Libertin, C.R.

    1994-01-01

    Previous work has shown that HeLa cells stably transfected with an HIV-LTR-CAT construct are induced to express chloramphenicol acetyl transferase (CAT) following exposure to DNA-damaging agents such as ultraviolet radiation, {gamma} rays, neutrons, and others. In this report, the authors demonstrate that this induction of HIV-LTR transcription occurs when stably transfected HeLa cells are exposed to agents which mediate cell killing, such as UV radiation, electroporation of sucrose buffer, prolonged heating, and low and high pH. Cells cultured following UV exposure demonstrated a peak in CAT expression that is evidence in viable (but not necessarily cell division-competent) cells 24 h after exposure; this inductive response continued until at least 72 h after exposure. HIV-LTR induction was dose-dependent, and the amount of CAT transcription induced was correlated with the amount of cell killing that occurred in the culture. Other agents which caused no cell killing (such as heat-shock for up to 2 h, treatment with metronidazole, exposure to sunlight, vitamin C treatment, and others) had no effect on HIV-LTR induction. These results suggest that HIV transcription is induced as a consequence of the turn on of a cellular death or apoptotic pathway.

  1. Designing surfaces that kill bacteria on contact

    PubMed Central

    Tiller, Joerg C.; Liao, Chun-Jen; Lewis, Kim; Klibanov, Alexander M.

    2001-01-01

    Poly(4-vinyl-N-alkylpyridinium bromide) was covalently attached to glass slides to create a surface that kills airborne bacteria on contact. The antibacterial properties were assessed by spraying aqueous suspensions of bacterial cells on the surface, followed by air drying and counting the number of cells remaining viable (i.e., capable of growing colonies). Amino glass slides were acylated with acryloyl chloride, copolymerized with 4-vinylpyridine, and N-alkylated with different alkyl bromides (from propyl to hexadecyl). The resultant surfaces, depending on the alkyl group, were able to kill up to 94 ± 4% of Staphylococcus aureus cells sprayed on them. A surface alternatively created by attaching poly(4-vinylpyridine) to a glass slide and alkylating it with hexyl bromide killed 94 ± 3% of the deposited S. aureus cells. On surfaces modified with N-hexylated poly(4-vinylpyridine), the numbers of viable cells of another Gram-positive bacterium, Staphylococcus epidermidis, as well as of the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, dropped more than 100-fold compared with the original amino glass. In contrast, the number of viable bacterial cells did not decline significantly after spraying on such common materials as ceramics, plastics, metals, and wood. PMID:11353851

  2. Designing surfaces that kill bacteria on contact.

    PubMed

    Tiller, J C; Liao, C J; Lewis, K; Klibanov, A M

    2001-05-22

    Poly(4-vinyl-N-alkylpyridinium bromide) was covalently attached to glass slides to create a surface that kills airborne bacteria on contact. The antibacterial properties were assessed by spraying aqueous suspensions of bacterial cells on the surface, followed by air drying and counting the number of cells remaining viable (i.e., capable of growing colonies). Amino glass slides were acylated with acryloyl chloride, copolymerized with 4-vinylpyridine, and N-alkylated with different alkyl bromides (from propyl to hexadecyl). The resultant surfaces, depending on the alkyl group, were able to kill up to 94 +/- 4% of Staphylococcus aureus cells sprayed on them. A surface alternatively created by attaching poly(4-vinylpyridine) to a glass slide and alkylating it with hexyl bromide killed 94 +/- 3% of the deposited S. aureus cells. On surfaces modified with N-hexylated poly(4-vinylpyridine), the numbers of viable cells of another Gram-positive bacterium, Staphylococcus epidermidis, as well as of the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, dropped more than 100-fold compared with the original amino glass. In contrast, the number of viable bacterial cells did not decline significantly after spraying on such common materials as ceramics, plastics, metals, and wood.

  3. Designing surfaces that kill bacteria on contact

    NASA Astrophysics Data System (ADS)

    Tiller, Joerg C.; Liao, Chun-Jen; Lewis, Kim; Klibanov, Alexander M.

    2001-05-01

    Poly(4-vinyl-N-alkylpyridinium bromide) was covalently attached to glass slides to create a surface that kills airborne bacteria on contact. The antibacterial properties were assessed by spraying aqueous suspensions of bacterial cells on the surface, followed by air drying and counting the number of cells remaining viable (i.e., capable of growing colonies). Amino glass slides were acylated with acryloyl chloride, copolymerized with 4-vinylpyridine, and N-alkylated with different alkyl bromides (from propyl to hexadecyl). The resultant surfaces, depending on the alkyl group, were able to kill up to 94 ± 4% of Staphylococcus aureus cells sprayed on them. A surface alternatively created by attaching poly(4-vinylpyridine) to a glass slide and alkylating it with hexyl bromide killed 94 ± 3% of the deposited S. aureus cells. On surfaces modified with N-hexylated poly(4-vinylpyridine), the numbers of viable cells of another Gram-positive bacterium, Staphylococcus epidermidis, as well as of the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, dropped more than 100-fold compared with the original amino glass. In contrast, the number of viable bacterial cells did not decline significantly after spraying on such common materials as ceramics, plastics, metals, and wood.

  4. Killing, letting die, and withdrawing aid.

    PubMed

    McMahan, Jeff

    1993-01-01

    One of the aims of this article is to contribute to the identification of the empirical criteria governing the use of the concepts of killing and letting die. I will not attempt a comprehensive analysis of the concepts but will limit the inquiry to certain problematic cases -- namely, cases involving the removal or withdrawal of life-supporting aid or protection. The analysis of these cases will, however, shed light on the criteria for distinguishing killing and letting die in other cases as well. My overall aims in the article are partly constructive and partly skeptical. I hope to advance our understanding of the nature of the distinction between killing and letting die. This, I believe, will enable us to defend the moral relevance of the distinction against certain objections -- in particular, objections that claim that the distinction fails to coincide with commonsense moral intuitions. Yet I will suggest that, as we get clearer about the nature of the distinction and the sources of its intuitive appeal, it may seem that the intuitions it supports are not so well grounded as one could wish.

  5. Killing spinors, twistor - spinors and Hijazi inequality

    NASA Astrophysics Data System (ADS)

    Lichnerowicz, Andre

    Let (W, g) be a spin manifold of dimension n. In terms of the Dirac operator P of (W, g), we introduce on the spinor fields a conformally covariant first-order operator D that is strictly connected with the twistor-spinors. We show that the operator (Δ - ρ) (ρ = (n/4(n - 1))R) is positive. For a compact spin manifold of dimension n ⩾ 3, the existences of harmonic spinors and twistor-spinors ≠ O are mutually exclusive, except for the parallel spinors. By means of a universal formula, we show that the Hijazi inequality [8] holds for every spinor field such that (Pψ, Pψ) = λ 2(ψ, ψ) (λ = const). In the limiting case, the manifold admits a Killing spinor which can be evaluated in terms of ψ. Using the Yamabe-Schoen theorem [15], we prove that, if the space K of the twistor-spinors of (W, g) is not reduced to zero, there is a conformal change of the metric g giving a manifold with Killing spinors ≠ 0. Interpretation of dim K in terms of these spaces of Killing spinors. If the compact spin manifold (W, g) of dimension n ⩾ 3 is not conformally isometric with the sphere, every twistor-spinor is without zero on W.

  6. 9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Newcastle Disease Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.205 Newcastle Disease Vaccine, Killed Virus. Newcastle Disease Vaccine... Newcastle disease virus supplied by or approved by Veterinary Services and the vaccinates observed each...

  7. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... postvaccination, challenge 20 vaccinates and 10 controls by eyedrop with a virulent infectious bursal...

  8. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... postvaccination, challenge 20 vaccinates and 10 controls by eyedrop with a virulent infectious bursal...

  9. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Bursal Disease Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine... postvaccination, challenge 20 vaccinates and 10 controls by eyedrop with a virulent infectious bursal...

  10. Road-Killed Animals as Resources for Ecological Studies.

    ERIC Educational Resources Information Center

    Adams, Clark E.

    1983-01-01

    Summarizes 19 literature sources identifying road-killed vertebrates and frequency of kill by numbers. Examples of how these animals can be incorporated into curricula (integrating biology, society, people, and values) are given, followed by an illustrated example of how a road-killed raccoon's skull demonstrated a human/wildlife interaction prior…

  11. It's not just conflict that motivates killing of orangutans.

    PubMed

    Davis, Jacqueline T; Mengersen, Kerrie; Abram, Nicola K; Ancrenaz, Marc; Wells, Jessie A; Meijaard, Erik

    2013-01-01

    We investigated why orangutans are being killed in Kalimantan, Indonesia, and the role of conflict in these killings. Based on an analysis of interview data from over 5,000 respondents in over 450 villages, we also assessed the socio-ecological factors associated with conflict and non-conflict killings. Most respondents never kill orangutans. Those who reported having personally killed an orangutan primarily did so for non-conflict reasons; for example, 56% of these respondents said that the reason they had killed an orangutan was to eat it. Of the conflict-related reasons for killing, the most common reasons orangutans were killed was fear of orangutans or in self-defence. A similar pattern was evident among reports of orangutan killing by other people in the villages. Regression analyses indicated that religion and the percentage of intact forest around villages were the strongest socio-ecological predictors of whether orangutans were killed for conflict or non-conflict related reasons. Our data indicate that between 44,170 and 66,570 orangutans were killed in Kalimantan within the respondents' active hunting lifetimes: between 12,690 and 29,024 for conflict reasons (95%CI) and between 26,361 and 41,688 for non-conflict reasons (95% CI). These findings confirm that habitat protection alone will not ensure the survival of orangutans in Indonesian Borneo, and that effective reduction of orangutan killings is urgently needed.

  12. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine...

  13. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine...

  14. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  15. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine...

  16. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Parvovirus Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine...

  17. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  18. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Parvovirus Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine...

  19. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  20. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  1. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  2. Road-Killed Animals as Resources for Ecological Studies.

    ERIC Educational Resources Information Center

    Adams, Clark E.

    1983-01-01

    Summarizes 19 literature sources identifying road-killed vertebrates and frequency of kill by numbers. Examples of how these animals can be incorporated into curricula (integrating biology, society, people, and values) are given, followed by an illustrated example of how a road-killed raccoon's skull demonstrated a human/wildlife interaction prior…

  3. 7 CFR 29.1018 - Fire-killed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Fire-killed. 29.1018 Section 29.1018 Agriculture... Type 92) § 29.1018 Fire-killed. Any leaf of which 5 percent or more of its surface has a set green... tobacco may be described as fire-killed. (See Rule 23.)...

  4. 7 CFR 29.1018 - Fire-killed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Fire-killed. 29.1018 Section 29.1018 Agriculture... Type 92) § 29.1018 Fire-killed. Any leaf of which 5 percent or more of its surface has a set green... tobacco may be described as fire-killed. (See Rule 23.)...

  5. 78 FR 43063 - Drawbridge Operation Regulations; Arthur Kill, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Arthur Kill, NY AGENCY: Coast Guard... District, has issued a temporary deviation from the regulations governing the operation of the Arthur Kill AK Railroad Bridge across Arthur Kill, mile 11.6, between Staten Island, New York and Elizabeth,...

  6. Noether versus Killing symmetry of conformally flat Friedmann metric

    NASA Astrophysics Data System (ADS)

    Bokhari, Ashfaque H.; Kara, A. H.

    2007-12-01

    In a recent study Noether symmetries of some static spacetime metrics in comparison with Killing vectors of corresponding spacetimes were studied. It was shown that Noether symmetries provide additional conservation laws that are not given by Killing vectors. In an attempt to understand how Noether symmetries compare with conformal Killing vectors, we find the Noether symmetries of the flat Friedmann cosmological model. We show that the conformally transformed flat Friedman model admits additional conservation laws not given by the Killing or conformal Killing vectors. Inter alia, these additional conserved quantities provide a mechanism to twice reduce the geodesic equations via the associated Noether symmetries.

  7. Dynamic kill: controlling wild wells a new way

    SciTech Connect

    Blount, E.M.; Soeiinah, E.

    1981-10-01

    Dynamic kill describes a technique for terminating a blowout utilizing flowing frictional pressure to supplement the hydrostatic pressure of the kill fluid being injected through the relief well and up the blowing well. Therefore, a lighter kill fluid such as water can be implemented. The objective is to allow a blowout to be killed without breaking down the formation so the maximum amount of fluid can be circulated through the relief well by not losing fluid to a fractured formation. This allows optimum control during the kill operation and stable communication between the two wells. By allowing more fluid to be applied to the kill through one relief well, dynamic kill also increases the probability that one relief well will be sufficient. When the well is dynamically dead, the initial kill fluid, which will usually be too light to hold the well dead in a static condition, is replaced with a heavier kill mud. In fact, three weights of mud may be required to allow control during the transition from low density initial dynamic kill mud to heavy final kill mud. 5 refs.

  8. Triops (Entomostraca) eggs killed only by boiling.

    PubMed

    Carlisle, D B

    1968-07-19

    Temporary rainpools near Khartoum, Sudan, are inhabited by the notostracan crustacean Triops which completes its life cycle within 4 weeks. The annual rains fall in late summer, and throughout the winter and early summer the eggs of Triops remain in the dried mud or dust where they may be exposed to temperatures up to 80 degrees C. Laboratory experiments show that they can withstand temperatures up to within 1 degrees C of boiling, but are killed in partial vacuum by 70 degrees C, at atmospheric pressure by 100 degrees C, or under pressure by 105 degrees C. Exposure to high temperature seems to be necessary to break the egg diapause.

  9. The killing efficiency of soft iron shot

    USGS Publications Warehouse

    Andrews, R.; Longcore, J.R.

    1969-01-01

    A cooperative research effort between the ammunition industry and the Bureau of Sport Fisheries and Wildlife is aimed at finding a suitable non-toxic substitute for lead shot. A contract study by an independent research organization evaluated ways of coating or detoxifying lead shot or replacing it with another metal. As a result of that study, the only promising candidate is soft iron. Previous tests of hard iron shot had suggested that its killing effectiveness was poor at longer ranges due to the lower density. In addition, its hardness caused excessive damage to shotgun barrels. A unique, automated shooting facility was constructed at the Patuxent Wildlife Research Center to test the killing effectiveness of soft iron shot under controlled conditions. Tethered game-farm mallards were transported across a shooting point in a manner simulating free flight. A microswitch triggered a mounted shotgun so that each shot was 'perfect.' A soft iron shot, in Number 4 size, was produced by the ammunition industry and loaded in 12-gauge shells to give optimum ballistic performance. Commercial loads of lead shot in both Number 4 and Number 6 size were used for comparison. A total of 2,010 ducks were shot at ranges of 30 to 65 yards and at broadside and head-on angles in a statistically designed procedure. The following data were recorded for each duck: time until death, broken wing or leg bones, and number of embedded shot. Those ducks not killed outright were held for 10 days. From these data, ducks were categorized as 'probably bagged,' 'probably lost cripples,' or survivors. The test revealed that the killing effectiveness of this soft iron shot was superior to its anticipated performance and close to that obtained with commercial lead loads containing an equal number of pellets. Bagging a duck, in terms of rapid death or broken wing, was primarily dependent on the probability of a shot striking that vital area, and therefore a function of range. There was no indication

  10. Bacterial Killing by Dry Metallic Copper Surfaces▿

    PubMed Central

    Santo, Christophe Espírito; Lam, Ee Wen; Elowsky, Christian G.; Quaranta, Davide; Domaille, Dylan W.; Chang, Christopher J.; Grass, Gregor

    2011-01-01

    Metallic copper surfaces rapidly and efficiently kill bacteria. Cells exposed to copper surfaces accumulated large amounts of copper ions, and this copper uptake was faster from dry copper than from moist copper. Cells suffered extensive membrane damage within minutes of exposure to dry copper. Further, cells removed from copper showed loss of cell integrity. Acute contact with metallic copper surfaces did not result in increased mutation rates or DNA lesions. These findings are important first steps for revealing the molecular sensitive targets in cells lethally challenged by exposure to copper surfaces and provide a scientific explanation for the use of copper surfaces as antimicrobial agents for supporting public hygiene. PMID:21148701

  11. Micro-sociology of mass rampage killings.

    PubMed

    Collins, Randall

    2014-01-01

    Spectacular but very rare violent events such as mass killings by habitual non-criminals cannot be explained by factors which are very widespread, such as possession of firearms, being a victim of bullying, an introvert, or a career failure. A stronger clue is clandestine preparation of attack by one or two individuals, against randomly chosen representatives of a hated collective identity. Mass killers develop a deep back-stage, obsessed with planning their attack, overcoming social inferiority and isolation by an emotion of clandestine excitement.

  12. Kill: boosting HIV-specific immune responses.

    PubMed

    Trautmann, Lydie

    2016-07-01

    Increasing evidence suggests that purging the latent HIV reservoir in virally suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV-infected cells ('Shock and Kill' strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in-vivo and in-silico models to accelerate the design of new clinical trials. New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment.

  13. The Calabi complex and Killing sheaf cohomology

    NASA Astrophysics Data System (ADS)

    Khavkine, Igor

    2017-03-01

    It has recently been noticed that the degeneracies of the Poisson bracket of linearized gravity on constant curvature Lorentzian manifold can be described in terms of the cohomologies of a certain complex of differential operators. This complex was first introduced by Calabi and its cohomology is known to be isomorphic to that of the (locally constant) sheaf of Killing vectors. We review the structure of the Calabi complex in a novel way, with explicit calculations based on representation theory of GL(n) , and also some tools for studying its cohomology in terms of locally constant sheaves. We also conjecture how these tools would adapt to linearized gravity on other backgrounds and to other gauge theories. The presentation includes explicit formulas for the differential operators in the Calabi complex, arguments for its local exactness, discussion of generalized Poincaré duality, methods of computing the cohomology of locally constant sheaves, and example calculations of Killing sheaf cohomologies of some black hole and cosmological Lorentzian manifolds.

  14. 75 FR 62469 - Drawbridge Operation Regulations; Newtown Creek, Dutch Kills, English Kills, and Their...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... Kills, and Their Tributaries, NY, Maintenance AGENCY: Coast Guard, DHS. ACTION: Notice of temporary... facilitate bridge rehabilitation maintenance. DATES: This deviation is effective from October 26, 2010... scheduled bridge rehabilitation maintenance previously authorized for two six-week closures from July 5...

  15. Where and How Wolves (Canis lupus) Kill Beavers (Castor canadensis)

    PubMed Central

    Gable, Thomas D.; Windels, Steve K.; Bruggink, John G.; Homkes, Austin T.

    2016-01-01

    Beavers (Castor canadensis) can be a significant prey item for wolves (Canis lupus) in boreal ecosystems due to their abundance and vulnerability on land. How wolves hunt beavers in these systems is largely unknown, however, because observing predation is challenging. We inferred how wolves hunt beavers by identifying kill sites using clusters of locations from GPS-collared wolves in Voyageurs National Park, Minnesota. We identified 22 sites where wolves from 4 different packs killed beavers. We classified these kill sites into 8 categories based on the beaver-habitat type near which each kill occurred. Seasonal variation existed in types of kill sites as 7 of 12 (58%) kills in the spring occurred at sites below dams and on shorelines, and 8 of 10 (80%) kills in the fall occurred near feeding trails and canals. From these kill sites we deduced that the typical hunting strategy has 3 components: 1) waiting near areas of high beaver use (e.g., feeding trails) until a beaver comes near shore or ashore, 2) using vegetation, the dam, or other habitat features for concealment, and 3) immediately attacking the beaver, or ambushing the beaver by cutting off access to water. By identifying kill sites and inferring hunting behavior we have provided the most complete description available of how and where wolves hunt and kill beavers. PMID:27992441

  16. Where and How Wolves (Canis lupus) Kill Beavers (Castor canadensis).

    PubMed

    Gable, Thomas D; Windels, Steve K; Bruggink, John G; Homkes, Austin T

    2016-01-01

    Beavers (Castor canadensis) can be a significant prey item for wolves (Canis lupus) in boreal ecosystems due to their abundance and vulnerability on land. How wolves hunt beavers in these systems is largely unknown, however, because observing predation is challenging. We inferred how wolves hunt beavers by identifying kill sites using clusters of locations from GPS-collared wolves in Voyageurs National Park, Minnesota. We identified 22 sites where wolves from 4 different packs killed beavers. We classified these kill sites into 8 categories based on the beaver-habitat type near which each kill occurred. Seasonal variation existed in types of kill sites as 7 of 12 (58%) kills in the spring occurred at sites below dams and on shorelines, and 8 of 10 (80%) kills in the fall occurred near feeding trails and canals. From these kill sites we deduced that the typical hunting strategy has 3 components: 1) waiting near areas of high beaver use (e.g., feeding trails) until a beaver comes near shore or ashore, 2) using vegetation, the dam, or other habitat features for concealment, and 3) immediately attacking the beaver, or ambushing the beaver by cutting off access to water. By identifying kill sites and inferring hunting behavior we have provided the most complete description available of how and where wolves hunt and kill beavers.

  17. Heterosigma bloom and associated fish kill

    USGS Publications Warehouse

    Hershberger, P.K.; Rensel, J.E.; Postel, J.R.; Taub, F.B.

    1997-01-01

    A bloom of the harmful marine phytoplankton, Heterosigma carterae occurred in upper Case Inlet, south Puget Sound, Washington in late September, 1994, correlating with the presence of at least 35 dead salmon. This marks the first time that this alga has been closely correlated with a wild fish kill; in the past it was thought to be associated with kills of penned fish at fish farms only. We were informed of the presence of a possible harmful algal bloom and dead salinois Ilear the town of Allyn on 27 September and a team was formed to investigate. We arrived at the Allyn waterfront at 17:30 hours the same day. Prior to our arrival, state agency personnel walked approximatcly two miles of shoreline from the powerlines north of the dock, to the mouth of Sherwood Creek and conducted the only official count of dead fish present along the shore consisting of 12 coho salmon (Oncorhynchus kisutch), 11 chum salmon (Oncorhynchus keta), 12 chinook salmon (Oncorhynchus tschawytscha), one flat fish, and one sculpin on the morning of 9/27. Since previous harmful blooms of Heterosigma have resultedin the majority of net penreared salmon sinking to the bottom of pens, and only approximately two miles of shoreline were sampled, it is suspected that many more exposed fish may have succumbed than were counted. Witnesses who explored the east side of the bay reported seeing many dead salmon there as well, but no counts were made. State agency personnel who observed the fish kill reported seeing “dying fish coming to the beach, gulping at the surface, trying to get out of the water” Scavengers were seen consuming the salmon carcasses; these included two harbor seals, a house cat, and Hymenopteran insects. None suffered any noticeable acute ill effects. Although precise cause of death has not been ascertained, visual inspection of the reproductive organs from a deceased male chum salmon found on the shore at Allyn confirmed that the fish was not yet reproductively mature and

  18. The eyeball killer: serial killings with postmortem globe enucleation.

    PubMed

    Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A

    2015-05-01

    Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides. © 2015 American Academy of Forensic Sciences.

  19. Using Chemoattractants to Lure Bacteria to Contact-Killing Surfaces.

    PubMed

    Jain, Rishabh; Faith, Nancy G; Milkowski, Andrew; Nelson, Kevin; Busche, David; Lynn, David M; Czuprynski, Charles J; Abbott, Nicholas L

    2016-05-04

    Antimicrobial surfaces with covalently attached biocidal functionalities only kill microbes that come into direct contact with the surfaces (contact-killing surfaces). Herein, the activity of contact-killing surfaces is shown to be enhanced by using gradients in the concentration of soluble chemoattractants (CAs) to attract bacteria to the surfaces. Two natural and nonbiocidal CAs (aspartate and glucose) were used to attract bacteria to model surfaces decorated with quaternary ammonium groups (known to kill bacteria that come into contact with them). These results demonstrate the killing of Escherichia coli and Salmonella typhimurium, two common pathogens, at levels 10- to 20-times greater than that of the native surfaces alone. This approach is general and provides new strategies for the design of active or dynamic contact-killing surfaces with enhanced antimicrobial activities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. f(R)-gravity from Killing tensors

    NASA Astrophysics Data System (ADS)

    Paliathanasis, Andronikos

    2016-04-01

    We consider f(R)-gravity in a Friedmann-Lemaître-Robertson-Walker spacetime with zero spatial curvature. We apply the Killing tensors of the minisuperspace in order to specify the functional form of f(R) and for the field equations to be invariant under Lie-Bäcklund transformations, which are linear in momentum (contact symmetries). Consequently, the field equations to admit quadratic conservation laws given by Noether’s theorem. We find three new integrable f(R)-models, for which, with the application of the conservation laws, we reduce the field equations to a system of two first-order ordinary differential equations. For each model we study the evolution of the cosmological fluid. We find that for each integrable model the cosmological fluid has an equation of state parameter, in which there is linear behavior in terms of the scale factor which describes the Chevallier, Polarski and Linder parametric dark energy model.

  1. Killing, letting die and moral perception.

    PubMed

    Gillett, Grant

    1994-10-01

    There are a number of arguments that purport to show, in general terms, that there is no difference between killing and letting die. These are used to justify active euthanasia on the basis of the reasons given for allowing patients to die. I argue that the general and abstract arguments fail to take account of the complex and particular situations which are found in the care of those with terminal illness. When in such situations, there are perceptions and intuitions available that do not easily find propositional form but lead most of those whose practice is in the care of the dying to resist active euthanasia. I make a plea for their intuitions to be heeded above the sterile voice of abstract premises and arguments by examining the completeness of the outline form of the pro-euthanasia argument. In doing so, I make use of Nussbaum's discussion of moral perception and general claims to be found in the literature of moral particularism.

  2. Advanced gel propulsion controls for kill vehicles

    NASA Astrophysics Data System (ADS)

    Yasuhara, W. K.; Olson, A.; Finato, S.

    1993-06-01

    A gel propulsion control concept for tactical applications is reviewed, and the status of the individual component technologies currently under development at the Aerojet Propulsion Division is discussed. It is concluded that a gel propellant Divert and Attitude Control Subsystem (DACS) provides a safe, insensitive munitions compliant alternative to current liquid Theater Missile Defense (TMD) DACS approaches. The gel kill vehicle (KV) control system packages a total impulse typical of a tactical weapon interceptor for the ground- or sea-based TMD systems. High density packaging makes it possible to increase firepower and to eliminate long-term high pressure gas storage associated with bipropellant systems. The integrated control subsystem technologies encompass solid propellant gas generators, insulated composite overwrapped propellant tanks, lightweight endoatmospheric thrusters, and insensitive munition gel propellants, which meet the requirements of a deployable, operationally safe KV.

  3. Heat production due to intracellular killing activity.

    PubMed

    Hayatsu, H; Masuda, S; Miyamae, T; Yamamura, M

    1990-09-01

    Using Saccharomyces ceravisiae, Candida albicans and Stapylococcus aureus, heat production during phagocytosis was measured in U937 cells which are capable of differentiating to monocytic phagocytes. No increase in heat production of non-differentiated U937 was observed since they were not phagocytic cells. However after differentiation to monocytic phagocytes by lymphokine, U937 cells produced a remarkable amount of heat during phagocytosis. Although Ehrlich ascites tumor cells sensitized with antibody were capable of engulfing S. aureus, no increase in heat nor in superoxide anion production during phagocytosis was detected. It was also found that no heat increase occurred in neutrophils from a patient with chronic granulomatous disease (CGD). It can thus be concluded that the heat production during phagocytosis is due to the intercellular killing process of phagocytic cells.

  4. Killing Sections and Sigma Models with Lie Algebroid Targets

    NASA Astrophysics Data System (ADS)

    Bruce, Andrew James

    2016-08-01

    We define and examine the notion of a Killing section of a Riemannian Lie algebroid as a natural generalisation of a Killing vector field. We show that the various expression for a vector field to be Killing naturally generalise to the setting of Lie algebroids. As an application we examine the internal symmetries of a class of sigma models for which the target space is a Riemannian Lie algebroid. Critical points of these sigma models are interpreted as generalised harmonic maps.

  5. Cholate-dependent killing of Giardia lamblia by human milk.

    PubMed Central

    Gillin, F D; Reiner, D S; Gault, M J

    1985-01-01

    We showed previously that nonimmune human milk (NHM) kills Giardia lamblia trophozoites in vitro and presented evidence that killing requires the bile salt-stimulated lipase of milk. Since this enzyme is activated by bile salts, killing should be dependent on the presence of bile salts. We now show that killing by fresh NHM or NHM stored at -70 degrees C is totally dependent on sodium cholate (a bile salt). With less than 0.4 mM cholate, no parasites were killed, whereas with 1 mM cholate, greater than 99.7% were killed by 5% NHM in 30 min. Moreover, killing activity was completely heat labile. The G. lamblia-killing activity of human milk was greatly altered by storage at -10 or -20 degrees C. In less than 23 days, the 50% lethal dose decreased, cholate dependence was lost, and killing activity became heat stable. In contrast, the activity of milk stored at -70 degrees C remained unchanged. Milk lipase activity, like killing activity, became cholate independent during storage at -10 or -20 degrees C. On the basis of these results, we hypothesize that killing of G. lamblia by fresh NHM or NHM stored at -70 degrees C depends on bile salt-stimulated lipase, which must be activated by bile salts. In contrast, NHM stored at -20 degrees C accumulated free fatty acids which kill G. lamblia. In support of this thesis, milk stored at -10 degrees C had a concentration of 18.7 mM free fatty acids compared with only 1.1 mM in an identical sample stored at -70 degrees C. PMID:3972442

  6. Roles of antibodies and complement in phagocytic killing of enterococci.

    PubMed Central

    Arduino, R C; Murray, B E; Rakita, R M

    1994-01-01

    The contributions of complement and antibodies to polymorphonuclear leukocyte (PMN)-mediated killing of enterococci were investigated with pooled normal human serum (PNHS) or immune human sera (IHS) from patients with serious enterococcal infections. Each IHS containing antienterococcal antibodies demonstrated by enzyme-linked immunosorbent assay and Western blotting (immunoblotting) was examined with the enterococcus strain isolated from the same patient. PNHS promoted PMN-mediated killing of enterococci similar to that for IHS. PMN-mediated killing was consistently abrogated after preopsonization with heat-inactivated PNHS, but some heat-inactivated IHS supported neutrophil bactericidal activity. Inhibition of the classical pathway of complement by chelation of either PNHS or IHS with Mg-EGTA [Mg-ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] did not alter PMN-mediated killing, suggesting that activation of the alternative pathway of complement is sufficient to promote killing of enterococci by PMNs. PMN-mediated killing assays were also performed with normal rabbit serum and immune rabbit serum against enterococci. Preopsonization with heat-inactivated immune rabbit serum resulted in PMN-mediated killing of enterococci, which was ablated after adsorption of the serum with the same isolate used for immunization. The influence of different phenotypic enterococcal traits on neutrophil-mediated killing was also investigated. Similar kinetics of killing were observed for derivatives of Enterococcus faecalis strains regardless of resistance to antimicrobial agents or production of beta-lactamase, hemolysin, gelatinase, or surface proteins involved in the aggregative response to pheromones. In summary, PMN-mediated killing of enterococci appears to depend primarily on complement activation by either the classical or the alternative pathway. Human antienterococcal antibodies generated during infection variably promoted neutrophil bactericidal

  7. Transverse conformal Killing forms on Kähler foliations

    NASA Astrophysics Data System (ADS)

    Jung, Seoung Dal

    2015-04-01

    On a closed, connected Riemannian manifold with a Kähler foliation of codimension q = 2 m, any transverse Killing r(≥ 2) -form is parallel (Jung and Jung, 2012). In this paper, we study transverse conformal Killing forms on Kähler foliations. In fact, if the foliation is minimal, then for any transverse conformal Killing r-form ϕ(2 ≤ r ≤ q - 2), Jϕ is parallel. Here J is defined in Section 4.

  8. Picloram herbicide for killing chaparral species...a preliminary rating

    Treesearch

    Lisle R. Green; Joe R. Goodin; Theordore R. Plumb

    1966-01-01

    Picloram, in spray and pellet forms, was tested for its ability to kill chaparral species at several sites in southern California, in 1963. This herbicide proved to be as effective as brushkiller (2.4-D and 2,4, 5-T) or slightly more so. Both herbicides kilIed chamise readily at low rates, but failed to kill scrub oak. Kill of other species varied between these two...

  9. Killing spinors as a characterisation of rotating black hole spacetimes

    NASA Astrophysics Data System (ADS)

    Cole, Michael J.; Valiente Kroon, Juan A.

    2016-06-01

    We investigate the implications of the existence of Killing spinors in a spacetime. In particular, we show that in vacuum and electrovacuum a Killing spinor, along with some assumptions on the associated Killing vector in an asymptotic region, guarantees that the spacetime is locally isometric to the Kerr or Kerr-Newman solutions. We show that the characterisation of these spacetimes in terms of Killing spinors is an alternative expression of characterisation results of Mars (Kerr) and Wong (Kerr-Newman) involving restrictions on the Weyl curvature and matter content.

  10. Killing-Yano tensors of order n - 1

    NASA Astrophysics Data System (ADS)

    Batista, Carlos

    2014-08-01

    The properties of a Killing-Yano tensor of order n-1 in an n-dimensional manifold are investigated. The integrability conditions are worked out and all metrics admitting a Killing-Yano tensor of order n-1 are found. A connection between such tensors and a generalization of the concept of angular momentum is pointed out. A theorem on how to generate closed conformal Killing vectors using the symmetries of a manifold is proved and used to find all Killing-Yano tensors of order n-1 of a maximally symmetric space.

  11. Advancements in dynamic kill calculations for blowout wells

    SciTech Connect

    Kouba, G.E. . Production Fluids Div.); MacDougall, G.R. ); Schumacher, B.W. . Information Technology Dept.)

    1993-09-01

    This paper addresses the development, interpretation, and use of dynamic kill equations. To this end, three simple calculation techniques are developed for determining the minimum dynamic kill rate. Two techniques contain only single-phase calculations and are independent of reservoir inflow performance. Despite these limitations, these two methods are useful for bracketing the minimum flow rates necessary to kill a blowing well. For the third technique, a simplified mechanistic multiphase-flow model is used to determine a most-probable minimum kill rate.

  12. Antibacterial activity of silver-killed bacteria: the "zombies" effect

    NASA Astrophysics Data System (ADS)

    Wakshlak, Racheli Ben-Knaz; Pedahzur, Rami; Avnir, David

    2015-04-01

    We report a previously unrecognized mechanism for the prolonged action of biocidal agents, which we denote as the zombies effect: biocidally-killed bacteria are capable of killing living bacteria. The concept is demonstrated by first killing Pseudomonas aeruginosa PAO1 with silver nitrate and then challenging, with the dead bacteria, a viable culture of the same bacterium: Efficient antibacterial activity of the killed bacteria is observed. A mechanism is suggested in terms of the action of the dead bacteria as a reservoir of silver, which, due to Le-Chatelier's principle, is re-targeted to the living bacteria. Langmuirian behavior, as well as deviations from it, support the proposed mechanism.

  13. Antibacterial activity of silver-killed bacteria: the "zombies" effect.

    PubMed

    Wakshlak, Racheli Ben-Knaz; Pedahzur, Rami; Avnir, David

    2015-04-23

    We report a previously unrecognized mechanism for the prolonged action of biocidal agents, which we denote as the zombies effect: biocidally-killed bacteria are capable of killing living bacteria. The concept is demonstrated by first killing Pseudomonas aeruginosa PAO1 with silver nitrate and then challenging, with the dead bacteria, a viable culture of the same bacterium: Efficient antibacterial activity of the killed bacteria is observed. A mechanism is suggested in terms of the action of the dead bacteria as a reservoir of silver, which, due to Le-Chatelier's principle, is re-targeted to the living bacteria. Langmuirian behavior, as well as deviations from it, support the proposed mechanism.

  14. On the Lie subalgebra of Killing-Milne and Killing-Cartan vector fields in Newtonian spacetime

    NASA Astrophysics Data System (ADS)

    Chamel, Nicolas

    2015-12-01

    The Galilean (and more generally Milne) invariance of Newtonian theory allows for Killing vector fields of a general kind, whereby the Lie derivative of a field is not required to vanish but only to be cancellable by some infinitesimal Galilean (respectively Milne) gauge transformation. In this paper, it is shown that both the Killing-Milne vector fields, which preserve the background Newtonian spacetime structure and the Killing-Cartan vector fields, which in addition preserve the gravitational field, form a Lie subalgebra.

  15. Killing a Peacock: A Case Study of the Targeted Killing of Admiral Isoroku Yamamoto

    DTIC Science & Technology

    2015-03-24

    operation to kill Yamamoto. Lastly, analysis of the end, the aftermath of mission, will give insight into its effectiveness. Examining the immediate...section carries the greatest significance for current and future operations of this nature. Analysis of the circumstances surrounding the decision...on his dash. Mitscher had come through. Likewise, the other pilots strapped in their aircraft as the mechanics buttoned up the last of the open

  16. Kinetics of killing Listeria monocytogenes by macrophages: rapid killing accompanying phagocytosis

    SciTech Connect

    Davies, W.A.

    1983-08-01

    The kinetics of bactericidal activity of activated macrophages can be precisely described by a mathematical model in which phagocytosis, killing, digestion, and release of degraded bacterial material are considered to occur continuously. To gain a better understanding of these events, I have determined the period of time between first contact of bacteria with macrophages and the onset of killing. Activated rat peritoneal macrophages were incubated for various times up to 15 min with Listeria monocytogenes previously labeled with /sup 3/H-thymidine and the unassociated bacteria removed by two centrifugations through a density interface. Both cell-associated radioactivity and cell-associated viable bacteria, determined as colony forming units after sonication of the cell pellet, increased with time of incubation. However, the specific viability of these bacteria, expressed as the ratio of number of viable bacteria per unit radioactivity declined with time, as an approximate inverse exponential, after a lag period of 2.9 +/- 0.8 min. Evidence is given that other possible causes for this decline in specific viability, other than death of the bacteria, such as preferential ingestion of dead Listeria, clumping of bacteria, variations in autolytic activity, or release of Listericidins are unlikely. I conclude therefore that activated macrophages kill Listeria approximately 3 min after the cell and the bacterium first make contact.

  17. A herpes simplex virus 2 (HSV-2) glycoprotein D-expressing nonreplicating dominant-negative HSV-2 virus vaccine is superior to a gD2 subunit vaccine against HSV-2 genital infection in guinea pigs.

    PubMed

    Zhang, Pengwei; Xie, Lining; Balliet, John W; Casimiro, Danilo R; Yao, Feng

    2014-01-01

    We recently constructed a novel non-replicating dominant-negative HSV-2 recombinant viral vaccine (CJ2-gD2) capable of expressing various HSV-2 antigens that are dominant targets of HSV-2-specific CD8 T-cell response. Importantly, CJ2-gD2 expresses gD2, the HSV-2 major antigen glycoprotein D, as efficiently as wild-type HSV-2 infection and can lead to a nearly 500-fold reduction in wild-type HSV-2 viral replication in cells co-infected with CJ2-gD2 and wild-type HSV-2. In this report, we show that CJ2-gD2 elicits a strong antibody response to various HSV-2 antigens and is highly effective in the prevention of primary and recurrent HSV-2 genital infection and disease in the immunized guinea pigs. The direct comparison study between CJ2-gD2 and a gD2 subunit vaccine (gD2-alum/MPL) with a formulation akin to a vaccine tested in phase III clinical trials shows that CJ2-gD2 is 8 times more effective than the gD2-alum/MPL subunit vaccine in eliciting an anti-HSV-2 specific neutralizing antibody response and offers significantly superior protection against primary and recurrent HSV-2 genital infections. Importantly, no challenge wild-type HSV-2 viral DNA was detectable in dorsal root ganglia DNA isolated from CJ2-gD2-immunized guinea pigs on day 60 post-challenge. CJ2-gD2 should be an excellent HSV-2 vaccine candidate for protection against HSV-2 genital infection and disease in humans.

  18. 7 CFR 29.1018 - Fire-killed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Fire-killed. 29.1018 Section 29.1018 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1018 Fire-killed. Any leaf of which 5 percent or more of its surface has a set green...

  19. Null conformal Killing-Yano tensors and Birkhoff theorem

    NASA Astrophysics Data System (ADS)

    Ferrando, Joan Josep; Sáez, Juan Antonio

    2016-04-01

    We study the space-times admitting a null conformal Killing-Yano tensor whose divergence defines a Killing vector. We analyze the similarities and differences with the recently studied non null case (Ferrando and Sáez in Gen Relativ Gravit 47:1911, 2015). The results by Barnes concerning the Birkhoff theorem for the case of null orbits are analyzed and generalized.

  20. 9. GENERAL INTERIOR VIEW OF BEEF KILLING FLOOR; LOOKING SOUTHEAST; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. GENERAL INTERIOR VIEW OF BEEF KILLING FLOOR; LOOKING SOUTHEAST; PLATFORMS IN FOREGROUND WERE USED BY SPLITTERS, TRIMMERS AND GOVERNMENT INSPECTORS; SKINNING TABLE RAN ALONG THE WINDOWS NEAR THE CENTER OF THE PHOTO - Rath Packing Company, Beef Killing Building, Sycamore Street between Elm & Eighteenth Streets, Waterloo, Black Hawk County, IA

  1. Killing of bacteria during solar eclipse and its biological implications.

    PubMed

    Banerjee, S K; Chatterjee, S N

    1983-01-01

    Enhanced killing of bacteria was obtained by radiation reaching the earth during total solar eclipse (February 16, 1980) than during the corresponding time of a normal day (February 26, 1980). The killing was not due to the formation of sunlight induced photoproducts of tryptophan. The damage to the bacteria exposed to sunlight could be repaired by photoreactivation.

  2. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    ERIC Educational Resources Information Center

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  3. 9 CFR 113.216 - Bovine Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Virus. 113.216 Section 113.216 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.216 Bovine Rhinotracheitis Vaccine, Killed Virus. Infectious Bovine...

  4. 9 CFR 113.216 - Bovine Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Virus. 113.216 Section 113.216 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.216 Bovine Rhinotracheitis Vaccine, Killed Virus. Infectious Bovine...

  5. 9 CFR 113.216 - Bovine Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Virus. 113.216 Section 113.216 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.216 Bovine Rhinotracheitis Vaccine, Killed Virus. Infectious Bovine...

  6. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    ERIC Educational Resources Information Center

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  7. Pseudomonas piscicida kills vibrios by two distinct mechanisms

    USDA-ARS?s Scientific Manuscript database

    Pseudoalteromonas piscicida is a naturally-occurring marine bacterium which kills competing bacteria, including vibrios. In studies by Richards et al. (AEM00175-17), three strains of P. piscicida were isolated and characterized. Strains secreted proteolytic enzymes which likely killed competing or...

  8. Male Brown-headed Cowbird Attacks and Kills a Nestling

    USGS Publications Warehouse

    Igl, L.D.

    2003-01-01

    I observed a male Brown-headed Cowbird (Molothrus ater) attack and kill a nestling of an unidentified passerine in a grassland field in Day County, South Dakota, in June 2000. The killing or removal of nestlings by female cowbirds has been reported by others, but this behavior has not been documented previously in male cowbirds.

  9. 7 CFR 29.1018 - Fire-killed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Fire-killed. 29.1018 Section 29.1018 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1018 Fire-killed. Any leaf of which 5 percent or more of its surface has a set...

  10. 7 CFR 29.1018 - Fire-killed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Fire-killed. 29.1018 Section 29.1018 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1018 Fire-killed. Any leaf of which 5 percent or more of its surface has a set...

  11. 7. LOOKING WEST TOWARD SHEEP KILL AREA ON SOUTH END ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. LOOKING WEST TOWARD SHEEP KILL AREA ON SOUTH END OF BUILDING 149; INCLINED CONVEYOR AT LEFT CENTER CARRIED TROLLEYS TO THE AUTOMATIC WASHER/OILER ON THE GALLERY LEVEL - Rath Packing Company, Beef Killing Building, Sycamore Street between Elm & Eighteenth Streets, Waterloo, Black Hawk County, IA

  12. PDE5 Inhibitors Enhance Celecoxib Killing in Multiple Tumor Types

    PubMed Central

    BOOTH, LAURENCE; ROBERTS, JANE L.; CRUICKSHANKS, NICHOLA; TAVALLAI, SEYEDMEHRAD; WEBB, TIMOTHY; SAMUEL, PETER; CONLEY, ADAM; BINION, BRITTANY; YOUNG, HAROLD F.; POKLEPOVIC, ANDREW; SPIEGEL, SARAH; DENT, PAUL

    2015-01-01

    The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 activation was dependent on nitric oxide and ceramide signaling. CD95 signaling activated the JNK pathway and inhibition of JNK suppressed cell killing. The drug combination inactivated mTOR and increased the levels of autophagy and knock down of Beclin1 or ATG5 strongly suppressed killing by the drug combination. The drug combination caused an ER stress response; knock down of IRE1α/XBP1 enhanced killing whereas knock down of eIF2α/ATF4/CHOP suppressed killing. Sildenafil and celecoxib treatment suppressed the growth of mammary tumors in vivo. Collectively our data demonstrate that clinically achievable concentrations of celecoxib and sildenafil have the potential to be a new therapeutic approach for cancer. PMID:25303541

  13. The Seal Killing Controversy: What Are the Facts?

    ERIC Educational Resources Information Center

    Scheffer, Victor B.

    1973-01-01

    Discusses the seal controversy using the harp and Alaska fur seals to illustrate the two distinct issues, i.e., conservation (the effect of killing upon the animal population); and two, morality (the effect of killing upon the human spirit). Factual information combines with personal philosophy. (LK)

  14. Killing Unwanted West Indies Mahogany Trees by Peeling and Frilling

    Treesearch

    R. W. Nobles; C. B. Briscoe

    1966-01-01

    Peeling and frilling each killed approximately 70 percent of treated West Indies mahogany, but peeling killed a higher percentage of trees between 18 and 33 centimeters (7 and 13 inches) than did frilling. Essentially all mortality occurred within the first 15 months following treatment.

  15. The Seal Killing Controversy: What Are the Facts?

    ERIC Educational Resources Information Center

    Scheffer, Victor B.

    1973-01-01

    Discusses the seal controversy using the harp and Alaska fur seals to illustrate the two distinct issues, i.e., conservation (the effect of killing upon the animal population); and two, morality (the effect of killing upon the human spirit). Factual information combines with personal philosophy. (LK)

  16. Killing of bacteria by copper surfaces involves dissolved copper.

    PubMed

    Molteni, Cristina; Abicht, Helge K; Solioz, Marc

    2010-06-01

    Bacteria are rapidly killed on copper surfaces. However, the mechanism of this process remains unclear. Using Enterococcus hirae, the effect of inactivation of copper homeostatic genes and of medium compositions on survival and copper dissolution was tested. The results support a role for dissolved copper ions in killing.

  17. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine, Killed Virus. 113.201 Section 113.201 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed Virus which has...

  18. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Mink Enteritis Vaccine, Killed Virus. 113.204 Section 113.204 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or tissues obtained from mink that...

  19. 9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  20. 9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  1. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Mink Enteritis Vaccine, Killed Virus. 113.204 Section 113.204 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or tissues obtained from mink that...

  2. 9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  3. 9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203 Section 113.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  4. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bursal Disease Vaccine, Killed Virus. 113.212 Section 113.212 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only...

  5. 9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  6. 9 CFR 113.216 - Bovine Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Bovine Rhinotracheitis Vaccine, Killed Virus. 113.216 Section 113.216 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  7. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Mink Enteritis Vaccine, Killed Virus. 113.204 Section 113.204 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or tissues obtained from mink that...

  8. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Parvovirus Vaccine, Killed Virus (Canine). 113.214 Section 113.214 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, recommended for use in dogs, shall be prepared from virus-bearing cell culture fluids. Only...

  9. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bursal Disease Vaccine, Killed Virus. 113.212 Section 113.212 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only...

  10. 9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  11. 9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  12. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Mink Enteritis Vaccine, Killed Virus. 113.204 Section 113.204 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or tissues obtained from mink that...

  13. 9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203 Section 113.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  14. 9 CFR 113.216 - Bovine Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Bovine Rhinotracheitis Vaccine, Killed Virus. 113.216 Section 113.216 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  15. 9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  16. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine, Killed Virus. 113.201 Section 113.201 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed Virus which has...

  17. 9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Rhinotracheitis Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed...

  18. 9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203 Section 113.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  19. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Parvovirus Vaccine, Killed Virus (Canine). 113.214 Section 113.214 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, recommended for use in dogs, shall be prepared from virus-bearing cell culture fluids. Only...

  20. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mink Enteritis Vaccine, Killed Virus. 113.204 Section 113.204 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE..., Killed Virus, shall be prepared from virus-bearing cell culture fluids or tissues obtained from mink that...

  1. 9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  2. 9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203 Section 113.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  3. 9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  4. 9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Feline Panleukopenia Vaccine, Killed Virus. 113.203 Section 113.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  5. Mechanisms of Dendritic Cell Lysosomal Killing of Cryptococcus

    NASA Astrophysics Data System (ADS)

    Hole, Camaron R.; Bui, Hoang; Wormley, Floyd L.; Wozniak, Karen L.

    2012-10-01

    Cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that disseminates to the CNS causing fatal meningitis in immunocompromised patients. Dendritic cells (DCs) phagocytose C. neoformans following inhalation. Following uptake, cryptococci translocate to the DC lysosomal compartment and are killed by oxidative and non-oxidative mechanisms. DC lysosomal extracts kill cryptococci in vitro; however, the means of antifungal activity remain unknown. Our studies determined non-oxidative antifungal activity by DC lysosomal extract. We examined DC lysosomal killing of cryptococcal strains, anti-fungal activity of purified lysosomal enzymes, and mechanisms of killing against C. neoformans. Results confirmed DC lysosome fungicidal activity against all cryptococcal serotypes. Purified lysosomal enzymes, specifically cathepsin B, inhibited cryptococcal growth. Interestingly, cathepsin B combined with its enzymatic inhibitors led to enhanced cryptococcal killing. Electron microscopy revealed structural changes and ruptured cryptococcal cell walls following treatment. Finally, additional studies demonstrated that osmotic lysis was responsible for cryptococcal death.

  6. Killing (absorption) versus survival in random motion

    NASA Astrophysics Data System (ADS)

    Garbaczewski, Piotr

    2017-09-01

    We address diffusion processes in a bounded domain, while focusing on somewhat unexplored affinities between the presence of absorbing and/or inaccessible boundaries. For the Brownian motion (Lévy-stable cases are briefly mentioned) model-independent features are established of the dynamical law that underlies the short-time behavior of these random paths, whose overall lifetime is predefined to be long. As a by-product, the limiting regime of a permanent trapping in a domain is obtained. We demonstrate that the adopted conditioning method, involving the so-called Bernstein transition function, works properly also in an unbounded domain, for stochastic processes with killing (Feynman-Kac kernels play the role of transition densities), provided the spectrum of the related semigroup operator is discrete. The method is shown to be useful in the case, when the spectrum of the generator goes down to zero and no isolated minimal (ground state) eigenvalue is in existence, like in the problem of the long-term survival on a half-line with a sink at origin.

  7. The Cell Killing Mechanisms of Hydroxyurea

    PubMed Central

    Singh, Amanpreet; Xu, Yong-Jie

    2016-01-01

    Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative disorders. Due to its reversible inhibitory effect on DNA replication in various organisms, hydroxyurea is also commonly used in laboratories for cell cycle synchronization or generating replication stress. However, incubation with high concentrations or prolonged treatment with low doses of hydroxyurea can result in cell death and the DNA damage generated at arrested replication forks is generally believed to be the direct cause. Recent studies in multiple model organisms have shown that oxidative stress and several other mechanisms may contribute to the majority of the cytotoxic effect of hydroxyurea. This review aims to summarize the progress in our understanding of the cell-killing mechanisms of hydroxyurea, which may provide new insights towards the improvement of chemotherapies that employ this agent. PMID:27869662

  8. Clomipramine kills Trypanosoma brucei by apoptosis.

    PubMed

    de Silva Rodrigues, Jean Henrique; Stein, Jasmin; Strauss, Mariana; Rivarola, Héctor Walter; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; Duszenko, Michael

    2016-06-01

    Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite's physiology and induces stress in a way that trypanosomes cannot cope with.

  9. On pseudo-Riemannian manifolds with many Killing spinors

    SciTech Connect

    Alekseevsky, D. V.; Cortes, V.

    2009-02-02

    Let M be a pseudo-Riemannian spin manifold of dimension n and signature s and denote by N the rank of the real spinor bundle. We prove that M is locally homogeneous if it admits more than (3/4)N independent Killing spinors with the same Killing number, unless n {identical_to} 1(mod 4) and s {identical_to} 3(mod 4). We also prove that M is locally homogeneous if it admits k{sub +} independent Killing spinors with Killing number {lambda} and k{sub -} independent Killing spinors with Killing number -{lambda} such that k{sub +}+k{sub -}>(3/2)N, unless n {identical_to} s {identical_to} 3(mod 4). Similarly, a pseudo-Riemannian manifold with more than (3/4)N independent conformal Killing spinors is conformally locally homogeneous. For (positive or negative) definite metrics, the bounds (3/4)N and (3/2)N in the above results can be relaxed to (1/2)N and N, respectively. Furthermore, we prove that a pseudo-Riemannnian spin manifold with more than (3/4)N parallel spinors is flat and that (1/4)N parallel spinors suffice if the metric is definite. Similarly, a Riemannnian spin manifold with more than (3/8)N Killing spinors with the Killing number {lambda}(set-membership sign)R has constant curvature 4{lambda}{sup 2}. For Lorentzian or negative definite metrics the same is true with the bound (1/2)N. Finally, we give a classification of (not necessarily complete) Riemannian manifolds admitting Killing spinors, which provides an inductive construction of such manifolds.

  10. [Time point and methods for emergency killing in cattle].

    PubMed

    Khol, J L; Schafbauer, T; Wittek, T

    2016-01-01

    Emergency killing is defined as the killing of injured or ill animals to avoid excessive pain or harm. Decision-making for emergency killing or a prolonged therapy can be difficult and has to be based on the case history and results of the clinical examination contributing to the prognosis, particularly in downer cows. Evaluation of enzyme activities and total bilirubin can be used as additional factors pointing to a guarded prognosis; however, none of these parameters provides a clear cut-off value indicating a poor prognosis and mandatory emergency killing. Euthanasia by intravenous drug application is seen as the least stressful method of killing and should therefore always be the first method of choice for emergency killing in cattle. Drugs containing pentobarbital as well as a combination of three different drugs (T61-Injektionslösung, MSD Animal Health) are available for euthanasia in cattle. All drugs must be administered by a veterinarian. Before application of pentobarbital, an animal should be deeply sedated. The administration of T61 requires anaesthesia of the animal and it is not licensed for use in pregnant animals. Alternative methods for emeragency killing, including captive bolt stunning and the use of firearms, although not regularly performed by veterinarians, should be assessed concerning their correct application and performance. When captive bolt stunning or emergency killing using firearms is performed, the correct position of the device is crucial as well as a quick exsanguination or the application of a pithing rod for the actual killing of the animal after captive bolt stunning. In addition to medical considerations, economic and personal factors contribute to the decision about emergency killing in cattle. Therefore, veterinarians should aim to evaluate each case thoroughly based on personal knowledge and experience, case history, clinical findings and laboratory parameters to avoid prolonged suffering of the animal.

  11. Managing Threat, Cost, and Incentive to Kill: The Short- and Long-Term Effects of Intervention in Mass Killings

    ERIC Educational Resources Information Center

    Kathman, Jacob D.; Wood, Reed M.

    2011-01-01

    How do third-party interventions affect the severity of mass killings? The authors theorize that episodes of mass killing are the consequence of two factors: (1) the threat perceptions of the perpetrators and (2) the cost of implementing genocidal policies relative to other alternatives. To reduce genocidal hostilities, interveners must address…

  12. Managing Threat, Cost, and Incentive to Kill: The Short- and Long-Term Effects of Intervention in Mass Killings

    ERIC Educational Resources Information Center

    Kathman, Jacob D.; Wood, Reed M.

    2011-01-01

    How do third-party interventions affect the severity of mass killings? The authors theorize that episodes of mass killing are the consequence of two factors: (1) the threat perceptions of the perpetrators and (2) the cost of implementing genocidal policies relative to other alternatives. To reduce genocidal hostilities, interveners must address…

  13. Psychological traits underlying different killing methods among Malaysian male murderers.

    PubMed

    Kamaluddin, Mohammad Rahim; Shariff, Nadiah Syariani; Nurfarliza, Siti; Othman, Azizah; Ismail, Khaidzir H; Mat Saat, Geshina Ayu

    2014-04-01

    Murder is the most notorious crime that violates religious, social and cultural norms. Examining the types and number of different killing methods that used are pivotal in a murder case. However, the psychological traits underlying specific and multiple killing methods are still understudied. The present study attempts to fill this gap in knowledge by identifying the underlying psychological traits of different killing methods among Malaysian murderers. The study adapted an observational cross-sectional methodology using a guided self-administered questionnaire for data collection. The sampling frame consisted of 71 Malaysian male murderers from 11 Malaysian prisons who were selected using purposive sampling method. The participants were also asked to provide the types and number of different killing methods used to kill their respective victims. An independent sample t-test was performed to establish the mean score difference of psychological traits between the murderers who used single and multiple types of killing methods. Kruskal-Wallis tests were carried out to ascertain the psychological trait differences between specific types of killing methods. The results suggest that specific psychological traits underlie the type and number of different killing methods used during murder. The majority (88.7%) of murderers used a single method of killing. Multiple methods of killing was evident in 'premeditated' murder compared to 'passion' murder, and revenge was a common motive. Examples of multiple methods are combinations of stabbing and strangulation or slashing and physical force. An exception was premeditated murder committed with shooting, when it was usually a single method, attributed to the high lethality of firearms. Shooting was also notable when the motive was financial gain or related to drug dealing. Murderers who used multiple killing methods were more aggressive and sadistic than those who used a single killing method. Those who used multiple methods or

  14. Did Vertigo Kill America's Forgotten Astronaut?

    NASA Technical Reports Server (NTRS)

    Bendrick, Gregg A.; Merlin, Peter W.

    2007-01-01

    On November 15, 1967, U.S. Air Force test pilot Major Michael J. Adams was killed while flying the X-15 rocket-propelled research vehicle in a parabolic spaceflight profile. This flight was part of a joint effort with NASA. An electrical short in one of the experiments aboard the vehicle caused electrical transients, resulting in excessive workload by the pilot. At altitude Major Adams inappropriately initiated a flat spin that led to a series of unusual aircraft attitudes upon atmospheric re-entry, ultimately causing structural failure of the airframe. Major Adams was known to experience vertigo (i.e. spatial disorientation) while flying the X-15, but all X-15 pilots most likely experienced vertigo (i.e. somatogravic, or "Pitch-Up", illusion) as a normal physiologic response to the accelerative forces involved. Major Adams probably experienced vertigo to a greater degree than did others, since prior aeromedical testing for astronaut selection at Brooks AFB revealed that he had an unusually high degree of labyrinthine sensitivity. Subsequent analysis reveals that after engine burnout, and through the zenith of the flight profile, he likely experienced the oculoagravic ("Elevator") illusion. Nonetheless, painstaking investigation after the mishap revealed that spatial disorientation (Type II, Recognized) was NOT the cause, but rather, a contributing factor. The cause was in fact the misinterpretation of a dual-use flight instrument (i.e. Loss of Mode Awareness), resulting in confusion between yaw and roll indications, with subsequent flight control input that was inappropriate. Because of the altitude achieved on this flight, Major Adams was awarded Astronaut wings posthumously. Understanding the potential for spatial disorientation, particularly the oculoagravic illusion, associated with parabolic spaceflight profiles, and understanding the importance of maintaining mode awareness in the context of automated cockpit design, are two lessons that have direct

  15. Can Nanomedicines Kill Cancer Stem Cells?

    PubMed Central

    Zhao, Yi; Alakhova, Daria Y.; Kabanov, Alexander V.

    2014-01-01

    Most tumors are heterogeneous and many cancers contain small population of highly tumorigenic and intrinsically drug resistant cancer stem cells (CSCs). Like normal stem cell, CSCs have ability to self-renew and differentiate to other tumor cell types. They are believed to be a source for drug resistance, tumor recurrence and metastasis. CSCs often overexpress drug efflux transporters, spend most of their time in non-dividing G0 cell cycle state, and therefore, can escape the conventional chemotherapies. Thus, targeting CSCs is essential for developing novel therapies to prevent cancer relapse and emerging of drug resistance. Nanocarrier-based therapeutic agents (nanomedicines) have been used to achieve longer circulation times, better stability and bioavailability over current therapeutics. Recently, some groups have successfully applied nanomedicines to target CSCs to eliminate the tumor and prevent its recurrence. These approaches include 1) delivery of therapeutic agents (small molecules, siRNA, antibodies) that affect embryonic signaling pathways implicated in self-renewal and differentiation in CSCs, 2) inhibiting drug efflux transporters in an attempt to sensitize CSCs to therapy, 3) targeting metabolism in CSCs through nanoformulated chemicals and field-responsive magnetic nanoparticles and carbon nanotubes, and 4) disruption of multiple pathways in drug resistant cells using combination of chemotherapeutic drugs with amphiphilic Pluronic block copolymers. Despite clear progress of these studies the challenges of targeting CSCs by nanomedicines still exist and leave plenty of room for improvement and development. This review summarizes biological processes that are related to CSCs, overviews the current state of anti-CSCs therapies, and discusses state-of-the-art nanomedicine approaches developed to kill CSCs. PMID:24120657

  16. Kill a brand, keep a customer.

    PubMed

    Kumar, Nirmalya

    2003-12-01

    Most brands don't make much money. Year after year, businesses generate 80% to 90% of their profits from less than 20% of their brands. Yet most companies tend to ignore loss-making brands, unaware of the hidden costs they incur. That's because executives believe it's easy to erase a brand; they have only to stop investing in it, they assume, and it will die a natural death. But they're wrong. When companies drop brands clumsily, they antagonize loyal customers: Research shows that seven times out of eight, when firms merge two brands, the market share of the new brand never reaches the combined share of the two original ones. It doesn't have to be that way. Smart companies use a four-step process to kill brands methodically. First, CEOs make the case for rationalization by getting groups of senior executives to conduct joint audits of the brand portfolio. These audits make the need to prune brands apparent throughout the organization. In the next stage, executives need to decide how many brands will be retained, which they do either by setting broad parameters that all brands must meet or by identifying the brands they need in order to cater to all the customer segments in their markets. Third, executives must dispose of the brands they've decided to drop, deciding in each case whether it is appropriate to merge, sell, milk, or just eliminate the brand outright. Finally, it's critical that executives invest the resources they've freed to grow the brands they've retained. Done right, dropping brands will result in a company poised for new growth from the source where it's likely to be found--its profitable brands.

  17. Macrophage elastase kills bacteria within murine macrophages.

    PubMed

    Houghton, A McGarry; Hartzell, William O; Robbins, Clinton S; Gomis-Rüth, F Xavier; Shapiro, Steven D

    2009-07-30

    Macrophages are aptly positioned to function as the primary line of defence against invading pathogens in many organs, including the lung and peritoneum. Their ability to phagocytose and clear microorganisms has been well documented. Macrophages possess several substances with which they can kill bacteria, including reactive oxygen species, nitric oxide, and antimicrobial proteins. We proposed that macrophage-derived proteinases may contribute to the antimicrobial properties of macrophages. Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages and is implicated in several disease processes, including emphysema. Physiological functions for MMP12 have not been described. Here we show that Mmp12(-/-) mice exhibit impaired bacterial clearance and increased mortality when challenged with both gram-negative and gram-positive bacteria at macrophage-rich portals of entry, such as the peritoneum and lung. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxy-terminal domain. This domain contains a unique four amino acid sequence on an exposed beta loop of the protein that is required for the observed antimicrobial activity. The present study represents, to our knowledge, the first report of direct antimicrobial activity by a matrix metallopeptidase, and describes a new antimicrobial peptide that is sequentially and structurally unique in nature.

  18. Laser Microbial Killing and Biofilm Disruption

    NASA Astrophysics Data System (ADS)

    Krespi, Yosef P.; Kizhner, Victor

    2009-06-01

    Objectives: To analyze the ability of NIR lasers to reduce bacterial load and demonstrate the capability of fiber-based Q-switched Nd:YAG laser disrupting biofilm. Study Design: NIR diode laser was tested in vitro and in vivo using pathogenic microorganisms (S. aureus, S. pneumoniae, P. aeruginosa). In addition biofilms were grown from clinical Pseudomonas isolates and placed in culture plates, screws, tympanostomy tubes and PET sutures. Methods: In the animal experiments acute rhinosinusitis model was created by packing the rabbit nose with bacteria soaked solution. The nasal pack was removed in two days and nose was exposed to laser irradiation. A 940 nm diode laser with fiber diffuser was used. Nasal cultures were obtained before and after the laser treatments. Animals were sacrificed fifteen days following laser treatment and bacteriologic/histologic results analyzed. Q-switched Nd:YAG laser generated shockwave pulses were delivered on biofilm using special probes over culture plates, screws, tubes, and PET sutures for the biofilm experiments. Results: Average of two log bacteria reduction was achieved with NIR laser compared to controls. Histologic studies demonstrated preservation of tissue integrity without significant damage to mucosa. Biofilms were imaged before, during and after treatment using a confocal microscope. During laser-generated shockwave application, biofilm was initially seen to oscillate and eventually break off. Large and small pieces of biofilm were totally and instantly removed from the surface to which they were attached in seconds. Conclusions: Significant bacterial reduction was achieved with NIR laser therapy in this experimental in vitro and animal study. In addition we disrupted Pseudomonas aeruginosa biofilms using Q-switched Nd:YAG laser and special probes generating plasma and shockwave. This new and innovative method of bacteria killing and biofilm disruption without injuring host tissue may have clinical application in the

  19. Copper Reduction and Contact Killing of Bacteria by Iron Surfaces.

    PubMed

    Mathews, Salima; Kumar, Ranjeet; Solioz, Marc

    2015-09-01

    The well-established killing of bacteria by copper surfaces, also called contact killing, is currently believed to be a combined effect of bacterial contact with the copper surface and the dissolution of copper, resulting in lethal bacterial damage. Iron can similarly be released in ionic form from iron surfaces and would thus be expected to also exhibit contact killing, although essentially no contact killing is observed by iron surfaces. However, we show here that the exposure of bacteria to iron surfaces in the presence of copper ions results in efficient contact killing. The process involves reduction of Cu(2+) to Cu(+) by iron; Cu(+) has been shown to be considerably more toxic to cells than Cu(2+). The specific Cu(+) chelator, bicinchoninic acid, suppresses contact killing by chelating the Cu(+) ions. These findings underline the importance of Cu(+) ions in the contact killing process and infer that iron-based alloys containing copper could provide novel antimicrobial materials. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Potassium channels mediate killing by human natural killer cells

    SciTech Connect

    Schlichter, L.; Sidell N.; Hagiwara, S.

    1986-01-01

    Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. Using the whole-cell variation of the patch-clamp technique, the authors found a voltage-dependent potassium (K/sup +/) current in NK cells. The K/sup +/ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd/sup 2 +/. They tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard /sup 51/Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd/sup 2 +/, and 4-aminopyridine at concentrations comparable to those that blocked the K/sup +/ current in NK cells. In K562 target cells only a voltage-dependent Na= current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K/sup +/ current was found that was similar to the one in NK cells. The findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process.

  1. HIV transcription is induced with some forms of cell killing

    SciTech Connect

    Woloschak, G.E.; Schreck, S.; Panozzo, J.; Chang-Liu, C.-M.; Libertin, C.R.

    1996-11-01

    Using HeLa cells stably transfected with an HIV-LTR-CAT construct`, we demonstrated a peak in CAT induction that occurs in viable (but not necessarily cell-division-competent) cells 24 h following exposure to some cell-killing agents. {Gamma} rays were the only cell-killing agent which did not induce HIV transcription; this can be attributed to the fact that {gamma}-ray-induced apoptotic death requires function p53, which is missing in HeLa cells. For all other agents, HIV-LTR induction was dose-dependent and correlated with the amount of cell killing that occurred in the culture.

  2. Role of Peroxide in Phagocytic Killing of Pneumococci

    PubMed Central

    Pitt, Jane; Bernheimer, Harriet P.

    1974-01-01

    Two mutants of a pneumococcus type I with diminished peroxide production were selected from a population of nitrosoguanidine-treated cells. White cells of normal patients killed the mutant pneumococci as well as the otherwise isogenic wild-type strain. In patients studied with chronic granulomatous disease, however, the peroxide-poor strain was killed far less well than the wild type. These studies indicate that the removal of a peroxide-generating system in the phagocytic vacuole specifically brings forth the killing defect in chronic granulomatous disease. PMID:4148725

  3. Factors Affecting Zebra Mussel Kill by the Bacterium Pseudomonas fluorescens

    SciTech Connect

    Daniel P. Molloy

    2004-02-24

    The specific purpose of this research project was to identify factors that affect zebra mussel kill by the bacterium Pseudomonas fluorescens. Test results obtained during this three-year project identified the following key variables as affecting mussel kill: treatment concentration, treatment duration, mussel siphoning activity, dissolved oxygen concentration, water temperature, and naturally suspended particle load. Using this latter information, the project culminated in a series of pipe tests which achieved high mussel kill inside power plants under once-through conditions using service water in artificial pipes.

  4. Exoatmospheric Kill Vehicle Quality Assurance and Reliability Assessment - Part A

    DTIC Science & Technology

    2014-09-08

    No. DODIG-2014-111 S E P T E M B E R 8 , 2 0 1 4 Exoatmospheric Kill Vehicle Quality Assurance and Reliability Assessment – Part A Report...REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Exoatmospheric Kill Vehicle Quality Assurance and Reliability...Department of Defense F r a u d , W a s t e & A b u s e DODIG-2014-111 (Project No. D2013-DT0TAD-0005.000) │ i Results in Brief Exoatmospheric Kill Vehicle

  5. Hidden symmetries and killing tensors on curved spaces

    SciTech Connect

    Ianus, S.; Visinescu, M.; Vilcu, G. E.

    2010-11-15

    Higher-order symmetries corresponding to Killing tensors are investigated. The intimate relation between Killing-Yano tensors and nonstandard supersymmetries is pointed out. In the Dirac theory on curved spaces, Killing-Yano tensors generate Dirac-type operators involved in interesting algebraic structures as dynamical algebras or even infinite dimensional algebras or superalgebras. The general results are applied to space-times which appear in modern studies. One presents the infinite dimensional superalgebra of Dirac type operators on the 4-dimensional Euclidean Taub-NUT space that can be seen as a twisted loop algebra. The existence of the conformal Killing-Yano tensors is investigated for some spaces with mixed 3-Sasakian structures.

  6. Surface structure influences contact killing of bacteria by copper

    PubMed Central

    Zeiger, Marco; Solioz, Marc; Edongué, Hervais; Arzt, Eduard; Schneider, Andreas S

    2014-01-01

    Copper kills bacteria rapidly by a mechanism that is not yet fully resolved. The antibacterial property of copper has raised interest in its use in hospitals, in place of plastic or stainless steel. On the latter surfaces, bacteria can survive for days or even weeks. Copper surfaces could thus provide a powerful accessory measure to curb nosocomial infections. We here investigated the effect of the copper surface structure on the efficiency of contact killing of Escherichia coli, an aspect which so far has received very little attention. It was shown that electroplated copper surfaces killed bacteria more rapidly than either polished copper or native rolled copper. The release of ionic copper was also more rapid from electroplated copper compared to the other materials. Scanning electron microscopy revealed that the bacteria nudged into the grooves between the copper grains of deposited copper. The findings suggest that, in terms of contact killing, more efficient copper surfaces can be engineered. PMID:24740976

  7. PFIESTERIA SHUMWAYAE KILLS FISH BY MICROPREDATION NOT ECOTOXIN SECRETION

    EPA Science Inventory

    Massive fish kills in mid-Atlantic USA estuaries involving several million Atlantic menhaden, Brevoortia tyrannus,have been attributed to dinoflagellates of the toxic Pfiesteria complex (TPC). Potent ichthyotoxins secreted during Pfiesteria blooms are thought to be responsible fo...

  8. PFIESTERIA SHUMWAYAE KILLS FISH BY MICROPREDATION NOT ECOTOXIN SECRETION

    EPA Science Inventory

    Massive fish kills in mid-Atlantic USA estuaries involving several million Atlantic menhaden, Brevoortia tyrannus,have been attributed to dinoflagellates of the toxic Pfiesteria complex (TPC). Potent ichthyotoxins secreted during Pfiesteria blooms are thought to be responsible fo...

  9. US EPA, Pesticide Product Label, MOLE-NOTS KILLS MOLES ...

    EPA Pesticide Factsheets

    2011-04-14

    ... ' . I' \\ ~,I' !/~'k .' j /' ,I, ~~:, 11), Kills Moles & Gophers - -- -. J. ... r . • :: I \\ .• ~_. P G r""' l- i • ... • r I , -' .. j . , , . ' I , , "'. Is Mole ~ .s. (iuptle r

  10. Erythrocyte and leukocyte: two partners in bacteria killing.

    PubMed

    Minasyan, Hayk A

    2014-01-01

    Leukocytes can't perform phagocytosis in blood stream. Blood velocity prevents phagocytosis because there is no time for leukocyte to recognize and catch bacteria. Bloodstream clearance from pathogens is performed by erythrocytes. During motion in bloodstream erythrocytes become charged by triboelectric effect. This charge attracts bacteria and fixes them on the surface of erythrocyte, then bacteria are engulfed and killed by hemoglobin oxygen. In bloodstream, leukocyte thin-wrinkled elastic membrane can't be charged by triboelectric effect and so leukocyte can't catch bacteria by means of electrostatic attraction force. Leukocytes engulf and kill bacteria out of blood circulatory system: in tissues, lymph nodes, slow velocity lymph, etc. Erythrocyte and leukocyte are bactericidal partners: the first kills bacteria in bloodstream, the second kills them locally, out of blood circulation.

  11. 'Superbug' Resistant to All Antibiotics Killed Nevada Woman

    MedlinePlus

    ... gov/news/fullstory_163038.html 'Superbug' Resistant to All Antibiotics Killed Nevada Woman She died after possibly ... in September from a "superbug" infection that resisted all antibiotics, according to a report released Friday. The ...

  12. Superoxide dismutase protects Escherichia coli against killing by human serum.

    PubMed

    McManus, D C; Josephy, P D

    1995-02-20

    To assess the role of superoxide dismutase in protecting Escherichia coli from killing by human serum and neutrophils, we constructed isogenic, smooth-lipopolysaccharide K-12 strains, either sod wild-type, delta sodA, or delta sodA delta sodB. The delta sodA delta sodB strain was killed by serum much more readily than either the wild-type or delta sodA strain. After allowing for this serum sensitivity difference, the delta sodA delta sodB strain also showed increased susceptibility to phagocytic killing by human neutrophils. These results indicate that superoxide dismutase protects E. coli from killing by serum (complement system) and by human neutrophils, possibly by a role in maintaining bacterial membrane structure.

  13. Killing superalgebra deformations of ten-dimensional supergravity backgrounds

    NASA Astrophysics Data System (ADS)

    Figueroa-O'Farrill, José; Vercnocke, Bert

    2007-12-01

    We explore Lie superalgebra deformations of the Killing superalgebras of some ten-dimensional supergravity backgrounds. We prove the rigidity of the Poincaré superalgebras in types I, IIA and IIB, as well as of the Killing superalgebra of the Freund Rubin vacuum of type IIB supergravity. We also prove rigidity of the Killing superalgebras of the NS5-, D0-, D3-, D4- and D5-branes, whereas we exhibit the possible deformations of the D1-, D2-, D6- and D7-brane Killing superalgebras, as well as of that of the type II fundamental string solutions. We relate the superalgebra deformations of the D2- and D6-branes to those of the (delocalized) M2-brane and the Kaluza Klein monopole, respectively. The good behaviour under Kaluza Klein reduction suggests that the deformed superalgebras ought to have a geometric interpretation.

  14. Surface structure influences contact killing of bacteria by copper.

    PubMed

    Zeiger, Marco; Solioz, Marc; Edongué, Hervais; Arzt, Eduard; Schneider, Andreas S

    2014-06-01

    Copper kills bacteria rapidly by a mechanism that is not yet fully resolved. The antibacterial property of copper has raised interest in its use in hospitals, in place of plastic or stainless steel. On the latter surfaces, bacteria can survive for days or even weeks. Copper surfaces could thus provide a powerful accessory measure to curb nosocomial infections. We here investigated the effect of the copper surface structure on the efficiency of contact killing of Escherichia coli, an aspect which so far has received very little attention. It was shown that electroplated copper surfaces killed bacteria more rapidly than either polished copper or native rolled copper. The release of ionic copper was also more rapid from electroplated copper compared to the other materials. Scanning electron microscopy revealed that the bacteria nudged into the grooves between the copper grains of deposited copper. The findings suggest that, in terms of contact killing, more efficient copper surfaces can be engineered.

  15. Mouthwash Helps Kill Gonorrhea Germs in Mouth, Throat: Study

    MedlinePlus

    ... gov/news/fullstory_162649.html Mouthwash Helps Kill Gonorrhea Germs in Mouth, Throat: Study Listerine's maker has ... A commercial brand of mouthwash can help control gonorrhea bacteria in the mouth, and daily use may ...

  16. Antibacterial activity of silver-killed bacteria: the "zombies" effect

    PubMed Central

    Wakshlak, Racheli Ben-Knaz; Pedahzur, Rami; Avnir, David

    2015-01-01

    We report a previously unrecognized mechanism for the prolonged action of biocidal agents, which we denote as the zombies effect: biocidally-killed bacteria are capable of killing living bacteria. The concept is demonstrated by first killing Pseudomonas aeruginosa PAO1 with silver nitrate and then challenging, with the dead bacteria, a viable culture of the same bacterium: Efficient antibacterial activity of the killed bacteria is observed. A mechanism is suggested in terms of the action of the dead bacteria as a reservoir of silver, which, due to Le-Chatelier's principle, is re-targeted to the living bacteria. Langmuirian behavior, as well as deviations from it, support the proposed mechanism. PMID:25906433

  17. Nonreplicating vaccinia vector efficiently expresses recombinant genes.

    PubMed

    Sutter, G; Moss, B

    1992-11-15

    Modified vaccinia Ankara (MVA), a highly attenuated vaccinia virus strain that has been safety tested in humans, was evaluated for use as an expression vector. MVA has multiple genomic deletions and is severely host cell restricted: it grows well in avian cells but is unable to multiply in human and most other mammalian cells tested. Nevertheless, we found that replication of viral DNA appeared normal and that both early and late viral proteins were synthesized in human cells. Proteolytic processing of viral structural proteins was inhibited, however, and only immature virus particles were detected by electron microscopy. We constructed an insertion plasmid with the Escherichia coli lacZ gene under the control of the vaccinia virus late promoter P11, flanked by sequences of MVA DNA, to allow homologous recombination at the site of a naturally occurring 3500-base-pair deletion within the MVA genome. MVA recombinants were isolated and propagated in permissive avian cells and shown to express the enzyme beta-galactosidase upon infection of nonpermissive human cells. The amount of enzyme made was similar to that produced by a recombinant of vaccinia virus strain Western Reserve, which also had the lacZ gene under control of the P11 promoter, but multiplied to high titers. Since recombinant gene expression is unimpaired in nonpermissive human cells, MVA may serve as a highly efficient and exceptionally safe vector.

  18. Potassium Channels Mediate Killing by Human Natural Killer Cells

    NASA Astrophysics Data System (ADS)

    Schlichter, Lyanne; Sidell, Neil; Hagiwara, Susumu

    1986-01-01

    Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. However, no direct evidence exists for ion channels in NK cells or in their target cells. Using the whole-cell variation of the patch-clamp technique, we found a voltage-dependent potassium (K+) current in NK cells. The K+ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd2+. We tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard 51Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd2+, and 4-aminopyridine at concentrations comparable to those that blocked the K+ current in NK cells. In K562 target cells only a voltage-dependent Na+ current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K+ current was found that was similar to the one in NK cells. We could not find any evidence of a Ca2+ current in target cells or in NK cells; therefore, our results cannot explain the Ca dependence of killing. Our findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process. In contrast, the endogenous channel type in the target cell is probably not a factor in determining target cell

  19. Comparison of methods to evaluate bacterial contact-killing materials.

    PubMed

    van de Lagemaat, Marieke; Grotenhuis, Arjen; van de Belt-Gritter, Betsy; Roest, Steven; Loontjens, Ton J A; Busscher, Henk J; van der Mei, Henny C; Ren, Yijin

    2017-09-01

    Cationic surfaces with alkylated quaternary-ammonium groups kill adhering bacteria upon contact by membrane disruption and are considered increasingly promising as a non-antibiotic based way to eradicate bacteria adhering to surfaces. However, reliable in vitro evaluation methods for bacterial contact-killing surfaces do not yet exist. More importantly, results of different evaluation methods are often conflicting. Therefore, we compared five methods to evaluate contact-killing surfaces. To this end, we have copolymerized quaternary-ammonium groups into diurethane dimethacrylate/glycerol dimethacrylate (UDMA/GDMA) and determined contact-killing efficacies against five different Gram-positive and Gram-negative strains. Spray-coating bacteria from an aerosol onto contact-killing surfaces followed by air-drying as well as ASTM E2149-13a (American Society for Testing and Materials) were found unsuitable, while the Petrifilm® system and JIS Z 2801 (Japanese Industrial Standards) were found to be excellent methods to evaluate bacterial contact-killing surfaces. It is recommended however, that these methods be used in combination with a zone of inhibition on agar assay to exclude that leakage of antimicrobials from the material interferes with the contact-killing ability of the surface. Bacterial adhesion to surfaces of biomaterials implants can be life-threatening. Antimicrobials to treat biomaterial-associated infections often fail due to the bacterial biofilm-mode-of-growth or are ineffective due to antibiotic-resistance of causative organisms. Positively-charged, quaternized surfaces can kill bacteria upon contact and are promising as a non-antibiotic-based treatment of biomaterial-associated infections. Reliable methods to determine efficacies of contact-killing surfaces are lacking, however. Here, we show that three out of five methods compared, including an established ASTM, are unsuitable. Methods found suitable should be used in combination with a zone

  20. Potency of killed plague vaccines prepared from avirulent Yersinia pestis*

    PubMed Central

    Williams, James E.; Altieri, Patricia L.; Berman, Sanford; Lowenthal, Joseph P.; Cavanaugh, Dan C.

    1980-01-01

    Killed plague vaccines prepared from avirulent strains A1122 and EV76S of Yersinia pestis were more effective in mouse potency tests than samples of Plague Vaccine, USP, prepared from killed Y. pestis of the virulent strain 195/P. Manufacture of vaccine from avirulent Y. pestis would obviate requirements for the large containment facilities that are currently needed for producing Plague Vaccine, USP. PMID:6975184

  1. 1. GENERAL VIEW OF HOG KILLING ROOM ON LEVEL 4; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. GENERAL VIEW OF HOG KILLING ROOM ON LEVEL 4; LOOKING NORTHWEST; A PORTION OF THE SCALDING TANK IS VISIBLE AT EXTREME RIGHT, CENTER; CONCRETE PYLONS AT LOWER RIGHT SUPPORTED BY SCRAPING MACHINE; FINAL SCRAPING WAS DONE BY WORKERS STANDING ON ELEVATED PLATFORMS AT LEFT; BATHTUB-SHAPED CART NEAR CENTER OF PHOTO WAS USED TO TRANSPORT OFFAL TO RENDERING AREAS - Rath Packing Company, Hog Killing Building, Sycamore Street between Elm & Eighteenth Streets, Waterloo, Black Hawk County, IA

  2. Approximate Killing vectors on S{sup 2}

    SciTech Connect

    Cook, Gregory B.; Whiting, Bernard F.

    2007-08-15

    We present a new method for computing the best approximation to a Killing vector on closed 2-surfaces that are topologically S{sup 2}. When solutions of Killing's equation do not exist, this method is shown to yield results superior to those produced by existing methods. In addition, this method appears to provide a new tool for studying the horizon geometry of distorted black holes.

  3. Killing tensors in stationary and axially symmetric space-times

    NASA Astrophysics Data System (ADS)

    Vollmer, Andreas

    2017-05-01

    We discuss the existence of Killing tensors for certain (physically motivated) stationary and axially symmetric vacuum space-times. We show nonexistence of a nontrivial Killing tensor for a Tomimatsu-Sato metric (up to valence 7), for a C-metric (up to valence 9) and for a Zipoy-Voorhees metric (up to valence 11). The results are obtained by mathematically completely rigorous, nontrivial computer algebra computations with a huge number of equations involved in the problem.

  4. Moral dilemma: to kill or allow to die?

    PubMed

    Cole, J J

    1989-01-01

    The thesis of this paper is that while allowing a person to die with care can be morally justified in particular cases, the option of mercy killing can never be morally defended. There is a significant moral difference between these two concepts. Furthermore, the wedge argument, the medical fallibility argument, and the medical care and trust argument provide cogent and convincing reasons for maintaining a legal distinction between mercy killing and letting a person die.

  5. Oxidative and nonoxidative killing of Actinobacillus actinomycetemcomitans by human neutrophils.

    PubMed Central

    Miyasaki, K T; Wilson, M E; Brunetti, A J; Genco, R J

    1986-01-01

    Actinobacillus actinomycetemcomitans is a facultative gram-negative microorganism which has been implicated as an etiologic agent in localized juvenile periodontitis and in subacute bacterial endocarditis and abscesses. Although resistant to serum bactericidal action and to oxidant injury mediated by superoxide anion (O2-) and hydrogen peroxide (H2O2), this organism is sensitive to killing by the myeloperoxidase-hydrogen peroxide-chloride system (K.T. Miyasaki, M.E. Wilson, and R.J. Genco, Infect. Immun. 53:161-165, 1986). In this study, we examined the sensitivity of A. actinomycetemcomitans to killing by intact neutrophils under aerobic conditions, under anaerobic conditions, and under aerobic conditions in the presence of the heme-protein inhibitor sodium cyanide. Intact neutrophils killed opsonized A. actinomycetemcomitans under aerobic and anaerobic conditions, and the kinetics of these reactions indicated that both oxidative and nonoxidative mechanisms were operative. Oxidative mechanisms contributed significantly, and most of the killing attributable to oxidative mechanisms was inhibited by sodium cyanide, which suggested that the myeloperoxidase-hydrogen peroxide-chloride system participated in the oxidative process. We conclude that human neutrophils are capable of killing A. actinomycetemcomitans by both oxygen-dependent and oxygen-independent pathways, and that most oxygen-dependent killing requires myeloperoxidase activity. PMID:3013778

  6. Role of nitric oxide and superoxide in Giardia lamblia killing.

    PubMed

    Fernandes, P D; Assreuy, J

    1997-01-01

    Giardia lamblia trophozoites were incubated for 2 h with activated murine macrophages, nitric oxide (NO) donors or a superoxide anion generator (20 mU/ml xanthine oxidase plus 1 mM xanthine). Activated macrophages were cytotoxic to Giardia trophozoites (approximately 60% dead trophozoites). The effect was inhibited (> 90%) by an NO synthase inhibitor (200 microM) and unaffected by superoxide dismutase (SOD, 300 U/ml). Giardia trophozoites were killed by the NO donors, S-nitroso-acetyl-penicillamine (SNAP) and sodium nitroprusside (SNP) in a dose-dependent manner (LD50 300 and 50 microM, respectively). A dual NO-superoxide anion donor, 3-morpholino-sydnonimine hydrochloride (SIN-1), did not have a killing effect in concentrations up to 1 mM. However, when SOD (300 U/ml) was added simultaneously with SIN-1 to Giardia, a significant trophozoite-killing effect was observed (approximately 35% dead trophozoites at 1 mM). The mixtures of SNAP or SNP with superoxide anion, which yields peroxynitrite, abolished the trophozoite killing induced by NO donors. Authentic peroxynitrite only killed trophozoites at very high concentrations (3 mM). These results indicate that NO accounts for Giardia trophozoites killing and this effect is not mediated by peroxynitrite.

  7. Rotating Killing horizons in generic F( R) gravity theories

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Sourav

    2016-10-01

    We discuss various properties of rotating Killing horizons in generic F( R) theories of gravity in dimension four for spacetimes endowed with two commuting Killing vector fields. Assuming there is no curvature singularity anywhere on or outside the horizon, we construct a suitable (3+1)-foliation. We show that similar to Einstein's gravity, we must have T_{ab}k^ak^b=0 on the Killing horizon, where k^a is a null geodesic tangent to the horizon. For axisymmetric spacetimes, the effective gravitational coupling ˜ F'^{-1}(R) should usually depend upon the polar coordinate and hence need not necessarily be a constant on the Killing horizon. We prove that the surface gravity of such a Killing horizon must be a constant, irrespective of whether F'(R) is a constant there or not. We next apply these results to investigate some further basic features. In particular, we show that any hairy solution for the real massive vector field in such theories is clearly ruled out, as long as the potential of the scalar field generated in the corresponding Einstein's frame is a positive definite quantity.

  8. Prairie dogs increase fitness by killing interspecific competitors.

    PubMed

    Hoogland, John L; Brown, Charles R

    2016-03-30

    Interspecific competition commonly selects for divergence in ecology, morphology or physiology, but direct observation of interspecific competition under natural conditions is difficult. Herbivorous white-tailed prairie dogs (Cynomys leucurus) employ an unusual strategy to reduce interspecific competition: they kill, but do not consume, herbivorous Wyoming ground squirrels (Urocitellus elegans) encountered in the prairie dog territories. Results from a 6-year study in Colorado, USA, revealed that interspecific killing of ground squirrels by prairie dogs was common, involving 47 different killers; 19 prairie dogs were serial killers in the same or consecutive years, and 30% of female prairie dogs killed at least one ground squirrel over their lifetimes. Females that killed ground squirrels had significantly higher annual and lifetime fitness than non-killers, probably because of decreased interspecific competition for vegetation. Our results document the first case of interspecific killing of competing individuals unrelated to predation (IK) among herbivorous mammals in the wild, and show that IK enhances fitness for animals living under natural conditions. © 2016 The Author(s).

  9. Honor killing attitudes amongst adolescents in Amman, Jordan.

    PubMed

    Eisner, Manuel; Ghuneim, Lana

    2013-01-01

    The present study examines attitudes towards honor crimes amongst a sample of 856 ninth grade students (mean age = 14.6, SD = 0.56) from 14 schools in Amman, Jordan. Descriptive findings suggest that about 40% of boys and 20% of girls believe that killing a daughter, sister, or wife who has dishonored the family can be justified. A number of theoretically meaningful predictors were examined: Findings suggest that attitudes in support of honor killings are more likely amongst adolescents who have collectivist and patriarchal world views, believe in the importance of female chastity amongst adolescents, and morally neutralize aggressive behavior in general. Findings for parental harsh discipline are mixed: While the father's harsh discipline is predictive of honor killing attitudes, the mother's behavior is not. Furthermore, support for honor killing is stronger amongst male adolescents and adolescents for low education backgrounds. After controlling for other factors religion and the intensity of religious beliefs are not associated with support for honor killings. Models were tested separately for male and female respondents and suggested no systematic differences in predictors. Limitations and implications are discussed. © 2013 Wiley Periodicals, Inc.

  10. Acceptance of killing and homicide rates in nineteen nations.

    PubMed

    McAlister, Alfred L

    2006-06-01

    International variation in homicide rates may be attributable to cultural differences in acceptance of moral justifications for killing. The aim of this study is to investigate the relationships between measures of attitudes towards the justification of killing and homicide rates in diverse international populations. Four studies assessed variations in acceptance of killing among adults and young people in nineteen nations and four areas in the USA. Study 1 (1996-1997) assessed adult attitudes in Brazil, Chile, Costa Rica, Spain, and Venezuela with personal interviews in major cities. Study 2 (1999-2001) assessed attitudes among high school students in Denmark, Finland, Malta, Mexico, Netherlands, Slovenia, Sweden, Taiwan, and the UK with paper surveys administered in classrooms. Study 3 (2001) used telephone interviews to measure the equivalent attitudes among the US samples nationally and from regions in Texas. Study 4 (2002-2003) used paper surveys in classrooms to measure attitudes among high school students in Armenia, Belarus, Georgia, and the Russian Federation. The acceptance of killing varied significantly among genders and national/regional groups. The mean attitude scores in the four studies combined were significantly correlated with national/regional homicide rates and the amount of variance explained was similar to that for social inequality (GINI). Together the attitude scores and GINI explained 65% of the variance in homicide rates. This study provides evidence that variations in attitudes toward the justification of killing may be related to international differences in homicide rates.

  11. Killing the spores of Bacillus species by molecular iodine.

    PubMed

    Li, Q; Korza, G; Setlow, P

    2017-01-01

    To determine the responses of spores of Bacillus subtilis and Bacillus anthracis surrogate Bacillus thuringiensis Al Hakam to I2 treatment. Spores of B. subtilis and B. thuringiensis killed by aqueous 30°C-I2 could germinate, and their inner membrane (IM) was intact. Spore coats were important in I2 resistance, DNA-protective proteins were not important, and survivors of I2 treatment were not mutagenized. Viabilities of I2 -treated, 90-98% killed spores were much lower on high-salinity media, and the treated spores were more heat sensitive than the untreated spores. Germinated I2 -killed spores were dead as determined by staining with nucleic acid dyes, and many appeared to have been lysed. Aqueous I2 appeared to kill B. subtilis and B. thuringiensis spores such that spores lyse soon after they germinate, and not by causing DNA damage or rupture of spores' IM. I2 treatment also generated many damaged spores that could only be recovered under nonstressful conditions. This work shows that spores of the model organism B. subtilis, and B. thuringiensis, a surrogate for B. anthracis spores, exhibit similar mechanisms of resistance to and killing by I2 . Generation by I2 treatment of conditionally dead spores indicates that appropriate media are essential to efficiently enumerate viable I2 -treated spores. © 2016 The Society for Applied Microbiology.

  12. Prairie dogs increase fitness by killing interspecific competitors

    PubMed Central

    Brown, Charles R.

    2016-01-01

    Interspecific competition commonly selects for divergence in ecology, morphology or physiology, but direct observation of interspecific competition under natural conditions is difficult. Herbivorous white-tailed prairie dogs (Cynomys leucurus) employ an unusual strategy to reduce interspecific competition: they kill, but do not consume, herbivorous Wyoming ground squirrels (Urocitellus elegans) encountered in the prairie dog territories. Results from a 6-year study in Colorado, USA, revealed that interspecific killing of ground squirrels by prairie dogs was common, involving 47 different killers; 19 prairie dogs were serial killers in the same or consecutive years, and 30% of female prairie dogs killed at least one ground squirrel over their lifetimes. Females that killed ground squirrels had significantly higher annual and lifetime fitness than non-killers, probably because of decreased interspecific competition for vegetation. Our results document the first case of interspecific killing of competing individuals unrelated to predation (IK) among herbivorous mammals in the wild, and show that IK enhances fitness for animals living under natural conditions. PMID:27009223

  13. Disruption of Membrane by Colistin Kills Uropathogenic Escherichia coli Persisters and Enhances Killing of Other Antibiotics.

    PubMed

    Cui, Peng; Niu, Hongxia; Shi, Wanliang; Zhang, Shuo; Zhang, Hao; Margolick, Joseph; Zhang, Wenhong; Zhang, Ying

    2016-11-01

    Persisters are small populations of quiescent bacterial cells that survive exposure to bactericidal antibiotics and are responsible for many persistent infections and posttreatment relapses. However, little is known about how to effectively kill persister bacteria. In the work presented here, we found that colistin, a membrane-active antibiotic, was highly active against Escherichia coli persisters at high concentrations (25 or 50 μg/ml). At a clinically relevant lower concentration (10 μg/ml), colistin alone had no apparent effect on E. coli persisters. In combination with other drugs, this concentration of colistin enhanced the antipersister activity of gentamicin and ofloxacin but not that of ampicillin, nitrofurans, and sulfa drugs in vitro The colistin enhancement effect was most likely due to increased uptake of the other antibiotics, as demonstrated by increased accumulation of fluorescence-labeled gentamicin. Interestingly, colistin significantly enhanced the activity of ofloxacin and nitrofurantoin but not that of gentamicin or sulfa drugs in the murine model of urinary tract infection. Our findings suggest that targeting bacterial membranes is a valuable approach to eradicating persisters and should have implications for more effective treatment of persistent bacterial infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Killing and Noether Symmetries of Plane Symmetric Spacetime

    NASA Astrophysics Data System (ADS)

    Shamir, M. Farasat; Jhangeer, Adil; Bhatti, Akhlaq Ahmad

    2013-09-01

    This paper is devoted to investigate the Killing and Noether symmetries of static plane symmetric spacetime. For this purpose, five different cases have been discussed. The Killing and Noether symmetries of Minkowski spacetime in cartesian coordinates are calculated as a special case and it is found that Lie algebra of the Lagrangian is 10 and 17 dimensional respectively. The symmetries of Taub's universe, anti-deSitter universe, self similar solutions of infinite kind for parallel perfect fluid case and self similar solutions of infinite kind for parallel dust case are also explored. In all the cases, the Noether generators are calculated in the presence of gauge term. All these examples justify the conjecture that Killing symmetries form a subalgebra of Noether symmetries (Bokhari et al. in Int. J. Theor. Phys. 45:1063, 2006).

  15. Supersymmetric backgrounds, the Killing superalgebra, and generalised special holonomy

    NASA Astrophysics Data System (ADS)

    Coimbra, André; Strickland-Constable, Charles

    2016-11-01

    We prove that, for M theory or type II, generic Minkowski flux backgrounds preserving N supersymmetries in dimensions D ≥ 4 correspond precisely to integrable generalised {G}_{N} structures, where {G}_{N} is the generalised structure group defined by the Killing spinors. In other words, they are the analogues of special holonomy manifolds in {E}_{d(d)}× {R}+ generalised geometry. In establishing this result, we introduce the Kosmann-Dorfman bracket, a generalisation of Kosmann's Lie derivative of spinors. This allows us to write down the internal sector of the Killing superalgebra, which takes a rather simple form and whose closure is the key step in proving the main result. In addition, we find that the eleven-dimensional Killing superalgebra of these backgrounds is necessarily the supertranslational part of the N -extended super-Poincaré algebra.

  16. [Serial killings in a nursing home for the elderly].

    PubMed

    Doberentz, Elke; Musshoff, Frank; Madea, Burkhard

    2009-01-01

    In 2005, a 27-year-old nurse had been sentenced to life imprisonment for killing 9 female residents of the home within 3 years. After the post-mortem examination a natural death had been certified for all the victims. These 9 deaths were retrospectively analysed as to the motive and circumstances of the crime, the method applied, the results of the postmortem examination and the autopsy as well as the profile of the perpetrator. 8 victims had been smothered by blocking the external air passages with a soft fabric and one had been killed by omitting to remove secretion from the respiratory tract. The autopsies performed after exhumation did not furnish unequivocal evidence of homicide. Generally, the method of killing applied in these cases is known to leave almost no traces. Apart from the circumstantial evidence, the court had to base its decision on the confessions of the emotionally disturbed perpetrator, although she partly revoked these confessions later.

  17. Mathematical model for comparison of time-killing curves.

    PubMed Central

    Guerillot, F; Carret, G; Flandrois, J P

    1993-01-01

    The relevance of mathematical modeling to investigations of the bactericidal effects of antimicrobial agents has been emphasized in many studies of killing kinetics. We propose here a descriptive model of general use, with four parameters which account for the lag phase, the initial number of bacteria, and the limit of effectiveness and bactericidal rate of antimicrobial agents. The model has been applied to several kinetic datum sets with amoxicillin, cephalothin, nalidixic acid, pefloxacin, and ofloxacin against two Escherichia coli strains. It is a useful tool to compare killing curves by taking into account model parameter confidence limits. This can be illustrated by studying drug effects, strain effects, and concentration effects. For the antibiotics used here, concentration effects had an influence mainly on the length of the lag phase and the minimum number of living cells observed. It is therefore clear that differences in the killing curves with changes in one or more parameters could occur. PMID:8215284

  18. Aeromonas salmonicida resistance to complement-mediated killing.

    PubMed Central

    Merino, S; Albertí, S; Tomás, J M

    1994-01-01

    The resistance of Aeromonas salmonicida to complement-mediated killing was investigated by using different strains and their isogenic mutants that had been previously characterized for their surface components. We found that the classical complement pathway is involved in serum killing of susceptible A. salmonicida strains, while the alternative complement pathway seems not to be involved. All of the A. salmonicida strains are able to activate complement, but the smooth strains (with or without the A-layer) are resistant to complement-mediated killing. The reasons for this resistance are that C3b may be bound far from the cell membrane and that it is rapidly degraded; therefore, the lytic final complex C5b-9 (membrane attack complex) is not formed. Isogenic rough mutants are serum sensitive because they bind more C3b than the smooth strains, and if C3b is not completely degraded, then the lytic complex (C5b-9) is formed. Images PMID:7525485

  19. Humane killing of animals for disease control purposes.

    PubMed

    Thornber, P M; Rubira, R J; Styles, D K

    2014-04-01

    Killing for disease control purposes is an emotional issue for everyone concerned. Large-scale euthanasia or depopulation of animals may be necessary for the emergency control or eradication of animal diseases, to remove animals from a compromised situation (e.g. following flood, storm, fire, drought or a feed contamination event), to effect welfare depopulation when there is an oversupply due to a dysfunctional or closed marketing channel, or to depopulate and dispose of animals with minimal handling to decrease the risk of a zoonotic disease infecting humans. The World Organisation for Animal Health (OIE) developed international standards to provide advice on humane killing for various species and situations. Some fundamental issues are defined, such as competency of animal handling and implementation of humane killing techniques. Some of these methods have been used for many years, but novel approaches for the mass killing of particular species are being explored. Novel vaccines and new diagnostic techniques that differentiate between vaccinated and infected animals will save many animals from being killed as part of biosecurity response measures. Unfortunately, the destruction of affected livestock will still be required to control diseases whilst vaccination programmes are activated or where effective vaccines are not available. This paper reviews the principles of humane destruction and depopulation and explores available techniques with their associated advantages and disadvantages. It also identifies some current issues that merit consideration, such as legislative conflicts (emergency disease legislation versus animal welfare legislation, occupational health and safety), media issues, opinions on the future approaches to killing for disease control, and animal welfare.

  20. Azithromycin kills invasive Aggregatibacter actinomycetemcomitans in gingival epithelial cells.

    PubMed

    Lai, Pin-Chuang; Walters, John D

    2013-03-01

    Aggregatibacter actinomycetemcomitans invades periodontal pocket epithelium and is therefore difficult to eliminate by periodontal scaling and root planing. It is susceptible to azithromycin, which is taken up by many types of mammalian cells. This led us to hypothesize that azithromycin accumulation by gingival epithelium could enhance the killing of intraepithelial A. actinomycetemcomitans. [(3)H]azithromycin transport by Smulow-Glickman gingival epithelial cells and SCC-25 oral epithelial cells was characterized. To test our hypothesis, we infected cultured Smulow-Glickman cell monolayers with A. actinomycetemcomitans (Y4 or SUNY 465 strain) for 2 h, treated them with gentamicin to eliminate extracellular bacteria, and then incubated them with azithromycin for 1 to 4 h. Viable intracellular bacteria were released, plated, and enumerated. Azithromycin transport by both cell lines exhibited Michaelis-Menten kinetics and was competitively inhibited by l-carnitine and several other organic cations. Cell incubation in medium containing 5 μg/ml azithromycin yielded steady-state intracellular concentrations of 144 μg/ml in SCC-25 cells and 118 μg/ml in Smulow-Glickman cells. Azithromycin induced dose- and time-dependent intraepithelial killing of both A. actinomycetemcomitans strains. Treatment of infected Smulow-Glickman cells with 0.125 μg/ml azithromycin killed approximately 29% of the intraepithelial CFU of both strains within 4 h, while treatment with 8 μg/ml azithromycin killed ≥82% of the CFU of both strains (P < 0.05). Addition of carnitine inhibited the killing of intracellular bacteria by azithromycin (P < 0.05). Thus, human gingival epithelial cells actively accumulate azithromycin through a transport system that facilitates the killing of intraepithelial A. actinomycetemcomitans and is shared with organic cations.

  1. [Killing Effect of Carpesium abrotanoides on Taenia asiatica Cysticercus].

    PubMed

    Liu, Xiao-yan; Guo, Guang-wu; Wang, Heng

    2015-06-01

    The cysticerci of Taenia asiatica were cultured in vitro with different concentrations of water decoction of Carpesium abrotanoides (20, 40, and 60 mg/ml). The killing effect of C. abrotanoides on T. asiatica and the morphological change of cysticerci were observed under microscope 24 hours post-culture. The water decoction of C. abrotanoides showed significant killing effect on the cysticerci. The mortality of the parasites(95.0%, 57/60) was highest in 60 mg/ml group. The dead body of cysticercus shows shrunken with the enlarged scolex, and sucker tissue degenerated.

  2. Cars kill chimpanzees: case report of a wild chimpanzee killed on a road at Bulindi, Uganda.

    PubMed

    McLennan, Matthew R; Asiimwe, Caroline

    2016-07-01

    Roads have broadly adverse impacts on wildlife, including nonhuman primates. One direct effect is mortality from collisions with vehicles. While highly undesirable, roadkills provide valuable information on the health and condition of endangered species. We present a case report of a wild chimpanzee (Pan troglodytes schweinfurthii) killed crossing a road in Bulindi, Uganda, where chimpanzees inhabit forest fragments amid farmland. Details of the collision are constructed from eyewitness accounts of pedestrians. Physical examination of the cadaver indicated good overall body condition; at 40 kg, the deceased female was heavier than usual for an adult female East African chimpanzee. No external wounds or fractures were noted. Coprological assessment demonstrated infection by several gastrointestinal parasites commonly reported in living wild chimpanzees. Histopathology revealed eosinophilic enteritis and biliary hyperplasia potentially caused by parasite infection. However, eosinophilia was not widely spread into the submucosa, while egg/cyst counts suggested low-intensity parasite infections compared to healthy female chimpanzees of similar age in nearby Budongo Forest. No behavioral indicators of ill health were noted in the deceased female in the month prior to the accident. We conclude that cause of death was acute, i.e., shock from the collision, and was probably unrelated to parasite infection or any other underlying health condition. Notably, this female had asymmetrical polythelia, and, while nursing at the time of her death, had one functioning mammary gland only. In Uganda, where primates often inhabit human-dominated landscapes, human population growth and economic development has given rise to increasing motor traffic, while road development is enabling motorists to travel at greater speeds. Thus, the danger of roads to apes and other wildlife is rising, necessitating urgent strategies to reduce risks. Installation of simple speed-bumps-common on Ugandan

  3. Killing Range: Explaining Lethality Variance within a Terrorist Organization.

    PubMed

    Asal, Victor; Gill, Paul; Rethemeyer, R Karl; Horgan, John

    2015-04-01

    This paper presents an analysis of the Provisional Irish Republican Army's (PIRA) brigade level behavior during the Northern Ireland Conflict (1970-1998) and identifies the organizational factors that impact a brigade's lethality as measured via terrorist attacks. Key independent variables include levels of technical expertise, cadre age, counter-terrorism policies experienced, brigade size, and IED components and delivery methods. We find that technical expertise within a brigade allows for careful IED usage, which significantly minimizes civilian casualties (a specific strategic goal of PIRA) while increasing the ability to kill more high value targets with IEDs. Lethal counter-terrorism events also significantly affect a brigade's likelihood of killing both civilians and high-value targets but in different ways. Killing PIRA members significantly decreases IED fatalities but also significantly decreases the possibility of zero civilian IED-related deaths in a given year. Killing innocent Catholics in a Brigade's county significantly increases total and civilian IED fatalities. Together the results suggest the necessity to analyze dynamic situational variables that impact terrorist group behavior at the sub-unit level.

  4. Neocognitron trained with winner-kill-loser rule.

    PubMed

    Fukushima, Kunihiko

    2010-09-01

    The neocognitron, which was proposed by Fukushima (1980), is a hierarchical multi-layered neural network capable of robust visual pattern recognition. It acquires the ability to recognize patterns through learning. This paper proposes a new rule for competitive learning, named winner-kill-loser, and apply it to the neocognitron. The winner-kill-loser rule resembles the winner-take-all rule. Every time when a training stimulus is presented, non-silent cells compete with each other. The winner, however, not only takes all, but also kills losers. In other words, the winner learns the training stimulus, and losers are removed from the network. If all cells are silent, a new cell is generated and it learns the training stimulus. Thus feature-extracting cells gradually come to distribute uniformly in the feature space. The use of winner-kill-loser rule is not limited to the neocognitron. It is useful for various types of competitive learning, in general. This paper also proposes several improvements made on the neocognitron: such as, disinhibition to the inhibitory surround in the connections to C-cells (or complex cells) from S-cells (or simple cells); and square root shaped saturation in the input-to-output characteristics of C-cells. As a result of these improvements, the recognition rate of the neocognitron has been largely increased.

  5. What Is John Dewey Doing in "To Kill a Mockingbird"?

    ERIC Educational Resources Information Center

    Frank, Jeff

    2015-01-01

    Harper Lee's novel "To Kill a Mockingbird" is taught in countless public schools and is beloved by many teachers and future teachers. Embedded within this novel--interestingly--is a strong criticism of an approach to education mockingly referred to as the "Dewey Decimal System." In this essay I explore Lee's criticism of…

  6. Binary black hole spacetimes with a helical Killing vector

    SciTech Connect

    Klein, Christian

    2004-12-15

    Binary black hole spacetimes with a helical Killing vector, which are discussed as an approximation for the early stage of a binary system, are studied in a projection formalism. In this setting the four-dimensional Einstein equations are equivalent to a three-dimensional gravitational theory with a SL(2,R)/SO(1,1) sigma model as the material source. The sigma model is determined by a complex Ernst equation. 2+1 decompositions of the three-metric are used to establish the field equations on the orbit space of the Killing vector. The two Killing horizons of spherical topology which characterize the black holes, the cylinder of light where the Killing vector changes from timelike to spacelike, and infinity are singular points of the equations. The horizon and the light cylinder are shown to be regular singularities, i.e., the metric functions can be expanded in a formal power series in the vicinity. The behavior of the metric at spatial infinity is studied in terms of formal series solutions to the linearized Einstein equations. It is shown that the spacetime is not asymptotically flat in the strong sense to have a smooth null infinity under the assumption that the metric tends asymptotically to the Minkowski metric. In this case the metric functions have an oscillatory behavior in the radial coordinate in a nonaxisymmetric setting, the asymptotic multipoles are not defined. The asymptotic behavior of the Weyl tensor near infinity shows that there is no smooth null infinity.

  7. Comparison microbial killing efficacy between sonodynamic therapy and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Drantantiyas, Nike Dwi Grevika; Astuti, Suryani Dyah; Nasution, Aulia M. T.

    2016-11-01

    Biofilm is a way used by bacteria to survive from their environmental conditions by forming colony of bacteria. Specific characteristic in biofilm formation is the availability of matrix layer, known as extracellular polymer substance. Treatment using antibiotics may lead bacteria to be to resistant. Other treatments to reduce microbial, like biofilm, can be performed by using photodynamic therapy. Successful of this kind of therapy is induced by penetration of light and photosensitizer into target cells. The sonodynamic therapy offers greater penetrating capability into tissues. This research aimed to use sonodynamic therapy in reducing biofilm. Moreover, it compares also the killing efficacy of photodynamic therapy, sonodynamic therapy, and the combination of both therapeutic schemes (known as sono-photodynamic) to achieve higher microbial killing efficacy. Samples used are Staphylococcus aureus biofilm. Treatments were divided into 4 groups, i.e. group under ultrasound treatment with variation of 5 power levels, group of light treatment with exposure of 75s, group of combined ultrasound-light with variation of ultrasound power levels, and group of combined lightultrasound with variation of ultrasound power levels. Results obtained for each treatment, expressed in % efficacy of log CFU/mL, showed that the treatment of photo-sonodynamic provides greater killing efficacy in comparison to either sonodynamic and sono-photodynamic. The photo-sonodynamic shows also greater efficacy to photodynamic. So combination of light-ultrasound (photo-sonodynamic) can effectively kill microbial biofilm. The combined therapy will provide even better efficacy using exogenous photosensitizer.

  8. Illegal killing for ivory drives global decline in African elephants

    PubMed Central

    Wittemyer, George; Northrup, Joseph M.; Blanc, Julian; Douglas-Hamilton, Iain; Omondi, Patrick; Burnham, Kenneth P.

    2014-01-01

    Illegal wildlife trade has reached alarming levels globally, extirpating populations of commercially valuable species. As a driver of biodiversity loss, quantifying illegal harvest is essential for conservation and sociopolitical affairs but notoriously difficult. Here we combine field-based carcass monitoring with fine-scale demographic data from an intensively studied wild African elephant population in Samburu, Kenya, to partition mortality into natural and illegal causes. We then expand our analytical framework to model illegal killing rates and population trends of elephants at regional and continental scales using carcass data collected by a Convention on International Trade in Endangered Species program. At the intensively monitored site, illegal killing increased markedly after 2008 and was correlated strongly with the local black market ivory price and increased seizures of ivory destined for China. More broadly, results from application to continental data indicated illegal killing levels were unsustainable for the species between 2010 and 2012, peaking to ∼8% in 2011 which extrapolates to ∼40,000 elephants illegally killed and a probable species reduction of ∼3% that year. Preliminary data from 2013 indicate overharvesting continued. In contrast to the rest of Africa, our analysis corroborates that Central African forest elephants experienced decline throughout the last decade. These results provide the most comprehensive assessment of illegal ivory harvest to date and confirm that current ivory consumption is not sustainable. Further, our approach provides a powerful basis to determine cryptic mortality and gain understanding of the demography of at-risk species. PMID:25136107

  9. Partner Killing by Men in Cohabiting and Marital Relationships

    ERIC Educational Resources Information Center

    Shackelford, Todd K.; Mouzos, Jenny

    2005-01-01

    Using a national-level U.S. database, T. K. Shackelford (2001) calculated rates of uxoricide (the murder of a woman by her romantic partner) by relationship type (cohabiting or marital), by ages of the partners, and by the age difference between partners. Women in cohabiting relationships were 9 times more likely to be killed by their partner than…

  10. An attract-and-kill strategy for Asian citrus psyllid

    USDA-ARS?s Scientific Manuscript database

    Asian citrus psyllids (ACP) transmit the pathogen responsible for citrus greening disease. Psyllids use color, smell, taste and vibrational cues to identify their host plants and conspecifics. The main goal of this project is to develop an attract-and-kill device strategy that will exploit the psyll...

  11. Painless killing of crabs and other large crustaceans.

    PubMed

    GUNTER, G

    1961-02-03

    Large crustaceans used for food are customarily scalded to death. This is unnecessary torture, for it can be avoided easily. It is possible to kill the animals quickly, without pain, by placing them in cool fresh water and raising the temperature steadily to about 40 degrees C.

  12. Prevent Tipping Furniture from Injuring or Killing Young Children

    MedlinePlus

    ... more upsetting than the sudden death of a child — killed by a piece of a furniture, appliance or a television falling on them. “It can happen in a ... be secured. Check with home improvement stores or child retail stores and ask experts what they ... television and computer equipment low to the ground. Do ...

  13. Selecting timber species to replace killed firetree in Hawaii

    Treesearch

    Gerald A. Walters

    1970-01-01

    A species with little commercial value, firetree (Myrica faya Ait.) infests several islands of Hawaii. A test of replacing herbicide-killed firetrees by underplanting selected timber species is underway. Among the seven species planted, Austrailan toon-on the basis of its initial survival and growth-shows the most promise for reforestation. Falling...

  14. Killing for Girls: Predation Play and Female Empowerment

    ERIC Educational Resources Information Center

    Bertozzi, Elena

    2012-01-01

    Predation games--games in which the player is actively encouraged and often required to hunt and kill in order to survive--have historically been the purview of male players. Females, though now much more involved in digital games than before, generally play games that stress traditionally feminine values such as socializing with others, shopping,…

  15. Male-killing Wolbachia in two species of insect

    PubMed Central

    Hurst, G. D. D.; Jiggins, F. M.; Schulenburg, J. H. G. von der; Bertrand, D.; West, S. A.; Goriacheva, I. I.; Zakharov, I. A.; Werren, J. H.; Stouthamer, R.; Majerus, M. E. N.

    1999-01-01

    The inherited bacterium Wolbachia spreads through the manipulation of host reproduction, and has been suggested to be an important factor in arthropod evolution, from host speciation to the evolution of sex-determination systems. Past work has shown that members of this group may produce cytoplasmic incompatibility, feminize genetically male hosts, and induce host parthenogenesis. Here, we report an expansion of the range of reproductive manipulations produced by members of this clade, recording Wolbachia strains that kill male hosts during embryogenesis in two host species, the ladybird Adalia bipunctata, and the butterfly Acraea encedon. Both male-killing bacteria belong to the B group of Wolbachia. However, phylogenetic analyses were unable to resolve whether the bacteria in the two species are monophyletic, or represent independent origins of male-killing among the B-group Wolbachia. We also found significant divergence within the wsp gene of Wolbachia strains found in different A. bipunctata individuals, suggesting this host species contains two Wolbachia strains, diverged in wsp sequence but monophyletic. Our observations reinforce the notion that Wolbachia may be an important agent driving arthropod evolution, and corroborates previous suggestions that male-killing behaviour is easily evolved by invertebrate symbionts.

  16. Saying the Unsaid: Girl Killing and the Curriculum.

    ERIC Educational Resources Information Center

    Perlstein, Daniel

    1998-01-01

    Although students in Jonesboro, Arkansas, repeatedly claimed that the March 1998 killing of four schoolgirls and a teacher was motivated by a rejected boy's desire for revenge, reporters and authorities dismissed this explanation and gender's role in the crime. Closer analysis suggests opportunities and difficulties for educators who want…

  17. Copper as a magic bullet for targeted microbial killing.

    PubMed

    Cavet, Jennifer S

    2014-08-14

    The innate toxicity of copper can be exploited as an antimicrobial. In this issue of Chemistry & Biology Festa and colleagues report the use of QBP, a prochelator form of the metal-chelate 8-hydroxyquinolone, which allows for targeted copper-dependent microbial killing at sites of infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Karo-kari: a form of honour killing in pakistan.

    PubMed

    Patel, Sujay; Gadit, Amin Muhammad

    2008-12-01

    Karo-Kari is a type of premeditated honour killing, which originated in rural and tribal areas of Sindh, Pakistan. The homicidal acts are primarily committed against women who are thought to have brought dishonour to their family by engaging in illicit pre-marital or extra-marital relations. In order to restore this honour, a male family member must kill the female in question. We conducted a systematic review of the published literature other sources on karo-kari and related forms of honour killing or violence against women. Media and non-governmental organization reports were utilized for case studies and analysis. Although legally proscribed, socio-cultural factors and gender role expectations have given legitimacy to karo-kari within some tribal communities. In addition to its persistence in areas of Pakistan, there is evidence that karo-kari may be increasing in incidence in other parts of the world in association with migration. Moreover, perpetrators of ;honour killings' often have motives outside of female adultery. Analysis of the socio-cultural and psycho-pathological factors associated with the practice of karo-kari can guide the development of prevention strategies.

  19. The Fish Kill Mystery: Learning about Aquatic Communities

    ERIC Educational Resources Information Center

    Kosal, Erica F.

    2004-01-01

    This paper presents a case where students can learn about aquatic communities. In this case, students speculate on what may have caused a major fish kill in an estuary in North Carolina. In the process, they explore how land runoff and excess nutrients affect aquatic communities. They also learn about the complex life cycle of the dinoflagellate…

  20. Killing of Gyrodactylus salaris (Platyhelminthes, Monogenea) mediated by host complement.

    PubMed

    Harris, P D; Soleng, A; Bakke, T A

    1998-08-01

    Gyrodactylus salaris, an important pathogen of Atlantic salmon Salmo salar, has been shown to be highly sensitive to factors in host serum and mucus, being killed rapidly (50% within 1 h) by serum at a dilution of 1:200. The time needed for killing was inversely proportional to serum concentration. Similar effects were noted using host mucus, which contained approximately 1/20th of the anti-Gyrodactylus activity of serum. Serum activity was abolished completely by heating at 45 degrees C for 30 min, and by addition of EDTA, but not by EGTA + 1 mM magnesium ions. Activity was not dependent on whether the serum was from infected or naive fishes, nor was it species specific. Attempts to pre-coat parasites in salmon anti-Gyrodactylus antibodies also failed to enhance the activity of fresh serum. These observations suggest that killing is due to the complement system of the host, acting via the alternate pathway. G. salaris appears to be exceptionally sensitive to complement, being killed at concentrations which could be experienced in vivo. The role of complement in the protection of fishes against gyrodactylid infection therefore deserves further investigation.

  1. Pfiesteria shumwayae kills fish by micropredation not exotoxin secretion.

    PubMed

    Vogelbein, Wolfgang K; Lovko, Vincent J; Shields, Jeffrey D; Reece, Kimberly S; Mason, Patrice L; Haas, Leonard W; Walker, Calvin C

    2002-08-29

    Pfiesteria piscicida and P. shumwayae reportedly secrete potent exotoxins thought to cause fish lesion events, acute fish kills and human disease in mid-Atlantic USA estuaries. However, Pfiesteria toxins have never been isolated or characterized. We investigated mechanisms by which P. shumwayae kills fish using three different approaches. Here we show that larval fish bioassays conducted in tissue culture plates fitted with polycarbonate membrane inserts exhibited mortality (100%) only in treatments where fish and dinospores were in physical contact. No mortalities occurred in treatments where the membrane prevented contact between dinospores and fish. Using differential centrifugation and filtration of water from a fish-killing culture, we produced 'dinoflagellate', 'bacteria' and 'cell-free' fractions. Larval fish bioassays of these fractions resulted in mortalities (60-100% in less than 24 h) only in fractions containing live dinospores ('whole water', 'dinoflagellate'), with no mortalities in 'cell-free' or 'bacteria'-enriched fractions. Videomicrography and electron microscopy show dinospores swarming toward and attaching to skin, actively feeding, and rapidly denuding fish of epidermis. We show here that our cultures of actively fish-killing P. shumwayae do not secrete potent exotoxins; rather, fish mortality results from micropredatory feeding.

  2. Illegal killing for ivory drives global decline in African elephants.

    PubMed

    Wittemyer, George; Northrup, Joseph M; Blanc, Julian; Douglas-Hamilton, Iain; Omondi, Patrick; Burnham, Kenneth P

    2014-09-09

    Illegal wildlife trade has reached alarming levels globally, extirpating populations of commercially valuable species. As a driver of biodiversity loss, quantifying illegal harvest is essential for conservation and sociopolitical affairs but notoriously difficult. Here we combine field-based carcass monitoring with fine-scale demographic data from an intensively studied wild African elephant population in Samburu, Kenya, to partition mortality into natural and illegal causes. We then expand our analytical framework to model illegal killing rates and population trends of elephants at regional and continental scales using carcass data collected by a Convention on International Trade in Endangered Species program. At the intensively monitored site, illegal killing increased markedly after 2008 and was correlated strongly with the local black market ivory price and increased seizures of ivory destined for China. More broadly, results from application to continental data indicated illegal killing levels were unsustainable for the species between 2010 and 2012, peaking to ∼ 8% in 2011 which extrapolates to ∼ 40,000 elephants illegally killed and a probable species reduction of ∼ 3% that year. Preliminary data from 2013 indicate overharvesting continued. In contrast to the rest of Africa, our analysis corroborates that Central African forest elephants experienced decline throughout the last decade. These results provide the most comprehensive assessment of illegal ivory harvest to date and confirm that current ivory consumption is not sustainable. Further, our approach provides a powerful basis to determine cryptic mortality and gain understanding of the demography of at-risk species.

  3. What Is John Dewey Doing in "To Kill a Mockingbird"?

    ERIC Educational Resources Information Center

    Frank, Jeff

    2015-01-01

    Harper Lee's novel "To Kill a Mockingbird" is taught in countless public schools and is beloved by many teachers and future teachers. Embedded within this novel--interestingly--is a strong criticism of an approach to education mockingly referred to as the "Dewey Decimal System." In this essay I explore Lee's criticism of…

  4. Developing a Critical Literacy Approach with "To Kill a Mockingbird."

    ERIC Educational Resources Information Center

    Spires, Marian

    2000-01-01

    Ponders why the novel "To Kill a Mockingbird" has held a place in the secondary school canon for 40 years. Describes a 10-week unit for year 10 English students that takes a critical literacy approach to the novel. Outlines a set of pre-reading activities, during reading activities and post-reading activities. (SR)

  5. Natural falling of beetle-killed ponderosa pine

    Treesearch

    J. M. Schmid; S. A. Mata; W. F. McCambridge

    1985-01-01

    Beetle-killed trees in the Front Range of Colorado were observed for their rate and direction of falling. No trees fell within the 2 years following infestation. Thereafter, trees generally fell at the rate of 3-5% per year unless winds exceeded 75 mph. Most trees fell to the east and broke off between ground level and 2 feet above ground.

  6. Male-killing Wolbachia in a flour beetle.

    PubMed Central

    Fialho, R F; Stevens, L

    2000-01-01

    The bacteria in the genus Wolbachia are cytoplasmically inherited symbionts of arthropods. Infection often causes profound changes in host reproduction, enhancing bacterial transmission and spread in a population. The reproductive alterations known to result from Wolbachia infection include cytoplasmic incompatibility (CI), parthenogenesis, feminization of genetic males, fecundity enhancement, male killing and, perhaps, lethality Here, we report male killing in a third insect, the black flour beetle Tribolium madens, based on highly female-biased sex ratios of progeny from females infected with Wolbachia. The bias is cytoplasmic in nature as shown by repeated backcrossing of infected females with males of a naturally uninfected strain. Infection also lowers the egg hatch rates significantly to approximately half of those observed for uninfected females. Treatment of the host with antibiotics eliminated infection, reverted the sex ratio to unbiased levels and increased the percentage hatch. Typically Wolbachia infection is transmitted from mother to progeny, regardless of the sex of the progeny; however, infected T. madens males are never found. Virgin females are sterile, suggesting that the sex-ratio distortion in T. madens results from embryonic male killing rather than parthenogenesis. Based on DNA sequence data, the male-killing strain of Wolbachia in T. madens was indistinguishable from the CI-inducing Wolbachia in Tribolium confusum, a closely related beetle. Our findings suggest that host symbiont interaction effects may play an important role in the induction of Wolbachia reproductive phenotypes. PMID:10983833

  7. Killing for Girls: Predation Play and Female Empowerment

    ERIC Educational Resources Information Center

    Bertozzi, Elena

    2012-01-01

    Predation games--games in which the player is actively encouraged and often required to hunt and kill in order to survive--have historically been the purview of male players. Females, though now much more involved in digital games than before, generally play games that stress traditionally feminine values such as socializing with others, shopping,…

  8. Partner Killing by Men in Cohabiting and Marital Relationships

    ERIC Educational Resources Information Center

    Shackelford, Todd K.; Mouzos, Jenny

    2005-01-01

    Using a national-level U.S. database, T. K. Shackelford (2001) calculated rates of uxoricide (the murder of a woman by her romantic partner) by relationship type (cohabiting or marital), by ages of the partners, and by the age difference between partners. Women in cohabiting relationships were 9 times more likely to be killed by their partner than…

  9. 20. Bronx Kill Bridge with Hell Gate Bridge in background. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Bronx Kill Bridge with Hell Gate Bridge in background. Randalls Island, New York Co., NY. Sec. 4207, MP 8.54. - Northeast Railroad Corridor, Amtrak Route between New Jersey/New York & New York/Connecticut State Lines, New York County, NY

  10. AKT and oxidative stress team up to kill cancer cells.

    PubMed

    Dolado, Ignacio; Nebreda, Angel R

    2008-12-09

    AKT, a protein kinase frequently hyperactivated in cancer, plays an important role in cell survival and contributes to tumor cell resistance to cytotoxic therapies. A new study in this issue of Cancer Cell shows that AKT also induces the accumulation of oxygen radicals, which can be exploited to selectively kill cancer cells containing high levels of AKT activity.

  11. Killing cull trees with ammate crystals - a case study

    Treesearch

    Harry W. Yawney

    1961-01-01

    The use of ammate (ammonium sulfamate) as a tree-killing agent has become widespread during recent years; it is well established as an effective and economical silvicide. The purpose of this report is to supplement present knowledge and also to present a case study on the use of ammate in practical application.

  12. Pseudomonas Exotoxin A: optimized by evolution for effective killing

    PubMed Central

    Michalska, Marta; Wolf, Philipp

    2015-01-01

    Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa. This review describes current knowledge about the intoxication pathways of PE. Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells. PMID:26441897

  13. The Fish Kill Mystery: Learning about Aquatic Communities

    ERIC Educational Resources Information Center

    Kosal, Erica F.

    2004-01-01

    This paper presents a case where students can learn about aquatic communities. In this case, students speculate on what may have caused a major fish kill in an estuary in North Carolina. In the process, they explore how land runoff and excess nutrients affect aquatic communities. They also learn about the complex life cycle of the dinoflagellate…

  14. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been...

  15. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Rabies Vaccine, Killed Virus. 113.209 Section 113.209 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...

  16. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been...

  17. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Rabies Vaccine, Killed Virus. 113.209 Section 113.209 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...

  18. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Rabies Vaccine, Killed Virus. 113.209 Section 113.209 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...

  19. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been...

  20. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Killed Virus. 113.209 Section 113.209 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...

  1. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Rabies Vaccine, Killed Virus. 113.209 Section 113.209 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF...

  2. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which has been...

  3. 9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Newcastle Disease Vaccine, Killed Virus. 113.205 Section 113.205 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... eggs or cell cultures. With the exception of § 113.200(c)(2)(iii), each serial shall meet the...

  4. 9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Newcastle Disease Vaccine, Killed Virus. 113.205 Section 113.205 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... eggs or cell cultures. With the exception of § 113.200(c)(2)(iii), each serial shall meet the...

  5. 9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Newcastle Disease Vaccine, Killed Virus. 113.205 Section 113.205 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... eggs or cell cultures. With the exception of § 113.200(c)(2)(iii), each serial shall meet the...

  6. 9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Newcastle Disease Vaccine, Killed Virus. 113.205 Section 113.205 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... eggs or cell cultures. With the exception of § 113.200(c)(2)(iii), each serial shall meet the...

  7. Hidden symmetries and Lie algebra structures from geometric and supergravity Killing spinors

    NASA Astrophysics Data System (ADS)

    Açık, Özgür; Ertem, Ümit

    2016-08-01

    We consider geometric and supergravity Killing spinors and the spinor bilinears constructed out of them. The spinor bilinears of geometric Killing spinors correspond to the antisymmetric generalizations of Killing vector fields which are called Killing-Yano forms. They constitute a Lie superalgebra structure in constant curvature spacetimes. We show that the Dirac currents of geometric Killing spinors satisfy a Lie algebra structure up to a condition on 2-form spinor bilinears. We propose that the spinor bilinears of supergravity Killing spinors give way to different generalizations of Killing vector fields to higher degree forms. It is also shown that those supergravity Killing forms constitute a Lie algebra structure in six- and ten-dimensional cases. For five- and eleven-dimensional cases, the Lie algebra structure depends on an extra condition on supergravity Killing forms.

  8. Killing of Klebsiella pneumoniae by human alveolar macrophages.

    PubMed

    Hickman-Davis, Judy M; O'Reilly, Philip; Davis, Ian C; Peti-Peterdi, Janos; Davis, Glenda; Young, K Randall; Devlin, Robert B; Matalon, Sadis

    2002-05-01

    We investigated putative mechanisms by which human surfactant protein A (SP-A) effects killing of Klebsiella pneumoniae by human alveolar macrophages (AMs) isolated from bronchoalveolar lavagates of patients with transplanted lungs. Coincubation of AMs with human SP-A (25 microg/ml) and Klebsiella resulted in a 68% decrease in total colony forming units by 120 min compared with AMs infected with Klebsiella in the absence of SP-A, and this SP-A-mediated effect was abolished by preincubation with N(G)-monomethyl-L-arginine. Incubation of transplant AMs with SP-A increased intracellular Ca(2+) concentration ([Ca(2+)](i)) by 70% and nitrite and nitrate (NO(x)) production by 45% (from 0.24 +/- 0.02 to 1.3 +/- 0.21 nmol small middle dot 10(6) AMs(-1).h(-1)). Preincubation with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester inhibited the increase in [Ca(2+)](i) and abrogated the SP-A-mediated Klebsiella phagocytosis and killing. In contrast, incubation of AMs from normal volunteers with SP-A decreased both [Ca(2+)](i) and NO(x) production and did not result in killing of Klebsiella. Significant killing of Klebsiella was also seen in a cell-free system by sustained production of peroxynitrite (>1 microM/min) at pH 5 but not at pH 7.4. These findings indicate that SP-A mediates pathogen killing by AMs from transplant lungs by stimulating phagocytosis and production of reactive oxygen-nitrogen intermediates.

  9. Spiroplasma infection causes either early or late male killing in Drosophila, depending on maternal host age

    NASA Astrophysics Data System (ADS)

    Kageyama, Daisuke; Anbutsu, Hisashi; Shimada, Masakazu; Fukatsu, Takema

    2007-04-01

    Symbiont-induced male-killing phenotypes have been found in a variety of insects. Conventionally, these phenotypes have been divided into two categories according to the timing of action: early male killing at embryonic stages and late male killing at late larval stages. In Drosophila species, endosymbiotic bacteria of the genus Spiroplasma have been known to cause early male killing. Here, we report that a spiroplasma strain normally causing early male killing also induces late male killing depending on the maternal host age: male-specific mortality of larvae and pupae was more frequently observed in the offspring of young females. As the lowest spiroplasma density and occasional male production were also associated with newly emerged females, we proposed the density-dependent hypothesis for the expression of early and late male-killing phenotypes. Our finding suggested that (1) early and late male-killing phenotypes can be caused by the same symbiont and probably by the same mechanism; (2) late male killing may occur as an attenuated expression of early male killing; (3) expression of early and late male-killing phenotypes may be dependent on the symbiont density, and thus, could potentially be affected by the host immunity and regulation; and (4) early male killing and late male killing could be alternative strategies adopted by microbial reproductive manipulators.

  10. Secondary Kill Effect of Deltamethrin on Triatoma infestans

    PubMed Central

    MALONEY, KATHLEEN M.; ANCCA-JUAREZ, JENNY; SALAZAR, RENZO; BORRINI-MAYORI, KATTY; PAMO-TITO, DANITZA; KEATING, JOSEPH A.; LEVY, MICHAEL Z.

    2012-01-01

    Control of the Chagas disease vector, Triatoma infestans, relies on the application of pyrethroid insecticides, especially deltamethrin. We performed laboratory studies to determine whether a T. infestans nymph that comes into contact with a deltamethrin-treated surface horizontally transfers the insecticide to subsequent triatomines. We found that a triatomine that walks on a deltamethrin-treated surface for a short period of time has the ability to transport the insecticide in concentrations sufficient to kill other triatomines with which it comes into contact. The effect was limited to high-density environments, and mortality as a result of secondary exposure was greater among second-instar nymphs compared with fifth-instar nymphs. Our results suggest that deltamethrin could be killing triatomines through both direct and indirect contact, although it remains unclear whether the phenomenon occurs in natural conditions. PMID:21845956

  11. Great tits search for, capture, kill and eat hibernating bats

    PubMed Central

    Estók, Péter; Zsebők, Sándor; Siemers, Björn M.

    2010-01-01

    Ecological pressure paired with opportunism can lead to surprising innovations in animal behaviour. Here, we report predation of great tits (Parus major) on hibernating pipistrelle bats (Pipistrellus pipistrellus) at a Hungarian cave. Over two winters, we directly observed 18 predation events. The tits specifically and systematically searched for and killed bats for food. A substantial decrease in predation on bats after experimental provisioning of food to the tits further supports the hypothesis that bat-killing serves a foraging purpose in times of food scarcity. We finally conducted a playback experiment to test whether tits would eavesdrop on calls of awakening bats to find them in rock crevices. The tits could clearly hear the calls and were attracted to the loudspeaker. Records for tit predation on bats at this cave now span more than ten years and thus raise the question of whether cultural transmission plays a role for the spread of this foraging innovation. PMID:19740892

  12. Increased Lytic Efficiency of Bovine Macrophages Trained with Killed Mycobacteria.

    PubMed

    Juste, Ramon A; Alonso-Hearn, Marta; Garrido, Joseba M; Abendaño, Naiara; Sevilla, Iker A; Gortazar, Christian; de la Fuente, José; Dominguez, Lucas

    2016-01-01

    Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.

  13. "Reversed" intraguild predation: red fox cubs killed by pine marten.

    PubMed

    Brzeziński, Marcin; Rodak, Lukasz; Zalewski, Andrzej

    2014-01-01

    Camera traps deployed at a badger Meles meles set in mixed pine forest in north-eastern Poland recorded interspecific killing of red fox Vulpes vulpes cubs by pine marten Martes martes. The vixen and her cubs settled in the set at the beginning of May 2013, and it was abandoned by the badgers shortly afterwards. Five fox cubs were recorded playing in front of the den each night. Ten days after the first recording of the foxes, a pine marten was filmed at the set; it arrived in the morning, made a reconnaissance and returned at night when the vixen was away from the set. The pine marten entered the den several times and killed at least two fox cubs. It was active at the set for about 2 h. This observation proves that red foxes are not completely safe from predation by smaller carnivores, even those considered to be subordinate species in interspecific competition.

  14. Increased Lytic Efficiency of Bovine Macrophages Trained with Killed Mycobacteria

    PubMed Central

    Juste, Ramon A.; Alonso-Hearn, Marta; Garrido, Joseba M.; Abendaño, Naiara; Sevilla, Iker A.; Gortazar, Christian; de la Fuente, José; Dominguez, Lucas

    2016-01-01

    Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis (M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response. PMID:27820836

  15. Great tits search for, capture, kill and eat hibernating bats.

    PubMed

    Estók, Péter; Zsebok, Sándor; Siemers, Björn M

    2010-02-23

    Ecological pressure paired with opportunism can lead to surprising innovations in animal behaviour. Here, we report predation of great tits (Parus major) on hibernating pipistrelle bats (Pipistrellus pipistrellus) at a Hungarian cave. Over two winters, we directly observed 18 predation events. The tits specifically and systematically searched for and killed bats for food. A substantial decrease in predation on bats after experimental provisioning of food to the tits further supports the hypothesis that bat-killing serves a foraging purpose in times of food scarcity. We finally conducted a playback experiment to test whether tits would eavesdrop on calls of awakening bats to find them in rock crevices. The tits could clearly hear the calls and were attracted to the loudspeaker. Records for tit predation on bats at this cave now span more than ten years and thus raise the question of whether cultural transmission plays a role for the spread of this foraging innovation.

  16. Spin manifolds, killing spinors and universality of the Hijazi inequality

    NASA Astrophysics Data System (ADS)

    Lichnerowicz, André

    1987-05-01

    In terms of the Dirac operator P, we introduce on any field a first-order operator D and show that the operator (Δ-ρ) on the spinors (ρ=( n/4( n-1)) R; dim W= n) is positive. By means of a universal formula, we show that, on a compact spin manifold of dimension ≥3, the Hijazi inequality [8] holds for every spinor field such that ( Pψ, Pψ) = λ 2( ψ, ψ) (λ=const.). In the limiting case, the manifold admits a Killing spinor which can be evaluated in terms of ψ. Different properties of spin manifolds admitting Killing spinors are proved. D is nothing but the ‘twistor operator’.

  17. Charged Particles Kill Pathogens and Round Up Dust

    NASA Technical Reports Server (NTRS)

    2015-01-01

    To keep plants fresh longer in space, Marshall Space Flight Center awarded funding to the University of Wisconsin-Madison to develop a titanium oxide-based device that reduced the amount of decay-inducing ethylene gas in the air. Electrolux (now Dallas-based Aerus Holdings) furthered the technology by developing an air purification product that kills pathogens both in the atmosphere and on surfaces.

  18. Comments on conformal Killing vector fields and quantum field theory

    SciTech Connect

    Brown, M.R.; Ottewill, A.C.; Siklos, S.T.C.

    1982-10-15

    We give a comprehensive analysis of those vacuums for flat and conformally flat space-times which can be defined by timelike, hypersurface-orthogonal, conformal Killing vector fields. We obtain formulas for the difference in stress-energy density between any two such states and display the correspondence with the renormalized stress tensors. A brief discussion is given of the relevance of these results to quantum-mechanical measurements made by noninertial observers moving through flat space.

  19. Stopping Mass Killings in Africa: Genocide, Airpower and Intervention

    DTIC Science & Technology

    2008-07-01

    improvised explosive device killed four American soldiers. Still, Aspin refused a corollary request for additional armor and airpower assets, based on his...ethnic conflict between the Tutsis and Hutus since 1960. There had been a population explosion within Rwanda together with the constant cycle of attacks...professor Ervin Staub conducted extensive research in the field of psychology to show nearly all twentieth century genocides only occurred within very

  20. The Role of Targeted Killing in the Campaign against Terror

    DTIC Science & Technology

    2008-01-01

    computer wallpaper at ndupress.ndu.edu 26 JFQ / issue 48, 1st quarter 2008 ndupress .ndu.edu FORUM | The Role of Targeted Killing in the Campaign...with MK12 sniper rifle Combat Camera Group Pacific (Eli J. Medellin) Download as computer wallpaper at ndupress.ndu.edu ndupress .ndu.edu issue 48...availability of precision- guided munitions is both a benefit and a hindrance Download as computer wallpaper at ndupress.ndu.edu 28 JFQ / issue 48, 1st

  1. Morphological effect of oscillating magnetic nanoparticles in killing tumor cells

    NASA Astrophysics Data System (ADS)

    Cheng, Dengfeng; Li, Xiao; Zhang, Guoxin; Shi, Hongcheng

    2014-04-01

    Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was firstly used to kill cancer cells in vitro. After being loaded by human cervical cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically damaged cell membranes and cytoplasm, decreasing the cell viability. It was found that the concentration and morphology of the MNPs significantly influenced the cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa cells were pre-incubated with 100 μg/mL rod-shaped MNPs (rMNP, length of 200 ± 50 nm and diameter of 50 to 120 nm) for 20 h, MTT assay proved that the cell viability decreased by 30.9% after being exposed to AMF for 2 h, while the cell viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200 ± 50 nm) were used for investigation. Furthermore, the morphological effect of MNPs on cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and 15.1% sMNP-loaded cells were stained after being exposed to AMF for 2 h. It was also interesting to find that killing tumor cells at either higher (500 μg/mL) or lower (20 μg/mL) concentration of MNPs was less efficient than that achieved at 100 μg/mL concentration. In conclusion, the relatively asymmetric morphological rod-shaped MNPs can kill cancer cells more effectively than spherical MNPs when being exposed to AMF by virtue of their mechanical oscillations.

  2. Newcastle disease virus selectively kills human tumor cells.

    PubMed

    Reichard, K W; Lorence, R M; Cascino, C J; Peeples, M E; Walter, R J; Fernando, M B; Reyes, H M; Greager, J A

    1992-05-01

    Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index.

  3. Pulpability of beetle-killed spruce. Forest Service research paper

    SciTech Connect

    Scott, G.M.; Bormett, D.W.; Sutherland, N.R.; Abubakr, S.; Lowell, E.

    1996-08-01

    Infestation of the Dendroctonus rufipennis beetle has resulted in large stands of dead and dying timber on the Kenai Peninsula in Alaska. Tests were conducted to evaluate the value of beetle-killed spruce as pulpwood. The results showed that live and dead spruce wood can be pulped effectively. The two least deteriorated classes and the most deteriorated class of logs had similar characteristics when pulped; the remaining class had somewhat poorer pulpability.

  4. The Killing of African Trypanosomes by Ethidium Bromide

    PubMed Central

    Roy Chowdhury, Arnab; Bakshi, Rahul; Wang, Jianyang; Yildirir, Gokben; Liu, Beiyu; Pappas-Brown, Valeria; Tolun, Gökhan; Griffith, Jack D.; Shapiro, Theresa A.; Jensen, Robert E.; Englund, Paul T.

    2010-01-01

    Introduced in the 1950s, ethidium bromide (EB) is still used as an anti-trypanosomal drug for African cattle although its mechanism of killing has been unclear and controversial. EB has long been known to cause loss of the mitochondrial genome, named kinetoplast DNA (kDNA), a giant network of interlocked minicircles and maxicircles. However, the existence of viable parasites lacking kDNA (dyskinetoplastic) led many to think that kDNA loss could not be the mechanism of killing. When recent studies indicated that kDNA is indeed essential in bloodstream trypanosomes and that dyskinetoplastic cells survive only if they have a compensating mutation in the nuclear genome, we investigated the effect of EB on kDNA and its replication. We here report some remarkable effects of EB. Using EM and other techniques, we found that binding of EB to network minicircles is low, probably because of their association with proteins that prevent helix unwinding. In contrast, covalently-closed minicircles that had been released from the network for replication bind EB extensively, causing them, after isolation, to become highly supertwisted and to develop regions of left-handed Z-DNA (without EB, these circles are fully relaxed). In vivo, EB causes helix distortion of free minicircles, preventing replication initiation and resulting in kDNA loss and cell death. Unexpectedly, EB also kills dyskinetoplastic trypanosomes, lacking kDNA, by inhibiting nuclear replication. Since the effect on kDNA occurs at a >10-fold lower EB concentration than that on nuclear DNA, we conclude that minicircle replication initiation is likely EB's most vulnerable target, but the effect on nuclear replication may also contribute to cell killing. PMID:21187912

  5. Einstein Finsler metrics and killing vector fields on Riemannian manifolds

    NASA Astrophysics Data System (ADS)

    Cheng, XinYue; Shen, ZhongMin

    2017-01-01

    In this paper, we use a Killing form on a Riemannian manifold to construct a class of Finsler metrics. We find equations that characterize Einstein metrics among this class. In particular, we construct a family of Einstein metrics on $S^3$ with ${\\rm Ric} = 2 F^2$, ${\\rm Ric}=0$ and ${\\rm Ric}=- 2 F^2$, respectively. This family of metrics provide an important class of Finsler metrics in dimension three, whose Ricci curvature is a constant, but the flag curvature is not.

  6. Killing of Gyrodactylus salaris by heat and chemical disinfection.

    PubMed

    Koski, Perttu; Anttila, Pasi; Kuusela, Jussi

    2016-03-23

    Gyrodactylus salaris is a monogenean, which has collapsed tens of wild Atlantic salmon populations. One of the means of preventing the spread of the parasite is the disinfection of the fishing equipment, which is used in the rivers having susceptible salmon populations. Little is known about the dosage of disinfectants against G. salaris. There are not standards for the testing of disinfectants against multicellular parasites. The present investigation developed a method to test disinfectants and examined the effectiveness of heated water and a commercially available disinfectant (Virkon S) in killing G. salaris. Individual G. salaris worms were followed under the microscope during treatment with heated water or Virkon S disinfectant blend. The logarithm of the time needed to kill the parasite was used as a dependent variable in linear regression. The upper 99.98 % prediction line for the dependent variable was used to obtain a value resembling the time needed for a 4 log reduction of the microbial pathogen, which is commonly used as a criterion for disinfectants. Also 6 log reduction was applied. Exposure to a relatively low temperature was found to kill the parasite. Even 5-50 min treatment (=10-100 times the 99.98 % upper prediction value) with heated water at 40 °C might be used. This would enable the utilisation of hot tap water in the disinfection of fishing gear. The present practice of 1 % Virkon S for 15 min was also found to kill the parasite. The follow-up of single parasites of a test population and the use of the calculated upper predictive line in the regression analysis offers a method to analyse the effects of disinfectants on parasites like G. salaris. The results of our tests give possibilities for using disinfection methods, which may be more acceptable by the fishermen than the present ones.

  7. [The vegetarian appeal and killing animals. An ethical challenge].

    PubMed

    Luy, J; Hildebrandt, G; von Mickwitz, G

    2001-01-01

    The demand for renunciation of killing animals has already been discussed by mankind since ancient times. Many arguments for and against this demand have accumulated in the meantime. The reproaches of the vegetarians repeatedly forced the ones who eat meat to justify their diet. Today most of these historical justifications however have to be rejected because of lacking plausibility. Many of the vegetarian arguments on the other hand must be rejected for similar reasons as well. Remaining as morally convincing is the demand for doing the killing absolutely painless and without frightening the animals, which was already formulated for example by Kant and Schopenhauer. Arguments which consider this way of killing as still immoral belong in a broad sense to the "anthropocentric" animal ethics. They do not belong to what is called in Germany "pathocentric" animal ethics, because an animal that is killed without being frightened or tortured, has not suffered, for it hasn't consciously realized anything like danger or harm. We do even argue that these animals are not harmed at all, because it seems senseless to talk about harm without negative conscious phenomena. To push ahead a ban on animal slaughter for moral reasons could be itself morally wrong because it would disturb indirectly many people's conscious well-being without being justified by protecting an animal's conscious well-being. It is however possible to derive from a general duty not to make animals suffer (pathocentric animal ethics) a duty to boycott food of animal origin if these animals had to suffer during their lives.

  8. Killing of Plasmodium falciparum in vitro by nitric oxide derivatives.

    PubMed Central

    Rockett, K A; Awburn, M M; Cowden, W B; Clark, I A

    1991-01-01

    We have investigated the in vitro susceptibility of the human malaria parasite Plasmodium falciparum to killing by nitric oxide and related molecules. A saturated solution of nitric oxide did not inhibit parasite growth, but two oxidation products of nitric oxide (nitrite and nitrate ions) were toxic to the parasite in millimolar concentrations. Nitrosothiol derivatives of cysteine and glutathione were found to be about a thousand times more active (50% growth inhibitory concentration, approximately 40 microM) than nitrite. PMID:1879941

  9. Invisible CO2 gas killing trees at Mammoth Mountain, California

    USGS Publications Warehouse

    Sorey, Michael L.; Farrar, Christopher D.; Evans, William C.; Hill, David P.; Bailey, Roy A.; Hendley, James W.; Stauffer, Peter H.

    1996-01-01

    Since 1980, scientists have monitored geologic unrest in Long Valley Caldera and at adjacent Mammoth Mountain, California. After a persistent swarm of earthquakes beneath Mammoth Mountain in 1989, earth scientists discovered that large volumes of carbon dioxide (CO2) gas were seeping from beneath this volcano. This gas is killing trees on the mountain and also can be a danger to people. The USGS continues to study the CO2 emissions to help protect the public from this invisible potential hazard.

  10. From Attitudes to Actions: Predictors of Lion Killing by Maasai Warriors.

    PubMed

    Hazzah, Leela; Bath, Alistair; Dolrenry, Stephanie; Dickman, Amy; Frank, Laurence

    2017-01-01

    Despite legal protection, deliberate killing by local people is one of the major threats to the conservation of lions and other large carnivores in Africa. Addressing this problem poses particular challenges, mainly because it is difficult to uncover illicit behavior. This article examined two groups of Maasai warriors: individuals who have killed African lions (Panthera leo) and those who have not. We conducted interviews to explore the relationship between attitudes, intentions and known lion killing behavior. Factor analysis and logistic regression revealed that lion killing was mainly determined by: (a) general attitudes toward lions, (b) engagement in traditional customs, (c) lion killing intentions to defend property, and (d) socio-cultural killing intentions. Our results indicated that general attitudes toward lions were the strongest predictor of lion killing behavior. Influencing attitudes to encourage pro-conservation behavior may help reduce killing.

  11. From Attitudes to Actions: Predictors of Lion Killing by Maasai Warriors

    PubMed Central

    Dickman, Amy; Frank, Laurence

    2017-01-01

    Despite legal protection, deliberate killing by local people is one of the major threats to the conservation of lions and other large carnivores in Africa. Addressing this problem poses particular challenges, mainly because it is difficult to uncover illicit behavior. This article examined two groups of Maasai warriors: individuals who have killed African lions (Panthera leo) and those who have not. We conducted interviews to explore the relationship between attitudes, intentions and known lion killing behavior. Factor analysis and logistic regression revealed that lion killing was mainly determined by: (a) general attitudes toward lions, (b) engagement in traditional customs, (c) lion killing intentions to defend property, and (d) socio-cultural killing intentions. Our results indicated that general attitudes toward lions were the strongest predictor of lion killing behavior. Influencing attitudes to encourage pro-conservation behavior may help reduce killing. PMID:28135338

  12. Default risk modeling with position-dependent killing

    NASA Astrophysics Data System (ADS)

    Katz, Yuri A.

    2013-04-01

    Diffusion in a linear potential in the presence of position-dependent killing is used to mimic a default process. Different assumptions regarding transport coefficients, initial conditions, and elasticity of the killing measure lead to diverse models of bankruptcy. One “stylized fact” is fundamental for our consideration: empirically default is a rather rare event, especially in the investment grade categories of credit ratings. Hence, the action of killing may be considered as a small parameter. In a number of special cases we derive closed-form expressions for the entire term structure of the cumulative probability of default, its hazard rate, and intensity. Comparison with historical data on aggregate global corporate defaults confirms the validity of the perturbation method for estimations of long-term probability of default for companies with high credit quality. On a single company level, we implement the derived formulas to estimate the one-year likelihood of default of Enron on a daily basis from August 2000 to August 2001, three months before its default, and compare the obtained results with forecasts of traditional structural models.

  13. Effects of lead on the killing mechanisms of polymorphonuclear leukocytes

    SciTech Connect

    Silberstein, C.F.

    1984-01-01

    The effects of lead on the killing mechanisms of rat polymorphonuclear leukocytes (PMN) were investigated, using male Long-Evans rats exposed to 1% lead acetate in the drinking water for varying periods of time to achieve blood lead levels ranging from 20-200 ..mu..g/dl. Studies of PMN bacterial and fungal killing activity, chemotaxis and phagocytosis demonstrated that: 1) bactericidal activity of PMN from rats exposed to lead was not altered; 2) chemotactic activity remained within normal limits; 3) the phagocytic ability of the PMN also remained unaltered. In addition to these normal findings, one major abnormality was demonstrated: a significant decrease in the ability of PMN from rats exposed to lead to kill Candida albicans. This defect was not related to age or to length of exposure. It could not be produced by addition of lead to the test system in vitro. Further investigation revealed significant decreases in PMN glucose-6-phosphate dehydrogenase, catalase, and myeloperoxidase activities. These data support two possible mechanisms for the abnormal fungicidal activity of PMN from lead-exposed rats: decrease in ability to reduce oxygen to active metabolites, or reduction in myeloperoxidase activity due to diminshed synthesis of the heme moiety required for its function.

  14. Photoexcited quantum dots for killing multidrug-resistant bacteria

    NASA Astrophysics Data System (ADS)

    Courtney, Colleen M.; Goodman, Samuel M.; McDaniel, Jessica A.; Madinger, Nancy E.; Chatterjee, Anushree; Nagpal, Prashant

    2016-05-01

    Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

  15. From coprophagy to predation: a dung beetle that kills millipedes.

    PubMed

    Larsen, Trond H; Lopera, Alejandro; Forsyth, Adrian; Génier, François

    2009-04-23

    The dung beetle subfamily Scarabaeinae is a cosmopolitan group of insects that feed primarily on dung. We describe the first case of an obligate predatory dung beetle and contrast its behaviour and morphology with those of its coprophagous sympatric congeners. Deltochilum valgum Burmeister killed and consumed millipedes in lowland rainforest in Peru. Ancestral ball-rolling behaviour shared by other canthonine species is abandoned, and the head, hind tibiae and pygidium of D. valgum are modified for novel functions during millipede predation. Millipedes were killed by disarticulation, often through decapitation, using the clypeus as a lever. Beetles killed millipedes much larger than themselves. In pitfall traps, D. valgum was attracted exclusively to millipedes, and preferred injured over uninjured millipedes. Morphological similarities placing D. valgum in the same subgenus with non-predatory dung-feeding species suggest a major and potentially rapid behavioural shift from coprophagy to predation. Ecological transitions enabling the exploitation of dramatically atypical niches, which may be more likely to occur when competition is intense, may help explain the evolution of novel ecological guilds and the diversification of exceptionally species-rich groups such as insects.

  16. From coprophagy to predation: a dung beetle that kills millipedes

    PubMed Central

    Larsen, Trond H.; Lopera, Alejandro; Forsyth, Adrian; Génier, François

    2009-01-01

    The dung beetle subfamily Scarabaeinae is a cosmopolitan group of insects that feed primarily on dung. We describe the first case of an obligate predatory dung beetle and contrast its behaviour and morphology with those of its coprophagous sympatric congeners. Deltochilum valgum Burmeister killed and consumed millipedes in lowland rainforest in Peru. Ancestral ball-rolling behaviour shared by other canthonine species is abandoned, and the head, hind tibiae and pygidium of D. valgum are modified for novel functions during millipede predation. Millipedes were killed by disarticulation, often through decapitation, using the clypeus as a lever. Beetles killed millipedes much larger than themselves. In pitfall traps, D. valgum was attracted exclusively to millipedes, and preferred injured over uninjured millipedes. Morphological similarities placing D. valgum in the same subgenus with non-predatory dung-feeding species suggest a major and potentially rapid behavioural shift from coprophagy to predation. Ecological transitions enabling the exploitation of dramatically atypical niches, which may be more likely to occur when competition is intense, may help explain the evolution of novel ecological guilds and the diversification of exceptionally species-rich groups such as insects. PMID:19158030

  17. Photoexcited quantum dots for killing multidrug-resistant bacteria.

    PubMed

    Courtney, Colleen M; Goodman, Samuel M; McDaniel, Jessica A; Madinger, Nancy E; Chatterjee, Anushree; Nagpal, Prashant

    2016-05-01

    Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

  18. Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

    PubMed Central

    Denton, Paul W.; Long, Julie M.; Wietgrefe, Stephen W.; Sykes, Craig; Spagnuolo, Rae Ann; Snyder, Olivia D.; Perkey, Katherine; Archin, Nancie M.; Choudhary, Shailesh K.; Yang, Kuo; Hudgens, Michael G.; Pastan, Ira; Haase, Ashley T.; Kashuba, Angela D.; Berger, Edward A.; Margolis, David M.; Garcia, J. Victor

    2014-01-01

    Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA+ cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies. PMID:24415939

  19. Targeted cytotoxic therapy kills persisting HIV infected cells during ART.

    PubMed

    Denton, Paul W; Long, Julie M; Wietgrefe, Stephen W; Sykes, Craig; Spagnuolo, Rae Ann; Snyder, Olivia D; Perkey, Katherine; Archin, Nancie M; Choudhary, Shailesh K; Yang, Kuo; Hudgens, Michael G; Pastan, Ira; Haase, Ashley T; Kashuba, Angela D; Berger, Edward A; Margolis, David M; Garcia, J Victor

    2014-01-01

    Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA(+) cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.

  20. S. Typhimurium strategies to resist killing by cationic antimicrobial peptides.

    PubMed

    Matamouros, Susana; Miller, Samuel I

    2015-11-01

    S. Typhimurium is a broad host range Gram-negative pathogen that must evade killing by host innate immune systems to colonize, replicate, cause disease, and be transmitted to other hosts. A major pathogenic strategy of Salmonellae is entrance, survival, and replication within eukaryotic cell phagocytic vacuoles. These phagocytic vacuoles and gastrointestinal mucosal surfaces contain multiple cationic antimicrobial peptides (CAMPs) which control invading bacteria. S. Typhimurium possesses several key mechanisms to resist killing by CAMPs which involve sensing CAMPs and membrane damage to activate signaling cascades that result in remodeling of the bacterial envelope to reduce its overall negative charge with an increase in hydrophobicity to decrease binding and effectiveness of CAMPs. Moreover Salmonellae have additional mechanisms to resist killing by CAMPs including an outer membrane protease which targets cationic peptides at the surface, and specific efflux pumps which protect the inner membrane from damage. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Influence of killing method on Lepidoptera DNA barcode recovery.

    PubMed

    Willows-Munro, Sandi; Schoeman, M Corrie

    2015-05-01

    The global DNA barcoding initiative has revolutionized the field of biodiversity research. Such large-scale sequencing projects require the collection of large numbers of specimens, which need to be killed and preserved in a way that is both DNA-friendly and which will keep voucher specimens in good condition for later study. Factors such as time since collection, correct storage (exposure to free water and heat) and DNA extraction protocol are known to play a role in the success of downstream molecular applications. Limited data are available on the most efficient, DNA-friendly protocol for killing. In this study, we evaluate the quality of DNA barcode (cytochrome oxidase I) sequences amplified from DNA extracted from specimens collected using three different killing methods (ethyl acetate, cyanide and freezing). Previous studies have suggested that chemicals, such as ethyl acetate and formaldehyde, degraded DNA and as such may not be appropriate for the collection of insects for DNA-based research. All Lepidoptera collected produced DNA barcodes of good quality, and our study found no clear difference in nucleotide signal strength, probability of incorrect base calling and phylogenetic utility among the three different treatment groups. Our findings suggest that ethyl acetate, cyanide and freezing can all be used to collect specimens for DNA analysis.

  2. Mating and male pheromone kill Caenorhabditis males through distinct mechanisms

    PubMed Central

    Shi, Cheng; Runnels, Alexi M; Murphy, Coleen T

    2017-01-01

    Differences in longevity between sexes is a mysterious yet general phenomenon across great evolutionary distances. To test the roles of responses to environmental cues and sexual behaviors in longevity regulation, we examined Caenorhabditis male lifespan under solitary, grouped, and mated conditions. We find that neurons and the germline are required for male pheromone-dependent male death. Hermaphrodites with a masculinized nervous system secrete male pheromone and are susceptible to male pheromone killing. Male pheromone-mediated killing is unique to androdioecious Caenorhabditis, and may reduce the number of males in hermaphroditic populations; neither males nor females of gonochoristic species are susceptible to male pheromone killing. By contrast, mating-induced death, which is characterized by germline-dependent shrinking, glycogen loss, and ectopic vitellogenin expression, utilizes distinct molecular pathways and is shared between the sexes and across species. The study of sex- and species-specific regulation of aging reveals deeply conserved mechanisms of longevity and population structure regulation. DOI: http://dx.doi.org/10.7554/eLife.23493.001 PMID:28290982

  3. Antimicrobial metallic copper surfaces kill Staphylococcus haemolyticus via membrane damage

    PubMed Central

    Santo, Christophe Espírito; Quaranta, Davide; Grass, Gregor

    2012-01-01

    Recently, copper (Cu) in its metallic form has regained interest for its antimicrobial properties. Use of metallic Cu surfaces in worldwide hospital trials resulted in remarkable reductions in surface contaminations. Yet, our understanding of why microbes are killed upon contact to the metal is still limited and different modes of action have been proposed. This knowledge, however, is crucial for sustained use of such surfaces in hospitals and other hygiene-sensitive areas. Here, we report on the molecular mechanisms by which the Gram-positive Staphylococcus haemolyticus is inactivated by metallic Cu. Staphylococcus haemolyticus was killed within minutes on Cu but not on stainless steel demonstrating the antimicrobial efficacy of metallic Cu. Inductively coupled plasma mass spectroscopy (ICP-MS) analysis and in vivo staining with Coppersensor-1 indicated that cells accumulated large amounts of Cu ions from metallic Cu surfaces contributing to lethal damage. Mutation rates of Cu- or steel-exposed cells were similarly low. Instead, live/dead staining indicated cell membrane damage in Cu- but not steel-exposed cells. These findings support a model of the cellular targets of metallic Cu toxicity in bacteria, which suggests that metallic Cu is not genotoxic and does not kill via DNA damage. In contrast, membranes constitute the likely Achilles’ heel of Cu surface-exposed cells. PMID:22950011

  4. Surface Acoustic Waves Enhance Neutrophil Killing of Bacteria

    PubMed Central

    Loike, John D.; Plitt, Anna; Kothari, Komal; Zumeris, Jona; Budhu, Sadna; Kavalus, Kaitlyn; Ray, Yonatan; Jacob, Harold

    2013-01-01

    Biofilms are structured communities of bacteria that play a major role in the pathogenicity of bacteria and are the leading cause of antibiotic resistant bacterial infections on indwelling catheters and medical prosthetic devices. Failure to resolve these biofilm infections may necessitate the surgical removal of the prosthetic device which can be debilitating and costly. Recent studies have shown that application of surface acoustic waves to catheter surfaces can reduce the incidence of infections by a mechanism that has not yet been clarified. We report here the effects of surface acoustic waves (SAW) on the capacity of human neutrophils to eradicate S. epidermidis bacteria in a planktonic state and within biofilms. Utilizing a novel fibrin gel system that mimics a tissue-like environment, we show that SAW, at an intensity of 0.3 mW/cm2, significantly enhances human neutrophil killing of S. epidermidis in a planktonic state and within biofilms by enhancing human neutrophil chemotaxis in response to chemoattractants. In addition, we show that the integrin CD18 plays a significant role in the killing enhancement observed in applying SAW. We propose from out data that this integrin may serve as mechanoreceptor for surface acoustic waves enhancing neutrophil chemotaxis and killing of bacteria. PMID:23936303

  5. AIDS gets the headlines, but TB kills more. International (Asia).

    PubMed

    1997-04-21

    Tuberculosis (TB) kills 2-3 million people each year. However, the World Health Organization estimates that only up to 6 million people have died of AIDS since the start of the epidemic in the late 1970s and early 1980s. Tuberculosis therefore kills many more people than AIDS, but AIDS gets more media attention and funding for research and prevention. One key reason why AIDS garners so much attention and funding is that it remains incurable, while TB can be cured. An aggressive anti-TB campaign is nonetheless needed in the Asia-Pacific region. One-third of the world's population is infected with the TB bacilli, with most TB cases reported in recent years being in China, India, the Philippines, Indonesia, and Bangladesh. It is also in these countries where careless or intermittent treatment of TB has allowed the disease to thrive and spread, giving rise to drug-resistant bacilli. TB kills an increasing number of HIV-positive people. The World Health Organization's Directly Observed Treatment, Short-course (DOTS) could save 10 million lives over the next decade.

  6. Exploring racial variations in the spousal sex ratio of killing.

    PubMed

    Regoeczi, W C

    2001-12-01

    The following article examines differences in the social situation of intimate partners as an explanation of racial differences in the female to male ratio of spousal homicides in Canada. An analysis of homicide data from 1961 to 1983 generated by the Canadian Centre for Justice Statistics reveals that the ratio of women killing their husbands to men killing their wives is highest for Aboriginals and lowest for Blacks, with the ratio for Whites falling in between. The possible sources of racial differences in this ratio include the proportion of couples (a) in common-law relationships, (b) who are co-residing as opposed to being separated, and (c) for whom there is a substantial age disparity between the partners. These factors are related to the spousal sex ratio of killing more generally. An exploration of interracial homicide patterns and racial variation in jealousy-motivated homicides was also undertaken. The findings reveal that controlling for the above factors substantially reduces the importance of race in predicting the gender of the homicide victim.

  7. Human platelets efficiently kill IgG-opsonized E. coli

    PubMed Central

    Riaz, Anum H.; Tasma, Brian E.; Woodman, Michael E.; Wooten, R. Mark; Worth, Randall G.

    2012-01-01

    Platelets are known contributors of hemostasis but have recently been shown to be important in inflammation and infectious diseases. Moreover, thrombocytopenia is often observed in patients with sepsis. We previously reported that platelets actively phagocytosed IgG-coated latex beads. In the current study, the capacity of human platelets to participate in host defense against bacterial infections was determined by assessing their ability to kill E. coli. Washed human platelets were incubated with unopsonized or IgG-opsonized E. coli and evaluated for binding and killing of E. coli. We found that although both unopsonized and IgG-opsonized E. coli associated with platelets, only IgG-opsonized E. coli were efficiently killed unless platelets were activated by a potent agonist. The bactericidal activity was dependent on FcγRIIA, was sensitive to cytochalasin D, but was not due to reactive oxygen metabolites. These data suggest that platelets may play an important role in protection against infection. PMID:22340259

  8. Measurement of bacterial ingestion and killing by macrophages.

    PubMed

    Drevets, Douglas A; Canono, Beth P; Campbell, Priscilla A

    2015-04-01

    This unit presents assays that allow accurate measurement of phagocytosis and killing of bacteria by macrophages. The first basic protocol describes how to measure the ability of macrophages to ingest bacteria. Importantly, because macrophage phagocytosis entails separate binding and internalization steps, assays are described here that will also determine the extent to which bacteria bound to the macrophage are in fact internalized. Two effective methods to do this are described in alternate protocols. Both of these alternate protocols rely on enumeration of differentially labeled bacteria by fluorescence microscopy to distinguish intracellular from extracellular bacteria. The unit also presents two protocols to measure the ability of a macrophage to kill bacteria it has internalized. The second basic is a straightforward assay in which bacterial colonies are enumerated before and after a killing period. Bactericidal activity is evidenced by reduced CFU bacteria on agar plates. Because it is critical to remove residual extracellular organisms, the protocol presents two alternative steps to accomplish this: a washing procedure and a more stringent method in which cells are sedimented through sucrose. An alternate protocol describes a way to measure bacterial viability based on bacterial metabolism, in which the ability of bacterial dehydrogenases to mediate the reduction of a tetrazolium salt to purple formazan is monitored by measuring absorbance spectrophotometrically. Copyright © 2015 John Wiley & Sons, Inc.

  9. Heat killing of bacterial spores analyzed by differential scanning calorimetry.

    PubMed

    Belliveau, B H; Beaman, T C; Pankratz, H S; Gerhardt, P

    1992-07-01

    Thermograms of the exosporium-lacking dormant spores of Bacillus megaterium ATCC 33729, obtained by differential scanning calorimetry, showed three major irreversible endothermic transitions with peaks at 56, 100, and 114 degrees C and a major irreversible exothermic transition with a peak at 119 degrees C. The 114 degrees C transition was identified with coat proteins, and the 56 degrees C transition was identified with heat inactivation. Thermograms of the germinated spores and vegetative cells were much alike, including an endothermic transition attributable to DNA. The ascending part of the main endothermic 100 degrees C transition in the dormant-spore thermograms corresponded to a first-order reaction and was correlated with spore death; i.e., greater than 99.9% of the spores were killed when the transition peak was reached. The maximum death rate of the dormant spores during calorimetry, calculated from separately measured D and z values, occurred at temperatures above the 73 degrees C onset of thermal denaturation and was equivalent to the maximum inactivation rate calculated for the critical target. Most of the spore killing occurred before the release of most of the dipicolinic acid and other intraprotoplast materials. The exothermic 119 degrees C transition was a consequence of the endothermic 100 degrees C transition and probably represented the aggregation of intraprotoplast spore components. Taken together with prior evidence, the results suggest that a crucial protein is the rate-limiting primary target in the heat killing of dormant bacterial spores.

  10. Killing, letting die and the bare difference argument.

    PubMed

    Perrett, Roy W

    1996-04-01

    I believe that there is no intrinsic moral difference between killing and letting die. That is, there is no difference that depends solely on the distinction between an act and an omission. I also believe that we can reasonably establish this thesis by appeal to the Bare Difference Argument. The form of this argument involves considering two imaginary cases in which there are no morally relevant differences present, save the bare difference that one is a case of killing and one a case of letting die. But in the pair of cases under consideration this bare difference makes no moral difference. Hence it cannot be that the bare difference between killing and letting die is in itself a morally important difference. Winston Nesbitt has recently argued that the Bare Difference Argument fails because "the examples produced typically possess a feature which makes their use in this context illegitimate, and that when modified to remove this feature, they provide support for the view which they were designed to undermine". I argue that Nesbitt misunderstands the logic of the Bare Difference Argument and that accordingly his objections are mistaken.

  11. Surface acoustic waves enhance neutrophil killing of bacteria.

    PubMed

    Loike, John D; Plitt, Anna; Kothari, Komal; Zumeris, Jona; Budhu, Sadna; Kavalus, Kaitlyn; Ray, Yonatan; Jacob, Harold

    2013-01-01

    Biofilms are structured communities of bacteria that play a major role in the pathogenicity of bacteria and are the leading cause of antibiotic resistant bacterial infections on indwelling catheters and medical prosthetic devices. Failure to resolve these biofilm infections may necessitate the surgical removal of the prosthetic device which can be debilitating and costly. Recent studies have shown that application of surface acoustic waves to catheter surfaces can reduce the incidence of infections by a mechanism that has not yet been clarified. We report here the effects of surface acoustic waves (SAW) on the capacity of human neutrophils to eradicate S. epidermidis bacteria in a planktonic state and within biofilms. Utilizing a novel fibrin gel system that mimics a tissue-like environment, we show that SAW, at an intensity of 0.3 mW/cm(2), significantly enhances human neutrophil killing of S. epidermidis in a planktonic state and within biofilms by enhancing human neutrophil chemotaxis in response to chemoattractants. In addition, we show that the integrin CD18 plays a significant role in the killing enhancement observed in applying SAW. We propose from out data that this integrin may serve as mechanoreceptor for surface acoustic waves enhancing neutrophil chemotaxis and killing of bacteria.

  12. Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms

    PubMed Central

    Binnebose, Andrea M.; Haughney, Shannon L.; Martin, Richard; Imerman, Paula M.; Narasimhan, Balaji; Bellaire, Bryan H.

    2015-01-01

    Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment. PMID:26496201

  13. Spacetimes with Killing tensors. [for Einstein-Maxwell fields with certain spinor indices

    NASA Technical Reports Server (NTRS)

    Hughston, L. P.; Sommers, P.

    1973-01-01

    The characteristics of the Killing equation and the Killing tensor are discussed. A conformal Killing tensor is of interest inasmuch as it gives rise to a quadratic first integral for null geodesic orbits. The Einstein-Maxwell equations are considered together with the Bianchi identity and the conformal Killing tensor. Two examples for the application of the considered relations are presented, giving attention to the charged Kerr solution and the charged C-metric.

  14. Spacetimes with Killing tensors. [for Einstein-Maxwell fields with certain spinor indices

    NASA Technical Reports Server (NTRS)

    Hughston, L. P.; Sommers, P.

    1973-01-01

    The characteristics of the Killing equation and the Killing tensor are discussed. A conformal Killing tensor is of interest inasmuch as it gives rise to a quadratic first integral for null geodesic orbits. The Einstein-Maxwell equations are considered together with the Bianchi identity and the conformal Killing tensor. Two examples for the application of the considered relations are presented, giving attention to the charged Kerr solution and the charged C-metric.

  15. It’s Not Just Conflict That Motivates Killing of Orangutans

    PubMed Central

    Davis, Jacqueline T.; Mengersen, Kerrie; Abram, Nicola K.; Ancrenaz, Marc; Wells, Jessie A.; Meijaard, Erik

    2013-01-01

    We investigated why orangutans are being killed in Kalimantan, Indonesia, and the role of conflict in these killings. Based on an analysis of interview data from over 5,000 respondents in over 450 villages, we also assessed the socio-ecological factors associated with conflict and non-conflict killings. Most respondents never kill orangutans. Those who reported having personally killed an orangutan primarily did so for non-conflict reasons; for example, 56% of these respondents said that the reason they had killed an orangutan was to eat it. Of the conflict-related reasons for killing, the most common reasons orangutans were killed was fear of orangutans or in self-defence. A similar pattern was evident among reports of orangutan killing by other people in the villages. Regression analyses indicated that religion and the percentage of intact forest around villages were the strongest socio-ecological predictors of whether orangutans were killed for conflict or non-conflict related reasons. Our data indicate that between 44,170 and 66,570 orangutans were killed in Kalimantan within the respondents’ active hunting lifetimes: between 12,690 and 29,024 for conflict reasons (95%CI) and between 26,361 and 41,688 for non-conflict reasons (95% CI). These findings confirm that habitat protection alone will not ensure the survival of orangutans in Indonesian Borneo, and that effective reduction of orangutan killings is urgently needed. PMID:24130707

  16. 33 CFR 165.T01-0727 - Regulated Navigation Area; Arthur Kill, NY and NJ.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Kill, NY and NJ. 165.T01-0727 Section 165.T01-0727 Navigation and Navigable Waters COAST GUARD... § 165.T01-0727 Regulated Navigation Area; Arthur Kill, NY and NJ. (a) Regulated area. The following area..., and Gulfport Reach in the Arthur Kill; bounded in the northeast by a line drawn from position 40°...

  17. 33 CFR 165.T01-0727 - Regulated Navigation Area; Arthur Kill, NY and NJ.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Kill, NY and NJ. 165.T01-0727 Section 165.T01-0727 Navigation and Navigable Waters COAST GUARD... § 165.T01-0727 Regulated Navigation Area; Arthur Kill, NY and NJ. (a) Regulated area. The following area..., and Gulfport Reach in the Arthur Kill; bounded in the northeast by a line drawn from position 40°...

  18. 77 FR 10960 - Security Zone, East River and Bronx Kill; Randalls and Wards Islands, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA87 Security Zone, East River and Bronx Kill; Randalls and... establishing a temporary security zone on the waters of the East River and Bronx Kill, in the vicinity of... is intended to restrict vessels from a portion of the East River and Bronx Kill when public officials...

  19. The Evil Animal: A Terror Management Theory Perspective on the Human Tendency to Kill Animals.

    PubMed

    Lifshin, Uri; Greenberg, Jeff; Zestcott, Colin A; Sullivan, Daniel

    2017-06-01

    This research tested whether support for the killing of animals serves a terror management function. In five studies, death primes caused participants to support the killing of animals more than control primes, unless the participants' self-esteem had been elevated (Study 4). This effect was not moderated by gender, preexisting attitudes toward killing animals or animal rights, perceived human-animal similarity, religiosity, political orientation, or by the degree to which the killing was justified. Support for killing animals after subliminal death primes was also associated with an increased sense of power and invulnerability (Study 5). Implications and future directions are discussed.

  20. Broadening the future of value account of the wrongness of killing.

    PubMed

    Di Nucci, Ezio

    2015-11-01

    On Don Marquis's future of value account of the wrongness of killing, 'what makes it wrong to kill those individuals we all believe it is wrong to kill, is that killing them deprives them of their future of value'. Marquis has recently argued for a narrow interpretation of his future of value account of the wrongness of killing and against the broad interpretation that I had put forward in response to Carson Strong. In this article I argue that the narrow view is problematic because it violates some basic principles of equality and because it allows for some of the very killing that Marquis sets out to condemn; further, I argue that the chief reason why Marquis chooses the narrow view over the broad view-namely that the broad view would take the killing of some non-human animals to be also wrong-should rather be considered a welcome upshot of the broad view.

  1. Killed oral cholera vaccines: history, development and implementation challenges

    PubMed Central

    Gonzales, Maria Liza Antoinette; Aldaba, Josephine G.; Nair, G. Balakrish

    2014-01-01

    Cholera is still a major global health problem, affecting mainly people living in unsanitary conditions and who are at risk for outbreaks of cholera. During the past decade, outbreaks are increasingly reported from more countries. From the early killed oral cholera vaccine, rapid improvements in vaccine development occurred as a result of a better understanding of the epidemiology of the disease, pathogenesis of cholera infection and immunity. The newer-generation oral killed cholera vaccines have been shown to be safe and effective in field trials conducted in cholera endemic areas. Likewise, they have been shown to be protective when used during outbreak settings. Aside from providing direct protection to vaccinated individuals, recent studies have demonstrated that these killed oral vaccines also confer indirect protection through herd immunity. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches in countries where they are most needed, especially improved water quality and sanitation, these vaccines serve as immediately available public health tools for preventing further morbidity and mortality from cholera. However, despite its availability for more than two decades, use of these vaccines has not been optimized. Although there are limitations of the currently available oral cholera vaccines, recent data show that the vaccines are safe, feasible to use even in difficult circumstances and able to provide protection in various settings. Clear identification of the areas and target population groups who will benefit from the use of the cholera vaccines will be required and strategies to facilitate accessibility and usage of these vaccines in these areas and population groups will need to be developed. PMID:25177492

  2. Killed oral cholera vaccines: history, development and implementation challenges.

    PubMed

    Lopez, Anna Lena; Gonzales, Maria Liza Antoinette; Aldaba, Josephine G; Nair, G Balakrish

    2014-09-01

    Cholera is still a major global health problem, affecting mainly people living in unsanitary conditions and who are at risk for outbreaks of cholera. During the past decade, outbreaks are increasingly reported from more countries. From the early killed oral cholera vaccine, rapid improvements in vaccine development occurred as a result of a better understanding of the epidemiology of the disease, pathogenesis of cholera infection and immunity. The newer-generation oral killed cholera vaccines have been shown to be safe and effective in field trials conducted in cholera endemic areas. Likewise, they have been shown to be protective when used during outbreak settings. Aside from providing direct protection to vaccinated individuals, recent studies have demonstrated that these killed oral vaccines also confer indirect protection through herd immunity. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches in countries where they are most needed, especially improved water quality and sanitation, these vaccines serve as immediately available public health tools for preventing further morbidity and mortality from cholera. However, despite its availability for more than two decades, use of these vaccines has not been optimized. Although there are limitations of the currently available oral cholera vaccines, recent data show that the vaccines are safe, feasible to use even in difficult circumstances and able to provide protection in various settings. Clear identification of the areas and target population groups who will benefit from the use of the cholera vaccines will be required and strategies to facilitate accessibility and usage of these vaccines in these areas and population groups will need to be developed.

  3. Mothers who kill: evolutionary underpinnings and infanticide law.

    PubMed

    Friedman, Susan Hatters; Cavney, James; Resnick, Phillip J

    2012-01-01

    Women who kill their children present a profound challenge to accepted notions of motherhood and the protection offered by mothers to their children. Historically, societies have varied in the sanctions applied to perpetrators of such acts, across both time and place. Where penalties were once severe and punitive for mothers, in modern times some two dozen nations now have infanticide acts that reduce the penalties for mothers who kill their infants. Embedded within these acts are key criteria that relate (a) only to women who are (b) suffering the hormonal or mood effects of pregnancy/lactation at the time of the offence which is (c) usually restricted to within the first year after delivery. Criticisms of infanticide legislation have largely centered on inherent gender bias, misconceptions about the hormonal basis of postpartum psychiatric disorders, and the nexus and contribution of these disorders to the offending in relation to issues of culpability and sentencing. Important differences between female perpetrators relative to the age of the child victim have also highlighted problems in the implementation of infanticide legislation. For example, women who commit neonaticide (murder during the first day of life) differ substantially from mentally ill mothers who kill older children. However, despite these shortcomings, many nations have in recent years chosen to retain their infanticide acts. This article reviews the central controversies of infanticide legislation in relation to current research and fundamental fairness. Using evolutionary psychology as a theoretical framework to organize this discussion, it is argued that infanticide legislation is at best unnecessary and at worst misapplied, in that it exculpates criminal intent and fails to serve those for whom an infanticide defense might otherwise have been intended. Copyright © 2012 John Wiley & Sons, Ltd.

  4. Microbots Decorated with Silver Nanoparticles Kill Bacteria in Aqueous Media.

    PubMed

    Vilela, Diana; Stanton, Morgan M; Parmar, Jemish; Sánchez, Samuel

    2017-07-12

    Water contamination is one of the most persistent problems of public health. Resistance of some pathogens to conventional disinfectants can require the combination of multiple disinfectants or increased disinfectant doses, which may produce harmful byproducts. Here, we describe an efficient method for disinfecting Escherichia coli and removing the bacteria from contaminated water using water self-propelled Janus microbots decorated with silver nanoparticles (AgNPs). The structure of a spherical Janus microbot consists of a magnesium (Mg) microparticle as a template that also functions as propulsion source by producing hydrogen bubbles when in contact with water, an inner iron (Fe) magnetic layer for their remote guidance and collection, and an outer AgNP-coated gold (Au) layer for bacterial adhesion and improving bactericidal properties. The active motion of microbots increases the chances of the contact of AgNPs on the microbot surface with bacteria, which provokes the selective Ag(+) release in their cytoplasm, and the microbot self-propulsion increases the diffusion of the released Ag(+) ions. In addition, the AgNP-coated Au cap of the microbots has a dual capability of capturing bacteria and then killing them. Thus, we have demonstrated that AgNP-coated Janus microbots are capable of efficiently killing more than 80% of E. coli compared with colloidal AgNPs that killed only less than 35% of E. coli in contaminated water solutions in 15 min. After capture and extermination of bacteria, magnetic properties of the cap allow collection of microbots from water along with the captured dead bacteria, leaving water with no biological contaminants. The presented biocompatible Janus microbots offer an encouraging method for rapid disinfection of water.

  5. [The killing of surplus and old animals in zoos].

    PubMed

    Engel, H

    2001-03-01

    The painless killing of animals in order to avoid considerable suffering has a legal basis and is sufficiently accepted by the society. The situation is, however, different when the matter concerns zoological gardens having on some occasions to put down apparently healthy animals. Since the natural populations of many species have almost been extinguished in the wild or are already eradicated, zoos play a prominent role in the ex-situ survival-breeding of many wild animals. This means that zoos often have self-supporting populations of species rather than only single individuals, as was frequently the case in the past. Such breeding also brings with it the possibility that animals will survive without the option of transferring them to other acceptable locations. In the wild, natural environmental factors prevent excessive population growth, whereas in zoos and in other protective reservations, such regulatory mechanisms are simply not existent. Such regulation can, however, often be achieved by animal transfers and other stock regulating measures. If these measures are not available the option of putting the animals down must be considered. Preventing suffering is of course the priority, as is demanded by zoos together with recognised animal protection organisations. This is compliant with German law and takes place for obvious and sensible reasons. The scientific zoological gardens organised in the German Zoo Directors Council discussed the problem of killing animals at the 1999 conference at Rostock and drafted a paper presenting its position on the subject. The paper argues that even under optimal husbandry conditions, while alternative options of breeding, planning and stabilisation of stock must be considered, the humane killing of animals will sometimes be unavoidable.

  6. The epidemiological patterns of honour killing of women in Pakistan.

    PubMed

    Nasrullah, Muazzam; Haqqi, Sobia; Cummings, Kristin J

    2009-04-01

    Honour killing (HK) is a problem of public health concern but published data on the phenomenon are limited and many cases likely go unrecognized. Our study focuses on the epidemiological patterns of HK of women in Pakistan, where domestic violence is common and HK occurs but is poorly described. Human Rights Commission of Pakistan (HRCP) systematically collected data on HK of women using newspaper reports from January 2004 till December 2007. We analysed the aggregated data on HK through December 2007 and estimated the rates of HK. A total of 1957 HK events occurred from 2004 to 2007; complete data was not available for all variables. Adults (>or=18 years) constituted 82% (803/978) of death toll with 88% (1257/1435) being married. Alleged extramarital relation was the major reason for the killing (92%; 1759/1902). Husbands (43%; 749/1739), brothers (24%; 421/1739) and 'other' close relatives (12%; 200/1739) were the perpetrators in known HK events. Among the weapons/methods used for killing, firearms (61%; 1071/1768), stabbing (4%; 65/1768), use of axe (12%; 220/1768), edged tool (8%;136/1768) and strangulation (9%; 167/1768) were the main means of execution. The mean annual rate of HK in females (age 15-64 years) was found to be 15.0 per million. Newspaper reports are good source of surveillance when information is limited. We found that adult married women constituted the majority of victims of HK. Ongoing surveillance would serve to better characterize HK in Pakistan and assess the effectiveness of preventive strategies.

  7. Nexavar/Stivarga and Viagra Interact to Kill Tumor Cells

    PubMed Central

    Tavallai, Mehrad; Hamed, Hossein A.; Roberts, Jane L.; Cruickshanks, Nichola; Chuckalovcak, John; Poklepovic, Andrew; Booth, Laurence

    2015-01-01

    We determined whether the multi‐kinase inhibitor sorafenib or its derivative regorafenib interacted with phosphodiesterase 5 (PDE5) inhibitors such as Viagra (sildenafil) to kill tumor cells. PDE5 and PDGFRα/β were over‐expressed in liver tumors compared to normal liver tissue. In multiple cell types in vitro sorafenib/regorafenib and PDE5 inhibitors interacted in a greater than additive fashion to cause tumor cell death, regardless of whether cells were grown in 10 or 100% human serum. Knock down of PDE5 or of PDGFRα/β recapitulated the effects of the individual drugs. The drug combination increased ROS/RNS levels that were causal in cell killing. Inhibition of CD95/FADD/caspase 8 signaling suppressed drug combination toxicity. Knock down of ULK‐1, Beclin1, or ATG5 suppressed drug combination lethality. The drug combination inactivated ERK, AKT, p70 S6K, and mTOR and activated JNK. The drug combination also reduced mTOR protein expression. Activation of ERK or AKT was modestly protective whereas re‐expression of an activated mTOR protein or inhibition of JNK signaling almost abolished drug combination toxicity. Sildenafil and sorafenib/regorafenib interacted in vivo to suppress xenograft tumor growth using liver and colon cancer cells. From multiplex assays on tumor tissue and plasma, we discovered that increased FGF levels and ERBB1 and AKT phosphorylation were biomarkers that were directly associated with lower levels of cell killing by ‘rafenib + sildenafil. Our data are now being translated into the clinic for further determination as to whether this drug combination is a useful anti‐tumor therapy for solid tumor patients. J. Cell. Physiol. 230: 2281–2298, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25704960

  8. Invisible CO2 gas killing trees at Mammoth Mountain, California

    USGS Publications Warehouse

    Sorey, Michael L.; Farrar, Christopher D.; Gerlach, Terrance M.; McGee, Kenneth A.; Evans, William C.; Colvard, Elizabeth M.; Hill, David P.; Bailey, Roy A.; Rogie, John D.; Hendley, James W.; Stauffer, Peter H.

    2000-01-01

    Since 1980, scientists have monitored geologic unrest in Long Valley Caldera and at adjacent Mammoth Mountain, California. After a persistent swarm of earthquakes beneath Mammoth Mountain in 1989, geologists discovered that large volumes of carbon dioxide (CO2 ) gas were seeping from beneath this volcano. This gas is killing trees on the mountain and also can be a danger to people. The U.S. Geological Survey (USGS) continues to study the CO2 emissions to help protect the public from this invisible potential hazard.

  9. Homicide by direct snake bite: a case of contract killing.

    PubMed

    Ambade, Vipul Namdeorao; Borkar, Jaydeo Laxman; Meshram, Satin Kalidas

    2012-01-01

    It has been estimated that five million snake bite cases occur worldwide every year, causing about 100,000 deaths. Snake bite is exclusively accidental in nature. Suicide by snake bite is very rare and homicidal snake bite is not reported. In the present case, a contract killer was hired, who used a poisonous snake to kill an elderly couple by way of direct snake bite. We believe this to be the first case reported where a snake was directly used for the murder of two victims through a contract killer.

  10. (M-theory-)Killing spinors on symmetric spaces

    SciTech Connect

    Hustler, Noel; Lischewski, Andree

    2015-08-15

    We show how the theory of invariant principal bundle connections for reductive homogeneous spaces can be applied to determine the holonomy of generalised Killing spinor covariant derivatives of the form D = ∇ + Ω in a purely algebraic and algorithmic way, where Ω : TM → Λ{sup ∗}(TM) is a left-invariant homomorphism. Specialising this to the case of symmetric M-theory backgrounds (i.e., (M, g, F) with (M, g) an eleven-dimensional Lorentzian (locally) symmetric space and F an invariant closed 4-form), we derive several criteria for such a background to preserve some supersymmetry and consequently find all supersymmetric symmetric M-theory backgrounds.

  11. Mitochondria: An intriguing target for killing tumour-initiating cells.

    PubMed

    Yan, Bing; Dong, Lanfeng; Neuzil, Jiri

    2016-01-01

    Tumour-initiating cells (TICs) play a pivotal role in cancer initiation, metastasis and recurrence, as well as in resistance to therapy. Therefore, development of drugs targeting TICs has become a focus of contemporary research. Mitochondria have emerged as a promising target of anti-cancer therapies due to their specific role in cancer metabolism and modulation of apoptotic pathways. Mitochondria of TICs possess special characteristics, some of which can be utilised to design drugs specifically targeting these cells. In this paper, we will review recent research on TICs and their mitochondria, and introduce drugs that kill these cells by way of mitochondrial targeting.

  12. Thou Shalt Not Kill: Conscientious Objection and the Decalogue

    DTIC Science & Technology

    2012-04-01

    is a child of God. Without the manward look religion can become a remote and detached mysticism in which a man is concerned with his own soul and...Brave New World, 118-1 9; c( Matt 22:39; Eph 5:28-29, 33. 92 Matt 27:5; Acts I: 18. 93 I.e. suicide, assisted suicide, voluntary euthanasia , mercy...killing, etc. 22 94 For a comprehensive treatment of the historical, legal, ethical, and theological aspects of euthanasia , see Edward J. Larson and

  13. Attachment of killed Mycoplasma gallisepticum cells and membranes to erythrocytes

    SciTech Connect

    Banai, M.; Kahane, I.; Feldner, J.; Razin, S.

    1981-11-01

    To correlate viability with attachment capacity, Mycoplasma gallisepticum cells harvested at different growth phases and treated by various agents were tested for their capacity to attach to human erythrocytes. The results show that viability per se is not essential for M. gallisepticum attachment to erythrocytes, as cells killed by ultraviolet irradiation and membranes isolated by lysing M. gallisepticum cells by various means retained attachment capacity. However, treatment of the mycoplasmas by protein-denaturing agents, such as heart, glutaraldehyde, or prolonged exposure to low pH, drastically affected or even abolished attachment, supporting the protein nature of the mycoplasma membrane components responsible for specific binding to the sialoglycoprotein receptors on the erythrocytes.

  14. Selective Killing of T Lymphocytes by Phototoxic Liposomes

    NASA Astrophysics Data System (ADS)

    Yemul, Shrishailam; Berger, Carole; Estabrook, Alison; Suarez, Sylvia; Edelson, Richard; Bayley, Hagan

    1987-01-01

    Two-fold specificity in drug delivery obtained through (i) the localized activation of drugs by physical means and (ii) the attachment of drugs to proteins that bind to target cells might be used for highly selective cancer chemotherapy or for immunosuppression. Toward this end, a monoclonal antibody against an antigen on the surface of T lymphocytes was covalently attached to liposomes containing a phototoxic drug, pyrene, bound to the lipid bilayer. When unfractionated peripheral blood lymphocytes, or B- and T-cell lines, were irradiated after treatment with these liposomes, T cells were killed while B cells were spared, demonstrating the validity of the approach in a simple in vitro assay.

  15. Induced melanin reduces mutations and cell killing in mouse melanoma.

    PubMed

    Li, W; Hill, H Z

    1997-03-01

    When melanin absorbs light energy, it can produce potentially damaging active oxygen species. There is little doubt that constitutive pigment in dark-skinned individuals is photoprotective against skin cancer, but induced pigment-as in tanning-may not be. The first step in cancer induction is mutation in DNA. The most suitable systems for evaluating the role of melanin are those in which pigment can be varied and mutations can be measured. Several cell lines from Cloudman S91 mouse melanoma can be induced to form large quantities of melanin pigment after treatment with a number of different agents enabling comparison of mutant yields in the same cells differing principally in pigment concentration. In these studies, melanin was induced with synthetic alpha-melanocyte-stimulating hormone and with isobutyl methyl xanthine in the cell line S91/mel. The former inducer produced about 50% more pigment than the latter. Survival and mutation induction at the Na+/K(+)-ATPase locus were studied using ethyl methane sulfonate (EMS), a standard mutagen and five UV lamps emitting near monochromatic and polychromatic UV light in the three wave-length ranges of UV. There was greater protection against killing and mutation induction in the more heavily pigmented cells after exposure to EMS and after irradiation with monochromatic UVC and UVB. There was significant protection against killing by polychromatic UVB + UVA (FS20), but the small degree of protection against mutation was not significant. No significant change in killing and mutation using the same protocol was seen in S91/amel, a related cell line that does not respond to these inducers. No mutants were produced by either monochromatic or polychromatic UVA at doses that killed 50% of the cells. Our results show that induced pigment-shown earlier to be eumelanin (K. A. Cieszka et al., Exp. Dermatol. 4, 192-198, 1995)-is photo- and chemoprotective, but it is less effective in protection against mutagenesis by polychromatic

  16. Emergence of Buprestidae, Cerambycidae, and Scolytinae (Coleoptera) from mountain pine beetle-killed and fire-killed ponderosa pines in the Black Hills, South Dakota, USA

    Treesearch

    Sheryl L. Costello; William R. Jacobi; Jose F. Negron

    2013-01-01

    Wood borers (Coleoptera: Cerambycidae and Buprestidae) and bark beetles (Coleoptera: Curculionidae) infest ponderosa pines, Pinus ponderosa P. Lawson and C. Lawson, killed by mountain pine beetle (MPB), Dendroctonus ponderosae Hopkins, and fire. No data is available comparing wood borer and bark beetle densities or species guilds associated with MPB-killed or fire-...

  17. Physical process first law for bifurcate Killing horizons

    SciTech Connect

    Amsel, Aaron J.; Marolf, Donald; Virmani, Amitabh

    2008-01-15

    The physical process version of the first law for black holes states that the passage of energy and angular momentum through the horizon results in a change in area ({kappa}/8{pi}){delta}A={delta}E-{omega}{delta}J, so long as this passage is quasistationary. A similar physical process first law can be derived for any bifurcate Killing horizon in any spacetime dimension d{>=}3 using much the same argument. However, to make this law nontrivial, one must show that sufficiently quasistationary processes do in fact occur. In particular, one must show that processes exist for which the shear and expansion remain small, and in which no new generators are added to the horizon. Thorne, MacDonald, and Price considered related issues when an object falls across a d=4 black hole horizon. By generalizing their argument to arbitrary d{>=}3 and to any bifurcate Killing horizon, we derive a condition under which these effects are controlled and the first law applies. In particular, by providing a nontrivial first law for Rindler horizons, our work completes the parallel between the mechanics of such horizons and those of black holes for d{>=}3. We also comment on the situation for d=2.

  18. TLR ligands stimulation protects MSC from NK killing.

    PubMed

    Giuliani, Massimo; Bennaceur-Griscelli, Annelise; Nanbakhsh, Arash; Oudrhiri, Noufissa; Chouaib, Salem; Azzarone, Bruno; Durrbach, Antoine; Lataillade, Jean-Jacques

    2014-01-01

    Mesenchymal stem cells (MSCs) play a fundamental role in allograft rejection and graft-versus-host disease through their immunosuppressive abilities. Recently, Toll-like receptors (TLR) have been shown to modulate MSC functions. The aim of this study was to investigate the effects of several TLR ligands on the interaction between MSC and natural killer (NK) cells. Our results show that TLR-primed adult bone marrow and embryonic MSC are more resistant than unprimed MSC to IL-2-activated NK-induced killing. Such protection can be explained by the modulation of Natural Killer group 2D ligands major histocompatibility complex class I chain A and ULBP3 and DNAM-1 ligands by TLR-primed MSC. These results indicate that MSCs are able to adapt their immuno-behavior in an inflammatory context, decreasing their susceptibility to NK killing. In addition, TLR3 but not TLR4-primed MSC enhance their suppressive functions against NK cells. However, the efficiency of this response is heterogeneous, even if the phenotypes of different analyzed MSC are rather homogeneous. The consequences could be important in MSC-mediated cell therapy, since the heterogeneity of adult MSC responders may be explored in order to select the more efficient responders. © 2013 AlphaMed Press.

  19. Aggregatibacter actinomycetemcomitans biofilm killing by a targeted ciprofloxacin prodrug

    PubMed Central

    Reeves, Benjamin D.; Young, Mark; Grieco, Paul A.; Suci, Peter

    2013-01-01

    A pH-sensitive ciprofloxacin prodrug was synthesized and targeted against biofilms of the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). The dose required to reduce the viability of a mature biofilm of Aa by ~80% was in the range of ng cm−2 of colonized area (mean biofilm density 2.33 x109 cells cm−2). A mathematical model was formulated that predicts the temporal change in the concentration of ciprofloxacin in the Aa biofilm as the drug is released and diffuses into the bulk medium. The predictions of the model were consistent with the extent of killing obtained. The results demonstrate the feasibility of the strategy to induce mortality, and together with the mathematical model, provide the basis for design of targeted antimicrobial prodrugs for the topical treatment of oral infections such as periodontitis. The targeted prodrug approach offers the possibility of optimizing the dose of available antimicrobials in order to kill a chosen pathogen while leaving the commensal microbiota relatively undisturbed. PMID:23952779

  20. Protecting the normal in order to better kill the cancer.

    PubMed

    Liu, Bingya; Ezeogu, Lewis; Zellmer, Lucas; Yu, Baofa; Xu, Ningzhi; Joshua Liao, Dezhong

    2015-09-01

    Chemotherapy is the only option for oncologists when a cancer has widely spread to different body sites. However, almost all currently available chemotherapeutic drugs will eventually encounter resistance after their initial positive effect, mainly because cancer cells develop genetic alterations, collectively coined herein as mutations, to adapt to the therapy. Some patients may still respond to a second chemo drug, but few cases respond to a third one. Since it takes time for cancer cells to develop new mutations and then select those life-sustaining ones via clonal expansion, "run against time for mutations to emerge" should be a crucial principle for treatment of those currently incurable cancers. Since cancer cells constantly change to adapt to the therapy whereas normal cells are stable, it may be a better strategy to shift our focus from killing cancer cells per se to protecting normal cells from chemotherapeutic toxicity. This new strategy requires the development of new drugs that are nongenotoxic and can quickly, in just hours or days, kill cancer cells without leaving the still-alive cells with time to develop mutations, and that should have their toxicities confined to only one or few organs, so that specific protections can be developed and applied. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Killing for the state: the darkest side of American nursing.

    PubMed

    Holmes, Dave; Federman, Cary

    2003-03-01

    The aim of this article is to bring to the attention of the international nursing community the discrepancy between a pervasive 'caring' nursing discourse and a most unethical nursing practice in the United States. In this article, we present a duality: the conflict in American prisons between nursing ethics and the killing machinery. The US penal system is a setting in which trained healthcare personnel practice the extermination of life. We look upon the sanitization of deathwork as an application of healthcare professionals' skills and knowledge and their appropriation by the state to serve its ends. A review of the states' death penalty statutes shows that healthcare workers are involved in the capital punishment process and shielded by American laws (and to a certain extent by professional boards through their inaction). We also argue that the law's language often masks that involvement; and explain how states further that duplicity behind legal formalisms. In considering the important role healthcare providers, namely nurses and physicians, play in administering death to the condemned, we assert that nurses and physicians are part of the states' penal machinery in America. Nurses and physicians (as carriers of scientific knowledge, and also as agents of care) are intrinsic to the American killing enterprise. Healthcare professionals who take part in execution protocols are state functionaries who approach the condemned body as angels of death: they constitute an extension of the state which exercises its sovereign power over captive prisoners.

  2. Midgut microbiota and host immunocompetence underlie Bacillus thuringiensis killing mechanism

    PubMed Central

    Caccia, Silvia; Di Lelio, Ilaria; La Storia, Antonietta; Marinelli, Adriana; Varricchio, Paola; Franzetti, Eleonora; Banyuls, Núria; Tettamanti, Gianluca; Casartelli, Morena; Giordana, Barbara; Ferré, Juan; Gigliotti, Silvia; Pennacchio, Francesco

    2016-01-01

    Bacillus thuringiensis is a widely used bacterial entomopathogen producing insecticidal toxins, some of which are expressed in insect-resistant transgenic crops. Surprisingly, the killing mechanism of B. thuringiensis remains controversial. In particular, the importance of the septicemia induced by the host midgut microbiota is still debated as a result of the lack of experimental evidence obtained without drastic manipulation of the midgut and its content. Here this key issue is addressed by RNAi-mediated silencing of an immune gene in a lepidopteran host Spodoptera littoralis, leaving the midgut microbiota unaltered. The resulting cellular immunosuppression was characterized by a reduced nodulation response, which was associated with a significant enhancement of host larvae mortality triggered by B. thuringiensis and a Cry toxin. This was determined by an uncontrolled proliferation of midgut bacteria, after entering the body cavity through toxin-induced epithelial lesions. Consequently, the hemolymphatic microbiota dramatically changed upon treatment with Cry1Ca toxin, showing a remarkable predominance of Serratia and Clostridium species, which switched from asymptomatic gut symbionts to hemocoelic pathogens. These experimental results demonstrate the important contribution of host enteric flora in B. thuringiensis-killing activity and provide a sound foundation for developing new insect control strategies aimed at enhancing the impact of biocontrol agents by reducing the immunocompetence of the host. PMID:27506800

  3. Midgut microbiota and host immunocompetence underlie Bacillus thuringiensis killing mechanism.

    PubMed

    Caccia, Silvia; Di Lelio, Ilaria; La Storia, Antonietta; Marinelli, Adriana; Varricchio, Paola; Franzetti, Eleonora; Banyuls, Núria; Tettamanti, Gianluca; Casartelli, Morena; Giordana, Barbara; Ferré, Juan; Gigliotti, Silvia; Ercolini, Danilo; Pennacchio, Francesco

    2016-08-23

    Bacillus thuringiensis is a widely used bacterial entomopathogen producing insecticidal toxins, some of which are expressed in insect-resistant transgenic crops. Surprisingly, the killing mechanism of B. thuringiensis remains controversial. In particular, the importance of the septicemia induced by the host midgut microbiota is still debated as a result of the lack of experimental evidence obtained without drastic manipulation of the midgut and its content. Here this key issue is addressed by RNAi-mediated silencing of an immune gene in a lepidopteran host Spodoptera littoralis, leaving the midgut microbiota unaltered. The resulting cellular immunosuppression was characterized by a reduced nodulation response, which was associated with a significant enhancement of host larvae mortality triggered by B. thuringiensis and a Cry toxin. This was determined by an uncontrolled proliferation of midgut bacteria, after entering the body cavity through toxin-induced epithelial lesions. Consequently, the hemolymphatic microbiota dramatically changed upon treatment with Cry1Ca toxin, showing a remarkable predominance of Serratia and Clostridium species, which switched from asymptomatic gut symbionts to hemocoelic pathogens. These experimental results demonstrate the important contribution of host enteric flora in B. thuringiensis-killing activity and provide a sound foundation for developing new insect control strategies aimed at enhancing the impact of biocontrol agents by reducing the immunocompetence of the host.

  4. Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans

    PubMed Central

    Cezairliyan, Brent; Vinayavekhin, Nawaporn; Grenfell-Lee, Daniel; Yuen, Grace J.; Saghatelian, Alan; Ausubel, Frederick M.

    2013-01-01

    Pathogenic microbes employ a variety of methods to overcome host defenses, including the production and dispersal of molecules that are toxic to their hosts. Pseudomonas aeruginosa, a Gram-negative bacterium, is a pathogen of a diverse variety of hosts including mammals and the nematode Caenorhabditis elegans. In this study, we identify three small molecules in the phenazine class that are produced by P. aeruginosa strain PA14 that are toxic to C. elegans. We demonstrate that 1-hydroxyphenazine, phenazine-1-carboxylic acid, and pyocyanin are capable of killing nematodes in a matter of hours. 1-hydroxyphenazine is toxic over a wide pH range, whereas the toxicities of phenazine-1-carboxylic acid and pyocyanin are pH-dependent at non-overlapping pH ranges. We found that acidification of the growth medium by PA14 activates the toxicity of phenazine-1-carboxylic acid, which is the primary toxic agent towards C. elegans in our assay. Pyocyanin is not toxic under acidic conditions and 1-hydroxyphenazine is produced at concentrations too low to kill C. elegans. These results suggest a role for phenazine-1-carboxylic acid in mammalian pathogenesis because PA14 mutants deficient in phenazine production have been shown to be defective in pathogenesis in mice. More generally, these data demonstrate how diversity within a class of metabolites could affect bacterial toxicity in different environmental niches. PMID:23300454

  5. Spacetimes foliated by nonexpanding and Killing horizons: Higher dimension

    NASA Astrophysics Data System (ADS)

    Lewandowski, Jerzy; Szereszewski, Adam; Waluk, Piotr

    2016-09-01

    The theory of nonexpanding horizons (NEHs) geometry and the theory of near-horizon geometries (NHGs) are two mathematical relativity frameworks generalizing the black hole theory. From the point of view of the NEHs theory, a NHG is just a very special case of a spacetime containing a NEH of many extra symmetries. It can be obtained as the Horowitz limit of a neighborhood of an arbitrary extremal Killing horizon. An unexpected relation between the two of them was discovered in the study of spacetimes foliated by a family of NEHs. The class of four-dimensional NHG solutions (either vacuum or coupled to a Maxwell field) was found as a family of examples of spacetimes admitting a NEH foliation. In the current paper, we systematically investigate geometries of the NEHs foliating a spacetime for arbitrary matter content and in arbitrary spacetime dimensions. We find that each horizon belonging to the foliation satisfies a condition that may be interpreted as an invitation for a transversal NEH to exist and to admit the structure of an extremal isolated horizon. Assuming the existence of a transversal extremal isolated horizon, we derive all the spacetime metrics satisfying the vacuum Einstein's equations. In this case, the NEHs become bifurcated Killing horizons.

  6. Light controllable surface coating for effective photothermal killing of bacteria.

    PubMed

    Kim, Sung Han; Kang, Eun Bi; Jeong, Chan Jin; Sharker, Shazid Md; In, Insik; Park, Sung Young

    2015-07-22

    Although the electronic properties of conducting films have been widely explored in optoelectronic fields, the optical absorption abilities of surface-coated films for photothermal conversion have been relatively less explored in the production of antibacterial coatings. Here, we present catechol-conjugated poly(vinylpyrrolidone) sulfobetaine (PVPS) and polyaniline (PANI) tightly linked by ionic interaction (PVPS:PANI) as a novel photothermal antibacterial agent for surface coating, which can absorb broadband near-infrared (NIR) light. Taking advantage of the NIR light absorption, this coating film can release eminent photothermal heat for the rapid killing of surface bacteria. The NIR light triggers a sharp rise in photothermal heat, providing the rapid and effective killing of 99.9% of the Gram-positive and -negative bacteria tested within 3 min of NIR light exposure when used at the concentration of 1 mg/mL. Although considerable progress has been made in the design of antibacterial coatings, the user control of NIR-irradiated rapid photothermal destruction of surface bacteria holds increasing attention beyond the traditional boundaries of typical antibacterial surfaces.

  7. Protecting the normal in order to better kill the cancer

    PubMed Central

    Liu, Bingya; Ezeogu, Lewis; Zellmer, Lucas; Yu, Baofa; Xu, Ningzhi; Joshua Liao, Dezhong

    2015-01-01

    Chemotherapy is the only option for oncologists when a cancer has widely spread to different body sites. However, almost all currently available chemotherapeutic drugs will eventually encounter resistance after their initial positive effect, mainly because cancer cells develop genetic alterations, collectively coined herein as mutations, to adapt to the therapy. Some patients may still respond to a second chemo drug, but few cases respond to a third one. Since it takes time for cancer cells to develop new mutations and then select those life-sustaining ones via clonal expansion, “run against time for mutations to emerge” should be a crucial principle for treatment of those currently incurable cancers. Since cancer cells constantly change to adapt to the therapy whereas normal cells are stable, it may be a better strategy to shift our focus from killing cancer cells per se to protecting normal cells from chemotherapeutic toxicity. This new strategy requires the development of new drugs that are nongenotoxic and can quickly, in just hours or days, kill cancer cells without leaving the still-alive cells with time to develop mutations, and that should have their toxicities confined to only one or few organs, so that specific protections can be developed and applied. PMID:26177855

  8. Univalent antibodies kill tumour cells in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Glennie, M. J.; Stevenson, G. T.

    1982-02-01

    Antibody molecules are bivalent, or less often multivalent, with each antibody site within a single molecule having the same specificity. Bivalency must enhance the tenacity of antibody attachment to cell surfaces, as dissociation will require simultaneous release at both sites. However, the bivalency of the antibody sometimes induces a target cell to undergo antigenic modulation1-3, thereby offering the cell a means of evading complement and the various effector cells recruited by the antibody. We have investigated the attack by univalent antibodies, which, despite removal of one antibody site, retain their Fc zones and hence their ability to recruit the killing agents, on neoplastic B lymphocytes of the guinea pig L2C line. Rabbit antibodies raised against surface immunoglobulin of these cells were partially digested with papain to yield the univalent Fab/c derivatives4,5. We report here that these derivatives showed enhanced cell killing both in vitro and in vivo, and that this enhancement appeared to derive from avoiding antigenic modulation.

  9. Aggregatibacter actinomycetemcomitans biofilm killing by a targeted ciprofloxacin prodrug.

    PubMed

    Reeves, Benjamin D; Young, Mark; Grieco, Paul A; Suci, Peter

    2013-09-01

    A pH-sensitive ciprofloxacin prodrug was synthesized and targeted against biofilms of the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). The dose required to reduce the viability of a mature biofilm of Aa by ~80% was in the range of ng cm(-2) of colonized area (mean biofilm density 2.33 × 10(9) cells cm(-2)). A mathematical model was formulated that predicts the temporal change in the concentration of ciprofloxacin in the Aa biofilm as the drug is released and diffuses into the bulk medium. The predictions of the model were consistent with the extent of killing obtained. The results demonstrate the feasibility of the strategy to induce mortality, and together with the mathematical model, provide the basis for design of targeted antimicrobial prodrugs for the topical treatment of oral infections such as periodontitis. The targeted prodrug approach offers the possibility of optimizing the dose of available antimicrobials in order to kill a chosen pathogen while leaving the commensal microbiota relatively undisturbed.

  10. Bacterial resistance to arsenic protects against protist killing.

    PubMed

    Hao, Xiuli; Li, Xuanji; Pal, Chandan; Hobman, Jon; Larsson, D G Joakim; Saquib, Quaiser; Alwathnani, Hend A; Rosen, Barry P; Zhu, Yong-Guan; Rensing, Christopher

    2017-04-01

    Protists kill their bacterial prey using toxic metals such as copper. Here we hypothesize that the metalloid arsenic has a similar role. To test this hypothesis, we examined intracellular survival of Escherichia coli (E. coli) in the amoeba Dictyostelium discoideum (D. discoideum). Deletion of the E. coli ars operon led to significantly lower intracellular survival compared to wild type E. coli. This suggests that protists use arsenic to poison bacterial cells in the phagosome, similar to their use of copper. In response to copper and arsenic poisoning by protists, there is selection for acquisition of arsenic and copper resistance genes in the bacterial prey to avoid killing. In agreement with this hypothesis, both copper and arsenic resistance determinants are widespread in many bacterial taxa and environments, and they are often found together on plasmids. A role for heavy metals and arsenic in the ancient predator-prey relationship between protists and bacteria could explain the widespread presence of metal resistance determinants in pristine environments.

  11. Effect of the method of killing, interval between killing and neck cutting and blood vessels cut on blood loss in broilers.

    PubMed

    Raj, A B; Johnson, S P

    1997-05-01

    1. Broiler chickens were killed using 90% argon in air, or 30% carbon dioxide and 60% argon in air or 120 mA per bird in a waterbath with a 50 Hz alternating electric current. Ventral or unilateral neck cutting was performed at 1, 3 or 5 min after killing. In addition, a group of broilers was stunned with 120 mA per bird in a waterbath using 1500 Hz alternating current and were bled out-with a ventral neck cut within 20 s from stunning. 2. Blood leaving the neck wound was collected in a bin placed on an electronic balance and a computer program calculated the cumulative blood loss up to 100 s after neck cutting. 3. Bleed-out was significantly affected by killing method and time of neck cutting. Broilers killed with the carbon dioxide-argon mixture bled-out less than those killed with argon or 50 Hz electric current. When compared with the 1 min neck cutting interval, a delay of 3-or 5 min resulted in a lower bleed-out. High frequency electrical stunning and ventral neck cutting within 20 s resulted in a slightly higher bleed-out than those recorded for the killing methods. However, within argon killing, a delay of 3 or 5 min in ventral or unilateral neck cutting had no significant effect on the bleed-out. In broilers killed with the carbon dioxide-argon mixture a 3 min delay in ventral neck cutting or a 5 min delay in unilateral neck cutting resulted in lower bleed-out. 4. Neck cutting of broilers within 5 min after argon killing or 3 min after killing with the carbon dioxide-argon mixture would result in a satisfactory bleed-out.

  12. Imaging burst kinetics and spatial coordination during serial killing by single natural killer cells.

    PubMed

    Choi, Paul J; Mitchison, Timothy J

    2013-04-16

    Cytotoxic lymphocytes eliminate virus-infected and cancerous cells by immune recognition and killing through the perforin-granzyme pathway. Traditional killing assays measure average target cell lysis at fixed times and high effector:target ratios. Such assays obscure kinetic details that might reveal novel physiology. We engineered target cells to report on granzyme activity, used very low effector:target ratios to observe potential serial killing, and performed low magnification time-lapse imaging to reveal time-dependent statistics of natural killer (NK) killing at the single-cell level. Most kills occurred during serial killing, and a single NK cell killed up to 10 targets over a 6-h assay. The first kill was slower than subsequent kills, especially on poor targets, or when NK signaling pathways were partially inhibited. Spatial analysis showed that sequential kills were usually adjacent. We propose that NK cells integrate signals from the previous and current target, possibly by simultaneous contact. The resulting burst kinetics and spatial coordination may control the activity of NK cells in tissues.

  13. Competition between apex predators? Brown bears decrease wolf kill rate on two continents.

    PubMed

    Tallian, Aimee; Ordiz, Andrés; Metz, Matthew C; Milleret, Cyril; Wikenros, Camilla; Smith, Douglas W; Stahler, Daniel R; Kindberg, Jonas; MacNulty, Daniel R; Wabakken, Petter; Swenson, Jon E; Sand, Håkan

    2017-02-08

    Trophic interactions are a fundamental topic in ecology, but we know little about how competition between apex predators affects predation, the mechanism driving top-down forcing in ecosystems. We used long-term datasets from Scandinavia (Europe) and Yellowstone National Park (North America) to evaluate how grey wolf (Canis lupus) kill rate was affected by a sympatric apex predator, the brown bear (Ursus arctos). We used kill interval (i.e. the number of days between consecutive ungulate kills) as a proxy of kill rate. Although brown bears can monopolize wolf kills, we found no support in either study system for the common assumption that they cause wolves to kill more often. On the contrary, our results showed the opposite effect. In Scandinavia, wolf packs sympatric with brown bears killed less often than allopatric packs during both spring (after bear den emergence) and summer. Similarly, the presence of bears at wolf-killed ungulates was associated with wolves killing less often during summer in Yellowstone. The consistency in results between the two systems suggests that brown bear presence actually reduces wolf kill rate. Our results suggest that the influence of predation on lower trophic levels may depend on the composition of predator communities.

  14. Competition between apex predators? Brown bears decrease wolf kill rate on two continents

    PubMed Central

    Ordiz, Andrés; Metz, Matthew C.; Milleret, Cyril; Wikenros, Camilla; Smith, Douglas W.; Stahler, Daniel R.; Kindberg, Jonas; MacNulty, Daniel R.; Wabakken, Petter; Swenson, Jon E.; Sand, Håkan

    2017-01-01

    Trophic interactions are a fundamental topic in ecology, but we know little about how competition between apex predators affects predation, the mechanism driving top-down forcing in ecosystems. We used long-term datasets from Scandinavia (Europe) and Yellowstone National Park (North America) to evaluate how grey wolf (Canis lupus) kill rate was affected by a sympatric apex predator, the brown bear (Ursus arctos). We used kill interval (i.e. the number of days between consecutive ungulate kills) as a proxy of kill rate. Although brown bears can monopolize wolf kills, we found no support in either study system for the common assumption that they cause wolves to kill more often. On the contrary, our results showed the opposite effect. In Scandinavia, wolf packs sympatric with brown bears killed less often than allopatric packs during both spring (after bear den emergence) and summer. Similarly, the presence of bears at wolf-killed ungulates was associated with wolves killing less often during summer in Yellowstone. The consistency in results between the two systems suggests that brown bear presence actually reduces wolf kill rate. Our results suggest that the influence of predation on lower trophic levels may depend on the composition of predator communities. PMID:28179516

  15. Lactoferricin Peptides Increase Macrophages' Capacity To Kill Mycobacterium avium

    PubMed Central

    Silva, Tânia; Moreira, Ana C.; Nazmi, Kamran; Moniz, Tânia; Vale, Nuno; Rangel, Maria; Gomes, Paula; Bolscher, Jan G. M.; Rodrigues, Pedro N.; Bastos, Margarida

    2017-01-01

    ABSTRACT Mycobacterial infections cause a significant burden of disease and death worldwide. Their treatment is long, toxic, costly, and increasingly prone to failure due to bacterial resistance to currently available antibiotics. New therapeutic options are thus clearly needed. Antimicrobial peptides represent an important source of new antimicrobial molecules, both for their direct activity and for their immunomodulatory potential. We have previously reported that a short version of the bovine antimicrobial peptide lactoferricin with amino acids 17 to 30 (LFcin17–30), along with its variants obtained by specific amino acid substitutions, killed Mycobacterium avium in broth culture. In the present work, those peptides were tested against M. avium living inside its natural host cell, the macrophage. We found that the peptides increased the antimicrobial action of the conventional antibiotic ethambutol inside macrophages. Moreover, the d-enantiomer of the lactoferricin peptide (d-LFcin17–30) was more stable and induced significant killing of intracellular mycobacteria by itself. Interestingly, d-LFcin17–30 did not localize to M. avium-harboring phagosomes but induced the production of proinflammatory cytokines and increased the formation of lysosomes and autophagosome-like vesicles. These results lead us to conclude that d-LFcin17–30 primes macrophages for intracellular microbial digestion through phagosomal maturation and/or autophagy, culminating in mycobacterial killing. IMPORTANCE The genus Mycobacterium comprises several pathogenic species, including M. tuberculosis, M. leprae, M. avium, etc. Infections caused by these bacteria are particularly difficult to treat due to their intrinsic impermeability, low growth rate, and intracellular localization. Antimicrobial peptides are increasingly acknowledged as potential treatment tools, as they have a high spectrum of activity, low tendency to induce bacterial resistance, and immunomodulatory properties. In

  16. Spacetime encodings. IV. The relationship between Weyl curvature and Killing tensors in stationary axisymmetric vacuum spacetimes

    SciTech Connect

    Brink, Jeandrew

    2010-01-15

    The problem of obtaining an explicit representation for the fourth invariant of geodesic motion (generalized Carter constant) of an arbitrary stationary axisymmetric vacuum spacetime generated from an Ernst potential is considered. The coupling between the nonlocal curvature content of the spacetime as encoded in the Weyl tensor, and the existence of a Killing tensor is explored and a constructive, algebraic test for a fourth-order Killing tensor suggested. The approach used exploits the variables defined for the Baecklund transformations to clarify the relationship between Weyl curvature, constants of geodesic motion, expressed as Killing tensors, and the solution-generation techniques. A new symmetric noncovariant formulation of the Killing equations is given. This formulation transforms the problem of looking for fourth-order Killing tensors in 4D into one of looking for four interlocking two-manifolds admitting fourth-order Killing tensors in 2D.

  17. Efficient Kill-Save Ratios Ease Up the Cognitive Demands on Counterintuitive Moral Utilitarianism.

    PubMed

    Trémolière, Bastien; Bonnefon, Jean-François

    2014-07-01

    The dual-process model of moral judgment postulates that utilitarian responses to moral dilemmas (e.g., accepting to kill one to save five) are demanding of cognitive resources. Here we show that utilitarian responses can become effortless, even when they involve to kill someone, as long as the kill-save ratio is efficient (e.g., 1 is killed to save 500). In Experiment 1, participants responded to moral dilemmas featuring different kill-save ratios under high or low cognitive load. In Experiments 2 and 3, participants responded at their own pace or under time pressure. Efficient kill-save ratios promoted utilitarian responding and neutered the effect of load or time pressure. We discuss whether this effect is more easily explained by a parallel-activation model or by a default-interventionist model.

  18. Opinions of university students on honour killings: Perspective from Islamabad and Rawalpindi.

    PubMed

    Shaikh, Masood Ali; Kamal, Anila; Naqvi, Irum

    2015-04-01

    Honour killing incidents have been reported from every province of Pakistan. In 2014 a pregnant woman was killed in front of Lahore High Court, by her family members, in the name of honour. This study was conducted to determine the perspective of university students on honour killing with specific reference to one such killing incident in Lahore. Cumulatively, 989 students participated in the survey. Compared with female students, male students were less likely to agree and were more unequivocal that a woman has a right to marry any man she wants despite her family's disapproval, in a statistically significant manner. Similarly, male students were statistically significantly more likely to report that killing in the name of honour is always justified and were less equivocal about it compared to female students. Nonetheless, cumulatively 824 (83.3%) students believed that killing in the name of honour is not always justified.

  19. The moral distinction between killing and letting die in medical cases.

    PubMed

    Asscher, Joachim

    2008-06-01

    In some medical cases there is a moral distinction between killing and letting die, but in others there is not. In this paper I present an original and principled account of the moral distinction between killing and letting die. The account provides both an explanation of the moral distinction and an explanation for why the distinction does not always hold. If these explanations are correct, the moral distinction between killing and letting die must be taken seriously in medical contexts. Defeasibly, when an agent kills she takes responsibility, but when an agent lets die she does not take responsibility. Therein lies the moral distinction between killing and letting die. The distinction, however, is defeated when an agent is already responsible for the surrounding situation. In such cases, killing does not involve taking any further responsibility and letting die does not avoid taking any responsibility. Medical examples are frequently complicated because patients' autonomous choices impact upon medical practitioners' surrounding responsibility.

  20. Towards fluid instabilities of stationary non-Killing horizons

    NASA Astrophysics Data System (ADS)

    Fischetti, Sebastian; Way, Benson

    2016-12-01

    Flowing black holes are asymptotically locally AdS spacetimes that are stationary but have non-Killing horizons. Holographically, they are dual to a steady-state heat flow in the boundary field theory. We investigate the stability of these black holes in the limit in which they are well-described by the relativistic conformal Navier-Stokes equation. More precisely, we study the quasi-normal modes of the linearized ideal fluid equations. Though we find no unstable modes, there are an infinite number of modes at finite transverse momentum which are arbitrarily long-lived. This suggests the possibility that either non-modal effects or nonlinear interactions between these modes can give rise to new types of gravitational instabilities.

  1. Myeloperoxidase binds to and kills Entamoeba histolytica trophozoites.

    PubMed

    Pacheco-Yépez, J; Rivera-Aguilar, V; Barbosa-Cabrera, E; Rojas Hernández, S; Jarillo-Luna, R A; Campos-Rodríguez, R

    2011-05-01

    During amebic invasion, neutrophils are a key component in either protecting against invading trophozoites or contributing to tissue damage. Upon degranulating or being lysed, neutrophils release toxic substances that can kill amebas as well as damage host tissue. In a previous study we identified a protein from nonspecifically stimulated peritoneal exudates of hamster that has peroxidase and marked amebicidal activity. In the current study we analyzed the in vitro amebicidal effect of purified hamster myeloperoxidase (MPO). The results demonstrate that MPO must bind directly to the surface of Entamoeba histolytica trophozoites in order to carry out amebicidal activity by using the H(2) O(2) produced by the amebas themselves. Myeloperoxidase-incubated amebas showed important morphological and ultrastructural alterations that increased with incubation time. Changes included an increase of vacuoles in the cytoplasm, a decrease of glycogen, alterations of nuclear morphology and disturbances in the plasma membrane culminating in complete ameba destruction.

  2. Biosystems Engineering of Prokaryotes with Tumor-Killing Capacities.

    PubMed

    Kalyoncu, Ebuzer; Olmez, Tolga T; Ozkan, Alper D; Sarioglu, Omer F

    2016-01-01

    Certain bacteria selectively attack tumor tissues and trigger tumor shrinkage by producing toxins and modulating the local immune system, but their clinical utility is limited because of the dangers posed by systemic infection. Genetic engineering can be used to minimize the risks associated with tumor-targeting pathogens, as well as to increase their efficiency in killing tumor cells. Advances in genetic circuit design have led to the development of bacterial strains with enhanced tumor-targeting capacities and the ability to secrete therapeutics, cytotoxic proteins and prodrug-cleaving enzymes, which allows their safe and effective use for cancer treatment. The present review details the recent advances in the design and application of these modified bacterial strains.

  3. How antibiotics kill bacteria: from targets to networks

    PubMed Central

    Kohanski, Michael A; Dwyer, Daniel J; Collins, James J

    2010-01-01

    Preface Antibiotic drug-target interactions, and their respective direct effects, are generally well-characterized. In contrast, the bacterial responses to antibiotic drug treatments that contribute to cell death are not as well understood and have proven to be quite complex, involving multiple genetic and biochemical pathways. Here, we review the multi-layered effects of drug-target interactions, including the essential cellular processes inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing by bactericidal antibiotics. We also discuss new insights into these mechanisms that have been revealed through the study of biological networks, and describe how these insights, together with related developments in synthetic biology, may be exploited to create novel antibacterial therapies. PMID:20440275

  4. Bacteria can mobilize nematode-trapping fungi to kill nematodes

    PubMed Central

    Wang, Xin; Li, Guo-Hong; Zou, Cheng-Gang; Ji, Xing-Lai; Liu, Tong; Zhao, Pei-Ji; Liang, Lian-Ming; Xu, Jian-Ping; An, Zhi-Qiang; Zheng, Xi; Qin, Yue-Ke; Tian, Meng-Qing; Xu, You-Yao; Ma, Yi-Cheng; Yu, Ze-Fen; Huang, Xiao-Wei; Liu, Shu-Qun; Niu, Xue-Mei; Yang, Jin-Kui; Huang, Ying; Zhang, Ke-Qin

    2014-01-01

    In their natural habitat, bacteria are consumed by bacterivorous nematodes; however, they are not simply passive preys. Here we report a defensive mechanism used by certain bacteria to mobilize nematode-trapping fungi to kill nematodes. These bacteria release urea, which triggers a lifestyle switch in the fungus Arthrobotrys oligospora from saprophytic to nematode–predatory form; this predacious form is characterized by formation of specialized cellular structures or ‘traps’. The bacteria significantly promote the elimination of nematodes by A. oligospora. Disruption of genes involved in urea transport and metabolism in A. oligospora abolishes the urea-induced trap formation. Furthermore, the urea metabolite ammonia functions as a signal molecule in the fungus to initiate the lifestyle switch to form trap structures. Our findings highlight the importance of multiple predator–prey interactions in prey defense mechanisms. PMID:25514608

  5. Glucose Augments Killing Efficiency of Daptomycin Challenged Staphylococcus aureus Persisters.

    PubMed

    Prax, Marcel; Mechler, Lukas; Weidenmaier, Christopher; Bertram, Ralph

    2016-01-01

    Treatment of Staphylococcus aureus in stationary growth phase with high doses of the antibiotic daptomycin (DAP) eradicates the vast majority of the culture and leaves persister cells behind. Despite resting in a drug-tolerant and dormant state, persister cells exhibit metabolic activity which might be exploited for their elimination. We here report that the addition of glucose to S. aureus persisters treated with DAP increased killing by up to five-fold within one hour. This glucose-DAP effect also occurred with strains less sensitive to the drug. The underlying mechanism is independent of the proton motive force and was not observed with non-metabolizable 2-deoxy-glucose. Our results are consistent with two hypotheses on the glucose-DAP interplay. The first is based upon glucose-induced carbohydrate transport proteins that may influence DAP and the second suggests that glucose may trigger the release or activity of cell-lytic proteins to augment DAP's mode of action.

  6. Medicolegal investigation of political killings in El Salvador.

    PubMed

    Thomsen, J L; Gruschow, J; Stover, E

    1989-06-17

    An axiom of Thomas Hobbes states that "people are never more helpless than when the force meant to protect their rights turns against them." Hobbes' axiom holds true today, with Amnesty International reporting that hundreds of thousands have been murdered by their governments. This article examines the medicolegal aspects of an investigation into the deaths of two Salvadoran peasants who were reportedly tortured and executed by soldiers in February 1988. One of the authors, Thomsen, participated in the investigation as a court-ordered expert, and as a representative of the American Association for the Advancement of Science and of a Salvadoran legal aid organization. His necropsy findings are reported with observations and comments. The article concludes with suggestions for initiatives that might be undertaken by individual physicians and institutions to improve the quality and impartiality of medicolegal investigations into political killings.

  7. Eat, kill or die: when amoeba meets bacteria.

    PubMed

    Cosson, Pierre; Soldati, Thierry

    2008-06-01

    The core function of the innate immune response, phagocytosis, did not evolve first in metazoans but rather in primitive unicellular eukaryotes. Thus, though amoebae separated from the tree leading to metazoan shortly after the divergence of plants, they share many specific functions with mammalian phagocytic cells. Dictyostelium discoideum is by far the most studied amoeba, and it is proving useful to analyze phagocytosis and intracellular killing of bacteria. Since the basic mechanisms involved appear extremely conserved, Dictyostelium provides novel insights into the function of many new gene products. Bacterial pathogenicity was certainly largely developed to resist predatory amoebae in the environment, and this accounts for the fact that a large number of bacterial virulence traits can be studied using Dictyostelium as a host. This provides a particularly powerful system to analyze the complex interactions between pathogenic bacteria and host cells, where both the Dictyostelium host and the bacteria can be manipulated genetically with relative ease.

  8. Could Giant Basin-Forming Impacts Have Killed Martian Dynamo?

    NASA Technical Reports Server (NTRS)

    Kuang, W.; Jiang, W.; Roberts, J.; Frey, H. V.

    2014-01-01

    The observed strong remanent crustal magnetization at the surface of Mars suggests an active dynamo in the past and ceased to exist around early to middle Noachian era, estimated by examining remagnetization strengths in extant and buried impact basins. We investigate whether the Martian dynamo could have been killed by these large basin-forming impacts, via numerical simulation of subcritical dynamos with impact-induced thermal heterogeneity across the core-mantle boundary. We find that subcritical dynamos are prone to the impacts centered on locations within 30 deg of the equator but can easily survive those at higher latitudes. Our results further suggest that magnetic timing places a strong constraint on postimpact polar reorientation, e.g., a minimum 16 deg polar reorientation is needed if Utopia is the dynamo killer.

  9. Manners of killing and rituals in Apulian mafia murders.

    PubMed

    De Donno, Antonio; Santoro, Valeria; Rossi, Anna Paola; Grattagliano, Ignazio; Introna, Francesco

    2009-07-01

    The Apulian (South of Italy) territory saw the birth of a criminal organization called Sacra Corona Unita (SCU, United Holy Crown) which transformed the rules of traditional mafia organizations. This work examined 83 victims of the SCU between 1980 and 2000. The bodies were mainly of SCU members and in some cases, of police and law enforcement officers and other citizens caught in the crossfire. Some of these were discovered; thanks to the collaboration of "repented" SCU members who became police informers. The condition of the bodies varied in relation to the date and manner of killing. In some cases anthropometric research methods were necessary. In 73% of the cases, lesions of the head were the only marks left on the body. In conclusion, the existence of some social aspects connected with the symbolisms and membership rites that characterized the origin, evolution, and decline of the SCU is stressed.

  10. Roadblocks on the kill curve: Testing the Raup hypothesis

    USGS Publications Warehouse

    Poag, C.W.

    1997-01-01

    The documented presence of two large (???100-km diameter), possibly coeval impact craters of late Eocene age, requires modification of the impact-kill curve proposed by David M. Raup. Though the estimated meteorite size for each crater alone is large enough to have produced considerable global environmental stress, no horizons of mass mortality or pulsed extinction are known to be associated with either crater or their ejecta deposits. Thus, either there is no fixed relationship between extinction magnitude and crater diameter, or a meteorite that would produce a crater of >100-km diameter is required to raise extinction rates significantly above a ???5% background level. Both impacts took place ???1-2 m.y. before the "Terminal Eocene Event"( =early Oligocene pulsed extinction). Their collective long-term environmental effects, however, may have either delayed that extinction pulse or produced threshold conditions necessary for it to take place.

  11. The efficacy of the heat killing of Mycobacterium tuberculosis

    PubMed Central

    Doig, C; Seagar, A L; Watt, B; Forbes, K J

    2002-01-01

    There is concern that current procedures for the heat inactivation of Mycobacterium tuberculosis may not be adequate. This raises serious safety issues for laboratory staff performing molecular investigations such as IS6110 restriction fragment length polymorphism typing. This paper confirms that the protocol of van Embden et al, as performed routinely in this laboratory, is safe and effective for the heat inactivation of M tuberculosis. This procedure involves complete immersion of a tube containing a suspension of one loopfull of growth in a water bath at 80°C for 20 minutes. Seventy four isolates were included in this investigation. Despite prolonged incubation for 20 weeks, none of the heat killed M tuberculosis suspensions produced visible colonies or gave a positive growth signal from liquid culture. This method did not affect the integrity of the DNA for subsequent molecular investigations. PMID:12354807

  12. Could giant basin-forming impacts have killed Martian dynamo?

    NASA Astrophysics Data System (ADS)

    Kuang, W.; Jiang, W.; Roberts, J.; Frey, H. V.

    2014-11-01

    The observed strong remanent crustal magnetization at the surface of Mars suggests an active dynamo in the past and ceased to exist around early to middle Noachian era, estimated by examining remagnetization strengths in extant and buried impact basins. We investigate whether the Martian dynamo could have been killed by these large basin-forming impacts, via numerical simulation of subcritical dynamos with impact-induced thermal heterogeneity across the core-mantle boundary. We find that subcritical dynamos are prone to the impacts centered on locations within 30° of the equator but can easily survive those at higher latitudes. Our results further suggest that magnetic timing places a strong constraint on postimpact polar reorientation, e.g., a minimum 16° polar reorientation is needed if Utopia is the dynamo killer.

  13. Bacteria can mobilize nematode-trapping fungi to kill nematodes.

    PubMed

    Wang, Xin; Li, Guo-Hong; Zou, Cheng-Gang; Ji, Xing-Lai; Liu, Tong; Zhao, Pei-Ji; Liang, Lian-Ming; Xu, Jian-Ping; An, Zhi-Qiang; Zheng, Xi; Qin, Yue-Ke; Tian, Meng-Qing; Xu, You-Yao; Ma, Yi-Cheng; Yu, Ze-Fen; Huang, Xiao-Wei; Liu, Shu-Qun; Niu, Xue-Mei; Yang, Jin-Kui; Huang, Ying; Zhang, Ke-Qin

    2014-12-16

    In their natural habitat, bacteria are consumed by bacterivorous nematodes; however, they are not simply passive preys. Here we report a defensive mechanism used by certain bacteria to mobilize nematode-trapping fungi to kill nematodes. These bacteria release urea, which triggers a lifestyle switch in the fungus Arthrobotrys oligospora from saprophytic to nematode-predatory form; this predacious form is characterized by formation of specialized cellular structures or 'traps'. The bacteria significantly promote the elimination of nematodes by A. oligospora. Disruption of genes involved in urea transport and metabolism in A. oligospora abolishes the urea-induced trap formation. Furthermore, the urea metabolite ammonia functions as a signal molecule in the fungus to initiate the lifestyle switch to form trap structures. Our findings highlight the importance of multiple predator-prey interactions in prey defense mechanisms.

  14. Nonfeeding: lawful killing in CA, homicide in NJ.

    PubMed

    Annas, George J

    1983-12-01

    Appellate courts in California and New Jersey have reached conflicting conclusions in the first legal tests of whether artificial feeding is a "medical treatment," and whether it is ever legally permissible to allow a patient to die from dehydration or starvation. In a criminal prosecution of physicians Robert Nejdl and Neil Barber, the California court ruled that there was no significant difference between a respirator and intravenous feeding, and that the two doctors had no legal duty to continue "futile" treatment of their irreversibly comatose patient. The New Jersey court rejected as purposeful killing a request to remove the nasogastric tube from elderly nursing home patient Claire Conroy, who was incompetent but not comatose. Annas considers the issue of pain or suffering to be central to decision making in such cases.

  15. Phosphate Starvation Induces the Sporulation Killing Factor of Bacillus subtilis

    PubMed Central

    Allenby, Nicholas E. E.; Watts, Carys A.; Homuth, Georg; Prágai, Zoltán; Wipat, Anil; Ward, Alan C.; Harwood, Colin R.

    2006-01-01

    Bacillus subtilis produces and exports a peptide sporulation killing factor (SkfA) that induces lysis of sibling cells. skfA is part of the skf operon (skfA-H), which is responsible for immunity to SkfA, as well as for production and export of SkfA. Here we report that transcription of skfA is markedly induced when cells of B. subtilis are subjected to phosphate starvation. The role of PhoP in regulation of the skf operon was confirmed by in vitro gel shift assays, which showed that this operon is a new member of the PhoP regulon. A putative stem-loop structure in the skfA-skfB intergenic region is proposed to act as a stabilizer of an skfA-specific transcript. PMID:16816204

  16. Phosphate starvation induces the sporulation killing factor of Bacillus subtilis.

    PubMed

    Allenby, Nicholas E E; Watts, Carys A; Homuth, Georg; Prágai, Zoltán; Wipat, Anil; Ward, Alan C; Harwood, Colin R

    2006-07-01

    Bacillus subtilis produces and exports a peptide sporulation killing factor (SkfA) that induces lysis of sibling cells. skfA is part of the skf operon (skfA-H), which is responsible for immunity to SkfA, as well as for production and export of SkfA. Here we report that transcription of skfA is markedly induced when cells of B. subtilis are subjected to phosphate starvation. The role of PhoP in regulation of the skf operon was confirmed by in vitro gel shift assays, which showed that this operon is a new member of the PhoP regulon. A putative stem-loop structure in the skfA-skfB intergenic region is proposed to act as a stabilizer of an skfA-specific transcript.

  17. Could Giant Basin-Forming Impacts Have Killed Martian Dynamo?

    NASA Technical Reports Server (NTRS)

    Kuang, W.; Jiang, W.; Roberts, J.; Frey, H. V.

    2014-01-01

    The observed strong remanent crustal magnetization at the surface of Mars suggests an active dynamo in the past and ceased to exist around early to middle Noachian era, estimated by examining remagnetization strengths in extant and buried impact basins. We investigate whether the Martian dynamo could have been killed by these large basin-forming impacts, via numerical simulation of subcritical dynamos with impact-induced thermal heterogeneity across the core-mantle boundary. We find that subcritical dynamos are prone to the impacts centered on locations within 30 deg of the equator but can easily survive those at higher latitudes. Our results further suggest that magnetic timing places a strong constraint on postimpact polar reorientation, e.g., a minimum 16 deg polar reorientation is needed if Utopia is the dynamo killer.

  18. Killing Prostate Cancer Cells and Endothelial Cells with a VEGF-Triggered Cell Death Receptor

    DTIC Science & Technology

    2005-06-01

    AD_________________ Award Number: DAMD17-02- 1 -0029 TITLE: Killing Prostate Cancer Cells and...CONTRACT NUMBER Killing Prostate Cancer Cells and Endothelial Cells with a VEGF-Triggered Cell Death Receptor 5b. GRANT NUMBER DAMD17-02- 1 -0029...as a means to kill prostate cancer cells and vascular endothelial cells in vitro. The scope of this project involved: ( 1 ) creating adenoviral

  19. Age and sex composition of seals killed by polar bears in the eastern Beaufort Sea.

    PubMed

    Pilfold, Nicholas W; Derocher, Andrew E; Stirling, Ian; Richardson, Evan; Andriashek, Dennis

    2012-01-01

    Polar bears (Ursus maritimus) of the Beaufort Sea enter hyperphagia in spring and gain fat reserves to survive periods of low prey availability. We collected information on seals killed by polar bears (n=650) and hunting attempts on ringed seal (Pusa hispida) lairs (n=1396) observed from a helicopter during polar bear mark-recapture studies in the eastern Beaufort Sea in spring in 1985-2011. We investigated how temporal shifts in ringed seal reproduction affect kill composition and the intraspecific vulnerabilities of ringed seals to polar bear predation. Polar bears primarily preyed on ringed seals (90.2%) while bearded seals (Erignathus barbatus) only comprised 9.8% of the kills, but 33% of the biomass. Adults comprised 43.6% (150/344) of the ringed seals killed, while their pups comprised 38.4% (132/344). Juvenile ringed seals were killed at the lowest proportion, comprising 18.0% (62/344) of the ringed seal kills. The proportion of ringed seal pups was highest between 2007-2011, in association with high ringed seal productivity. Half of the adult ringed seal kills were ≥ 21 years (60/121), and kill rates of adults increased following the peak of parturition. Determination of sex from DNA revealed that polar bears killed adult male and adult female ringed seals equally (0.50, n=78). The number of hunting attempts at ringed seal subnivean lair sites was positively correlated with the number of pup kills (r(2) =0.30, P=0.04), but was not correlated with the number of adult kills (P=0.37). Results are consistent with decadal trends in ringed seal productivity, with low numbers of pups killed by polar bears in spring in years of low pup productivity, and conversely when pup productivity was high. Vulnerability of adult ringed seals to predation increased in relation to reproductive activities and age, but not gender.

  20. Targeting the Human Complement Membrane Attack Complex to Selectively Kill Prostate Cancer Cells

    DTIC Science & Technology

    2014-12-01

    1 AD_________________ Award Number: W81XWH-11-1-0309 TITLE: Targeting the Human Complement Membrane Attack Complex to Selectively Kill Prostate...Attack Complex to Selectively Kill Prostate Cancer Cells 5b. GRANT NUMBER W81XWH-11-1-0309 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Samuel R...leading to the lytic death of PSA- producing prostate cancer cells as well as a significant bystander effect and killing of non-PSA producing cancer

  1. Comparative Killing Rates of Fluoroquinolones and Cell Wall-Active Agents

    PubMed Central

    Fung-Tomc, Joan C.; Gradelski, Elizabeth; Valera, Lourdes; Kolek, Benjamin; Bonner, Daniel P.

    2000-01-01

    Killing rates of fluoroquinolones, β-lactams, and vancomycin were compared against Enterobacteriaceae, Staphylococcus aureus, pneumococci, streptococci, and Enterococcus faecalis. The times required for fluoroquinolones to decrease viability by 3 log10 were 1.5 h for Enterobacteriaceae, 4 to 6 h for staphylococci, and ≥6 h for streptococci and enterococci. Thus, the rate of killing by fluoroquinolones is organism group dependent; overall, they killed more rapidly than β-lactams and vancomycin. PMID:10770784

  2. A Sequential Model of Host Cell Killing and Phagocytosis by Entamoeba histolytica

    PubMed Central

    Sateriale, Adam; Huston, Christopher D.

    2011-01-01

    The protozoan parasite Entamoeba histolytica is responsible for invasive intestinal and extraintestinal amebiasis. The virulence of Entamoeba histolytica is strongly correlated with the parasite's capacity to effectively kill and phagocytose host cells. The process by which host cells are killed and phagocytosed follows a sequential model of adherence, cell killing, initiation of phagocytosis, and engulfment. This paper presents recent advances in the cytolytic and phagocytic processes of Entamoeba histolytica in context of the sequential model. PMID:21331284

  3. Male killing Spiroplasma protects Drosophila melanogaster against two parasitoid wasps

    PubMed Central

    Xie, J; Butler, S; Sanchez, G; Mateos, M

    2014-01-01

    Maternally transmitted associations between endosymbiotic bacteria and insects are diverse and widespread in nature. Owing to imperfect vertical transmission, many heritable microbes have evolved compensational mechanisms to enhance their persistence in host lineages, such as manipulating host reproduction and conferring fitness benefits to host. Symbiont-mediated defense against natural enemies of hosts is increasingly recognized as an important mechanism by which endosymbionts enhance host fitness. Members of the genus Spiroplasma associated with distantly related Drosophila hosts are known to engage in either reproductive parasitism (i.e., male killing) or defense against natural enemies (the parasitic wasp Leptopilina heterotoma and a nematode). A male-killing strain of Spiroplasma (strain Melanogaster Sex Ratio Organism (MSRO)) co-occurs with Wolbachia (strain wMel) in certain wild populations of the model organism Drosophila melanogaster. We examined the effects of Spiroplasma MSRO and Wolbachia wMel on Drosophila survival against parasitism by two common wasps, Leptopilina heterotoma and Leptopilina boulardi, that differ in their host ranges and host evasion strategies. The results indicate that Spiroplasma MSRO prevents successful development of both wasps, and confers a small, albeit significant, increase in larva-to-adult survival of flies subjected to wasp attacks. We modeled the conditions under which defense can contribute to Spiroplasma persistence. Wolbachia also confers a weak, but significant, survival advantage to flies attacked by L. heterotoma. The host protective effects exhibited by Spiroplasma and Wolbachia are additive and may provide the conditions for such cotransmitted symbionts to become mutualists. Occurrence of Spiroplasma-mediated protection against distinct parasitoids in divergent Drosophila hosts suggests a general protection mechanism. PMID:24281548

  4. Male killing Spiroplasma protects Drosophila melanogaster against two parasitoid wasps.

    PubMed

    Xie, J; Butler, S; Sanchez, G; Mateos, M

    2014-04-01

    Maternally transmitted associations between endosymbiotic bacteria and insects are diverse and widespread in nature. Owing to imperfect vertical transmission, many heritable microbes have evolved compensational mechanisms to enhance their persistence in host lineages, such as manipulating host reproduction and conferring fitness benefits to host. Symbiont-mediated defense against natural enemies of hosts is increasingly recognized as an important mechanism by which endosymbionts enhance host fitness. Members of the genus Spiroplasma associated with distantly related Drosophila hosts are known to engage in either reproductive parasitism (i.e., male killing) or defense against natural enemies (the parasitic wasp Leptopilina heterotoma and a nematode). A male-killing strain of Spiroplasma (strain Melanogaster Sex Ratio Organism (MSRO)) co-occurs with Wolbachia (strain wMel) in certain wild populations of the model organism Drosophila melanogaster. We examined the effects of Spiroplasma MSRO and Wolbachia wMel on Drosophila survival against parasitism by two common wasps, Leptopilina heterotoma and Leptopilina boulardi, that differ in their host ranges and host evasion strategies. The results indicate that Spiroplasma MSRO prevents successful development of both wasps, and confers a small, albeit significant, increase in larva-to-adult survival of flies subjected to wasp attacks. We modeled the conditions under which defense can contribute to Spiroplasma persistence. Wolbachia also confers a weak, but significant, survival advantage to flies attacked by L. heterotoma. The host protective effects exhibited by Spiroplasma and Wolbachia are additive and may provide the conditions for such cotransmitted symbionts to become mutualists. Occurrence of Spiroplasma-mediated protection against distinct parasitoids in divergent Drosophila hosts suggests a general protection mechanism.

  5. Inactivated- or killed-virus HIV/AIDS vaccines.

    PubMed

    Sheppard, Haynes W

    2005-06-01

    Inactivated or "killed" virus (KV) is a "classical" approach that has produced safe and effective human and veterinary vaccines but has received relatively little attention in the effort to develop an HIV/AIDS vaccine. Initially, KV and rgp120 subunit vaccines were the two most obvious approaches but, unfortunately, rgp120 has not been efficacious and the KV approach has been limited by a variety of scientific, technical, and sociological factors. For example, when responses to cellular antigens, present on SIV grown in human cells, proved to be largely responsible for efficacy, the KV approach was widely discounted. Similarly, when lab-adapted HIV-1 appeared to lose envelope glycoprotein during preparation (not the case for primary isolates), this was viewed as a fundamental barrier to the KV concept. Also, a preference for "safer", genetically-engineered vaccines, and emphasis on cellular immunity, have left KV low on the priority list for funding agencies and investigators. The recent suggestion that "native" trimeric gp120 displays conserved conformational neutralization epitopes, along with the failure of rgp120, and difficulties in raising strong cellular responses with DNA or vectored vaccines, has restored some interest in the KV concept. In the past 15 years, several groups have initiated pre-clinical development of KV candidates for SIV or HIV and promising, albeit limited, information has been produced. In this chapter we discuss the rationale (including pros and cons) for producing and testing killed-HIV vaccines, the prospects for success, the nature and scope of research needed to test the KV concept, what has been learned to date, and what remains undone.

  6. Pyruvate protects pathogenic spirochetes from H2O2 killing.

    PubMed

    Troxell, Bryan; Zhang, Jun-Jie; Bourret, Travis J; Zeng, Melody Yue; Blum, Janice; Gherardini, Frank; Hassan, Hosni M; Yang, X Frank

    2014-01-01

    Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (≈0.6 µM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected ΔuvrB and ΔmutS from H2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi, which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H2O2 generated by the host antibacterial response generated during infection.

  7. Bystander Host Cell Killing Effects of Clostridium perfringens Enterotoxin

    PubMed Central

    Shrestha, Archana; Hendricks, Matthew R.; Bomberger, Jennifer M.

    2016-01-01

    ABSTRACT Clostridium perfringens enterotoxin (CPE) binds to claudin receptors, e.g., claudin-4, and then forms a pore that triggers cell death. Pure cultures of host cells that do not express claudin receptors, e.g., fibroblasts, are unaffected by pathophysiologically relevant CPE concentrations in vitro. However, both CPE-insensitive and CPE-sensitive host cells are present in vivo. Therefore, this study tested whether CPE treatment might affect fibroblasts when cocultured with CPE-sensitive claudin-4 fibroblast transfectants or Caco-2 cells. Under these conditions, immunofluorescence microscopy detected increased death of fibroblasts. This cytotoxic effect involved release of a toxic factor from the dying CPE-sensitive cells, since it could be reproduced using culture supernatants from CPE-treated sensitive cells. Supernatants from CPE-treated sensitive cells, particularly Caco-2 cells, were found to contain high levels of membrane vesicles, often containing a CPE species. However, most cytotoxic activity remained in those supernatants even after membrane vesicle depletion, and CPE was not detected in fibroblasts treated with supernatants from CPE-treated sensitive cells. Instead, characterization studies suggest that a major cytotoxic factor present in supernatants from CPE-treated sensitive cells may be a 10- to 30-kDa host serine protease or require the action of that host serine protease. Induction of caspase-3-mediated apoptosis was found to be important for triggering release of the cytotoxic factor(s) from CPE-treated sensitive host cells. Furthermore, the cytotoxic factor(s) in these supernatants was shown to induce a caspase-3-mediated killing of fibroblasts. This bystander killing effect due to release of cytotoxic factors from CPE-treated sensitive cells could contribute to CPE-mediated disease. PMID:27965452

  8. Ecological approaches to oral biofilms: control without killing.

    PubMed

    Marsh, Phil D; Head, David A; Devine, Deirdre A

    2015-01-01

    Humans have co-evolved with micro-organisms and have a symbiotic or mutualistic relationship with their resident microbiome. As at other body surfaces, the mouth has a diverse microbiota that grows on oral surfaces as structurally and functionally organised biofilms. The oral microbiota is natural and provides important benefits to the host, including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and colonisation by exogenous microbes. On occasions, this symbiotic relationship breaks down, and previously minor components of the microbiota outcompete beneficial bacteria, thereby increasing the risk of disease. Antimicrobial agents have been formulated into many oral care products to augment mechanical plaque control. A delicate balance is needed, however, to control the oral microbiota at levels compatible with health, without killing beneficial bacteria and losing the key benefits delivered by these resident microbes. These antimicrobial agents may achieve this by virtue of their recommended twice daily topical use, which results in pharmacokinetic profiles indicating that they are retained in the mouth for relatively long periods at sublethal levels. At these concentrations they are still able to inhibit bacterial traits implicated in disease (e.g. sugar transport/acid production; protease activity) and retard growth without eliminating beneficial species. In silico modelling studies have been performed which support the concept that either reducing the frequency of acid challenge and/or the terminal pH, or by merely slowing bacterial growth, results in maintaining a community of beneficial bacteria under conditions that might otherwise lead to disease (control without killing). 2015 S. Karger AG, Basel

  9. An evaluation of sex-age-kill (SAK) model performance

    USGS Publications Warehouse

    Millspaugh, Joshua J.; Skalski, John R.; Townsend, Richard L.; Diefenbach, Duane R.; Boyce, Mark S.; Hansen, Lonnie P.; Kammermeyer, Kent

    2009-01-01

    The sex-age-kill (SAK) model is widely used to estimate abundance of harvested large mammals, including white-tailed deer (Odocoileus virginianus). Despite a long history of use, few formal evaluations of SAK performance exist. We investigated how violations of the stable age distribution and stationary population assumption, changes to male or female harvest, stochastic effects (i.e., random fluctuations in recruitment and survival), and sampling efforts influenced SAK estimation. When the simulated population had a stable age distribution and λ > 1, the SAK model underestimated abundance. Conversely, when λ < 1, the SAK overestimated abundance. When changes to male harvest were introduced, SAK estimates were opposite the true population trend. In contrast, SAK estimates were robust to changes in female harvest rates. Stochastic effects caused SAK estimates to fluctuate about their equilibrium abundance, but the effect dampened as the size of the surveyed population increased. When we considered both stochastic effects and sampling error at a deer management unit scale the resultant abundance estimates were within ±121.9% of the true population level 95% of the time. These combined results demonstrate extreme sensitivity to model violations and scale of analysis. Without changes to model formulation, the SAK model will be biased when λ ≠ 1. Furthermore, any factor that alters the male harvest rate, such as changes to regulations or changes in hunter attitudes, will bias population estimates. Sex-age-kill estimates may be precise at large spatial scales, such as the state level, but less so at the individual management unit level. Alternative models, such as statistical age-at-harvest models, which require similar data types, might allow for more robust, broad-scale demographic assessments.

  10. Pyruvate Protects Pathogenic Spirochetes from H2O2 Killing

    PubMed Central

    Troxell, Bryan; Zhang, Jun-Jie; Bourret, Travis J.; Zeng, Melody Yue; Blum, Janice; Gherardini, Frank; Hassan, Hosni M.; Yang, X. Frank

    2014-01-01

    Pathogenic spirochetes cause clinically relevant diseases in humans and animals, such as Lyme disease and leptospirosis. The causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of leptospirosis, Leptospria interrogans, encounter reactive oxygen species (ROS) during their enzootic cycles. This report demonstrated that physiologically relevant concentrations of pyruvate, a potent H2O2 scavenger, and provided passive protection to B. burgdorferi and L. interrogans against H2O2. When extracellular pyruvate was absent, both spirochetes were sensitive to a low dose of H2O2 (≈0.6 µM per h) generated by glucose oxidase (GOX). Despite encoding a functional catalase, L. interrogans was more sensitive than B. burgdorferi to H2O2 generated by GOX, which may be due to the inherent resistance of B. burgdorferi because of the virtual absence of intracellular iron. In B. burgdorferi, the nucleotide excision repair (NER) and the DNA mismatch repair (MMR) pathways were important for survival during H2O2 challenge since deletion of the uvrB or the mutS genes enhanced its sensitivity to H2O2 killing; however, the presence of pyruvate fully protected ΔuvrB and ΔmutS from H2O2 killing further demonstrating the importance of pyruvate in protection. These findings demonstrated that pyruvate, in addition to its classical role in central carbon metabolism, serves as an important H2O2 scavenger for pathogenic spirochetes. Furthermore, pyruvate reduced ROS generated by human neutrophils in response to the Toll-like receptor 2 (TLR2) agonist zymosan. In addition, pyruvate reduced neutrophil-derived ROS in response to B. burgdorferi, which also activates host expression through TLR2 signaling. Thus, pathogenic spirochetes may exploit the metabolite pyruvate, present in blood and tissues, to survive H2O2 generated by the host antibacterial response generated during infection. PMID:24392147

  11. First integrals of motion in a gauge covariant framework, Killing-Maxwell system and quantum anomalies

    SciTech Connect

    Visinescu, M.

    2012-10-15

    Hidden symmetries in a covariant Hamiltonian framework are investigated. The special role of the Stackel-Killing and Killing-Yano tensors is pointed out. The covariant phase-space is extended to include external gauge fields and scalar potentials. We investigate the possibility for a higher-order symmetry to survive when the electromagnetic interactions are taken into account. Aconcrete realization of this possibility is given by the Killing-Maxwell system. The classical conserved quantities do not generally transfer to the quantized systems producing quantum gravitational anomalies. As a rule the conformal extension of the Killing vectors and tensors does not produce symmetry operators for the Klein-Gordon operator.

  12. [Ethical and legal questions regarding the killing of animals to avoid considerable pain and suffering].

    PubMed

    Möbius, G

    1994-09-01

    The ethical and legal problems that are connected with the killing of animals are continuously discussed. Problems with the interpretation of "reasonable reason" and the public criticism of killing to get luxury goods as well as of the methods of killing show the main points. In contrast to the killing of animals in the interest of people the euthanasia of animals to prevention of considerable, not to soothed pain and suffering is appreciated generally as reasonably and ethically justified. The ethical justification confronts with legal problems based on the conflicting position of animals in civil law. These problems are important for a practising veterinarian.

  13. Extracellular stimulation by serum proteins required for maximal intracellular killing of microorganisms by mouse peritoneal macrophages.

    PubMed Central

    Leijh, P C; van Zwet, T L; van Furth, R

    1984-01-01

    Intracellular killing of catalase-positive Staphylococcus aureus by resident mouse peritoneal macrophages was very low in the absence of serum but maximal in the presence of fresh normal serum. A large proportion of catalase-negative Streptococcus pyogenes were killed in the absence of extracellular serum, and maximal killing was reached only when serum was present extracellularly. Further investigations revealed that stimulation of intracellular killing by extracellular serum is dependent on the interaction of immunoglobulin G and Fc receptors and of complement component C3b with C3b receptors in the macrophage membrane. PMID:6238911

  14. Killing of Pseudomonas pseudomallei by polymorphonuclear leukocytes and peritoneal macrophages from chicken, sheep, swine and rabbits.

    PubMed

    Markova, N; Kussovski, V; Radoucheva, T

    1998-07-01

    Differences in the kinetics of Pseudomonas pseudomallei killing by peritoneal macrophages (PM) and polymorphonuclear leucocytes (PMNL) from chickens, sheep, swine and rabbits were found. P. pseudomallei was rapidly killed by porcine PM and PMNL. However the bacterial killing by ovine and lapine PM and PMNL proceeded at a slower rate. In contrast, chicken PM and PMNL ingested and killed the lowest number of P. pseudomallei bacteria. The differences in the bactericidal activity of PM and PMNL from different animal species correlated with the level of their acid phosphatase and glycolytic activity.

  15. In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide

    PubMed Central

    Villar, Raquel; Vicente, Esther; Solano, Beatriz; Pérez-Silanes, Silvia; Aldana, Ignacio; Maddry, Joseph A.; Lenaerts, Anne J.; Franzblau, Scott G.; Cho, Sang-Hyun; Monge, Antonio; Goldman, Robert C.

    2008-01-01

    Objectives To evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB). Methods Ketone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824. Results Ten compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of ≤4.00. One compound, 5, was orally active in a murine model of TB, bactericidal, active against NRP bacteria and active on MDR-TB and poly drug-resistant clinical isolates (resistant to 3–5 antitubercular drugs). Conclusions Quinoxaline 1,4-di-N-oxides represent a new class of orally active antitubercular drugs. They are likely bioreduced to an active metabolite, but the pathway of bacterial activation was different from PA-824, a bioreducible nitroimidazole in clinical trials. Compound 5 was bactericidal and active on NRP organisms indicating that activation occurred in both growing and non-replicating bacteria leading to cell death. The presence of NRP bacteria is believed to be a major factor responsible for the prolonged nature of antitubercular therapy. If the bactericidal activity and activity on non-replicating bacteria in vitro translate to in vivo conditions, quinoxaline 1,4-di-N-oxides may offer a path to shortened therapy. PMID:18502817

  16. Carbon stocks of trees killed by bark beetles and wildfire in the western United States

    NASA Astrophysics Data System (ADS)

    Hicke, Jeffrey A.; Meddens, Arjan J. H.; Allen, Craig D.; Kolden, Crystal A.

    2013-09-01

    Forests are major components of the carbon cycle, and disturbances are important influences of forest carbon. Our objective was to contribute to the understanding of forest carbon cycling by quantifying the amount of carbon in trees killed by two disturbance types, fires and bark beetles, in the western United States in recent decades. We combined existing spatial data sets of forest biomass, burn severity, and beetle-caused tree mortality to estimate the amount of aboveground and belowground carbon in killed trees across the region. We found that during 1984-2010, fires killed trees that contained 5-11 Tg C year-1 and during 1997-2010, beetles killed trees that contained 2-24 Tg C year-1, with more trees killed since 2000 than in earlier periods. Over their periods of record, amounts of carbon in trees killed by fires and by beetle outbreaks were similar, and together these disturbances killed trees representing 9% of the total tree carbon in western forests, a similar amount to harvesting. Fires killed more trees in lower-elevation forest types such as Douglas-fir than higher-elevation forest types, whereas bark beetle outbreaks also killed trees in higher-elevation forest types such as lodgepole pine and Engelmann spruce. Over 15% of the carbon in lodgepole pine and spruce/fir forest types was in trees killed by beetle outbreaks; other forest types had 5-10% of the carbon in killed trees. Our results document the importance of these natural disturbances in the carbon budget of the western United States.

  17. The Kill Date as a Management Tool for Cover Cropping Success

    PubMed Central

    Alonso-Ayuso, María; Gabriel, José Luis; Quemada, Miguel

    2014-01-01

    Integrating cover crops (CC) in rotations provides multiple ecological services, but it must be ensured that management does not increase pre-emptive competition with the subsequent crop. This experiment was conducted to study the effect of kill date on: (i) CC growth and N content; (ii) the chemical composition of residues; (iii) soil inorganic N and potentially mineralizable N; and (iv) soil water content. Treatments were fallow and a CC mixture of barley (Hordeum vulgare L.) and vetch (Vicia sativa L.) sown in October and killed on two different dates in spring. Above-ground biomass and chemical composition of CC were determined at harvest, and ground cover was monitored based on digital image analysis. Soil mineral N was determined before sowing and after killing the CC, and potentially mineralizable N was measured by aerobic incubation at the end of the experiment. Soil water content was monitored daily to a depth of 1.1 m using capacitance sensors. Under the present conditions of high N availability, delaying kill date increased barley above-ground biomass and N uptake from deep soil layers; little differences were observed in vetch. Postponing kill date increased the C/N ratio and the fiber content of plant residues. Ground cover reached >80% by the first kill date (∼1250°C days). Kill date was a means to control soil inorganic N by balancing the N retained in the residue and soil, and showed promise for mitigating N losses. The early kill date decreased the risk of water and N pre-emptive competition by reducing soil depletion, preserving rain harvested between kill dates and allowing more time for N release in spring. The soil potentially mineralizable N was enhanced by the CC and kill date delay. Therefore kill date is a crucial management variable for maximizing the CC benefits in agricultural systems. PMID:25296333

  18. Effects of Vegetation Structure on the Location of Lion Kill Sites in African Thicket

    PubMed Central

    Davies, Andrew B.; Tambling, Craig J.; Kerley, Graham I. H.; Asner, Gregory P.

    2016-01-01

    Predator-prey relationships are integral to ecosystem stability and functioning. These relationships are, however, difficult to maintain in protected areas where large predators are increasingly being reintroduced and confined. Where predators make kills has a profound influence on their role in ecosystems, but the relative importance of environmental variables in determining kill sites, and how these might vary across ecosystems is poorly known. We investigated kill sites for lions in South Africa’s thicket biome, testing the importance of vegetation structure for kill site locations compared to other environmental variables. Kill sites were located over four years using GPS telemetry and compared to non-kill sites that had been occupied by lions, as well as to random sites within lion ranges. Measurements of 3D vegetation structure obtained from Light Detection and Ranging (LiDAR) were used to calculate the visible area (viewshed) around each site and, along with wind and moonlight data, used to compare kill sites between lion sexes, prey species and prey sexes. Viewshed area was the most important predictor of kill sites (sites in dense vegetation were twice as likely to be kill sites compared to open areas), followed by wind speed and, less so, moonlight. Kill sites for different prey species varied with vegetation structure, and male prey were killed when wind speeds were higher compared to female prey of the same species. Our results demonstrate that vegetation structure is an important component of predator-prey interactions, with varying effects across ecosystems. Such differences require consideration in terms of the ecological roles performed by predators, and in predator and prey conservation. PMID:26910832

  19. Effects of Vegetation Structure on the Location of Lion Kill Sites in African Thicket.

    PubMed

    Davies, Andrew B; Tambling, Craig J; Kerley, Graham I H; Asner, Gregory P

    2016-01-01

    Predator-prey relationships are integral to ecosystem stability and functioning. These relationships are, however, difficult to maintain in protected areas where large predators are increasingly being reintroduced and confined. Where predators make kills has a profound influence on their role in ecosystems, but the relative importance of environmental variables in determining kill sites, and how these might vary across ecosystems is poorly known. We investigated kill sites for lions in South Africa's thicket biome, testing the importance of vegetation structure for kill site locations compared to other environmental variables. Kill sites were located over four years using GPS telemetry and compared to non-kill sites that had been occupied by lions, as well as to random sites within lion ranges. Measurements of 3D vegetation structure obtained from Light Detection and Ranging (LiDAR) were used to calculate the visible area (viewshed) around each site and, along with wind and moonlight data, used to compare kill sites between lion sexes, prey species and prey sexes. Viewshed area was the most important predictor of kill sites (sites in dense vegetation were twice as likely to be kill sites compared to open areas), followed by wind speed and, less so, moonlight. Kill sites for different prey species varied with vegetation structure, and male prey were killed when wind speeds were higher compared to female prey of the same species. Our results demonstrate that vegetation structure is an important component of predator-prey interactions, with varying effects across ecosystems. Such differences require consideration in terms of the ecological roles performed by predators, and in predator and prey conservation.

  20. Patterns and Composition of Road-Killed Wildlife in Northwest Argentina.

    PubMed

    Cuyckens, Griet An Erica; Mochi, Lucía Sol; Vallejos, María; Perovic, Pablo Gastón; Biganzoli, Fernando

    2016-11-01

    Roads have important effects on wildlife, such as natural habitat fragmentation and degradation and direct killing of fauna, which leads to reductions in wildlife population size. We focused on a principal road in Northwest Argentina to test for the effect of seasonality and landscape features on the composition of road-killed wildlife. We conducted regularly scheduled road trips during the dry and wet seasons. We recorded the presence or absence of a vegetation curtain or hedge along the road. We measured land use by remote sensing in a 500 m buffer along the road. We compared the abundance of animals killed between seasons (dry and wet) for different taxonomic groups (mammals, birds and reptiles) and for different origins (domestic and native). We built linear mixed models to test the effect of landscape features on the abundance of killed animals. Two hundred and ninety-three individuals were killed, belonging to 35 species; 75.8 % were native and 24.2 % domestic species. The majority of animals killed were mid-sized mammals. More animals were killed during the dry season. The most important factors to explain the wildlife road-killing were the season and the proportion of agricultural landscape. The composition of the killed animals changed with the season. The proportion of agricultural landscape incremented the number of killed birds and mammals during both seasons, without affecting reptiles. The ratio of wild to domestic animals killed was dependent on the season. This study sets a precedent as the first in road ecology in Northwest Argentina and should be taken into account for road planning and regulation.